xml: <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/NCT05999383</url>
    </required_header>
    <id_info>
      <org_study_id>23-38884</org_study_id>
      <secondary_id>1R01DA056451-01A1</secondary_id>
      <nct_id>NCT05999383</nct_id>
    </id_info>
    <brief_title>Understanding the Clinical Pharmacology of Marijuana-Tobacco Co-administration</brief_title>
    <acronym>CANNIC</acronym>
    <official_title>Understanding the Clinical Pharmacology of Marijuana-Tobacco Co-administration</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of California, San Francisco</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institute on Drug Abuse (NIDA)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
      <collaborator>
        <agency>National Institutes of Health (NIH)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
      <collaborator>
        <agency>Food and Drug Administration (FDA)</agency>
        <agency_class>U.S. Fed</agency_class>
      </collaborator>
    </sponsors>
    <source>University of California, San Francisco</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a crossover, randomized, double-blinded clinical pharmacology study enrolling dual&#xD;
        cannabis-tobacco smokers to better understand the combined effects of co-administering&#xD;
        cannabis and tobacco. The project aims to describe the pharmacokinetics and pharmacodynamics&#xD;
        of marijuana-tobacco co-administration by delivering THC and nicotine in various&#xD;
        combinations. This foundational study will establish a research program focused on&#xD;
        elucidating the public health consequences of marijuana-tobacco co-use.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a single-center, within-subject (crossover), randomized, double-blinded clinical&#xD;
        pharmacology study of over 8 study visits (days). Participants will be non-treatment-seeking,&#xD;
        healthy frequent users of both marijuana and tobacco/nicotine, age 21 to 65 years (21 years&#xD;
        because of California tobacco control law). Participants will be marijuana users of any race&#xD;
        who smoke or vape marijuana or THC extracts at least three days a week for the past 3 months&#xD;
        or more. The study investigators will use positive urine toxicology THC results and&#xD;
        self-report of marijuana smoking/vaping to determine eligibility. Participants must also be&#xD;
        current users of inhaled forms of tobacco/nicotine (cigarettes, cigars, e-cigarettes) who use&#xD;
        the product daily over the past 3 months.&#xD;
  &#xD;
        Each study day will consist of a standardized session of 5 puffs of one of 8 study conditions&#xD;
        using a PAX-3 vaporizer (PAX Labs, Inc.). Blood will be sampled multiple times for plasma&#xD;
        THC, nicotine, and catecholamines, questionnaires administered for sensory and subjective&#xD;
        effects, and heart rate, skin blood flow, and skin temperature will be measured. After 6&#xD;
        hours of abstinence, participants will have 60 minutes of ad libitum access to the assigned&#xD;
        study condition, during which heart rate and blood pressure will be continuously monitored,&#xD;
        blood sampled before and after for THC, nicotine, and platelet aggregation measured, and&#xD;
        questionnaires administered.&#xD;
  &#xD;
        Studies will be conducted at the CTSI Clinical Research Services-supported research ward at&#xD;
        Zuckerberg San Francisco General.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 31, 2023</start_date>
    <completion_date type="Anticipated">October 31, 2028</completion_date>
    <primary_completion_date type="Anticipated">October 31, 2028</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>Crossover Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in peak plasma concentration of THC</measure>
      <time_frame>Baseline and Day 1</time_frame>
      <description>To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in peak plasma concentration of THC</measure>
      <time_frame>Day 1 and Day 2</time_frame>
      <description>To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in peak plasma concentration of THC</measure>
      <time_frame>Day 2 and Day 3</time_frame>
      <description>To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in peak plasma concentration of THC</measure>
      <time_frame>Day 3 and Day 4</time_frame>
      <description>To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in peak plasma concentration of THC</measure>
      <time_frame>Day 4 and Day 5</time_frame>
      <description>To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in peak plasma concentration of THC</measure>
      <time_frame>Day 5 and Day 6</time_frame>
      <description>To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in peak plasma concentration of THC</measure>
      <time_frame>Day 6 and Day 7</time_frame>
      <description>To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in peak plasma concentration of THC</measure>
      <time_frame>Day 7 and Day 8</time_frame>
      <description>To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Peak plasma concentration of nicotine</measure>
      <time_frame>Baseline and Day 1</time_frame>
      <description>To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Peak plasma concentration of nicotine</measure>
      <time_frame>Day 1 and Day 2</time_frame>
      <description>To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Peak plasma concentration of nicotine</measure>
      <time_frame>Day 2 and Day 3</time_frame>
      <description>To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Peak plasma concentration of nicotine</measure>
      <time_frame>Day 3 and Day 4</time_frame>
      <description>To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Peak plasma concentration of nicotine</measure>
      <time_frame>Day 4 and Day 5</time_frame>
      <description>To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Peak plasma concentration of nicotine</measure>
      <time_frame>Day 5 and Day 6</time_frame>
      <description>To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Peak plasma concentration of nicotine</measure>
      <time_frame>Day 6 and Day 7</time_frame>
      <description>To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Peak plasma concentration of nicotine</measure>
      <time_frame>Day 7 and Day 8</time_frame>
      <description>To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cardiovascular effects among dosages using heart rate as a measure</measure>
      <time_frame>Baseline and Day 1</time_frame>
      <description>The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cardiovascular effects among dosages using heart rate as a measure</measure>
      <time_frame>Day 1 and Day 2</time_frame>
      <description>The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cardiovascular effects among dosages using heart rate as a measure</measure>
      <time_frame>Day 2 and Day 3</time_frame>
      <description>The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cardiovascular effects among dosages using heart rate as a measure</measure>
      <time_frame>Day 3 and Day 4</time_frame>
      <description>The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cardiovascular effects among dosages using heart rate as a measure</measure>
      <time_frame>Day 4 and Day 5</time_frame>
      <description>The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cardiovascular effects among dosages using heart rate as a measure</measure>
      <time_frame>Day 5 and Day 6</time_frame>
      <description>The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cardiovascular effects among dosages using heart rate as a measure</measure>
      <time_frame>Day 6 and Day 7</time_frame>
      <description>The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cardiovascular effects among dosages using heart rate as a measure</measure>
      <time_frame>Day 7 and Day 8</time_frame>
      <description>The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration versus time curve (AUC)</measure>
      <time_frame>Baseline and Day 1</time_frame>
      <description>To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration versus time curve (AUC)</measure>
      <time_frame>Day 1 and Day 2</time_frame>
      <description>To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration versus time curve (AUC)</measure>
      <time_frame>Day 2 and Day 3</time_frame>
      <description>To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration versus time curve (AUC)</measure>
      <time_frame>Day 3 and Day 4</time_frame>
      <description>To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration versus time curve (AUC)</measure>
      <time_frame>Day 4 and Day 5</time_frame>
      <description>To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration versus time curve (AUC)</measure>
      <time_frame>Day 5 and Day 6</time_frame>
      <description>To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration versus time curve (AUC)</measure>
      <time_frame>Day 6 and Day 7</time_frame>
      <description>To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration versus time curve (AUC)</measure>
      <time_frame>Day 7 and Day 8</time_frame>
      <description>To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)</measure>
      <time_frame>Baseline and Day 1</time_frame>
      <description>Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)</measure>
      <time_frame>Day 1 and Day 2</time_frame>
      <description>Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased craving of marijuana.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)</measure>
      <time_frame>Day 2 and Day 3</time_frame>
      <description>Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)</measure>
      <time_frame>Day 3 and Day 4</time_frame>
      <description>Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)</measure>
      <time_frame>Day 4 and Day 5</time_frame>
      <description>Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)</measure>
      <time_frame>Day 5 and Day 6</time_frame>
      <description>Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)</measure>
      <time_frame>Day 6 and Day 7</time_frame>
      <description>Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)</measure>
      <time_frame>Day 7 and Day 8</time_frame>
      <description>Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.</description>
    </secondary_outcome>
    <number_of_arms>8</number_of_arms>
    <enrollment type="Anticipated">48</enrollment>
    <condition>THC</condition>
    <condition>Cannabis</condition>
    <condition>Cannabis Use</condition>
    <condition>Cannabis Smoking</condition>
    <condition>Tobacco Use</condition>
    <condition>Vaping</condition>
    <arm_group>
      <arm_group_label>Placebo marijuana and regular cigarette</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will vape a 50/50 mixture of placebo marijuana (0% THC) and regular cigarette (25.94 mg/g nicotine content)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo marijuana and Very Low Nicotine Content cigarette</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will vape a 50/50 mixture of placebo marijuana (0% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Medium marijuana and regular cigarette</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will vape a 50/50 mixture of medium marijuana (&lt;5% THC) and regular cigarette (25.94 mg/g nicotine content)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Medium marijuana and Very Low Nicotine Content cigarette</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will vape a 50/50 mixture of medium marijuana (&lt;5% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>High marijuana and regular cigarette</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will vape a 50/50 mixture of high marijuana (&gt;10% THC) and regular cigarette (25.94 mg/g nicotine content)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>High marijuana and Very Low Nicotine Content cigarette</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will vape a 50/50 mixture of high marijuana (&gt;10% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>High marijuana only</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will vape high marijuana (&gt;10% THC)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Regular cigarette only</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will vape a regular cigarette (25.94 mg/g nicotine content)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cannabis</intervention_name>
      <description>Participants will vape marijuana in varying doses from the PAX device</description>
      <arm_group_label>High marijuana and Very Low Nicotine Content cigarette</arm_group_label>
      <arm_group_label>High marijuana and regular cigarette</arm_group_label>
      <arm_group_label>High marijuana only</arm_group_label>
      <arm_group_label>Medium marijuana and Very Low Nicotine Content cigarette</arm_group_label>
      <arm_group_label>Medium marijuana and regular cigarette</arm_group_label>
      <arm_group_label>Placebo marijuana and Very Low Nicotine Content cigarette</arm_group_label>
      <arm_group_label>Placebo marijuana and regular cigarette</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Nicotine</intervention_name>
      <description>Participants will vape regular and Very Low Nicotine content cigarettes from the PAX device</description>
      <arm_group_label>High marijuana and Very Low Nicotine Content cigarette</arm_group_label>
      <arm_group_label>High marijuana and regular cigarette</arm_group_label>
      <arm_group_label>Medium marijuana and Very Low Nicotine Content cigarette</arm_group_label>
      <arm_group_label>Medium marijuana and regular cigarette</arm_group_label>
      <arm_group_label>Placebo marijuana and Very Low Nicotine Content cigarette</arm_group_label>
      <arm_group_label>Placebo marijuana and regular cigarette</arm_group_label>
      <arm_group_label>Regular cigarette only</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Pax Loose Leaf Vaporizer</intervention_name>
      <description>In all arms, participants will be using the PAX Loose Leave Vaporizer.</description>
      <arm_group_label>High marijuana and Very Low Nicotine Content cigarette</arm_group_label>
      <arm_group_label>High marijuana and regular cigarette</arm_group_label>
      <arm_group_label>High marijuana only</arm_group_label>
      <arm_group_label>Medium marijuana and Very Low Nicotine Content cigarette</arm_group_label>
      <arm_group_label>Medium marijuana and regular cigarette</arm_group_label>
      <arm_group_label>Placebo marijuana and Very Low Nicotine Content cigarette</arm_group_label>
      <arm_group_label>Placebo marijuana and regular cigarette</arm_group_label>
      <arm_group_label>Regular cigarette only</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Heart rate &lt; 105 BPM*&#xD;
  &#xD;
            -  Systolic Blood Pressure &lt; 160 and &gt; 90*&#xD;
  &#xD;
            -  Diastolic Blood Pressure &lt; 100 and &gt; 50*&#xD;
  &#xD;
               *Considered out of range if both machine and manual readings are above/below these&#xD;
               thresholds.&#xD;
  &#xD;
            -  Body Mass Index ≤ 38.0 (at investigator's discretion for higher BMI if no other&#xD;
               concurrent health issues)&#xD;
  &#xD;
            -  Current regular user of cannabis who smokes or vapes cannabis or THC extracts at least&#xD;
               three days a week for the past 3 months or more&#xD;
  &#xD;
            -  Test positive for D-9-tetrahydrocannabinol (THC) at screening and self-report of&#xD;
               cannabis use&#xD;
  &#xD;
            -  Current user of inhaled forms of tobacco/nicotine (cigarette, cigars, e-cigarettes)&#xD;
               who use the product daily for the past 3 months or more&#xD;
  &#xD;
            -  Saliva cotinine ≥ 30 ng/mL&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Unstable medical conditions:&#xD;
  &#xD;
                 -  Heart disease&#xD;
  &#xD;
                 -  Seizures&#xD;
  &#xD;
                 -  Cancer&#xD;
  &#xD;
                 -  Thyroid disease (okay if controlled with medication)&#xD;
  &#xD;
                 -  Diabetes&#xD;
  &#xD;
                 -  Hepatitis B or C or Liver disease&#xD;
  &#xD;
                 -  Glaucoma&#xD;
  &#xD;
                 -  Kidney disease or urinary retention&#xD;
  &#xD;
                 -  An ulcer in the past year&#xD;
  &#xD;
                 -  Active use of an inhaler for asthma or COPD&#xD;
  &#xD;
            -  Hypertension if uncontrolled (meaning participant has a diagnosis, but they are not&#xD;
               taking medication/under treatment (e.g., diet or exercise plan)&#xD;
  &#xD;
            -  Drug/Alcohol Dependence&#xD;
  &#xD;
                 -  Alcohol or illicit drug dependence within the past 12 months (currently in&#xD;
                    treatment) with the exception of those who recently completed an alcohol/drug&#xD;
                    treatment program&#xD;
  &#xD;
                 -  Positive toxicology test at the screening visit (THC &amp; prescribed medications&#xD;
                    okay)&#xD;
  &#xD;
                 -  Opioid replacement therapy (including methadone, buprenorphine, or other)&#xD;
  &#xD;
            -  Psychiatric conditions&#xD;
  &#xD;
                 -  Current or past schizophrenia, and/or current or past bipolar disorder&#xD;
  &#xD;
                 -  Major depression, current or within the past year&#xD;
  &#xD;
                 -  Major personality disorder&#xD;
  &#xD;
                 -  Participants with current or past minor or moderate depression and/or anxiety&#xD;
                    disorders will be reviewed by the PI [study physician] and considered for&#xD;
                    inclusion&#xD;
  &#xD;
                 -  History of psychiatric hospitalizations are not exclusionary, but study&#xD;
                    participation will be determined as per PI's [study physician's] approval&#xD;
  &#xD;
            -  Current regular use of any psychiatric medications with the exception of SSRIs and&#xD;
               SNRIs and current evaluation by the PI that the participant is otherwise healthy,&#xD;
               stable, and able to participate&#xD;
  &#xD;
            -  Congenital or acquired immunodeficiency disorders (i.e. HIV, congenital immune&#xD;
               deficiency syndrome, chronic diseases)&#xD;
  &#xD;
            -  Other disorders (i.e. ICU, malnutrition, immunosuppressive therapy)&#xD;
  &#xD;
            -  Traumatic brain injury&#xD;
  &#xD;
            -  Recent onset or change (worsening) in cough, fever and/or abdominal symptoms (vomiting&#xD;
               or pain) in the past two weeks&#xD;
  &#xD;
            -  Medications&#xD;
  &#xD;
                 -  Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6&#xD;
                    (Example: rifampicin, dexamethasone, phenobarbital, and other anticonvulsant&#xD;
                    drugs)&#xD;
  &#xD;
                 -  Concurrent use of nicotine-containing medications&#xD;
  &#xD;
                 -  Any stimulant medications (ex. Adderall) generally given for ADHD treatment&#xD;
  &#xD;
            -  Other/Misc. Chronic Health Problems&#xD;
  &#xD;
                 -  Oral thrush&#xD;
  &#xD;
                 -  Fainting&#xD;
  &#xD;
                 -  Other &quot;life threatening illnesses&quot; as per study physician's discretion&#xD;
  &#xD;
            -  Pregnancy&#xD;
  &#xD;
                 -  Pregnancy (self-reported and urine pregnancy test)&#xD;
  &#xD;
                 -  Breastfeeding (determined by self-report)&#xD;
  &#xD;
            -  Concurrent participation in another clinical trial&#xD;
  &#xD;
            -  Inability to communicate in English&#xD;
  &#xD;
            -  History of marijuana-induced psychosis or paranoia after smoking marijuana&#xD;
  &#xD;
            -  Scoring a 7 or higher on the Severity of Dependence Scale (SDS) for cannabis use&#xD;
  &#xD;
            -  Planning to quit smoking or vaping within the next 60 days&#xD;
  &#xD;
            -  Planning to quit cannabis use within the next 60 days&#xD;
  &#xD;
            -  Uncomfortable with getting blood drawn&#xD;
  &#xD;
            -  Willingness to abstain from tobacco smoking and all combustible products for 13 hours&#xD;
               before admission&#xD;
  &#xD;
            -  Willingness to abstain from smoking/ingestion of cannabis 13 hours before&#xD;
  &#xD;
            -  Willingness to abstain from nicotine products 13 hours before each admission&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>21 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Gideon St Helen</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of California, San Francisco</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Armando Barraza</last_name>
      <phone>6282064226</phone>
      <email>armando.barraza@ucsf.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Zuckerberg San Francisco General Hospital</name>
        <address>
          <city>San Francisco</city>
          <state>California</state>
          <zip>94110</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 11, 2023</last_update_submitted>
    <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>THC</keyword>
    <keyword>Cannabis</keyword>
    <keyword>Marijuana</keyword>
    <keyword>Nicotine</keyword>
    <keyword>Vape</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Marijuana Abuse</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Nicotine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05999383
  org study id: 23-38884
  secondary id: 1R01DA056451-01A1
  nct id: NCT05999383
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a crossover, randomized, double-blinded clinical pharmacology study enrolling dual
        cannabis-tobacco smokers to better understand the combined effects of co-administering
        cannabis and tobacco. The project aims to describe the pharmacokinetics and pharmacodynamics
        of marijuana-tobacco co-administration by delivering THC and nicotine in various
        combinations. This foundational study will establish a research program focused on
        elucidating the public health consequences of marijuana-tobacco co-use.
  This is a single-center, within-subject (crossover), randomized, double-blinded clinical
        pharmacology study of over 8 study visits (days). Participants will be non-treatment-seeking,
        healthy frequent users of both marijuana and tobacco/nicotine, age 21 to 65 years (21 years
        because of California tobacco control law). Participants will be marijuana users of any race
        who smoke or vape marijuana or THC extracts at least three days a week for the past 3 months
        or more. The study investigators will use positive urine toxicology THC results and
        self-report of marijuana smoking/vaping to determine eligibility. Participants must also be
        current users of inhaled forms of tobacco/nicotine (cigarettes, cigars, e-cigarettes) who use
        the product daily over the past 3 months.
  
        Each study day will consist of a standardized session of 5 puffs of one of 8 study conditions
        using a PAX-3 vaporizer (PAX Labs, Inc.). Blood will be sampled multiple times for plasma
        THC, nicotine, and catecholamines, questionnaires administered for sensory and subjective
        effects, and heart rate, skin blood flow, and skin temperature will be measured. After 6
        hours of abstinence, participants will have 60 minutes of ad libitum access to the assigned
        study condition, during which heart rate and blood pressure will be continuously monitored,
        blood sampled before and after for THC, nicotine, and platelet aggregation measured, and
        questionnaires administered.
  
        Studies will be conducted at the CTSI Clinical Research Services-supported research ward at
        Zuckerberg San Francisco General.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Basic Science
  masking: Double (Participant, Investigator)
  measure: Change in peak plasma concentration of THC
  time frame: Baseline and Day 1
  description: To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
  measure: Change in peak plasma concentration of THC
  time frame: Day 1 and Day 2
  description: To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
  measure: Change in peak plasma concentration of THC
  time frame: Day 2 and Day 3
  description: To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
  measure: Change in peak plasma concentration of THC
  time frame: Day 3 and Day 4
  description: To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
  measure: Change in peak plasma concentration of THC
  time frame: Day 4 and Day 5
  description: To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
  measure: Change in peak plasma concentration of THC
  time frame: Day 5 and Day 6
  description: To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
  measure: Change in peak plasma concentration of THC
  time frame: Day 6 and Day 7
  description: To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
  measure: Change in peak plasma concentration of THC
  time frame: Day 7 and Day 8
  description: To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
  measure: Change in Peak plasma concentration of nicotine
  time frame: Baseline and Day 1
  description: To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
  measure: Change in Peak plasma concentration of nicotine
  time frame: Day 1 and Day 2
  description: To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
  measure: Change in Peak plasma concentration of nicotine
  time frame: Day 2 and Day 3
  description: To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
  measure: Change in Peak plasma concentration of nicotine
  time frame: Day 3 and Day 4
  description: To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
  measure: Change in Peak plasma concentration of nicotine
  time frame: Day 4 and Day 5
  description: To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
  measure: Change in Peak plasma concentration of nicotine
  time frame: Day 5 and Day 6
  description: To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
  measure: Change in Peak plasma concentration of nicotine
  time frame: Day 6 and Day 7
  description: To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
  measure: Change in Peak plasma concentration of nicotine
  time frame: Day 7 and Day 8
  description: To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
  measure: Cardiovascular effects among dosages using heart rate as a measure
  time frame: Baseline and Day 1
  description: The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
  measure: Cardiovascular effects among dosages using heart rate as a measure
  time frame: Day 1 and Day 2
  description: The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
  measure: Cardiovascular effects among dosages using heart rate as a measure
  time frame: Day 2 and Day 3
  description: The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
  measure: Cardiovascular effects among dosages using heart rate as a measure
  time frame: Day 3 and Day 4
  description: The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
  measure: Cardiovascular effects among dosages using heart rate as a measure
  time frame: Day 4 and Day 5
  description: The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
  measure: Cardiovascular effects among dosages using heart rate as a measure
  time frame: Day 5 and Day 6
  description: The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
  measure: Cardiovascular effects among dosages using heart rate as a measure
  time frame: Day 6 and Day 7
  description: The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
  measure: Cardiovascular effects among dosages using heart rate as a measure
  time frame: Day 7 and Day 8
  description: The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
  measure: Area under the plasma concentration versus time curve (AUC)
  time frame: Baseline and Day 1
  description: To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
  measure: Area under the plasma concentration versus time curve (AUC)
  time frame: Day 1 and Day 2
  description: To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
  measure: Area under the plasma concentration versus time curve (AUC)
  time frame: Day 2 and Day 3
  description: To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
  measure: Area under the plasma concentration versus time curve (AUC)
  time frame: Day 3 and Day 4
  description: To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
  measure: Area under the plasma concentration versus time curve (AUC)
  time frame: Day 4 and Day 5
  description: To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
  measure: Area under the plasma concentration versus time curve (AUC)
  time frame: Day 5 and Day 6
  description: To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
  measure: Area under the plasma concentration versus time curve (AUC)
  time frame: Day 6 and Day 7
  description: To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
  measure: Area under the plasma concentration versus time curve (AUC)
  time frame: Day 7 and Day 8
  description: To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
  measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
  time frame: Baseline and Day 1
  description: Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
  measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
  time frame: Day 1 and Day 2
  description: Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased craving of marijuana.
  measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
  time frame: Day 2 and Day 3
  description: Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
  measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
  time frame: Day 3 and Day 4
  description: Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
  measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
  time frame: Day 4 and Day 5
  description: Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
  measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
  time frame: Day 5 and Day 6
  description: Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
  measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
  time frame: Day 6 and Day 7
  description: Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
  measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
  time frame: Day 7 and Day 8
  description: Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
  arm group label: Placebo marijuana and regular cigarette
  arm group type: Experimental
  description: Participants will vape a 50/50 mixture of placebo marijuana (0% THC) and regular cigarette (25.94 mg/g nicotine content)
  arm group label: Placebo marijuana and Very Low Nicotine Content cigarette
  arm group type: Experimental
  description: Participants will vape a 50/50 mixture of placebo marijuana (0% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
  arm group label: Medium marijuana and regular cigarette
  arm group type: Experimental
  description: Participants will vape a 50/50 mixture of medium marijuana (<5% THC) and regular cigarette (25.94 mg/g nicotine content)
  arm group label: Medium marijuana and Very Low Nicotine Content cigarette
  arm group type: Experimental
  description: Participants will vape a 50/50 mixture of medium marijuana (<5% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
  arm group label: High marijuana and regular cigarette
  arm group type: Experimental
  description: Participants will vape a 50/50 mixture of high marijuana (>10% THC) and regular cigarette (25.94 mg/g nicotine content)
  arm group label: High marijuana and Very Low Nicotine Content cigarette
  arm group type: Experimental
  description: Participants will vape a 50/50 mixture of high marijuana (>10% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
  arm group label: High marijuana only
  arm group type: Experimental
  description: Participants will vape high marijuana (>10% THC)
  arm group label: Regular cigarette only
  arm group type: Experimental
  description: Participants will vape a regular cigarette (25.94 mg/g nicotine content)
  intervention type: Drug
  intervention name: Cannabis
  description: Participants will vape marijuana in varying doses from the PAX device
  arm group label: High marijuana and Very Low Nicotine Content cigarette
  arm group label: High marijuana and regular cigarette
  arm group label: High marijuana only
  arm group label: Medium marijuana and Very Low Nicotine Content cigarette
  arm group label: Medium marijuana and regular cigarette
  arm group label: Placebo marijuana and Very Low Nicotine Content cigarette
  arm group label: Placebo marijuana and regular cigarette
  intervention type: Drug
  intervention name: Nicotine
  description: Participants will vape regular and Very Low Nicotine content cigarettes from the PAX device
  arm group label: High marijuana and Very Low Nicotine Content cigarette
  arm group label: High marijuana and regular cigarette
  arm group label: Medium marijuana and Very Low Nicotine Content cigarette
  arm group label: Medium marijuana and regular cigarette
  arm group label: Placebo marijuana and Very Low Nicotine Content cigarette
  arm group label: Placebo marijuana and regular cigarette
  arm group label: Regular cigarette only
  intervention type: Device
  intervention name: Pax Loose Leaf Vaporizer
  description: In all arms, participants will be using the PAX Loose Leave Vaporizer.
  arm group label: High marijuana and Very Low Nicotine Content cigarette
  arm group label: High marijuana and regular cigarette
  arm group label: High marijuana only
  arm group label: Medium marijuana and Very Low Nicotine Content cigarette
  arm group label: Medium marijuana and regular cigarette
  arm group label: Placebo marijuana and Very Low Nicotine Content cigarette
  arm group label: Placebo marijuana and regular cigarette
  arm group label: Regular cigarette only
  criteria: 
  gender: All
  minimum age: 21 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Gideon St Helen
  role: Principal Investigator
  affiliation: University of California, San Francisco
  last name: Armando Barraza
  phone: 6282064226
  email: armando.barraza@ucsf.edu
  facility: 
  country: United States
  responsible party type: Sponsor
  mesh term: Marijuana Abuse
  mesh term: Nicotine
  sharing ipd: No