<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02203786</url>
  </required_header>
  <id_info>
    <org_study_id>232-2009</org_study_id>
    <nct_id>NCT02203786</nct_id>
  </id_info>
  <brief_title>D1 and D2 Dopamine Receptors in Gambling and Amphetamine Reinforcement</brief_title>
  <acronym>HFDEX</acronym>
  <official_title>Comparative Effects of a D2 and Mixed D1-D2 Dopamine Antagonist on Gambling and Amphetamine Reinforcement in Pathological Gamblers and Healthy Controls</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre for Addiction and Mental Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre for Addiction and Mental Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine if:&#xD;
&#xD;
        1. pathological gambling is similar to psychostimulant addiction as reflected by parallel&#xD;
           roles for D1 and D2 receptors in gambling and stimulant reinforcement.&#xD;
&#xD;
        2. these parallel roles are linked with gambling pathology or if they are evident in both&#xD;
           gamblers and controls.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND: No previous research appears to have investigated the role of dopamine (DA) D1 or&#xD;
      D2 receptors in psychostimulant reinforcement in pathological gamblers. Effects of&#xD;
      haloperidol vs. placebo will reveal the role of D2 and the effects of fluphenazine vs.&#xD;
      haloperidol will reveal the role of D1 in this process.&#xD;
&#xD;
      OBJECTIVE: This study will begin to define the neurochemistry of Pathological Gambling by&#xD;
      examining the roles of dopamine D1 and D2 receptors in gambling reinforcement and&#xD;
      psychostimulant reinforcement, and exploring genetic predictors of response to DA probes in&#xD;
      Pathological Gambling subjects (subjects) and healthy controls.&#xD;
&#xD;
      METHODS: A double-blind, placebo controlled, counterbalanced between-within design will be&#xD;
      employed. Each participant will attend 4 sessions with a minimum of 1 week between sessions&#xD;
      to ensure drug washout. Responses to the slot machine will be assessed in sessions 1 and 2&#xD;
      (Phase I), and responses to amphetamine will be assessed in sessions 3 and 4 (Phase II). A&#xD;
      second capsule (dummy) will be administered at expected peak levels for each antagonist on&#xD;
      sessions 1 and 2 to standardize the procedure across sessions.&#xD;
&#xD;
      Subjective reinforcement self-report scales will be administered at key intervals throughout&#xD;
      the study.&#xD;
&#xD;
      HYPOTHESIS: It is hypothesized that haloperidol (3-mg) will increase priming (Desire to&#xD;
      Gamble, Gambling word salience) and pleasurable effects (e.g., Enjoyment/Liking) induced by&#xD;
      playing a slot machine in Pathological Gambling subjects (N = 40). If gambling and stimulant&#xD;
      reinforcement are mediated by common mechanisms, haloperidol will also increase priming and&#xD;
      pleasurable effects of amphetamine (20-mg) in Pathological Gambling subjects.&#xD;
&#xD;
      If D1 mediates effects of haloperidol, the mixed D1-D2 antagonist, fluphenazine&#xD;
      (fluphenazine; 3-mg) will decrease or not alter responses to the slot machine and amphetamine&#xD;
      in Pathological Gambling subjects. If D2 deficits are linked with gambling pathology,&#xD;
      haloperidol will not affect slot machine or amphetamine reinforcement in controls (N= 40).&#xD;
&#xD;
      If D1 deficits are linked with gambling pathology, fluphenazine will increase gambling and&#xD;
      amphetamine reinforcement in controls, by mitigating undue D1 activation in subjects with&#xD;
      high baseline D1 function. If D1 or D2 genes contribute to gambling or amphetamine&#xD;
      reinforcement, genotype will predict responses to the manipulations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2009</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Subjective Reinforcement Self-report Scales</measure>
    <time_frame>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).</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Diastolic Blood Pressure (DBP)</measure>
    <time_frame>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).</time_frame>
    <description>Measure changes from baseline, especially physiologic reactivity to the slot machine and amphetamine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Task Performance</measure>
    <time_frame>At key points during testing: immediately after the slot machine, at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration)</time_frame>
    <description>Response time to words (gambling, alcohol, positive affect, negative affect) as a percentage of neutral categorized words (parts of a building). This provides an index of the relative salience of stimuli from these four categories against a baseline of reaction to words with no clinical relevance or emotional valence. Smaller scores indicate faster relative response time to the test stimuli vs. neutral stimuli (i.e., greater salience)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Betting Behaviour in Laboratory-based Slot Machine Game</measure>
    <time_frame>1x per test session (total of 4 test sessions) for duration of the study: 4 weeks (1 session/week)</time_frame>
    <description>Risk taking was operationally defined as credits wagered per spin (mean computed for total spins)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Speed of Play on Slot Machine Game</measure>
    <time_frame>15-minutes</time_frame>
    <description>Number of individual spins in a 15-minute slot machine game. Each spin corresponds to one wager.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Winnings on Slot Machine Upon Completion of Game</measure>
    <time_frame>15-minutes</time_frame>
    <description>Credits</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Pathological Gambling</condition>
  <arm_group>
    <arm_group_label>Haloperidol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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).&#xD;
Dose 1: 3 visually identical capsules, each containing 1 mg haloperidol OR 3 visually identical placebo (lactose) capsules&#xD;
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.&#xD;
Response measured to 15 min session of a commercial slot machine game.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fluphenazine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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).&#xD;
Dose 1: 3 visually identical capsules, each containing 1 mg fluphenazine OR 3 visually identical placebo (lactose) capsules&#xD;
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.&#xD;
Response measured to 15 min session of a commercial slot machine game.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Haloperidol</intervention_name>
    <description>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).&#xD;
Dose 1: 3 visually identical capsules, each containing 1 mg haloperidol.</description>
    <arm_group_label>Haloperidol</arm_group_label>
    <other_name>Teva-Haloperidol</other_name>
    <other_name>DIN: 00396818</other_name>
    <other_name>Haldol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluphenazine</intervention_name>
    <description>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).&#xD;
Dose 1: 3 visually identical capsules, each containing 1 mg fluphenazine.</description>
    <arm_group_label>Fluphenazine</arm_group_label>
    <other_name>APO-Fluphenazine</other_name>
    <other_name>DIN: 00405345</other_name>
    <other_name>Prolixin</other_name>
    <other_name>Permitil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexedrine</intervention_name>
    <description>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.&#xD;
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.</description>
    <arm_group_label>Fluphenazine</arm_group_label>
    <arm_group_label>Haloperidol</arm_group_label>
    <other_name>Dextro-amphetamine sulphate</other_name>
    <other_name>DIN: 01924516</other_name>
    <other_name>D-amphetamine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Dose 1: On alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing) participants will receive 3 visually identical placebo (lactose) capsules.&#xD;
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.</description>
    <arm_group_label>Fluphenazine</arm_group_label>
    <arm_group_label>Haloperidol</arm_group_label>
    <other_name>lactose capsule</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Slot Machine</intervention_name>
    <description>15 minute play of a commercial slot machine game in bar-simulated laboratory setting.</description>
    <arm_group_label>Fluphenazine</arm_group_label>
    <arm_group_label>Haloperidol</arm_group_label>
    <other_name>reward cue</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  PATHOLOGICAL GAMBLERS&#xD;
&#xD;
          -  otherwise healthy, non-treatment seeking, non-abstinent&#xD;
&#xD;
          -  male or female&#xD;
&#xD;
          -  ages 19-65&#xD;
&#xD;
          -  DSM-IV PG symptom scale score &gt; 5&#xD;
&#xD;
          -  SOGS (South Oaks Gambling Screen) score &gt; 5&#xD;
&#xD;
          -  nicotine dependence acceptable&#xD;
&#xD;
          -  CONTROLS&#xD;
&#xD;
          -  healthy&#xD;
&#xD;
          -  male or female&#xD;
&#xD;
          -  ages 19-65&#xD;
&#xD;
          -  DSM-IV PG symptom scale score = 0&#xD;
&#xD;
          -  SOGS score = 0&#xD;
&#xD;
          -  nicotine dependence acceptable&#xD;
&#xD;
          -  must have played slot machine &gt; 5 times&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  both Pathological Gamblers and Controls&#xD;
&#xD;
          -  Axis I psychopathology aside from nicotine dependence (or PG) based on SCID&#xD;
&#xD;
          -  Schizotypal or Borderline Personality Disorder based on psychiatric interview&#xD;
&#xD;
          -  Family history of schizophrenia or bipolar disorder&#xD;
&#xD;
          -  English comprehension below grade 7 level.&#xD;
&#xD;
          -  ADS (Alcohol Dependence Scale) &gt; 13 (more than low dependence)&#xD;
&#xD;
          -  BDI (Beck Depression Inventory) short form &gt; 10 (more than low depression)&#xD;
&#xD;
          -  DAST (Drug Abuse Screening Test) &gt; 4 (possible drug abuse)&#xD;
&#xD;
          -  Consumption of &gt; 20/15 (men/women) standard alcoholic drinks/ week (hazardous&#xD;
             drinking)&#xD;
&#xD;
          -  Smoking &gt; 20 cigarettes/day to help minimize withdrawal symptoms during test phase&#xD;
&#xD;
          -  Any prior use of psychostimulant drugs&#xD;
&#xD;
          -  Current use of medication that could interact with any of the study medications&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniela Lobo, MD, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre for Addiction and Mental Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre for Addiction and Mental Health</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5S 2S1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>http://www.camh.ca/en/research</url>
    <description>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.</description>
  </link>
  <reference>
    <citation>APA (2000) Diagnostic and Statistical Manual of Mental Disorders. IV-TR ed. American Psychiatric Association: Washington, DC.</citation>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>11696664</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>6831826</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>3631315</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>6662169</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>12167550</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>9807980</PMID>
  </reference>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>July 23, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <results_first_submitted>January 20, 2016</results_first_submitted>
  <results_first_submitted_qc>April 11, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">April 25, 2016</results_first_posted>
  <last_update_submitted>April 11, 2016</last_update_submitted>
  <last_update_submitted_qc>April 11, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 25, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre for Addiction and Mental Health</investigator_affiliation>
    <investigator_full_name>Daniela Lobo</investigator_full_name>
    <investigator_title>Clinician Scientist</investigator_title>
  </responsible_party>
  <keyword>amphetamine</keyword>
  <keyword>d1 and d2 receptors</keyword>
  <keyword>dopamine antagonists</keyword>
  <keyword>pathological gambling</keyword>
  <keyword>priming</keyword>
  <keyword>reinforcement</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gambling</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Haloperidol</mesh_term>
    <mesh_term>Haloperidol decanoate</mesh_term>
    <mesh_term>Fluphenazine</mesh_term>
    <mesh_term>Fluphenazine depot</mesh_term>
    <mesh_term>Fluphenazine enanthate</mesh_term>
    <mesh_term>Amphetamine</mesh_term>
    <mesh_term>Dextroamphetamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment was conducted for all groups between January 2010 and May 2015</recruitment_details>
      <pre_assignment_details>Pathological Gamblers and healthy Controls were each randomized to receive Haloperidol or Fluphenazine. In each group, treatment sequence (antagonist first, placebo second; or vice versa) was counterbalanced across participants, to control for order effects only (sequence was not a test factor). Two Haloperidol-Controls dropped out after session 1.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Haloperidol - Pathological Gamblers</title>
          <description>Dose 1: 3 mg haloperidol (3 capsules @ 1mg each) OR 3 identical placebo capsules on alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing). Dose 2: administered when peak blood levels for dose 1 are reached. 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 identical capsules each containing 10 mg dexedrine. Response measured to 15 min session of a commercial slot machine game.&#xD;
Haloperidol: Dose/maximum dose 3 mg oral. Participants assigned to the haloperidol antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between doses).&#xD;
Dexedrine: Dose/maximum dose 20mg oral. All participants will receive 2 doses (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between doses.</description>
        </group>
        <group group_id="P2">
          <title>Fluphenazine - Pathological Gamblers</title>
          <description>Dose 1: 3 mg fluphenazine (3 capsules @ 1 mg each) OR 3 visually identical placebo capsules on alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing). Dose 2: administered when participants reach peak blood levels for dose 1. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 identical capsules each containing 10 mg dexedrine.&#xD;
Response measured to 15 min session of a commercial slot machine game. Participants assigned to the fluphenazine antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between individual doses).&#xD;
All participants will receive 2 doses of Dexedrine (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between individual doses.</description>
        </group>
        <group group_id="P3">
          <title>Haloperidol - Controls</title>
          <description>Dose 1: 3 mg haloperidol (3 capsules @ 1 mg each) OR 3 identical placebo capsules on alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing). Dose 2: administered when peak blood levels for dose 1 are reached. 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 identical capsules each containing 10 mg dexedrine. Response measured to 15 min session of a commercial slot machine game.&#xD;
Haloperidol: Dose/maximum dose 3 mg oral. Participants assigned to the haloperidol antagonist group receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between doses). Dexedrine: Dose/maximum dose 20 mg oral. All participants will receive 2 doses (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between doses.</description>
        </group>
        <group group_id="P4">
          <title>Fluphenazine - Controls</title>
          <description>Dose 1: 3 mg fluphenazine (3 capsules @ 1mg each) OR 3 visually identical placebo capsules on alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing). Dose 2: administered when participants reach peak blood levels for dose 1. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 identical capsules each containing 10 mg dexedrine.&#xD;
Response measured to 15 min session of a commercial slot machine game. Participants assigned to the fluphenazine antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between individual doses).&#xD;
All participants will receive 2 doses of Dexedrine (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between individual doses.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="17"/>
                <participants group_id="P4" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="15"/>
                <participants group_id="P4" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants were above 18 years of age.</population>
      <group_list>
        <group group_id="B1">
          <title>Haloperidol - Pathological Gamblers</title>
          <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
        </group>
        <group group_id="B2">
          <title>Fluphenazine - Pathological Gamblers</title>
          <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
        </group>
        <group group_id="B3">
          <title>Haloperidol - Controls</title>
          <description>A total of 15 control subjects were enrolled in this arm.</description>
        </group>
        <group group_id="B4">
          <title>Fluphenazine - Controls</title>
          <description>A total of 15 control subjects were enrolled in this arm.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="15"/>
            <count group_id="B4" value="15"/>
            <count group_id="B5" value="60"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35.8" lower_limit="22" upper_limit="53"/>
                    <measurement group_id="B2" value="33.5" lower_limit="19" upper_limit="49"/>
                    <measurement group_id="B3" value="36.1" lower_limit="19" upper_limit="56"/>
                    <measurement group_id="B4" value="39.9" lower_limit="23" upper_limit="62"/>
                    <measurement group_id="B5" value="36.3" lower_limit="19" upper_limit="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>South Oaks Gambling Screen (SOGS)</title>
          <description>Range of possible scores on the SOGS is 0-20. A score of 5 or more indicates &quot;probable pathological gambling&quot; with respect to DSM criteria.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11.1" lower_limit="6" upper_limit="18"/>
                    <measurement group_id="B2" value="11.7" lower_limit="5" upper_limit="20"/>
                    <measurement group_id="B3" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="B4" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="B5" value="5.7" lower_limit="0" upper_limit="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Beck Depression Inventory - past 2 weeks</title>
          <description>Measure of depressive symptoms in the past 2 weeks. The scale contains 13 items scored 0-3 in increasing severity (range of possible scores: 0-39). A score of 10 is considered the cut-off for clinically relevant depressive symptoms.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.3" spread="3.6"/>
                    <measurement group_id="B2" value="5.6" spread="4.5"/>
                    <measurement group_id="B3" value="0.9" spread="1.2"/>
                    <measurement group_id="B4" value="1.3" spread="2.1"/>
                    <measurement group_id="B5" value="3.02" spread="2.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eysenck Impulsivity Scale</title>
          <description>This 19-item yes/no scale measures trait impulsivity. Scores range from 0-19. The normative mean in the general population is 9. The mean score in large samples of people with pathological gambling is also 9.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.2" spread="4.4"/>
                    <measurement group_id="B2" value="8.5" spread="4.4"/>
                    <measurement group_id="B3" value="2.6" spread="2.1"/>
                    <measurement group_id="B4" value="1.6" spread="2.5"/>
                    <measurement group_id="B5" value="5.47" spread="3.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Alcohol Dependence Scale</title>
          <description>This 25-item scale assesses severity of the Alcohol Dependence syndrome. Total scores range from 0-51. A score of 13 corresponds to the 1st quartile and scores from 0-13 are said to indicate low dependence. A score of 9 or more has been associated with alcohol &quot;abuse.&quot;</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.1" lower_limit="0" upper_limit="4"/>
                    <measurement group_id="B2" value="1.6" lower_limit="0" upper_limit="11"/>
                    <measurement group_id="B3" value="0.6" lower_limit="0" upper_limit="3"/>
                    <measurement group_id="B4" value="0.3" lower_limit="0" upper_limit="4"/>
                    <measurement group_id="B5" value="0.9" lower_limit="0" upper_limit="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Timeline Followback</title>
          <description>number of alcoholic drinks per week</description>
          <units>number of alcoholic drinks per week</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.3" lower_limit="0" upper_limit="8"/>
                    <measurement group_id="B2" value="1.5" lower_limit="0" upper_limit="3"/>
                    <measurement group_id="B3" value="1.5" lower_limit="0" upper_limit="6"/>
                    <measurement group_id="B4" value="1.8" lower_limit="0" upper_limit="5.5"/>
                    <measurement group_id="B5" value="1.7" lower_limit="0" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Subjective Reinforcement Self-report Scales</title>
        <description>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.</description>
        <time_frame>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).</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Haloperidol - Pathological Gamblers</title>
            <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
          </group>
          <group group_id="O2">
            <title>Fluphenazine - Pathological Gamblers</title>
            <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
          </group>
          <group group_id="O3">
            <title>Haloperidol - Controls</title>
            <description>A total of 15 controls were enrolled in this arm.</description>
          </group>
          <group group_id="O4">
            <title>Fluphenazine - Controls</title>
            <description>A total of 15 controls were enrolled in this arm.</description>
          </group>
        </group_list>
        <measure>
          <title>Subjective Reinforcement Self-report Scales</title>
          <description>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.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Drug - Confidence not to gamble after slot machine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" spread="2.3"/>
                    <measurement group_id="O2" value="4.8" spread="2.9"/>
                    <measurement group_id="O3" value="9.5" spread="1.1"/>
                    <measurement group_id="O4" value="9.3" spread="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Placebo - Confidence not to gamble after slot mach</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2" spread="2.5"/>
                    <measurement group_id="O2" value="4.8" spread="3.4"/>
                    <measurement group_id="O3" value="9" spread="1.6"/>
                    <measurement group_id="O4" value="8.2" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug - Confidence not to gamble at peak amphetamin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" spread="2.5"/>
                    <measurement group_id="O2" value="6.4" spread="3.2"/>
                    <measurement group_id="O3" value="9.8" spread="0.5"/>
                    <measurement group_id="O4" value="9.8" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plac -Confidence not to gamble at peak amphetamine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.5" spread="2.3"/>
                    <measurement group_id="O2" value="5.7" spread="3.5"/>
                    <measurement group_id="O3" value="9.4" spread="1.1"/>
                    <measurement group_id="O4" value="9.3" spread="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Diastolic Blood Pressure (DBP)</title>
        <description>Measure changes from baseline, especially physiologic reactivity to the slot machine and amphetamine.</description>
        <time_frame>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).</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Haloperidol - Pathological Gamblers</title>
            <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
          </group>
          <group group_id="O2">
            <title>Fluphenazine - Pathological Gamblers</title>
            <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
          </group>
          <group group_id="O3">
            <title>Haloperidol - Controls</title>
            <description>A total of 15 controls were enrolled in this arm.</description>
          </group>
          <group group_id="O4">
            <title>Fluphenazine - Controls</title>
            <description>A total of 15 controls were enrolled in this arm.</description>
          </group>
        </group_list>
        <measure>
          <title>Diastolic Blood Pressure (DBP)</title>
          <description>Measure changes from baseline, especially physiologic reactivity to the slot machine and amphetamine.</description>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Drug-Change in DBP pre-to-post slot machine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.2" spread="24.5"/>
                    <measurement group_id="O2" value="22" spread="23.6"/>
                    <measurement group_id="O3" value="15.1" spread="18.6"/>
                    <measurement group_id="O4" value="23.6" spread="23.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Placebo-Change in DBP pre-to-post slot machine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.5" spread="24.8"/>
                    <measurement group_id="O2" value="21.6" spread="29.3"/>
                    <measurement group_id="O3" value="19.1" spread="24.8"/>
                    <measurement group_id="O4" value="19" spread="23.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug-Change in DBP pre-amphetamine to peak amph</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.2" spread="24.4"/>
                    <measurement group_id="O2" value="32.1" spread="25.1"/>
                    <measurement group_id="O3" value="28.5" spread="30"/>
                    <measurement group_id="O4" value="32.7" spread="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Placebo-Change in DBP pre-amphetamine to peak amp</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.6" spread="29.8"/>
                    <measurement group_id="O2" value="35.2" spread="28"/>
                    <measurement group_id="O3" value="26.6" spread="24.5"/>
                    <measurement group_id="O4" value="36.3" spread="28.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Task Performance</title>
        <description>Response time to words (gambling, alcohol, positive affect, negative affect) as a percentage of neutral categorized words (parts of a building). This provides an index of the relative salience of stimuli from these four categories against a baseline of reaction to words with no clinical relevance or emotional valence. Smaller scores indicate faster relative response time to the test stimuli vs. neutral stimuli (i.e., greater salience)</description>
        <time_frame>At key points during testing: immediately after the slot machine, at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Haloperidol - Pathological Gamblers</title>
            <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
          </group>
          <group group_id="O2">
            <title>Fluphenazine - Pathological Gamblers</title>
            <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
          </group>
          <group group_id="O3">
            <title>Haloperidol - Controls</title>
            <description>A total of 15 controls were enrolled in this arm.</description>
          </group>
          <group group_id="O4">
            <title>Fluphenazine - Controls</title>
            <description>A total of 15 controls were enrolled in this arm.</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Task Performance</title>
          <description>Response time to words (gambling, alcohol, positive affect, negative affect) as a percentage of neutral categorized words (parts of a building). This provides an index of the relative salience of stimuli from these four categories against a baseline of reaction to words with no clinical relevance or emotional valence. Smaller scores indicate faster relative response time to the test stimuli vs. neutral stimuli (i.e., greater salience)</description>
          <units>percentage of neutral categorized words</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>post-slots-GAM words under drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.6" spread="7.9"/>
                    <measurement group_id="O2" value="94.0" spread="6.0"/>
                    <measurement group_id="O3" value="94.8" spread="6.1"/>
                    <measurement group_id="O4" value="91.0" spread="7.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>post-slots-ALC words under drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.5" spread="8.4"/>
                    <measurement group_id="O2" value="98.1" spread="7.6"/>
                    <measurement group_id="O3" value="96.5" spread="6.6"/>
                    <measurement group_id="O4" value="93.1" spread="8.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>post-slots POS words under drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.3" spread="8.7"/>
                    <measurement group_id="O2" value="95.3" spread="7.6"/>
                    <measurement group_id="O3" value="93.7" spread="8.3"/>
                    <measurement group_id="O4" value="88.3" spread="8.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>post-slots NEG words under drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89.1" spread="9.5"/>
                    <measurement group_id="O2" value="96.5" spread="7.3"/>
                    <measurement group_id="O3" value="89.6" spread="7.6"/>
                    <measurement group_id="O4" value="87.9" spread="10.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>post-slots GAM words under placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.6" spread="8.1"/>
                    <measurement group_id="O2" value="95.0" spread="5.3"/>
                    <measurement group_id="O3" value="97.2" spread="7.2"/>
                    <measurement group_id="O4" value="92.1" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>post-slots ALC words under placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.8" spread="6.1"/>
                    <measurement group_id="O2" value="99.0" spread="7.2"/>
                    <measurement group_id="O3" value="97.0" spread="6.5"/>
                    <measurement group_id="O4" value="93.3" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>post-slots POS words under placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.7" spread="8.1"/>
                    <measurement group_id="O2" value="94.9" spread="5.8"/>
                    <measurement group_id="O3" value="93.7" spread="6.1"/>
                    <measurement group_id="O4" value="86.8" spread="10.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>post-slots NEG words under placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93.0" spread="10.4"/>
                    <measurement group_id="O2" value="97.2" spread="13.4"/>
                    <measurement group_id="O3" value="92.3" spread="4.8"/>
                    <measurement group_id="O4" value="84.7" spread="6.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>peak AMPH GAM words under drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.7" spread="3.4"/>
                    <measurement group_id="O2" value="95.8" spread="4.5"/>
                    <measurement group_id="O3" value="98.1" spread="4.5"/>
                    <measurement group_id="O4" value="97.0" spread="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>peak AMPH ALC words under drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="101.2" spread="3.6"/>
                    <measurement group_id="O2" value="99.5" spread="4.6"/>
                    <measurement group_id="O3" value="99.1" spread="3.9"/>
                    <measurement group_id="O4" value="100.3" spread="5.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>peak AMPH POS words under drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.2" spread="3.3"/>
                    <measurement group_id="O2" value="98.7" spread="4.6"/>
                    <measurement group_id="O3" value="97.2" spread="4.7"/>
                    <measurement group_id="O4" value="96.3" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>peak AMPH NEG words under drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.5" spread="5.1"/>
                    <measurement group_id="O2" value="99.4" spread="4.8"/>
                    <measurement group_id="O3" value="96.8" spread="3.6"/>
                    <measurement group_id="O4" value="98.7" spread="5.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>peak AMPH GAM words under placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.0" spread="4.9"/>
                    <measurement group_id="O2" value="97.9" spread="5.8"/>
                    <measurement group_id="O3" value="96.8" spread="2.9"/>
                    <measurement group_id="O4" value="96.9" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>peak AMPH ALC words under placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.9" spread="6.2"/>
                    <measurement group_id="O2" value="99.9" spread="5.3"/>
                    <measurement group_id="O3" value="100.2" spread="4.7"/>
                    <measurement group_id="O4" value="97.5" spread="6.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>peak AMPH POS words under placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.4" spread="4.7"/>
                    <measurement group_id="O2" value="97.7" spread="5.5"/>
                    <measurement group_id="O3" value="97.8" spread="4.0"/>
                    <measurement group_id="O4" value="95.1" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>peak AMPH NEG words under placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.0" spread="6.5"/>
                    <measurement group_id="O2" value="100.0" spread="3.4"/>
                    <measurement group_id="O3" value="98.1" spread="5.7"/>
                    <measurement group_id="O4" value="96.7" spread="4.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Betting Behaviour in Laboratory-based Slot Machine Game</title>
        <description>Risk taking was operationally defined as credits wagered per spin (mean computed for total spins)</description>
        <time_frame>1x per test session (total of 4 test sessions) for duration of the study: 4 weeks (1 session/week)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Haloperidol - Pathological Gamblers</title>
            <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
          </group>
          <group group_id="O2">
            <title>Fluphenazine - Pathological Gamblers</title>
            <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
          </group>
          <group group_id="O3">
            <title>Haloperidol - Controls</title>
            <description>A total of 15 controls were enrolled in this arm.</description>
          </group>
          <group group_id="O4">
            <title>Fluphenazine - Controls</title>
            <description>A total of 15 controls were enrolled in this arm.</description>
          </group>
        </group_list>
        <measure>
          <title>Betting Behaviour in Laboratory-based Slot Machine Game</title>
          <description>Risk taking was operationally defined as credits wagered per spin (mean computed for total spins)</description>
          <units>credits/spin on slot machine</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mean bet under drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.8" spread="7.2"/>
                    <measurement group_id="O2" value="16.0" spread="10.4"/>
                    <measurement group_id="O3" value="11.6" spread="7.8"/>
                    <measurement group_id="O4" value="14.4" spread="10.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean bet under placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.4" spread="9.3"/>
                    <measurement group_id="O2" value="16.1" spread="12.4"/>
                    <measurement group_id="O3" value="9.5" spread="10.8"/>
                    <measurement group_id="O4" value="12.2" spread="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Speed of Play on Slot Machine Game</title>
        <description>Number of individual spins in a 15-minute slot machine game. Each spin corresponds to one wager.</description>
        <time_frame>15-minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Haloperidol - Pathological Gamblers</title>
            <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
          </group>
          <group group_id="O2">
            <title>Fluphenazine - Pathological Gamblers</title>
            <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
          </group>
          <group group_id="O3">
            <title>Haloperidol - Controls</title>
            <description>A total of 15 control subjects were enrolled in this arm.</description>
          </group>
          <group group_id="O4">
            <title>Fluphenazine - Controls</title>
            <description>A total of 15 control subjects were enrolled in this arm.</description>
          </group>
        </group_list>
        <measure>
          <title>Speed of Play on Slot Machine Game</title>
          <description>Number of individual spins in a 15-minute slot machine game. Each spin corresponds to one wager.</description>
          <units>individual spins/15-minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Spins/15-minutes under Drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.9" spread="35.4"/>
                    <measurement group_id="O2" value="78.5" spread="34.5"/>
                    <measurement group_id="O3" value="66.4" spread="27.9"/>
                    <measurement group_id="O4" value="71.8" spread="30.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spins/15-minutes under Placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.6" spread="32.9"/>
                    <measurement group_id="O2" value="68.4" spread="47.3"/>
                    <measurement group_id="O3" value="72.2" spread="40.5"/>
                    <measurement group_id="O4" value="66.7" spread="31.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Winnings on Slot Machine Upon Completion of Game</title>
        <description>Credits</description>
        <time_frame>15-minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Haloperidol - Pathological Gamblers</title>
            <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
          </group>
          <group group_id="O2">
            <title>Fluphenazine - Pathological Gamblers</title>
            <description>A total of 15 pathological gamblers were enrolled in this arm.</description>
          </group>
          <group group_id="O3">
            <title>Haloperidol - Controls</title>
            <description>A total of 15 controls were enrolled in this arm.</description>
          </group>
          <group group_id="O4">
            <title>Fluphenazine - Controls</title>
            <description>A total of 15 controls were enrolled in this arm.</description>
          </group>
        </group_list>
        <measure>
          <title>Winnings on Slot Machine Upon Completion of Game</title>
          <description>Credits</description>
          <units>credits</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Winnings (Final Credit Tally) under drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="239" spread="305.1"/>
                    <measurement group_id="O2" value="277.8" spread="300.2"/>
                    <measurement group_id="O3" value="449.1" spread="669.6"/>
                    <measurement group_id="O4" value="544.3" spread="820"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Winnings (Final Credit Tally) under Placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="562.4" spread="658"/>
                    <measurement group_id="O2" value="140.8" spread="325.7"/>
                    <measurement group_id="O3" value="339.2" spread="427.4"/>
                    <measurement group_id="O4" value="215" spread="214.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Same day as drug administration</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Haloperidol - Pathological Gamblers</title>
          <description>Drug sequence 1 (haloperidol on day 1 of each phase), or drug sequence 2 (haloperidol on day 2 of each phase).&#xD;
Dose 1: 3mg haloperidol (3 capsules @ 1mg each) OR 3 identical placebo capsules on alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing). Dose 2: administered when peak blood levels for dose 1 are reached. 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 identical capsules each containing 10 mg dexedrine.&#xD;
Response measured to 15 min session of a commercial slot machine game. Haloperidol: Dose/maximum dose 3mg oral. Participants assigned to the haloperidol antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between doses).&#xD;
Dexedrine: Dose/maximum dose 20mg oral. All participants will receive 2 doses (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between doses.</description>
        </group>
        <group group_id="E2">
          <title>Fluphenazine - Pathological Gamblers</title>
          <description>Drug sequence 1 (fluphenazine on day 1 of each phase), or drug sequence 2 (fluphenazine on day 2 of each phase).&#xD;
Dose 1: 3 mg fluphenazine (3 capsules @ 1mg each) OR 3 visually identical placebo capsules on alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing). Dose 2: administered when participants reach peak blood levels for dose 1. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 identical capsules each containing 10 mg dexedrine.&#xD;
Response measured to 15 min session of a commercial slot machine game. Participants assigned to the fluphenazine antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between individual doses).&#xD;
All participants will receive 2 doses of Dexedrine (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between individual doses.</description>
        </group>
        <group group_id="E3">
          <title>Haloperidol - Controls</title>
          <description>Drug sequence 1 (haloperidol on day 1 of each phase), or drug sequence 2 (haloperidol on day 2 of each phase).&#xD;
Dose 1: 3mg haloperidol (3 capsules @ 1mg each) OR 3 identical placebo capsules on alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing). Dose 2: administered when peak blood levels for dose 1 are reached. 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 identical capsules each containing 10 mg dexedrine.&#xD;
Response measured to 15 min session of a commercial slot machine game. Haloperidol: Dose/maximum dose 3mg oral. Participants assigned to the haloperidol antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between doses).&#xD;
Dexedrine: Dose/maximum dose 20mg oral. All participants will receive 2 doses (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between doses.</description>
        </group>
        <group group_id="E4">
          <title>Fluphenazine - Controls</title>
          <description>Drug sequence 1 (fluphenazine on day 1 of each phase), or drug sequence 2 (fluphenazine on day 2 of each phase).&#xD;
Dose 1: 3 mg fluphenazine (3 capsules @ 1mg each) OR 3 visually identical placebo capsules on alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing). Dose 2: administered when participants reach peak blood levels for dose 1. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 identical capsules each containing 10 mg dexedrine.&#xD;
Response measured to 15 min session of a commercial slot machine game. Participants assigned to the fluphenazine antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between individual doses).&#xD;
All participants will receive 2 doses of Dexedrine (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between individual doses.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <description>Mild restlessness which is an expected side effect of haloperidol</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Daniela Lobo, Qualified Investigator for Study, Clinician-Scientist</name_or_title>
      <organization>Centre for Addiction and Mental Health</organization>
      <phone>416-535-8501 ext 36568</phone>
      <email>Daniela.Lobo@camh.ca</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02203786
org study id: 232-2009
nct id: NCT02203786
lead sponsor: 
collaborator: 
has dmc: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Subjective Reinforcement Self-report Scales
time frame: 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).
description: 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.
measure: Diastolic Blood Pressure (DBP)
time frame: 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).
description: Measure changes from baseline, especially physiologic reactivity to the slot machine and amphetamine.
measure: Cognitive Task Performance
time frame: At key points during testing: immediately after the slot machine, at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration)
description: Response time to words (gambling, alcohol, positive affect, negative affect) as a percentage of neutral categorized words (parts of a building). This provides an index of the relative salience of stimuli from these four categories against a baseline of reaction to words with no clinical relevance or emotional valence. Smaller scores indicate faster relative response time to the test stimuli vs. neutral stimuli (i.e., greater salience)
measure: Betting Behaviour in Laboratory-based Slot Machine Game
time frame: 1x per test session (total of 4 test sessions) for duration of the study: 4 weeks (1 session/week)
description: Risk taking was operationally defined as credits wagered per spin (mean computed for total spins)
measure: Speed of Play on Slot Machine Game
time frame: 15-minutes
description: Number of individual spins in a 15-minute slot machine game. Each spin corresponds to one wager.
measure: Winnings on Slot Machine Upon Completion of Game
time frame: 15-minutes
description: Credits
arm group label: Haloperidol
arm group type: Active Comparator
description: 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.
arm group label: Fluphenazine
arm group type: Active Comparator
description: 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.
intervention type: Drug
intervention name: Haloperidol
description: 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.
arm group label: Haloperidol
other name: Teva-Haloperidol
other name: DIN: 00396818
other name: Haldol
intervention type: Drug
intervention name: Fluphenazine
description: 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.
arm group label: Fluphenazine
other name: APO-Fluphenazine
other name: DIN: 00405345
other name: Prolixin
other name: Permitil
intervention type: Drug
intervention name: Dexedrine
description: 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.
arm group label: Fluphenazine
arm group label: Haloperidol
other name: Dextro-amphetamine sulphate
other name: DIN: 01924516
other name: D-amphetamine
intervention type: Drug
intervention name: Placebo
description: 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.
arm group label: Fluphenazine
arm group label: Haloperidol
other name: lactose capsule
intervention type: Behavioral
intervention name: Slot Machine
description: 15 minute play of a commercial slot machine game in bar-simulated laboratory setting.
arm group label: Fluphenazine
arm group label: Haloperidol
other name: reward cue
criteria: 
gender: All
minimum age: 19 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Daniela Lobo, MD, Ph.D.
role: Principal Investigator
affiliation: Centre for Addiction and Mental Health
facility: 
country: Canada
url: http://www.camh.ca/en/research
description: 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.
citation: APA (2000) Diagnostic and Statistical Manual of Mental Disorders. IV-TR ed. American Psychiatric Association: Washington, DC.
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
responsible party type: Principal Investigator
investigator affiliation: Centre for Addiction and Mental Health
investigator full name: Daniela Lobo
investigator title: Clinician Scientist
mesh term: Gambling
mesh term: Haloperidol
mesh term: Haloperidol decanoate
mesh term: Fluphenazine
mesh term: Fluphenazine depot
mesh term: Fluphenazine enanthate
mesh term: Amphetamine
mesh term: Dextroamphetamine
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 