Abstract
Despite management with opioids and other pain modifying therapies, neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals. Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception. 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). Eligible subjects had neuropathic pain refractory to at least two previous analgesic classes; they continued on their prestudy analgesic regimens throughout the trial. Regulatory considerations dictated that subjects smoke under direct observation in a hospital setting. Treatments were placebo and active cannabis ranging in potency between 1 and 8% Δ-9-tetrahydrocannabinol, four times daily for 5 consecutive days during each of 2 treatment weeks, separated by a 2-week washout. The primary outcome was change in pain intensity as measured by the Descriptor Differential Scale (DDS) from a pretreatment baseline to the end of each treatment week. Secondary measures included assessments of mood and daily functioning. Of 127 volunteers screened, 34 eligible subjects enrolled and 28 completed both cannabis and placebo treatments. Among the completers, pain relief was greater with cannabis than placebo (median difference in DDS pain intensity change, 3.3 points, effect size=0.60; p=0.016). The proportions of subjects achieving at least 30% pain relief with cannabis versus placebo were 0.46 (95%CI 0.28, 0.65) and 0.18 (0.03, 0.32). Mood and daily functioning improved to a similar extent during both treatment periods. Although most side effects were mild and self-limited, two subjects experienced treatment-limiting toxicities. Smoked cannabis was generally well tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV DSPN.
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Acknowledgements
This project was supported by Grant C00-SD-104 from the University of California, Center for Medicinal Cannabis Research. We thank Dr Geoffrey Sheean and the staff of the General Clinical Research Center at the University of California, San Diego Medical Center for supporting this project. Statistical analyses were conducted by Florin Vaida.
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DISCLOSURE
Heather Bentley and Ben Gouaux are employees of the Center for Medicinal Cannabis Research at the University of California, San Diego, the study sponsor. Ms Bentley is Project Manager for the CMCR and assisted the investigator with regulatory issues, oversight/monitoring, and preparation of the manuscript. Mr. Gouaux is a Research Associate with the CMCR and assisted the investigator with regulatory issues, oversight/monitoring, data preparation and analysis, and preparation and submission of the article. The authors declare that over the past 3 years Dr. Atkinson has received compensation from Eli Lilly Pharmaceuticals. The authors declare that they have not received other financial support or compensation in the past 3 years or have any personal financial holdings that could be perceived as constituting a conflict of interest.
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Ellis, R., Toperoff, W., Vaida, F. et al. Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial. Neuropsychopharmacol 34, 672–680 (2009). https://doi.org/10.1038/npp.2008.120
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DOI: https://doi.org/10.1038/npp.2008.120
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