Adolescent Development, Cannabis, Cannabis Dependence, Cannabis Intoxication, Cannabis Use, CBD, Marijuana, THC
Conditions
Keywords
Cannabis, Marijuana, THC, CBD, Adolescence, fMRI, Cognition, Subjective effects, Psychotomimetic effects
Brief summary
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).
Interventions
DRUGCannabis with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)
Cannabis with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) - inhaled and vaporised cannabis flower
DRUGCannabis with THC without CBD
Cannabis with THC without CBD - inhaled and vaporised cannabis flower
DRUGPlacebo cannabis
Placebo cannabis, without THC and without CBD - inhaled and vaporised
Sponsors
Medical Research Council
Invicro
University College, London
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
16 Years to 29 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Psychotomimetic effect | Measured once, 2 hours after the start of drug administration, on each drug condition | Measured by total Psychotomimetic States Inventory (PSI) score |
| Verbal episodic memory | Measured once, 2 hours after the start of drug administration, on each drug condition | Measured by delayed prose recall performance |
| Strength of subjective drug effect | Measured 20 minutes after the start of drug administration, on each drug condition | Measured by self-reported 'feel drug effect', rated from 0 (not at all) to 10 (extremely) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive and negative syndrome scale | Measured 2 hours & 40 minutes after the start of drug administration, on each drug condition | Kay et al. (1987). Higher scores reflect stronger positive and negative symptoms. |
| Effort-related decision-making (i.e. amotivation) | Measured 2 hours & 20 minutes after the start of drug administration, on each drug condition | Measured by the physical effort task ('apple-gathering' task) as described in Husain & Roiser (2018) |
| Pleasure processing | Measured 2 hours & 30 minutes after the start of drug administration, on each drug condition | 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) |
| Visual attentional bias to cannabis and food stimuli | Measured 2 hours & 10 minutes after the start of drug administration, on each drug condition | Measured by the visual dot-probe task, as described in Morgan et al. (2010) |
| Self-reported subjective effects | Measured -30 minutes, 20 minutes, 30 minutes, 2 hours, and 2 hours & 40 minutes after the start of drug administration, on each drug condition | 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) |
| 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 | Measuring systolic and diastolic blood pressure. |
| Exogenous and endogenous cannabinoid levels in plasma | Measured -30 minutes, 20 minutes, 30 minutes, and 2 hours & 40 minutes after the start of drug administration, on each drug condition | Measuring THC and CBD and metabolites; and endocannabinoids |
| Dissociative states scale | Measured 2 hours & 40 minutes after the start of drug administration, on each drug condition | Bremner et al. (1998). Higher scores reflect greater dissociation. |
| 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 | Measuring heart rate |
| Functional magnetic resonance imaging (fMRI) measured neural correlates | Measured between 40 minutes and 1 hour & 20 minutes after the start of drug administration, on each drug condition | Reward anticipation and reward feedback, response inhibition, spatial working memory, and resting-state |
| Magnetic resonance spectroscopy | Measured 1 hour & 30 minutes after the start of drug administration, on each drug condition | Measuring glutamate levels in the dorsal striatum |
Countries
United Kingdom
Outcome results
None listed