Marijuana may relieve nerve pain when other drugs don’t – USAToday

“Smoking cannabis, also known as marijuana, reduced pain in patients with nerve pain stemming from injuries or surgical complications, new research shows.

Twenty-one adults with chronic nerve pain were taught to take a single inhalation of 25 milligrams of cannabis through a pipe, three times a day, for five days. The cannabis contained one of three levels of potency of tetrahydrocannabinol (THC), the active ingredient in marijuana, as well as a placebo dosage containing no THC.

All of the patients rotated through each of the four dosages, with nine days of no smoking in between.

Patients smoking the highest potency marijuana (9.4%) reported less pain than those smoking samples containing no THC. Patients also reported better sleep and less anxiety, according to the Canadian study. 

On an 11-point scale, the average daily pain intensity was 6.1 for those smoking 9.4% THC concentration, compared to 5.4 for those smoking cannabis containing no THC.

“Patients have repeatedly made claims that smoked cannabis helps to treat pain, but the issue for me had always been the lack of clinical research to support that claim,” said Dr. Mark Ware, director of clinical research at the Alan Edwards Pain Management Unit of the McGill University Health Centre in Montreal. In this small but randomized, controlled trial, “the pain reductions were modest, but significant,” he said. “And it was in people for whom nothing else worked.”

Read more: http://usatoday30.usatoday.com/yourlife/health/medical/2010-09-05-marijuana-pain_N.htm

Medicinal Marijuana Eases Neuropathic Pain in HIV – ABC News

“(HealthDay News) — Medicinal marijuana helps relieve neuropathic pain in people with HIV, says a University of California, San Diego, School of Medicine study.

It included 28 HIV patients with neuropathic pain that wasn’t adequately controlled by opiates or other pain relievers. The researchers found that 46 percent of patients who smoked medicinal marijuana reported clinically meaningful pain relief, compared with 18 percent of those who smoked a placebo.

The study, published online Aug. 6 in Neuropsychopharmacology, was sponsored by the University of California Center for Medical Cannabis Research (CMCR).

“Neuropathy is a chronic and significant problem in HIV patients as there are few existing treatments that offer adequate pain management to sufferers,” study leader Dr. Ronald J. Ellis, an associate professor of neurosciences, said in an UCSD news release. “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.”

The findings are consistent with and extend other recent CMCR-sponsored research supporting the short-term effectiveness of medicinal marijuana in treating 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,” Dr. Igor Grant, a professor of psychiatry and director of the CMCR, said in the UCSD news release.”

http://abcnews.go.com/Health/Healthday/story?id=5528635&page=1

Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain.

“Neuropathic pain is caused by injury to the peripheral or central nervous system (CNS)…”

“…novel approaches for identifying safe and effective analgesics with limited abuse liability are necessary.”

“Cannabinoids share the same target as the psychoactive ingredient in maijuana. Cannabinoids suppress neuropathic nociception through CB1 and CB2 mechanisms. CB1 is predominantly located within the CNS… CB2 activation is not associated with CNS side-effects linked to CB1. However, abuse potential of CB2 agonists is unknown.”

“We used a drug self-administration approach to ask whether rats with a spared nerve injury (SNI) would self-medicate with a CB2 agonist to attenuate a neuropathic pain state…”

 “Our results suggest that cannabinoid CB2 agonists may be exploited to treat neuropathic pain with limited drug abuse liability and central nervous system (CNS) side-effects. These studies validate the use of drug self-administration methods for identifying nonpsychotropic analgesics possessing limited abuse potential…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157548/

Role of cannabinoids in the management of neuropathic pain.

Abstract

“The treatment of pain, particularly neuropathic pain, is one of the therapeutic applications of cannabis and cannabinoids that is currently under investigation and that stimulates interest among clinicians and basic researchers. Animal pain models, including models of acute, antinociceptive, inflammatory and neuropathic pain, have demonstrated the antinociceptive efficacy of cannabinoids without causing serious alterations in animal behaviour. These data, together with the historic and current empiric use of cannabinoids, support the interest in the analysis of their effectiveness in treating neuropathic pain. The evaluation of controlled trials that focus on the effect of cannabinoids on neuropathic pain reveals that this class of drugs is able to significantly reduce pain perception. Nevertheless, this effect is generally weak and clinical relevance remains under evaluation. Moreover, there is a lack of controlled trials and, in particular, comparisons with other drugs generally used in the treatment of neuropathic pain. Despite the fact that further research is required to achieve a definitive assessment, current data obtained from basic research and from analysis of the available controlled trials indicate that cannabinoids can be accepted as a useful option in the treatment of neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/18601303

More evidence cannabis can help in neuropathic pain.

“It’s good to see the trial of smoked cannabis in neuropathic pain reported by Ware and colleagues because smoking is the most common way in which patients try this drug. The authors should be congratulated for tackling the question of whether cannabis helps in neuropathic pain, particularly given that the regulatory hurdles for their trial must have been a nightmare. The question is worth investigating because of the ongoing publicity — which patients see, hear and read — that suggests an analgesic activity of cannabis in neuropathic pain, and because of the paucity of robust evidence for such an analgesic effect. If patients are not achieving a good response with conventional treatment of their pain, then they may, reasonably, wish to try cannabis. If medical cannabis is not available where a patient lives, then obtaining it will take the patient outside of the law, often for the first time in his or her life. Good evidence would at least buttress that decision.”

“This trial adds to the three previous studies of smoked cannabis in neuropathic pain that I could find using PubMed and reference lists…”

“Putting together the four trials of smoked cannabis, the provisional conclusions are that an analgesic effect is evident, that this effect, though not great, may be of use to some patients, and that it often carries with it some adverse effects on the central nervous system (though not obviously so in this trial). These conclusions make biological sense, given that cannabinoids taken orally have shown the same sorts of effects. Interestingly, the “moderate” analgesic effect shown here for neuropathic pain seems to hold true for nociceptive pain.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950178/

Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial.

“1′,1’dimethylheptyl-Delta8-tetrahydrocannabinol-11-oic acid (CT-3), a potent analog of THC-11-oic acid, produces marked antiallodynic and analgesic effects in animals without evoking the typical effects described in models of cannabinoids. Therefore, CT-3 may be an effective analgesic for poorly controlled resistant neuropathic pain.”

 

“OBJECTIVE: To examine the analgesic efficacy and safety of CT-3 in chronic neuropathic pain in humans.”

 

“CONCLUSIONS: In this preliminary study, CT-3 was effective in reducing chronic neuropathic pain compared with placebo. No major adverse effects were observed.”

 

http://www.ncbi.nlm.nih.gov/pubmed/14519710

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