Reducing the Harmful Effects of Cannabis Use: Finding the Optimal CBD:THC Ratio (eCBD)

This study will recruit healthy volunteers who use cannabis infrequently. Each participant will attend the laboratory on five occasions: an initial visit to check that they are safe to join the study and four days of testing.

Participants will be administered, in a randomized order, vaporized cannabis containing one of four different ratios of CBD:THC (0:1, 1:1, 2:1, 3:1). The cannabis administration will follow a standardised inhalation procedure using a medical-grade vaporizer device.

Participants will complete a series of tasks measuring cognition, psychosis, anxiety and other subjective experiences.

The study will be carried out at the NIHR-Wellcome Trust Clinical Research Facility at King's College Hospital.

Study Overview

• Status: Completed
• Conditions: Cannabis Use
• Intervention / Treatment: Drug: THC; Drug: Cannabidiol; Drug: Cannabidiol; Drug: Cannabidiol

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 8AF
    • Institute of Psychiatry, Psychology and Neuroscience, King's College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female and male volunteers aged 21-50
• Have used cannabis at least once
• Willing to provide written informed consent
• Willing to provide blood samples
• Fluent English speaker

Exclusion Criteria:

• Past or present major mental illness
• Past or present major physical illness
• Past or present substance use disorder
• Past or present use of anti-psychotic or anti-depressant medications
• First degree relative with psychotic disorder
• Currently taking psychotropic medication
• Positive urine drug screen at screening or experimental visits
• Use of alcohol 24h prior to experimental visit or tobacco on the day of experiment
• Pregnancy (current or planned) or lactation in women
• Significant abnormality detected during physical examination at screening visit
• Cannabis use (defined as days in which cannabis is used recreationally) more than once per week on average over the last 12 months
• Any past use of synthetic cannabinoids
• Score of 5 and above on the Fagerstrom Nicotine dependence questionnaire
• BMI classified as obese or underweight
• Taken part in any drug study within the last 30 days or taking part in another study over the course of the trial
• Known drug sensitivity/allergy towards cannabis or Lorazepam

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CBD:THC 0:1; Inhalation of cannabis containing only THC	Drug: THC; Inhaled cannabis containing 10mg THC
Experimental: CBD:THC 1:1; Inhalation of cannabis containing THC and CBD	Drug: THC; Inhaled cannabis containing 10mg THC; Drug: Cannabidiol; Inhaled cannabis containing 10mg CBD; Drug: Cannabidiol; Inhaled cannabis containing 20mg CBD; Drug: Cannabidiol; Inhaled cannabis containing 30mg CBD
Experimental: CBD:THC 2:1; Inhalation of cannabis containing THC and CBD	Drug: THC; Inhaled cannabis containing 10mg THC; Drug: Cannabidiol; Inhaled cannabis containing 10mg CBD; Drug: Cannabidiol; Inhaled cannabis containing 20mg CBD; Drug: Cannabidiol; Inhaled cannabis containing 30mg CBD
Experimental: CBD:THC 3:1; Inhalation of cannabis containing THC and CBD	Drug: THC; Inhaled cannabis containing 10mg THC; Drug: Cannabidiol; Inhaled cannabis containing 10mg CBD; Drug: Cannabidiol; Inhaled cannabis containing 20mg CBD; Drug: Cannabidiol; Inhaled cannabis containing 30mg CBD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hopkins Verbal Learning Task	Delayed verbal recall	40-45 minutes post cannabis inhalation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hopkins Verbal Learning Task	Immediate verbal recall	20-40 minutes post cannabis inhalation
Forward and Reverse Digit span	Working memory	20-40 minutes post cannabis inhalation
Spatial N-back task	Spatial working memory	20-40 minutes post cannabis inhalation
Positive and Negative Syndrome Scale	Positive subscale	Baseline; 3-4 hours post cannabis inhalation
State Social Paranoia Scale		3-4 hours post cannabis inhalation
Community assessment of Psychic Experiences - state		3-4 hours post cannabis inhalation
Psychotomimetic states inventory		3-4 hours post cannabis inhalation
Visual analogue scales (0 to 100 millimetres)	Feel drug effect; Like drug effect; Want more drug; Mentally impaired; Dry Mouth; Enhanced colour perception; Enhanced sound perception; Want food; Want alcohol; Feel high; Feel anxious; Feel paranoid; Feel tired; Feel calm and relaxed; Feel stoned; The drug effects are pleasurable	Baseline; Pre-cannabis, 10 minutes post-cannabis, 50 minutes post-cannabis, 1 hour 10 minutes post-cannabis, discharge
Pleasurable responses - Visual analogue scale (-50 to 50 millimetres)	Increased or decreased pleasure from chocolate and music during intoxication	1 hour post-cannabis
Plasma THC concentration		Pre-cannabis, 0 minutes post-cannabis, 5 minutes post-cannabis, 15 minutes post-cannabis, 90 minutes post-cannabis
Plasma CBD concentration		Pre-cannabis, 0 minutes post-cannabis, 5 minutes post-cannabis, 15 minutes post-cannabis, 90 minutes post-cannabis
Plasma 11-OH-THC concentration		Pre-cannabis, 0 minutes post-cannabis, 5 minutes post-cannabis, 15 minutes post-cannabis, 90 minutes post-cannabis
Plasma 11-COOH-THC concentration		Pre-cannabis, 0 minutes post-cannabis, 5 minutes post-cannabis, 15 minutes post-cannabis, 90 minutes post-cannabis
Plasma 7-OH-CBD concentration		Pre-cannabis, 0 minutes post-cannabis, 5 minutes post-cannabis, 15 minutes post-cannabis, 90 minutes post-cannabis

Collaborators and Investigators

• Sponsor: King's College London

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2017
• Primary Completion (Actual): June 9, 2019
• Study Completion (Actual): June 9, 2019

Study Registration Dates

• First Submitted: November 17, 2021
• First Submitted That Met QC Criteria: December 9, 2021
• First Posted (Actual): December 27, 2021

Study Record Updates

• Last Update Posted (Actual): December 27, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: HR-16/17-4163

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