Back to results

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

Primary Purpose

Schizophrenia, Cannabis Use

Status

Completed

Phase

Not Applicable

Locations

United Kingdom

Study Type

Interventional

Intervention

Cannabidiol

Placebo

Delta-9-THC

About this trial

This is an interventional basic science trial for Schizophrenia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

South London and Maudsley NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Placebo/THC

CBD/THC

Arm Description

Oral placebo followed by inhalation of cannabis containing THC.

Oral CBD 1000mg followed by inhalation of cannabis containing THC.

Outcomes

Primary Outcome Measures

Hopkins Verbal Learning Test

Delayed verbal recall

Positive and Negative Syndrome Scale

Positive Subscale

Secondary Outcome Measures

State-Trait Anxiety Inventory

State Scale

Digit span

Forward & Reverse

Hopkins Verbal Learning Test

Immediate verbal recall

Positive and Negative Syndrome Scale

Negative Subscale

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

Psychotomimetic states inventory

State Social Paranoia Scale

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.

Advice Taking Task

White Noise Task

Plasma delta-9-tetrahydrocannabinol (THC) concentration

Plasma cannabidiol (CBD) concentration

Plasma THC-COOH concentraion

Plasma 11-COOH-THC concentration

Plasma 11-OH-THC concentration

Plasma 6-OH-CBD concentration

Plasma anandamide concentration

Plasma 2-arachidonoylglycerol concentration.

Full Information

NCT ID

NCT04605393

First Posted

October 5, 2020

Last Updated

August 15, 2023

Sponsor

King's College London

1. Study Identification

Unique Protocol Identification Number

NCT04605393

Brief Title

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

Acronym

INTEGRATE

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

January 1, 2021 (Actual)

Primary Completion Date

July 7, 2023 (Actual)

Study Completion Date

July 7, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

King's College London

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia, Cannabis Use

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo/THC

Arm Type

Experimental

Arm Description

Oral placebo followed by inhalation of cannabis containing THC.

Arm Title

CBD/THC

Arm Type

Experimental

Arm Description

Oral CBD 1000mg followed by inhalation of cannabis containing THC.

Intervention Type

Drug

Intervention Name(s)

Cannabidiol

Intervention Description

CBD

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Delta-9-THC

Intervention Description

THC

Primary Outcome Measure Information:

Title

Hopkins Verbal Learning Test

Description

Delayed verbal recall

Time Frame

Baseline visit; 20 mins post-THC

Title

Positive and Negative Syndrome Scale

Description

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 Outcome Measure Information:

Title

State-Trait Anxiety Inventory

Description

State Scale

Time Frame

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

Title

Digit span

Description

Forward & Reverse

Time Frame

Baseline; 25 mins post-THC

Title

Hopkins Verbal Learning Test

Description

Immediate verbal recall

Time Frame

Baseline; 20 mins post-THC

Title

Positive and Negative Syndrome Scale

Description

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)

Title

Visual analogue scales

Description

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)

Title

Psychotomimetic states inventory

Time Frame

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

Title

State Social Paranoia Scale

Time Frame

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

Title

Study drug preference

Description

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

Title

Advice Taking Task

Time Frame

Baseline visit; 30 mins post-THC

Title

White Noise Task

Time Frame

Baseline visit; 50 mins post-THC

Title

Plasma delta-9-tetrahydrocannabinol (THC) concentration

Time Frame