tag:blogger.com,1999:blog-26665820013861427202024-03-13T12:42:21.818-07:00California Tears Hemp OilUnknownnoreply@blogger.comBlogger84125tag:blogger.com,1999:blog-2666582001386142720.post-46308003629939291652018-02-28T09:45:00.001-08:002018-02-28T09:45:36.624-08:00Marijuana Compound Removes Toxic Alzheimer’s Protein from the Brainhttps://futurism.com/marijuana-compound-removes-toxic-alzheimers-protein-from-the-brain/<br />
The results have been published in <a href="https://www.nature.com/articles/npjamd201612" target="_blank"><em>Aging and Mechanisms of Disease.</em></a> <br />
<blockquote class="tr_bq">
<br /></blockquote>
<div class="post-content module">
<blockquote>
<div class="synopsis module">
<h5>
In Brief</h5>
Scientists have new evidence that suggests that THC inhibits the
formation of amyloid plaques by blocking the enzyme in the brain that
produces them. Neurodegenerative diseases such as Alzheimer's are caused
by the poor formation of those proteins in the brain. </div>
</blockquote>
<div class="summary module">
<blockquote>
An active compound in marijuana called tetrahydrocannabinol
(THC) has been found to promote the removal of toxic clumps of amyloid
beta protein in the brain, which are thought to kickstart the
progression of Alzheimer’s disease.</blockquote>
<br />
The finding supports the results of previous studies that found
evidence of the protective effects of cannabinoids, including THC, on
patients with neurodegenerative disease.<br />
“Although other studies have offered evidence that cannabinoids might
be neuroprotective against the symptoms of Alzheimer’s, we believe our
study is the first to demonstrate that cannabinoids affect both
inflammation and amyloid beta accumulation in nerve cells,” <a href="https://www.sciencedaily.com/releases/2016/06/160629095609.htm" target="_blank">says one of the team</a>, David Schubert from the Salk Institute for Biological Studies in California.<br />
Schubert and his colleagues tested the effects of THC on human
neurons grown in the lab that mimic the effects of Alzheimer’s disease.<br />
If you’re not familiar with this special little compound, it’s not
only responsible for the majority of marijuana’s psychological effects –
including the high – thanks to its natural pain-relieving properties,
it’s also been touted as an <a href="http://www.scientificamerican.com/article/medical-marijuana-how-the-evidence-stacks-up/" target="_blank">effective treatment</a> for the symptoms of everything from HIV and chemotherapy to chronic pain, post-traumatic stress disorder, and <a href="https://www.sciencealert.com/cannabis-gives-stroke-patients-hope" target="_blank">stroke</a>.<br />
In fact, THC appears to be such an amazing medical agent, researchers are working on <a href="https://www.sciencealert.com/scientists-engineer-yeast-to-produce-active-marijuana-compound-thc" target="_blank">breeding genetically modified yeast</a> that can produce it way more efficiently than it would be to make synthetic versions.<br />
The compound works by passing from the lungs to the bloodstream, where it attaches to <a href="http://www.medicaldaily.com/what-does-marijuana-do-your-brain-and-body-thc-interacts-memory-time-perception-273366" target="_blank">two types of receptors</a>, cannabinoid receptor (CB) 1 and 2, which are found on cell surfaces all over the body.<br />
In the brain, these receptors are most concentrated in neurons
associated with pleasure, memory, thinking, coordination and time
perception, and usually bind with a class of lipid molecules called
endocannabinoids that are produced by the body during physical activity
to promote cell-to-cell signaling in the brain.<br />
But THC can also bind to them in much the same way, and when they do,
they start messing with your brain’s ability to communicate with
itself. The can be a good and a bad thing, because while you might
forget something important or suddenly be incapable of swinging a
baseball bat, you’ll probably feel amazing, and want to eat all the
snacks:<br />
<br />
<div class="separator" style="clear: both; text-align: center;">
<iframe width="320" height="266" class="YOUTUBE-iframe-video" data-thumbnail-src="https://i.ytimg.com/vi/FsJzCdFlpyQ/0.jpg" src="https://www.youtube.com/embed/FsJzCdFlpyQ?feature=player_embedded" frameborder="0" allowfullscreen></iframe></div>
<br />
<br />
<a href="https://www.scripps.edu/news/press/2006/080906.html" target="_blank">Over the years</a>,
research has suggested that by binding to these receptors, THC could be
having another effect on aging brains, because it appears to helps the
body clear out the toxic accumulations – or ‘plaques’ – of amyloid beta.<br />
No one’s entirely sure what causes Alzheimer’s disease, but it’s thought to result from a build-up of <a href="https://www.sciencealert.com/new-alzheimer-s-treatment-fully-restores-memory-function" target="_blank">two types of lesions:</a> amyloid plaques and neurofibrillary tangles.<br />
Amyloid plaques sit between the neurons as dense clusters of
beta-amyloid molecules – a sticky type of protein that easily clumps
together – and neurofibrillary tangles are caused by defective tau
proteins that clump up into a thick, insoluble mass in the neurons.<br />
It’s not clear why these lesions begin to appear in the brain, but <a href="http://www.sciencedirect.com/science/article/pii/S1357272504002699" target="_blank">studies have linked</a>
inflammation in the brain tissue to the proliferation of plaques and
neurofibrillary tangles. So if we can find something that eases brain
inflammation while at the same time encourages the body to clear out
these lesions, we could be on the way to finding the first effective
treatment for Alzheimer’s ever.<br />
<a href="http://pubs.acs.org/doi/abs/10.1021/mp060066m?journalCode=mpohbp" target="_blank">Back in 2006</a>,
researchers at the Scripps Research Institute found that THC inhibits
the formation of amyloid plaques by blocking the enzyme in the brain
that produces them, and now Schubert and his team have demonstrated that
it can also eliminate a dangerous inflammatory response from the nerve
cells, ensuring their survival.<br />
“Inflammation within the brain is a major component of the damage
associated with Alzheimer’s disease, but it has always been assumed that
this response was coming from immune-like cells in the brain, not the
nerve cells themselves,” <a href="https://www.sciencedaily.com/releases/2016/06/160629095609.htm" target="_blank">says one of the team, Antonio Currais</a>.<br />
“When we were able to identify the molecular basis of the
inflammatory response to amyloid beta, it became clear that THC-like
compounds that the nerve cells make themselves may be involved in
protecting the cells from dying.”<br />
It’s exciting stuff, but it’s so far only been demonstrated in
neurons in the lab, so the next step will be for Schubert and his team
to observe the link between THC and reduced inflammation and plaque
build-up in a clinical trial. And they’ve reportedly already found a
drug candidate called J147 that appears to have the same effects as THC,
so this might be the way they can test the effects of THC without the <a href="https://www.sciencealert.com/scientists-claim-the-government-is-still-blocking-proper-cannabis-research?0_30606783414259553=" target="_blank">government getting in the way.</a><br />
The results have been published in <a href="https://www.nature.com/articles/npjamd201612" target="_blank"><em>Aging and Mechanisms of Disease.</em></a><br />
</div>
</div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-63336958403848768422017-02-09T00:24:00.001-08:002017-02-09T00:24:24.320-08:00GW Pharmaceuticals Achieves Positive Results in Phase 2 Proof of Concept Study in Gliomahttp://ir.gwpharm.com/releasedetail.cfm?ReleaseID=1010672<br />
<br />
<div class="node-formatted-date formatted-date__news-post">
Feb 7, 2017</div>
<div align="center">
<strong>- GW intends to advance oncology research and development efforts -</strong></div>
<div align="justify">
LONDON,
Feb. 07, 2017 (GLOBE NEWSWIRE) -- GW Pharmaceuticals plc
(Nasdaq:GWPH) ("GW," "the Company" or "the Group"), a biopharmaceutical
company focused on discovering, developing and commercializing novel
therapeutics from its proprietary cannabinoid product platform, today
announced positive top-line results from an exploratory<b> Phase 2
placebo-controlled clinical study of a proprietary combination of
tetrahydrocannabinol (THC) and cannabidiol (CBD) in 21 patients with
recurrent glioblastoma multiforme, or GBM</b>. GBM is a particularly
aggressive brain tumor, with a poor prognosis. GW has received Orphan
Drug Designation from the U.S. Food and Drug Administration (FDA) and
the European Medicines Agency (EMA) for THC:CBD in the treatment of
glioma.</div>
<div align="justify">
<b>The study showed that patients with
documented recurrent GBM treated with THC:CBD had an 83 percent one year
survival rate compared with 53 percent for patients in the placebo
cohort (p=0.042). Median survival for the THC:CBD group was greater than
550 days compared with 369 days in the placebo group.</b> THC:CBD was
generally well tolerated with treatment emergent adverse events leading
to discontinuation in two patients in each group. The most common
adverse events (three patients or more and greater than placebo) were
vomiting (75%), dizziness (67%), nausea (58%), headache (33%), and
constipation (33%). The results of some biomarker analyses are still
awaited.</div>
<div align="justify">
"The findings from this well-designed
controlled study suggest that the addition of a combination of THC and
CBD to patients on dose-intensive temozolomide produced relevant
improvements in survival compared with placebo and this is a good signal
of potential efficacy," said Professor Susan Short, PhD, Professor of
Clinical Oncology and Neuro-Oncology at Leeds Institute of Cancer and
Pathology at St James's University Hospital and principal investigator
of the study. "Moreover, the cannabinoid medicine was generally well
tolerated. These promising results are of particular interest as the
pharmacology of the THC:CBD product appears to be distinct from existing
oncology medications and may offer a unique and possibly synergistic
option for future glioma treatment."</div>
<div align="justify">
"We believe
that the signals of efficacy demonstrated in this study further
reinforce the potential role of cannabinoids in the field of oncology
and provide GW with the prospect of a new and distinct cannabinoid
product candidate in the treatment of glioma," stated Justin Gover, GW's
Chief Executive Officer. "These data are a catalyst for the
acceleration of GW's oncology research interests and over the coming
months, we expect to consult with external experts and regulatory
agencies on a pivotal clinical development program for THC:CBD in GBM
and to expand our research interests in other forms of cancer."</div>
<div align="justify">
The
study, designed to evaluate a number of safety and efficacy endpoints,
comprised an initial phase where the safety of THC:CBD in combination
with dose-intense temozolomide (an oral alkylating agent that is a
standard first-line treatment for GBM) was assessed in 2 cohorts of 3
patients each. Following a satisfactory independent safety evaluation,
the study then entered a randomized placebo-controlled phase where 12
patients were randomized to THC:CBD as add-on therapy compared with 9
patients randomized to placebo (plus standard of care). </div>
<div align="justify">
Beginning
in 2007 and prior to initiating this study, GW conducted substantial
pre-clinical oncologic research on several cannabinoids in various forms
of cancer including brain, lung, breast, pancreatic, melanoma, ovarian,
gastric, renal, prostate and bladder. These studies have resulted in
approximately 15 publications and show the multi-modal effects of
cannabinoids on a number of the key pathways associated with tumor
growth and progression. Cannabinoids have been shown to promote
autophagy (the process of regulated self-degradation by cells) via
several distinct mechanisms, including acting on the AKT/mTOR pathway,
an important intracellular signalling pathway that is overactive in many
cancers.</div>
<div align="justify">
In glioma, THC and CBD appear to act
via distinct signalling pathways. The combination of THC and CBD showed
good efficacy in various animal models of glioma, particularly when used
in combination with temozolomide. Initial <em>in vitro</em> studies
showed that the combined administration of THC and CBD led to a
synergistic reduction in the viability of U87MG glioma cells when
compared to the administration of each cannabinoid individually. The
co-administration of temozolomide with THC and CBD had further
synergistic effects, causing a significant reduction in cell viability.
These pre-clinical studies justified the initiation of the Phase 2
clinical study.</div>
<div align="justify">
GW's portfolio of intellectual
property related to the use of cannabinoids in oncology includes a
number of issued patents and pending applications in both the U.S. and
Europe. This portfolio is designed to protect the use of various
cannabinoids individually or in combination, in the treatment of a
variety of oncology-specific disorders and product formulations.</div>
<div align="justify">
<strong>About GBM </strong></div>
<div align="justify">
Gliomas
are tumors that arise from glial cells mainly in the brain but can also
be found within the spinal cord. Within the category of Glioma there
are multiple different tumor types. GBM is the most common Glioma and is
one of the most common primary brain tumors, accounting for 15.6% of
all primary brain tumors (Ostrom et al. 2013). They are also the most
aggressive with only 28.4% of patients surviving one year and only 3.4%
surviving to year five (Brodbelt et al. 2015). Studies of patients with
high-grade gliomas showed that headache was the most common initial
presenting symptom. These headaches can be persistent lasting more than
six months and are often associated with other symptoms, including
seizures, visual disturbances, cognitive impairment and nausea and
vomiting depending on the location and growth rate of the tumor.</div>
<div align="justify">
<strong>About GW Pharmaceuticals plc</strong></div>
<div align="justify">
<em>Founded
in 1998, GW is a biopharmaceutical company focused on discovering,
developing and commercializing novel therapeutics from its proprietary
cannabinoid product platform in a broad range of disease areas. GW is
advancing an orphan drug program in the field of childhood epilepsy with
a focus on Epidiolex<sup>®</sup> (cannabidiol), which is in Phase 3
clinical development for the treatment of Dravet syndrome,
Lennox-Gastaut syndrome, Tuberous Sclerosis Complex and Infantile
Spasms. GW commercialized the world's first plant-derived cannabinoid
prescription drug, Sativex<sup>®</sup> (nabiximols), which is approved
for the treatment of spasticity due to multiple sclerosis in 31
countries outside the United States. The Company has a deep pipeline of
additional cannabinoid product candidates which includes compounds in
Phase 1 and 2 trials for glioma, schizophrenia and epilepsy. For further
information, please visit <a href="https://www.globenewswire.com/Tracker?data=Pua2Pa07wwa-1Jc2h3jtYFxe3yxzeOcRvrJNPKOqavYjqJ0AZ7q5TcvlQm0kRo59g-e9722bzLW5zTVClz2dDg==" rel="nofollow" target="_blank">www.gwpharm.com</a>.</em></div>
<div align="justify">
<strong>Forward-looking statements </strong></div>
<div align="justify">
<em>This
news release contains forward-looking statements that reflect GW's
current expectations regarding future events, including statements
regarding financial performance, the timing of clinical trials, the
timing and outcomes of regulatory or intellectual property decisions,
the relevance of GW products commercially available and in development,
the clinical benefits of Sativex® and Epidiolex® and the safety profile
and commercial potential of Sativex and Epidiolex. Forward-looking
statements involve risks and uncertainties. Actual events could differ
materially from those projected herein and depend on a number of
factors, including (inter alia), the success of GW's research
strategies, the applicability of the discoveries made therein, the
successful and timely completion of uncertainties related to the
regulatory process, and the acceptance of Sativex, Epidiolex and other
products by consumer and medical professionals. A further list and
description of risks and uncertainties associated with an investment in
GW can be found in GW's filings with the U.S. Securities and Exchange
Commission, including the most recent Form 20-F filed on 5 December
2016. Existing and prospective investors are cautioned not to place
undue reliance on these forward-looking statements, which speak only as
of the date hereof. GW undertakes no obligation to update or revise the
information contained in this press release, whether as a result of new
information, future events or circumstances or otherwise.</em></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-53313617604512896612016-12-26T23:48:00.003-08:002016-12-26T23:50:17.393-08:00Cannabinoid derivatives exert a potent anti-myeloma activity both in vitro and in vivo.<a href="https://www.ncbi.nlm.nih.gov/pubmed/27778331">https://www.ncbi.nlm.nih.gov/pubmed/27778331</a><br />
<br />
<ul class="social-buttons inline_list"><div class="results_settings one_setting" id="result_action_bar">
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<li><a class="jig-ncbipopper" data-jigconfig="triggerPosition : 'bottom center',destPosition : 'top center',destSelector : '#display_settings_menu_report', hasArrow : false,openEvent : 'click',closeEvent : 'click',isTriggerElementCloseClick: false,addCloseButton : false, groupName: 'entrez_pg'" href="https://www.ncbi.nlm.nih.gov/pubmed/27778331#" id="Display" name="Display" role="button"></a></li>
</ul>
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<div>
</div>
<div class="">
<div>
<span class="nowrap" id="result_sel"></span></div>
</div>
<div class="empty" id="messagearea">
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<div class="rprt_all">
<div class="rprt abstract">
<div class="cit">
<span role="menubar"><a href="https://www.ncbi.nlm.nih.gov/pubmed/27778331#" role="menuitem" title="International journal of cancer.">Int J Cancer.</a></span> 2017 Feb 1;140(3):674-685. doi: 10.1002/ijc.30483. Epub 2016 Nov 10.</div>
<h1>
</h1>
<div class="auths">
<a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Barbado%20MV%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">Barbado MV</a><sup>1</sup>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Medrano%20M%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">Medrano M</a><sup>1</sup>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Caballero-Vel%C3%A1zquez%20T%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">Caballero-Velázquez T</a><sup>1</sup>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=%C3%81lvarez-Laderas%20I%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">Álvarez-Laderas I</a><sup>1</sup>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=S%C3%A1nchez-Abarca%20LI%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">Sánchez-Abarca LI</a><sup>1</sup>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Garc%C3%ADa-Guerrero%20E%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">García-Guerrero E</a><sup>1</sup>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Mart%C3%ADn-S%C3%A1nchez%20J%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">Martín-Sánchez J</a><sup>1</sup>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Rosado%20IV%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">Rosado IV</a><sup>1</sup>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Piruat%20JI%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">Piruat JI</a><sup>1</sup>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Gonzalez-Naranjo%20P%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">Gonzalez-Naranjo P</a><sup>2</sup>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Campillo%20NE%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">Campillo NE</a><sup>2</sup>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=P%C3%A1ez%20JA%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">Páez JA</a><sup>2</sup>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=P%C3%A9rez-Sim%C3%B3n%20JA%5BAuthor%5D&cauthor=true&cauthor_uid=27778331">Pérez-Simón JA</a><sup>1</sup>.</div>
<div class="afflist">
<h3>
<a class="jig-ncbitoggler ui-widget ui-ncbitoggler" href="https://www.ncbi.nlm.nih.gov/pubmed/27778331#" id="ui-ncbitoggler-2" role="button" title="Open/close author information list"><span class="ui-ncbitoggler-master-text">Author information</span><span class="ui-icon ui-icon-triangle-1-e"></span></a></h3>
</div>
<div class="abstr">
<h3>
Abstract</h3>
<div class="">
Although
hematopoietic and immune system show high levels of the cannabinoid
receptor CB2, the potential effect of cannabinoids on hematologic
malignancies has been poorly determined. Here we have investigated their
anti-tumor effect in multiple myeloma (MM). <b>We demonstrate that
cannabinoids induce a selective apoptosis in MM cell lines and in
primary plasma cells of MM patients, while sparing normal cells from
healthy donors, including hematopoietic stem cells. </b>This effect was
mediated by caspase activation, mainly caspase-2, and was partially
prevented by a pan-caspase inhibitor. Their pro-apoptotic effect was
correlated with an increased expression of Bax and Bak, a decrease of
Bcl-xL and Mcl-1, a biphasic response of Akt/PKB and an increase in the
levels of ceramide in MM cells. Inhibition of ceramide synthesis
partially prevented apoptosis, indicating that these sphingolipids play a
key role in the pro-apoptotic effect of cannabinoids in MM cells.
Remarkably, blockage of the CB2 receptor also inhibited
cannabinoid-induced apoptosis. Cannabinoid derivative WIN-55 enhanced
the anti-myeloma activity of dexamethasone and melphalan overcoming
resistance to melphalan in vitro. Finally, administration of cannabinoid
WIN-55 to plasmacytoma-bearing mice significantly suppressed tumor
growth in vivo. <b>Together, our data suggest that cannabinoids may be
considered as potential therapeutic agents in the treatment of MM.</b><br />
<div class="copyright">
© 2016 UICC.</div>
</div>
</div>
<div class="keywords">
<h4>
KEYWORDS: </h4>
apoptosis; cannabinoids; caspases; ceramides; multiple myeloma</div>
<div class="aux">
<div class="resc">
<dl class="rprtid">
<dt>PMID:</dt>
<dd>27778331</dd>
<dt>DOI:</dt>
<dd><a href="https://dx.doi.org/10.1002/ijc.30483">10.1002/ijc.30483</a></dd></dl>
</div>
<div class="resc status">
<dl class="rprtid"><dd>[PubMed - in process] </dd></dl>
</div>
</div>
</div>
</div>
</ul>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-17806189422629228492016-12-16T07:46:00.000-08:002016-12-16T07:46:25.228-08:00U.S.: Hemp Industry Association Says DEA Ruling Does Not Make CBD Illegal http://crrh.org/news/blog/1582<br />
<br />
<div id="stcpDiv" style="left: -1988px; position: absolute; top: -1999px;">
By Derrick Stanley<br />
Hemp News<br />
The National Hemp Association has made an announcement that a recent
ruling by the U.S. DEA (Drug Enforcement Administration) did not make
cannabidoids (CBD) illegal.<br />
The following statement was issued by the Hemp Industries Association:<br />
Yesterday the Drug Enforcement Administration (DEA) issued a Final
Rule on the coding of marijuana extracts. Unfortunately some misleading
media stories and social media postings lead quite a few people to panic
at reports that CBD was being banned under this new rule.<br />
The Sky is NOT Falling. The Final Rule published by DEA did not
change the legal status of CBD. This can only be done by a scheduling
action which has NOT occurred.<br />
HIA has carefully reviewed this with our legal advisors and discussed
it with industry experts. While there are some differing opinions on
the effect of the rule, there is general agreement that yesterday's
ruling did not change the status of CBD. Here are some important facts
to know:<br />
Cannabidiol is not listed on the federal schedule of controlled substances<br />
Sec. 7606 of the Farm Bill defines hemp as distinct from marijuana and
does not treat it as a controlled substance when grown under a compliant
state program.<br />
Despite these facts, DEA has stated that CBD is a controlled substance previously.<br />
- See more at: http://crrh.org/news/blog/1582#sthash.8DMXosgI.dpuf</div>
<br />
By Derrick Stanley<br />
Hemp News<br />
The National Hemp Association has made an announcement that a recent
ruling by the U.S. DEA (Drug Enforcement Administration) did not make
cannabidoids (CBD) illegal.<br />
The following statement was issued by the Hemp Industries Association:<br />
Yesterday the Drug Enforcement Administration (DEA) issued a Final
Rule on the coding of marijuana extracts. Unfortunately some misleading
media stories and social media postings lead quite a few people to panic
at reports that CBD was being banned under this new rule.<br />
The Sky is NOT Falling. The Final Rule published by DEA did not
change the legal status of CBD. This can only be done by a scheduling
action which has NOT occurred.<br />
HIA has carefully reviewed this with our legal advisors and discussed
it with industry experts. While there are some differing opinions on
the effect of the rule, there is general agreement that yesterday's
ruling did not change the status of CBD. Here are some important facts
to know:<br />
Cannabidiol is not listed on the federal schedule of controlled substances<br />
Sec. 7606 of the Farm Bill defines hemp as distinct from marijuana and
does not treat it as a controlled substance when grown under a compliant
state program.<br />
Despite these facts, DEA has stated that CBD is a controlled substance previously.<br />
HIA strongly disagrees with the DEA position and is ready to take action
to defend should DEA take any action to block the production,
processing or sale of hemp under Sec. 7606.<br />
The Final Rule published on December 14th was not a scheduling action
but rather an administrative action related to record keeping.<br />
<div id="stcpDiv" style="left: -1988px; position: absolute; top: -1999px;">
By Derrick Stanley<br />
Hemp News<br />
The National Hemp Association has made an announcement that a recent
ruling by the U.S. DEA (Drug Enforcement Administration) did not make
cannabidoids (CBD) illegal.<br />
The following statement was issued by the Hemp Industries Association:<br />
Yesterday the Drug Enforcement Administration (DEA) issued a Final
Rule on the coding of marijuana extracts. Unfortunately some misleading
media stories and social media postings lead quite a few people to panic
at reports that CBD was being banned under this new rule.<br />
The Sky is NOT Falling. The Final Rule published by DEA did not
change the legal status of CBD. This can only be done by a scheduling
action which has NOT occurred.<br />
HIA has carefully reviewed this with our legal advisors and discussed
it with industry experts. While there are some differing opinions on
the effect of the rule, there is general agreement that yesterday's
ruling did not change the status of CBD. Here are some important facts
to know:<br />
Cannabidiol is not listed on the federal schedule of controlled substances<br />
Sec. 7606 of the Farm Bill defines hemp as distinct from marijuana and
does not treat it as a controlled substance when grown under a compliant
state program.<br />
Despite these facts, DEA has stated that CBD is a controlled substance previously.<br />
- See more at: http://crrh.org/news/blog/1582#sthash.8DMXosgI.dpuf</div>
<div id="stcpDiv" style="left: -1988px; position: absolute; top: -1999px;">
</div>
<div id="stcpDiv" style="left: -1988px; position: absolute; top: -1999px;">
By Derrick Stanley<br />
Hemp News<br />
The National Hemp Association has made an announcement that a recent
ruling by the U.S. DEA (Drug Enforcement Administration) did not make
cannabidoids (CBD) illegal.<br />
The following statement was issued by the Hemp Industries Association:<br />
Yesterday the Drug Enforcement Administration (DEA) issued a Final
Rule on the coding of marijuana extracts. Unfortunately some misleading
media stories and social media postings lead quite a few people to panic
at reports that CBD was being banned under this new rule.<br />
The Sky is NOT Falling. The Final Rule published by DEA did not
change the legal status of CBD. This can only be done by a scheduling
action which has NOT occurred.<br />
HIA has carefully reviewed this with our legal advisors and discussed
it with industry experts. While there are some differing opinions on
the effect of the rule, there is general agreement that yesterday's
ruling did not change the status of CBD. Here are some important facts
to know:<br />
Cannabidiol is not listed on the federal schedule of controlled substances<br />
Sec. 7606 of the Farm Bill defines hemp as distinct from marijuana and
does not treat it as a controlled substance when grown under a compliant
state program.<br />
Despite these facts, DEA has stated that CBD is a controlled substance previously.<br />
HIA strongly disagrees with the DEA position and is ready to take action
to defend should DEA take any action to block the production,
processing or sale of hemp under Sec. 7606.<br />
The Final Rule published on December 14th was not a scheduling action
but rather an administrative action related to record keeping.<br />
- See more at: http://crrh.org/news/DEA-did-not-make-CBD-illegal-after-all-despite-reports-to-the-contrary#sthash.hLXbgO4d.dpuf</div>
<div id="stcpDiv" style="left: -1988px; position: absolute; top: -1999px;">
</div>
<div id="stcpDiv" style="left: -1988px; position: absolute; top: -1999px;">
<div id="stcpDiv" style="left: -1988px; position: absolute; top: -1999px;">
By Derrick Stanley<br />
Hemp News<br />
The National Hemp Association has made an announcement that a recent
ruling by the U.S. DEA (Drug Enforcement Administration) did not make
cannabidoids (CBD) illegal.<br />
The following statement was issued by the Hemp Industries Association:<br />
Yesterday the Drug Enforcement Administration (DEA) issued a Final
Rule on the coding of marijuana extracts. Unfortunately some misleading
media stories and social media postings lead quite a few people to panic
at reports that CBD was being banned under this new rule.<br />
The Sky is NOT Falling. The Final Rule published by DEA did not
change the legal status of CBD. This can only be done by a scheduling
action which has NOT occurred.<br />
HIA has carefully reviewed this with our legal advisors and discussed
it with industry experts. While there are some differing opinions on
the effect of the rule, there is general agreement that yesterday's
ruling did not change the status of CBD. Here are some important facts
to know:<br />
Cannabidiol is not listed on the federal schedule of controlled substances<br />
Sec. 7606 of the Farm Bill defines hemp as distinct from marijuana and
does not treat it as a controlled substance when grown under a compliant
state program.<br />
Despite these facts, DEA has stated that CBD is a controlled substance previously.<br />
HIA strongly disagrees with the DEA position and is ready to take action
to defend should DEA take any action to block the production,
processing or sale of hemp under Sec. 7606.<br />
The Final Rule published on December 14th was not a scheduling action
but rather an administrative action related to record keeping.<br />
- See more at: http://crrh.org/news/DEA-did-not-make-CBD-illegal-after-all-despite-reports-to-the-contrary#sthash.hLXbgO4d.dpuf</div>
</div>
<div id="stcpDiv" style="left: -1988px; position: absolute; top: -1999px;">
By Derrick Stanley<br />
Hemp News<br />
The National Hemp Association has made an announcement that a recent
ruling by the U.S. DEA (Drug Enforcement Administration) did not make
cannabidoids (CBD) illegal.<br />
The following statement was issued by the Hemp Industries Association:<br />
Yesterday the Drug Enforcement Administration (DEA) issued a Final
Rule on the coding of marijuana extracts. Unfortunately some misleading
media stories and social media postings lead quite a few people to panic
at reports that CBD was being banned under this new rule.<br />
The Sky is NOT Falling. The Final Rule published by DEA did not
change the legal status of CBD. This can only be done by a scheduling
action which has NOT occurred.<br />
HIA has carefully reviewed this with our legal advisors and discussed
it with industry experts. While there are some differing opinions on
the effect of the rule, there is general agreement that yesterday's
ruling did not change the status of CBD. Here are some important facts
to know:<br />
Cannabidiol is not listed on the federal schedule of controlled substances<br />
Sec. 7606 of the Farm Bill defines hemp as distinct from marijuana and
does not treat it as a controlled substance when grown under a compliant
state program.<br />
Despite these facts, DEA has stated that CBD is a controlled substance previously.<br />
HIA strongly disagrees with the DEA position and is ready to take action
to defend should DEA take any action to block the production,
processing or sale of hemp under Sec. 7606.<br />
The Final Rule published on December 14th was not a scheduling action
but rather an administrative action related to record keeping.<br />
- See more at: http://crrh.org/news/DEA-did-not-make-CBD-illegal-after-all-despite-reports-to-the-contrary#sthash.hLXbgO4d.dpuf</div>
<div id="stcpDiv" style="left: -1988px; position: absolute; top: -1999px;">
<div class="meta">
<div class="submitted">
Fri, 12/16/2016 - 04:11 - derrickstanley</div>
</div>
<div class="terms">
<ul class="taxonomy">
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/2016" rel="tag" title="">2016</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/marijuana" rel="tag" title="">Marijuana</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/taxonomy/term/16916" rel="tag" title="">Hemp Industry Association</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/industrial-hemp" rel="tag" title="">Industrial Hemp</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/cannabidiol" rel="tag" title="">cannabidiol</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/cbd" rel="tag" title="">CBD</a></li>
</ul>
</div>
<div class="content">
<div class="all-attached-images">
<div class="image-attach-body image-attach-node-8637" style="width: 259px;">
<a href="http://crrh.org/news/node/8637"><img alt="hemp field.jpg" class="pure-img image image-thumbnail " height="194" src="http://crrh.org/news/sites/default/files/images/hemp%20field_1.jpg" title="hemp field.jpg" width="259" /></a></div>
</div>
By Derrick Stanley<br />
Hemp News<br />
The National Hemp Association has made an announcement that a recent
ruling by the U.S. DEA (Drug Enforcement Administration) did not make
cannabidoids (CBD) illegal.<br />
The following statement was issued by the Hemp Industries Association:<br />
Yesterday the Drug Enforcement Administration (DEA) issued a Final
Rule on the coding of marijuana extracts. Unfortunately some misleading
media stories and social media postings lead quite a few people to panic
at reports that CBD was being banned under this new rule.<br />
The Sky is NOT Falling. The Final Rule published by DEA did not
change the legal status of CBD. This can only be done by a scheduling
action which has NOT occurred.<br />
HIA has carefully reviewed this with our legal advisors and discussed
it with industry experts. While there are some differing opinions on
the effect of the rule, there is general agreement that yesterday's
ruling did not change the status of CBD. Here are some important facts
to know:<br />
Cannabidiol is not listed on the federal schedule of controlled substances<br />
Sec. 7606 of the Farm Bill defines hemp as distinct from marijuana and
does not treat it as a controlled substance when grown under a compliant
state program.<br />
Despite these facts, DEA has stated that CBD is a controlled substance previously.<br />
HIA strongly disagrees with the DEA position and is ready to take action
to defend should DEA take any action to block the production,
processing or sale of hemp under Sec. 7606.<br />
The Final Rule published on December 14th was not a scheduling action
but rather an administrative action related to record keeping.</div>
- See more at: http://crrh.org/news/DEA-did-not-make-CBD-illegal-after-all-despite-reports-to-the-contrary#sthash.hLXbgO4d.dpuf</div>
<div id="stcpDiv" style="left: -1988px; position: absolute; top: -1999px;">
<div class="meta">
<div class="submitted">
Fri, 12/16/2016 - 04:11 - derrickstanley</div>
</div>
<div class="terms">
<ul class="taxonomy">
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/2016" rel="tag" title="">2016</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/marijuana" rel="tag" title="">Marijuana</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/taxonomy/term/16916" rel="tag" title="">Hemp Industry Association</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/industrial-hemp" rel="tag" title="">Industrial Hemp</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/cannabidiol" rel="tag" title="">cannabidiol</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/cbd" rel="tag" title="">CBD</a></li>
</ul>
</div>
<div class="content">
<div class="all-attached-images">
<div class="image-attach-body image-attach-node-8637" style="width: 259px;">
<a href="http://crrh.org/news/node/8637"><img alt="hemp field.jpg" class="pure-img image image-thumbnail " height="194" src="http://crrh.org/news/sites/default/files/images/hemp%20field_1.jpg" title="hemp field.jpg" width="259" /></a></div>
</div>
By Derrick Stanley<br />
Hemp News<br />
The National Hemp Association has made an announcement that a recent
ruling by the U.S. DEA (Drug Enforcement Administration) did not make
cannabidoids (CBD) illegal.<br />
The following statement was issued by the Hemp Industries Association:<br />
Yesterday the Drug Enforcement Administration (DEA) issued a Final
Rule on the coding of marijuana extracts. Unfortunately some misleading
media stories and social media postings lead quite a few people to panic
at reports that CBD was being banned under this new rule.<br />
The Sky is NOT Falling. The Final Rule published by DEA did not
change the legal status of CBD. This can only be done by a scheduling
action which has NOT occurred.<br />
HIA has carefully reviewed this with our legal advisors and discussed
it with industry experts. While there are some differing opinions on
the effect of the rule, there is general agreement that yesterday's
ruling did not change the status of CBD. Here are some important facts
to know:<br />
Cannabidiol is not listed on the federal schedule of controlled substances<br />
Sec. 7606 of the Farm Bill defines hemp as distinct from marijuana and
does not treat it as a controlled substance when grown under a compliant
state program.<br />
Despite these facts, DEA has stated that CBD is a controlled substance previously.<br />
HIA strongly disagrees with the DEA position and is ready to take action
to defend should DEA take any action to block the production,
processing or sale of hemp under Sec. 7606.<br />
The Final Rule published on December 14th was not a scheduling action
but rather an administrative action related to record keeping.</div>
- See more at: http://crrh.org/news/DEA-did-not-make-CBD-illegal-after-all-despite-reports-to-the-contrary#sthash.hLXbgO4d.dpuf</div>
<div id="stcpDiv" style="left: -1988px; position: absolute; top: -1999px;">
<div class="meta">
<div class="submitted">
Fri, 12/16/2016 - 04:11 - derrickstanley</div>
</div>
<div class="terms">
<ul class="taxonomy">
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/2016" rel="tag" title="">2016</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/marijuana" rel="tag" title="">Marijuana</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/taxonomy/term/16916" rel="tag" title="">Hemp Industry Association</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/industrial-hemp" rel="tag" title="">Industrial Hemp</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/cannabidiol" rel="tag" title="">cannabidiol</a> | </li>
<li class="vocab-term"><a href="http://crrh.org/news/category/cannabis/cbd" rel="tag" title="">CBD</a></li>
</ul>
</div>
<div class="content">
<div class="all-attached-images">
<div class="image-attach-body image-attach-node-8637" style="width: 259px;">
<a href="http://crrh.org/news/node/8637"><img alt="hemp field.jpg" class="pure-img image image-thumbnail " height="194" src="http://crrh.org/news/sites/default/files/images/hemp%20field_1.jpg" title="hemp field.jpg" width="259" /></a></div>
</div>
By Derrick Stanley<br />
Hemp News<br />
The National Hemp Association has made an announcement that a recent
ruling by the U.S. DEA (Drug Enforcement Administration) did not make
cannabidoids (CBD) illegal.<br />
The following statement was issued by the Hemp Industries Association:<br />
Yesterday the Drug Enforcement Administration (DEA) issued a Final
Rule on the coding of marijuana extracts. Unfortunately some misleading
media stories and social media postings lead quite a few people to panic
at reports that CBD was being banned under this new rule.<br />
The Sky is NOT Falling. The Final Rule published by DEA did not
change the legal status of CBD. This can only be done by a scheduling
action which has NOT occurred.<br />
HIA has carefully reviewed this with our legal advisors and discussed
it with industry experts. While there are some differing opinions on
the effect of the rule, there is general agreement that yesterday's
ruling did not change the status of CBD. Here are some important facts
to know:<br />
Cannabidiol is not listed on the federal schedule of controlled substances<br />
Sec. 7606 of the Farm Bill defines hemp as distinct from marijuana and
does not treat it as a controlled substance when grown under a compliant
state program.<br />
Despite these facts, DEA has stated that CBD is a controlled substance previously.<br />
HIA strongly disagrees with the DEA position and is ready to take action
to defend should DEA take any action to block the production,
processing or sale of hemp under Sec. 7606.<br />
The Final Rule published on December 14th was not a scheduling action
but rather an administrative action related to record keeping.</div>
- See more at: http://crrh.org/news/DEA-did-not-make-CBD-illegal-after-all-despite-reports-to-the-contrary#sthash.hLXbgO4d.dpuf</div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-70809004521014712872016-11-25T09:30:00.000-08:002016-11-25T09:30:04.222-08:00Cannabinoids Improve Efficiency Of Mitochondria And Remove Damaged Brain Cellshttp://www.collective-evolution.com/2013/05/30/new-study-shows-cannabinoids-improve-efficiency-of-mitochondria-and-remove-damaged-brain-cells/<br />
<br />
<div class="cb-byline">
<span class="cb-author"> <a href="http://www.collective-evolution.com/author/arjun/">Arjun Walia</a></span><span class="cb-separator"></span><span class="cb-date"><time class="updated" datetime="2013-05-30"> </time></span></div>
<div class="cb-byline">
<span class="cb-date"><time class="updated" datetime="2013-05-30">May 30, 2013</time></span></div>
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<img alt="mary j" class="attachment-cb-759-500 size-cb-759-500 wp-post-image" height="500" src="http://cdn1.collective-evolution.com/assets/uploads/2013/05/mary-j-759x500.jpg" width="759" /></div>
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<img alt="mj" class="alignleft size-full wp-image-40931" height="183" src="http://cdn1.collective-evolution.com/assets/uploads/2013/05/mj.jpg" width="275" />A
recent study conducted by Andras Biokei-Gorzo at the Institute of
Molecular Psychiatry at the University of Bonn in Germany is suggesting
that marijuana(or the activation of the brain’s cannabinoid system)
triggers the release of antioxidants, which act as a cleansing
mechanism. This process is known to remove damaged cells and improve the
efficiency of mitochondria. Mitochondria is the energy source that
powers cells. The study was published in <em>Philosophical Transactions Of The Royal Society, B. </em>You can read the entire study <a href="http://rstb.royalsocietypublishing.org/content/367/1607/3326.abstract?sid=20cf2c23-e4fd-49e3-9398-ec8be2e00226">here</a>.</div>
<div class="article_float_right text-center">
</div>
<div style="text-align: justify;">
These discoveries shed new insight on
how natural marijuana cannabinoids hold the capacity to literally kill
the brain inflammation responsible for causing cognitive decline, neural
failure, and brain degeneration. By supplying these receptor sites with
cannabinoids, patients may be able to overcome brain conditions like
Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and
more, not to mention premature brain aging. The human brain contains an
extensive network of special receptor sites that modulate nervous system
function only when activated by the appropriate cannabinoid compounds,
which are found in the marijuana plant.</div>
<div style="text-align: justify;">
Cannabinoids refer to any of a group of
related compounds that include cannabinol and the active constituents of
cannabis. They activate canbinoid receptors in the body. The body
itself produces compounds called endocannabinoids and they play a role
in many processes within the body that help to create a healthy
environment. Cannabinoids also play a role in immune system generation
and re-generation. The body regenerates best when it’s saturated with
Phyto-Cannabinoids. Cannabinoids can also be found in Cannabis.
Cannabinoids may very well be the best cancer fighting substance out
there!</div>
<blockquote>
Cannabinoid system activity is neuroprotective, and
increasing it could be a promising strategy for slowing down the
progression of brain aging and for alleviating the systems of
neurodegenerative disorders -Andras Biokei</blockquote>
<div style="text-align: justify;">
Gery Wenk, a professor of neuroscience,
immunology and medical genetics at Ohio State University conducted some
of the research that came out of the study from Germany. He stated that
this is a positive step, and that it is encouraging to see the potential
development of cannabinoid solutions without going overboard. Here is
what he said.</div>
<blockquote>
I’ve been trying to find a drug that will reduce brain
inflammation and restore cognitive function in rats for over 25 years;
cannabinoids are the first and only class of drugs that have ever been
effective. I think that the perception about this drug is changing and
in the future people will be less fearful. – Gerry Wenk, Professor of
neuroscience, immunology and medical genetics at Ohio State University<br />
<div style="border-bottom: 1px solid #ccc; border-top: 1px solid #ccc; padding: 20px 0;">
<div id="647812857">
</div>
</div>
</blockquote>
<div style="text-align: justify;">
Biokei-Gorzo and his collegues said that
the greatest hurdle for moving forward with their research are the
social and political challenges. This isn’t something new, our world
seems to be dominated by belief systems instead of obvious fact. It’s
discouraging to see beliefs and persuasion overrule truth. At the same
time it’s very encouraging to see truth slowly creep its way into the
norm. That’s always how it has been done throughout human history. It’s
quite evident that the powers that be do not want to legalize marijuana,
and we know that they do not have our best interest at hand. If it was
legalized, I’m sure it would be distributed and tweaked by big
pharmaceutical companies.</div>
<div style="text-align: justify;">
On the other hand there have been a
number of studies that show how marijuana can actually reduce brain
power and impair working memory. The amount of studies that show the
potential benefits of marijuana is outstanding, and the potential
harmful effects are in the few, if any at all. As far as medicinal use
goes, I think that is a no brainer. I definitely believe nature intended
marijuana to be used for its health and healing properties.</div>
<div style="text-align: justify;">
<strong>Sources:</strong></div>
<div style="text-align: justify;">
<a href="http://rstb.royalsocietypublishing.org/content/367/1607/3326.abstract?sid=20cf2c23-e4fd-49e3-9398-ec8be2e00226">http://rstb.royalsocietypublishing.org/content/367/1607/3326.abstract?sid=20cf2c23-e4fd-49e3-9398-ec8be2e00226</a></div>
<div style="text-align: justify;">
<a href="http://healthland.time.com/2012/10/29/how-cannabinoids-may-slow-brain-aging/">http://healthland.time.com/2012/10/29/how-cannabinoids-may-slow-brain-aging/</a></div>
<div style="text-align: justify;">
<a href="http://www.drugscience.org/Petition/C3D.html">http://www.drugscience.org/Petition/C3D.html</a></div>
<div style="text-align: justify;">
<a href="http://www.naturalnews.com/040456_marijuana_cannabinoids_dementia.html">http://www.naturalnews.com/040456_marijuana_cannabinoids_dementia.html</a></div>
<div style="text-align: justify;">
<a href="http://www.rawhemp.tk/" target="_blank">http://www.rawhemp.tk/</a></div>
<div style="text-align: justify;">
<a href="http://www.phoenixtears.ca/" target="_blank">http://www.phoenixtears.ca/</a></div>
<em id="__mceDel"><a href="http://cannabisinternational.org/" target="_blank">http://cannabisinternational.org/</a></em><br />
<em id="__mceDel"><em id="__mceDel"><a href="http://edrv.endojournals.org/content/27/1/73.full" target="_blank">http://edrv.endojournals.org/content/27/1/73.full</a><a href="http://edrv.endojournals.org/content/27/1/73.full" target="_blank">http://cannabisclinicians.org/wp-content/uploads/2011/12/OS-2011-Terpenes+Minor-CBs.pdf</a></em></em><br />
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-78342689711829683492016-09-23T07:01:00.003-07:002016-09-23T07:04:59.526-07:00U.S. Attorney General Admits Marijuana Is Not a Gateway Drughttps://www.merryjane.com/news/us-attorney-general-admits-marijuana-not-gateway-drug<br />
<br />
<div class="subtitle">
<h4>
<b>Top federal official crushes this popular anti-legalization argument.</b></h4>
</div>
<div class="header-image" data-interchange="[https://files.merryjane.com/uploads/article/hero_image/1934/main_content_US_ATTORNY_GENERAL_LORETTA_LYNCH_WIDE.jpg, (default)], [https://files.merryjane.com/uploads/article/mobile_image/1934/US_ATTORNY_GENERAL_LORETTA_LYNCH_TALL.jpg, (small-only)]" data-uuid="interchange-itfu4nyj0" style="background-image: url("https://files.merryjane.com/uploads/article/hero_image/1934/main_content_US_ATTORNY_GENERAL_LORETTA_LYNCH_WIDE.jpg");" title="U.S. Attorney General Admits Marijuana Is Not a Gateway Drug">
</div>
<div class="article-content">
One of the most popular arguments against the legalization of
marijuana is that pot is a “gateway” drug with the potential to turn the
great American populous into a nation of dope fiends. But today the
country’s leading law enforcement official denounced this common
misconception by admitting that the consumption of marijuana does not
lead to the use of harder drugs.<br />
As part of what President Obama has declared National Prescription
Opioid and Heroin Epidemic Awareness Week, U.S Attorney General Loretta
Lynch appeared at town hall meeting this morning in Richmond, Kentucky
to discuss the dangers of opioid abuse with a group of teens.<br />
In her opening statement, Lynch was adamant that the leading culprit
behind Kentucky’s heroin epidemic was the use of prescription drugs.<br />
“When you look at someone that, for example, has a heroin problem, it
very often started with a prescription drug problem. Something totally
legal. Something in every medicine cabinet. Something you can have
prescribed to you in good faith by a doctor,” Lynch <a href="https://www.youtube.com/watch?v=aRUWSz-EqJ4" target="_blank">said</a> before taking questions from the audience.<br />
It did not take long before the discussion turned to the issue of marijuana.<br />
Tyler Crafton, a student at Madison Central High School, took the
opportunity to ask Lynch whether she thought the recreational use of
marijuana among high school kids would lead to opioid abuse.<br />
Shockingly, Lynch, the top dog at the U.S. Department of Justice, did
provide the young man with a response straight out of the federal
government’s propaganda handbook.<br />
“There a lot of discussion about marijuana these days. Some states
are making it legal, people are looking into medical uses for it, and I
understand that it still is as common as almost anything,” Lynch <a href="https://www.youtube.com/watch?v=aRUWSz-EqJ4" target="_blank">replied</a>.
“When we talk about heroin addiction, we unusually, as we have
mentioned, are talking about individuals that started out with a
prescription drug problem, and then because they need more and more,
they turn to heroin. It isn’t so much that marijuana is the step right
before using prescription drugs or opioids.”<br />
For a moment, it sounded as though the Attorney General was preparing
to backtrack on her statement to some degree, adding that, “if you tend
to experiment with a lot of things if life you may be more inclined to
experiment with drugs.”<br />
But then Lynch followed up with what should be considered one of the
most important statements a federal official has made in 2016.<br />
“It’s not as though we are seeing that marijuana is a specific gateway,” she said.<br />
The attorney general’s admission that marijuana is not a gateway drug
is fairly consistent with the National Institute on Drug Abuse, <a href="https://www.drugabuse.gov/publications/research-reports/marijuana/marijuana-gateway-drug" target="_blank">which finds</a>
“the majority of people who use marijuana do not go on to use other,
“harder” substances. Yet many of marijuana’s opposing forces are going
up against ballot measure in several states this election season by
trying to convince the general public that legal weed will cause the
opioid epidemic to spin further out of control.<br />
Interestingly, an investigational report published earlier this week
by the Associated Press and the Center for Public Integrity <a href="https://www.publicintegrity.org/2016/09/18/20203/pharma-lobbying-held-deep-influence-over-opioid-policies" target="_blank">found</a>
that lobbyists for the drug makers responsible for the same
prescription drugs that Attorney General Lynch says is responsible for
the opioid epidemic have spent $880 million legally bribing state
representatives and senators to vote against legislation concerning the
restricting of opioid use. It stands to reason that these lobbyists are
also responsible for getting federal lawmakers to turn a blind eye to
marijuana.<br />
Attorney General Lynch will be speaking at more than <a href="http://www.courier-journal.com/story/news/local/2016/09/20/heroin-crisis-brings-ag-loretta-lynch-ky/90437604/" target="_blank">250 events this week</a>
in support of Prescription Opioid and Heroin Epidemic Awareness Week.
It will be interesting to see if she offers additional comments about
the safety of marijuana.</div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-3698945465233879202016-09-20T01:56:00.001-07:002017-03-20T06:03:59.673-07:00Where to find good quality RSO or Hemp Extracts?I get this question quite a bit, if you aren't able to make the oil yourself, then here is a list of legit providers<br />
<br />
California<br />
<a href="http://www.californiatears.com/" target="_blank">California Tears CBD and RSO</a><br />
<a href="http://synergycbd.com/" target="_blank">Synergy Wellness</a><br />
<br />
Oregon<br />
<a href="https://www.facebook.com/genesis.pharms/" target="_blank">Genesis Pharms</a><br />
<br />
Worldwide<br />
<a href="http://www.hempoilshop.nl/" target="_blank">Hemp Oil Shop</a><br />
<br />
<br />Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-48813529646717256032016-09-05T17:12:00.001-07:002016-09-05T17:12:22.597-07:00Boy on His Deathbed is Cured with Cannabis<div class="post_author_plugin">
<span class="post_author_author">by <a href="http://ireadculture.com/author/190-2-2/" title="More about Sheryll Alexander ">Sheryll Alexander</a> | </span><span class="post_author_create">May 5, 2016</span></div>
<img alt="1455762186682" class="aligncenter size-full wp-image-74799" height="1200" src="http://ireadculture.com/wp-content/uploads/2016/05/1455762186682.jpg" width="900" /><br />
<span class="kp-dropcap radius">I</span>n a last ditch effort to save
his life, 17-year-old Alexander “AJ” Kephart’s dedicated parents,
Sheila and Chris, decided to try out cannabis oil on their dying son
with miraculous results. Here’s one American family’s painful,
inspirational, devastating and heroic medical cannabis cures-cancer
story.<br />
AJ’s super supportive father, Chris, admits his son’s story is
complicated–even doctors have a hard time understanding everything he is
now “missing” and how he’s been put back together (with titanium,
prosthetics and even a “cage” around his back after having three
vertebrae removed).<br />
It all started in August 2012 when AJ noticed a persistent pain in
his knee. In January 2013, he was diagnosed as having bone cancer. Later
it was found that he also had stage four lung carcinoma as well.<br />
That’s when AJ started chemotherapy. In May of the same year, his
entire knee was removed along with some bone in his thigh and calf. At
this point, doctors also found six tumors on all four of his lung
chambers. To keep his lungs from collapsing, AJ was kept in the hospital
for months hooked up to a breathing apparatus.<br />
AJ was healing up when the cancer returned in 2014. He had his first
three vertebrae removed, his top two ribs and sections of his back
removed. The surgery itself even had to be stopped halfway as AJ was
losing the use of his nerves. He ended up having to wear a cage around
his body until the surgery could be completed a week or so later.<br />
Just a few months after the spine surgery, AJ’s oncologist, Dr. Susan
Storch, informed Sheila and Chris that his left lung lobe was covered
with 20 plus cancerous tumors. They started chemo. Again.<br />
<img alt="Aj" class="aligncenter size-full wp-image-74800" height="1200" src="http://ireadculture.com/wp-content/uploads/2016/05/Aj.jpg" width="900" /><br />
That’s when they got the news: It’s time to “get your son’s things in
order,” said the doctors. They gave AJ only a month more to live.<br />
In complete desperation, Sheila and Chris asked their doctor about
medical cannabis and its cancer-fighting effects. Dr. Storch agreed
cannabis oil would be a good “alternative” medicine to pursue along with
another series of chemotherapy sessions. She recommended cannabis
pioneer Dr. Bonni Goldstein.<br />
In her Lawndale, California office, Dr. Goldstein explained how
cannabinoids–especially CBD–work by telling cancer cells to commit
suicide plus it stops the formation of new capillaries, which cancer
cells need to grow and spread. But even Dr. Goldstein had to admit AJ’s
case was going to be experimental as she has never before treated a
child with this particular cancer.<br />
On the way home to Simi Valley, the Kepharts made a stop in Beverly
Hills to Tracy Ryan’s then new cannabis clinical built specifically for
children, CannaKids. “When we met AJ, he was super frail and was wearing
a neck brace. He was taking handfuls of pain medications daily. His
Mother Sheila was terrified and she looked like her soul had been ripped
out,” remembers Ryan, whose daughter Sophie was healed of a brain tumor
via cannabis oil.<br />
In fact, AJ was in excruciating pain. His father Chris says AJ was
taking two of the following each day for pain: OxyContin, Norco, Tylenol
and Motrin. Without the pain killers, AJ would scream and cry in
horrendous pain whenever he was awake.<br />
After five days on CBD and THC oils by CannaKids, Chris says AJ’s
pain has decreased so much that he was down to taking only one OxyContin
daily. “Wow,” he exclaimed when remembering this stress-relieving
moment for the whole family.<br />
Because AJ had nothing to lose, his loving parents decided to speed
up the dosage process. Dr. Goldstein had recommended a three-month
process to increase the dosage, but Chris decided to fly at warp speed.<br />
In two weeks, AJ was up to the highest dosage, but he was also tired
all the time and felt loopy. “No, son,” father Chris said to AJ, “you
are just stoned out of your mind.” Chris admits that this was a sad, but
comical moment for father and son.<br />
Two months later, the Kepharts visited their oncologist who was
shocked that AJ looked much better and stronger. She also discovered his
white blood cell counts showed lots of improvement. Four months later, a
scan showed the multiple tumors on AJ’s lungs were completely gone.<br />
Chris says Dr. Storch told them something like: “I can’t explain it.
There’s no reason for it. But your scan came back totally clear. There’s
no cancer. There’s no tumors in his lungs. It’s all gone.”<br />
Since then, every scan has shown there’s no longer any cancer. “I believe cannabis is keeping him alive,” says Chris.<br />
Very unfortunately, high dosage medical grade cannabis oil is
expensive and costs the Kepharts almost $2,000 a month to keep AJ cancer
and pain free. The stress this financial burden has put on the family
has even affected AJ’s mental health.<br />
“He was freaking out about everything,” says Chris, who made sure to
provide AJ with a psychotherapist and as relaxing an environment as he
can provide given the extreme circumstances.<br />
Today, AJ is still cancer free. He has completely stopped
chemotherapy after having more complications. He and his family are
seeking less expensive ways to get high-grade cannabis oils, but they
have yet to find a more affordable answer before this health crisis
literally puts the family in bankruptcy.<br />
AJ’s very brave cancer survival story truly is a medical miracle and
another reason cannabis needs to be legalized and affordable for
everyone who needs it.<br />
<a href="https://www.gofundme.com/ajkephart"><strong><em>www.gofundme.com/ajkephart</em></strong></a><br />
<br />
<strong><em>http://ireadculture.com/boy-on-his-deathbed-is-cured-with-cannabis/</em></strong><br />
<br />
<strong><em>normally we do not post testimonials, but this one was especially touching </em></strong>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-44283894816707660322016-08-23T20:41:00.002-07:002016-08-23T20:41:36.831-07:00New July 2016 Granny's Storm Crow List<pre wrap="">To: stormcrow <a class="moz-txt-link-rfc2396E" href="mailto:stormcrow@greenpassion.org"><stormcrow greenpassion.org=""></stormcrow></a>
I've put the List on the cloud! Click the link to download the new
2016 Granny Storm Crow's List!
<a class="moz-txt-link-freetext" href="https://1drv.ms/b/s%21AkiTiWAuHrKLbx7-n63PHKx_T9I">https://1drv.ms/b/s!AkiTiWAuHrKLbx7-n63PHKx_T9I</a>
Just opening the link will show you the List, but you will need to
download it to access the very useful Navigation Index. Click the
"Bookmark" icon if it doesn't automatically show up. No more scrolling
"forever" to get to that study you want! It may take a minute or so
to download- it's over 3,300 pages!
The first section of the List is over 475 pages of links to news
articles, so you won't need a PhD to use the List. Reading a news
article about something first, really makes understanding the actual
medical study much easier!
The second section is devoted to the more recent medical studies and
articles from 2010 to the beginning of August 2016. For people
seriously looking into cannabis and the cannabinoids, this will likely
be the most useful section for a lot of you.
Further down are the older studies that go into detail about some of
the basic questions (how long to hold a hit, storage of cannabis,
effects on hormone levels, etc). The older studies also tend to be
easier to understand, so they are a good place to begin your
education.
At the very bottom is a small mini-dictionary of words you will run
across in the studies. You might even want to print up a copy of it just
as a handy reference until you get used to all of the "Sci-speak"!
And take your Omega 3! It is needed to properly make the CB receptors
that the cannabinoids (like THC and CBD) activate to get you "high",
and also, more importantly, heal you. You want lots of working CB
receptors, and not just for the better "high" that daily use of Omega
3 can bring after a month or two!
And one last thank you to "Old Hippie" (of the "Beyond Chronic" blog)
for his invaluable technical help in getting this List out to all of
you! "Nugs and Hugs" to you, my friend!
I hope you enjoy my List,
Granny</pre>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-84064705011868552172016-08-01T18:24:00.002-07:002016-08-01T18:25:44.906-07:00Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis.<div class="cit">
<span role="menubar">http://www.ncbi.nlm.nih.gov/pubmed/26517407 </span></div>
<div class="cit">
</div>
<div class="cit">
<span role="menubar"><a href="http://www.ncbi.nlm.nih.gov/pubmed/26517407#" role="menuitem" title="European journal of pain (London, England).">Eur J Pain.</a></span> 2016 Jul;20(6):936-48. doi: 10.1002/ejp.818. Epub 2015 Oct 30.</div>
<h1>
</h1>
<div class="auths">
<a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Hammell%20DC%5BAuthor%5D&cauthor=true&cauthor_uid=26517407">Hammell DC</a><sup>1</sup>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Zhang%20LP%5BAuthor%5D&cauthor=true&cauthor_uid=26517407">Zhang LP</a><sup>2</sup>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Ma%20F%5BAuthor%5D&cauthor=true&cauthor_uid=26517407">Ma F</a><sup>2</sup>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Abshire%20SM%5BAuthor%5D&cauthor=true&cauthor_uid=26517407">Abshire SM</a><sup>2</sup>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=McIlwrath%20SL%5BAuthor%5D&cauthor=true&cauthor_uid=26517407">McIlwrath SL</a><sup>2</sup>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Stinchcomb%20AL%5BAuthor%5D&cauthor=true&cauthor_uid=26517407">Stinchcomb AL</a><sup>1</sup>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Westlund%20KN%5BAuthor%5D&cauthor=true&cauthor_uid=26517407">Westlund KN</a><sup>2</sup>.</div>
<div class="afflist">
<h3>
<a class="jig-ncbitoggler ui-widget ui-ncbitoggler" href="http://www.ncbi.nlm.nih.gov/pubmed/26517407#" id="ui-ncbitoggler-2" role="button" title="Open/close author information list"><span class="ui-ncbitoggler-master-text">Author information</span><span class="ui-icon ui-icon-triangle-1-e"></span></a></h3>
</div>
<div class="abstr">
<h3>
Abstract</h3>
<div class="">
<h4>
BACKGROUND: </h4>
Current
arthritis treatments often have side-effects attributable to active
compounds as well as route of administration. Cannabidiol (CBD)
attenuates inflammation and pain without side-effects, but CBD is
hydrophobic and has poor oral bioavailability. Topical drug application
avoids gastrointestinal administration, first pass metabolism, providing
more constant plasma levels.<br />
<h4>
METHODS: </h4>
This
study examined efficacy of transdermal CBD for reduction in
inflammation and pain, assessing any adverse effects in a rat complete
Freund's adjuvant-induced monoarthritic knee joint model. CBD gels (0.6,
3.1, 6.2 or 62.3 mg/day) were applied for 4 consecutive days after
arthritis induction. Joint circumference and immune cell invasion in
histological sections were measured to indicate level of inflammation.
Paw withdrawal latency (PWL) in response to noxious heat stimulation
determined nociceptive sensitization, and exploratory behaviour
ascertained animal's activity level.<br />
<h4>
RESULTS: </h4>
<b><i>Measurement
of plasma CBD concentration provided by transdermal absorption revealed
linearity with 0.6-6.2 mg/day doses. Transdermal CBD gel significantly
reduced joint swelling, limb posture scores as a rating of spontaneous
pain, immune cell infiltration and thickening of the synovial membrane
in a dose-dependent manner. PWL recovered to near baseline level.
Immunohistochemical analysis of spinal cord (CGRP, OX42) and dorsal root
ganglia (TNFα) revealed dose-dependent reductions of pro-inflammatory
biomarkers. Results showed 6.2 and 62 mg/day were effective doses.
Exploratory behaviour was not altered by CBD indicating limited effect
on higher brain function.</i></b><br />
<h4>
CONCLUSIONS: </h4>
<i><b>These
data indicate that topical CBD application has therapeutic potential
for relief of arthritis pain-related behaviours and inflammation without
evident side-effects.</b></i><br />
<i><b>© 2015 European Pain Federation - EFIC®</b></i></div>
</div>
<div class="resc">
<dl class="rprtid">
<dt>PMID:</dt>
<dd><a href="http://www.ncbi.nlm.nih.gov/pubmed/26517407">26517407</a></dd>
<dt>PMCID:</dt>
<dd><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851925/">PMC4851925</a></dd>
<dt>DOI:</dt>
<dd><a href="http://dx.doi.org/10.1002/ejp.818">10.1002/ejp.818</a></dd></dl>
</div>
<div class="resc status">
<dl class="rprtid"><dd>[PubMed - in process] </dd></dl>
<a class="status_icon" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851925/">Free PMC Article</a></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-72039932764136576182016-07-25T11:47:00.000-07:002016-07-25T11:48:47.302-07:00Anticancer mechanisms of cannabinoids.http://www.ncbi.nlm.nih.gov/pubmed/27022311<br />
<br />
<div class="cit">
<span role="menubar"><a href="http://www.ncbi.nlm.nih.gov/pubmed/27022311#" role="menuitem" title="Current oncology (Toronto, Ont.).">Curr Oncol.</a></span> 2016 Mar;23(2):S23-32. doi: 10.3747/co.23.3080. Epub 2016 Mar 16.</div>
<h1>
</h1>
<div class="auths">
<a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Velasco%20G%5BAuthor%5D&cauthor=true&cauthor_uid=27022311">Velasco G</a><sup>1</sup>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=S%C3%A1nchez%20C%5BAuthor%5D&cauthor=true&cauthor_uid=27022311">Sánchez C</a><sup>2</sup>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Guzm%C3%A1n%20M%5BAuthor%5D&cauthor=true&cauthor_uid=27022311">Guzmán M</a><sup>3</sup>.</div>
<div class="afflist">
<h3>
<a class="jig-ncbitoggler ui-widget ui-ncbitoggler" href="http://www.ncbi.nlm.nih.gov/pubmed/27022311#" id="ui-ncbitoggler-2" role="button" title="Open/close author information list"><span class="ui-ncbitoggler-master-text">Author information</span><span class="ui-icon ui-icon-triangle-1-e"></span></a></h3>
</div>
<div class="abstr">
<h3>
Abstract</h3>
<div class="">
In
addition to the <b>well-known palliative effects of cannabinoids on some
cancer-associated symptoms, a large body of evidence shows that these
molecules can decrease tumour growth in animal models of cancer. They do
so by modulating key cell signalling pathways involved in the control
of cancer cell proliferation and survival. In addition, cannabinoids
inhibit angiogenesis and decrease metastasis in various tumour types in
laboratory animals.</b> In this review, we discuss the current understanding
of cannabinoids as antitumour agents, focusing on recent discoveries
about their molecular mechanisms of action, including resistance
mechanisms and opportunities for their use in combination therapy. Those
observations have already contributed to the foundation for the
development of the first clinical studies that will analyze the safety
and potential clinical benefit of cannabinoids as anticancer agents. </div>
</div>
<div class="keywords">
<h4>
KEYWORDS: </h4>
Cannabinoids; angiogenesis; apoptosis; autophagy; cell proliferation; cell signalling; combination therapy</div>
<div class="rprt abstract">
<div class="resc">
<dl class="rprtid">
<dt>PMID:</dt>
<dd><a href="http://www.ncbi.nlm.nih.gov/pubmed/27022311">27022311</a></dd>
<dt>PMCID:</dt>
<dd><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791144/">PMC4791144</a></dd>
<dt>DOI:</dt>
<dd><a href="http://dx.doi.org/10.3747/co.23.3080">10.3747/co.23.3080</a></dd></dl>
</div>
</div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-17225622933936764802016-06-29T01:55:00.003-07:002016-06-29T01:55:51.822-07:00Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells<a href="http://www.salk.edu/news-release/cannabinoids-remove-plaque-forming-alzheimers-proteins-from-brain-cells/">http://www.salk.edu/news-release/cannabinoids-remove-plaque-forming-alzheimers-proteins-from-brain-cells/</a><br />
<br />
<time>June 27, 2016</time>
<br />
<h2>
</h2>
<strong>Preliminary lab studies at the Salk Institute find THC reduces beta amyloid proteins in human neurons</strong><br />
LA JOLLA–Salk Institute scientists have found
preliminary evidence that tetrahydrocannabinol (THC) and other compounds
found in marijuana can promote the cellular removal of amyloid beta, a
toxic protein associated with <a href="http://www.salk.edu/science/research/neuroscience-and-neurological-disorders/" target="_blank">Alzheimer’s disease</a>.<br />
While these exploratory studies were conducted in neurons grown in
the laboratory, they may offer insight into the role of inflammation in
Alzheimer’s disease and could provide clues to developing novel
therapeutics for the disorder.<br />
“Although other studies have offered evidence that cannabinoids might
be neuroprotective against the symptoms of Alzheimer’s, we believe our
study is the first to demonstrate that cannabinoids affect both
inflammation and amyloid beta accumulation in nerve cells,” says Salk
Professor <a href="http://www.salk.edu/scientist/dave-schubert/" target="_blank">David Schubert</a>, the senior author of the paper.<br />
Alzheimer’s disease is a progressive brain disorder that leads to
memory loss and can seriously impair a person’s ability to carry out
daily tasks. It affects more than five million Americans according to
the National Institutes of Health, and is a leading cause of death. It
is also the most common cause of dementia and its incidence is expected
to triple during the next 50 years.<br />
It has long been known that amyloid beta accumulates within the nerve
cells of the aging brain well before the appearance of Alzheimer’s
disease symptoms and plaques. Amyloid beta is a major component of the
plaque deposits that are a hallmark of the disease. But the precise role
of amyloid beta and the plaques it forms in the disease process remains
unclear.<br />
<figure class="wp-caption alignright" id="attachment_9225"><img alt="David-Schubert" class="img-responsive wp-image-9225 size-col-md-5" src="http://www.salk.edu/wp-content/uploads/2016/06/David-Schubert-458x305.jpg" /><figcaption class="wp-caption-text">David Schubert, Professor of Salk’s Cellular Neurobiology Laboratory
<a href="http://www.salk.edu/wp-content/uploads/2016/06/David-Schubert.jpg" target="_blank">Click here</a> for a high resolution image<br />
Credit: Salk Institute</figcaption></figure>
In a manuscript published in June 2016’s <em><a href="http://www.nature.com/articles/npjamd201612" target="_blank">Aging and Mechanisms of Disease</a></em>, the Salk team studied nerve cells altered to produce high levels of amyloid beta to mimic aspects of Alzheimer’s disease.<br />
The researchers found that high levels of amyloid beta were
associated with cellular inflammation and higher rates of neuron death.
They demonstrated that exposing the cells to THC reduced amyloid beta
protein levels and eliminated the inflammatory response from the nerve
cells caused by the protein, thereby allowing the nerve cells to
survive.<br />
“Inflammation within the brain is a major component of the damage
associated with Alzheimer’s disease, but it has always been assumed that
this response was coming from immune-like cells in the brain, not the
nerve cells themselves,” says Antonio Currais, a postdoctoral researcher
in Schubert’s laboratory and first author of the paper. “When we were
able to identify the molecular basis of the inflammatory response to
amyloid beta, it became clear that THC-like compounds that the nerve
cells make themselves may be involved in protecting the cells from
dying.”<br />
Brain cells have switches known as receptors that can be activated by
endocannabinoids, a class of lipid molecules made by the body that are
used for intercellular signaling in the brain. The psychoactive effects
of marijuana are caused by THC, a molecule similar in activity to
endocannabinoids that can activate the same receptors. Physical activity
results in the production of endocannabinoids and some studies have
shown that exercise may slow the progression of Alzheimer’s disease.<br />
Schubert emphasized that his team’s findings were conducted in
exploratory laboratory models, and that the use of THC-like compounds as
a therapy would need to be tested in clinical trials.<br />
In separate but related research, his lab found an Alzheimer’s drug
candidate called J147 that also removes amyloid beta from nerve cells
and reduces the inflammatory response in both nerve cells and the brain.
It was the study of J147 that led the scientists to discover that
endocannabinoids are involved in the removal of amyloid beta and the
reduction of inflammation.<br />
Other authors on the paper include Oswald Quehenberger and Aaron Armando at the <a href="https://ucsd.edu/" target="_blank">University of California, San Diego</a>; and Pamela Maher and Daniel Daughtery at the Salk Institute.<br />
The study was supported by the <a href="https://www.nih.gov/" target="_blank">National Institutes of Health</a>, The Burns Foundation and The Bundy Foundation.<br />
<section class="publication-information">
<div class="container">
<div class="row">
<div class="col-sm-12 col-md-10 col-md-offset-1">
<h5 class="category">
PUBLICATION INFORMATION</h5>
<hr />
<div>
<strong>JOURNAL</strong><br />
<div class="-serif">
<em>Aging and Mechanisms of Disease</em></div>
</div>
<div>
<strong>TITLE</strong><br />
<div class="-serif">
<a class="underline" href="http://www.nature.com/articles/npjamd201612" target="_blank"> Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids
</a> </div>
</div>
<div>
<strong>AUTHORS</strong><br />
<div class="-serif">
Antonio Currais, Oswald Quehenberger, Aaron M Armando, Daniel Daugherty, Pam Maher & David Schubert</div>
</div>
</div>
</div>
</div>
</section>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-79468161579341042722016-01-19T16:55:00.005-08:002016-01-19T16:55:55.476-08:00Marijuana helps Alzheimer’s patients, study finds<a href="http://blog.sfgate.com/smellthetruth/2016/01/14/marijuana-helps-alzheimers-patients-study-finds/">http://blog.sfgate.com/smellthetruth/2016/01/14/marijuana-helps-alzheimers-patients-study-finds/</a><br />
<br />
<div class="byline ">
By <a href="http://blog.sfgate.com/smellthetruth/author/sttm6/" rel="author" title="Posts by David Downs">David Downs</a>
<span class="post-date">on January 14, 2016 at 9:34 AM</span>
</div>
<div class="sharedaddy sd-sharing-enabled">
<br /></div>
<div class="wp-caption aligncenter" id="attachment_17371" style="width: 600px;">
<a href="http://blog.sfgate.com/smellthetruth/files/2016/01/Julianne-Moore.jpg"><img alt="Alzheimer's Disease patients benefited from marijuana, Israeli researchers report. Above, Julianne Moore in 2015's 'Still Alice'." class="size-large wp-image-17371" height="316" src="http://blog.sfgate.com/smellthetruth/files/2016/01/Julianne-Moore-600x316.jpg" width="600" /></a><div class="wp-caption-text">
Alzheimer’s
Disease patients benefited from marijuana, Israeli researchers report.
Above, Julianne Moore in 2015’s ‘Still Alice’.</div>
</div>
Adding marijuana to the treatment of Alzheimer’s Disease “is safe
and a promising treatment option”, Israeli researchers conclude, in the
latest study on the burgeoning practice.<br />
Alzheimer’s Disease is a devastating and fatal degenerative
neurological disease affecting more than five million Americans today.
One in three seniors will die with Alzheimer’s or another dementia, and
Alzheimer’s is the sixth leading cause of death in the nation, costing
America about $203 billion in 2013.<br />
Past <a href="https://www.projectcbd.org/alzheimers-disease" target="_blank">studies</a>
indicate the active ingredients in cannabis can provide palliative
relief to Alzheimer’s patients with dementia — calming them down and
allowing them to sleep. Cell studies also indicate cannabis’ active
ingredients could prevent the onset and progression of Alzheimer’s, by
interrupting the cycle of beta-amyloid plaque creation thought to cause
Alzheimer’s Disease.<br />
Researchers at the Abarbanel Mental Health Center and the Sackler
Faculty of Medicine at Tel-Aviv University, in Israel, along with the
Department of Psychology, at Bar-Ilan University conducted one of the
first clinical studies of cannabis on human Alzheimer’s patients.<br />
The main active ingredient in cannabis “tetrahydrocannabinol (THC) is
a potential treatment for Alzheimer’s disease (AD)” researchers wrote.
They wanted to measure the safety and efficacy of giving a medical
cannabis oil containing THC as an add-on to existing Alzheimer’s drugs.
Their goal: relieving the terrifying behavioral and psychological
symptoms of dementia. <br />
Eleven patients were recruited into an open-label, month-long trial.
Ten patients finished the trial, and researchers reported “significant
reduction” in mental illness severity, especially with regard to
delusions, agitation/aggression, irritability, apathy, sleep, and
caregiver distress.<br />
“Adding [medical cannabis oil] to [Alzheimer’s Disease] patients’
pharmacotherapy is safe and a promising treatment option,” researchers
concluded.<br />
Read: “<a href="http://www.ncbi.nlm.nih.gov/pubmed/26757043" target="_blank">Safety
and Efficacy of Medical Cannabis Oil for Behavioral and Psychological
Symptoms of Dementia: An-Open Label, Add-On, Pilot Study</a>”<br />
<em>Smell the Truth</em> editor <em>David Downs is the author of</em> <a href="http://www.usmmj.org/" target="_blank">The Medical Marijuana Guidebook</a><em>, out in paperback this February (Whitman Publishing).</em>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-58499122757368978082015-10-11T14:06:00.004-07:002015-10-11T14:07:51.354-07:00Here's What Marijuana Does to Pain<br />
http://www.attn.com/stories/3515/what-marijuana-does-to-pain<br />
<br />
<h1 class="story__header--title">
Here's What Marijuana Does to Pain</h1>
<div class="mobile-extras">
</div>
For people suffering from <a href="http://www.attn.com/stories/2378/medical-marijuana-anti-gateway-drug" rel="nofollow" target="_blank">chronic pain</a>, treatment options are generally limited. You can take <a href="http://www.attn.com/stories/1578/prescription-painkillers-americans-heroin-problem" rel="nofollow" target="_blank">prescription painkillers</a>
such as Vicodin or Oxycotin, but while they might alleviate your
discomfort, they are also addictive and dangerous. And as the U.S.
continues to struggle with <a href="http://www.attn.com/stories/1895/heroin-addiction-painkiller-problem-america" rel="nofollow" target="_blank">rising rates of opiate addiction</a>, the search is on for a safer alternative. Cannabis appears to be a good candidate.<br />
<h3>
<a href="http://www.attn.com/stories/3038/marijuana-and-sleep?utm_source=onsite&utm_medium=instorylink&utm_campaign=relatedlinks" rel="nofollow" target="_blank">RELATED: What Does Marijuana Do To Your Sleep Patterns?</a></h3>
<div class="separator" style="clear: both; text-align: center;">
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<h3>
</h3>
<br />
A <a href="http://www.sciencedirect.com/science/article/pii/S1526590015008378" rel="nofollow" target="_blank">new study</a>
published in the Journal of Pain found that chronic pain patients who
used marijuana for one year had reduced discomfort, improved quality of
life, and experienced no increased risk of serious side effects. McGill
University researchers analyzed reports from 216 cannabis users and 215
non-users, finding that pot is effective at treating pain.<br />
"[W]e
noted significant improvements in pain intensity and the physical
dimension of quality of life over one year among the cannabis users
compared to controls,"<a href="http://www.sciencedirect.com/science/article/pii/S1526590015008378" rel="nofollow" target="_blank"> the researchers wrote</a>.
"There was also significant improvement among cannabis users in
measures of the sensory component of pain, symptom distress, and total
mood disturbance compared to controls."<br />
<h3>
<a href="http://www.attn.com/stories/2378/medical-marijuana-anti-gateway-drug?utm_source=onsite&utm_medium=instorylink&utm_campaign=relatedlinks" rel="nofollow" target="_blank">RELATED: Marijuana Might Actually be an Anti-Gateway Drug</a></h3>
This
isn't the first study to look at the effects of marijuana on pain. In
2009, the National Association of Boards of Pharmacy announced that
cannabis could help with "multiple pain syndromes," including
neuropathic (burning), mechanical (aching), and inflammatory (acute,
sharp) pain. Not only is the substance an effective analgesic, but it
also carries "minimal physical dependence" with limited drug
interactions, <a href="https://www.nabp.net/events/assets/Carter_Aggarwal.pdf" rel="nofollow" target="_blank">the organization wrote</a>.<br />
What's more, a review of cannabis trials <a href="http://www.ncbi.nlm.nih.gov/pubmed/21426373" rel="nofollow" target="_blank">published in the British Journal of Clinical Pharmacology</a>
concluded that "it is reasonable to consider cannabinoids as a
treatment option for the management of chronic neuropathic pain with
evidence of efficacy in other types of chronic pain such as fibromyalgia
and rheumatoid arthritis as well."<br />
And a 2013 study <a href="http://www.ncbi.nlm.nih.gov/pubmed/22367503" rel="nofollow" target="_blank">published in the Clinical Journal of Pain</a>
found that "cannabinergic pain medicines have been shown to be modestly
effective and safe treatments in patients with a variety of chronic
pain conditions," leading researchers to conclude that incorporating
medical cannabis into pain medicine education "seems warranted and
continuing clinical research and empiric treatment trials are
appropriate."<br />
<img alt="Cannabis Bud" class="Image img__fid__3425 img__view_mode__default attr__format__default attr__data-file-image-alt-text__Cannabis Bud attr__data-file-image-title-text__Cannabis attr__data-media-attribution__ attr__data-media-url__" data-file-image-alt-text="Cannabis Bud" data-file-image-title-text="Cannabis Bud" data-media-attribution="" data-media-url="" src="http://publisher.attn.com/sites/default/files/marijuana%20study.jpg" height="336" title="Cannabis Bud" width="640" /><br />
The
takeaway here is something that might seem obvious to regular marijuana
users: pot is good for pain. But it's not just good, it's safe. Even
over-the-counter medication such as Tylenol <a href="https://www.nlm.nih.gov/medlineplus/ency/article/002598.htm" rel="nofollow" target="_blank">carries risk of overdose</a>
if you take too much, threatening to damage your liver. Cannabis, on
the other hand, has no serious side effects, and numerous studies have
demonstrated that it is similarly effective at treating various types of
pain.<br />
What's remarkable about this potential health benefit is what it could mean in the context of <a href="http://www.attn.com/stories/1895/heroin-addiction-painkiller-problem-america" rel="nofollow" target="_blank">America's heroin epidemic</a>. According to the National Institute on Drug Abuse, abuse of painkillers <a href="http://www.drugabuse.gov/related-topics/trends-statistics/infographics/abuse-prescription-pain-medications-risks-heroin-use" rel="nofollow" target="_blank">directly correlates with the rise of heroin addiction</a>
in the U.S. If a person becomes addicted to prescription pain
medication, there is a strong chance that they could transition to
cheaper, more potent drugs such as heroin.<br />
<h3>
<a href="http://www.attn.com/stories/855/marijuana-depression-research-mental-health?utm_source=onsite&utm_medium=instorylink&utm_campaign=relatedlinks" rel="nofollow" target="_blank">RELATED: Here's What Marijuana Does to Your Stress</a></h3>
But
in states where pain patients have access to medical marijuana, the
rate of fatal drug overdose is reduced, suggesting that pot is something
of an "<a href="http://www.attn.com/stories/2378/medical-marijuana-anti-gateway-drug" rel="nofollow" target="_blank">anti-gateway drug.</a>"
By legalizing marijuana and allowing people to manage their pain with
cannabis, we could effectively stop the cycle and help patients who
might benefit from a safe and non-addictive alternative to pills.<br />
<br />
<br />
<br />
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Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-32569299323259848972015-08-12T12:40:00.004-07:002015-08-12T12:40:38.071-07:00Medical Marijuana States See Painkiller Deaths Drop by 25%<a href="http://archinte.jamanetwork.com/article.aspx?articleid=1898878">http://archinte.jamanetwork.com/article.aspx?articleid=1898878</a><br />
<br />
<h1 class="aTitle">
<span id="scm6MainContent_lblArticleTitle">Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010</span>
</h1>
<div class="authorSection sans" id="scm6MainContent_dvAuthorSection">
<span class="authorNames" id="scm6MainContent_lblAuthors">Marcus A. Bachhuber, MD<sup id="scm6MainContent_rptAuthors_supAuthorAffiliations_0">1,2,3</sup>; Brendan Saloner, PhD<sup id="scm6MainContent_rptAuthors_supAuthorAffiliations_1">3,4</sup>; Chinazo O. Cunningham, MD, MS<sup id="scm6MainContent_rptAuthors_supAuthorAffiliations_2">5</sup>; Colleen L. Barry, PhD, MPP<sup id="scm6MainContent_rptAuthors_supAuthorAffiliations_3">3,6</sup></span>
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<span id="scm6MainContent_lblClientName"><i>JAMA Intern Med. </i>2014;174(10):1668-1673. doi:10.1001/jamainternmed.2014.4005. </span>
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<span class="Abstract 0" id="scm6MainContent_ucArticleContent_rptSections_lblSection_0"><strong>Importance</strong>
<span>Opioid analgesic overdose mortality continues to rise in the
United States, driven by increases in prescribing for chronic pain.
Because chronic pain is a major indication for medical cannabis, laws
that establish access to medical cannabis may change overdose mortality
related to opioid analgesics in states that have enacted them.</span><br />
<strong>Objective</strong>
<span>To determine the association between the presence of state medical cannabis laws and opioid analgesic overdose mortality.</span><br />
<strong>Design, Setting, and Participants</strong>
<span>A time-series analysis was conducted of medical cannabis laws
and state-level death certificate data in the United States from 1999 to
2010; all 50 states were included.</span><br />
<strong>Exposures</strong>
<span>Presence of a law establishing a medical cannabis program in the state.</span><br />
<strong>Main Outcomes and Measures</strong>
<span>Age-adjusted opioid analgesic overdose death rate per 100 000
population in each state. Regression models were developed including
state and year fixed effects, the presence of 3 different policies
regarding opioid analgesics, and the state-specific unemployment rate.</span><br />
<strong>Results</strong>
<span>Three states (California, Oregon, and Washington) had medical
cannabis laws effective prior to 1999. Ten states (Alaska, Colorado,
Hawaii, Maine, Michigan, Montana, Nevada, New Mexico, Rhode Island, and
Vermont) enacted medical cannabis laws between 1999 and 2010. States
with medical cannabis laws had a 24.8% lower mean annual opioid overdose
mortality rate (95% CI, −37.5% to −9.5%; <i>P</i> = .003) compared with
states without medical cannabis laws. Examination of the association
between medical cannabis laws and opioid analgesic overdose mortality in
each year after implementation of the law showed that such laws were
associated with a lower rate of overdose mortality that generally
strengthened over time: year 1 (−19.9%; 95% CI, −30.6% to −7.7%; <i>P</i> = .002), year 2 (−25.2%; 95% CI, −40.6% to −5.9%; <i>P</i> = .01), year 3 (−23.6%; 95% CI, −41.1% to −1.0%; <i>P</i> = .04), year 4 (−20.2%; 95% CI, −33.6% to −4.0%; <i>P</i> = .02), year 5 (−33.7%; 95% CI, −50.9% to −10.4%; <i>P</i> = .008), and year 6 (−33.3%; 95% CI, −44.7% to −19.6%; <i>P</i> < .001). In secondary analyses, the findings remained similar.</span><br />
<span style="font-size: large;"><strong>Conclusions and Relevance
<span>Medical cannabis laws are associated with significantly lower
state-level opioid overdose mortality rates. Further investigation is
required to determine how medical cannabis laws may interact with
policies aimed at preventing opioid analgesic overdose.</span></strong></span></span>
</div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-53949504253307383492015-07-22T03:36:00.001-07:002015-07-22T03:37:38.746-07:00Exploiting Cannabinoid-Induced Cytotoxic Autophagy to Drive Melanoma Cell Death<div id="aug">
TL;DR <b>THC is effective and shows promise in causing melanoma cancer cell death, in addition 1:1 ration of THC:CBD seems to be equally effective.</b><br />
<br />
Jane L Armstrong<sup><a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff1" title="affiliated with 1">1</a>,<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff2" title="affiliated with 2">2</a></sup>, David S Hill<sup><a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff1" title="affiliated with 1">1</a></sup>, Christopher S McKee<sup><a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff1" title="affiliated with 1">1</a></sup>, Sonia Hernandez-Tiedra<sup><a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff3" title="affiliated with 3">3</a></sup>, Mar Lorente<sup><a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff3" title="affiliated with 3">3</a></sup>, Israel Lopez-Valero<sup><a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff3" title="affiliated with 3">3</a>,<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff4" title="affiliated with 4">4</a></sup>, Maria Eleni Anagnostou<sup><a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff1" title="affiliated with 1">1</a></sup>, Fiyinfoluwa Babatunde<sup><a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff1" title="affiliated with 1">1</a></sup>, Marco Corazzari<sup><a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff5" title="affiliated with 5">5</a></sup>, Christopher P F Redfern<sup><a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff6" title="affiliated with 6">6</a></sup>, Guillermo Velasco<sup><a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff3" title="affiliated with 3">3</a>,<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff4" title="affiliated with 4">4</a>,<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#note1" title="author note">7</a></sup> and Penny E Lovat<sup><a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#aff1" title="affiliated with 1">1</a>,<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#note1" title="author note">7</a></sup></div>
<div id="affiliations-notes">
<ol>
<li id="aff1"><sup>1</sup>Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK</li>
<li id="aff2"><sup>2</sup>Faculty of Applied Sciences, University of Sunderland, Sunderland, UK</li>
<li id="aff3"><sup>3</sup>Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain</li>
<li id="aff4"><sup>4</sup>Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain</li>
<li id="aff5"><sup>5</sup>Department of Biology, University of Rome “Tor Vergata”, Rome, Italy</li>
<li id="aff6"><sup>6</sup>Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK</li>
</ol>
<div class="caff">
Correspondence:
Penny E. Lovat, Dermatological Sciences, Institute of Cellular
Medicine, The Medical School, Newcastle University, Framlington Place,
Newcastle-upon-Tyne NE2 4HH, UK. E mail: <a href="mailto:penny.lovat@ncl.ac.uk">penny.lovat@ncl.ac.uk</a></div>
<div class="aunote">
<sup id="note1">7</sup>These are joint senior authors.</div>
<div class="prdates">
Received 5 November 2014; Revised 9 January 2015; Accepted 21 January 2015<br />
Accepted article preview online 10 February 2015; Advance online publication 12 March 2015</div>
</div>
<div id="abs">
<a class="backtotop" href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#top">Top<span class="hidden"> of page</span></a><br />
<h3>
Abstract</h3>
<div class="abs lead">
<b>Although
the global incidence of cutaneous melanoma is increasing, survival
rates for patients with metastatic disease remain <10 class="mb" span="">%<!--10--></10></b></div>
</div>
. Novel treatment strategies are therefore urgently required, particularly for patients bearing BRAF<span class="mb">/</span>NRAS
wild-type tumors. Targeting autophagy is a means to promote cancer cell
death in chemotherapy-resistant tumors, and the aim of this study was
to test the hypothesis that cannabinoids promote autophagy-dependent
apoptosis in melanoma. Treatment with Δ<sup>9</sup>-Tetrahydrocannabinol
(THC) resulted in the activation of autophagy, loss of cell viability,
and activation of apoptosis, whereas cotreatment with chloroquine or
knockdown of Atg7, but not Beclin-1 or Ambra1, prevented THC-induced
autophagy and cell death <i>in vitro</i>. Administration of Sativex-like
(a laboratory preparation comprising equal amounts of THC and
cannabidiol (CBD)) to mice bearing BRAF wild-type melanoma xenografts
substantially inhibited melanoma viability, proliferation, and tumor
growth paralleled by an increase in autophagy and apoptosis compared
with standard single-agent temozolomide. Collectively, our findings
suggest that THC activates noncanonical autophagy-mediated apoptosis of
melanoma cells, suggesting that cytotoxic autophagy induction with
Sativex warrants clinical evaluation for metastatic disease.<br />
<div class="keyw-abbr">
<h4 class="abbreviations">
Abbreviations: </h4>
<div class="abbreviations">
ANOVA,
analysis of variance; BDS, botanical drug substance; CBD, cannabidiol;
ER, endoplasmic reticulum; siRNA, small interfering RNA; THC, Δ<sup>9</sup>-Tetrahydrocannabinol</div>
</div>
<div id="Introduction">
<a class="backtotop" href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#top">Top<span class="hidden"> of page</span></a><br />
<h3>
Introduction</h3>
<div class="norm">
Cutaneous
melanoma incidence continues to increase, and response rates of
patients with metastatic melanoma to current therapy remain poor (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib13">Garbe <i>et al.</i>, 2011</a>). Identification of driver mutations and development of targeted therapies to BRAF<span class="mb">/</span>MEK have revolutionized melanoma therapy, although clinical resistance is inevitable (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib7">Chen and Davies, 2014</a>). The emergence of immunotherapies that are able to promote tumor T-cell responses is further changing melanoma management (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib40">Wolchok <i>et al.</i>, 2010</a>); however, not all patients respond (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib25">Prieto <i>et al.</i>, 2012</a>).
<b>It is therefore clear that there is no consistently beneficial
treatment for metastatic melanoma and alternative approaches should be
explored.</b></div>
<div class="norm">
<b>Autophagy (macroautophagy) is the principal
lysosomal-mediated mechanism for the degradation of damaged or
long-lived organelles and proteins</b>. Under physiological conditions,
autophagy maintains normal turnover of cellular components, as well as
responding to metabolic stress, whereas in pathological settings
autophagy activation mediates defense against extracellular insults and
pathogens (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib8">Choi <i>et al.</i>, 2013</a>).
The current model for the role of autophagy in cancer is that in the
early stages of tumor development, quality control by autophagy inhibits
tumorigenesis, whereas in advanced cancer autophagy provides energy to
meet the increased demands and a means to resist cell death caused by
cytotoxic therapy (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib39">White, 2012</a>).
Preclinical data suggest that lysosomal inhibition can cause tumor
regression, and the lysosome inhibitors chloroquine or
hydroxychloroquine are now being evaluated in clinical trials either
alone or in combination with chemotherapy (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib41">Yang <i>et al.</i>, 2011</a>). However, recent studies suggest that chloroquine<span class="mb">/</span>hydroxychloroquine treatment may promote tumor development (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib23">Michaud <i>et al.</i>, 2011</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib21">Maycotte <i>et al.</i>, 2012</a>),
questioning the benefit of autophagy inhibition. An alternative
approach for autophagy modulation is via exacerbation; although
initially this appears counterintuitive to treat advanced cancer, recent
evidence suggests that in particular circumstances a consequence of
autophagy activation is cell death (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib10">Ding <i>et al.</i>, 2007</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib31">Scarlatti <i>et al.</i>, 2008</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib36">Tomic <i>et al.</i>, 2011</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib4">Basit <i>et al.</i>, 2013</a>).
<b>Therapeutic exploitation of cytotoxic autophagy to drive cancer cell
death is therefore an emerging concept for the development of novel
cancer treatments.</b></div>
<div class="norm">
Cannabinoids are a diverse class of compounds derived from <i>Cannabis sativa</i>, with Δ<sup>9</sup>-tetrahydrocannabinol (THC) the most relevant owing to its high potency and abundance (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib24">Pertwee, 2008</a>).
THC exerts its biological effects by mimicking endocannabinoids that
bind to and activate two G protein–coupled cannabinoid receptors: CB1
and CB2 (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib17">Howlett <i>et al.</i>, 2002</a>). CB1<span class="mb">/</span>CB2 receptors are expressed in many cancer cell types (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib38">Velasco <i>et al.</i>, 2012</a>),
and cannabinoids are currently being investigated as anticancer agents,
including glioblastoma for which THC has shown considerable promise (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib38">Velasco <i>et al.</i>, 2012</a>)<b>.
Preclinical data demonstrate that THC exerts its antitumoral action via
induction of endoplasmic reticulum (ER) stress, upregulation of the
transcriptional coactivator p8 and the pseudo-kinase tribbles homolog 3
(TRIB3), the stimulation of autophagy, and execution of apoptosis (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib6">Carracedo <i>et al.</i>, 2006</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib28">Salazar <i>et al.</i>, 2009a</a>, <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib29">b</a>).</b>
Blockade of autophagy prevents THC-induced apoptosis and cell death,
indicating that autophagy is upstream of apoptosis and demonstrating the
potential of p8<span class="mb">/</span>TRIB3-mediated autophagy as a cytotoxic pathway.</div>
<div class="norm">
Alongside
genetic changes, adaption to ER stress and the aberrant control of
autophagy have emerged as key drivers of malignancy and therapy
resistance in advanced melanoma (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib1">Armstrong <i>et al.</i>, 2011</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib9">Corazzari <i>et al.</i>, 2013</a>). The cannabinoid receptors have previously been identified as potential therapeutic targets (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib5">Blazquez <i>et al.</i>, 2006</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib6">Carracedo <i>et al.</i>, 2006</a>);
hence, targeting ER stress responses combined with cytotoxic autophagy
using cannabinoids may represent a valuable therapeutic approach for
metastatic melanoma. <b>The aim of this study was to determine whether THC
activates cytotoxic autophagy in melanoma cells <i>in vitro</i> and <i>in vivo</i>.
Our data suggest a noncanonical mechanism of autophagy-mediated
apoptosis, highlighting the potential to harness autophagy for
therapeutic benefit in advanced melanoma.</b></div>
</div>
<div id="Results">
<a class="backtotop" href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#top">Top<span class="hidden"> of page</span></a><br />
<h3>
Results</h3>
<h4 class="norm">
THC activates autophagy and apoptosis in melanoma cells</h4>
<div class="follows-h4">
Characteristic
features of early and late stages of autophagy were assessed using LC3
lipidation (LC3-II) and analysis of autophagic flux using chloroquine
and visualization of tandem mRFP–GFP (monomeric red fluorescent
protein–green fluorescent protein)–tagged LC3 (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib19">Kimura <i>et al.</i>, 2007</a>),
respectively. LC3-II induction was observed in three human melanoma
cell lines in response to THC, and LC3-II accumulated further in the
presence of chloroquine in both BRAF wild-type (CHL-1) and mutated (A375
and SK-MEL-28) melanoma cells. In addition, increased numbers of
LC3-positive autophagosomes (yellow puncta) and autolysosomes (red
puncta) and total red fluorescence (CHL-1: <i>t</i><sub>43</sub><span class="mb">=</span>4.17, <i>P</i><0 .001="" a375:="" i="">t<!--0--></0></div>
</div>
<sub>42</sub><span class="mb">=</span>3.289, <i>P</i><span class="mb">=</span>0.002) were observed in A375 and CHL-1 cells in response to THC treatment, indicating activation of autophagic flux (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig1">Figure 1</a>).
<span class="cleardiv"></span>
<br />
<div class="figure-table" id="fig1">
<h5 class="norm">
<a href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f1.html#figure-title">Figure 1.</a></h5>
<a href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f1.html#figure-title"><img alt="Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author" class="thumb" src="http://www.nature.com/jid/journal/v135/n6/thumbs/jid201545f1th.jpg" /></a><b>The Δ<sup>9</sup>-Tetrahydrocannabinol (THC) induces autophagy in melanoma cells.</b> (<b>a</b>–<b>c</b>) A375, SK-MEL-28, and CHL-1 cells were treated with vehicle or THC (4.5 or 5<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) for 24<span class="mb"><span class="mb"> </span></span>hours in the presence or absence of chloroquine (CQ; 10<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) for the final 2<span class="mb"><span class="mb"> </span></span>hours,
and LC3 and β-actin expression was determined by western blotting.
LC3-II expression was quantified and band intensity normalized to
β-actin. Data are expressed as fold change relative to the mean LC3-II<span class="mb">/</span>β-actin value for a representative experiment and are shown above the western blot (representative data from <i>n</i><span class="mb">=</span>3 independent experiments). (<b>d</b>, <b>e</b>) mRFP–GFP–LC3 expressing (<b>d</b>) A375 or (<b>e</b>) CHL-1 cells were treated with vehicle or THC (4.5<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) for 18<span class="mb"><span class="mb"> </span></span>hours. Data are representative fluorescent micrographs (bar<span class="mb">=</span>20<span class="mb"><span class="mb"> </span></span>μm) of three independent experiments. (<b>f</b>)
Total red fluorescence values were generated from ≥20 cells per
treatment condition, from two independent experiments. Pixel intensities
were divided by a factor of 10<sup>6</sup>, and data are shown as mean±SD (<span class="mb">*</span><span class="mb">*</span><i>P</i><0 .01="" and="" class="mb" span="">*<!--0--></0></div>
<span class="mb">*</span><span class="mb">*</span><i>P</i><0 .001="" cell="" control="" each="" fluorescent="" for="" green="" line="" monomeric="" mrfp="" p="" protein.="" protein="" red="" vs.=""><a class="full" href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f1.html#figure-title">Full figure and legend (165<abbr title="Kilobyte">K</abbr>)</a><a class="ppt" href="http://www.nature.com/jid/journal/v135/n6/slides/jid201545-pf1.ppt">Download Power<span class="hidden"> </span>Point slide (290 <abbr title="Kilobyte">KB</abbr>)</a><!--0--></0><br />
<div class="norm">
<b>THC
reduced melanoma cell viability in a dose-dependent manner while having
little effect on primary melanocytes at doses up to 6<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span> THC (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig2">Figure 2a</a>).</b>
Cotreatment of melanoma cells with submaximal concentrations of THC and
the pan-caspase inhibitor ZVAD-fmk significantly increased cell
viability compared with treatment with THC alone (CHL-1: <i>t</i><sub>22</sub><span class="mb">=</span>3.962, <i>P</i><span class="mb">=</span>0.0007; A375: <i>t</i><sub>16</sub><span class="mb">=</span>3.74, <i>P</i><span class="mb">=</span>0.0018; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig2">Figure 2b</a>), suggesting that cell death is caspase dependent. In addition, the cytochrome <i>c–</i>labeled structures present in vehicle-treated cells were substantially reduced in THC-treated cells (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig2">Figure 2c</a>), indicating apoptosis activation.</div>
<div class="figure-table" id="fig2">
<h5 class="norm">
<a href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f2.html#figure-title">Figure 2.</a></h5>
<a href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f2.html#figure-title"><img alt="Figure 2 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author" class="thumb" src="http://www.nature.com/jid/journal/v135/n6/thumbs/jid201545f2th.jpg" /></a><b>The Δ<sup>9</sup>-Tetrahydrocannabinol (THC) induces apoptosis of melanoma cells.</b> (<b>a</b>) Primary melanocytes, A375, and CHL-1 cells were treated with vehicle or THC (3–10<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) for 24<span class="mb"><span class="mb"> </span></span>hours. (<b>b</b>) A375 (i) or CHL-1 (ii) cells were treated with vehicle or THC (5<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) in the presence or absence of ZVAD (20<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) for 24<span class="mb"><span class="mb"> </span></span>hours.
Cell viability was determined by the
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
assay. Data generated in triplicate were expressed relative to the mean
of vehicle-treated cells in each experiment, for three independent
experiments, and shown as mean±SD (<i>t</i>-test; <span class="mb">*</span><span class="mb">*</span><i>P</i><0 .01="" and="" class="mb" span="">*<!--0--></0></div>
<span class="mb">*</span><span class="mb">*</span><i>P</i><0 .001="" class="mb" span="" thc="" vs.="">+<!--0-->ZVAD). (<b>c</b>) A375 cells were treated with THC (5<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) for 24<span class="mb"><span class="mb"> </span></span>hours. Data are representative fluorescent micrographs of cytochrome <i>c</i> immunostaining (bar<span class="mb">=</span>20<span class="mb"><span class="mb"> </span></span>μm) of three independent experiments.<a class="full" href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f2.html#figure-title">Full figure and legend (143<abbr title="Kilobyte">K</abbr>)</a><a class="ppt" href="http://www.nature.com/jid/journal/v135/n6/slides/jid201545-pf2.ppt">Download Power<span class="hidden"> </span>Point slide (266 <abbr title="Kilobyte">KB</abbr>)</a></0><br />
<h4 class="norm">
THC-induced apoptosis is dependent on autophagy</h4>
<div class="follows-h4">
In glioma, THC activates apoptosis via a mechanism involving TRIB3 and Beclin-1-dependent autophagy (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib6">Carracedo <i>et al.</i>, 2006</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib29">Salazar <i>et al.</i>, 2009b</a>).
The small interfering RNA (siRNA)-mediated knockdown of TRIB3
significantly prevented loss of cell viability in response to THC in
A375 cells (one-way analysis of variance (ANOVA); F<sub>5, 48</sub><span class="mb">=</span>5.053, <i>P</i><span class="mb">=</span>0.001; THC compared with vehicle treatment in siCtrl cells; Tukey’s <i>P</i><0 .05="" a="" href="http://www.nature.com/jid/journal/v135/n6/suppinfo/jid201545s1.html">Supplementary Figure S1<!--0--></0></div>
online), demonstrating that TRIB3 mediates THC-induced cell death.
Furthermore, siRNA-mediated knockdown of Atg7 prevented THC-induced
accumulation of LC3-II in the presence of chloroquine (one-way ANOVA; F<sub>11, 24</sub><span class="mb">=</span>6.878, <i>P</i><0 .001="" chloroquine="" class="mb" compared="" span="" with="">+<!--0-->THC-treated siCtrl cells contrast <i>P</i><0 .05="" a="" href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig3">Figure 3a and b<!--0-->). THC-induced caspase 3 cleavage was also inhibited by Atg7 knockdown in A375 (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig3">Figure 3a</a>), as well as in CHL-1 and SK-MEL-28 cells (CHL-1: one-way ANOVA; F<sub>5, 12</sub><span class="mb">=</span>6.57, <i>P</i><span class="mb">=</span>0.004; THC compared with vehicle-treated siCtrl cells; Tukey’s <i>P</i><0 .05="" anova="" f="" one-way="" sk-mel-28:="" sub="">3, 8<!--0--><span class="mb">=</span>4.646, <i>P</i><span class="mb">=</span>0.037; THC compared with vehicle-treated siCtrl cells; Tukey’s <i>P</i><0 .05="" a="" href="http://www.nature.com/jid/journal/v135/n6/suppinfo/jid201545s1.html">Supplementary Figure S2<!--0-->
online). <b>In addition, THC treatment resulted in a significant loss of
melanoma cell viability only in the absence of chloroquine or Atg7 siRNA
</b>(<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig3">Figure 3</a> and <a href="http://www.nature.com/jid/journal/v135/n6/suppinfo/jid201545s1.html">Supplementary Figure S2</a> online; <i>post hoc</i> tests, Games–Howell, or Tukey’s <i>P</i><0 .01="" a375="" a="" alone="" and="" atg7="" cell="" cells="" chl-1="" downregulation="" effect="" had="" however="" i="" in="" knockdown="" loss="" no="" of="" on="" resulted="" s="" significant="" sk-mel-28="" ukey="" viability="">P<!--0--><0 .001="" a="" href="http://www.nature.com/jid/journal/v135/n6/suppinfo/jid201545s1.html">Supplementary Figure S2a<!--0-->
online), suggesting that basal autophagy is required to maintain
viability in these cells. Collectively, these data demonstrate that
THC-induced apoptosis of melanoma cells requires TRIB3 and is mediated
by Atg7-dependent autophagy.</0></0></0></0></0></0><br />
<div class="figure-table" id="fig3">
<h5 class="norm">
<a href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f3.html#figure-title">Figure 3.</a></h5>
<a href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f3.html#figure-title"><img alt="Figure 3 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author" class="thumb" src="http://www.nature.com/jid/journal/v135/n6/thumbs/jid201545f3th.jpg" /></a><b>The Δ<sup>9</sup>-Tetrahydrocannabinol (THC)-induced apoptosis requires autophagy.</b> (<b>a</b>–<b>c</b>)
A375 cells were transfected with small interfering RNAs (siRNAs) for
Atg7 (siAtg7) or with a nonsilencing control siRNA (siCtrl) before
treatment with vehicle or THC (4.5, 5<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) for 24<span class="mb"><span class="mb"> </span></span>hours in the presence or absence of chloroquine (CQ; 10<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) for the (<b>a</b>, <b>b</b>) final 2<span class="mb"><span class="mb"> </span></span>hours or for (<b>c</b>) 24<span class="mb"><span class="mb"> </span></span>hours. (<b>a</b>, <b>b</b>)
Atg7, LC3, cleaved caspase 3, and β-actin expression were determined by
western blotting. LC3-II expression was quantified and band intensity
normalized to β-actin. Data are expressed as fold change relative to the
mean LC3-II<span class="mb">/</span>β-actin value for each experiment, for three separate experiments (mean±SD, <i>n</i><span class="mb">=</span>3). (<b>c</b>)
Cell viability was determined by the
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
assay. Data generated in triplicate were expressed relative to the mean
of vehicle-treated siCtrl cells in each experiment, for three
independent experiments, and shown as mean±SD (<span class="mb">*</span><i>P</i><0 .05="" class="mb" span="">*<!--0--></0></div>
<span class="mb">*</span><i>P</i><0 .01="" and="" i=""><span class="mb">*</span><!--0--><span class="mb">*</span><span class="mb">*</span><i>P</i><0 .001="" cells="" p="" sictrl="" vehicle-treated="" vs.=""><a class="full" href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f3.html#figure-title">Full figure and legend (121<abbr title="Kilobyte">K</abbr>)</a><a class="ppt" href="http://www.nature.com/jid/journal/v135/n6/slides/jid201545-pf3.ppt">Download Power<span class="hidden"> </span>Point slide (248 <abbr title="Kilobyte">KB</abbr>)</a><!--0--></0></0><br />
<div class="norm">
Beclin-1 promotes autophagy induction and autophagosome formation (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib27">Russell <i>et al.</i>, 2013</a>); however, Beclin-1-independent autophagy has been reported (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib31">Scarlatti <i>et al.</i>, 2008</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib14">Grishchuk <i>et al.</i>, 2011</a>). Unlike in glioma cells, Beclin-1 knockdown did not prevent THC-induced LC3-II accumulation or caspase 3 cleavage (<i>t</i><sub>4</sub><span class="mb">=</span>4.494, <i>P</i><span class="mb">=</span>0.011; <a href="http://www.nature.com/jid/journal/v135/n6/suppinfo/jid201545s1.html">Supplementary Figure S3a</a> online) in A375 cells (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig4">Figure 4a</a>),
and THC treatment resulted in a significant loss of cell viability
under both control and Beclin-1 knockdown conditions (Welch ANOVA; F<sub>5, 19.63</sub><span class="mb">=</span>94.53, <i>P</i><0 .001="" cells="" compared="" games="" i="" owell="" shrna="" thc="" treatments="" vehicle-treated="" with="">P<!--0--></0></div>
<0 .001="" a="" href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig4">Figure 4a i<!--0-->) and <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig4">ii</a>)).
These results suggest that autophagy and subsequent apoptosis occur
independently of Beclin-1. Furthermore, knockdown of the
Beclin-1-interacting protein Ambra1 failed to prevent THC-induced LC3-II
induction and caspase 3 cleavage (<i>t</i><sub>4</sub><span class="mb">=</span>6.097, <i>P</i><span class="mb">=</span>0.004; <a href="http://www.nature.com/jid/journal/v135/n6/suppinfo/jid201545s1.html">Supplementary Figure S3b</a> online and <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig4">Figure 4b</a>).
The effect of Ambra1 knockdown alone on A375 viability was variable;
however, THC treatment resulted in a significant loss of cell viability
under both control (<i>t</i><sub>16</sub><span class="mb">=</span>9.44, <i>P</i><0 .001="" ambra1="" and="" conditions="" i="" knockdown="">t<!--0--><sub>16</sub><span class="mb">=</span>10.61, <i>P</i><0 .001="" a="" href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig4">Figure 4biii<!--0-->).
<b>Collectively, these data suggest that THC activates noncanonical
autophagy-mediated apoptosis of melanoma cells that is dependent on Atg7
but not Beclin-1 or Ambra1.</b></0></0></0><br />
<div class="figure-table" id="fig4">
<h5 class="norm">
<a href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f4.html#figure-title">Figure 4.</a></h5>
<a href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f4.html#figure-title"><img alt="Figure 4 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author" class="thumb" src="http://www.nature.com/jid/journal/v135/n6/thumbs/jid201545f4th.jpg" /></a><b>The Δ<sup>9</sup>-Tetrahydrocannabinol (THC)-induced autophagy and cell death is not dependent on Beclin-1 or Ambra1.</b> (<b>a</b>)
A375 cells stably expressing short hairpin RNA (shRNA) for Beclin-1
(shBeclin1) or a nonsilencing control shRNA (shCtrl) were treated with
vehicle or THC (4.5 and 5<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) for 48<span class="mb"><span class="mb"> </span></span>hours in the presence or absence of chloroquine (CQ; 10<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) for the final 2<span class="mb"><span class="mb"> </span></span>hours
(i). Beclin-1, LC3, cleaved caspase 3, and β-actin expression were
determined by western blotting (i). Cell viability (ii) was determined
by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
(MTT) assay. Data generated in triplicate were expressed relative to the
mean of vehicle-treated shCtrl cells in each experiment, for three
independent experiments, and shown as mean±SD (<span class="mb">*</span><span class="mb">*</span><span class="mb">*</span><i>P</i><0 .001="" b="" cells="" shctrl="" vehicle-treated="" vs.="">b<!--0--></0></div>
)
A375 cells stably expressing shRNA for Ambra1 (shAmbra1) or a
nonsilencing control shRNA (shCtrl) were treated with vehicle or THC (5<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) for 24<span class="mb"><span class="mb"> </span></span>hours in the presence or absence of CQ (10<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>) for the final 2<span class="mb"><span class="mb"> </span></span>hours
(i). Ambra1, LC3, cleaved caspase 3, and β-actin expression were
determined by western blotting (i). Cell viability (ii) was determined
by the MTT assay. Data generated in triplicate were normalized to the
mean of vehicle-treated cells for each shRNA in each experiment, for
three independent experiments, and shown as mean±SD (<span class="mb">*</span><span class="mb">*</span><span class="mb">*</span><i>P</i><0 .001="" cells="" each="" for="" p="" shrna="" vehicle-treated="" vs.=""><a class="full" href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f4.html#figure-title">Full figure and legend (109<abbr title="Kilobyte">K</abbr>)</a><a class="ppt" href="http://www.nature.com/jid/journal/v135/n6/slides/jid201545-pf4.ppt">Download Power<span class="hidden"> </span>Point slide (253 <abbr title="Kilobyte">KB</abbr>)</a><!--0--></0><br />
<h4 class="norm">
Cannabinoid treatment stimulates autophagy and apoptosis and the abrogation of melanoma growth <i>in vivo</i></h4>
<div class="follows-h4">
<b>A
1:1 mixture of submaximal doses of THC–botanical drug substance (BDS)
and the nonpsychoactive cannabinoid cannabidiol (CBD) –BDS, a laboratory
mimic of the clinical cannabinoid Sativex (Sat-L) (an oromucosal spray
of standardized cannabis extract comprising equal amounts of THC and CBD
(GW Pharmaceuticals)), reduced glioma growth <i>in vivo</i> to the same extent as an identical dose of THC (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib37">Torres <i>et al.</i>, 2011</a>). Treatment of melanoma cells with THC<span class="mb">+</span>CBD resulted in a substantial loss of melanoma cell viability at a concentration of 1<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span> THC<span class="mb">+</span>1<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>
CBD in CHL-1, A375, and SK-MEL-28 cells compared with equivalent
concentrations of THC, whereas temozolomide had little effect (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig5">Figure 5</a>). </b>Temozolomide is an alkylating agent currently indicated as standard single-agent chemotherapy for metastatic melanoma. The <i>in vivo</i>
relevance of these findings was evaluated in the context of BRAF
wild-type melanoma tumors, for which there is a particular demand for
novel therapeutic approach in the absence of targeted therapies in this
tumor group. CHL-1 xenograft tumors were treated for 20 days with
temozolomide, THC, or Sativex-L. Both THC and Sativex-L significantly
inhibited the growth of xenografts (one-way ANOVA; F<sub>3, 16</sub><span class="mb">=</span>9.347, <i>P</i><span class="mb">=</span>0.001; THC or Sat-L compared with vehicle, Sat-L compared with Temozolomide: <i>P</i><0 .05="" a="" href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig6">Figure 6a<!--0--></0></div>
).
Tumors removed from animals at the time of killing were processed for
immunohistochemical analysis of proliferative activity (Ki67), apoptosis
(TUNEL), and autophagy (LC3). Ki67 fluorescence differed significantly
between drug treatments (Welch ANOVA; F<sub>3, 16.28</sub><span class="mb">=</span>61.363, <i>P</i><0 .001="" a="" href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig6">Figure 6b<!--0-->)
and was significantly reduced in tumors from animals treated with
temozolomide, THC, or Sativex-L compared with control animals
(Games–Howell; <i>P</i>≤0.001), as well as in tumors from animals
treated with THC or Sativex-L compared with those treated with
temozolomide (Games–Howell; <i>P</i><0 .001="" also="" anova="" between="" differed="" f="" fluorescence="" one-way="" significantly="" sub="" treatments="" tunel="">3, 32<!--0--><span class="mb">=</span>13.31, <i>P</i><0 .001="" and="" animals="" control="" from="" higher="" i="" in="" or="" s="" sativex-l="" than="" thc="" treated="" tumors="" ukey="" was="" with="">P<!--0-->≤0.001) and higher in tumors from animals treated with Sativex-L compared with those treated with temozolomide (Tukey’s <i>P</i><0 .05="" a="" href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig6">Figure 6c<!--0-->). Correspondingly, LC3 fluorescence differed between treatments (one-way ANOVA; F<sub>3, 32</sub><span class="mb">=</span>3.539, <i>P</i><0 .05="" animals="" compared="" from="" i="" in="" increased="" lc3="" or="" s="" sativex-l="" significantly="" staining="" temozolomide="" treated="" tumors="" ukey="" vehicle="" with="">P<!--0-->≤0.05, <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#fig6">Figure 6d</a>).
Staining for Ki67, TUNEL, and LC3 was not significantly different in
tumors from animals treated with THC compared with Sativex-L.
<b>Collectively, these data suggest that THC and Sativex-L are more
effective than temozolomide in terms of apoptosis induction and
antitumor response, further validating the therapeutic relevance of
cannabinoid treatment for melanoma.</b></0></0></0></0></0><br />
<div class="figure-table" id="fig5">
<h5 class="norm">
<a href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f5.html#figure-title">Figure 5.</a></h5>
<a href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f5.html#figure-title"><img alt="Figure 5 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author" class="thumb" src="http://www.nature.com/jid/journal/v135/n6/thumbs/jid201545f5th.jpg" /></a><b>Cannabinoids inhibit melanoma cell viability <i>in vitro</i>.</b> (<b>a</b>–<b>c</b>) CHL-1 (<b>a</b>), A375 (<b>b</b>), or SK-MEL-28 (<b>c</b>) cells were treated with temozolomide (Temo; 10–50<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>), Δ<sup>9</sup>-Tetrahydrocannabinol (THC; 1–5<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span>), or THC<span class="mb">+</span>CBD (0.5<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span> THC<span class="mb">+</span>0.5<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span> CBD to 2.5<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span> THC<span class="mb">+</span>2.5<span class="mb"><span class="mb"> </span></span>μ<span class="scp">M</span> CBD) for 48<span class="mb"><span class="mb"> </span></span>hours.
Cell viability was determined by the
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
assay. Data generated in triplicate were expressed relative to the mean
of vehicle-treated cells for each drug treatment in each experiment, for
three independent experiments, and shown as mean±SD for a
representative experiment. CBD, cannabidiol.<br />
<a class="full" href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f5.html#figure-title">Full figure and legend (109<abbr title="Kilobyte">K</abbr>)</a><a class="ppt" href="http://www.nature.com/jid/journal/v135/n6/slides/jid201545-pf5.ppt">Download Power<span class="hidden"> </span>Point slide (227 <abbr title="Kilobyte">KB</abbr>)</a></div>
<br class="clear" />
<div class="figure-table" id="fig6">
<h5 class="norm">
<a href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f6.html#figure-title">Figure 6.</a></h5>
<a href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f6.html#figure-title"><img alt="Figure 6 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author" class="thumb" src="http://www.nature.com/jid/journal/v135/n6/thumbs/jid201545f6th.jpg" /></a><b>The Δ<sup>9</sup>-Tetrahydrocannabinol (THC) and Sativex-like cannabinoids promote autophagy and antitumor responses in melanoma xenografts.</b> Athymic nude mice were injected subcutaneously in the right flank with CHL-1 melanoma cells. When tumors reached a 250<span class="mb"><span class="mb"> </span></span>mm<sup>3</sup> size, mice were treated daily for 20 days with vehicle, temozolomide (TMZ; 5<span class="mb"><span class="mb"> </span></span>mg<span class="mb"><span class="mb"> </span></span>kg<sup>−1</sup>; local administration), THC (15<span class="mb"><span class="mb"> </span></span>mg<span class="mb"><span class="mb"> </span></span>kg<sup>−1</sup>; oral administration), or Sativex-like (Sat-L; 7.5<span class="mb"><span class="mb"> </span></span>mg<span class="mb"><span class="mb"> </span></span>kg<sup>−1</sup> THC–BDS<span class="mb">+</span>7.5<span class="mb"><span class="mb"> </span></span>mg<span class="mb"><span class="mb"> </span></span>kg<sup>−1</sup> CBD–BDS; oral administration). (<b>a</b>)
Tumor volumes were measured daily. Each point is the mean from ≥5
tumors±SD and is expressed relative to the tumor volume on day 1 of
treatment. (<b>b</b>–<b>d</b>) Immunohistochemical analysis of CHL-1 xenograft tumors treated with temozolomide, THC, or Sat-L. (<b>b–d</b>) Micrographs of tumor sections stained for (<b>b</b>) Ki67, (<b>c</b>) TUNEL, or (<b>d</b>)
LC3. In each, green is staining for Ki67, TUNEL, or LC3, and red is the
TO-PRO-3 counterstain. The bar graphs below each set of micrographs
summarize the data analysis from tumor sections (bar<span class="mb">=</span>20<span class="mb"><span class="mb"> </span></span>μm). Total fluorescence values (total fluorescence (LC3<span class="mb">/</span>Ki67<span class="mb">/</span>TUNEL)<span class="mb">/</span>total
nuclear fluorescence) were generated in triplicate for 3 tumors in each
treatment group. Data are expressed as fold change relative to the mean
value obtained from control animals, from two independent staining
analyses, and shown as mean±SD (<span class="mb">*</span><span class="mb">*</span><i>P</i><0 .01="" and="" class="mb" span="">*<!--0--></0></div>
<span class="mb">*</span><span class="mb">*</span><i>P</i><0 .001="" animals="" control="" p="" vs.=""><a class="full" href="http://www.nature.com/jid/journal/v135/n6/fig_tab/jid201545f6.html#figure-title">Full figure and legend (302<abbr title="Kilobyte">K</abbr>)</a><a class="ppt" href="http://www.nature.com/jid/journal/v135/n6/slides/jid201545-pf6.ppt">Download Power<span class="hidden"> </span>Point slide (428 <abbr title="Kilobyte">KB</abbr>)</a><!--0--></0><br />
<div id="Discussion">
<a class="backtotop" href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#top">Top<span class="hidden"> of page</span></a><br />
<h3>
Discussion</h3>
<div class="norm">
It
is apparent that autophagy modulation may offer considerable benefit in
cancer treatment; however, potential drawbacks to autophagy inhibition
have recently been identified (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib23">Michaud <i>et al.</i>, 2011</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib21">Maycotte <i>et al.</i>, 2012</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib35">Takahashi <i>et al.</i>, 2012</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib26">Rosenfeldt <i>et al.</i>, 2013</a>).
Emerging evidence indicates that activation of autophagy can, in some
circumstances, promote cell death; stimulation of cytotoxic autophagy
therefore represents an alternative approach to autophagy modulation (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib10">Ding <i>et al.</i>, 2007</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib31">Scarlatti <i>et al.</i>, 2008</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib29">Salazar <i>et al.</i>, 2009b</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib14">Grishchuk <i>et al.</i>, 2011</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib36">Tomic <i>et al.</i>, 2011</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib4">Basit <i>et al.</i>, 2013</a>).
<b> Here, we show that the cannabinoid THC exerts its antitumor effect on
melanoma cells via activation of noncanonical autophagy and subsequent
apoptosis, suggesting that cannabinoids may be of clinical benefit for
metastatic melanoma.</b></div>
<div class="norm">
The molecular mechanisms connecting autophagy to cell death remain poorly understood (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib32">Shen and Codogno, 2011</a>); however, reports describing autophagy-dependent apoptosis (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib10">Ding <i>et al.</i>, 2007</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib29">Salazar <i>et al.</i>, 2009b</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib14">Grishchuk <i>et al.</i>, 2011</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib36">Tomic <i>et al.</i>, 2011</a>) suggest multiple interactions between autophagic and apoptotic machinery. THC exerts its effect via the <i>de novo</i> synthesis of the sphingolipid ceramide, leading to the activation of ER stress, TRIB3-dependent inhibition of Akt<span class="mb">/</span>mTORC1 signaling, and autophagy-mediated apoptosis (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib6">Carracedo <i>et al.</i>, 2006</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib29">Salazar <i>et al.</i>, 2009b</a>). TRIB3 has been identified as a key switch between cell survival and apoptosis during stress responses (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib33">Shimizu <i>et al.</i>, 2012</a>),
and the participation of TRIB3 in the melanoma response to THC may
direct cellular fate toward apoptosis in the context of ER
stress–induced autophagy (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib30">Salazar <i>et al.</i>, 2013</a>).</div>
<div class="norm">
Autophagy
inhibition using both molecular and pharmacological approaches
prevented THC-induced autophagy and apoptosis of melanoma cells.
However, THC-induced autophagy was not prevented by knockdown of
Beclin-1, suggesting that, in contrast to glioma, noncanonical autophagy
mediates apoptosis in response to THC in melanoma. Beclin-1-independent
autophagy may promote caspase-independent cell death (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib31">Scarlatti <i>et al.</i>, 2008</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib4">Basit <i>et al.</i>, 2013</a>) as well as apoptosis (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib14">Grishchuk <i>et al.</i>, 2011</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib36">Tomic <i>et al.</i>, 2011</a>),
suggesting that autophagy mechanisms not involving Beclin-1 exist that
interact with cell death machinery. Interestingly, in contrast to
previous studies (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib29">Salazar <i>et al.</i>, 2009b</a>),
THC-induced autophagy was also independent of Ambra1 in melanoma cells.
Ambra1 is a Beclin-1 interacting protein that promotes autophagy by
stabilizing Beclin-1 complexes (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib11">Fimia <i>et al.</i>, 2007</a>);
although supporting the concept of Beclin-1-independent autophagy
activation in response to THC, these data highlight the complex
regulation of autophagy that likely occurs in a cell type- and
context-specific manner.</div>
<div class="norm">
<b>Tumor-selective killing can
be achieved by targeting pathways that are differentially regulated in
cancer cells compared with normal cells. In this respect, we have shown
that normal human melanocytes are resistant to THC at concentrations
that cause cell death in melanoma cells. This is consistent with studies
showing that cancerous cells are more sensitive to THC and other
cannabinoid receptor ligands compared with their nontransformed
counterparts, despite the presence of functional CB receptors</b> (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib38">Velasco <i>et al.</i>, 2012</a>). Together with previous studies demonstrating an effect of synthetic ligands of cannabinoid receptors in melanoma (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib5">Blazquez <i>et al.</i>, 2006</a>),
these data support clinical evaluation of cannabinoids in
advanced-stage disease. Furthermore, THC activates autophagy and
apoptosis in both BRAF wild-type and mutated melanoma cell lines,
suggesting that despite autophagy deregulation (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib1">Armstrong <i>et al.</i>, 2011</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib9">Corazzari <i>et al.</i>, 2013</a>),
<b>THC is likely effective in melanoma tumors regardless of BRAF mutation
status</b>. <b>Furthermore, our findings show that THC is able to reduce
melanoma cell viability and tumor xenograft growth alone, but when lower
doses of THC are combined with CBD the antitumor effect was enhanced <i>in vitro</i> and was at least equally effective as the higher dose of single-agent THC <i>in vivo</i>. Moreover, CBD induces apoptosis via the production of reactive oxygen species and caspase activation in cancer cells (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib20">Massi <i>et al.</i>, 2006</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib34">Shrivastava <i>et al.</i>, 2011</a>), indicating that THC and CBD engage different molecular machineries that cooperate to promote tumor cell death </b>(<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib34">Shrivastava <i>et al.</i>, 2011</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib37">Torres <i>et al.</i>, 2011</a>).</div>
<div class="norm">
In
summary, these data highlight the potential for cannabinoid-induced
cytotoxic autophagy as an effective strategy to drive melanoma cell
death, supporting the clinical evaluation of Sativex for the treatment
of metastatic disease.</div>
</div>
<div id="Materials-and-Methods">
<a class="backtotop" href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#top">Top<span class="hidden"> of page</span></a><br />
<h3>
Materials and Methods</h3>
<h4 class="norm">
Cell culture, viability assays, and drug treatment</h4>
<div class="follows-h4">
Melanoma
cell lines CHL-1, A375, and SK-MEL-28 were obtained from the ATCC
(Manassas, VA) in 2006 and cultured as described previously (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib3">Armstrong <i>et al.</i>, 2007</a>). Cell lines were verified by melan A staining (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib12">Flockhart <i>et al.</i>, 2009</a>) with <i>B-RAF<span class="mb">/</span>NRAS</i> mutational status confirmed using Custom TaqMan SNP genotyping assays (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib16">Hiscutt <i>et al.</i>, 2010</a>)
(Applera Europe BV, Life Technologies, Paisley, UK) (last tested
February 2014). Before drug treatment, culture medium was changed to 0.5<span class="mb">%</span>
fetal bovine serum medium. Temozolomide (OSI Pharmaceuticals, Melville,
NY) and ZVAD-fmk (benzyloxycarbonyl-V-A-D(OMe)-fluoromethylketone)
(Tocris Bioscience, Bristol, UK) were added in DMSO, and chloroquine
(Sigma-Aldrich Ltd, Poole, UK) was added in water. For <i>in vitro</i>
experiments, pure THC (THC Pharm, Frankfurt, Germany) and CBD
(synthesized by Professor Raphael Mechoulam (Hebrew University of
Jerusalem) and kindly provided by Dr Javier Fernandez Ruiz (Complutense
University, Madrid, Spain)) were prepared in DMSO. Control incubations
contained the same amount of DMSO (0.1–0.2<span class="mb">%</span> v<span class="mb">/</span>v). For treatment with THC<span class="mb">+</span>CBD, pure THC and pure CBD were mixed 1:1 (w<span class="mb">/</span>w).
Analysis of cell viability was performed using
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT;
Sigma). For <i>in vivo</i> experiments, THC–BDS (THC content 67.6<span class="mb">%</span> w<span class="mb">/</span>w; CBD content 0.3<span class="mb">%</span> w<span class="mb">/</span>w; other individual plant cannabinoids <1 .5="" class="mb" span="">%<!--1--></1></div>
</div>
w<span class="mb">/</span>w) and CBD–BDS (CBD content 65.4<span class="mb">%</span> w<span class="mb">/</span>w; THC content 2.5<span class="mb">%</span> w<span class="mb">/</span>w; other individual plant cannabinoids <1 .7="" class="mb" span="">%<!--1--> w<span class="mb">/</span>w) were provided by GW Pharmaceuticals (Cambridge, UK). THC–BDS and CBD–BDS were provided as a resin, dissolved in ethanol (100<span class="mb"><span class="mb"> </span></span>mg<span class="mb"><span class="mb"> </span></span>ml<sup>−1</sup>), dried, and prepared in DMSO. A 1:1 (w<span class="mb">/</span>w) preparation of THC–BDS and CBD–BDS was used to mimic Sativex (Sat-L). For oral administration, THC or Sat-L was solved in 100<span class="mb"><span class="mb"> </span></span>μl of sesame oil.</1><br />
<h4 class="norm">
Western blotting and reverse transcription–PCR analysis</h4>
<div class="follows-h4">
Preparation
of whole-cell lysates and western blotting for LC3B, cleaved caspase 3
(Cell Signaling Technology, Leiden, The Netherlands), Atg7 (Santa Cruz
Biotechnology, Heidelberg, Germany), Beclin-1 (BD Biosciences, Oxford,
UK), and Ambra1 (Novus Biologicals, Cambridge, UK) all diluted 1:4,000,
and β-actin (Sigma) diluted 1:30,000, were performed as described
previously (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib3">Armstrong <i>et al.</i>, 2007</a>).
Total RNA was isolated from cells using the RNeasy Mini Kit with DNase
digestion (Qiagen, Manchester, UK) according to the manufacturer’s
protocol. Reverse transcription–PCR was performed using the Access
Reverse transcription–PCR system (Promega, Southampton, UK) using
primers for TRIB3 (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib6">Carracedo <i>et al.</i>, 2006</a>) or β-actin (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib2">Armstrong <i>et al.</i>, 2005</a>). PCR products were analyzed by electrophoresis on ethidium bromide–stained 2<span class="mb">%</span> agarose gels and DNA visualized by exposure to UV light.</div>
<h4 class="norm">
siRNA transfections</h4>
<div class="follows-h4">
The
siRNA for Atg7 (HSS116182), TRIB3 (sc-44426, Santa Cruz Biotechnology),
or a nontargeting siRNA (Negative control Low GC Stealth RNAi) (Stealth
RNAi, Life Technologies, Paisley, UK) were transfected into cells in
OPTIMEM containing siRNA (2–4<span class="mb"><span class="mb"> </span></span>n<span class="scp">M</span>)
using Lipofectamine RNAiMAX (Life Technologies) according to the
manufacturer’s specification for reverse transfection. After 24<span class="mb"><span class="mb"> </span></span>hours, the medium was replaced with DMEM containing 0.5<span class="mb">%</span> fetal bovine serum and cells treated with drugs as appropriate.</div>
<h4 class="norm">
Retroviral or lentiviral infection</h4>
<div class="follows-h4">
Retroviral expression of mRFP–GFP–LC3 (provided by T Yoshimori, Osaka University, Osaka, Japan) (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib18">Kabeya <i>et al.</i>, 2000</a>; <a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib19">Kimura <i>et al.</i>, 2007</a>) was performed as described previously (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib1">Armstrong <i>et al.</i>, 2011</a>).
Lentiviral expression of shAmbra1 or a nontargeting sequence shCtrl
(MISSION shRNA, Sigma) was performed by cotransfection of 7.5<span class="mb"><span class="mb"> </span></span>μg lentivirus vector (pLKO.1-puro) with 2.5<span class="mb"><span class="mb"> </span></span>μg
of an expression plasmid for the vesicular stomatitis virus G protein
into 293 cells using the calcium precipitation method. After 48<span class="mb"><span class="mb"> </span></span>hours, melanoma cells were incubated with virus-containing supernatant supplemented with polybrene (4<span class="mb"><span class="mb"> </span></span>μg<span class="mb"><span class="mb"> </span></span>ml<sup>−1</sup>) for 6–8<span class="mb"><span class="mb"> </span></span>hours
and selected for puromycin resistance. Lentiviral expression of
shBeclin-1 (V3LHS_349509, Dharmacon, Chalfont St Giles, UK) or a
nontargeting sequence shCtrl (RHS4346, Dharmacon) was performed by
cotransfection of 20<span class="mb"><span class="mb"> </span></span>μg lentivirus vector with 5<span class="mb"><span class="mb"> </span></span>μg of an expression plasmid for the viral envelope (pMD2.G) and 15<span class="mb"><span class="mb"> </span></span>μg packaging plasmid (pCMVdelta8.91) into HEK293T cells using the calcium precipitation method. After 72<span class="mb"><span class="mb"> </span></span>hours, melanoma cells were spin transduced (1.5<span class="mb"><span class="mb"> </span></span>hours, 1,200<span class="mb"><span class="mb"> </span></span>r.p.m., Harrier 15<span class="mb">/</span>80, DJB Labcare, Newport Pagnell, UK) with virus-containing supernatant supplemented with polybrene (4<span class="mb"><span class="mb"> </span></span>μg<span class="mb"><span class="mb"> </span></span>ml<sup>−1</sup>) and selected for puromycin resistance.</div>
<h4 class="norm">
Confocal microscopy</h4>
<div class="follows-h4">
Cells were grown on glass coverslips before fixation in 4<span class="mb">%</span> paraformaldehyde. For immunolabeling, cells were incubated with 0.2<span class="mb">%</span> Triton X-100 before incubation with anti-cytochrome <i>c</i> (BD Biosciences) at room temperature for 1<span class="mb"><span class="mb"> </span></span>hour (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib22">McGill <i>et al.</i>, 2005</a>).
Secondary labeling was performed with Oregon Green 488 conjugated to
anti-rabbit IgG (Life Technologies). Nuclei were counterstained with
TO-PRO-3 iodide (Life Technologies). Cells were imaged under a Leica TCS
SP II laser-scanning confocal microscope with LCS Lite 2.61 software
(Leica Microsystems, Milton Keynes, UK), using a 63 × oil objective.</div>
<h4 class="norm">
Xenograft mouse model and immunohistochemical analysis</h4>
<div class="follows-h4">
Athymic nude (nu<span class="mb">/</span>nu) 5-week-old male mice (Harlan Iberica Laboratory, Madrid, Spain) were inoculated by subcutaneous injection of 7.5 × 10<sup>6</sup> CHL-1 cells in 100<span class="mb"><span class="mb"> </span></span>μl phosphate-buffered saline containing 0.1<span class="mb">%</span> glucose. On establishment of tumors 250<span class="mb"><span class="mb"> </span></span>mm<sup>3</sup>
in volume, mice were randomized into four treatment groups (5–8 mice
per group) and treated by daily administration for 20 days with
temozolomide (5<span class="mb"><span class="mb"> </span></span>mg<span class="mb"><span class="mb"> </span></span>kg<sup>−1</sup>, local peritumoral injection), THC (15<span class="mb"><span class="mb"> </span></span>mg<span class="mb"><span class="mb"> </span></span>kg<sup>−1</sup>, oral gavage), or Sativex (7.5<span class="mb"><span class="mb"> </span></span>mg<span class="mb"><span class="mb"> </span></span>kg<sup>−1</sup> THC–BDS<span class="mb">+</span>7.5<span class="mb"><span class="mb"> </span></span>mg<span class="mb"><span class="mb"> </span></span>kg<sup>−1</sup> CBD–BDS, oral gavage). The control group was treated with 100<span class="mb"><span class="mb"> </span></span>μl of vehicle (sesame oil). Caliper measurements of tumor length (<i>l</i>) and width (<i>w</i>) were taken each day, and tumor volume was calculated as (4<span class="mb">π</span><span class="mb">/</span>3) × (<i>w</i><span class="mb">/</span>2)<sup>2</sup> × (<i>l</i><span class="mb">/</span>2).
Mice were humanely killed on the final day of treatment, and tumors
extracted and snap frozen in liquid nitrogen before storage at −80<span class="mb"><span class="mb"> </span></span>°C. Frozen sections (6<span class="mb"><span class="mb"> </span></span>μm) prepared on (3-Aminopropyl)triethoxysilane (Sigma)-coated glass slides were fixed in 4<span class="mb">%</span> paraformaldehyde before staining by TUNEL or with a Ki67 antibody (ab-15580, Abcam, Cambridge, UK) as previously described (<a href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#bib15">Hill <i>et al.</i>, 2009</a>). For LC3 immunolabeling, frozen sections were fixed in acetone and incubated with anti-LC3B (ab48394, Abcam) for 1<span class="mb"><span class="mb"> </span></span>hour
at room temperature. Secondary labeling was performed with Oregon Green
488 conjugated to anti-rabbit IgG (Life Technologies). Cells were
imaged under a Leica TCS SP II laser-scanning confocal microscope with
LCS Lite 2.61 software (Leica Microsystems), using a 63 × oil objective.
All procedures involving animals were performed according to Spanish
and European regulations and were approved by the ethical committee for
animal experimentation from Complutense University.</div>
<h4 class="norm">
Statistical analysis</h4>
<div class="follows-h4">
Images
of LC3, Ki67, and TUNEL staining were analyzed using Velocity (v4.3.1)
(Improvision, Perkin Elmer, Coventry, UK). Total fluorescence was
obtained by multiplying pixel number to the mean pixel intensity, after
appropriate thresholding. TOPRO-3 fluorescence was determined by the
number of pixels with fluorescence above the threshold, which was
proportional to nuclei number. For each tumor (three animals per group,
three randomly selected images each), values were reported as normalized
total fluorescence (total fluorescence (LC3<span class="mb">/</span>Ki67<span class="mb">/</span>TUNEL)<span class="mb">/</span>total
nuclear fluorescence) and expressed as fold change relative to the mean
value obtained from control animals, from two independent staining
analyses. The mRFP fluorescence was analyzed using ImageJ (public domain
licence, <a href="http://imagej.nih.gov/ij/">http://imagej.nih.gov/ij/</a>); data are total pixel intensities<span class="mb">/</span>cell
minus the mean background fluorescence of nuclei. Homogeneity of
variances was checked using Levene’s test, and if variances were equal
(normalized data or after log transformation) data were analyzed by drug
treatment using Student’s <i>t-</i>test or one-way ANOVA with planned contrasts (LC3 expression) or Tukey’s <i>post hoc</i> test for multiple pair-wise comparisons. Where variances were not equal, Welch ANOVA test was used with Games–Howell <i>post hoc</i> tests for pair-wise comparisons (SPSS Statistics 20, SPSS, IBM, Portsmouth, UK).</div>
<span class="cleardiv"></span>
<br />
<div id="conflict-of-interest">
<a class="backtotop" href="http://www.nature.com/jid/journal/v135/n6/full/jid201545a.html#top">Top<span class="hidden"> of page</span></a><br />
<h3>
Conflict of interest</h3>
<div class="norm">
The authors state no conflict of interest.</div>
</div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-31266522799169333832015-07-18T13:03:00.000-07:002015-07-18T13:03:49.225-07:00Marijuana Helps Heal Broken Bones<div style="float: left; font-size: 11px;">
By <a href="http://www.newser.com/user/2261/1/rob-quinn.html" id="ctl00_ContentPlaceHolder1_HyperLinkAuthor">Rob Quinn</a>,
Newser Staff
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<br />
<div style="font-size: 11px;">
Posted Jul 17, 2015 7:17 AM CDT </div>
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<span class="source">
(Newser)
</span>
–
There's a new and very promising use for marijuana, or at least a
compound found in it. Researchers discovered that cannabidiol (CBD)
worked wonders for rats with broken limbs. When rats with mid-femoral
fractures were given CBD, the healing process was "markedly enhanced"
within just eight weeks, according to the Israeli researchers, whose
work is published in the <em><a href="http://www.ncbi.nlm.nih.gov/pubmed/25801536" target="_blank">Journal of Bone and Mineral Research</a>. </em>The
researchers say the healing properties of CBD remained even when the
non-psychotropic compound was separated from THC, the component that
gets people high, the <a href="http://www.timesofisrael.com/joint-relief-marijuana-helps-mend-broken-bones/" target="_blank"><em>Times of Israel</em></a> reports.
</div>
And
the treatment did more than just mend bones: The compound made bones
stronger during healing (scientifically, CBD enhanced "the maturation of
the collagenous matrix, which provides the basis for new mineralization
of bone tissue"). That means the limb "will be harder to break in the
future," the researchers say in <a href="http://www.eurekalert.org/pub_releases/2015-07/afot-nba071615.php" target="_blank">a press release</a>.
"The clinical potential of cannabinoid-related compounds is simply
undeniable at this point," lead researcher Dr. Yankel Gabet says. "While
there is still a lot of work to be done to develop appropriate
therapies, it is clear that it is possible to detach a clinical therapy
objective from the psychoactivity of cannabis." (In other marijuana
news, <a href="http://www.newser.com/story/209500/pot-smokers-hit-a-surprising-change-at-21.html">pot smokers hit a surprising change at 21</a>.)Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-43460052061640866062015-07-07T12:26:00.001-07:002015-07-07T12:26:34.512-07:00Doctor facing 175 year sentence for falsely diagnosing roughly 533 healthy people with cancer and forcing them to receive chemotherapy, only to 'line his pockets' with money.http://insider.foxnews.com/2015/07/07/doctor-farid-fata-be-sentenced-giving-chemo-healthy-patients<br />
<br />
Prosecutors are seeking a 175-year sentence for a Michigan doctor who
intentionally misdiagnosed hundreds of healthy patients with cancer to
line his pockets.<br />
A sentencing hearing began Monday for Dr. Farid Fata, who gave unnecessary cancer treatments to <a href="http://www.nbcnews.com/health/cancer/farid-fata-doctor-who-gave-chemo-healthy-patients-faces-sentencing-n385161" target="_blank">553 patients</a>. Fata was arrested back in 2013 for the health care fraud.<br />
“There is no real justice,” victim Geraldine Parkin said, adding that
she hopes her anger and frustration will finally go away once Fata is
sentenced.<br />
<hr />
<a href="http://insider.foxnews.com/2014/03/10/dr-farid-fata-michigan-doctor-accused-falsely-diagnosing-chemo-giving-chemotherapy"><strong>Horrifying Claims Against Cancer Doctor Accused of $35M in Medicare Fraud</strong></a><br />
<hr />
Arthur Aidala said this morning on “Fox and Friends” that getting chemo when you don’t have cancer “destroys your insides.”<br />
He said that the lesson to be learned here is to ask to see lab reports and paperwork.<br />
Dr. Keith Ablow added that this case proves that doctors aren’t good enough at supervising other doctors.Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-66993840804466620862015-07-03T03:11:00.001-07:002015-07-03T03:11:21.875-07:00 It's Official: Marijuana Is Medicine <h2 class="subheadline">
A series of papers in the <i>Journal of the American Medical Association</i> is starting to correct the shameful legacy of drug war politics over cannabis science. But a research catch-22 persists.
</h2>
by
<a href="http://m.eastbayexpress.com/oakland/ArticleArchives?author=1064917" rel="author">
David Downs
</a>
<br />
<time class="date" datetime="2015-07-01" pubdate="">
July 01, 2015
</time>
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<span class="caption"></span>The nation's top medical organization released a major series of papers on medical cannabis last week in the <i>Journal of the American Medical Association</i>, in a move that constitutes a small step for the AMA, but a giant leap in cannabis medical history.</div>
<div class="image-info">
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<div class="image-info">
In five key papers, teams of researchers systematically reviewed
dozens of clinical studies of marijuana, speaking in clear language that
the "use of marijuana for chronic pain, neuropathic pain, and
spasticity due to multiple sclerosis is supported by high-quality
evidence."</div>
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The review validated what doctors and patients in California have
risked their freedom to say for twenty years. The findings also directly
refute critics who maintain that "marijuana is not medicine."<br />
"They concluded cannabis is useful," said Dr. Frank Lucido, a
Berkeley physician who specializes in cannabis. "I don't think a single
study didn't show benefit. ... I think it was very positive."<br />
"It is somewhat affirming to see this come out," said Clint Werner, best-selling author of <i>Marijuana: Gateway to Health</i>. "It's invalidating that talking point that 'it's just a Cheech and Chong show.'"<br />
"What's driving this is a tremendous cultural shift that's preceding the political shift," said Martin Lee, of author <i>Smoke Signals</i>. The AMA is acknowledging "what's been known for 5,000 years."<br />
The AMA actually opposed federal cannabis prohibition in 1937. After
losing that round, most doctors have toed the Drug War line ever since.
"It's great that they have finally acknowledged there's some medicinal
value in cannabis, but the whole thing is so pathetic," Lee said.<br />
Most major news media outlets, however, have spun the JAMA papers
negatively, embracing the narrative that many uses for medical pot are
still based on poor science. News reports noted that of one of the JAMA
studies found that "there was low-quality evidence suggesting that
cannabinoids were associated with improvements in nausea and vomiting
due to chemotherapy, weight gain in HIV infection, sleep disorders, and
Tourette syndrome."<br />
News outlets also pointed to another review that found that "there is
some evidence to support the use of marijuana for nausea and vomiting
related to chemotherapy, specific pain syndromes, and spasticity from
multiple sclerosis. However, for most other indications that qualify by
state law for use of medical marijuana, such as hepatitis C, Crohn
disease, Parkinson disease, or Tourette syndrome, the evidence
supporting its use is of poor quality."<br />
Cannabis experts say the problem with some of the conclusions in the
JAMA studies, and the reporting about them, is that they fail to own up
to the main reason why study quality has often been poor: the systematic
blockade on pot research. For decades, the federal government has
refused to authorize research on the medical benefits of cannabis. As a
result, the inconclusiveness of some of the research is more a
reflection of the federal ban than of the medical effectiveness of pot.
"You know how incredibly hard it is to do research that is intended to
confirm benefits of cannabis?" said Warner. "It's impossible. We still
have a huge catch-22."<br />
Experts also say that the decision by AMA researchers to ignore the
research blockade shows their bias. "It's a national embarrassment. The
federal designation that cannabis has no medical value is like saying
the moon is made of green cheese," Lee said. "It seems the AMA can't
say, 'No, the moon is not made of green cheese.'"<br />
The AMA researchers also fail to acknowledge the real world benefits
reported by patients. For example, about one in twenty California adults
(1.4 million) have used medical cannabis for a "serious" condition and
92 percent of them have reported that it worked. "We have plenty of
evidence that it helps for a lot of things," Lucido said. "We should
always do more research. But we shouldn't stop people from using it in
the meantime."<br />
The AMA researchers also listed the side effects of cannabis without
providing context. "Adverse Effects included dizziness, dry mouth,
nausea, fatigue, somnolence, euphoria, vomiting, disorientation, and
hallucination," one of the reports concluded.<br />
But the AMA researchers didn't compare the adverse side effects of
cannabis to those of competing analgesics and anti-inflammatories.
Painkiller overdoses are America's leading epidemic. Ibuprofen, for
example, regularly causes kidney failure. But those facts were not
mentioned in the JAMA studies. "A full third of the <i>Physician's Desk Reference</i>
is adverse effects, including death," Lucido said. "Cannabis has about
ten adverse effects, at least two of which are often desired."<br />
The AMA researchers' statements about cannabis addiction also lacked
context. "I imagine sleeping pills probably have a much bigger
dependency ratio," Lucido said.<br />
Still, as half-hearted and equivocal as the JAMA papers were, they
contributed to a rising tide of mainstream validation for cannabis
that's washing away its prohibition.<br />
"Culturally, the fight is over. We won," Lee said. "The pro-cannabis
side has conquered the culture. Now politics is catching up."<br />
<br />
http://m.eastbayexpress.com/oakland/its-official-marijuana-is-medicine/Content?oid=4381482 </div>
</div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-86449402695461910112015-05-28T10:05:00.005-07:002015-05-28T10:05:48.070-07:00How Cannabis Cures Cancer (+30 Medical Researches) Good Collection<div class="post-byline">
by <a href="http://www.thoughtpursuits.com/author/admin/" rel="author" title="Posts by Thought Pursuits">Thought Pursuits</a> · November 16, 2013</div>
<div style="background-color: transparent; border: medium none; color: black; overflow: hidden; text-align: left; text-decoration: none;">
<br /><br />Read more at: <a href="http://www.thoughtpursuits.com/cannabis-cures-cancer-30-medical-reasearches/#">http://www.thoughtpursuits.com/cannabis-cures-cancer-30-medical-reasearches/#</a></div>
<br />
<div class="separator" style="clear: both; text-align: center;">
<a href="http://www.thoughtpursuits.com/wp-content/uploads/2013/11/growing-cannabis-720x340.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="http://www.thoughtpursuits.com/wp-content/uploads/2013/11/growing-cannabis-720x340.jpg" height="151" width="320" /></a></div>
<br />
<br />
Cannabis the magic plant that made noise over the last years, had
been recognized as the most efficient cure for the different types of
Cancer, so, in order to help clear things up, here is a list of 34
studies showing that marijuana cures cancer, categorized by the type of
cancers being cured in each study. As you sort through the articles,
note that the consistent theme between them is that cannabis shrinks
tumors and selectively targets cancer cells. As bills and voter
initiatives to legalize medical marijuana spread from state to state,
remember that we’re not just talking about mitigating the side effects
of chemo (though this is another viable use), we’re talking about curing
the cancer itself as well as preventing its spread. I’ve taken the
liberty of only including articles from credible scientific journals,
removing any biased or otherwise improperly cited studies. Enjoy!<br />
<strong>Brain Cancer</strong><br />
<div>
<a href="http://www.nature.com/bjc/journal/v95/n2/abs/6603236a.html">http://www.nature.com/bjc/journal/v95/n2/abs/6603236a.html</a><br />
</div>
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/11479216">http://www.ncbi.nlm.nih.gov/pubmed/11479216</a><br />
</div>
<div>
<a href="http://www.jneurosci.org/content/21/17/6475.abstract">http://www.jneurosci.org/content/21/17/6475.abstract</a><br />
</div>
<div>
<a href="http://jpet.aspetjournals.org/content/308/3/838.abstract">http://jpet.aspetjournals.org/content/308/3/838.abstract</a><br />
</div>
<div>
<a href="http://mct.aacrjournals.org/content/10/1/90.abstract">http://mct.aacrjournals.org/content/10/1/90.abstract</a><br />
</div>
<strong>Mouth and Throat Cancer</strong><br />
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/20516734">http://www.ncbi.nlm.nih.gov/pubmed/20516734</a><br />
</div>
<strong>Breast Cancer</strong><br />
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/20859676">http://www.ncbi.nlm.nih.gov/pubmed/20859676</a><br />
</div>
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/18025276">http://www.ncbi.nlm.nih.gov/pubmed/18025276</a><br />
</div>
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/21915267">http://www.ncbi.nlm.nih.gov/pubmed/21915267</a><br />
</div>
<div>
<a href="http://jpet.aspetjournals.org/content/early/2006/05/25/jpet.106.105247.full.pdf+html">http://jpet.aspetjournals.org/content/early/2006/05/25/jpet.106.105247.full.pdf+html</a><br />
</div>
<div>
<a href="http://www.molecular-cancer.com/content/9/1/196">http://www.molecular-cancer.com/content/9/1/196</a><br />
</div>
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/22776349">http://www.ncbi.nlm.nih.gov/pubmed/22776349</a><br />
</div>
<div>
<a href="http://www.pnas.org/content/95/14/8375.full.pdf+html">http://www.pnas.org/content/95/14/8375.full.pdf+html</a><br />
</div>
<strong>Lung Cancer</strong><br />
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/22198381?dopt=Abstract">http://www.ncbi.nlm.nih.gov/pubmed/22198381?dopt=Abstract</a><br />
</div>
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/21097714?dopt=Abstract">http://www.ncbi.nlm.nih.gov/pubmed/21097714?dopt=Abstract</a><br />
</div>
<div>
<a href="http://www.nature.com/onc/journal/v27/n3/abs/1210641a.html">http://www.nature.com/onc/journal/v27/n3/abs/1210641a.html</a><br />
</div>
<strong>Uterine, Testicular, and Pancreatic Cancers</strong><br />
<div>
<a href="http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page4">http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page4</a><br />
</div>
<div>
<a href="http://cancerres.aacrjournals.org/content/66/13/6748.abstract">http://cancerres.aacrjournals.org/content/66/13/6748.abstract</a><br />
</div>
<strong>Prostate Cancer</strong><br />
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/12746841?dopt=Abstract">http://www.ncbi.nlm.nih.gov/pubmed/12746841?dopt=Abstract</a><br />
</div>
<div>
<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339795/?tool=pubmed">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339795/?tool=pubmed</a><br />
</div>
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/22594963">http://www.ncbi.nlm.nih.gov/pubmed/22594963</a><br />
</div>
<strong>Colorectal Cancer</strong><br />
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/22231745">http://www.ncbi.nlm.nih.gov/pubmed/22231745</a><br />
</div>
<div>
<strong>Ovarian Cancer</strong><br />
</div>
<div>
<a href="http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/1084">http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/1084</a><br />
</div>
<strong>Blood Cancer</strong><br />
<div>
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/12091357">http://www.ncbi.nlm.nih.gov/pubmed/12091357</a><br />
</div>
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/16908594">http://www.ncbi.nlm.nih.gov/pubmed/16908594</a><br />
</div>
<div>
<a href="http://onlinelibrary.wiley.com/doi/10.1002/ijc.23584/abstract">http://onlinelibrary.wiley.com/doi/10.1002/ijc.23584/abstract</a><br />
</div>
<div>
<a href="http://molpharm.aspetjournals.org/content/70/5/1612.abstract">http://molpharm.aspetjournals.org/content/70/5/1612.abstract</a><br />
</div>
<strong>Skin Cancer</strong><br />
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/12511587">http://www.ncbi.nlm.nih.gov/pubmed/12511587</a><br />
</div>
<strong>Liver Cancer</strong><br />
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/21475304">http://www.ncbi.nlm.nih.gov/pubmed/21475304</a><br />
</div>
<strong>Biliary Tract Cancer</strong><br />
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/19916793">http://www.ncbi.nlm.nih.gov/pubmed/19916793</a><br />
</div>
<strong>Bladder Cancer</strong><br />
<div>
<a href="http://www.medscape.com/viewarticle/803983">http://www.medscape.com/viewarticle/803983</a> (Sign-up required to view study)<br />
</div>
<strong>Cancer in General</strong><br />
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/12514108">http://www.ncbi.nlm.nih.gov/pubmed/12514108</a><br />
</div>
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/15313899">http://www.ncbi.nlm.nih.gov/pubmed/15313899</a><br />
</div>
<div>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/15313899">http://www.ncbi.nlm.nih.gov/pubmed/15313899</a><br />
</div>
<address>
<span style="color: #888888;"><b>Disclaimer:</b> This article
is not intended to provide medical advice, diagnosis or treatment. Views
expressed here do not necessarily reflect those of WakingTimes or its
staff. This article is offered under Creative Commons license. It’s okay
to republish it anywhere as long as attribution bio is included and all
links remain intact.</span></address>
</div>
<div style="background-color: transparent; border: medium none; color: black; overflow: hidden; text-align: left; text-decoration: none;">
<br /><br />Read more at: <a href="http://www.thoughtpursuits.com/cannabis-cures-cancer-30-medical-reasearches/#">http://www.thoughtpursuits.com/cannabis-cures-cancer-30-medical-reasearches/#</a></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-75191075886374835852015-04-12T18:46:00.003-07:002015-04-12T18:46:47.160-07:00Israeli study finds cannabis delays cancer development<a href="http://www.i24news.tv/en/news/israel/society/67341-150411-israeli-study-finds-cannabis-delays-cancer-development" target="_blank">http://www.i24news.tv/en/news/israel/society/67341-150411-israeli-study-finds-cannabis-delays-cancer-development</a><br />
<br />
<strong>50 varieties of Israeli cannabis and its effects on 200 different cancer cells are being studied by scientists</strong><br />
<div class="container-image-article left-style" style="float: left; margin-right: 15px;">
<img alt="Frederic J. Brown (AFP/File)" class="image-on-left-side" longdesc="The highly-rated strain of medical marijuana 'Blue Dream' is displayed among others in glass jars at LA's first-ever cannabis farmer's market on July 4, 2014 in Los Angeles, California" src="http://cdn.i24news.tv/upload/cache/medium_image/upload/image/afp-2e211b349cfda36fa7a2cc2ac05a4c7eca86f399.jpg" style="float: left; height: 299px; width: 450px;" title="The highly-rated strain of medical marijuana 'Blue Dream' is displayed among others in glass jars at LA's first-ever cannabis farmer's market on July 4, 2014 in Los Angeles, California - Frederic J. Brown (AFP/File)" /><span class="credit-img" style="left: 0; width: 310px;">Frederic J. Brown (AFP/File)</span><span class="caption-img" style="left: 0; width: 310px;">"The
highly-rated strain of medical marijuana 'Blue Dream' is displayed
among others in glass jars at LA's first-ever cannabis farmer's market
on July 4, 2014 in Los Angeles, California"</span></div>
A preliminary
study conducted by Israeli scientists has discovered that cannabis may
help slow the growth of certain cancerous tumors, even eliminating them
completely, reported the Israeli daily <em>Haaretz</em>.
Already known for its therapeutic effects on certain diseases,
cannabis may also have reactive properties, according to Israeli
researchers at the Technion (Israel Institute of Technology) in Haifa
who conducted research on the healing properties of the plant.<br />
Dr. David Meiri, assistant professor in the biology department at the
Technion, is leading the research team. The project began a year ago
and is focused on the cytoskeleton and cell division in healthy and
cancerous cells.<br />
"There is a large body of scientific data which indicates that
cannabinoids specifically inhibit cancer cell growth and promote cancer
cell death," explained Meiri to <em>Haaretz</em>. "In addition to active
cannabinoids, cannabis plants also contain a multitude of other
therapeutic agents, such as terpenoids and flavonoids that are usually
present in small quantities, but can have beneficial therapeutic
effects, especially as synergistic compounds to cannabinoids."<br />
Meiri and his colleagues have succeeded in causing the cancer cells
responsible for brain cancer to "commit suicide,' and have also found
similar results in breast cancer cells, <br />
From there Meiri and his colleagues are hoping to find other cancer cells which react in the same way. <br />
Scientists are currently studying an estimated 50 different varieties
of cannabis produced in Israel and its effects on 200 different types
of cancer cells.<br />
Despite these promising results, Dr. Meiri said it was too early to draw definitive conclusions.<br />
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-48892075439348500362015-04-01T05:09:00.004-07:002015-04-30T14:09:00.827-07:00Article by Helen Bamber<div style="color: black; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 12px;">
<b><span style="text-decoration: underline;">The Legalization of Cannabis</span></b></div>
<div style="color: black; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 12px;">
The
questions and debate
surrounding the
legalisation of
cannabis have been
circling for
decades, but only
recently has the
weight of public
support swung in
favor of
legalisation. Whilst
the majority of
Americans now
support the concept
of cannabis
legalisation is some
format (whether for
medicinal or
recreational use)
the American
government still
spends around $1
billion every year
on enforcing the
current cannabis
prohibition laws.
Some key
commentators suspect
that we will soon
see this change. One
of the main problems
surrounding cannabis
legalisation, and
the main reason that
we haven’t seen
widespread
legalisation is in
getting the
legislation around
the issue right. If
marijuana is
legalised across the
board with open
access to all, in
the same way that
alcohol is
legalised, then we
are likely to see a
huge increase in the
number of cannabis
users, particularly
amongst the poor,
the young, and the
vulnerable:
something that no
government wants.
However there <a href="http://ricksimpsonhempoil.blogspot.co.uk/" target="_blank">are
many proven
benefits</a> of
marijuana use for
medicinal purposes,
and as more and more
studies prove its
worth, these really
cannot be ignored
any longer. So what
is the best way to
legalise marijuana
which will ensure
that the vulnerable
are protected,
whilst giving those
who need the drug
for medical use some
much needed
reassurance and
legal protection?</div>
<div style="color: black; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 12px;">
<br />
<b>Will
We Soon See
Federal Approval?</b></div>
<div style="color: black; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 12px;">
<a href="http://www.vox.com/2015/3/9/8177969/senate-medical-marijuana" target="_blank">It
was very recently
announced that</a>,
for the first time,
the Senate would
consider legalising
the medical use of
marijuana for people
who find the drug
beneficial in
assisting a list of
pre-approved
conditions. Whilst
several states have
already adopted this
policy and
incorporated it into
their state laws, so
far there has been
absolutely no
comment on the
process at a federal
level. Until now.
Senators Rand Paul
(R-KY), Cory Booker
(D-NJ), and Kirsten
Gillibrand (D-NY)
will join together
to introduce a bill
that would
reclassify marijuana
to schedule 1 rather
than schedule 2 in
the federal drugs
scheduling system.
The main benefit of
the bill is that it
would permanently
prohibit the federal
government from
shutting down
medical marijuana
operations in states
where the use of
marijuana is legal
for medicinal
purposes.
Rescheduling the
drug will allow for
further research
into the medical
benefits of taking
marijuana, enabling
at least three
different licenses
to be issued to
FDA-approved
research
institutions for
marijuana related
studies that will
only serve to
benefit the wider
population.</div>
<div style="color: black; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 12px;">
<br />
<b>The
Importance of
Smart Legislation</b></div>
<div style="color: black; font-family: Verdana,Arial,Helvetica,sans-serif; font-size: 12px;">
When
it comes to
legalizing cannabis,
it is important
that <a href="http://www.rehabs.com/pro-talk-articles/how-to-avoid-dumb-marijuana-legalization/" target="_blank">that
legalization is
sensible</a>, and
that it is
restricted to use
for medicinal
purposes, rather
than introduced in a
widespread way, in
the same way as
tobacco and
alcohol. An <a href="http://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/" target="_blank">estimated
42.1 million
adults</a> in
the United States
currently smoke cigarettes
(around 18% of the
population) and
around 130.6
million people
(which is more than
half of the
population)
currently regularly
drink alcohol. These
large figures are,
in a huge part,
because both of
these substances are
legal and people are
free to use them
without anything
other than age
restriction. In
comparison, there
are much fewer
people in the
country regularly
taking marijuana,
and the fear is that
complete
legalization would
change this, leaving
is living in a
nation of pot heads.
Nationwide and
unrestricted
legalization,
therefore, is
unlikely to ever
occur in the United
States and for good
reason.</div>
<br />
<br />
Now is the right time for the Senate to discuss this issue and for <span style="color: black;"><a href="http://www.drugpolicy.org/marijuana-legalization-and-regulation">this legislation to be passed</a>. As public opinion against the blanket prohibition of cannabis continues to grow, it is essential that the parameters within which the government are willing to consider legalizing the substance are outlined and discussed. Legalization on the basis of medical need makes good medical and national sense, and is something that has been recommended by a wide host of medical professionals. An across the board legalization, however, is yet to be recommended by any leading figure, and could well turn the tide of public opinion against the concept of legalization. Only time will tell if this new and exciting bill is passed by the Senate, and what it will mean for those in states where marijuana is not currently legal who wish to take the drug due to medical need. </span><br />
<br />
by Helen
Bamber<br />
<br />Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-20678100102198002942015-03-27T21:33:00.003-07:002015-03-27T21:34:54.869-07:00‘Vitamin Weed’: Neuroscientist says cannabis oil slows down aging process<br />
<div style="color: black;">
Neuroscientist Dr. Michelle Ross says she
believes everyone can benefit from ‘vitamin weed’, or daily cannabis oil
use. “Cannabis is the key to unlocking preventative medicine,” says
neuroscientist Dr. Michelle Ross. “It helps protect your DNA from
damage so it can actually slow down the aging process. I think everyone
should use cannabis oil, you should learn about it, you shouldn’t be
afraid.”</div>
<div style="color: black;">
In this clip from the <a href="http://reset.me/podcast/" style="color: #0252aa;" target="_blank"><i>Reset with Amber Lyon</i></a> podcast, Dr. Ross says she takes <a href="http://phoenixtears.ca/" style="color: #0252aa;" target="_blank">Rick Simpson Oil</a> on a daily basis to achieve endocannabinoid homeostasis. Endocannabinoids are your brain’s natural marijuana <a href="http://www.alternet.org/story/146151/not_feeling_well_perhaps_you%27re_%27marijuana_deficient%27" style="color: #0252aa;" target="_blank">and play a major role in overall health</a> including the regulation of <a href="http://norml.org/index.cfm?Group_ID=4166" style="color: #1c8585;">appetite</a>, <a href="http://norml.org/index.cfm?Group_ID=7791" style="color: #1c8585;">anxiety control</a>, <a href="http://norml.org/index.cfm?Group_ID=4316" style="color: #1c8585;">blood pressure</a>, <a href="http://norml.org/index.cfm?Group_ID=6780" style="color: #1c8585;">bone mass</a>, <a href="http://norml.org/index.cfm?Group_ID=6965" style="color: #1c8585;">reproduction</a>, and <a href="http://norml.org/index.cfm?Group_ID=3966" style="color: #1c8585;">motor coordination</a>. Deficient cannabinoid levels may be the underlying cause of numerous health conditions alleviated by cannabis.</div>
<div class="" style="clear: both; text-align: left;">
Dr. Ross is a former drug researcher for the National Institute on Drug Abuse, turned medical marijuana advocate.</div>
<div class="separator" style="clear: both; text-align: center;">
<br /></div>
<br />
<div class="separator" style="clear: both; text-align: left;">
<iframe allowfullscreen="" frameborder="0" height="315" src="https://www.youtube.com/embed/_R3swGg9iUw" width="560"></iframe><br /></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-63166362495942515042015-01-26T09:34:00.001-08:002015-01-26T09:34:26.557-08:00Proapoptotic effect of endocannabinoids in prostate cancer cells<a href="http://www.spandidos-publications.com/10.3892/or.2015.3746">http://www.spandidos-publications.com/10.3892/or.2015.3746</a><br />
<br />
<ul class="article_details">
<li><span class="bold">Authors:</span>
<ul>
<li>O. Orellana-Serradell</li>
<li>C. E. Poblete</li>
<li>C. Sanchez</li>
<li>E. A. Castellón</li>
<li>I. Gallegos</li>
<li>C. Huidobro</li>
<li>M. N. Llanos</li>
<li class="corresponding" title="hcontrer@med.uchile.cl">H. R. Contreras</li>
</ul>
</li>
<li><span class="bold">Corresponding author:</span>
<ul>
<li>
<span>H. R. Contreras [</span>
<a href="mailto:hcontrer@med.uchile.cl">
<span>hcontrer@med.uchile.cl</span>
</a>
]
</li>
</ul>
</li>
<li><a class="bold" href="http://www.spandidos-publications.com/10.3892/or.2015.3746#" id="toggle">View Affiliations</a><br />
</li>
<li>
<div>
<span class="bold">Published online on:</span> <span>Wednesday, January 21, 2015</span>
</div>
</li>
<li><span class="bold">DOI:</span> <span id="doi">10.3892/or.2015.3746</span> </li>
</ul>
<h4>
Abstract</h4>
<div>
In the early stages, prostate cancer is androgen‑ dependent;
therefore, medical castration has shown significant results during the
initial stages of this pathology. Despite this early effect, advanced
prostate cancer is resilient to such treatment. <b>Recent evidence shows
that derivatives of Cannabis sativa and its analogs may exert a
protective effect against different types of oncologic pathologies. </b>The
purpose of the present study was to detect the presence of cannabinoid
receptors (CB1 and CB2) on cancer cells with a prostatic origin and to
evaluate the effect of the in vitro use of synthetic analogs. In order
to do this, we used a commercial cell line and primary cultures derived
from prostate cancer and benign prostatic hyperplasia. The presence of
the CB1 and CB2 receptors was determined by immunohistochemistry where
we showed a higher expression of these receptors in later stages of the
disease (samples with a high Gleason score). Later, treatments were
conducted using anandamide, 2-arachidonoyl glycerol and a synthetic
analog of anandamide, methanandamide. <b>Using the MTT assay, we proved
that the treatments produced a cell growth inhibitory effect on all the
different prostate cancer cultures. This effect was demonstrated to be
dose-dependent. The use of a specific CB1 receptor blocker (SR141716)
confirmed that this effect was produced primarily from the activation of
the CB1 receptor.</b> In order to understand the MTT assay results, we
determined cell cycle distribution by flow cytometry, which showed no
variation at the different cell cycle stages in all the cultures after
treatment. <b>Treatment with endocannabinoids resulted in an increase in
the percentage of apoptotic cells as determined by Annexin V assays and
caused an increase in the levels of activated caspase-3 and a reduction
in the levels of Bcl-2 confirming that the reduction in cell viability
noted in the MTT assay was caused by the activation of the apoptotic
pathway. Finally, we observed that endocannabinoid treatment activated
the Erk pathway and at the same time, produced a decrease in the
activation levels of the Akt pathway. Based on these results, we suggest
that endocannabinoids may be a beneficial option for the treatment of
prostate cancer that has become nonresponsive to common therapies.</b></div>
<div>
<b> </b></div>
<div>
<a href="http://www.medicaljane.com/2015/01/25/endocannabinoids-in-the-treatment-of-prostate-cancer/" target="_blank">see also...<b> </b></a></div>
<div>
<a href="http://www.medicaljane.com/2015/01/25/endocannabinoids-in-the-treatment-of-prostate-cancer/" target="_blank"><br /></a><div class="wrapper wrapper--padded">
<a href="http://www.medicaljane.com/2015/01/25/endocannabinoids-in-the-treatment-of-prostate-cancer/" target="_blank">
</a><h1 class="heading heading--1">
<a href="http://www.medicaljane.com/2015/01/25/endocannabinoids-in-the-treatment-of-prostate-cancer/" target="_blank"><span style="font-size: large;">Endocannabinoids in the Treatment of Prostate Cancer</span></a></h1>
</div>
</div>
<div>
<br /></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-2666582001386142720.post-84558113200640047422015-01-23T23:13:00.002-08:002015-01-23T23:13:40.282-08:00German Scientists Have Confirmed an Amazing Link between Cannabis and Cancer Suppression <h2>
<a href="http://ireadculture.com/article-5046-german-scientists-have-confirmed-an-amazing-link-to-cannabis-between-cancer-suppression.html">Researchers at the Institute of Toxicology and Pharmacology of Rostock University in Germany further confirm the profound benefits of Cannabis</a></h2>
<h2>
</h2>
<h2>
<span style="font-family: arial; font-size: x-small;"><div class="CapitalLetter" style="float: left; font-size: 300%; margin: -8px 5px 0px 0px;">
R</div>
esearchers
at the Institute of Toxicology and Pharmacology of Rostock University
in Germany rang in the New Year with excellent news for the world. In a
study, Prof. Burkhard Hinz and his scientists put the active ingredients
in cannabis up to the claims of holding an ability to truly kill cancer
cells, even going further into the chemistry to find out exactly how
this medical miracle takes place. </span></h2>
<div class="MsoNormal">
<span style="font-family: arial; font-size: x-small;"><span lang="EN">Hinz’s
repertoire with cannabis goes back a ways. In 2008 his research team
was the first to discover that active ingredients actually <a href="http://jnci.oxfordjournals.org/content/100/1/59">slowed the migration of tumor cells</a> into
the surrounding tissues, this migration is what commonly leads
metastasis, which is when cancer moves out from one affected area and
into the rest of the body. </span></span></div>
<div class="MsoNormal">
<span style="font-family: arial; font-size: x-small;"><span class="hps"><span lang="EN">The research has been published in the January 2015 edition of the journal <i>Biochemical Pharmacology</i> with the title “New Insights into Antimetastic and Antiangiogenic Effects of Cannabinoids.” What they found was that both</span></span><span lang="EN"> <span class="hps">tetrahydrocannabinol (</span>THC <span class="hps">or</span> <span class="hps">known as</span> <span class="hps">Delta</span><span class="atn">-9-</span>Tetrahydrocannabinol) <span class="hps">and</span> <span class="hps">cannabidiol</span>, <span class="hps">also an active substance and</span> <span class="hps">originating from</span> <span class="hps">cannabis</span>, <span class="hps">contribute to the destruction</span> <span class="hps">of tumor cells</span> <span class="hps">by stimulating the formation</span> <span class="hps">of</span> <span class="hps">a specific protein</span>, <span class="hps">ICAM</span><span class="atn">-</span>1. By <span class="hps">acting</span> <span class="hps">on the surface</span> <span class="hps">of the cells</span> <span class="hps">attacked</span> <span class="hps">by</span> <span class="hps">cancer,</span> <span class="hps">the proteins link themselves</span> <span class="hps">to the immune system’s own defensive cells</span>, <span class="hps">making the cancerous cells</span> <span class="hps">burst.</span> The <span class="hps">active ingredients, thus,</span> <span class="hps">prevent</span> <span class="hps">cancerous cells</span> <span class="hps">from forming</span> <span class="hps">blood vessels</span> which allow <span class="hps">the cancer</span> to take root and <span class="hps">grow</span>.<br /><br /><span class="hps">This is, of course, very encouraging news, but </span>the
professor gave no timeline with respect to when his studies will
progress onward with the process of producing an actual medicine. <span class="hps">Hinz
emphasized that the study is still at an early stage, and said, “We are
far from putting our discoveries into practice on a clinical level.
However, our results are further evidence that cannabinoids mediate a
series of potentially therapeutic uses.” </span></span></span></div>
<h2>
</h2>
<h2>
<a href="http://www.sciencedirect.com/science/article/pii/S1937644814000082">http://www.sciencedirect.com/science/article/pii/S1937644814000082 </a></h2>
<h1 class="svTitle" id="title0010">
Chapter Two – New Insights into Antimetastatic and Antiangiogenic Effects of Cannabinoids</h1>
<br /><hr class="artHeader" id="abs_authorabs00101" />
<div class="abstract svAbstract " data-etype="ab">
<h2 class="secHeading" id="authorabs00101">
Abstract</h2>
<div id="abspara0010">
Cannabinoids
exert antitumorigenic effects via multiple mechanisms. Of these,
antimetastatic and antiangiogenic actions have attracted considerable
interest in the past years. Regarding the underlying antimetastatic
mechanism, several studies revealed cannabinoids to alter the gene
expression of cancer cells toward a less-aggressive phenotype and to
modulate their secretomic profile. Cannabinoids likewise modulate the
release of factors from tumor cells that subsequently suppress the
chemoattraction of vessel cells thereby conferring antiangiogenesis.
Among the diverse mediators of cannabinoids' antitumorigenic action, the
tissue inhibitor of matrix metalloproteinases-1, which is released from
cancer cells upon cannabinoid treatment, has been implicated as a
pivotal factor conferring both anti-invasive properties of cancer cells
as well as antiangiogenic capacities of endothelial cells. In addition,
cannabinoids have been shown to inhibit angiogenic capacities of
endothelial cells directly via suppressing their proliferation, tube
formation, and migration. This chapter reviews the cell- and
substance-specific antitumorigenic mechanisms of cannabinoids with
particular consideration of their antimetastatic/anti-invasive and
antiangiogenic actions. In addition, beneficial interactions of
cannabinoids with currently used chemotherapeutics as well as the
influence of cannabinoids on tumor-immune surveillance are addressed.
Collectively, the currently available data suggest cannabinoids as a
potential tool in modern cancer pharmacotherapy.</div>
</div>
<h2 class="svKeywords" id="kwd_1">
Keywords</h2>
<ul class="keyword" id="kwrds0010">
<li class="svKeywords" id="kwrd0010"><span id="">Angiogenesis</span>; </li>
<li class="svKeywords" id="kwrd0015"><span id="">Cancer</span>; </li>
<li class="svKeywords" id="kwrd0020"><span id="">Cannabinoids</span>; </li>
<li class="svKeywords" id="kwrd0025"><span id="">Metastasis</span>; </li>
<li class="svKeywords" id="kwrd0030"><span id="">Tumor cell invasion</span></li>
</ul>
<dl class="correspondence" id="cor1">
<dt class="label topPadd"><br /></dt>
<dd>Corresponding author: E-mail: burkhard.hinz@med.uni-rostock.de</dd></dl>
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