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

The endocannabinoid system and its therapeutic exploitation.

Image result for Nat Rev Drug Discov.

“The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the endocannabinoid system might be realized in the years to come.”  http://www.ncbi.nlm.nih.gov/pubmed/15340387

http://www.nature.com/nrd/journal/v3/n9/full/nrd1495.html

Cannabidiol as an Emergent Therapeutic Strategy for Lessening the Impact of Inflammation on Oxidative Stress

Figure 1

“Growing evidence suggests that the endocannabinoid system, which includes the CB1 and CB2 G protein-coupled receptors and their endogenous lipid ligands, may be an area that is ripe for therapeutic exploitation. In this context, the related nonpsychotropic cannabinoid cannabidiol, which may interact with the endocannabinoid system, but has actions that are distinct, offers promise as a prototype for anti-inflammatory drug development.

This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types I and II diabetes, atherosclerosis, Alzheimer’s disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.

Cannabidiol (CBD) is the major nonpsychotropic cannabinoid compound derived from the plant Cannabis sativa, commonly known as marijuana…

Conclusions

Inflammation and oxidative stress are intimately involved in the genesis of many human diseases. Unraveling that relationship therapeutically has proven challenging, in part because inflammation and oxidative stress “feed off” each other. However, CBD would seem to be a promising starting point for further drug development given its anti-oxidant (although relatively modest) and anti-inflammatory actions on immune cells, such as macrophages and microglia. CBD also has the advantage of not having psychotropic side effects. Studies on models of human diseases support the idea that CBD attenuates inflammation far beyond its antioxidant properties, for example, by targeting inflammation-related intracellular signaling events. The details on how CBD targets inflammatory signaling remain to be defined.

The therapeutic utility of CBD is a relatively new area of investigation that portends new discoveries on the interplay between inflammation and oxidative stress, a relationship that underlies tissue and organ damage in many human diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085542/