Cannabis may be safe and effective for HIV-related neuropathic pain

Participants and setting

In this prospective, randomised clinical trial, researchers from the University of California Center for Medicinal Cannabis Research investigated the use of smoked cannabis versus placebo in HIV-positive adults with neuropathic pain. Out of 223 potential participants assessed for eligibility, 55 participants were enrolled and 50 completed the trial, which involved a week in an inpatient setting in San Francisco General Hospital between May 2003 and May 2005.

All participants were HIV-positive adults with confirmed painful sensory neuropathy. The group was predominantly male (87%), largely white (45%), and most were taking anti-HIV therapy (76%), the mean duration of treatment being 14.5 years; 56% were also on other medications for neuropathic pain. To ensure familiarity with inhalation techniques and psychological effects, all had prior experience smoking cannabis; however, current cannabis users (73% of the group) discontinued their use before the study. People with any other “current substance abuse” (including tobacco) were excluded.

A prospective, randomised, placebo-controlled trial has found smoked cannabis to be significantly more effective than a smoked placebo at controlling pain from HIV-related neuropathy. The highly-anticipated study was published in the February 13^th edition of Neurology.

HIV infection and certain nucleoside analogue drugs can result in HIV-associated sensory neuropathy, a nerve disorder which causes pain in the extremities (usually toes and feet). Neuropathy is often treated with the anticonvulsant drugs lamotrigine and gabapentin, which not all patients find effective or tolerable. Other experimental treatments, including capsaicin cream and tricyclic antidepressants, have not proven more effective than placebo at treating neuropathic pain.

Study protocol and medication

The study consisted of four phases: preliminary screening, a two-day inpatient lead-in (primarily to familiarise participants with the setting), and a five-day inpatient intervention period during which active smoking of medication or placebo occurred. Finally, participants continued to record daily pain ratings during a seven-day outpatient follow-up.

During the five-day intervention phase, all participants received pre-rolled cigarettes provided by the US National Institute on Drug Abuse (NIDA). These weighed roughly 0.9 grams and appeared identical; cannabis cigarettes contained 3.56% delta-9-tetrahydrocannabinol (THC) while placebo cigarettes contained cannabis from which active components had been extracted, yielding 0% THC content. Participants were assigned to cannabis or placebo cigarettes in a random, double-blind manner: neither the participants nor the investigators knew which had been assigned until the intervention was completed. Participants smoked a maximum of three cigarettes per day while continuing any existing pain medication prescribed outside the study.

Participants rated their own pain levels along a 100mm ruler-like “visual analogue scale” (VAS), with 0 being “no pain” and 100 being “worst imaginable pain”. A baseline VAS rating of at least 30 was required for eligibility. Participants tracked their daily pain levels during the five-day intervention and seven-day follow-up, as well as rating their current pain at 40-minute intervals before and after the first and last cigarettes.

Pain modelling

To help control for the subjective nature of pain reporting, 30 of the participants took part in an additional ‘pain modelling’ component of the trial. A probe heated to 45º C was applied to the skin on the forearm, and the area was then treated with capsaicin cream. The skin area thus treated was then stimulated with a brush and a “noxious pin-like sensation”, and measurements were made of the resulting skin area hypersensitised to these stimuli. Active cannabis reduced the size of the skin area reported as hypersensitive, compared to placebo (34% vs. 11 % reduction, p = 0.05).

Outcomes

Twenty-five participants completed each of the two arms of the trial. The median pain reduction reported in the cannabis arm was twice that of placebo: 34% vs. 17% (p = 0.03). Pain reduction of greater than 30% on the VAS scale was reported by 13 (52%) in the cannabis group vs. 6 (24%) in the placebo group (p= 0.04). Smoking the first cannabis cigarette reduced chronic pain ratings by a median of 72%, vs. 15% with placebo (p < 0.001).

Reported side-effects in the placebo group were minimal. Cannabis smokers reported varying, but generally minimal to mild, degrees of anxiety, sedation, disorientation and confusion, paranoia, dizziness, and nausea. Nobody withdrew from the study due to side-effects.

Conclusions and reactions

The Neurology report concludes that “smoking cannabis cigarettes three times a day reduced [sensory neuropathy] pain by 34%, significantly more than the 17% reduction with placebo cigarettes… the present study provides evidence that cannabis has analgesic effects… [and] an acceptable safety margin has been shown”.

As the medical use of marijuana (an illegal drug) is highly politicised, the results of this study received widespread publicity and commentary. David Murray, chief scientist of the White House Office of National Drug Control Policy, stated that the study was “not terribly convincing” due to methodological problems, and that “people who smoke marijuana are subject to bacterial infections in the lungs.” (A recently released publication review has found that “[l]ong-term marijuana smoking is associated with increased respiratory symptoms suggestive of obstructive lung disease.”)

Lead investigator Donald Abrams said in an interview that “there are people out there who say there is no evidence that marijuana is medicine, that this is all just a smoke screen”, but hoped his findings would “help answer this question in an intelligent fashion.”