D1 and D2 Dopamine Receptors in Gambling and Amphetamine Reinforcement

NCT02203786 | Completed Phase 2 Results

• 1 other identifier: 232-2009
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

To determine if:

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

Conditions

Pathological Gambling

Keywords

amphetamine; d1 and d2 receptors; dopamine antagonists; pathological gambling; priming; reinforcement

Outcome Measures

Primary Outcomes (1)

• Subjective Reinforcement Self-report Scales

  Self-reported Confidence to Refrain from Gambling (0 - 10) was assessed at test session baseline, before the slot machine and after the slot machine (Phase 1); and before amphetamine and at peak amphetamine (Phase 2). The maximum score (10) denotes complete confidence to refrain from gambling (i.e., NO urge or compulsion to gamble); the minimum score (0) denotes complete lack of confidence to refrain from gambling (i.e., overwhelming urge to gamble). Scores between 10 and 0 denote intermediate confidence to refrain from gambling with LOWER scores denoting less confidence to refrain from gambling -- i.e., GREATER urge or compulsive motivation to gamble. Scores shown are based on single item visual analogue ratings 0-10 from each participant at the specified time point. The mean (SD) of these single item ratings is presented for each sub-group.

  At key points in testing: immediately after the slot machine game, and at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration).

Secondary Outcomes (5)

• Diastolic Blood Pressure (DBP)

  At key points in testing: immediately after the slot machine game (change from session baseline), and at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration)(change from session baseline).

• Cognitive Task Performance

  At key points during testing: immediately after the slot machine, at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration)

• Betting Behaviour in Laboratory-based Slot Machine Game

  1x per test session (total of 4 test sessions) for duration of the study: 4 weeks (1 session/week)

• Speed of Play on Slot Machine Game

  15-minutes

• Winnings on Slot Machine Upon Completion of Game

  15-minutes

Study Arms (2)

Haloperidol

ACTIVE COMPARATOR

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.

Drug: Haloperidol; Drug: Dexedrine; Drug: Placebo; Behavioral: Slot Machine

Fluphenazine

ACTIVE COMPARATOR

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.

Drug: Fluphenazine; Drug: Dexedrine; Drug: Placebo; Behavioral: Slot Machine

Interventions

Haloperidol DRUG

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.

Also known as: Teva-Haloperidol, DIN: 00396818, Haldol

Haloperidol

Fluphenazine DRUG

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.

Also known as: APO-Fluphenazine, DIN: 00405345, Prolixin, Permitil

Fluphenazine

Dexedrine DRUG

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.

Also known as: Dextro-amphetamine sulphate, DIN: 01924516, D-amphetamine

Fluphenazine; Haloperidol

Placebo DRUG

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.

Also known as: lactose capsule

Fluphenazine; Haloperidol

Slot Machine BEHAVIORAL

15 minute play of a commercial slot machine game in bar-simulated laboratory setting.

Also known as: reward cue

Fluphenazine; Haloperidol

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PATHOLOGICAL GAMBLERS
• 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

You may not qualify if:

• 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 (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

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5S 2S1, Canada

Location

Related Publications (8)

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

  BACKGROUND

• 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.

  PMID: 11696664 BACKGROUND

• 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.

  PMID: 6831826 BACKGROUND

• 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.

  PMID: 3631315 BACKGROUND

• 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.

  PMID: 6662169 BACKGROUND

• 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.

  PMID: 12167550 BACKGROUND

• 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.

  PMID: 9807980 BACKGROUND

• 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.

  PMID: 36919514 DERIVED

Related Links

• 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.

MeSH Terms

Conditions

Gambling

Interventions

Haloperidol; Fluphenazine; Dextroamphetamine; Lactose

Condition Hierarchy (Ancestors)

Risk-Taking; Behavior; Disruptive, Impulse Control, and Conduct Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Butyrophenones; Ketones; Organic Chemicals; Phenothiazines; Sulfur Compounds; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Amphetamine; Amphetamines; Phenethylamines; Ethylamines; Amines; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Results Point of Contact

• Title: Dr. Daniela Lobo, Qualified Investigator for Study, Clinician-Scientist
• Organization: Centre for Addiction and Mental Health

Daniela.Lobo@camh.ca

416-535-8501

Study Officials

• Daniela Lobo, MD, Ph.D.

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician Scientist

Study Record Dates

• First Submitted: July 23, 2014
• First Posted: July 30, 2014
• Study Start: September 1, 2009
• Primary Completion: June 1, 2015
• Study Completion: September 1, 2015
• Last Updated: April 25, 2016
• Results First Posted: April 25, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)