Tag Archives: Cannabinoids

Autophagy activation by novel inducers prevents BECN2-mediated drug tolerance to cannabinoids.

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“Cannabinoids and related drugs generate profound behavioral effects (such as analgesic effects) through activating CNR1 (cannabinoid receptor 1 [brain]). However, repeated cannabinoid administration triggers lysosomal degradation of the receptor and rapid development of drug tolerance, limiting the medical use of marijuana in chronic diseases.

Here we show that a protein involved in macroautophagy/autophagy (a conserved lysosomal degradation pathway), BECN2 (beclin 2), mediates cannabinoid tolerance by preventing CNR1 recycling and resensitization after prolonged agonist exposure, and deletion of Becn2 rescues CNR1 activity in mouse brain and conveys resistance to analgesic tolerance to chronic cannabinoids.

Overall, our findings demonstrate the functional link among autophagy, receptor signaling and animal behavior regulated by psychoactive drugs, and develop a new strategy to prevent tolerance and improve medical efficacy of cannabinoids by modulating the BECN2 interactome and autophagy activity.”

http://www.ncbi.nlm.nih.gov/pubmed/27305347

Cannabinoid receptor 2 as anti-obesity target: inflammation, fat storage and browning modulation.

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“Obesity is associated with a low-grade inflammatory state, and adipocyte hyperplasia/hypertrophy.

Obesity inhibits the “browning” of white adipose tissue.

Cannabinoid receptor 2 (CB2) agonists reduce food intake and induce anti-obesity effect in mice.

CB2 receptor is a novel pharmacological target that should be considered for obesity.”

http://www.ncbi.nlm.nih.gov/pubmed/27294325

http://www.thctotalhealthcare.com/category/obesity-2/

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain from Spinal Cord Injury and Disease.

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“Using eight hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, the majority of whom were experiencing pain despite traditional treatment.

After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta-9-tetrahydrocannabinol on three separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was utilized to attempt to reduce the placebo effect.

Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model demonstrated a significant analgesic response for vaporized cannabis.

When subjective and psychoactive side effects (e.g., good drug effect, feeling high, etc.) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all p<0.0004). Psychoactive and subjective effects were dose dependent.

Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. As the two active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord.

PERSPECTIVE:

A cross-over, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months in order to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/27286745

Cannabinoids cool the intestine

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“Inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn’s disease affects over a million people in the United States, with an estimated indirect cost from work loss of $3.6 billion annually. Many of these individuals suffer from pain, diarrhea and poor ability to digest their food, and in up to half of those with IBD, the disease is so severe that it ultimately requires surgery to remove the affected bowel segment.

Historically, marijuana has been used to treat diarrhea and has been advocated for the treatment of a variety of other gastrointestinal problems, including Crohn’s disease.

More recent pharmacological studies have clearly established that cannabinoids inhibit gastrointestinal motility and secretion by acting on CB1 receptors located on the terminals of both intrinsic and extrinsic submucosal neurons.

When administered to mice with chemically induced enteritis, cannabinoids also reduce inflammation and fluid accumulation in the gut.

Cannabinoids inhibit motility and secretion in the intestine.

They are now assigned the additional task of curbing excessive inflammation, suggesting that drugs targeting the endogenous cannabinoid system could be exploited for inflammatory bowel disease.

These findings may offer a new therapeutic approach to IBD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516444/

 

CANNABIS CHEMICALS STOP PROSTATE CANCER GROWTH

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“ACTIVE chemicals in cannabis have been shown to halt prostate cancer cell growth according to research published in the British Journal of Cancer*.

Researchers from the University of Alcala, in Madrid tested the effects of the active chemicals in cannabis called cannabinoids** on three human prostate cancer cell lines – called PC-3, DU-a45 and LNCaP.

The prostate cancer cells carry molecular ‘garages’- called receptors- in which cannabinoids can ‘park’.

The scientists showed for the first time that if cannabinoids ‘park’ on a receptor called CB2, the cancer cells stop multipyling.

“This research suggest that prostate cancer cells might stop growing if they are treated with chemicals found in cannabis but more work needs to be done to explore the potential of the cannabinoids in treatment.”

To confirm the findings the scientists switched off the CB2 receptors – or ‘closed the garage doors’- on the prostate cells. When cannabinoids were then added to cells without the CB2 receptor, the prostate cancer cells carried on dividing and growing. This suggests that cannabinoids connect with the CB2 receptors on prostate cancer cells to stop cell division and spread.

Professor Ines Diaz-Laviada, study author at the University of Alcala said: “Our research shows that there are areas on prostate cancer cells which can recognise and talk to chemicals found in cannabis called cannabinoids. These chemicals can stop the division and growth of prostate cancer cells and could become a target for new research into potential drugs to treat prostate cancer.””

http://www.nature.com/bjc/press_releases/p_r_aug09_6605248.html

https://www.news-medical.net/news/20090821/Cannabis-chemicals-stop-prostate-cancer-growth.aspx

Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R(+)-Methanandamide and JWH-015: Involvement of CB2

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“We have previously shown that cannabinoids induce growth inhibition and apoptosis in prostate cancer PC-3 cells, which express high levels of cannabinoid receptor types 1 and 2 (CB1 and CB2). In this study, we investigated the role of CB2 receptor in the anti-proliferative action of cannabinoids and the signal transduction triggered by receptor ligation.

This study defines the involvement of CB2-mediated signalling in the in vivo and in vitro growth inhibition of prostate cancer cells and suggests that CB2 agonists have potential therapeutic interest and deserve to be explored in the management of prostate cancer.

Cannabinoids, the active components of Cannabis sativa and their derivatives, exert a wide spectrum of modulatory actions and pharmacological activities in the brain as well as in the periphery, and therefore, the therapeutic potential of cannabinoids has gained much attention during the past few years. One of the most exciting areas of current research in the therapeutic potential of cannabinoids is cancer.

Recent evidence suggests that cannabinoids are powerful regulators of cell growth and differentiation. They have been shown to exert anti-tumoural effects by decreasing viability, proliferation, adhesion and migration on various cancer cells, thereby suggesting the potential use of cannabinoids in the treatment of gliomas, prostate and breast cancers and malignancies of immune origin.

Overall, our data show a role for the cannabinoid receptor CB2 in the anti-tumour effect of cannabinoids on prostate cells in vitroand in vivo. There is considerable interest in the application of selective CB2 receptor agonists, which are devoid of typical marijuana-like psychoactive properties of CB1 agonists, for future cannabinoid-based anticancer therapies. Therefore, our findings point to the potential application of cannabinoid receptor type 2 ligands as anti-tumour agents in prostate cancer.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743360/
http://www.thctotalhealthcare.com/category/prostate-cancer/

Activation of cannabinoid CB1 receptors in the ventral hippocampus improved stress-induced amnesia in rat.

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“The ventral hippocampus (VH) has a high distribution of cannabinoid CB1 receptors which are important in modulating stress responses. Stress exposure activates the hypothalamic-pituitary-adrenal axis (HPA) which can impact hippocampal formation to change hippocampus-based memories.

The purpose of the present study was to determine the possible role of the VH cannabinoid CB1 receptors in stress-induced amnesia using a step-through passive avoidance procedure in male Wistar rats.

Taken together, it can be concluded that exposure to post-training inescapable stress impaired memory consolidation. The impairing effects of stress on memory retrieval may be mediated by the VH cannabinoid CB1 receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27282634

The effect of spinally administered WIN 55,212-2, a cannabinoid agonist, on thermal pain sensitivity in diabetic rats.

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“These data show that cannabinoids have potent antinociceptive effects through direct actions in the spinal dorsal horn of nociceptive pathway. This suggests that intrathecally administered cannabinoids may offer hopeful strategies for the treatment of diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/27279983

Dronabinol for chemotherapy-induced nausea and vomiting unresponsive to antiemetics.

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“Chemotherapy-induced nausea and vomiting (CINV) is one of the most common symptoms feared by patients, but may be prevented or lessened with appropriate medications.

Several antiemetic options exist to manage CINV. Corticosteroids, serotonin receptor antagonists, and neurokinin receptor antagonists are the classes most commonly used in the prevention of CINV. There are many alternative drug classes utilized for the prevention and management of CINV such as antihistamines, benzodiazepines, anticonvulsants, cannabinoids, and dopamine receptor antagonists.

Medications belonging to these classes generally have lower efficacy and are associated with more adverse effects. They are also not as well studied compared to the aforementioned agents.

This review will focus on dronabinol, a member of the cannabinoid class, and its role in CINV.

Cannabis sativa L. (also known as marijuana) contains naturally occurring delta-9-tetrahydrocannibinol (delta-9-THC). The synthetic version of delta-9-THC is the active ingredient in dronabinol that makes dronabinol an orally active cannabinoid.

Evidence for clinical efficacy of dronabinol will be analyzed in this review as monotherapy, in combination with ondansetron, and in combination with prochlorperazine.”

http://www.ncbi.nlm.nih.gov/pubmed/27274310

Medicinal cannabis: Principal cannabinoids concentration and their stability evaluated by a high performance liquid chromatography coupled to diode array and quadrupole time of flight mass spectrometry method.

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“In the last few years, there has been a boost in the use of cannabis-based extracts for medicinal purposes, although their preparation procedure has not been standardized but rather decided by the individual pharmacists.

The present work describes the development of a simple and rapid high performance liquid chromatography method with UV detection (HPLC-UV) for the qualitative and quantitative determination of the principalcannabinoids (CBD-A, CBD, CBN, THC and THC-A) that could be applied to all cannabis-based medicinal extracts (CMEs) and easily performed by a pharmacist.

In order to evaluate the identity and purity of the analytes, a high-resolution mass spectrometry (HPLC-ESI-QTOF) analysis was also carried out. Full method validation has been performed in terms of specificity, selectivity, linearity, recovery, dilution integrity and thermal stability. Moreover, the influence of the solvent (ethyl alcohol and olive oil) was evaluated on cannabinoids degradation rate.

An alternative extraction method has then been proposed in order to preserve cannabis monoterpene component in final CMEs.”

http://www.ncbi.nlm.nih.gov/pubmed/27268223