Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans

Abstract

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 (30mg 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 60mg, dronabinol 5, 10, 20, and 30mg [decreased from 40mg]). Placebo was substituted for oxycodone maintenance doses for 21 hours 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 10mg produced effects most similar to placebo, while the 20 and 30mg 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.

How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review

“…Opioid dependence (F11.20 ICD-10) Severity of withdrawal, retention in treatment or safety were assessed in 2 RCTs (3 reports, 70 patients) [ 12 , 37 , 48 ] (Table 3 ). The first intervention [ 12 ] was dronabinol (titrated to 30 mg/day, 3 weeks) ( n = 40) compared to placebo ( n = 20).…”

“…They were considered to be consistent with symptoms of naltrexone-related protracted withdrawal. Jicha et al [ 37 ] and Lofwall et al [ 48 ] tested the safety of dronabinol with n = 12 adults physically dependent on short-acting opioids. Participants were maintained on oral 30 mg oxycodone.…”

High‐intensity cannabis use is associated with retention in opioid agonist treatment: a longitudinal analysis

“…This potential of THC for the treatment of acute opioid withdrawal has been suggested subsequently in small clinical trials using dronabinol (i.e. oral capsules of synthetic THC) . However, some concerns regarding dose‐related side effects, including cardiovascular and psychoactive effects, also arose in these studies which may limit the clinical utility of dronabinol in this context .…”

“…oral capsules of synthetic THC) . However, some concerns regarding dose‐related side effects, including cardiovascular and psychoactive effects, also arose in these studies which may limit the clinical utility of dronabinol in this context . In rat models, cannabidiol (CBD, a non‐intoxicating phytocannabinoid) has also been found to attenuate withdrawal symptoms and cue‐induced heroin‐seeking behaviour, with long‐lasting effects .…”

Emerging Evidence for Cannabis' Role in Opioid Use Disorder

“…Low-dose adjunct dronabinol improved the tolerability of symptoms such as insomnia, reduced appetite, and reduced energy levels during opioid detoxification, whereas adverse events such as tachycardia were reported at higher dronabinol doses. 113 , 116 , 117 In many studies, cannabinoids were safe and tolerable when coadministered with an opioid or opioid replacement medication. 47 , 113 , 118–120 However, the comparative efficacy of dronabinol or other cannabinoids versus traditional replacement therapies such as methadone or buprenorphine remains to be elucidated.…”