Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment

Abstract

Background Methamphetamine dependence is a significant public health concern without any approved medications for treatment. We evaluated ibudilast, a non-selective phosphodiesterase inhibitor, to assess the safety and tolerability during intravenous (IV) methamphetamine administration. We conducted a randomized, double-blind, placebo-controlled, within-subjects crossover clinical trial. Methods Participants received ibudilast (20 mg twice daily followed by 50 mg twice daily) and placebo, with order determined by randomization, and then underwent IV methamphetamine challenges (15 and 30 mg). We monitored cardiovascular effects, methamphetamine pharmacokinetics and reported adverse events. Results Ibudilast treatment had similar rates of adverse events compared to placebo and there was no significant augmentation of cardiovascular effects of methamphetamine. Pharmacokinetic analysis revealed no clinically significant change in maximum concentration or half-life of methamphetamine with ibudilast. Conclusions Methamphetamine administration during ibudilast treatment was well-tolerated without additive cardiovascular effects or serious adverse events, providing initial safety data to pursue ibudilast’s effectiveness for the treatment of methamphetamine dependence.

A Mutation inHnrnph1That Decreases Methamphetamine-Induced Reinforcement, Reward, and Dopamine Release and Increases Synaptosomal hnRNP H and Mitochondrial Proteins

“…Whole striata (left and right sides) were flash frozen in ethanol/dry ice bath and stored at Ϫ80°C. Tissue were then shipped on dry ice to University of Utah Health Science Center for MA and amphetamine metabolite quantification as previously described (Slawson et al, 2002;DeYoung et al, 2016).…”

Glial and neuroinflammatory targets for treating substance use disorders

“…For this indication ibudilast has shown promise in clinical laboratory studies. Ibudilast was safe and well tolerated in combination with IV methamphetamine (DeYoung et al, 2016). Worley and colleagues (2016) examined whether ibudilast would reduce subjective effects of methamphetamine among non-treatment seeking, methamphetamine-dependent volunteers (n=11).…”

Does the Neuroimmune Modulator Ibudilast Alter Food Craving? Results in a Sample With Alcohol Use Disorder

“…The trial showed that IBUD reduced tonic levels of alcohol craving (Ray et al, 2017a). Other research on IBUD has demonstrated its safety and initial efficacy for methamphetamine use disorder (DeYoung et al, 2016; Worley et al, 2016) and opioid use disorder (Cooper et al, 2016; Metz et al, 2017). IBUD, however, did not reduce tonic levels of high-fat/high-sugar food craving.…”

“…A randomized, placebo-control, human laboratory trial advanced IBUD development for alcohol use disorder (AUD) and found that IBUD reduced tonic levels of alcohol craving—and for individuals reporting higher levels of depressive symptoms—reduced the stimulant and rewarding effects of alcohol (Ray et al, 2017a). IBUD has similarly been studied for its safety and initial efficacy among individuals with methamphetamine use disorder (DeYoung et al, 2016; Worley et al, 2016) and opioid use disorder (Cooper et al, 2016; Metz et al, 2017). In sum, IBUD may be a promising pharmacotherapy for AUD and other substance use disorders.…”