Does Cannabidiol Attenuate the Acute Effects of ∆9-tetrahydrocannabinol Intoxication in Individuals Diagnosed With Schizophrenia? A Double-blind, Randomised, Placebo-controlled Experimental Study

King's College London36 enrolled

Overview

This study will recruit schizophrenia patients who use cannabis recreationally. Each participant will attend the laboratory on three occasions: an initial visit to check that they are safe to join the study and two days of testing. Participants will be administered, in a randomized order, a pre-treatment with either CBD (1000mg) orally or a matching placebo. On both experiments, participants will then inhale cannabis containing THC. The THC 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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

Conditions

Schizophrenia Cannabis Use

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion criteria: * Age 18-65 years. * Clinical diagnosis of schizophrenia (i.e. documented as such in the patient's clinical records and satisfying ICD-10 criteria for F20) * Clinically stable for at least three months (since discharge from hospital, home treatment team, or prior clinical deterioration, and with agreement from the patient's responsible clinician) * Regular (at least weekly) cannabis use for the past 3 months or more * Evidence from either clinicians or from the patient that cannabis use exacerbates their symptoms or increases their risk of relapse * Treatment with regular doses of antipsychotic medication for at least 1 month, confirmed by a blood test at the baseline visit, and with the participant agreeing to be maintained at a stable dose over the course of the experiment * The participant agrees to abstain from cannabis use for at least 24hours prior to study visits * The participant is willing to have an intravenous cannula inserted to collect blood samples on experimental visits * Sufficiently fluent English * Providing written informed consent Exclusion criteria: * Extreme cannabis use: participant is estimate to be using over 1gram of cannabis/day * Dependence on alcohol or illicit substances other than cannabis as defined by ICD-10 * Pregnancy (current or planned) or breastfeeding * Physical health disorder or another mental health disorder that the study psychiatrist judges may influence the patient's ability to tolerate the procedure, or that may alter the results of the study. * Taken part in any drug study within the last 3 months or taking part in another study over the course of the trial * Drug sensitivity/allergy to cannabis or Lorazepam * Unlikely to be able to complete the study sessions for any reason, as judged by the study psychiatrist Additional criteria which must be met on experimental visits: * Negative alcohol breath test * Negative urine drug screen (apart from cannabis and prescribed medication) * Negative urine pregnancy test * Stable mental state as judged by the study psychiatrist

Outcomes

Primary Outcomes

Hopkins Verbal Learning Test

Delayed verbal recall

Time frame: Baseline visit; 20 mins post-THC

Positive and Negative Syndrome Scale

Positive Subscale

Time frame: pre-CBD/placebo administration, and from immediately after THC inhalation until the end of study visit (i.e. 2-3 hours post-THC)

Secondary Outcomes

State-Trait Anxiety Inventory

State Scale

Time frame: pre-CBD/placebo administration, pre-THC and 20mins post-THC

Digit span

Forward \& Reverse

Time frame: Baseline; 25 mins post-THC

Hopkins Verbal Learning Test

Immediate verbal recall

Time frame: Baseline; 20 mins post-THC

Positive and Negative Syndrome Scale

Negative Subscale

Time frame: pre-CBD/placebo administration, and from immediately after THC inhalation until the end of study visit (i.e. 2-3 hours post-THC)

Visual analogue scales

* Feel drug effect * Like drug effect * Want more drug * Thinking clearly * Tired * Excited * Want to talk * Anxious * Relaxed * Happy * Irritable * Suspicious * Hearing voices * Dry mouth * Hungry

Time frame: pre-CBD/placebo, 90mins post CBD, pre-THC, and +10mins, +45mins, +90mins post-THC inhalation, and at the end of study visit (i.e. 2-3 hours post-THC)

Psychotomimetic states inventory

Time frame: pre-CBD/placebo administration, and at the end of study visit (i.e. 2-3 hours post-THC)

State Social Paranoia Scale

Time frame: pre-CBD/placebo administration, and at the end of study visit (i.e. 2-3 hours post-THC)

Study drug preference

At the end of the final experimental visit (i.e. 2-3 hours post-THC), participants will be asked to order the two experimental visits according to which drug combination they found most pleasurable.

Time frame: End of Experiment 2

Advice Taking Task

Time frame: Baseline visit; 30 mins post-THC

White Noise Task

Time frame: Baseline visit; 50 mins post-THC

Plasma delta-9-tetrahydrocannabinol (THC) concentration