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

University College, London48 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Cannabis Cannabis Intoxication Cannabis Use Cannabis Dependence Marijuana THC

Interventions

Cannabis with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)DRUG

Cannabis with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) - inhaled and vaporised cannabis flower

Cannabis with THC without CBDDRUG

Cannabis with THC without CBD - inhaled and vaporised cannabis flower

Placebo cannabisDRUG

Placebo cannabis, without THC and without CBD - inhaled and vaporised

Eligibility

Sex: ALLMin age: 16 YearsMax age: 29 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Psychotomimetic effect

Measured by total Psychotomimetic States Inventory (PSI) score

Time frame: Measured once, 2 hours after the start of drug administration, on each drug condition

Verbal episodic memory

Measured by delayed prose recall performance

Time frame: 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)

Time frame: Measured 20 minutes after the start of drug administration, on each drug condition

Secondary Outcomes

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)

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: Measured 2 hours & 10 minutes after the start of drug administration, on each drug condition

Heart rate

Measuring heart rate

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: Measured 2 hours & 40 minutes after the start of drug administration, on each drug condition

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes