Effect of myrcene on nociception in mice.

“Myrcene, a monoterpene… The results suggest that myrcene is capable of inducing antinociception in mice, probably mediated by alpha 2-adrenoceptor stimulated release of endogenous opioids.” http://www.ncbi.nlm.nih.gov/pubmed/1983154

“Myrcene as a natural base chemical in sustainable chemistry: a critical review.”  http://www.ncbi.nlm.nih.gov/pubmed/20013989

“Single dose toxicity study of beta-myrcene, a natural analgesic substance.”  http://www.ncbi.nlm.nih.gov/pubmed/2101331

“Myrcene mimics the peripheral analgesic activity of lemongrass tea.  Terpenes such as myrcenemay constitute a lead for the development of new peripheral analgesics with a profile of action different from that of the aspirin-like drugs.”  http://www.ncbi.nlm.nih.gov/pubmed/1753786

“Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol. The top five major compounds in Bedrocan extracts were Delta(9)-THC, cannabigerol (CBG), terpinolene, myrcene, and cis-ocimene in Bedrobinol Delta(9)-THC, myrcene, CBG, cannabichromene (CBC), and camphene in Bediol cannabidiol (CBD), Delta(9)-THC, myrcene, CBC, and CBG. The major components in Bedrocan smoke were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene. The major components in Bedrocan vapor were Delta(9)-THC, terpinolene, myrcene, CBG, cis-ocimene and CBD in Bedrobinol Delta(9)-THC, myrcene and CBD in Bediol CBD, Delta(9)-THC, myrcene, CBC and terpinolene. ” http://www.ncbi.nlm.nih.gov/pubmed/20118579

Dissecting the signaling pathways involved in the crosstalk between mGlu5 and CB1 receptors.

“The metabotropic glutamate (mGlu) receptor 5 and the cannabinoid type 1 (CB1) receptor are G-protein-coupled receptors (GPCR) that are widely expressed in the central nervous system (CNS). mGlu5 receptors, present at the postsynaptic site, are coupled to Gαq/11 proteins and display an excitatory response upon activation, while the CB1 receptor, mainly present at presynaptic terminals, is coupled to the Gi/o protein and triggers an inhibitory response. Recent studies suggest that the glutamatergic and endocannabinoid systems exhibit a functional interaction to modulate several neural processes. In this review we discuss possible mechanisms involved in this crosstalk and its relationship with physiological and pathological conditions, including nociception, addiction and fragil X syndrome.”

http://www.ncbi.nlm.nih.gov/pubmed/27338080

Pot a Common Remedy to Ease Back Pain

“Use of marijuana to ease back pain was common among patients at a university spine clinic in Colorado where pot has been legal for medical purposes since 2000, but most of the users did not have a prescription, according to research presented here.

Among 184 patients at a Colorado spine center, 19% said they used marijuana for pain relief, but less than half, 46%, actually had a prescription for the drug, according to study co-author Michael Finn, MD, an assistant professor of neurosurgery at the University of Colorado in Denver.

The most common way to use the drug was smoking it, 90%, followed by oral ingestion, 45%, and vaporization, 29%.

According to the users, marijuana worked. A total of 89% said it greatly or moderately relived their pain, and 81% said it worked as well as or better than narcotic painkillers.”

http://www.medpagetoday.com/MeetingCoverage/AdditionalMeetings/42228

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

“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

Opioid and cannabinoid synergy in a mouse neuropathic pain model.

“Clinical studies have reported that pan-cannabinoid receptor agonists may have efficacy in neuropathic pain states and that this might be enhanced by co-administration with opioids. While cannabinoid-opioid analgesic synergy has been demonstrated in animal models of acute pain, it has not been examined in neuropathic pain models. We examined the effect of combination treatment with cannabinoid and opioid receptor agonists on allodynia and side-effects in a nerve injury induced neuropathic pain model.

These findings indicate that combination administration of non-selective opioid and cannabinoid receptor agonists synergistically reduces nerve injury induced allodynia, while producing side-effects in an additive manner. This suggests that combination treatment has an improved anti-allodynic potency and therapeutic index in a neuropathic pain model.”

http://www.ncbi.nlm.nih.gov/pubmed/27278681

Medical Cannabis Use Is Associated With Decreased Opiate Medication Use in a Retrospective Cross-Sectional Survey of Patients With Chronic Pain

“Cannabis use was associated with 64% lower opioid use in patients with chronic pain.

Cannabis use was associated with better quality of life in patients with chronic pain.

Cannabis use was associated with fewer medication side effects and medications used.”

  • Journal of Pain Home

“Opioids are commonly used to treat patients with chronic pain (CP), though there is little evidence that they are effective for long term CP treatment. Previous studies reported strong associations between passage of medical cannabis laws and decrease in opioid overdose statewide. Our aim was to examine whether using medical cannabis for CP changed individual patterns of opioid use.

Using an online questionnaire, we conducted a cross-sectional retrospective survey of 244 medical cannabis patients with CP who patronized a medical cannabis dispensary in Michigan between November 2013 and February 2015. Data collected included demographic information, changes in opioid use, quality of life, medication classes used, and medication side effects before and after initiation of cannabis usage. Among study participants, medical cannabis use was associated with a 64% decrease in opioid use (n = 118), decreased number and side effects of medications, and an improved quality of life (45%).

This study suggests that many CP patients are essentially substituting medical cannabis for opioids and other medications for CP treatment, and finding the benefit and side effect profile of cannabis to be greater than these other classes of medications. More research is needed to validate this finding.

Perspective

This article suggests that using medical cannabis for CP treatment may benefit some CP patients. The reported improvement in quality of life, better side effect profile, and decreased opioid use should be confirmed by rigorous, longitudinal studies that also assess how CP patients use medical cannabis for pain management.”

http://www.jpain.org/article/S1526-5900(16)00567-8/abstract

Cannabinoid receptor 2 (CB2) agonists and antagonists: a patent update.

“Modulation of the CB2 receptor is an interesting approach for pain and inflammation, arthritis, addictions, neuroprotection, and cancer, among other possible therapeutic applications, and is devoid of central side effects.

Structural diversity of CB2 modulator scaffolds characterized the patent literature.

Several CB2 agonists reached clinical Phase II for pain management and inflammation.

Other therapeutic applications need to be explored such as neuroprotection and/or neurodegeneration.”

http://www.ncbi.nlm.nih.gov/pubmed/27215781

[MEDICAL CANNABIS].

“The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea and inflammation.

Current research is inspecting the use of cannabis for many diseases, including multiple sclerosis, epilepsy, dystonia, and chronic pain.

In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and: pain and diarrhea in Crohn’s disease.

Despite their therapeutic potential, cannabinoids are not free of side effects including psychosis, anxiety, paranoia, dependence and abuse.

Controlled clinical studies investigating the therapeutic potential of cannabis are few and small, whereas pressure for expanding cannabis use is increasing.

Currently, as long as cannabis is classified as an illicit drug and until further controlled studies are performed, the use of medical cannabis should be limited to patients who failed conventional better established treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/27215115

Interactions between cannabinoid receptor agonists and mu opioid receptor agonists in rhesus monkeys discriminating fentanyl.

“Cannabinoid receptor agonists such as delta-9-tetrahydrocannabinol (Δ9-THC) enhance some (antinociceptive) but not other (positive reinforcing) effects of mu opioid receptor agonists, suggesting that cannabinoids might be combined with opioids to treat pain without increasing, and possibly decreasing, abuse.

These data indicate that the discriminative stimulus effects of nalbuphine are more sensitive to attenuation by cannabinoids than those of fentanyl. That the discriminative stimulus effects of some opioids are more susceptible to modification by drugs from other classes has implications for developing maximally effective therapeutic drug mixtures with reduced abuse liability.”

http://www.ncbi.nlm.nih.gov/pubmed/27184925

Cannabis in Pain Treatment: Clinical and Research Considerations

“Cannabinoids show promise as therapeutic agents, particularly as analgesics, but their development and clinical use has been complicated by recognition of their botanical source, cannabis, as a substance of misuse.

Although research into endogenous cannabinoid systems and potential cannabinoid pharmaceuticals is slowly increasing, there has been intense societal interest in making herbal (plant) cannabis available for medicinal use; 23 U.S. States and all Canadian provinces currently permit use in some clinical contexts.

Whether or not individual professionals support the clinical use of herbal cannabis, all clinicians will encounter patients who elect to use it and therefore need to be prepared to advise them on cannabis-related clinical issues despite limited evidence to guide care.

Expanded research on cannabis is needed to better determine the individual and public health effects of increasing use of herbal cannabis and to advance understanding of the pharmaceutical potential of cannabinoids as medications.

This article reviews clinical, research, and policy issues related to herbal cannabis to support clinicians in thoughtfully advising and caring for patients who use cannabis, and it examines obstacles and opportunities to expand research on the health effects of herbal cannabis and cannabinoids.

Perspective

Herbal cannabis is increasingly available for clinical use in the United States despite continuing controversies over its efficacy and safety. This article explores important considerations in the use of plant Cannabis to better prepare clinicians to care for patients who use it, and identifies needed directions for research.”

http://www.jpain.org/article/S1526-5900%2816%2900543-5/fulltext

“APS Issues New Guidance on Medical Marijuana for Pain”  http://www.medscape.com/viewarticle/863396