Combined and Separate Effects of Cannabis and Tobacco: Psychomotor, Subjective and Physiological Outcomes

Study Overview
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Brief Summary
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Co-administration of cannabis and tobacco is a common practice, but there is little experimental evidence aimed at understanding the reasons for this prevalence. Some preliminary evidence suggests that tobacco may actually counteract the cognitive-impairing effects of cannabis, and may also increase the subjective ('liking') effects of cannabis, but results are inconclusive. Further, there are no studies into the effects of tobacco on other cannabis-related harms such as driving, or on the ability of tobacco to alter the blood levels of THC, the chemical responsible for the psychoactive properties of cannabis. The purpose of the present study will be to evaluate the effects of tobacco, cannabis or combinations of tobacco and cannabis on driving, cognition, subjective effects and blood THC. Driving will be assessed using a state-of-the-art driving simulator that allows for the safe and objective measurement of the effects of intoxicating substances on driving. Participants will be regular users of cannabis and will be invited to the lab for four counterbalanced test sessions. In these test sessions they will drive the simulator and undergo cognitive tests before and after smoking: 1) cannabis; 2) tobacco; 3) cannabis + tobacco; or 4) placebo. Outcomes will be measured at several time points after smoking the product. Participants will also give blood for determination of levels of THC, and will complete subjective effects questionnaires both before and after smoking the cigarette. This study will be one of the first experimental laboratory studies of the reasons behind co-administration of tobacco and cannabis.

Official Title
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Combined and Separate Effects of Cannabis and Tobacco: Psychomotor, Subjective and Physiological Outcomes

Conditions
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Driving Under the Influence

Intervention / Treatment
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* Drug: Cannabis
* Drug: Tobacco
* Drug: Cannabis tobacco
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Adults aged 19 years to 45 years (to control for the effects of age on cognition) Smoke or vape cannabis at least once a month but no more than 4 times a week (to avoid enrolling people with cannabis use disorder who may experience withdrawal when asked to abstain from cannabis) Experience with smoked cannabis in the past year Report use of at least 100 cigarettes in their lifetime to ensure familiarity with the tobacco used in the present study Use of any nicotine (smoked, vaped, etc) in the past year G2 or full G driver's licence for at least a year Willing to abstain from alcohol and other drugs (other than drugs required for treatment of a medical condition) for 48 hours prior to study session Normal heart rate and blood pressure as determined by the QI (because cannabis and tobacco increase heart rate) Normal ECG (because cannabis and tobacco increase heart rate) Willing to abstain from cannabis for 72 hours prior to the test session and from smoking tobacco for 12 hours Willing to use an accepted form of contraception during the study (both males and females) Past lifetime experience with co-use of cannabis or tobacco (either simultaneous or concurrent) Provides written and informed consent Exclusion Criteria: • Use of psychoactive medications or drugs Current alcohol or other substance use disorder, including cannabis (as assessed with the SCID) Current or past nicotine dependence (to avoid precipitating a relapse) Withdrawal symptoms as assessed with the Marijuana Withdrawal Checklist [57, 58] A score of less than 10 on the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) [59] Family history of schizophrenia or psychosis (to avoid giving cannabis to anyone with a predisposition to psychosis) Respiratory illnesses (due to the smoked route of administration in this study) Any serious medical condition precluding participation as judged by the responsible study physician Pregnancy or breastfeeding Negative urine screen for cannabis at eligibility assessment (to ensure experience with cannabis) Neurological disorders that may affect cognitive function Treatment-seeking for tobacco or cannabis use Use of more than 5 cigarettes a day (to avoid confound of the effects of chronic smoking on measures) Concomitant therapy with sedative-hypnotics or other psychoactive drugs (counter-indicated with cannabis)

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Placebo<br>A cigarette containing placebo cannabis and placebo tobacco | Drug: Placebo<br>* Dried flower cigarette with both placebo tobacco and cannabis<br>|
| Other: Tobacco<br>A cigarette with placebo cannabis and active tobacco | Drug: Tobacco<br>* Dried flower cigarette with active nicotine<br>|
| Other: Cannabis<br>A cigarette with active cannabis and placebo tobacco | Drug: Cannabis<br>* Dried flower cannabis cigarette with 22% THC<br>|
| Other: Tobacco and cannabis<br>A cigarette with active cannabis and active tobacco | Drug: Cannabis tobacco<br>* Dried flower cigarette with active nicotine and cannabis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standard deviation of lateral position | car 'weaving' | baseline | 
| Standard deviation of lateral position | car 'weaving' | 15 minutes post smoking | 
| Standard deviation of lateral position | car 'weaving' | 180 minutes post smoking | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Speed | Speed (in km) of the car | baseline | 
| Speed | Speed (in km) of the car | 15 minutes post smoking | 
| Speed | Speed (in km) of the car | 180 minutes post smoking | 
| Reaction time | Time to hit the brake after introduction of an obstacle | baseline | 
| Reaction time | Time to hit the brake after introduction of an obstacle | 15 minutes post smoking | 
| Reaction time | Time to hit the brake after introduction of an obstacle | 180 minutes post smoking | 
| Collisions | number of times the car hit an obstacle | baseline | 
| Collisions | number of times the car hit an obstacle | 15 minutes post smoking | 
| Collisions | number of times the car hit an obstacle | 180 minutes post smoking | 
| Concentration of THC (ng/ml) | Psychoactive component of cannabis | Baseline | 
| Concentration of THC (ng/ml) | Psychoactive component of cannabis | 15 minutes post smoking | 
| Useful Field of View Processing Speed | Mean threshold for discriminating stimuli presented in central vision | baseline | 
| Useful Field of View Processing Speed | Mean threshold for discriminating stimuli presented in central vision | 60 minutes post smoking | 
| Useful Field of View Processing Speed | Mean threshold for discriminating stimuli presented in central vision | 210 minutes post smoking | 
| Useful Field of View Divided attention | Mean threshold for discriminating stimuli presented in central vision, with a concurrent perpheral target task | baseline | 
| Useful Field of View Divided attention | Mean threshold for discriminating stimuli presented in central vision, with a concurrent perpheral target task | 60 minutes | 
| Useful Field of View Divided attention | Mean threshold for discriminating stimuli presented in central vision, with a concurrent perpheral target task | 210 minutes | 
| Useful Field of View Selective attention | Mean threshold for divided attention but with distractors | baseline | 
| Useful Field of View Selective attention | Mean threshold for divided attention but with distractors | 60 minutes | 
| Useful Field of View Selective attention | Mean threshold for divided attention but with distractors | 210 minutes | 
| Trail making task | Cognitive assessment | baseline | 
| Trail making task | Cognitive assessment | 60 minutes post smoking | 
| Trail making task | Cognitive assessment | 210 minutes post smoking | 
| Verbal free recall | Test of memory | baseline | 
| Verbal free recall | Test of memory | 60 minutes post smoking | 
| Verbal free recall | Test of memory | 210 minutes post smoking | 
| Addiction Research Centre Inventory | Test of mood with 53 true-false questions that are summed to produce a measure of the intensity of mood, with higher scores reflecting greater mood | baseline | 
| Addiction Research Centre Inventory | Test of mood with 53 true-false questions that are summed to produce a measure of the intensity of mood, with higher scores reflecting greater mood | 60 minutes post smoking | 
| Addiction Research Centre Inventory | Test of mood with 53 true-false questions that are summed to produce a measure of the intensity of mood, with higher scores reflecting greater mood | 210 minutes post smoking | 
| Profile of Mood States | Test of mood with 76 items with a five point scale that are summed to produce a measure of the intensity of mood, with higher scores indicating more agreemen | baseline | 
| Profile of Mood States | Test of mood with 76 items with a five point scale that are summed to produce a measure of the intensity of mood, with higher scores indicating more agreemen | 60 minutes post smoking | 
| Profile of Mood States | Test of mood with 76 items with a five point scale that are summed to produce a measure of the intensity of mood, with higher scores indicating more agreemen | 210 minutes post smoking | 
| Visual Analog Scale | test of mood on a scale from 0 to 100, with greater number indicating more agreement | baseline | 
| Visual Analog Scale | test of mood on a scale from 0 to 100, with greater number indicating more agreement | 15 minutes post smoking | 
| Visual Analog Scale | test of mood on a scale from 0 to 100, with greater number indicating more agreement | 60 minutes post smoking | 
| Visual Analog Scale | test of mood on a scale from 0 to 100, with greater number indicating more agreement | 120 minutes post smoking | 
| Visual Analog Scale | test of mood on a scale from 0 to 100, with greater number indicating more agreement | 180 minutes post smoking | 
| Visual Analog Scale | test of mood on a scale from 0 to 100, with greater number indicating more agreement | 240 minutes post smoking | 
| Visual Analog Scale | test of mood on a scale from 0 to 100, with greater number indicating more agreement | 300 minutes post smoking |