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D1 and D2 Dopamine Receptors in Gambling and Amphetamine Reinforcement

Information source: Centre for Addiction and Mental Health
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Pathological Gambling

Intervention: Haloperidol (Drug); Fluphenazine (Drug); Dexedrine (Drug); Placebo (Drug); Slot Machine (Behavioral)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Centre for Addiction and Mental Health

Official(s) and/or principal investigator(s):
Daniela Lobo, MD, Ph.D., Principal Investigator, Affiliation: Centre for Addiction and Mental Health


To determine if: 1. pathological gambling is similar to psychostimulant addiction as reflected by parallel roles for D1 and D2 receptors in gambling and stimulant reinforcement. 2. these parallel roles are linked with gambling pathology or if they are evident in both gamblers and controls.

Clinical Details

Official title: Comparative Effects of a D2 and Mixed D1-D2 Dopamine Antagonist on Gambling and Amphetamine Reinforcement in Pathological Gamblers and Healthy Controls

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Diagnostic

Primary outcome: Subjective Reinforcement self-report scales

Secondary outcome:


Cognitive Task Performance

Betting behaviour in laboratory-based slot machine game

Detailed description: BACKGROUND: No previous research appears to have investigated the role of dopamine (DA) D1 or D2 receptors in psychostimulant reinforcement in pathological gamblers. Effects of haloperidol vs. placebo will reveal the role of D2 and the effects of fluphenazine vs. haloperidol will reveal the role of D1 in this process. OBJECTIVE: This study will begin to define the neurochemistry of Pathological Gambling by examining the roles of dopamine D1 and D2 receptors in gambling reinforcement and psychostimulant reinforcement, and exploring genetic predictors of response to DA probes in Pathological Gambling subjects (subjects) and healthy controls. METHODS: A double-blind, placebo controlled, counterbalanced between-within design will be employed. Each participant will attend 4 sessions with a minimum of 1 week between sessions to ensure drug washout. Responses to the slot machine will be assessed in sessions 1 and 2 (Phase I), and responses to amphetamine will be assessed in sessions 3 and 4 (Phase II). A second capsule (dummy) will be administered at expected peak levels for each antagonist on sessions 1 and 2 to standardize the procedure across sessions. Subjective reinforcement self-report scales will be administered at key intervals throughout the study. HYPOTHESIS: It is hypothesized that haloperidol (3-mg) will increase priming (Desire to Gamble, Gambling word salience) and pleasurable effects (e. g., Enjoyment/Liking) induced by playing a slot machine in Pathological Gambling subjects (N = 40). If gambling and stimulant reinforcement are mediated by common mechanisms, haloperidol will also increase priming and pleasurable effects of amphetamine (20-mg) in Pathological Gambling subjects. If D1 mediates effects of haloperidol, the mixed D1-D2 antagonist, fluphenazine (fluphenazine; 3-mg) will decrease or not alter responses to the slot machine and amphetamine in Pathological Gambling subjects. If D2 deficits are linked with gambling pathology, haloperidol will not affect slot machine or amphetamine reinforcement in controls (N= 40). If D1 deficits are linked with gambling pathology, fluphenazine will increase gambling and amphetamine reinforcement in controls, by mitigating undue D1 activation in subjects with high baseline D1 function. If D1 or D2 genes contribute to gambling or amphetamine reinforcement, genotype will predict responses to the manipulations.


Minimum age: 19 Years. Maximum age: 65 Years. Gender(s): Both.


Inclusion Criteria:


- otherwise healthy, non-treatment seeking, non-abstinent

- male or female

- ages 19-65

- DSM-IV PG symptom scale (Beaudoin and Cox, 1999) score > 5

- SOGS score > 5

- nicotine dependence acceptable


- healthy

- male or female

- ages 19-65

- DSM-IV PG symptom scale score = 0

- SOGS score = 0

- nicotine dependence acceptable

- must have played slot machine > 5 times

Exclusion Criteria:

- both Pathological Gamblers and Controls

- Axis I psychopathology aside from nicotine dependence (or PG) based on SCID

- Schizotypal or Borderline Personality Disorder based on psychiatric interview

- Family history of schizophrenia or bipolar disorder

- English comprehension below grade 7 level.

- ADS > 13 (more than low dependence)

- BDI short form > 10 (more than low depression)

- DAST > 4 (possible drug abuse)

- Consumption of > 20/15 (men/women) standard alcoholic drinks/ week (hazardous


- Smoking > 20 cigarettes/day to help minimize withdrawal symptoms during test phase

- Any prior use of psychostimulant drugs

- Current use of medication that could interact with any of the study medications

- Women who are pregnant or breastfeeding

Locations and Contacts

Centre for Addiction and Mental Health, Toronto, Ontario M5S 2S1, Canada
Additional Information

The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world.

Related publications:

APA (2000) Diagnostic and Statistical Manual of Mental Disorders. IV-TR ed. American Psychiatric Association: Washington, DC.

Enggasser JL, de Wit H. Haloperidol reduces stimulant and reinforcing effects of ethanol in social drinkers. Alcohol Clin Exp Res. 2001 Oct;25(10):1448-56.

Holley FO, Magliozzi JR, Stanski DR, Lombrozo L, Hollister LE. Haloperidol kinetics after oral and intravenous doses. Clin Pharmacol Ther. 1983 Apr;33(4):477-84.

Lesieur HR, Blume SB. The South Oaks Gambling Screen (SOGS): a new instrument for the identification of pathological gamblers. Am J Psychiatry. 1987 Sep;144(9):1184-8.

Midha KK, McKay G, Edom R, Korchinski ED, Hawes EM, Hall K. Kinetics of oral fluphenazine disposition in humans by GC-MS. Eur J Clin Pharmacol. 1983;25(5):709-11.

Wachtel SR, Ortengren A, de Wit H. The effects of acute haloperidol or risperidone on subjective responses to methamphetamine in healthy volunteers. Drug Alcohol Depend. 2002 Sep 1;68(1):23-33.

Wong YN, Wang L, Hartman L, Simcoe D, Chen Y, Laughton W, Eldon R, Markland C, Grebow P. Comparison of the single-dose pharmacokinetics and tolerability of modafinil and dextroamphetamine administered alone or in combination in healthy male volunteers. J Clin Pharmacol. 1998 Oct;38(10):971-8.

Starting date: September 2009
Last updated: August 21, 2015

Page last updated: August 23, 2015

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