Dopamine D2/D3 Receptor Upregulation by Varenicline in Methamphetamine Users
Status:
Enrolling by invitation
Trial end date:
2021-12-01
Target enrollment:
Participant gender:
Summary
While deficits in dopamine D2-type receptor availability have been linked to substance use
disorders, higher availability associates with better behavioral treatment outcomes for
stimulant dependence and resilience to addiction. Varenicline has been shown to upregulate
D2-type receptors in drug-naive rats, and could be a useful therapeutic approach for the
treatment of addictive disorders in humans.
The purpose of the study is to assess the relationship between varenicline, dopamine
signaling (specifically, D2-type receptor availability), functional connectivity within
corticostriatal circuitry, genetic markers associated with smoking and methamphetamine abuse,
and measures of cognitive performance.
The investigators hypothesize that varenicline but not placebo will upregulate (increase)
striatal dopamine D2-type receptor availability and improve cognition, and that the change in
availability will correlate with the change in cognition. The investigators also hypothesize
that varenicline but not placebo treatment will repair dysregulated connectivity between the
striatum and prefrontal cortex observed in methamphetamine users, and will correlate with the
change in cognition.
The study design consists of two positron emission tomography (PET) and functional magnetic
resonance imaging (fMRI) scans to measure dopamine D2-type receptor availability and
functional connectivity between the prefrontal cortex and striatum, two cognitive testing
sessions including a battery of tests assessing working memory, declarative memory, sustained
attention, inhibitory control, and reward-based decision making. Following eligibility
screening, thirty six methamphetamine users will be enrolled and tested/scanned once prior to
initiation of varenicline or placebo treatment and then again after completion of treatment.