title: Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial.
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% Delta-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.
authors.affiliation: Department of Neurosciences, University of California, San Diego, CA 92103, USA. roellis@ucsd.edu
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Will
authors.initials: W
authors.lastname: Toperoff
authors.forename: Florin
authors.initials: F
authors.lastname: Vaida
authors.forename: Geoffrey
authors.initials: G
authors.lastname: van den Brande
authors.forename: James
authors.initials: J
authors.lastname: Gonzales
authors.forename: Ben
authors.initials: B
authors.lastname: Gouaux
authors.forename: Heather
authors.initials: H
authors.lastname: Bentley
authors.forename: J Hampton
authors.initials: JH
authors.lastname: Atkinson
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000339:Affect / Q000187:drug effects; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000523:psychology; D008875:Middle Aged; D010147:Pain Measurement; D010148:Intractable Pain / Q000150:complications / Q000188:drug therapy*; D010919:Placebos; D010946:Plants, Medicinal / Q000502:physiology; D011115:Polyneuropathies / Q000150:complications / Q000188:drug therapy*
chemical_list: D018712:Analgesics, Non-Narcotic; D010919:Placebos; D013759:Dronabinol