Cannabis may be safe and effective for HIV-related neuropathic pain
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.
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.
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.
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.
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.
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 45ยบ 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).
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.”
References
Abrams DI et al. Cannabis in painful HIV-related sensory neuropathy: a randomized placebo-controlled trial. Neurology 68: 515-521, 2007.
Tetrault JM et al. . Arch Intern Med 167: 221-228, 2007.
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Cannabis May Be Safe And Effective