Genetics of Cannabis Use Disorder and Cannabinoid Response in Humans

Study Overview
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Brief Summary
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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.

Official Title
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Genetics of Cannabis Use Disorder and Cannabinoid Response in Humans

Conditions
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Schizophrenia, Cannabis Use Disorder

Intervention / Treatment
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* Drug: Delta-9-THC
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale (VAS) | The VAS is a scale to document perceived reward. A higher score reflects a positive response. | 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. | 
| 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 mins, 90 mins, 165 mins, 210 mins, and 360 mins 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 mins, 90 mins, 165 mins, 210 mins, and 360 mins 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 mins, and 165 mins after the start of the initial THC/placebo drug infusion. |