Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment.
BACKGROUND
Methamphetamine dependence is a significant public health concern without any approved medications for treatment. We evaluated ibudilast, a nonselective phosphodiesterase inhibitor, to assess the safety and tolerability during intravenous 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 intravenous 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 with 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.
From the *Center for Behavioral and Addiction Medicine, Department of Family Medicine, David Geffen School of Medicine at UCLA, Los Angeles; †Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford; ‡Department of Psychiatry, Harbor-UCLA Medical Center, Torrance; §Department of Statistics, University of California, Los Angeles, CA; and ∥Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT.
Dustin Z
DZ
DeYoung
Keith G
KG
Heinzerling
Aimee-Noelle
AN
Swanson
John
J
Tsuang
Benjamin A
BA
Furst
Yi
Y
Yi
Ying Nian
YN
Wu
David E
DE
Moody
David M
DM
Andrenyak
Steven J
SJ
Shoptaw
D061605:Administration, Intravenous; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007212:Indolizines; D011720:Pyrazoles
D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles