The Impact of Oral Cannabis Administration and Co-Administration of Alcohol on Impairment

Johns Hopkins University60 enrolled

Overview

This study will evaluate the individual and interactive effects of oral cannabis and alcohol on subjective and behavioral measures of impairment.

This clinical laboratory study will be double-blind, placebo-controlled and will utilize a within-subjects experimental design. Participants will complete 7 outpatient drug administration sessions that will consist of self-administration of oral cannabis (0, 10 or 25mg THC) and alcohol (either placebo or active; BAC of 0.05 percent); participants will always receive both an alcohol drink (active or placebo) and dose of cannabis (active or placebo). Participants will also complete a condition in which they administer alcohol (BAC: 0.08 percent) with placebo cannabis, as a positive control. Primary outcomes include performance on field sobriety tests, cognitive and psychomotor impairment, subjective drug effects, and simulated driving performance. Blood concentrations of THC and THC metabolites will also be determined.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Cannabis Intoxication Alcohol Intoxication

Interventions

CannabisDRUG

Cannabis will be orally ingested via a brownie

AlcoholDRUG

Alcohol will be orally ingested via a flavored drink

Eligibility

Sex: ALLMin age: 21 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Have provided written informed consent 2. Be between the ages of 21 and 55 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 a body mass index (BMI) in the range of 19 to 36 kg/m2 6. Blood pressure at Screening Visit does not exceed a systolic blood pressure (SBP) of 150 mmHg or a diastolic blood pressure (DBP) of 90 mmHg 7. Have not donated blood in the prior 30 days. 8. Report at least 2 days of binge drinking in the past 90 days (greater than 4 or 5 drinks on a single occasion for women and men, respectively) 9. Report ≥ 1 use of cannabis in the past year 10. Provide negative urine test for illicit drug use (excluding THC) and negative breath alcohol test (0% BAC) at screening and before study sessions 11. Report at least 1 instance of simultaneous alcohol and use in the past year. Exclusion Criteria: 1. Psychoactive drug use (aside from cannabis, nicotine, alcohol, or caffeine) in past month 2. Current use of over-the-counter (OTC) drugs, supplements/vitamins, or prescription medications that, in the opinion of the investigator or medical staff, will impact the participant's safety 3. History of or current evidence of significant medical condition 4. Evidence of current psychiatric condition \[(MINI for Diagnostic and Statistical Manual (DSM)-V)\] 5. Meet criteria for severe alcohol use disorder (MINI for DSM-V) 6. Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar) score \> 9 7. Been in treatment previously for alcohol or cannabis use disorder 8. Use of cannabis, on average, more than 2 times/week over past 3 months 9. Liver function tests more than 2x normal range 10. Enrollment in another clinical trial or receiving of any drug as part of research within past 30 days 11. Shipley vocabulary score \<18 (corresponds to 5th grade reading level).

Locations (1)

Johns Hopkins Behavioral Pharmacology Research Unit

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

DRUID application global impairment score

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

Time frame: 7.5 hours

Correct Trials on Paced Auditory Serial Addition Task (PASAT)

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).

Time frame: 7.5 hours

Correct Trials on the Digit Symbol Substitution Task (DSST)

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).

Time frame: 7.5 hours

Cumulative score on Field Sobriety Tests

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. We will report the cumulative amount of clues observed across these tasks (out of a possible 22 clues).

Time frame: 7.5 hours

Drug Effect Questionnaire (DEQ) - Feel Drug Effect

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.

Time frame: 7.5 hours

Drug Effect Questionnaire - Feel High

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.

Time frame: 7.5 hours

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Driving performance as assessed by standard deviation of speed (SDSP)

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.

Time frame: 7.5 hours

Driving performance (mean speed)

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.

Time frame: 7.5 hours

Driving performance (number of speed exceedances)

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.

Time frame: 7.5 hours

Driving performance (number of accidents)

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.

Time frame: 7.5 hours

Driving performance (total rule violations)

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.

Time frame: 7.5 hours

Driving performance (distance to lead vehicles)

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.

Time frame: 7.5 hours

Attempted Trials on the Digit Symbol Substitution Task (DSST)

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

Time frame: 7.5 hours

Percentage Correct on attempted trials on the Digit Symbol Substitution Task (DSST)

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

Time frame: 7.5 hours

Reaction time on Paced Auditory Serial Addition Task

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.

Time frame: 7.5 hours

Field Sobriety Test - Score on Horizontal Gaze Nystagmus Test

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

Time frame: Up to 7.5 hours

Field Sobriety Test - Score on Walk and Turn test

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

Time frame: Up to 7.5 hours

Field Sobriety Test - Score on One Leg Stand

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

Time frame: Up to 7.5 hours

Field Sobriety Test - Score on Modified Romberg Balance

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

Time frame: Up to 7.5 hours

Drug Effect Questionnaire - Like Drug Effect

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

Time frame: 7.5 hours

Drug Effect Questionnaire - Want more

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

Time frame: 7.5 hours

Drug Effect Questionnaire - Dislike Drug Effect

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.

Time frame: 7.5 hours

Pharmacokinetics - CMax for THC and THC metabolites

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.

Time frame: 7.5 hours

Pharmacokinetics - AUC for THC and THC metabolites

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.

Time frame: Up to 7.5 hours

Pharmacokinetics - Breath Alcohol Concentration (BAC)

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.

Time frame: Up to 7.5 hours