Effects of Genotype on Resting State Connectivity During Methamphetamine Administration

17932

Addiction to methamphetamine (MA) is a serious health problem in the United States. Right now, there are no medically approved treatments for MA dependence. More research is needed to understand how MA affects the brain and to eventually develop medical interventions for MA addiction. The purpose of the study is to learn more about how MA use affects the brain by investigating a receptor in the brain called trace amine-associated receptor 1 (TAAR1). The investigators are hoping to find out if individuals with certain versions of the brain receptor react differently when given MA. The TAAR1 receptor has two prevalent genetic variations due to a single nucleotide polymorphism. These are the wild type (WT) and a common variant (CV). Preliminary studies have shown that these variants produce different connectivity (resting state functional connectivity or RSFC) in the brains of individuals with MA use disorder (MUD), specifically that individuals with the CV genotype exhibit lower RSFC than WT. In this study, MA will be administered to individuals with MA use disorder and healthy controls in order to: 1. Determine the influence of CV vs. WT genotype on RSFC and craving in individuals with chronic MUD and healthy controls. 2. Determine the effect of acute methamphetamine or placebo administration on the interaction of CV vs WT genotype on RSFC, craving, cognitive control, attention and subjective experience in MUD and healthy controls.

2019-08-16

2023-03-31

2023-03-31

Completed

Early phase I

69

Criteria for Inclusion: \[All groups\] * 18 to 55 years old * Homozygous or heterozygous for the hTAAR1 V288V genotype or wild type for hTAAR1 (determined during screening visit "Visit 1") \[Meth use group\] * Subjects must have a positive urine drug screen for methamphetamine during visit one * Meets current criteria for methamphetamine use disorder * Subjects should have been using at least 100mg of methamphetamine (not prescribed), 5 days per week for at least one year * Abstinent from methamphetamine for 24 hours on days of scans \[Healthy volunteer group\] - At least one exposure to a stimulant, either recreational or prescribed Criteria for Exclusion: \[All groups\] * Allergies to stimulants or hypersensitivity to taking a stimulant in the past * Diagnosis of a psychotic or mood disorder * Self-reported claustrophobia * Women who are pregnant or breast-feeding * Intoxicated on study days * Clinically significant neurological, cardiovascular, endocrine, renal, hepatic or systemic disease that could compromise safe participation or confound outcomes (including hepatitis C, HIV, severe anemia, or liver disease) * History of glaucoma * Metal in the body which is contraindicated for MRI or would compromise image quality * Current prescription use of stimulants, anti-psychotic drugs or anti-Parkinson's drugs * Use of monoamine oxidase inhibitors within 14 days * Use of serotonin reuptake inhibiters, serotonin norepinephrine reuptake inhibiters, triptans, tricyclic antidepressants, Fentanyl, lithium, tramadol, tryptophan, buspirone , St. John's Wort, insulin, phenothiazines, guanethidine, acidifying/alkalinizing agents, CYP2D6 inhibitors, proton pump inhibitors \[Meth use group\] * Positive urine drug screen at any point during the study (except for meth or marijuana) * History of any severe substance use disorders within the last 5 years, except for methamphetamine use disorder or tobacco use disorder \[Healthy volunteer group\] * History of any severe substance use disorders within the last 5 years except tobacco use disorder * Positive urine drug screen at any point in the study (except for marijuana or for verified medical reasons)

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2023-11-18