Original Article

Neuropsychopharmacology (2009) 34, 672–680; doi:10.1038/npp.2008.120; published online 6 August 2008

Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial

Ronald J Ellis1, Will Toperoff1, Florin Vaida2, Geoffrey van den Brande3, James Gonzales4, Ben Gouaux5, Heather Bentley5 and J Hampton Atkinson5

  1. 1Department of Neurosciences, University of California, San Diego, CA, USA
  2. 2Department of Family and Preventive Medicine, University of California, San Diego, CA, USA
  3. 3Department of Medicine, University of California, San Diego, CA, USA
  4. 4Department of Pharmacy, University of California, San Diego, CA, USA
  5. 5Department of Psychiatry, University of California, San Diego, CA, USA

Correspondence: Dr RJ Ellis, Department of Neurosciences, University of California, San Diego, 150 W Washington St., San Diego, CA 92103 USA. Tel: +1 619 543 5079; Fax: +1 619 543 4744; E-mail: roellis@ucsd.edu

Received 9 May 2008; Revised 28 June 2008; Accepted 29 June 2008; Published online 6 August 2008.



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.


HIV, clinical, neuropathic pain, cannabis, polyneuropathy



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