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

Psychosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01565174
• Other study ID #: 0541-11-HMO-CTIL
• Status: Not yet recruiting
• Phase: N/A
• First received: March 26, 2012
• Last updated: April 1, 2012
• Start date: October 2012
• Est. completion date: October 2014

Study information

• Verified date: April 2012
• Source: Hadassah Medical Organization
• Contact: Aviv M Weinstein, Ph.D
• Phone: 972-2-6776705
• Email: avivweinstein[@]yahoo.com
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 26 Years

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Cannabis Dependence
• Marijuana Abuse
• Mental Disorders
• Psychosis
• Psychotic Disorders

Locations

Country	Name	City	State
Israel	Hadassah Medical Organization, Jerusalem, Israel	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Hadassah Medical Organization

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes