D1 and D2 Dopamine Receptors in Gambling and Amphetamine Reinforcement
NCT ID: NCT02203786
Last Updated: 2016-04-25
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
60 participants
INTERVENTIONAL
2009-09-30
2015-09-30
Brief Summary
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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.
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
DIAGNOSTIC
TRIPLE
Study Groups
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Haloperidol
Subjects randomized to pre-treatment drug sequence 1 (haloperidol on day 1 of each phase), or drug sequence 2 (haloperidol on day 2 of each phase).
Dose 1: 3 visually identical capsules, each containing 1 mg haloperidol OR 3 visually identical placebo (lactose) capsules
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg dexedrine.
Response measured to 15 min session of a commercial slot machine game.
Haloperidol
Dose/maximum dose = 3-mg; route = oral. Participants assigned to the haloperidol antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between individual doses).
Dose 1: 3 visually identical capsules, each containing 1 mg haloperidol.
Dexedrine
Dose/maximum dose = 20-mg; route = oral. All participants will receive 2 doses (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between individual doses.
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg D-amphetamine.
Placebo
Dose 1: On alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing) participants will receive 3 visually identical placebo (lactose) capsules.
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1.
Slot Machine
15 minute play of a commercial slot machine game in bar-simulated laboratory setting.
Fluphenazine
Subjects randomized to pre-treatment drug sequence 1 (fluphenazine on day 1 of each phase), or drug sequence 2 (fluphenazine on day 2 of each phase).
Dose 1: 3 visually identical capsules, each containing 1 mg fluphenazine OR 3 visually identical placebo (lactose) capsules
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg dexedrine.
Response measured to 15 min session of a commercial slot machine game.
Fluphenazine
Dose/maximum dose = 3-mg; route = oral. Participants assigned to the fluphenazine antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between individual doses).
Dose 1: 3 visually identical capsules, each containing 1 mg fluphenazine.
Dexedrine
Dose/maximum dose = 20-mg; route = oral. All participants will receive 2 doses (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between individual doses.
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg D-amphetamine.
Placebo
Dose 1: On alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing) participants will receive 3 visually identical placebo (lactose) capsules.
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1.
Slot Machine
15 minute play of a commercial slot machine game in bar-simulated laboratory setting.
Interventions
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Haloperidol
Dose/maximum dose = 3-mg; route = oral. Participants assigned to the haloperidol antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between individual doses).
Dose 1: 3 visually identical capsules, each containing 1 mg haloperidol.
Fluphenazine
Dose/maximum dose = 3-mg; route = oral. Participants assigned to the fluphenazine antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between individual doses).
Dose 1: 3 visually identical capsules, each containing 1 mg fluphenazine.
Dexedrine
Dose/maximum dose = 20-mg; route = oral. All participants will receive 2 doses (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between individual doses.
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg D-amphetamine.
Placebo
Dose 1: On alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing) participants will receive 3 visually identical placebo (lactose) capsules.
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1.
Slot Machine
15 minute play of a commercial slot machine game in bar-simulated laboratory setting.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* otherwise healthy, non-treatment seeking, non-abstinent
* male or female
* ages 19-65
* DSM-IV PG symptom scale score \> 5
* SOGS (South Oaks Gambling Screen) score \> 5
* nicotine dependence acceptable
* CONTROLS
* 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
* 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 (Alcohol Dependence Scale) \> 13 (more than low dependence)
* BDI (Beck Depression Inventory) short form \> 10 (more than low depression)
* DAST (Drug Abuse Screening Test) \> 4 (possible drug abuse)
* Consumption of \> 20/15 (men/women) standard alcoholic drinks/ week (hazardous drinking)
* 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
19 Years
65 Years
ALL
Yes
Sponsors
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Canadian Institutes of Health Research (CIHR)
OTHER_GOV
Centre for Addiction and Mental Health
OTHER
Responsible Party
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Daniela Lobo
Clinician Scientist
Principal Investigators
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Daniela Lobo, MD, Ph.D.
Role: PRINCIPAL_INVESTIGATOR
Centre for Addiction and Mental Health
Locations
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Centre for Addiction and Mental Health
Toronto, Ontario, Canada
Countries
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References
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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. doi: 10.1038/clpt.1983.65.
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. doi: 10.1176/ajp.144.9.1184.
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. doi: 10.1007/BF00542363.
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. doi: 10.1016/s0376-8716(02)00104-7.
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. doi: 10.1002/j.1552-4604.1998.tb04395.x.
Zack M, Lobo D, Biback C, Fang T, Smart K, Tatone D, Kalia A, Digiacomo D, Kennedy JL. Priming effects of a slot machine game and amphetamine on probabilistic risk-taking in people with gambling disorder and healthy controls. J Clin Exp Neuropsychol. 2023 Feb;45(1):31-60. doi: 10.1080/13803395.2023.2187041. Epub 2023 Mar 15.
Related Links
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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.
Other Identifiers
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232-2009
Identifier Type: -
Identifier Source: org_study_id
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