A Pilot Study of the Safety and Initial Efficacy of Ivermectin for the Treatment of Alcohol Use Disorder

Abstract

Background Ivermectin (IVM) is an antiparasitic agent that has been shown to reduce alcohol intake in mice, suggesting IVM as a potential treatment for alcohol use disorder (AUD). However, the safety profile of IVM administered in combination with an intoxicating dose of alcohol has not been characterized in humans. Methods This pilot project sought to provide the first clinical evidence that IVM could be repositioned as an AUD pharmacotherapy by examining 1) the safety of combining IVM (30 mg oral QD) with an intoxicating dose of intravenous alcohol (0.08 g/dl) and 2) the effects of IVM on alcohol cue-induced craving and subjective response to alcohol. Eleven individuals with AUD participated in a randomized, placebo-controlled, crossover study in which they received the study medication, participated in a cue exposure paradigm followed by intravenous alcohol administration, and remained in an inpatient unit overnight for observation. Results Ivermectin treatment, vs. placebo, did not increase the number or severity of adverse effects during alcohol administration or throughout the visit. However, IVM did not reduce cue-induced craving nor did it significantly affect subjective response to alcohol. Conclusions These results suggest that IVM (30 mg oral, QD) is safe in combination with an intoxicating dose of alcohol, but do not provide evidence that this dose of IVM is effective in reducing alcohol craving or its reinforcing effects. Given the preclinical data suggesting IVM is effective in reducing alcohol consumption in mice, additional studies testing larger samples and alternate dosing regimens are warranted to further characterize the potential efficacy of IVM as an AUD treatment.

Preclinical development of moxidectin as a novel therapeutic for alcohol use disorder

“…Of note, the safety and initial efficacy of co-administration of a single 30-mg dose of ivermectin and intravenous alcohol infusion in alcoholic patients was recently tested. In this study, ivermectin (30 mg) was found to be safe and well tolerated where the number and severity of reported adverse effects were low and did not differ from the placebo session (Roche et al, 2016). Although ivermectin did not differ from placebo in regards to reducing alcohol cue-induced craving or basal alcohol craving, the study represented an important first step in developing this class of molecules as pharmacotherapies for AUD.…”

Alcohol, tobacco, and marijuana consumption is associated with increased odds of same-day substance co- and tri-use

“…The reported sample draws from baseline data collected as a part of four human laboratory studies. Three studies examined pharmacotherapies for alcohol use: naltrexone in an Asian American sample (n = 199; (Ray et al, 2018), ibudilast (n = 138; (Ray et al, 2017), and ivermectin (n = 74; (Roche et al, 2016b). The fourth study was an alcohol self-administration study (n = 140; (Bujarski et al, 2018), resulting in a total sample of 551 participants.…”

Convergence between the Penn Alcohol Craving Scale and diagnostic interview for the assessment of alcohol craving

“…Non-treatment seeking, heavy alcohol users (N = 338) were recruited from the greater Los Angeles community for participation in three human laboratory studies of AUD conducted at the University of California Los Angeles (UCLA). Two studies tested novel pharmacological interventions for AUD, specifically ibudilast (Ray et al, 2017a) and ivermectin (Roche et al, 2016) and a third study tested the relationship between subjective responses to alcohol and progressive ratio alcohol self-administration (Bujarski et al, 2018). All studies were approved by the UCLA Institutional Review Board.…”