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SchizophreniaPhase 1NCT01964404

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

A Phase 1 study testing Marijuana and Dronabinol in people with Schizophrenia and Dual Diagnosis, run by Dartmouth-Hitchcock Medical Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Schizophrenia, Dual Diagnosis, Psychotic Disorder
What is being tested?
Marijuana and Dronabinol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
263 participants
Where
2 sitesUnited States
Study dates
Jul 2014to 18 Sep 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
Show all 42Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • University of Vermont

    Burlington, Vermont, 05401

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

Other trials in United States

About this study

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.

Read the detailed description

Substance use disorders are strikingly common in patients with schizophrenia and contribute to its morbidity and cost to society. We have proposed a neurobiological formulation suggesting that cannabis and other substance use in these patients may ameliorate a dysfunction in the brain reward circuit(thus serving a "self-medication" function), while also worsening the symptoms and course of schizophrenia.

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. Also, by also testing the full range of effects produced by dronabinol (effects on brain reward circuitry assessed with task-based function MRI and resting state connectivity), as well as on reward responsiveness, mood, craving, cognition, psychiatric and extrapyramidal symptoms), we will provide clues as to whether dronabinol should be tried in low doses as an adjunctive agent (with an antipsychotic medication) to limit cannabis use in patients with schizophrenia.

This study will involve 8 groups of 25 participants each. Groups 1-3 will have diagnoses of schizophrenia and cannabis use disorder; Group 4 will have schizophrenia only, Groups 5-7 will have cannabis use disorder only and Group 8 will be healthy control participants. Following screening and baseline neuropsychiatric testing, participants will have two tests days (T1 and T2) that will include task-based functional MRI, including assessment of resting state connectivity, and measuring a number of other parameters including reward responsiveness, mood, craving, symptoms and cognition. The assessments at T1 will be virtually the same for all groups. At T2 Groups 1-3, and Groups 5-7 will be randomly assigned to one of the following conditions prior to the assessments: receiving 15mg of dronabinol and smoking a placebo marijuana cigarette, receiving a placebo pill and smoking a real marijuana cigarette, or receiving a placebo pill and smoking a placebo marijuana cigarette. Group 4 and Group 8 will receive no drug or placebo at T2. Participants receiving drug will have safety assessments before the drug is administered, after the drug is administered but before leaving the research clinic for the day, and again a week later.

Being tested
Marijuana, Dronabinol, Placebo
Keywords
Dronabinol, Schizophrenia, Dual Diagnosis, Substance Abuse, Cannabis Use Disorder
Medical subject headings
Schizophrenia, Psychotic Disorders, Substance-Related Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MarijuanaDrug

    Also called Cannabis

    Smoked plant with THC

  • DronabinolDrug

    Also called Marinol

    Capsule with THC

  • PlaceboDrug

    Capsule with no active ingredient

Study groups in NCT01964404
Study groupRoleWhat they receive
Marijuana cigarette and placebo capsuleExperimental3-5% 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.
Receives: Drug: Marijuana
Dronabinol and placebo cigaretteExperimentalDronabinol 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.
Receives: Drug: Dronabinol
Placebo cigarette and placebo capsulePlacebo comparatorPlacebo 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 3 hours

  2. 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)

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

Secondary outcomes (6)
  1. PANSS Positive Symptoms

    Positive and Negative Symptom Scale (PANSS) Positive Symptom Mean Subscale Score at 2nd Assessment Day, range 7-49, higher = more symptoms. The outcome measure was recorded at single time of measurement. The time frame includes 3 hours after oral THC/placebo and 1 hour after smoked THC/placebo (the three-hour window is inclusive of the one-hour post smoke). Each individual smoked THC or placebo AND took oral THC or placebo.

    Measured: 3 hours after oral THC/placebo

  2. PANSS Negative Symptoms

    Positive and Negative Symptom Scale Negative Symptom Mean Subscale Score at 2nd Assessment Day, range 7-49, higher = more symptoms. The time frame includes 3 hours after oral THC/placebo and 1 hour after smoked THC/placebo (the three-hour window is inclusive of the one-hour post smoke). Each individual smoked THC or placebo AND took oral THC or placebo.

    Measured: 3 hours after oral THC/placebo

  3. Cognitive Functioning, Verbal Learning

    Cognitive functioning, verbal learning Hopkins Verbal Learning Test (HVLT-R) total raw score. Possible range of scores is 0-35, higher is better functioning. The time frame includes 4 hours after oral THC/placebo and 2 hour after smoked THC/placebo (the three-hour window is inclusive of the one-hour post smoke). Each individual smoked THC or placebo AND took oral THC or placebo.

    Measured: 4 hours after oral drug

  4. Drug Experience, Anxiety

    Drug experience ratings of mood and desirability, anxiety rating on a scale of 0-100, higher means more anxiety.

    The time frame includes 3 hours after oral THC/placebo and 1 hour after smoked THC/placebo (the three-hour window is inclusive of the one-hour post smoke). Each individual smoked THC or placebo AND took oral THC or placebo.

    Measured: 3 hours after taking oral drug

  5. Drug Experience Ratings of Drug Liking

    Drug experience ratings of liking rating on a scale of 0-100, higher number = more liking

    The time frame includes 3 hours after oral THC/placebo and 1 hour after smoked THC/placebo (the three-hour window is inclusive of the one-hour post smoke). Each individual smoked THC or placebo AND took oral THC or placebo.

    Measured: 3 hours after taking oral drug

  6. Cognitive Function, CPT-IP 2 Digit

    Cognitive function, CPT-IP 2 digit measure of Attention. The Continuous Performance Test-Identical Pairs version (CPT-IP)80 assessed attention with range of 1-5, hirer scores indicating better function

    The outcome measure was recorded at single time of measurement. The time frame includes 4 hours after oral THC/placebo and 2 hour after smoked THC/placebo (the three-hour window is inclusive of the one-hour post smoke). Each individual smoked THC or placebo AND took oral THC or placebo.

    Measured: 4 hours after oral drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2013 (estimated)
  2. Study startJul 2014
  3. Primary completion18 Sep 2021
  4. Study completion18 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
263 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01964404
Sponsor's protocol ID
D14061
Other IDs
1R01DA034699-01A1
Status last verified
Oct 2025
First submitted
15 Oct 2013
Last updated
9 Dec 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Marijuana and Dronabinol in people with Schizophrenia and Dual Diagnosis, run by Dartmouth-Hitchcock Medical Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brain Reward Circuit Activation on fMRI Scan (time frame: 3 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2025.

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