INVESTIGATOR: Mark Wallace, M.D.
STUDY LOCATION: University of California, San Diego
PROJECT TITLE: Analgesic Efficacy of Smoked Cannabis
PROJECT TYPE: Clinical Study
In a randomized, double-blinded, placebo controlled, crossover trial in fifteen healthy volunteers, we evaluated the effects of low, medium, and high dose smoked cannabis (respectively 2%, 4%, and 8% 9-delta-tetrahydrocannibinol by weight) on pain and cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected into opposite forearms 5 and 45 minutes after drug exposure and pain, hyperalgesia, tetrahydrocannibinol plasma levels, and side effects were assessed.
Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 minutes 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 delta-9-tetrahydrocannibinol levels were found after adjusting for the overall dose effects. There was no significant difference in performance on the neuropsychological tests.
This study suggests that there is a window of modest analgesia for smoked cannabis with lower doses decreasing pain and higher doses increasing pain.
The full results of this study were published in the journal Anesthesiology.
By every criteria (deterioration in quality of life; loss of work days, and therapy directed dollars) pain is appreciated to be a major medical problem. Recent findings in the molecular biology and the pharmacology of pain transmission have shed light on mechanisms of nociceptive processing and the activity of a variety of "novel therapeutic" modalities that include the cannabinoids. Although the pre-clinical literature suggests that the cannabinoids produce antinociception and anti-hyperalgesic effects, the efficacy of the cannabinoids in the human pain state is unclear. As an experimental variable, clinical pain is a multidimensional phenomenon with few objective physical correlates. Many other factors such as emotional status and coping skills, make "pain" difficult to study in the clinical setting. An important development has been the implementation of well-controlled experimental pain models to investigate the sensory components of pain processing and to use these models in the assessment of analgesic efficacy in normal volunteers. To the degree that human experimental pain models can predict analgesic efficacy of novel agents, the role of mechanisms defined in preclinical studies can be translated to the human experience under well-controlled conditions. Human experimental pain has been used to test a wide range of currently available analgesics. Knowing the effect of these agents on human experimental pain, I now wish to study the effects of cannabis on human experimental pain and how this compares to commonly used analgesics.