Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans

Background: The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB₁ receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal. Methods: Twelve opioid dependent adults participated in this 5-week, inpatient, double-blind, randomized, placebo-controlled study. Volunteers were maintained on double-blind oxycodone (30 mg oral, four times/day) and participated in a training session followed by 7 experimental sessions, each testing a single oral test dose (placebo, oxycodone 30 and 60 mg, dronabinol 5, 10, 20, and 30 mg [decreased from 40 mg]). Placebo was substituted for oxycodone maintenance doses for 21 h before each session in order to produce measurable opioid withdrawal. Outcomes included observer- and participant-ratings of opioid agonist, opioid withdrawal and psychomotor/cognitive performance. Results: Oxycodone produced prototypic opioid agonist effects (i.e. suppressing withdrawal and increasing subjective effects indicative of abuse liability). Dronabinol 5 and 10 mg produced effects most similar to placebo, while the 20 and 30 mg doses produced modest signals of withdrawal suppression that were accompanied by dose-related increases in high, sedation, bad effects, feelings of heart racing, and tachycardia. Dronabinol was not liked more than placebo, showed some impairment in cognitive performance, and was identified as marijuana with increasing dose. Conclusion: CB₁ receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal; however, dronabinol is not a likely candidate given its modest withdrawal suppression effects of limited duration and previously reported tachycardia during opioid withdrawal.