Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation.

“There is now a large body of data indicating that the cannabinoid receptor type 2 (CB2) is linked to a variety of immune events. This functional relevance appears to be most salient in the course of inflammation, a process during which there is an increased number of receptors that are available for activation. Studies aimed at elucidating signal transduction events resulting from CB2 interaction with its native ligands, and of the role of exogenous cannabinoids in modulating this process, are providing novel insights into the role of CB2 in maintaining a homeostatic immune balance within the host. Furthermore, these studies suggest that the CB2 may serve as a selective molecular target for therapeutic manipulation of untoward immune responses, including those associated with a variety of neuropathies that exhibit a hyperinflammatory component.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768535/

Foot Pain Associated With HIV Reduced By Smoked Cannabis In Placebo Trial

“In a randomized placebo-controlled trial, patients smoking cannabis experienced a 34 percent reduction in intense foot pain associated with HIV- twice the rate experienced by patients who smoked placebo.

“This placebo-controlled clinical trial showed that people with HIV who smoked cannabis had substantially greater pain reduction than those who did not smoke the cannabis,” said study lead author Donald I. Abrams, MD, UCSF professor of clinical medicine.

 “These results provide evidence that there is a measurable medical benefit to smoking cannabis for these patients.”

The results of this first study indicate that cannabis may indeed be useful in the amelioration of a very distressing, disabling, and difficult to treat complication of HIV…”

More: http://www.medicalnewstoday.com/releases/62917.php

Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial.

“To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model…  randomized placebo-controlled trial… involving adults with painful HIV-associated sensory neuropathy.

Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days. Primary outcome measures included ratings of chronic pain and the percentage achieving >30% reduction in pain intensity.

Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model.

RESULTS:

Fifty patients completed the entire trial. Smoked cannabis reduced daily pain by 34% (median reduction; IQR = -71, -16) vs 17% (IQR = -29, 8) with placebo (p = 0.03). Greater than 30% reduction in pain was reported by 52% in the cannabis group and by 24% in the placebo group (p = 0.04).

The first cannabis cigarette reduced chronic pain by a median of 72% vs 15% with placebo (p < 0.001).

Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli (p < or = 0.05) but appeared to have little effect on the painfulness of noxious heat stimulation.

No serious adverse events were reported.

CONCLUSION:

Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/17296917

Medicinal Marijuana Effective For Neuropathic Pain In HIV – MedicalNewsToday

“In a double-blind, placebo-controlled clinical trial to assess the impact of smoked medical cannabis, or marijuana, on the neuropathic pain associated with HIV, researchers at the University of California, San Diego School of Medicine found that reported pain relief was greater with cannabis than with a placebo. The study, sponsored by the University of California Center for Medical Cannabis Research (CMCR) based at UC San Diego, will be published on line, in the journal Neuropsychopharmacology.

Led by Ronald J. Ellis, M.D., Ph.D., associate professor of neurosciences at UCSD School of Medicine, the study looked at 28 HIV patients with neuropathic pain not adequately controlled by other pain-relievers, including opiates. They took part in the controlled study as outpatients at the UCSD Medical Center. The proportion of subjects achieving pain reduction of 30 percent or more was greater for those smoking cannabis than those smoking the placebo.

“Neuropathy is a chronic and significant problem in HIV patients as there are few existing treatments that offer adequate pain management to sufferers,” Ellis said. “We found that smoked cannabis was generally well-tolerated and effective when added to the patient’s existing pain medication, resulting in increased pain relief.””

More:  http://www.medicalnewstoday.com/releases/117509.php

Medicinal Marijuana Effective For Neuropathic Pain In HIV, Study Finds – ScienceDaily

“In a double-blind, placebo-controlled clinical trial to assess the impact of smoked medical cannabis, or marijuana, on the neuropathic pain associated with HIV, researchers at the University of California, San Diego School of Medicine found that reported pain relief was greater with cannabis than with a placebo.

The study’s findings are consistent with and extend other recent research supporting the short-term efficacy of cannabis for neuropathic pain,

“This study adds to a growing body of evidence that indicates that cannabis is effective, in the short-term at least, in the management of neuropathic pain,” commented Igor Grant, M.D., professor of psychiatry and director of the CMCR.

Grant noted that this is the fourth CMCR sponsored study to provide convergent evidence that cannabis can help in relieving these types of pain…”

More: http://www.sciencedaily.com/releases/2008/08/080806113135.htm

Medical Marijuana Might Reduce Nerve Pain Among People Living With HIV/AIDS, Study Says – MedicalNewsToday

“Medical marijuana might reduce the pain of peripheral neuropathy, a type of nerve damage, among people living with HIV/AIDS, according to a study published in the Feb. 13 issue of the journal Neurology, the Washington Post reports (Weiss, Washington Post, 2/13). Donald Abrams of the University of California-San Francisco and colleagues examined the effects of smoking medicinal marijuana among people living with HIV/AIDS during a two-year period beginning in May 2003, the San Francisco Chronicle reports.

The results are “evidence, using the gold standard for clinical research, that cannabis has some medical benefits for a condition that can be severely debilitating,” Abrams said.”

More:  http://www.medicalnewstoday.com/releases/62955.php

Marijuana Spray Proves Effective as Cancer Pain Treatment

“A mouth spray containing cannabinoids is effective in reducing pain in cancer patients who are still in pain despite using opioid medicines, according to a new study published in The Journal of Pain.”

 
“The oral mucosal spray known as nabixmols, which is marketed under the trade name Sativex, contains a formulation of cannabinoids, marijuana’s most active ingredients.”
 

More: http://americannewsreport.com/nationalpainreport/marijuana-spray-proves-effective-as-cancer-pain-treatment-8814518.html

A Double-Blind, Placebo-Controlled, Crossover Pilot Trial With Extension Using an Oral Mucosal Cannabinoid Extract for Treatment of Chemotherapy-Induced Neuropathic Pain.

“Neuropathic pain caused by chemotherapy limits dosing and duration of potentially life-saving anti-cancer treatment and impairs quality of life. Chemotherapeutic neuropathy responds poorly to conventional treatments, and there is an urgent medical need for new treatments. Recent preclinical studies demonstrate that cannabinoid agonists suppress established chemotherapy-evoked neuropathy.

This was a pilot trial to begin to investigate a currently available cannabinoid agent, nabiximols (oral mucosal spray containing cannabinoids), in the treatment of chemotherapy-induced neuropathic pain.

CONCLUSION:

Chemotherapy-induced neuropathic pain is particularly resistant to currently available treatments. This pilot trial found a number needed to treat of five and an average decrease of 2.6 on an 11-point NRS-PI in five “responders” (as compared with a decrease of 0.6 with placebo) and supports that it is worthwhile to study nabiximols in a full randomized, placebo-controlled trial of chemotherapy-induced neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/23742737

Synthetic and Patented Cannabinoids

“Historically, laboratory synthesis of cannabinoids were often based on the structure of herbal cannabinoids, and a large number of analogs have been produced and tested, especially in a group led by Roger Adams as early as 1941 and later in a group led by Raphael Mechoulam.

Newer compounds are no longer related to natural cannabinoids or are based on the structure of the endogenous cannabinoids.

Synthetic cannabinoids are particularly useful in experiments to determine the relationship between the structure and activity of cannabinoid compounds, by making systematic, incremental modifications of cannabinoid molecules.

Medications containing natural or synthetic cannabinoids or cannabinoid analogs:

  • Dronabinol (Marinol), is Δ9-tetrahydrocannabinol (THC), used as an appetite stimulant, anti-emetic, and analgesic
  • Nabilone (Cesamet), a synthetic cannabinoid and an analog of Marinol. It is Schedule II unlike Marinol, which is Schedule III
  • Sativex, a cannabinoid extract oral spray containing THC, CBD, and other cannabinoids used for neuropathic pain and spasticity in Canada and Spain. Sativex develops whole-plant cannabinoid medicines
  • Rimonabant (SR141716), a selective cannabinoid (CB1) receptor antagonist used as an anti-obesity drug under the proprietary name Acomplia. It is also used for smoking cessation

Other notable synthetic cannabinoids include:

  • CP-55940, produced in 1974, this synthetic cannabinoid receptor agonist is many times more potent than THC
  • Dimethylheptylpyran
  • HU-210, about 100 times as potent as THC
  • HU-331 a potential anti-cancer drug derived from cannabidiol that specifically inhibits topoisomerase II.
  • SR144528, a CB2 receptor antagonists
  • WIN 55, a potent cannabinoid receptor agonist
  • JWH-133, a potent selective CB2 receptor agonist
  • Levonantradol (Nantrodolum), an anti-emetic and analgesic but not currently in use in medicine”

http://www.news-medical.net/health/Synthetic-and-Patented-Cannabinoids.aspx

Marijuana Vaporizer Provides Same Level Of THC, Fewer Toxins, Study Shows

“A smokeless cannabis-vaporizing device delivers the same level of active therapeutic chemical and produces the same biological effect as smoking cannabis…

…smoked cannabis can alleviate the chronic pain caused by HIV-related neuropathy, but a concern was expressed that smoking cannabis was not safe. This study demonstrates an alternative method that gives patients the same effects and allows controlled dosing but without inhalation of the toxic products in smoke,” said study lead author Donald I. Abrams, MD, UCSF professor of clinical medicine.

…pills tend to provide patients with more THC than they need for optimal therapeutic effect and increase side effects.

Patients rated the “high” they experienced from both smoking and vaporization and there was no difference between the two methods by patient self-report of the effect, according to study findings. In addition, patients were asked which method they preferred.

“By a significant majority, patients preferred vaporization to smoking, choosing the route of delivery with the fewest side effects and greatest efficiency,” said Benowitz.”

Read more: http://www.sciencedaily.com/releases/2007/05/070515151145.htm