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Completed

NCT Number: NCT04605393

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

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.

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

South London and Maudsley NHS Foundation Trust

London, SE58AZ, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Cannabidiol

Drug

CBD

Placebo

Drug

Placebo

Delta-9-THC

Drug

THC

Primary outcomes

  1. Hopkins Verbal Learning Test

    Time frame: Baseline visit; 20 mins post-THC

    Delayed verbal recall

  2. Positive and Negative Syndrome Scale

    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)

    Positive Subscale

Secondary outcomes

  1. State-Trait Anxiety Inventory

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

    State Scale

  2. Digit span

    Time frame: Baseline; 25 mins post-THC

    Forward & Reverse

  3. Hopkins Verbal Learning Test

    Time frame: Baseline; 20 mins post-THC

    Immediate verbal recall

  4. Positive and Negative Syndrome Scale

    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)

    Negative Subscale

  5. Visual analogue scales

    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)

    • 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
  6. Psychotomimetic states inventory

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

  7. State Social Paranoia Scale

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

  8. Study drug preference

    Time frame: End of Experiment 2

    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.

  9. Advice Taking Task

    Time frame: Baseline visit; 30 mins post-THC

  10. White Noise Task

    Time frame: Baseline visit; 50 mins post-THC

  11. Plasma delta-9-tetrahydrocannabinol (THC) concentration

    Time frame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC

  12. Plasma cannabidiol (CBD) concentration

    Time frame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC

  13. Plasma THC-COOH concentraion

    Time frame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC

  14. Plasma 11-COOH-THC concentration

    Time frame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC

  15. Plasma 11-OH-THC concentration

    Time frame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC

  16. Plasma 6-OH-CBD concentration

    Time frame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC

  17. Plasma anandamide concentration

    Time frame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC

  18. Plasma 2-arachidonoylglycerol concentration.

    Time frame: pre-CBD/placebo, 90mins post CBD, and 0mins, 5mins, 15mins, +90mins post-THC

Sponsors and collaborators

Lead sponsor

King's College London

Other

Registry information

Acronym: INTEGRATE

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Oct 28, 2020
Registry last updated
Aug 18, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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