Cannabinoid modulation of opioid analgesia and subjective drug effects in healthy humans

Abstract

RationaleDozens of preclinical studies have reported cannabinoid agonist potentiation of the analgesic effects of μ-opioid agonists.ObjectivesThe aim of this study was to determine if a cannabinoid agonist could potentiate opioid analgesia in humans using several laboratory pain models.MethodsHealthy participants (n\u2009=\u200910) with/out current drug use/pain conditions completed this within-subject, double-blind, placebo-controlled, randomized outpatient study. Nine 8-h sessions were completed during which dronabinol (0, 2.5, 5\xa0mg, p.o.) was administered 1\xa0h before oxycodone (0, 5, 10\xa0mg, p.o.) for a total of 9 test conditions. Outcomes included sensory threshold and tolerance from four experimental pain models (cold pressor, pressure algometer, hot thermode, cold hyperalgesia), along with participant- and observer-rated, performance and physiological effects.ResultsOxycodone produced miosis (p\u2009<\u20090.05) and analgesic responses (e.g., pressure algometer [p\u2009<\u20090.05]), while dronabinol did not (p\u2009>\u20090.05). Depending on the dose combination, dronabinol attenuated or did not alter oxycodone analgesia; for example, dronabinol (2.5\xa0mg) decreased the analgesic effects of oxycodone (10\xa0mg) on pressure tolerance. Conversely, dronabinol increased oxycodone subjective effects (e.g., drug liking) (p\u2009<\u20090.05); oxycodone (5\xa0mg) ratings of “high” were potentiated by 5\xa0mg dronabinol (p\u2009<\u20090.05; placebo\u2009=\u20091.1 [±\u20090.7]; 5\xa0mg oxycodone\u2009=\u20094.7 [±\u20092.2]; 5\xa0mg dronabinol\u2009=\u20099.9 [±\u20098.4]; 5\xa0mg oxycodone + 5\xa0mg dronabinol\u2009=\u200937.4 [±\u200911.3]).ConclusionsThis study indicates that dronabinol did not enhance the analgesic effects of oxycodone and increased abuse- and impairment-related subjective effects. These data suggest that dronabinol may not be an effective or appropriate opioid adjuvant; it could potentially increase opioid dose requirements, while increasing psychoactive opioid effects.