The Pharmaco-genetic and Brain Mechanisms Associated With Cannabis- Induced Psychosis

There is growing evidence of high rates of substance use disorders among individuals with psychotic disorders especially in young people with predisposition for psychosis. There is some genetic evidence that carriers of the valine158 allele of the catechol-O-methyltransferase (COMT) gene had increased risk to exhibit psychotic symptoms and to develop schizophrenia if they used cannabis by the age of 18. It was also shown that carriers of the COMT val/val genotype were most sensitive to THC-induced psychotic experiences but this was conditional on pre-existing susceptibility to psychosis. The investigators propose to use brain-imaging and molecular genetics to investigate whether genetic factors may contribute to the THC-induced dopamine release and possibly to cannabis- induced psychosis.

Study Overview

• Status: Unknown
• Conditions: Cannabis Dependence; Psychosis

Detailed Description

Genetic association study will be performed in 100 young cannabis users (age 18-26 years) for genes that are related to the neurotransmitters dopamine (D2, DAT, COMT), GABA, glutamate and the cannabinoid receptor CB1. Out of this cohort, 24 male subjects without history of cannabis or drug-induced psychosis will undergo brain imaging procedure in order to measure THC-induced dopamine release using [11C] Raclopride in PET imaging. Carriers of high activity COMT158Val allele are expected to show higher meso-limbic DA release than carriers of low activity COMT 158Met homozygotes and after smoking a cigarette with THC which in turn are thought to underlie the risk for THC-induced psychotic symptoms. The aim of the present study is to evaluate the relationship between the COMT genotype and cannabis-induced meso-limbic dopamine release as measured by D2 occupancy. In addition, the association between predisposition to psychosis, age of onset of cannabis dependence, and genotype of COMT and other neurotransmitters-related genes will be evaluated. Such finding could provide novel pharmaco-genetic explanation for the psychogenic effects of cannabis in vulnerable individuals.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel, 91120
    • Hadassah Medical Organization, Jerusalem, Israel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 26 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

100 current users of cannabis

Description

Inclusion Criteria:

• age 18-26 meeting DSM-IV-TR (American Psychiatric Association, 1994) diagnosis of THC dependence will be recruited from the general population by advertisement in the newspapers.

Exclusion Criteria:

• dependence on other substances or alcoholism
• a history of CNS disease
• a history of infection that might affect CNS (HIV, syphilis, cytomegalovirus, herpes)
• a history of head injury with loss of consciousness and pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
High activity COMT; Carriers of high activity COMT158Val allele who are expected to show higher THC-induced meso-limbic DA release
Low activity COMT; Carriers of low activity COMT 158Met homozygotes are expected to release low amount of dopamine after smoking a cigarette with THC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic variations of Dopamine, GABA, glutamate, cannabis CB1 receptor	DNA will be extracted from saliva of participants. Genetic variations of DA, GABA, glutamate and cannabis receptor CB1 will be coded.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measures of dopamine D2 receptor occupancy before and after smoking a cigarette containing THC.	Participants will be studied in a brain imaging study using [C 11] raclopride radioligand in Positron Emission Tomography (PET). Measures of D2 receptor occupancy will be taken at baseline and after smoking a cigarette containing 15 mg THC.	2 years

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization
• Investigators: Principal Investigator: Aviv Weinstein, Ph.D, Hadassah Medical Organization

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Anticipated): October 1, 2014
• Study Completion (Anticipated): October 1, 2014

Study Registration Dates

• First Submitted: March 26, 2012
• First Submitted That Met QC Criteria: March 27, 2012
• First Posted (Estimate): March 28, 2012

Study Record Updates

• Last Update Posted (Estimate): April 3, 2012
• Last Update Submitted That Met QC Criteria: April 1, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: psychosis; cannabis; THC; COMT; D2
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Substance-Related Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders; Marijuana Abuse; Shared Paranoid Disorder
• Other Study ID Numbers: 0541-11-HMO-CTIL