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

Roche, Daniel; Yardley, Megan M.; Lunny, Katy; Louie, Stan G.; Davies, Daryl L.; Miotto, Karen; Ray, Lara A.

doi:10.1111/acer.13064

Cited by 18 publications

(10 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.…”

Section: Discussionmentioning

confidence: 71%

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

et al. 2017

Self Cite

View full text Add to dashboard Cite

Current pharmacotherapies for alcohol used disorder (AUD) are few and relatively ineffective illustrating the need for the development of new, effective medications. Using a translational approach, our laboratory reported that ivermectin, an FDA-approved, human and animal anti-parasitic agent, can significantly reduce ethanol intake in male and female mice across different drinking paradigms. Extending this line of investigation, the current paper investigated the utility of moxidectin (MOX), an analogue of ivermectin, to reduce ethanol intake. Notably, MOX is widely held to have lower neurotoxicity potential and improved margin of safety compared to ivermectin. Using a 24-h-two-bottle choice paradigm, MOX significantly reduced ethanol intake in a dose dependent manner in both male and female C57BL/6J mice, respectively (1.25 – 7.5 mg/kg) and (1.25 – 10 mg/kg). Further, multi-day administration of MOX (2.5 mg/kg; intraperitoneal injection) for 5 consecutive days significantly reduced ethanol intake in both the 24-h-two-bottle choice and Drinking-in-the-Dark paradigms in female mice. No overt signs of behavioral toxicity were observed. Notably in both male and female mice, MOX significantly reduced ethanol intake starting approximately 4 h post-injection. Using a Xenopus oocyte expression system, we found that MOX significantly potentiated P2X4 receptors (P2X4R) function and antagonized the inhibitory effects of ethanol on ATP-gated currents in P2X4Rs. This latter finding represents the first report of MOX having activity on P2X4Rs. In addition, MOX potentiated GABAA receptors, but to a lesser degree as compared to ivermectin supporting the hypothesis that MOX would be advantageous (compared to ivermectin) with respect to reducing contraindications. Overall, the results illustrate the potential for development of MOX as a novel pharmacotherapy for the treatment of AUD.

show abstract

Section: Discussionmentioning

confidence: 71%

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

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: Methodsmentioning

confidence: 99%

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

Roche

Bujarski

Green

et al. 2019

Drug and Alcohol Dependence

View full text Add to dashboard Cite

Background: Little is known about event-level patterns of marijuana co-or tri-use with alcohol and tobacco. Thus, the study goal was to examine patterns of same-day alcohol, cigarette, and marijuana co-and tri-use at the individual level in non-treatment-seeking alcohol users. Methods: Participants (N = 551) completed an in-person interview for alcohol, cigarette, and marijuana use over the previous 30 days, and the event-level substance use patterns of n = 179 participants who reported using each of these substances at least once per month were analyzed. Results: The use of alcohol, marijuana, or cigarettes independently increased the probability of subsequent, simultaneous co-use of one of the two remaining substances. The co-use of alcohol with cigarettes and marijuana with cigarettes produced generally additive effects on the odds of same day tri-use of marijuana and alcohol, respectively. Conversely, the co-use of alcohol and marijuana produced sub-additive effects on likelihood of cigarette use. Sex moderated several of the observed patterns of co-and tri-use: the relationship between alcohol or cigarette use predicting marijuana co-use was stronger in men, whereas the observed additive relationships between drug co-use leading to tri-use was stronger in women.

show abstract

“…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.…”

Section: Methodsmentioning

confidence: 99%

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

Hartwell

Bujarski

Green

et al. 2019

Addictive Behaviors Reports

Self Cite

View full text Add to dashboard Cite

Introduction The Penn Alcohol Craving Scale (PACS) is one of the most widely used instruments to measure craving for alcohol. Recent research has suggested that scores on the PACS can be used as a “stand in” for the diagnostic criterion of alcohol craving with a proposed cutoff of >20 on the PACS indicating a “positive” alcohol craving symptom. The present study examined the convergence between the PACS and face-to-face diagnostic interview for the assessment of alcohol craving. Method A sample of non-treatment seeking heavy drinkers (N = 338) enrolled in experimental studies of AUD completed the PACS as well as a face-to-face diagnostic interview for AUD, which included the craving item from the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Results Using the PACS cut-off score of >20, 12.9% (N = 43) of the sample met criteria for alcohol craving compared to 21% (N = 74) of the sample meeting criteria based on the diagnostic interview. Using the PACS cutoff of >20, sensitivity (i.e., true positive rate) was 41% and specificity (i.e., true negative rate) was 95%. Exploratory analyses suggested that a cut-off score of ≥15 achieved the optimal balance of sensitivity (67%) and specificity (81%) in our sample. Conclusions Advancing the assessment of alcohol craving and the conversion from DSM-IV to DSM-5 diagnostic criteria represents an important research direction. The present study recommends that a PACS score cut off of ≥15 should be used as an indicator of clinically significant alcohol craving in community samples of non-treatment seekers.

show abstract

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

Cited by 18 publications

References 53 publications

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

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

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

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

Contact Info

Product

Resources

About