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

Study Overview
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Brief Summary
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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.

Official Title
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Reducing the Harmful Effects of Cannabis Use: Finding the Optimal CBD:THC Ratio

Conditions
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Cannabis Use

Intervention / Treatment
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* Drug: THC
* Drug: Cannabidiol
* Drug: Cannabidiol
* Drug: Cannabidiol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBD:THC 0:1<br>Inhalation of cannabis containing only THC | Drug: THC<br>* Inhaled cannabis containing 10mg THC<br>|
| Experimental: CBD:THC 1:1<br>Inhalation of cannabis containing THC and CBD | Drug: THC<br>* Inhaled cannabis containing 10mg THC<br>Drug: Cannabidiol<br>* Inhaled cannabis containing 10mg CBD<br>|
| Experimental: CBD:THC 2:1<br>Inhalation of cannabis containing THC and CBD | Drug: THC<br>* Inhaled cannabis containing 10mg THC<br>Drug: Cannabidiol<br>* Inhaled cannabis containing 20mg CBD<br>|
| Experimental: CBD:THC 3:1<br>Inhalation of cannabis containing THC and CBD | Drug: THC<br>* Inhaled cannabis containing 10mg THC<br>Drug: Cannabidiol<br>* Inhaled cannabis containing 30mg CBD<br>|

What is the study measuring?
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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 |