Genetics of Cannabis Use Disorder and Cannabinoid Response in Humans

NCT06058702 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2000036194RO1
• Study Type: interventional
• Target: 215
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Cannabis Use Disorder

Outcome Measures

Primary Outcomes (4)

• Visual Analog Scale (VAS)

  The VAS is a scale to document perceived reward. A higher score reflects a positive response.

  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.

• Positive and Negative Symptom Scale (PANSS)

  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.

  Measured at baseline, 45 minutes, 90 minutes, 165 minutes, 210 minutes, and 360 minutes after the start of the initial THC/placebo drug infusion.

• Clinician Administered Dissociative Symptoms Scale (CADSS),

  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.

  Measured at baseline, 45 minutes, 90 minutes, 165 minutes, 210 minutes, and 360 minutes after the start of the initial THC/placebo drug infusion.

• CogState Battery

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

  Measured at baseline, 45 minutes, and 165 minutes after the start of the initial THC/placebo drug infusion.

Study Arms (3)

Delta-9-THC Very Low Dose

ACTIVE COMPARATOR

Active delta-9-THC administered intravenously over 20 minutes.

Drug: Delta-9-THC Very Low Dose

Placebo

PLACEBO COMPARATOR

Control: small amount of alcohol administered intravenously (quarter teaspoon), with no delta-9-THC, over 20 minutes.

Drug: Placebo

Delta-9-THC Medium Dose

ACTIVE COMPARATOR

Active delta-9-THC administered intravenously over 20 minutes.

Drug: Delta-9-THC Medium Dose

Interventions

Delta-9-THC Very Low Dose DRUG

Active Delta-9-THC administered intravenously over 20 minutes.

Delta-9-THC Very Low Dose

Placebo DRUG

Control: Small amount of sterile 190 proof USP ethanol (1-2 mLs), with no THC, administered intravenously over 20 minutes.

Placebo

Delta-9-THC Medium Dose DRUG

Active Delta-9-THC administered intravenously over 20 minutes.

Delta-9-THC Medium Dose

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Ages 21-60 years old

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

West Haven Veterans Affairs Medical Center

West Haven, Connecticut, 06516, United States

RECRUITING

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Deepak D'Souza, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Deepak D'Souza, MD

CONTACT

203-932-5711; deepak.douza@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Albert E. Kent Endowed Professor of Psychiatry

Study Record Dates

• First Submitted: September 15, 2023
• First Posted: September 28, 2023
• Study Start: September 16, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 8, 2025

Record last verified: 2025-07

Locations

US (1)