Cannabis Cigarettes May Reduce Neuropathic Pain

Susan Jeffrey

June 27, 2008

June 27, 2008 — Results of a double-blind crossover study suggest that smoked cannabis may reduce pain intensity for patients with neuropathic pain.

The trial showed that both high-dose and low-dose cannabis provided relief from neuropathic pain compared with placebo.

"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," the researchers, with first author Barth Wilsey, MD, from the VA Northern California Health Care System and the University of California, Davis Medical Center, conclude. "However, the use of marijuana as medicine may be limited by its method of administration (smoking) and modest acute cognitive effects, particularly at higher doses."

Their findings are published in the June issue of the Journal of Pain.

No Sound Studies

The Food and Drug Administration, Substance Abuse and Mental Health Services Administration, and the National Institute of Drug Abuse have previously reported that no sound scientific studies support the medicinal use of cannabis, the authors write. "Despite this lack of scientific validation, many patients routinely use 'medical marijuana,' and in many cases this use is for pain related to nerve injury," they note.

There has been some support for its use in the basic and clinical sciences, the researchers point out, but despite this, "the clinical utility of cannabis in the United States remains mired in controversy. Akin to the medical and social controversy surrounding the use of opioids in chronic pain, clinical trials will be a critical factor in the debate concerning medical marijuana."

A National Institutes of Health panel in 1997, though, concluded that inhaled marijuana merited testing in randomized, double-blind trials, particularly in neuropathic pain, where present treatments are "at best, marginally effective."

Pain Intensity

In this double-blind, randomized, placebo-controlled crossover study, the researchers evaluated the analgesic efficacy of smoked cannabis for neuropathic pain. A total of 38 patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking high-dose (7% delta-9-THC), low-dose (3.5% delta-9-THC), or placebo cannabis.

The primary outcome measure was pain intensity, but they also examined secondary measures, including evoked pain using heat-pain threshold and sensitivity to light touch, as well as psychoactive adverse effects and neuropsychological performance.

"A mixed linear model demonstrated an analgesic response to smoking cannabis," the authors report. Identical levels of analgesia were produced at each cumulative dose level by both concentrations of the active agent, indicating that the top of the dose-response curve was reached within the doses used, they write.

In addition to pain intensity, the subjects completed a rating scale to measure pain unpleasantness, a tool that has been validated in pain states that are amplified by emotional turmoil, they note. "In the present experiment, cannabis reduced pain intensity and unpleasantness equally. Thus, as with opioids, cannabis does not rely on a relaxing or tranquilizing effect (eg, anxiolysis) but rather reduces both the core component of nociception and the emotional aspect of the pain experience to an equal degree."

No effect was seen on evoked pain, either by brushing the skin with a foam paintbrush or testing the heat-pain threshold. The latter finding was surprising, they note, and "has no apparent explanation."

Psychoactive effects were seen, including feeling high, although these were less apparent at the lower dose. No patient withdrew because of tolerability issues, and in general, adverse effects and changes in mood were "relatively inconsequential," they note.

Cognitive Performance

Of more concern, perhaps, were effects on cognitive performance, which in this chronic pain population was at or below the threshold for impairment already at baseline. Cannabis use was associated with modest declines in cognitive performance, particularly learning and recall, especially at higher doses. "The finding necessitates caution in the prescribing of medical marijuana for neuropathic pain, especially in instances in which learning and memory are integral to a patient's work and lifestyle," Dr. Wilsey and colleagues write.

It's possible that lower doses may obviate some of these issues, they speculate. The lowest effective dose might be used in combination with opioids, for example. It might also be used in combination with a cognitive enhancer such as modafinil, to reduce some of these effects.

Finally, the noxious byproducts of smoking cannabis might also be avoided in future studies by use of a recently developed vaporization technique, which heats the cannabis to a temperature where cannabinoid vapors form, but below the point of combustion, where toxins are released. "It is reasonable to assume that future clinical trials will utilize this alternative delivery method," they conclude.

The authors acknowledge the University of California Center for Medicinal Cannabis Research, which provided critical support and guidance. They derived direct financial support from the California legislature as well as logistic and scientific support from several national stakeholders, including the Food and Drug Administration, Department of Health and Human Services, National Institute on Drug Abuse, and the Drug Enforcement Agency. Publication was made possible by a grant from National Center for Research Resources and components of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research.

J Pain. 2008;9:506-521. Abstract


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