INTEGRATE: Does Cannabidiol Attenuate the Acute Effects of ∆9-tetrahydrocannabinol Intoxication in Individuals Diagnosed With Schizophrenia? A Double-blind, Randomised, Placebo-controlled Experimental Study
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| 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: Cannabidiol
CBD
Drug: Delta-9-THC
THC
|
Outcome Measures
Primary Outcome Measures
- Hopkins Verbal Learning Test [Baseline; 25mins after THC inhalation]
Delayed verbal recall
Secondary Outcome Measures
- Hopkins Verbal Learning Test [Baseline; 20 - 40 mins after THC inhalation]
Immediate verbal recall
- Digit spain [Baseline; 20 - 40 mins after THC inhalation]
Forward & Reverse
- White Noise Task [Baseline; 30-60 mins after THC inhalation]
- Advice Taking Task [Baseline; 30-60 mins after THC inhalation]
- Effort Expenditure for Rewards Task [Baseline; 30-60 mins after THC inhalation]
- Positive and Negative Syndrome Scale [pre-CBD/placebo administration and 4 hours after THC inhalation]
Positive Subscale & Negative Subscale
- State Social Paranoia Scale [pre-CBD/placebo administration and 4 hours after THC inhalation]
- State-Trait Anxiety Inventory [pre-CBD/placebo administration, pre-THC/placebo inhalation and 90mins hours after THC inhalation]
State Scale
- Study drug preference [Experiment 2, 4 hours after THC/placebo inhalation]
At the end of the final experimental visit, participants will be asked to order the two experimental visits according to which drug combination they found most pleasurable.
- Visual analogue scales [-210mins, -120mins, -30mins, +10mins, +45mins, +90mins, +210mins]
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
- Plasma delta-9-tetrahydrocannabinol (THC) concentration [-210mins, -90mins, 0mins, 5mins, 15mins, +90mins from end of THC inhalation]
- Plasma cannabidiol (CBD) concentration [-210mins, -90mins, 0mins, 5mins, 15mins, +90mins from end of THC inhalation]
- Plasma THC-COOH concentraion [-210mins, -90mins, 0mins, 5mins, 15mins, +90mins from end of THC inhalation]
- Plasma 11-COOH-THC concentration [-210mins, -90mins, 0mins, 5mins, 15mins, +90mins from end of THC inhalation]
- Plasma 11-OH-THC concentration [-210mins, -90mins, 0mins, 5mins, 15mins, +90mins from end of THC inhalation]
- Plasma 6-OH-CBD concentration [-210mins, -90mins, 0mins, 5mins, 15mins, +90mins from end of THC inhalation]
- Plasma anandamide concentration [-210mins, -90mins, 0mins, 5mins, 15mins, +90mins from end of THC inhalation]
- Plasma 2-arachidonoylglycerol concentration [-210mins, -90mins, 0mins, 5mins, 15mins, +90mins from end of THC inhalation]
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | South London and Maudsley NHS Foundation Trust | London | United Kingdom | SE58AZ |
Sponsors and Collaborators
- King's College London
Investigators
- Study Chair: Gill Dale, slam-ioppn.research@kcl.ac.uk
Study Documents (Full-Text)
More Information
Publications
None provided.- IRAS: 278595