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
Sponsored by
About this trial
This is an interventional basic science trial for Schizophrenia
Eligibility Criteria
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
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
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
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
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
pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Title
Plasma cannabidiol (CBD) concentration
Time Frame
pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Title
Plasma THC-COOH concentraion
Time Frame
pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Title
Plasma 11-COOH-THC concentration
Time Frame
pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Title
Plasma 11-OH-THC concentration
Time Frame
pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Title
Plasma 6-OH-CBD concentration
Time Frame
pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Title
Plasma anandamide concentration
Time Frame
pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Title
Plasma 2-arachidonoylglycerol concentration.
Time Frame
pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gill Dale
Organizational Affiliation
slam-ioppn.research@kcl.ac.uk
Official's Role
Study Chair
Facility Information:
Facility Name
South London and Maudsley NHS Foundation Trust
City
London
ZIP/Postal Code
SE58AZ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Does Cannabidiol Attenuate the Acute Effects of ∆9-tetrahydrocannabinol Intoxication in Individuals Diagnosed With Schizophrenia? A Double-blind, Randomised, Placebo-controlled Experimental Study
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