Phase 1 N=263 Randomized Quadruple-blind Basic Science

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

Schizophrenia · Dual Diagnosis · Psychotic Disorder · Cannabis Use Disorder

Bottom Line

View on ClinicalTrials.gov: NCT01964404 ↗

Enrolled (actual)

263

Serious AEs

3.9%

Results posted

Dec 2025

Primary outcome: Primary: Brain Reward Circuit Activation on fMRI Scan — 0.05; 0.14; 0.18; 0.12 z-score — p=0.87

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: Marijuana (Drug); Dronabinol (Drug); Placebo (Drug)
Age: Adult · 18+ yrs
Sex: All
Sponsor: Dartmouth-Hitchcock Medical Center
Primary completion: Sep 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Brain Reward Circuit Activation on fMRI Scan	0.05; 0.14; 0.18; 0.12; 0.10; 0.11	0.87
PRIMARY Resting State Connectivity Within the Brain Reward Circuitry	—	—
SECONDARY PANSS Positive Symptoms	11.0; 9.3; 10.2; 10.6	0.31
SECONDARY PANSS Negative Symptoms	17.1; 16.4; 15.8; 15.2	0.28
SECONDARY Cognitive Functioning, Verbal Learning	23.2; 21.8; 25.0; 25.0; 25.3; 27.9	0.004 sig
SECONDARY Drug Experience, Anxiety	10.03; 3.88; 3.96; 14.31	.22
SECONDARY Drug Experience Ratings of Drug Liking	56.5; 56.36; 5.54	0.13
SECONDARY Cognitive Function, CPT-IP 2 Digit	3.5; 3.3; 3.7; 4.1; 3.8; 3.9	0.002 sig

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.

Eligibility Criteria

Inclusion Criteria

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

Groups 5-7 - Control participants with cannabis use disorder

Ages 18 - 55 years
Diagnosis of cannabis abuse or dependence
Use of cannabis within the month prior to screening
Willing to remain abstinent as described above
Not seeking treatment for their cannabis use disorder.

Group 8 - Healthy control participants

Ages 18 - 55 years
Willing to remain abstinent as described above

Exclusion criteria

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
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

Groups 5-7 - Control participants with cannabis use disorder

Axis I psychiatric diagnosis other than a cannabis use disorder
Taking any psychotropic medication
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
History of a seizure disorder

Group 8 - Healthy control participants

Any Axis I psychiatric diagnosis
Taking any psychotropic medication
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
Current tobacco smokers

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01964404). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.