Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study - PubMed (original) (raw)

Randomized Controlled Trial

Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study

Matthew J Worley et al. Drug Alcohol Depend. 2016.

Erratum in

Abstract

Background: Despite numerous clinical trials no efficacious medications for methamphetamine (MA) have been identified. Neuroinflammation, which has a role in MA-related reward and neurodegeneration, is a novel MA pharmacotherapy target. Ibudilast inhibits activation of microglia and pro-inflammatory cytokines and has reduced MA self-administration in preclinical research. This study examined whether ibudilast would reduce subjective effects of MA in humans.

Methods: Adult, non-treatment seeking, MA-dependent volunteers (N=11) received oral placebo, moderate ibudilast (40 mg), and high-dose ibudilast (100mg) via twice-daily dosing for 7 days each in an inpatient setting. Following infusions of saline, MA 15 mg, and MA 30 mg participants rated 12 subjective drug effects on a visual analog scale (VAS).

Results: As demonstrated by statistically-significant ibudilast × MA condition interactions (p<.05), ibudilast reduced several MA-related subjective effects including High, Effect (i.e., any drug effect), Good, Stimulated and Like. The ibudilast-related reductions were most pronounced in the MA 30 mg infusions, with ibudilast 100mg significantly reducing Effect (97.5% CI [-12.54, -2.27]), High (97.5% CI [-12.01, -1.65]), and Good (97.5% CI [-11.20, -0.21]), compared to placebo.

Conclusions: Ibudilast appeared to reduce reward-related subjective effects of MA in this early-stage study, possibly due to altering the processes of neuroinflammation involved in MA reward. Given this novel mechanism of action and the absence of an efficacious medication for MA dependence, ibudilast warrants further study to evaluate its clinical efficacy.

Keywords: Ibudilast; Methamphetamine; Neuroinflammation; Pharmacotherapy; Subjective reward.

Published by Elsevier Ireland Ltd.

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Conflict of interest statement

Conflict of Interest

Dr. Shoptaw and Dr. Heinzerling have received clinical research supplies from Pfizer, Inc. and Medicinova, Inc.

Figures

Figure 1

Figure 1

Schedule of ibudilast dosing and saline/methamphetamine infusions for the two ibudilast sequence conditions, placebo-40 mg-100 mg (n = 5) and 40 mg-100 mg-placebo (n = 6).

Figure 2

Figure 2

Mean visual analogue scale ratings (Range = 0–100) of “Any Effect”, “High”, and “Good” for the 30mg methamphetamine infusions, displayed separately by ibudilast condition. Error bars indicate 95% confidence interval of model-adjusted contrast between each ibudilast dose and placebo.

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