Dose-dependent Effects of Smoked Cannabis on Capsaicin-induced Pain and Hyperalgesia in Healthy Volunteers

[Pain and Regional Anesthesia]

Abstract

Background: Although the preclinical literature suggests that cannabinoids produce antinociception and antihyperalgesic effects, efficacy in the human pain state remains unclear. Using a human experimental pain model, the authors hypothesized that inhaled cannabis would reduce the pain and hyperalgesia induced by intradermal capsaicin.

Methods: In a randomized, double-blinded, placebo-controlled, crossover trial in 15 healthy volunteers, the authors evaluated concentration-response effects of low-, medium-, and high-dose smoked cannabis (respectively 2%, 4%, and 8% 9-δ-tetrahydrocannabinol by weight) on pain and cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected into opposite forearms 5 and 45 min after drug exposure, and pain, hyperalgesia, tetrahydrocannabinol plasma levels, and side effects were assessed.

Results: Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 min after cannabis exposure, however, there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose. There was no effect seen with the low dose, nor was there an effect on the area of hyperalgesia at any dose. Significant negative correlations between pain perception and plasma δ-9-tetrahydrocannabinol levels were found after adjusting for the overall dose effects. There was no significant difference in performance on the neuropsychological tests.

Conclusions: This study suggests that there is a window of modest analgesia for smoked cannabis, with lower doses decreasing pain and higher doses increasing pain.

Anesthesiology:Volume 107(5)November 2007pp 785-796
Dose-dependent Effects of Smoked Cannabis on Capsaicin-induced Pain and Hyperalgesia in Healthy Volunteers
[Pain and Regional Anesthesia]

Wallace, Mark M.D.*; Schulteis, Gery Ph.D.*; Atkinson, J Hampton M.D.†; Wolfson, Tanya M.A.‡; Lazzaretto, Deborah M.S.§; Bentley, Heather∥; Gouaux, Ben#; Abramson, Ian Ph.D.**

* Professor, Department of Anesthesiology, † Professor IR, § Senior Statistician, HIV Neurobehavioral Research Center, ‡ Principal Statistician, Division of Biostatistics, Department of Family and Preventive Medicine, ∥ Project Manager, Center for Medicinal Cannabis Research, HIV Neurobehavioral Research Center, # Staff Research Associate, Center for Medicinal Cannabis Research, ** Professor, Department of Mathematics, HIV Neurobehavioral Research Center, University of California, San Diego.

Received from the Department of Anesthesiology, University of California, San Diego, California. Submitted for publication December 11, 2006. Accepted for publication June 6, 2007. Supported by grant No. C00-SD-107 from the University of California Center for Medicinal Cannabis Research, La Jolla, California.

Address correspondence to Dr. Wallace: 9500 Gilman Drive, No. 0924, La Jolla, California 92093. mswallace@ucsd.edu. This article may be accessed for personal use at no charge through the Journal Web site, The Journal of the American Society of Anesthesiologists, Inc. - Anesthesiology home .