Association between Cannabinoid CB1 Receptor Expression and Akt Signalling in Prostate Cancer

“In prostate cancer, tumour expression of cannabinoid CB1 receptors is associated with a poor prognosis. One explanation for this association comes from experiments with transfected astrocytoma cells, where a high CB receptor expression recruits the Akt signalling survival pathway. In the present study, we have investigated the association between CB1 receptor expression and the Akt pathway in a well-characterised prostate cancer tissue microarray.

Conclusions/Significance

The present study provides data that is consistent with the hypothesis that at a high CB1 receptor expression, the Akt signalling pathway becomes operative.”

Full Text: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0065798

Study: Cannabis may prevent brain damage – FOX

“Marijuana continues to be a paradox as it makes its way from illicit drug to wonder medicine being used to treat a number of symptoms and disorders more safely than traditional pharmaceuticals.”

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“In the latest news, cannabis, which has been associated with long-term cognitive deficits in chronic users, is now being tested as a treatment to preserve brain function after traumatic injury.

…some reports have shown that cannabis has neuroprotective effects. Studies have suggested that it has protective effects in neurodegenerative diseases like multiple sclerosis, Alzheimer’s, Huntington’s and Parkinson’s diseases.”

More: http://www.foxnews.com/health/2013/06/06/study-cannabis-may-prevent-brain-damage/

Read more: http://www.foxnews.com/health/2013/06/06/study-cannabis-may-prevent-brain-damage/#ixzz2VXJJw9yc

Marijuana habit not linked to lung cancer – Clinical Psychiatry News

“Regular cannabis smokers are no more likely to develop lung cancer than are people who indulge occasionally.”

“The finding of no significant increased risk held true whether the smokers imbibed once or twice – or more – each day, and regardless of how many years they had smoked, Dr. Li Rita Zhang reported at the annual meeting of the American Association of Cancer Research.”More: http://www.clinicalpsychiatrynews.com/news/across-specialties/single-article/marijuana-habit-not-linked-to-lung-cancer/73840afd2cca226b9e6a9ddc7cb0d039.html

http://www.oncologypractice.com/single-view/marijuana-habit-not-linked-to-lung-cancer/73840afd2cca226b9e6a9ddc7cb0d039.html

Transient changes in the endocannabinoid system after acute and chronic ethanol exposure and abstinence in the rat: a combined PET and microdialysis study.

“Recent biochemical and post-mortem evidence suggests involvement of the endocannabinoid system in alcohol drinking behaviour and dependence…

CONCLUSION:

This study provides in vivo evidence that acute ethanol consumption is associated with enhanced endocannabinoid signalling in the NAcc, indicated by an increased CB1R binding and AEA content. In addition, chronic ethanol exposure leads to regional dysfunctions in CB1R levels, involving the hippocampus and caudate-putamen that are reversible within 2 weeks in this animal model.”

http://www.ncbi.nlm.nih.gov/pubmed/23740372

Cannabinoid (CB)1 receptors are critical for the innate immune response to TLR4 stimulation.

“Sickness behaviours are host defence adaptations that arise from integrated autonomic outputs in response to activation of the innate immune system. These behaviours include fever, anorexia, and hyperalgesia intended to promote survival of the host when encountering pathogens. Cannabinoid (CB) receptor activation can induce hypothermia and attenuate lipopolysaccharide (LPS)-evoked fever. The aim of the present study was to examine the role of CB1 receptors in the LPS-evoked febrile response. CB1 receptor-deficient (CB1-/-) mice did not display LPS-evoked fever; likewise pharmacological blockade of CB1 receptors in wild-type mice blocked LPS-evoked fever. This unresponsiveness is not limited to thermogenesis, as the animals were not hyperalgesic after LPS administration. A toll-like receptor (TLR)3 agonist and viral mimetic polyinosinic:polycytidylic acid evoked a robust fever in CB1-/- mice suggesting TLR3-mediated responses are functional. LPS-evoked c-Fos activation in areas of the brain associated with the febrile response was evident in wild-type mice but not in CB1-/- mice. Liver and spleen TLR4 mRNA were significantly lower in CB1-/- mice compared to wild-type, and peritoneal macrophages from CB1-/- mice did not release pro-inflammatory cytokines in response to LPS. These data indicate that CB1 receptors play a critical role in LPS-induced febrile responses through inhibiting TLR4-mediated cytokine production.”

http://www.ncbi.nlm.nih.gov/pubmed/23739343

An Effective Prodrug Strategy to Selectively Enhance Ocular Exposure of a Cannabinoid Receptor (CB1/2) Agonist.

“Glaucoma is a leading cause of vision loss and blindness, with increased intraocular pressure (IOP) a prominent risk factor. IOP can be efficaciously reduced by administration of topical agents. However, the repertoire of approved IOP-lowering drug classes is limited, and effective new alternatives are needed. Agonism of the cannabinoid receptors CB1/2 significantly reduces IOP clinically, and experimentally. However, development of CB1/2 agonists has been complicated by the need to avoid cardiovascular and psychotropic side effects. Compound A is a potent CB1/2 agonist that is highly excluded from the brain. In a phase I study, compound A eyedrops were well tolerated and generated an IOP-lowering trend, but were limited in dose and exposure due to poor solubility and ocular absorption. Here we present an innovative strategy to rapidly identify compound A prodrugs that are efficiently metabolized to the parent compound, for improved solubility and ocular permeability, while maintaining low systemic exposures.”

http://www.ncbi.nlm.nih.gov/pubmed/23738526

Medicinal Use of Marijuana — Polling Results – The New England Journal of Medicine

“Readers recently joined in a lively debate about the use of medicinal marijuana. In Clinical Decisions,1 an interactive feature in which experts discuss a controversial topic and readers vote and post comments, we presented the case of Marilyn, a 68-year-old woman with metastatic breast cancer. We asked whether she should be prescribed marijuana to help alleviate her symptoms. To frame this issue, we invited experts to present opposing viewpoints about the medicinal use of marijuana. J. Michael Bostwick, M.D., a professor of psychiatry at Mayo Clinic, proposed the use of marijuana “only when conservative options have failed for fully informed patients treated in ongoing therapeutic relationships.” Gary M. Reisfield, M.D., from the University of Florida, certified in anesthesiology and pain medicine, and Robert L. DuPont, M.D., a clinical professor of psychiatry at Georgetown Medical School, provide a counterpoint, concluding that “there is little scientific basis” for physicians to endorse smoked marijuana as a medical therapy.

We were surprised by the outcome of polling and comments, with 76% of all votes in favor of the use of marijuana for medicinal purposes — even though marijuana use is illegal in most countries. A total of 1446 votes were cast from 72 countries and 56 states and provinces in North America, and 118 comments were posted. However, despite the global participation, the vast majority of votes (1063) came from the United States, Canada, and Mexico. Given that North America represents only a minority of the general online readership of the Journal, this skew in voting suggests that the subject of this particular Clinical Decisions stirs more passion among readers from North America than among those residing elsewhere. Analysis of voting across all regions of North America showed that 76% of voters supported medicinal marijuana. Each state and province with at least 10 participants casting votes had more than 50% support for medicinal marijuana except Utah. In Utah, only 1% of 76 voters supported medicinal marijuana. Pennsylvania represented the opposite extreme, with 96% of 107 votes in support of medicinal marijuana.

Outside North America, we received the greatest participation from countries in Latin America and Europe, and overall results were similar to those of North America, with 78% of voters supporting the use of medicinal marijuana. All countries with 10 or more voters worldwide were at or above 50% in favor. There were only 43 votes from Asia and 7 votes from Africa, suggesting that in those continents, this topic does not resonate as much as other issues.

Where does this strong support for medicinal marijuana come from? Your comments show that individual perspectives were as polarized as the experts’ opinions. Physicians in favor of medicinal marijuana often focused on our responsibility as caregivers to alleviate suffering. Many pointed out the known dangers of prescription narcotics, supported patient choice, or described personal experience with patients who benefited from the use of marijuana. Those who opposed the use of medicinal marijuana targeted the lack of evidence, the lack of provenance, inconsistency of dosage, and concern about side effects, including psychosis. Common in this debate was the question of whether marijuana even belongs within the purview of physicians or whether the substance should be legalized and patients allowed to decide for themselves whether to make use of it.

In sum, the majority of clinicians would recommend the use of medicinal marijuana in certain circumstances. Large numbers of voices from all camps called for more research to move the discussion toward a stronger basis of evidence.”

http://www.nejm.org/doi/full/10.1056/NEJMclde1305159

“New England Journal of Medicine Endorses Medical Marijuana; San Francisco Medical Society Releases Study; New York Times Editorial Welcomes Debate” http://ndsn.org/feb97/nejm.html

Three out of four doctors recommend marijuana in New England Journal of Medicine poll

More than three out of four doctors support medical cannabis for a hypothetical breast cancer patient, New England Journal of Medicine reports“More than three out of four doctors support medical cannabis for a hypothetical breast cancer patient, New England Journal of Medicine reports

In a poll by the well-respected New England Journal of Medicine released today, more than three out of four doctors recommended medical cannabis for a hypothetical late-stage breast cancer patient.

“We were surprised by the outcome of polling and comments, with 76% of all votes in favor of the use of marijuana for medicinal purposes — even though marijuana use is illegal in most countries,” Jonathan N. Adler, M.D., and James A. Colbert, M.D. wrote for the NEJOM May 30th.

Marijuana is a federally illegal – schedule one drug – that the U.S. government claims has no medical value and is more dangerous than heroin or LSD. Yet 19 states have legalized cannabis for medical use, given its 10,000 year history as a safe herbal remedy for nausea, pain and insomnia among other conditions.”

More: http://blog.sfgate.com/smellthetruth/2013/05/30/three-out-of-four-doctors-recommend-marijuana-in-new-england-journal-of-medicine-poll/

Majority Support Medical Pot in New NEJM Poll

“To recommend, or not to recommend, medicinal marijuana? That’s the question recently posed in a New England Journal of Medicine interactive online poll. To get a feel for physicians’ opinions, NEJM presented readers with a fictional clinical situation. Here’s the scenario:

“Marilyn is a 68-year-old woman with breast cancer metastatic to the lungs and the thoracic and lumbar spine. She is currently undergoing chemotherapy with doxorubicin. She reports having very low energy, minimal appetite, and substantial pain in her thoracic and lumbar spine. For relief of nausea, she has taken ondansetron and prochlorperazine, with minimal success. She has been taking 1000 mg of acetaminophen every 8 hours for the pain. Sometimes at night she takes 5 mg or 10 mg of oxycodone to help provide pain relief. During a visit with her primary care physician she asks about the possibility of using marijuana to help alleviate the nausea, pain, and fatigue. She lives in a state that allows marijuana for personal medicinal use, and she says her family could grow the plants. As her physician, what advice would you offer with regard to the use of marijuana to alleviate her current symptoms? Do you believe that the overall medicinal benefits of marijuana outweigh the risks and potential harms?”

Readers weighed in with a variety of impassioned opinions. And the results, the authors said, were  surprising: 76% of respondents said they would recommend medicinal marijuana. Here’s part of the discussion:

“Physicians in favor of medicinal marijuana often focused on our responsibility as caregivers to alleviate suffering. Many pointed out the known dangers of prescription narcotics, supported patient choice, or described personal experience with patients who benefited from the use of marijuana. Those who opposed the use of medicinal marijuana targeted the lack of evidence, the lack of provenance, inconsistency of dosage, and concern about side effects, including psychosis. Common in this debate was the question of whether marijuana even belongs within the purview of physicians or whether the substance should be legalized and patients allowed to decide for themselves whether to make use of it.”” 

More: http://ripr.org/post/majority-support-medical-pot-new-nejm-poll 

Majority of Clinicians Support Medicinal Marijuana Use

“A majority of clinicians appears to support the use of medicinal marijuana, according to research published in the May 30 issue of the New England Journal of Medicine.”

Majority of Clinicians Support Medicinal Marijuana Use 
“(HealthDay News) – A majority of clinicians appears to support the use of medicinal marijuana, according to research published in the May 30 issue of the New England Journal of Medicine.
 

Jonathan N. Adler, MD, and James A. Colbert, MD, associate editors for the New England Journal of Medicine, describe the results of polling and comments in an interactive feature in which experts discussed the use of medicinal marijuana for a 68-year old woman with metastatic breast cancer.”

More: http://www.empr.com/majority-of-clinicians-support-medicinal-marijuana-use/article/295539/#