Cannabis, Schizophrenia and Reward: Self-Medication and Agonist Treatment?

NCT01964404 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: D140611R01DA034699-01A1
• Study Type: interventional
• Target: 263
• Locations: 1 country
• Sites: 2

Brief Summary

In this translational research proposal, based on our formulation, we seek to confirm and expand upon data obtained in our pilot study suggesting that cannabis and the cannabinoid agonist dronabinol, given in low dose to patients with schizophrenia and co-occurring cannabis use disorder, will in fact ameliorate the brain reward circuit dysregulation in these patients and, thereby, provide evidence in support of the role of cannabis as a "self-medication" agent for them.

Conditions

Schizophrenia; Dual Diagnosis; Psychotic Disorder; Cannabis Use Disorder

Keywords

Dronabinol; Schizophrenia; Dual Diagnosis; Substance Abuse; Cannabis Use Disorder

Outcome Measures

Primary Outcomes (2)

• Brain Reward Circuit Activation on fMRI Scan

  Activation of the Brain Reward Circuit (particularly the nucleus accumbens) in anticipation of monetary reward. The 'Measure' is a mean of the Fisher-Z transform of the inter-regional correlation measured for each participant between the nucleus accumbens and anterior cingulate cortex. The Fisher-transformation creates a normally distributed correlation value for statistical analyses assessing between group differences. A Fisher-Z transform of '0' represents a value of '0' for the estimated correlation, which represents no correlation in the activity time series between the regions. The values reflect strengths of functional connectivity between brain regions that can be compared between groups (e.g. Healthy controls and SCZ-CUD groups who received different study drugs). Means and standard deviations similar to healthy controls would be considered a good outcome.

  3 hours

• Resting State Connectivity Within the Brain Reward Circuitry

  Resting state connectivity within brain reward circuitry as measured with the Fisher-transformed r value of the connectivity maps between the nucleus accumbans and other brain areas. The Fisher-transformation creates a normally distributed correlation value for statistical analyses assessing between group differences (smoked THC vs placebo; oral dronabinol vs placebo)

  1 hour after smoking study drug, 3 hours after oral dronabinol

Secondary Outcomes (6)

• PANSS Positive Symptoms

  3 hours after oral THC/placebo

• PANSS Negative Symptoms

  3 hours after oral THC/placebo

• Cognitive Functioning, Verbal Learning

  4 hours after oral drug

• Drug Experience, Anxiety

  3 hours after taking oral drug

• Drug Experience Ratings of Drug Liking

  3 hours after taking oral drug

Study Arms (3)

Marijuana cigarette and placebo capsule

EXPERIMENTAL

3-5% tetrahydrocannabinol cannabis cigarette smoked immediately prior to the second functional MRI and a placebo capsule (for dronabinol) by mouth taken approximately 2.75 hours prior to the second functional MRI.

Drug: Marijuana

Dronabinol and placebo cigarette

EXPERIMENTAL

Dronabinol 15mg 3-5% by mouth taken approximately 2.75 hours prior to the second functional MRI and a placebo cigarette (for marijuana) smoked immediately prior to the second functional MRI.

Drug: Dronabinol

Placebo cigarette and placebo capsule

PLACEBO COMPARATOR

Placebo cigarette (for marijuana) smoked immediately prior to the second functional MRI and a placebo capsule (for dronabinol) by mouth taken approximately 2.75 hours prior to the second functional MRI.

Drug: Placebo

Interventions

Marijuana DRUG

Smoked plant with THC

Also known as: Cannabis

Marijuana cigarette and placebo capsule

Dronabinol DRUG

Capsule with THC

Also known as: Marinol

Dronabinol and placebo cigarette

Placebo DRUG

Capsule with no active ingredient

Placebo cigarette and placebo capsule

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Groups 1-3 Participants with schizophrenia and a cannabis use disorder
• Ages 18 - 55 years
• Diagnosis of schizophrenia
• Diagnosis of cannabis abuse or dependence
• Use of cannabis within the month prior to screening
• Willing to remain abstinent for the 14 days before the baseline assessments and throughout the two scans.
• Psychiatrically stable
• Treated with a stable dose of an antipsychotic medication (except clozapine) for the past month
• Not seeking treatment for their cannabis use disorder.
• Group 4 - Control participants with schizophrenia
• Ages 18 - 55 years
• Diagnosis of schizophrenia
• Willing to remain abstinent as described above
• Psychiatrically stable
• Treated with a stable dose of an antipsychotic medication (except clozapine) for the past month

You may not qualify if:

• Groups 1-3 with schizophrenia and a cannabis use disorder
• Positive symptoms of psychosis (\> 4 \[moderate\]) on any item of the Positive and Negative Syndrome Scale psychosis subscale (once abstinent) except for the hallucination item. We will exclude for a rating \> 5 for this item.
• Cocaine/stimulant use disorder
• Pharmacological treatment for addiction
• Mental retardation
• History of head injury
• Metal objects within the body that would contraindicate and MRI
• Pregnancy or currently nursing
• Uncontrolled medical condition
• Taking clozapine
• Any condition that would contraindicate use of cannabis or dronabinol.
• History of a seizure disorder
• Group 4 - Control participants with schizophrenia
• Positive symptoms of psychosis (\> 4 \[moderate\]) on any item of the Positive and Negative Syndrome Scale psychosis subscale (once abstinent) except for the hallucination item. We will exclude for a rating \> 5 for this item.
• Any history of a substance use disorder other than nicotine

Sponsors & Collaborators

• Columbia University: collaborator
• Nathan Kline Institute for Psychiatric Research: collaborator
• University of Vermont: collaborator
• National Institute on Drug Abuse (NIDA): collaborator
• Harvard Medical School (HMS and HSDM): collaborator
• Massachusetts Institute of Technology: collaborator
• Massachusetts General Hospital: collaborator
• Dartmouth-Hitchcock Medical Center: lead

Study Sites (2)

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

University of Vermont

Burlington, Vermont, 05401, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Substance-Related Disorders

Interventions

nabiximols; Dronabinol

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Mary F. Brunette
• Organization: Dartmouth Hitchcock

Mary.F.Brunette@Hitchcock.org

603-646-7019

Study Officials

• Mary F Brunette, MD

  Dartmouth College

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 15, 2013
• First Posted: October 17, 2013
• Study Start: July 1, 2014
• Primary Completion: September 18, 2021
• Study Completion: September 18, 2021
• Last Updated: December 9, 2025
• Results First Posted: December 9, 2025

Record last verified: 2025-10

Locations

US (2)