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

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

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 Overview

• Status: Completed
• Conditions: Cannabis; Cannabis Dependence; Cannabis Use; CBD; Adolescent Development; THC; Marijuana; Cannabis Intoxication
• Intervention / Treatment: Drug: Cannabis with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD); Drug: Cannabis with THC without CBD; Drug: Placebo cannabis

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, WC1E 7HB
    • University College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 29 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: THC condition; 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); Cannabis with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) - inhaled and vaporised cannabis flower
EXPERIMENTAL: THC+CBD condition; 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; Cannabis with THC without CBD - inhaled and vaporised cannabis flower
PLACEBO_COMPARATOR: PLA condition; 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; Placebo cannabis, without THC and without CBD - inhaled and vaporised

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Medical Research Council; Invicro

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 11, 2019
• Primary Completion (ACTUAL): June 16, 2021
• Study Completion (ACTUAL): June 16, 2021

Study Registration Dates

• First Submitted: April 5, 2021
• First Submitted That Met QC Criteria: April 15, 2021
• First Posted (ACTUAL): April 20, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: fMRI; Cognition; CBD; Adolescence; Cannabis; THC; Marijuana; Subjective effects; Psychotomimetic effects
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Anticonvulsants; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol; Cannabidiol
• Other Study ID Numbers: 5929/005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No