Study register · detailRCT · Opioid Reduction · 2016
Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.
Lofwall et al.·Drug and alcohol dependenceImpact 0.8
MixedGRADEModerate65 citations
Samplen = 12 Pat.
Duration5 Wochen
ControlPlacebo and oxycodone 30/60 mg
EndpointOpioid withdrawal symptoms
Blindingdoppelblind
DesignRCT
Cannabinoidthc
Max. dose30.0 mg
Routeoral
”Key finding
Dronabinol showed modest signals of withdrawal suppression at higher doses (20-30mg), but was not rated better than placebo and was associated with side effects such as sedation, tachycardia and cognitive impairment.
Summary
n=12 opioid-dependent adults, 5-week inpatient proof-of-concept study; dronabinol 5/10/20/30mg vs. placebo during oxycodone withdrawal (21h placebo substitution). Dronabinol 20–30mg showed moderate withdrawal suppression, but dose-dependent tachycardia, sedation and cognitive impairment. Dronabinol 5–10mg equivalent in effect to placebo. Duration of effect limited; no higher liking than placebo.
InterventionOral dronabinol (5, 10, 20, 30 mg single dose) under opioid withdrawal conditions
C
ControlPlacebo and oxycodone 30/60 mg (active control)
O
OutcomeDronabinol 20 and 30 mg showed moderate withdrawal suppression, accompanied by dose-dependent tachycardia, sedation and adverse subjective effects; no significant preference over placebo
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
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 21h 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 Cannabis 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.