Do Adolescents and Adults Differ in Their Acute Response to Cannabis?

Study Overview
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Brief Summary
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The acute effects of cannabis may differ between adolescents and adults. Furthermore, these effects may be tempered by the presence of cannabidiol. This double-blind, placebo-controlled, crossover experiment investigates the acute effects of cannabis (with and without cannabidiol) on subjective effects, behavioural responses and neural functioning in 16-17 year-olds and 26-29 year-olds who regularly use cannabis (0.5-3 days per week).

Official Title
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Do Adolescents and Adults Differ in Their Acute Subjective, Behavioural and Neural Responses to Cannabis, With and Without Cannabidiol?

Conditions
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Cannabis, Cannabis Intoxication, Cannabis Use, Cannabis Dependence, CBD, Adolescent Development, Marijuana, THC

Intervention / Treatment
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* Drug: Cannabis with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)
* Drug: Cannabis with THC without CBD
* Drug: Placebo cannabis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adolescents: Aged 16-17 Adults: Aged 26-29 years Self-reported cannabis use between 0.5 and 3 days/week, averaged over the last 3 months Adults: Body mass index (BMI) between 18.5 and 29.9 Adolescents: BMI between 2nd percentile and 98th percentile Self-reported ability to consume approximately half a typical joint of cannabis by themselves within 20 minutes Willing to be cannulated and have four blood samples taken at every acute session Right-handed Exclusion Criteria: Females: Pregnant or breast-feeding Adults: Before the age of 18, had a period of 3 or more months when cannabis was used once per week or more frequently. Severe cannabis use disorder (DSM-5) Illicit drug use of any specific drug more than twice per month, averaged over the last 3 months Receiving treatment (pharmacological or psychological) for a mental health problem within the last month Lifetime psychosis Lifetime psychosis of any immediate family member Hypertension (systolic > 160 or diastolic > 100) Dependent on tobacco or vaping nicotine (> 1 on the Heaviness of Smoking Index) Currently taking a psychotropic medication that will likely affect dependent variables or interact with cannabis Any physical or mental health condition, any medication, or any treatment, that the study doctor considers to be an exclusion MRI contraindications Significant asthma or respiratory problems - severity judged clinically Self-reported moderate/severe acute unpleasant effects from cannabis which occur often or always Positive alcohol breathalyser reading at any acute session (rearrange session) Self-reported use of alcohol within 24 hours at any acute session (rearrange session) Self-reported use of illicit drugs (including cannabis) within 72 hours at any acute session (rearrange session) Positive saliva drug screen at any acute session (rearrange session)

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 29 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: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-blind, placebo-controlled, crossover experiment with drug condition block randomised and stratified by age-group and gender, such that drug order is counterbalanced. There are two groups: adolescents (16-17 years old) and adults (26-29 years old). These groups are matched on current cannabis use frequency. There are three drug conditions: (1) cannabis with delta-9-tetrahydrocannabinol (THC) and without cannabidiol (CBD), (2) cannabis with THC but without CBD, and (3) placebo cannabis without THC and without CBD.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: THC condition<br>THC condition: Cannabis with delta-9-tetrahydrocannabinol (THC) and no cannabidiol (CBD). 0.107mg/kg of THC. A 75kg person receives 8mg of THC. Route of administration: vaporised and inhaled. Frequency: once. Duration: inhaled in < 18 minutes. | Drug: Cannabis with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)<br>* Cannabis with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) - inhaled and vaporised cannabis flower<br>|
| Experimental: THC+CBD condition<br>THC+CBD condition: Cannabis with THC and CBD (i.e. THC+CBD condition). 0.107mg/kg of THC and 0.320mg/kg of CBD. A 75kg person receives 8mg of THC and 24mg of CBD. Route of administration: vaporised and inhaled. Frequency: once. Duration: inhaled in < 18 minutes. | Drug: Cannabis with THC without CBD<br>* Cannabis with THC without CBD - inhaled and vaporised cannabis flower<br>|
| Placebo Comparator: PLA condition<br>PLA condition: Placebo cannabis with no THC or CBD. Route of administration: vaporised and inhaled. Frequency: once. Duration: inhaled in < 18 minutes. | Drug: Placebo cannabis<br>* Placebo cannabis, without THC and without CBD - inhaled and vaporised<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychotomimetic effect | Measured by total Psychotomimetic States Inventory (PSI) score | Measured once, 2 hours after the start of drug administration, on each drug condition | 
| Verbal episodic memory | Measured by delayed prose recall performance | Measured once, 2 hours after the start of drug administration, on each drug condition | 
| Strength of subjective drug effect | Measured by self-reported 'feel drug effect', rated from 0 (not at all) to 10 (extremely) | Measured 20 minutes after the start of drug administration, on each drug condition | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-reported subjective effects | Feel drug effect, like drug effect, dislike drug effect, alert, want to have cannabis, happy, relaxed, anxious, paranoid, mentally impaired, stoned, dry mouth, unmotivated, intensified sensory perception, want to listen to music, want food, want to see friends, rated from 0 (not at all) to 10 (extremely) | Measured -30 minutes, 20 minutes, 30 minutes, 2 hours, and 2 hours & 40 minutes after the start of drug administration, on each drug condition | 
| Functional magnetic resonance imaging (fMRI) measured neural correlates | Reward anticipation and reward feedback, response inhibition, spatial working memory, and resting-state | Measured between 40 minutes and 1 hour & 20 minutes after the start of drug administration, on each drug condition | 
| Magnetic resonance spectroscopy | Measuring glutamate levels in the dorsal striatum | Measured 1 hour & 30 minutes after the start of drug administration, on each drug condition | 
| Positive and negative syndrome scale | Kay et al. (1987). Higher scores reflect stronger positive and negative symptoms. | Measured 2 hours & 40 minutes after the start of drug administration, on each drug condition | 
| Effort-related decision-making (i.e. amotivation) | Measured by the physical effort task ('apple-gathering' task) as described in Husain & Roiser (2018) | Measured 2 hours & 20 minutes after the start of drug administration, on each drug condition | 
| Pleasure processing | Measured by subjective liking in response to chocolate, music and cartoons, rated from 0 (not at all) to 10 (extremely), similar to Lawn et al. (2015) | Measured 2 hours & 30 minutes after the start of drug administration, on each drug condition | 
| Visual attentional bias to cannabis and food stimuli | Measured by the visual dot-probe task, as described in Morgan et al. (2010) | Measured 2 hours & 10 minutes after the start of drug administration, on each drug condition | 
| Heart rate | Measuring heart rate | Measured -30 minutes, 20 minutes, 30 minutes, 2 hours, and 2 hours & 40 minutes after the start of drug administration, on each drug condition | 
| Blood pressure | Measuring systolic and diastolic blood pressure. | Measured -30 minutes, 20 minutes, 30 minutes, 2 hours, and 2 hours & 40 minutes after the start of drug administration, on each drug condition | 
| Exogenous and endogenous cannabinoid levels in plasma | Measuring THC and CBD and metabolites; and endocannabinoids | Measured -30 minutes, 20 minutes, 30 minutes, and 2 hours & 40 minutes after the start of drug administration, on each drug condition | 
| Dissociative states scale | Bremner et al. (1998). Higher scores reflect greater dissociation. | Measured 2 hours & 40 minutes after the start of drug administration, on each drug condition | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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THC, Cannabis, Marijuana, Adolescence, fMRI, Cognition, Subjective effects, Psychotomimetic effects, CBD