Imaging Cannabinoid Receptors Using Positron Emission Tomography (PET) Scanning

Characterization of CB1 Receptors Using [11-C]OMAR

The aim of the present study is to assess the availability of cannabinoid receptors (CB1R) in the human brain. CB1R are present in everyone's brain, regardless of whether or not someone has used cannabis. The investigators will image brain cannabinoid receptors using Positron Emission Tomography (PET) imaging and the radioligand OMAR, in healthy individuals and several conditions including 1) cannabis use disorders, 2) psychotic disorders, 3) prodrome of psychotic illness and 4) individuals with a family history of alcoholism, 5) Post-Traumatic Stress Disorder 6) Opioid Use Disorder using the PET imaging agent or radiotracer, [11C]OMAR. This will allow us to characterize the number and distribution of CB1R in these conditions. It is likely that the list of conditions will be expanded after the collection of pilot data and as new data on cannabinoids receptor function and psychiatric disorders becomes available.

Those in the cannabis us disorder arm of the study will have a PET scan on at least three occasions: once while smoking as usual, once after 48-hours of abstinence from cannabis, and a final time after 4 weeks of abstinence. Additional scans may be conducted within the 4 weeks and the last scan may be conducted well beyond 4 weeks. Similarly, while most schizophrenia patients may get scanned just once, a subgroup of patients may get scanned more than once. For example to tease out the effects of medications, unmedicated patients may get scanned while unmedicated and again after treatment with antipsychotic medications. Similarly prodromes may get scanned while in the prodromal stage off medications, on medications and after conversion to schizophrenia.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Post Traumatic Stress Disorder; Cannabis Dependence; Opioid-use Disorder; Healthy Control; Prodromal for Psychotic Illness; Family History of Alcoholism
• Intervention / Treatment: Radiation: [11-C]OMAR

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

Contacts and Locations

• Study Contact: Name: Alex Selloni, BA; Phone Number: 203-974-7489; Email: alexandria.selloni@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Connecticut Mental Health Center, Clinical Neuroscience Research Unit
      • Contact: Alex Selloni, BA; Phone Number: 203-974-7489; Email: alexandria.selloni@yale.edu
      • Principal Investigator: Deepak C D'Souza, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The study population is composed of schizophrenia, cannabis dependence, prodromal for psychotic illness, family history of alcoholism, healthy volunteers, Post-Traumatic Stress Disorder and Opioid Use Disorder.

Description

Inclusion Criteria:

• Males ages 18-55
• For cannabis users:
• Willing to abstain from cannabis use for four weeks
• For schizophrenia:
• Meets DSM-IV-TR criteria for schizophrenia or schizoaffective disorder
• For prodrome for psychotic illness:
• Meets SIPS criteria for prodromal syndrome
• For family history positive:
• First degree relative with alcoholism
• For Post-Traumatic Stress Disorder
• Meets DSM-IV-TR criteria for PTSD
• For OUD
• Meets DSM-IV-TR criteria for Opioid Use Disorder

Exclusion Criteria:

• Current neuro-psychiatric illness (including cannabis dependence) or severe systemic disease. Cannabis use disorder is permitted in the cannabis dependent group. Schizophrenia and schizoaffective disorder is permitted in the schizophrenia group. Psychotic symptoms are permitted in the prodromal group. Post-Traumatic Stress Disorder is permitted in the PTSD group and Opioid Use Disorder is permitted in the OUD group.
• Presence of ferromagnetic metal in the body or heart pacemaker
• Have had exposure to ionizing radiation that in combination with the study tracer would result in a cumulative exposure that exceeds recommended exposure limits
• Are claustrophobic

Study Plan

How is the study designed?

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Volunteers; Healthy volunteers with no current or past major medical or psychiatric history	Radiation: [11-C]OMAR; The radiotracer, [11-C]OMAR will be administered at no more than 10 micrograms at the beginning of each PET scan.
Schizophrenia; Patients diagnosed with schizophrenia both on medication and off medication	Radiation: [11-C]OMAR; The radiotracer, [11-C]OMAR will be administered at no more than 10 micrograms at the beginning of each PET scan.
Cannabis dependence; Frequent users of cannabis	Radiation: [11-C]OMAR; The radiotracer, [11-C]OMAR will be administered at no more than 10 micrograms at the beginning of each PET scan.
Family history of alcoholism; Healthy volunteers with a first degree relative with alcoholism	Radiation: [11-C]OMAR; The radiotracer, [11-C]OMAR will be administered at no more than 10 micrograms at the beginning of each PET scan.
Prodrome for psychotic illness; Not meeting full criteria for psychotic illness but exhibiting prodromal symptoms	Radiation: [11-C]OMAR; The radiotracer, [11-C]OMAR will be administered at no more than 10 micrograms at the beginning of each PET scan.
PTSD-Post Traumatic Stress Disorder; Patients diagnosed with Post Traumatic Stress Disorder	Radiation: [11-C]OMAR; The radiotracer, [11-C]OMAR will be administered at no more than 10 micrograms at the beginning of each PET scan.
Opioid Use Disorder; Patients diagnosed with Opioid Use Disorder	Radiation: [11-C]OMAR; The radiotracer, [11-C]OMAR will be administered at no more than 10 micrograms at the beginning of each PET scan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PET Imaging	This study will utilize the radioligand [11C]OMAR and High Resolution Research Tomography (HRRT) Positron Emission Tomography (PET) to measure brain CB1 receptor availability in all study populations. Those in the cannabis dependent population of the study will have PET scanning on three occasions: once within four weeks of screening while smoking as usual, once 48-hours later after remaining abstinent, and once four weeks later after remaining abstinent. The change in receptor density at each time point will be evaluated. Those in the other populations will have PET scanning done on one occasion within four weeks of screening.	One time within 4 weeks of screening

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA); National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Deepak C D'Souza, MD, Yale University

Publications and helpful links

General Publications

• Ranganathan M, Cortes-Briones J, Radhakrishnan R, Thurnauer H, Planeta B, Skosnik P, Gao H, Labaree D, Neumeister A, Pittman B, Surti T, Huang Y, Carson RE, D'Souza DC. Reduced Brain Cannabinoid Receptor Availability in Schizophrenia. Biol Psychiatry. 2016 Jun 15;79(12):997-1005. doi: 10.1016/j.biopsych.2015.08.021. Epub 2015 Aug 29.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 14, 2012
• First Submitted That Met QC Criteria: November 15, 2012
• First Posted (Estimated): November 21, 2012

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: PTSD; Schizophrenia; Brain Imaging; Control; OUD; Cannabis dependence
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Trauma and Stressor Related Disorders; Narcotic-Related Disorders; Alcoholism; Schizophrenia; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Marijuana Abuse; Opioid-Related Disorders
• Other Study ID Numbers: 1005006735; 1R21DA030702-01A1 (U.S. NIH Grant/Contract); 1R21MH094961-01A1 (U.S. NIH Grant/Contract)