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Vaporized Cannabis Administration and Co-Administration of Alcohol on Impairment

Phase 1
Recruiting
Conditions
Cannabis Intoxication
Alcohol Intoxication
Interventions
Registration Number
NCT06293040
Lead Sponsor
Johns Hopkins University
Brief Summary

This human laboratory study will use cognitive, behavioral, and subjective measures to characterize impairment associated with co-use of alcohol and vaporized cannabis. Participants (n=32) will complete 7 double-blind, double-dummy outpatient sessions in randomized order. In each session, participants will self-administer placebo (0 mg THC) or active vaporized cannabis (5 or 25 mg THC, via a handheld vaporizer called the Mighty Medic) and a placebo drink (BAC 0.0%) or alcohol drink calculated to produce a breath alcohol concentration (BAC) of 0.05%. Participants will also complete a positive control session in which the participant administers placebo cannabis and alcohol at a target BAC of 0.08% (the legal threshold for driving impairment in most U.S. states).

Detailed Description

This study will be conducted at the Johns Hopkins Behavioral Pharmacology Research Unit (BPRU). Participants will complete a screening visit, and, if eligible, will then complete 7 experimental drug administration sessions in randomized order where the participant will vaporize cannabis-containing capsules (or "pods") (containing 0, 5, or 25mg THC) with a drink that contains no alcohol or alcohol (alcohol-containing drinks will be calculated to produce a breath alcohol concentration, BAC, of 0.05%). There is also a positive control session where participants will vaporize placebo cannabis with an alcohol drink calculated to produce a BAC of 0.08%. Each session will last approximately 8 hours and will be separated by at least 48 hours to allow for sufficient drug washout. Participants may complete up to 2 sessions per week. Drugs will be administered in a double-blind and double-dummy fashion (i.e., participants will always receive both active or placebo cannabis and active or placebo alcohol). During each session, a battery of assessments including blood collection, subjective questionnaire administration, cognitive performance testing, and simulated driving will be conducted.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
90
Inclusion Criteria
  1. Have provided written informed consent
  2. Be at least 21 years of age
  3. Be in good general health based on a physical examination, medical history, vital signs, and screening urine and blood tests
  4. Not be pregnant or nursing (if female). All females must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at each study visit
  5. Have not donated blood in the prior 30 days
  6. Report at least 1 day of binge drinking in the past 3 months (greater than 4 or 5 drinks on a single occasion for women and men, respectively)
  7. Report at least 1 use of cannabis in the past 3 years
  8. Provide negative urine test for illicit drug use (excluding THC) and negative breath alcohol test (0% BAC) at screening and before study sessions
  9. Report at least 1 lifetime instance of simultaneous alcohol and cannabis use
  10. Current concomitant prescription medication use that may interact with the investigational study drug, including inhibitors and inducers of CYP2CP and CYP3A4 as well as highly-protein bound drugs and drugs with a narrow therapeutic index such as warfarin, cyclosporine, and amphotericin B
Exclusion Criteria
  1. Psychoactive drug use (aside from cannabis, nicotine, alcohol, or caffeine) in the past month
  2. History of or current evidence of significant medical condition that would put the participant at risk
  3. Evidence of current psychiatric condition (MINI for DSM-V)
  4. Meet criteria for severe alcohol use disorder (MINI for DSM-V)
  5. CIWA-Ar score > 9
  6. Use of cannabis, on average, more than 3 days/week over past 3 months
  7. Enrollment in another clinical trial or receiving of any drug as part of research within past 30 days
  8. Shipley vocabulary score <18 (corresponds to 5th grade reading level)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
High dose cannabis with placebo alcoholCannabisParticipants administer vaporized cannabis containing 25mg THC in combination with a placebo alcohol drink.
Placebo cannabis + placebo alcoholPlacebo CannabisParticipants administer vaporized cannabis containing 0mg THC in combination with a placebo alcohol drink.
Placebo cannabis + placebo alcoholPlacebo AlcoholParticipants administer vaporized cannabis containing 0mg THC in combination with a placebo alcohol drink.
Low dose cannabis with placebo alcoholCannabisParticipants administer vaporized cannabis containing 5mg THC in combination with a placebo alcohol drink.
Low dose cannabis with placebo alcoholPlacebo AlcoholParticipants administer vaporized cannabis containing 5mg THC in combination with a placebo alcohol drink.
High dose cannabis with placebo alcoholPlacebo AlcoholParticipants administer vaporized cannabis containing 25mg THC in combination with a placebo alcohol drink.
Low dose cannabis with low dose alcoholAlcoholParticipants administer vaporized cannabis containing 5mg THC in combination with an alcohol drink (0.05 percent BAC).
Placebo cannabis + low dose alcoholAlcoholParticipants administer vaporized cannabis containing 0mg THC in combination with an alcohol drink (0.05 percent BAC).
Placebo cannabis + low dose alcoholPlacebo CannabisParticipants administer vaporized cannabis containing 0mg THC in combination with an alcohol drink (0.05 percent BAC).
Placebo cannabis + high dose alcoholAlcoholParticipants administer vaporized cannabis containing 0mg THC in combination with an alcohol drink (0.08 percent BAC).
Placebo cannabis + high dose alcoholPlacebo CannabisParticipants administer vaporized cannabis containing 0mg THC in combination with an alcohol drink (0.08 percent BAC).
Low dose cannabis with low dose alcoholCannabisParticipants administer vaporized cannabis containing 5mg THC in combination with an alcohol drink (0.05 percent BAC).
High dose cannabis with low dose alcoholCannabisParticipants administer vaporized cannabis containing 25mg THC in combination with an alcohol drink (0.05 percent BAC).
High dose cannabis with low dose alcoholAlcoholParticipants administer vaporized cannabis containing 25mg THC in combination with an alcohol drink (0.05 percent BAC).
Primary Outcome Measures
NameTimeMethod
Driving performance as assessed by standard deviation of lateral position (SDLP)Up to 6 hours

The STISIM Drive® M4000-R Console system will be used to assess driving performance, a state-of-the-art technology that has been independently validated to reflect real-world driving conditions. SDLP (measured in cm) will be determined during each drive. This measure is a composite index of lateral control and incorporates lane weaving, swerving, and over-correcting. SDLP is the gold standard of quantifying the magnitude of driving impairment from drugs and alcohol and has excellent predictive validity to actual driving. Scores range from 0 to no upper limit. Higher scores represent higher magnitude of driving impairment.

Drug Effect Questionnaire (DEQ) - Willingness to DriveUp to 6 hours

The DEQ will be used to obtain subjective ratings of "willingness to drive". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.

Biphasic alcohol effects scale (BAES) - Stimulant ScoreUp to 6 hours

The BAES is used to assess sedative and stimulant subjective effects of alcohol. There are 7 stimulant-related questionnaire items, each presented on a scale of 0 (not at all) to 10 (extremely), which are integrated to produce an overall stimulant score (0-70).

DRUID application global impairment scoreUp to 6 hours

Acute cognitive and behavioral impairment will be assessed with global impairment score (range 0-100) on the DRUID app (higher scores indicate greater impairment).

Correct Trials on Paced Auditory Serial Addition Task (PASAT)Up to 6 hours

Computerized version of Paced Auditory Serial Addition Task will be administered to assess working memory performance. Will report the total correct trials out of 90 recorded (lower scores indicate worse performance). Score ranges from 0-90, with 0 representing no correct trials and 90 representing 100% correct trials.

Correct Trials on the Digit Symbol Substitution Task (DSST)Up to 6 hours

Computerized version of Digit Symbol Substitution Task will be administered to assess psychomotor performance. Will report the total correct trials in 90 seconds (lower scores indicate worse performance). There is no maximum score, with a score of 0 representing either no trials completed or no correct trials. The score reflects the number of correct trials.

Cumulative score on Field Sobriety TestsUp to 6 hours

Impairment will be assessed using a battery of standard field sobriety tests including: the Horizontal Gaze Nystagmus Test (HGN), the Walk and Turn, the One Leg Stand, and the Modified Romberg Balance. The cumulative amount of clues observed across these tasks (out of a possible 22 clues) will be reported.

Drug Effect Questionnaire (DEQ) - Feel Drug EffectUp to 6 hours

The DEQ will be used to obtain subjective ratings of "feel drug effects". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.

Drug Effect Questionnaire (DEQ) - Feel HighUp to 6 hours

The DEQ will be used to obtain subjective ratings of "feel high". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.

Biphasic alcohol effects scale (BAES) - Sedative ScoreUp to 6 hours

The BAES is used to assess sedative and stimulant subjective effects of alcohol. There are 7 sedative-related questionnaire items, each presented on a scale of 0 (not at all) to 10 (extremely), which are integrated to produce an overall sedative score (0-70).

Subjective high assessment scale (SHAS)Up to 6 hours

For the SHAS, participants are presented with 13 questionnaire items, displayed on a visual analog scale anchored from 0 (normal) to 10 (extremely), which assess subjective effects of alcohol. These items are integrated to produce an overall SHAS score (0-130)

Drug Effect Questionnaire (DEQ) - Confidence to DriveUp to 6 hours

The DEQ will be used to obtain subjective ratings of "confidence to drive". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.

Driving performance as assessed by composite drive scoreUp to 6 hours

Driving impairment will be assessed via a composite drive score (higher scores indicate greater impairment). The composite drive score is derived by integrating various driving outcomes. There is no upper or lower limit to possible scores.

Secondary Outcome Measures
NameTimeMethod
Driving performance (number of speed exceedances)Up to 6 hours

The STISIM Drive® M4000-R Console system will be used to assess driving performance, a state-of-the-art technology that has been independently validated to reflect real-world driving conditions. The cumulative number of times participants exceed the allowable speed limit during each drive.

Driving performance (number of accidents)Up to 6 hours

The STISIM Drive® M4000-R Console system will be used to assess driving performance, a state-of-the-art technology that has been independently validated to reflect real-world driving conditions. The cumulative number of accidents (including car collisions, pedestrians hit, etc.) during each drive.

Driving performance (total rule violations)Up to 6 hours

The STISIM Drive® M4000-R Console system will be used to assess driving performance, a state-of-the-art technology that has been independently validated to reflect real-world driving conditions. The cumulative number of rule violations (including number of missed stop signs, illegal turns, speed exceedances, etc.) during each drive.

Percentage Correct on attempted trials on the Digit Symbol Substitution Task (DSST)Up to 6 hours

Computerized version of Digit Symbol Substitution Task will be administered to assess psychomotor performance. Percentage of correct trials out of those attempted will be recorded

Field Sobriety Test - Score on Horizontal Gaze Nystagmus TestUp to 6 hours

Impairment will be assessed using performance on the Horizontal Gaze Nystagmus Test (HGN). Total score will be recorded (out of possible 6 clues, score ranges from 0-6) with higher scores indicating higher impairment.

Field Sobriety Test - Score on Walk and Turn testUp to 6 hours

Impairment will be assessed using performance on the the Walk and Turn. Total score will be recorded (out of a possible 8 clues, score ranges from 0-8) with higher scores indicating higher impairment.

Field Sobriety Test - Score on Modified Romberg BalanceUp to 6 hours

Impairment will be assessed using performance on the Modified Romberg Balance test. Total score will be recorded (out of a possible 4 clues, score ranges from 0-4)) with higher scores indicating higher impairment.

Driving performance (distance to lead vehicles)Up to 6 hours

The STISIM Drive® M4000-R Console system will be used to assess driving performance, a state-of-the-art technology that has been independently validated to reflect real-world driving conditions. The mean distance (in meters) maintained to lead vehicles during car-following segments of each drive.

Attempted Trials on the Digit Symbol Substitution Task (DSST)Up to 6 hours

Computerized version of Digit Symbol Substitution Task will be administered to assess psychomotor performance. The number of attempted trials will be recorded

Reaction time on Paced Auditory Serial Addition TaskUp to 6 hours

Computerized version of Paced Auditory Serial Addition Task will be administered to assess working memory performance. The mean reaction time (in milliseconds) to select correct responses will be recorded.

Field Sobriety Test - Score on One Leg StandUp to 6 hours

Impairment will be assessed using performance on the One Leg Stand test. Total score will be recorded (out of a possible 4 clues, score ranges from 0-4) with higher scores indicating higher impairment.

Drug Effect Questionnaire - Want moreUp to 6 hours

The DEQ will be used to obtain subjective ratings of "want more". Scores range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.

Drug Effect Questionnaire - Dislike Drug EffectUp to 6 hours

The DEQ will be used to obtain subjective ratings of "dislike drug effect". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.

Pharmacokinetics - AUC for THC and THC metabolitesUp to 6 hours

Whole blood concentrations of THC, 11-OH- THC, and THCCOOH will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The area under the curve (AUC) is calculated across all timepoints, minus the baseline. Characterizing these cannabinoids will allow for adequate control for individual differences in drug absorption and metabolism in statistical analyses and assist with interpretation of subjective and behavioral outcomes.

Pharmacokinetics - Breath Alcohol Concentration (BAC)Up to 6 hours

BAC will be measured using the Alco-Sensor IV. Measuring BAC is needed to confirm that participants reached the targeted BAC for a given session and to confirm adherence to pre-session alcohol abstinence requirements.

Driving performance as assessed by standard deviation of speed (SDSP)Up to 6 hours

The STISIM Drive® M4000-R Console system will be used to assess driving performance, a state-of-the-art technology that has been independently validated to reflect real-world driving conditions. SDSP will be determined during each drive; this measure quantifies the variability in speed (in MPH) observed.

Driving performance (mean speed)Up to 6 hours

The STISIM Drive® M4000-R Console system will be used to assess driving performance, a state-of-the-art technology that has been independently validated to reflect real-world driving conditions. Mean speed (in MPH) over the course of each drive will be determined.

Drug Effect Questionnaire - Like Drug EffectUp to 6 hours

The DEQ will be used to obtain subjective ratings of "like drug effect". Scores range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.

Pharmacokinetics - CMax for THC and THC metabolitesUp to 6 hours

Whole blood concentrations of THC, 11-OH- THC, and THCCOOH will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The maximum concentration (Cmax) is determined as the highest concentration reached for each individual. Characterizing these cannabinoids will allow for adequate control for individual differences in drug absorption and metabolism in statistical analyses and assist with interpretation of subjective and behavioral outcomes.

Trial Locations

Locations (1)

Johns Hopkins Behavioral Pharmacology Research Unit

🇺🇸

Baltimore, Maryland, United States

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