Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial.

“In 1999, a report of the United States Institute of Medicine recommended further investigations of the possible benefits of cannabis (marijuana) as a medicinal agent for a variety of conditions, including neuropathic pain due to HIV distal sensory polyneuropathy (DSPN). The most abundant active ingredient in cannabis, tetrahydro-cannabinol (THC), and its synthetic derivatives, produce effective analgesia in most animal models of pain. The antinociceptive effects of THC are mediated through cannabinoid receptors (CB1, CB2) in the central and peripheral nervous systems, which in turn interact with noradrenergic and κ-opioid systems in the spinal cord to modulate the perception of painful stimuli. The endogenous ligand of CB1, anandamide, itself is an effective antinociceptive agent. In open-label clinical trials and one recent controlled trial, medicinal cannabis has shown preliminary efficacy in relieving neuropathic pain.”

“We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV. This was a phase II, double-blind, placebo-controlled, crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy (DSPN).”

 “…pain relief was greater with cannabis than placebo…”

 “Smoked cannabis was generally well tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV DSPN.”

“Our findings suggest that cannabinoid therapy may be an effective option for pain relief in patients with medically intractable pain due to HIV-associated DSPN.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3066045/

Antihyperalgesic effect of a Cannabis sativa extract in a rat model of neuropathic pain: mechanisms involved.

Abstract

“This study aimed to give a rationale for the employment of phytocannabinoid formulations to treat neuropathic pain. It was found that a controlled cannabis extract, containing multiple cannabinoids, in a defined ratio, and other non-cannabinoid fractions (terpenes and flavonoids) provided better antinociceptive efficacy than the single cannabinoid given alone, when tested in a rat model of neuropathic pain. The results also demonstrated that such an antihyperalgesic effect did not involve the cannabinoid CB1 and CB2 receptors, whereas it was mediated by vanilloid receptors TRPV1. The non-psychoactive compound, cannabidiol, is the only component present at a high level in the extract able to bind to this receptor: thus cannabidiol was the drug responsible for the antinociceptive behaviour observed. In addition, the results showed that after chronic oral treatment with cannabis extract the hepatic total content of cytochrome P450 was strongly inhibited as well as the intestinal P-glycoprotein activity. It is suggested that the inhibition of hepatic metabolism determined an increased bioavailability of cannabidiol resulting in a greater effect. However, in the light of the well known antioxidant and antiinflammatory properties of terpenes and flavonoids which could significantly contribute to the therapeutic effects, it cannot be excluded that the synergism observed might be achieved also in the absence of the cytochrome P450 inhibition.”

http://www.ncbi.nlm.nih.gov/pubmed/18618522

Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial.

“The objective was to investigate the effectiveness of cannabis-based medicines for treatment of chronic pain associated with brachial plexus root avulsion…”

 “The primary outcome measure was the mean pain severity score during the last 7 days of treatment. Secondary outcome measures included pain related quality of life assessments. The primary outcome measure failed to fall by the two points defined in our hypothesis. However, both this measure and measures of sleep showed statistically significant improvements. The study medications were generally well tolerated with the majority of adverse events, including intoxication type reactions, being mild to moderate in severity and resolving spontaneously…”

http://www.ncbi.nlm.nih.gov/pubmed/15561385

A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain.

“…many patients routinely use “medical marijuana,” and in many cases this use is for pain related to nerve injury.”

“We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain… A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher dose. PERSPECTIVE: This study adds to a growing body of evidence that cannabis may be effective at ameliorating neuropathic pain, and may be an alternative for patients who do not respond to, or cannot tolerate, other drugs…”

http://www.ncbi.nlm.nih.gov/pubmed/18403272

Smoked cannabis for chronic neuropathic pain: a randomized controlled trial.

“Cannabis sativa has been used to treat pain since the third millennium BC. An endogenous pain-processing system has been identified, mediated by endogenous cannabinoid ligands acting on specific cannabinoid receptors.These findings, coupled with anecdotal evidence of the analgesic effects of smoked cannabis, support a reconsideration of cannabinoid agents as analgesics.”

“Oral cannabinoids such as tetrahydrocannabinol, cannabidiol and nabilone have, alone and in combination, shown efficacy in central and peripheral neuropathic pain, rheumatoid arthritis and fibromyalgia.”

“We conducted a clinical trial using a standardized single-dose delivery system to explore further the safety and efficacy of smoked cannabis in outpatients with chronic neuropathic pain.”

“Conclusion

A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated.”

“Our results support the claim that smoked cannabis reduces pain, improves mood and helps sleep. We believe that our trial provides a methodological approach that may be considered for further research. Clinical studies using inhaled delivery systems, such as vaporizers, are needed.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950205/

Low-Dose Vaporized Cannabis Significantly Improves Neuropathic Pain.

“We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment…”

“…cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated…”

“Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PERSPECTIVE: The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome…”

http://www.ncbi.nlm.nih.gov/pubmed/23237736

Reassessment of the role of cannabinoids in the management of pain.

“The aim of this article is to assess the role of cannabinoids in the treatment of acute and chronic pain in humans.

 …to date there is increasing evidence that cannabinoids are safe and effective for refractory chronic pain conditions including neuropathic pain associated with multiple sclerosis, rheumatoid arthritis, and peripheral neuropathy associated with HIV/AIDS.

SUMMARY:

The precise role of cannabinoids in pain treatment still needs further evaluation. Cannabinoid compounds may be more effective in the context of chronic neuropathic pain than for the management of acute pain.”

http://www.ncbi.nlm.nih.gov/pubmed/17873600

Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials.

“Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabis based medicine, nabilone, dronabinol and a novel THC analogue. Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Overall the quality of trials was excellent. Fifteen of the eighteen trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects. Adverse effects most commonly reported were generally well tolerated, mild to moderate in severity and led to withdrawal from the studies in only a few cases. Overall there is evidence that cannabinoids are safe and modestly effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. The context of the need for additional treatments for chronic pain is reviewed. Further large studies of longer duration examining specific cannabinoids in homogeneous populations are required.

In conclusion this systematic review of 18 recent good quality randomized trials demonstrates that cannabinoids are a modestly effective and safe treatment option for chronic non-cancer (predominantly neuropathic) pain. Given the prevalence of chronic pain, its impact on function and the paucity of effective therapeutic interventions, additional treatment options are urgently needed. More large scale trials of longer duration reporting on pain and level of function are required.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243008/

Cannabinoids for the treatment of neuropathic pain: clinical evidence.

Abstract

“Neuropathic pain is a worldwide epidemic that occurs in 3 to 8% of individuals in industrialized countries and is often refractory to existing treatments. Drugs currently available to target neuropathic pain are, at best, moderately effective and include antidepressants, gabapentin, NMDA receptor antagonists, as well as other anticonvulsants, all of which are limited by their adverse-effect profiles. Cannabinoid drugs are emerging as a promising class of drugs to treat neuropathic pain and have been tested for analgesic effects in a range of chronic pain conditions. Data show that cannabinoids are often effective in individuals with refractory pain receiving concomitant analgesic drugs. Clinical studies on cannabinoids for the treatment of neuropathic pain are reviewed, focusing on clinical trials published within the last five years. Data from large, well-controlled studies show that cannabinoids are moderately effective in reducing chronic pain and that side effects are comparable to existing treatments, suggesting that cannabinoids can play a useful role in the management of chronic pain. Like other drugs for neuropathic pain, cannabinoids have a dose titration that is limited by psychoactive side effects. The development of cannabinoid drugs to target neuropathic pain with improved therapeutic ratios will depend upon the development of cannabinoid treatments with reduced psychoactivity.”

http://www.ncbi.nlm.nih.gov/pubmed/18183533

Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain.

“OBJECTIVE:

Debilitating pain, occurring in 50-70% of multiple sclerosis (MS) patients, is poorly understood and infrequently studied. We summarized efficacy and safety data of cannabinoid-based drugs for neuropathic pain.

CONCLUSION:

Cannabinoids including the cannabidiol/THC buccal spray are effective in treating neuropathic pain in MS.”

http://www.ncbi.nlm.nih.gov/pubmed/17257464