TerminatedPhase 1

Dopamine D2/D3 Receptor Upregulation by Varenicline in Methamphetamine Users

Stopped: Global pandemic

United States62 participantsStarted 2018-01-11

Plain-language 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.

Who can participate

Age range18 Years – 60 Years

SexALL

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Inclusion Criteria: * English fluency in order to provide informed consent and complete questionnaires * Age of 18-60 years \[Children younger than 18 years will be excluded because of the potential risk of radiation exposure. Recruitment will be restricted to individuals within the first 5 decades of life to avoid effects of aging on DRD2/3 (dopamine type-2 receptor) BPND (binding potential). * Meeting DSM (Diagnostic and Statistical Manual of Mental Disorders) 5 criteria for stimulant-use disorder * Being within 2 weeks of admission to treatment and \< 2 months abstinent from stimulant use * Vital signs as follows: resting pulse between 50 and 95 beats per minute (bpm), blood pressures between 90-150 mm Hg (millimeter of mercury) systolic and 45-95 mm Hg diastolic * Hematology and chemistry laboratory test results within normal (+/- 10%) limits and normal kidney function (estimated glomerular filtration rate ≥ 90 ml/min/1.73m2) * Baseline ECG (electrocardiogram) demonstrating normal conduction (including QTc \[QT interval\]) without clinically significant arrhythmias * Absence of clinically significant contraindications for participation, in the judgment of the admitting physician and the principal investigator, assessed by a medical history and physical examination. Exclusion Criteria: * History or evidence of seizure disorder or brain injury with loss of consciousness \>30 min * Previous adverse reaction to varenicline (VAR) * Neurological disorder that would compromis…

What they're measuring

Dopamine D2-type receptor availability

Timeframe: 21 days

Trial details

NCT IDNCT03059563

SponsorUniversity of California, Los Angeles

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2023-09-28