Genetics of Cannabis Use Disorder and Cannabinoid Response in Humans

Phase 1

Recruiting

• Conditions: Schizophrenia; Cannabis Use Disorder
• Interventions: Drug: Delta-9-THC; Drug: Placebo

• Registration Number: NCT06058702
• Lead Sponsor: Yale University

Brief Summary

Cannabis is widely used worldwide and is associated with negative outcomes including cannabis use disorder (CanUD), psychosis, and cognitive impairment amongst others. Given the legalization of "recreational" and "medical" cannabis globally, the increasing availability of cannabis, the higher potency of cannabis, the availability of highly potent cannabinoid products, the commercialization of cannabis, and the rising rates of cannabis use, it is critical to understand how genetic factors influence 1) an individual's vulnerability for addiction and psychosis, 2) the response to cannabinoids, 3) the response to novel treatments for CanUD. CanUD is strongly genetically influenced; the investigators published the first CanUD genomewide association study (GWAS) with genomewide-significant results; however, the precise nature of the contribution of genetic factors in the development of CanUD is still not clear. Cannabis exposure has also been linked to a number of psychosis outcomes including schizophrenia (SCZ). SCZ is highly heritable and population-based and genetics studies both support a bidirectional genetic relationship between SCZ and CanUD. However, the precise contribution of genetic factors in the development of psychosis outcomes related to cannabis are not clear.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-15
• Study First Submitted QC: 2023-09-21
• Study First Posted: 2023-09-28
• Study Start: 2024-09-16
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-21
• Last Update Posted: 2025-01-24
• Primary Completion: 2028-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 215

Inclusion Criteria

-Ages 18-60 years old

Exclusion Criteria

• Major or unstable medical conditions based on history, the Structured Clinical Interview for DSM-5, collateral information, physical and laboratory examinations, ECG, and vital signs.
• Cannabis naïve individuals
• Positive pregnancy test

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Delta-9-THC	Delta-9-THC	Active delta-9-THC (0.036 mg/kg) administered intravenously over 20 minutes.
Delta-9-THC	Placebo	Active delta-9-THC (0.036 mg/kg) administered intravenously over 20 minutes.
Placebo	Delta-9-THC	Control: small amount of alcohol administered intravenously (quarter teaspoon), with no delta-9-THC, over 20 minutes.
Placebo	Placebo	Control: small amount of alcohol administered intravenously (quarter teaspoon), with no delta-9-THC, over 20 minutes.

Primary Outcome Measures

Name	Time	Method
Visual Analog Scale (VAS)	Measured at baseline, 20 minutes, 45 minutes, 90 minutes, 140 minutes, 165 minutes, 210 minutes, 270 minutes, and 360 minutes after the start of the initial THC/placebo drug infusion.	The VAS is a scale to document perceived reward. A higher score reflects a positive response.
Clinician Administered Dissociative Symptoms Scale (CADSS),	Measured at baseline, 45 minutes, 90 minutes, 165 minutes, 210 minutes, and 360 minutes after the start of the initial THC/placebo drug infusion.	Perceptual alterations will be measured using scales such as the Clinician Administered Dissociative Symptoms Scale (CADSS), a scale consisting of 19 self-report items and 8 clinician-rated items (0 = not at all, 4 = extremely) that we have shown to be sensitive to THC effects. The scale captures alterations in environmental/time/body perception, feelings of unreality, and memory impairment.
Positive and Negative Symptom Scale (PANSS)	Measured at baseline, 45 minutes, 90 minutes, 165 minutes, 210 minutes, and 360 minutes after the start of the initial THC/placebo drug infusion.	The Positive and Negative Syndrome Scale is a 30-item scale to assess both the positive and negative symptom symptoms of schizophrenia. The range total score is 30-210. An improvement in symptoms is reflected by a lower score.
CogState Battery	Measured at baseline, 45 minutes, and 165 minutes after the start of the initial THC/placebo drug infusion.	The CogState Battery measures cognition including verbal learning and recall and episodic memory.

Trial Locations

Locations (1)

West Haven Veterans Affairs Medical Center; 🇺🇸 West Haven, Connecticut, United States