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

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 Overview

• Status: Completed
• Conditions: Schizophrenia; Cannabis Use
• Intervention / Treatment: Drug: Placebo; Drug: Delta-9-THC; Drug: Cannabidiol

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE58AZ
    • South London and Maudsley NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo/THC; Oral placebo followed by inhalation of cannabis containing THC.	Drug: Placebo; Placebo; Drug: Delta-9-THC; THC
Experimental: CBD/THC; Oral CBD 1000mg followed by inhalation of cannabis containing THC.	Drug: Delta-9-THC; THC; Drug: Cannabidiol; CBD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hopkins Verbal Learning Test	Delayed verbal recall	Baseline visit; 20 mins post-THC
Positive and Negative Syndrome Scale	Positive Subscale	pre-CBD/placebo administration, and from immediately after THC inhalation until the end of study visit (i.e. 2-3 hours post-THC)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
State-Trait Anxiety Inventory	State Scale	pre-CBD/placebo administration, pre-THC and 20mins post-THC
Digit span	Forward & Reverse	Baseline; 25 mins post-THC
Hopkins Verbal Learning Test	Immediate verbal recall	Baseline; 20 mins post-THC
Positive and Negative Syndrome Scale	Negative Subscale	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	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		pre-CBD/placebo administration, and at the end of study visit (i.e. 2-3 hours post-THC)
State Social Paranoia Scale		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.	End of Experiment 2
Advice Taking Task		Baseline visit; 30 mins post-THC
White Noise Task		Baseline visit; 50 mins post-THC
Plasma delta-9-tetrahydrocannabinol (THC) concentration		pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Plasma cannabidiol (CBD) concentration		pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Plasma THC-COOH concentraion		pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Plasma 11-COOH-THC concentration		pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Plasma 11-OH-THC concentration		pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Plasma 6-OH-CBD concentration		pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Plasma anandamide concentration		pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Plasma 2-arachidonoylglycerol concentration.		pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC

Collaborators and Investigators

• Sponsor: King's College London
• Investigators: Study Chair: Gill Dale, slam-ioppn.research@kcl.ac.uk

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): July 7, 2023
• Study Completion (Actual): July 7, 2023

Study Registration Dates

• First Submitted: October 5, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 28, 2020

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 15, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; 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: IRAS: 278595

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