This investigation will be the first study assessing genetic modulation of naltrexone's NTX effects upon the abuse liability of a stimulant drug (methamphetamine). The study team will assess the ability of oral NTX to block the reinforcing and positive subjective effects of intranasal (IN) methamphetamine (30mg/70kg). This investigation could identify an important Gene x Pharmacological interaction, contributing to the personalization of stimulant abuse pharmacotherapy.
A recent meta-analysis concluded that the OPRM1 A118G SNP (rs1799971) significantly moderates the treatment efficacy of Naltrexone (NTX) in treating alcohol abuse, increasing the treatment efficacy by over 2-fold among G-allele carriers (AG/GG). The proposed application would be the first to investigate the moderating effect of this genotype in the efficacy of NTX to treat stimulant abuse. More specifically, the study team proposes to investigate the interaction between NTX and intranasal (IN) methamphetamine (30mg/70kg). Participants who meet DSM criteria for mild-to-severe stimulant use disorder (N=up to 70) will complete 4 testing sessions where drug effects are tested following pretreatment with NTX (0, 50 mg). Naltrexone pretreatment effects upon the abuse liability of IN methamphetamine will be assessed using self-report measurements of positive subjective effects and drug self-administration. Medication effects on these validated predictors of abuse potential will be compared between A118G A allele homozygotes (AA) and G-allele carriers (AG/GG; an anticipated 25% of the total sample), in order to assess genetic moderation of treatment outcome.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
18
Intranasal Methamphetamine HCL administered at a dose of 30mg per 70 kg of the participants' body weight)
New York State Psychiatric Institute
New York, New York, United States
Methamphetamine Self-Administration
To assess the reinforcing effects of methamphetamine, participants complete a drug self-administration procedure. The outcome measure for this procedure is the number of operant responses (clicks on a mouse) participant are willing to make in order to receive drug (methamphetamine).
Time frame: 1 day.
Positive Subjective Effects of Methamphetamine.
Participant ratings of methamphetamine "Liking," on a 100 mm visual analog scale. Participants are asked to indicate on a 100 mm line the extent to which they agree with the description of the drug provided. The 0 mm end of the line indicates "Not at All," while the 100 mm indicates "Extremely."
Time frame: 1 day
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