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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2012 by Hadassah Medical Organization
Sponsor:
Information provided by (Responsible Party):
VEINSHTEIN AVIV, Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT01565174
First received: March 26, 2012
Last updated: April 1, 2012
Last verified: April 2012
  Purpose

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.


Condition
Cannabis Dependence
Psychosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: The Pharmaco-genetic and Brain Mechanisms Associated With Cannabis- Induced Psychosis

Resource links provided by NLM:


Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • Genetic variations of Dopamine, GABA, glutamate, cannabis CB1 receptor [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    DNA will be extracted from saliva of participants. Genetic variations of DA, GABA, glutamate and cannabis receptor CB1 will be coded.


Secondary Outcome Measures:
  • Measures of dopamine D2 receptor occupancy before and after smoking a cigarette containing THC. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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.


Biospecimen Retention:   Samples With DNA

Samples of DNA will be taken from saliva of participants


Estimated Enrollment: 100
Study Start Date: October 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 26 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

100 current users of cannabis

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01565174

Contacts
Contact: Aviv M Weinstein, Ph.D 972-2-6776705 avivweinstein@yahoo.com
Contact: Roland Chisin, M.D 972-2-6776705 chisin@hadassah.org.il

Locations
Israel
Hadassah Medical Organization, Jerusalem, Israel Not yet recruiting
Jerusalem, Israel, 91120
Contact: Hadas Lemberg, Ph.D    00 972 2 6777572    lhadas@hadassah.org.il   
Principal Investigator: Aviv M Weinstein, Ph.D         
Sponsors and Collaborators
Hadassah Medical Organization
Investigators
Principal Investigator: Aviv Weinstein, Ph.D Hadassah Medical Organization
  More Information

No publications provided

Responsible Party: VEINSHTEIN AVIV, Senior Research Fellow, Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT01565174     History of Changes
Other Study ID Numbers: 0541-11-HMO-CTIL
Study First Received: March 26, 2012
Last Updated: April 1, 2012
Health Authority: Israel: Ministry of Health

Keywords provided by Hadassah Medical Organization:
cannabis
THC
COMT
psychosis
D2

Additional relevant MeSH terms:
Marijuana Abuse
Mental Disorders
Psychotic Disorders
Shared Paranoid Disorder
Substance-Related Disorders
Schizophrenia and Disorders with Psychotic Features
Schizophrenia

ClinicalTrials.gov processed this record on July 20, 2014