Dopamine D2/D3 Receptor Upregulation by Varenicline in Methamphetamine Users

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.

Conditions

• Dopamine D2/3 Receptor Availability
• Cognitive Function
• Methamphetamine Abuse

Interventions

DRUG

Varenicline

Varenicline is an FDA-approved medication to facilitate smoking cessation. it is also a promising candidate to enhance dopamine signaling by upregulating dopamine D2/D3 (type 2) receptors in the striatum and improve cognitive function.

OTHER

Placebo

A placebo containing no active ingredients will be used as a control to assess the effects of varenicline on dopamine D2/D3 receptor availability and cognitive function.

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA)

  collaborator NIH

• University of California, Los Angeles

  lead OTHER

Principal Investigators

• Edythe D London, Ph.D. · University of California, Los Angeles

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-01-11

Primary Completion

2023-09-28

Completion

2023-09-28

FDA Drug

Yes

Countries

• United States

Study Locations