Clinical trial NCT04605393: Does Cannabidiol Attenuate the Acute Effects of ∆9-tetrahydrocannabinol Intoxication in Individuals Diagnosed With Schizophrenia? A Double-blind, Randomised, Placebo-controlled Experimental Study
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
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Cannabis Use
Lead sponsor: King's College London
Sponsor class: OTHER
First posted: 2020-10-28
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Hopkins Verbal Learning Test
timeFrame: Baseline visit; 20 mins post-THC
measure: Positive and Negative Syndrome Scale
timeFrame: 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:
measure: State-Trait Anxiety Inventory
timeFrame: pre-CBD/placebo administration, pre-THC and 20mins post-THC
measure: Digit span
timeFrame: Baseline; 25 mins post-THC
measure: Hopkins Verbal Learning Test
timeFrame: Baseline; 20 mins post-THC
measure: Positive and Negative Syndrome Scale
timeFrame: pre-CBD/placebo administration, and from immediately after THC inhalation until the end of study visit (i.e. 2-3 hours post-THC)
measure: Visual analogue scales
timeFrame: 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)
measure: Psychotomimetic states inventory
timeFrame: pre-CBD/placebo administration, and at the end of study visit (i.e. 2-3 hours post-THC)
measure: State Social Paranoia Scale
timeFrame: pre-CBD/placebo administration, and at the end of study visit (i.e. 2-3 hours post-THC)
measure: Study drug preference
timeFrame: End of Experiment 2
measure: Advice Taking Task
timeFrame: Baseline visit; 30 mins post-THC
measure: White Noise Task
timeFrame: Baseline visit; 50 mins post-THC
measure: Plasma delta-9-tetrahydrocannabinol (THC) concentration
timeFrame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
measure: Plasma cannabidiol (CBD) concentration
timeFrame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
measure: Plasma THC-COOH concentraion
timeFrame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
measure: Plasma 11-COOH-THC concentration
timeFrame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
measure: Plasma 11-OH-THC concentration
timeFrame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
measure: Plasma 6-OH-CBD concentration
timeFrame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
measure: Plasma anandamide concentration
timeFrame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
measure: Plasma 2-arachidonoylglycerol concentration.
timeFrame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: South London and Maudsley NHS Foundation Trust
Study officials:
affiliation: slam-ioppn.research@kcl.ac.uk
name: Gill Dale
role: STUDY_CHAIR
References: