Naltrexone moderates the relationship between cue-induced craving and subjective response to methamphetamine in individuals with methamphetamine use disorder
Reductions in cue-induced craving and subjective response to drugs of abuse are commonly used as initial outcome measures when testing novel medications for the treatment of addiction. Yet neither the relationship between these two measures at the individual level nor the moderating effects of pharmacotherapies on this relationship has been examined.
This secondary data analysis sought to examine (1) the predictive relationship between cue-induced craving and subsequent acute subjective response to methamphetamine (MA) and (2) whether the opioid-receptor antagonist naltrexone moderated this association in a sample of non-treatment-seeking individuals who met DSM-IV criteria for MA use disorder (abuse or dependence).
Participants (n = 30) completed two 4-day medication regimens (oral naltrexone 50 mg or placebo, in a randomized, counterbalanced, and double-blind fashion). On day 4 of each medication regimen, participants completed a cue-reactivity paradigm followed by intravenous MA administration. Methamphetamine craving was assessed after the cue-reactivity paradigm, and subjective response to MA was assessed during MA infusion.
Cue-induced craving for MA was positively associated with post-infusion subjective MA effects, including positive (i.e., stimulation, good effects, feel drug, high), negative (i.e., anxious and depressed), and craving-related (i.e., want more, would like access to drug, crave) responses. Naltrexone, vs. placebo, significantly reduced the association between cue-induced craving and positive subjective response to MA.
The findings indicate that naltrexone moderates the predictive relationship between cue-induced craving and positive subjective effects of MA, thereby suggesting a behavioral mechanism by which naltrexone may be efficacious in treating MA use disorder.
KeywordsMethamphetamine Naltrexone Craving Subjective response
This research was supported by a grant from the National Institute on Drug Abuse (DA029831) to LAR. Support for this study was also provided by a grant from the UCLA Clinical and Translational Science Institute, grants UL1RR033176 and UL1TR000124. DR was supported by postdoctoral awards from the California Tobacco Related Disease Research Program (18KT-0020) and T32 DA024635. SB was supported by a training grant from the National Institutes of Alcohol Abuse and Alcoholism (F31 AA022569), and KEC was supported by a training grant from the National Institute on Drug Abuse (F31 DA035604). LAR has received study medication from Pfizer and MediciNova and served as a consultant for GSK. EDL received support from the Thomas P. and Katherine K. Pike Chair in Addiction Studies and the Marjorie Greene Family Trust.
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