Genetics of Cannabis Use Disorder and Cannabinoid Response in Humans

• Sponsor: Yale University (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06058702
• Collaborator: (none)
• Enrollment: 215
• Arms: 2
• Anticipated Duration (Months): 60

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Cannabis Use Disorder	Drug: Delta-9-THC; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 215 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Genetics of Cannabis Use Disorder and Cannabinoid Response in Humans
• Anticipated Study Start Date: Jan 1, 2024
• Anticipated Primary Completion Date: Dec 31, 2028
• Anticipated Study Completion Date: Dec 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Delta-9-THC Active delta-9-THC (0.036 mg/kg) administered intravenously over 20 minutes.	Drug: Delta-9-THC; Active Delta-9-THC (0.036 mg/kg) administered intravenously over 20 minutes.; Drug: Placebo; Control: Small amount of sterile 190 proof USP ethanol (1-2 mLs), with no THC, administered intravenously over 20 minutes.
Placebo Comparator: Placebo Control: small amount of alcohol administered intravenously (quarter teaspoon), with no delta-9-THC, over 20 minutes.	Drug: Delta-9-THC; Active Delta-9-THC (0.036 mg/kg) administered intravenously over 20 minutes.; Drug: Placebo; Control: Small amount of sterile 190 proof USP ethanol (1-2 mLs), with no THC, administered intravenously over 20 minutes.

Outcome Measures

Primary Outcome Measures

1. Visual Analog Scale (VAS) [Measured at baseline, 20 mins, 45 mins, 90 mins, 140 mins, 165 mins, 210 mins, 270 mins, and 360 mins 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.

2. Positive and Negative Symptom Scale (PANSS) [Measured at baseline, 45 mins, 90 mins, 165 mins, 210 mins, and 360 mins 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.

3. Clinician Administered Dissociative Symptoms Scale (CADSS), [Measured at baseline, 45 mins, 90 mins, 165 mins, 210 mins, and 360 mins 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.

4. CogState Battery [Measured at baseline, 45 mins, and 165 mins after the start of the initial THC/placebo drug infusion.]

   The CogState Battery measures cognition including verbal learning and recall and episodic memory.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Yale University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Deepak C. D'Souza, Albert E. Kent Endowed Professor of Psychiatry, Yale University
• ClinicalTrials.gov Identifier: NCT06058702
• Other Study ID Numbers: 2000036194
• First Posted: Sep 28, 2023
• Last Update Posted: Sep 28, 2023
• Last Verified: Sep 1, 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Marijuana Abuse; Schizophrenia; Dronabinol

Study Results

No Results Posted as of Sep 28, 2023