Cannabis Use Disorder, Dual Diagnosis, Psychotic Disorder, Schizophrenia
Conditions
Keywords
Dronabinol, Schizophrenia, Dual Diagnosis, Substance Abuse, Cannabis Use Disorder
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.
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.
Interventions
DRUGMarijuana
Smoked plant with THC
DRUGDronabinol
Capsule with THC
DRUGPlacebo
Capsule with no active ingredient
Sponsors
Columbia University
Harvard Medical School (HMS and HSDM)
Massachusetts Institute of Technology
Massachusetts General Hospital
Nathan Kline Institute for Psychiatric Research
University of Vermont
National Institute on Drug Abuse (NIDA)
Dartmouth-Hitchcock Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Groups 1-3 Participants with schizophrenia and a cannabis use disorder 1. Ages 18 - 55 years 2. Diagnosis of schizophrenia 3. Diagnosis of cannabis abuse or dependence 4. Use of cannabis within the month prior to screening 5. Willing to remain abstinent for the 14 days before the baseline assessments and throughout the two scans. 6. Psychiatrically stable 7. Treated with a stable dose of an antipsychotic medication (except clozapine) for the past month 8. Not seeking treatment for their cannabis use disorder. Group 4 - Control participants with schizophrenia 1. Ages 18 - 55 years 2. Diagnosis of schizophrenia 3. Willing to remain abstinent as described above 4. Psychiatrically stable 5. Treated with a stable dose of an antipsychotic medication (except clozapine) for the past month Groups 5-7 - Control participants with cannabis use disorder 1. Ages 18 - 55 years 2. Diagnosis of cannabis abuse or dependence 3. Use of cannabis within the month prior to screening 4. Willing to remain abstinent as described above 5. Not seeking treatment for their cannabis use disorder. Group 8 - Healthy control participants 1. Ages 18 - 55 years 2. Willing to remain abstinent as described above
Exclusion criteria
Groups 1-3 with schizophrenia and a cannabis use disorder 1. 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. 2. Cocaine/stimulant use disorder 3. Pharmacological treatment for addiction 4. Mental retardation 5. History of head injury 6. Metal objects within the body that would contraindicate and MRI 7. Pregnancy or currently nursing 8. Uncontrolled medical condition 9. Taking clozapine 10. Any condition that would contraindicate use of cannabis or dronabinol. 11. History of a seizure disorder Group 4 - Control participants with schizophrenia 1. 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. 2. Any history of a substance use disorder other than nicotine 3. Pharmacological treatment for addiction 4. Mental retardation 5. History of head injury 6. Metal objects within the body that would contraindicate and MRI 7. Pregnancy or currently nursing 8. Uncontrolled medical condition 9. Taking clozapine Groups 5-7 - Control participants with cannabis use disorder 1. Axis I psychiatric diagnosis other than a cannabis use disorder 2. Taking any psychotropic medication 3. Pharmacological treatment for addiction 4. Mental retardation 5. History of head injury 6. Metal objects within the body that would contraindicate and MRI 7. Pregnancy or currently nursing 8. Uncontrolled medical condition 9. History of a seizure disorder Group 8 - Healthy control participants 1. Any Axis I psychiatric diagnosis 2. Taking any psychotropic medication 3. Pharmacological treatment for addiction 4. Mental retardation 5. History of head injury 6. Metal objects within the body that would contraindicate and MRI 7. Pregnancy or currently nursing 8. Uncontrolled medical condition 9. Current tobacco smokers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain Reward Circuit Activation on fMRI Scan | 3 hours | 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. |
| Resting State Connectivity Within the Brain Reward Circuitry | 1 hour after smoking study drug, 3 hours after oral dronabinol | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PANSS Positive Symptoms | 3 hours after oral THC/placebo | 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. |
| PANSS Negative Symptoms | 3 hours after oral THC/placebo | 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. |
| Cognitive Functioning, Verbal Learning | 4 hours after oral drug | 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. |
| Drug Experience, Anxiety | 3 hours after taking oral drug | 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. |
| Drug Experience Ratings of Drug Liking | 3 hours after taking oral drug | 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. |
| Cognitive Function, CPT-IP 2 Digit | 4 hours after oral drug | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Marijuana Cigarette and Placebo Capsule SCZ-CUD 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.
Marijuana: Smoked plant with THC | 11 |
| Dronabinol and Placebo Cigarette SCZ-CUD 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.
Dronabinol: Capsule with THC | 12 |
| Placebo Cigarette and Placebo Capsule. SCZ-CUD 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.
Placebo: Capsule with no active ingredient | 11 |
| SCZ-CUD Not Randomized Dual diagnosis of Schizophrenia and Cannabis Use disorder, - Completed Scan 1 but not Randomized | 8 |
| Marijuana Cigarette and Placebo Capsule CUD Only CUD only 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.
Marijuana: Smoked plant | 17 |
| Dronabinol and Placebo Cigarette CUD Only CUD only 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. | 17 |
| Placebo Cigarette and Placebo Capsule CUD Only CUD only 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. | 17 |
| Cannabis Use Disorder - CUD Did Not Randomize Cannabis Use Disorder (CUD), Completed Scan 1 but not Randomized | 10 |
| SCZ Only No drug intervention - Completed Scan 1 and 2 | 18 |
| SCZ Only - Did Not Complete Scan 2 No drug intervention - Completed Scan 1 but not Scan 2 | 3 |
| Healthy Control - No drug intervention - Completed Scan 1 and 2 | 27 |
| Healthy Control - Did Not Complete Scan 2 No drug intervention - Completed Scan 1 but not Scan 2 | 4 |
| Total | 155 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Pre-Randomization - Scan 1 | Screen Fail | 49 | 36 | 12 | 9 | 0 | 0 | 0 | 0 | 0 | 0 |
| Pre-Randomization - Scan 1 | Withdrawal by Subject | 8 | 8 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Marijuana Cigarette and Placebo Capsule SCZ-CUD | Dronabinol and Placebo Cigarette SCZ-CUD | Placebo Cigarette and Placebo Capsule. SCZ-CUD | SCZ-CUD Not Randomized | Marijuana Cigarette and Placebo Capsule CUD Only | Dronabinol and Placebo Cigarette CUD Only | Placebo Cigarette and Placebo Capsule CUD Only | Cannabis Use Disorder - CUD Did Not Randomize | SCZ Only | SCZ Only - Did Not Complete Scan 2 | Healthy Control - | Healthy Control - Did Not Complete Scan 2 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.00 Years | 28.42 Years | 31.55 Years | 26.75 Years | 43.59 Years | 34.29 Years | 31.53 Years | 34.10 Years | 35.55 Years | 29.66 Years | 33.48 Years | 26.5 Years | 32.59 Years |
| Days of Cannabis Use in Past 35 | 10.73 Days STANDARD_DEVIATION 9.3 | 16.92 Days STANDARD_DEVIATION 10.1 | 16.64 Days STANDARD_DEVIATION 10.96 | 18.25 Days STANDARD_DEVIATION 14.76 | 29.76 Days STANDARD_DEVIATION 10.14 | 25.18 Days STANDARD_DEVIATION 12.86 | 24.24 Days STANDARD_DEVIATION 11.55 | 28.2 Days STANDARD_DEVIATION 10.35 | 0 Days STANDARD_DEVIATION 0 | 0 Days STANDARD_DEVIATION 0 | 0.037 Days STANDARD_DEVIATION 0.192 | 0.5 Days STANDARD_DEVIATION 1 | 14.85 Days STANDARD_DEVIATION 15.54 |
| Education, years | 12.45 Years STANDARD_DEVIATION 1.695 | 13.92 Years STANDARD_DEVIATION 1.782 | 13.82 Years STANDARD_DEVIATION 1.722 | 12.75 Years STANDARD_DEVIATION 1.165 | 14.12 Years STANDARD_DEVIATION 1.764 | 14.35 Years STANDARD_DEVIATION 2.548 | 14.35 Years STANDARD_DEVIATION 1.967 | 12.8 Years STANDARD_DEVIATION 1.033 | 13.33 Years STANDARD_DEVIATION 1.847 | 12 Years STANDARD_DEVIATION 1 | 17.19 Years STANDARD_DEVIATION 1.777 | 14.67 Years STANDARD_DEVIATION 1.155 | 14.28 Years STANDARD_DEVIATION 2.304 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 11 Participants | 10 Participants | 8 Participants | 17 Participants | 16 Participants | 17 Participants | 10 Participants | 18 Participants | 3 Participants | 27 Participants | 4 Participants | 152 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of Joints Smoked in Past 35 days | 18.41 Number of Joints STANDARD_DEVIATION 26.99 | 22.19 Number of Joints STANDARD_DEVIATION 18.82 | 19.70 Number of Joints STANDARD_DEVIATION 16.01 | 44.09 Number of Joints STANDARD_DEVIATION 62.2 | 39.4 Number of Joints STANDARD_DEVIATION 45.3 | 52.2 Number of Joints STANDARD_DEVIATION 78.6 | 52.2 Number of Joints STANDARD_DEVIATION 57.5 | 44.8 Number of Joints STANDARD_DEVIATION 51.2 | 0 Number of Joints STANDARD_DEVIATION 0 | 0 Number of Joints STANDARD_DEVIATION 0 | 0.0357 Number of Joints STANDARD_DEVIATION 0.188 | 0.333 Number of Joints STANDARD_DEVIATION 0.577 | 26.01 Number of Joints STANDARD_DEVIATION 43.45 |
| PANSS Negative | 15.82 units on a scale STANDARD_DEVIATION 8.34 | 12.0 units on a scale STANDARD_DEVIATION 4.41 | 15.09 units on a scale STANDARD_DEVIATION 7.91 | 13.63 units on a scale STANDARD_DEVIATION 3.54 | — | — | — | — | 14.61 units on a scale STANDARD_DEVIATION 3.96 | 17.66 units on a scale STANDARD_DEVIATION 6.81 | — | — | 14.19 units on a scale STANDARD_DEVIATION 5.6 |
| PANSS Positive | 12.09 units on a scale STANDARD_DEVIATION 3.91 | 12.83 units on a scale STANDARD_DEVIATION 3.74 | 12.82 units on a scale STANDARD_DEVIATION 3.34 | 15.88 units on a scale STANDARD_DEVIATION 4.88 | — | — | — | — | 13.11 units on a scale STANDARD_DEVIATION 3.31 | 15.0 units on a scale STANDARD_DEVIATION 2.65 | — | — | 13.01 units on a scale STANDARD_DEVIATION 3.73 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 9 Participants | 10 Participants | 9 Participants | 8 Participants | 16 Participants | 15 Participants | 15 Participants | 7 Participants | 17 Participants | 3 Participants | 23 Participants | 3 Participants | 135 Participants |
| Schizophrenia, schizoaffective diagnosis Schizoaffective disorder | 8 participants | 8 participants | 7 participants | 2 participants | 0 participants | 0 participants | 0 participants | 0 participants | 9 participants | 2 participants | 0 participants | 0 participants | 36 participants |
| Schizophrenia, schizoaffective diagnosis Schizophrenia disorder | 3 participants | 4 participants | 4 participants | 6 participants | 0 participants | 0 participants | 0 participants | 0 participants | 9 participants | 1 participants | 0 participants | 0 participants | 27 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 7 Participants | 1 Participants | 8 Participants | 2 Participants | 35 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 10 Participants | 5 Participants | 14 Participants | 15 Participants | 15 Participants | 9 Participants | 11 Participants | 2 Participants | 19 Participants | 2 Participants | 120 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 | 0 / 11 | 0 / 8 | 0 / 17 | 0 / 17 | 0 / 17 | 0 / 10 | 0 / 18 | 0 / 3 | 0 / 27 | 0 / 4 |
| other Total, other adverse events | 9 / 11 | 9 / 12 | 8 / 11 | 2 / 8 | 14 / 17 | 10 / 17 | 14 / 17 | 5 / 10 | 13 / 18 | 3 / 3 | 14 / 27 | 0 / 4 |
| serious Total, serious adverse events | 1 / 11 | 0 / 12 | 1 / 11 | 1 / 8 | 0 / 17 | 0 / 17 | 0 / 17 | 1 / 10 | 2 / 18 | 0 / 3 | 0 / 27 | 0 / 4 |
Outcome results
Primary
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.
Time frame: 3 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Marijuana cigarette and placebo capsule SCZ-CUD | Brain Reward Circuit Activation on fMRI Scan | 0.05 z-score | Standard Deviation 0.098 |
| Dronabinol and placebo cigarette. SCZ-CUD | Brain Reward Circuit Activation on fMRI Scan | 0.14 z-score | Standard Deviation 0.076 |
| Placebo cigarette and placebo capsule. SCZ-CUD | Brain Reward Circuit Activation on fMRI Scan | 0.18 z-score | Standard Deviation 0.127 |
| Marijuana cigarette and placebo capsule CUD only | Brain Reward Circuit Activation on fMRI Scan | 0.12 z-score | Standard Deviation 0.058 |
| Dronabinol and placebo cigarette CUD only | Brain Reward Circuit Activation on fMRI Scan | 0.10 z-score | Standard Deviation 0.087 |
| Placebo cigarette and placebo capsule. CUD only | Brain Reward Circuit Activation on fMRI Scan | 0.11 z-score | Standard Deviation 0.081 |
| SCZ only | Brain Reward Circuit Activation on fMRI Scan | 0.17 z-score | Standard Deviation 0.094 |
| Healthy Controls | Brain Reward Circuit Activation on fMRI Scan | 0.17 z-score | Standard Deviation 0.121 |
p-value: 0.87t-test, 2 sided
Primary
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)
Time frame: 1 hour after smoking study drug, 3 hours after oral dronabinol
Population: Data was collected but cannot be compiled and analysis could not be completed due to death of PI and resulting limited resources for scan data compilation and analyses. There are no immediate resources for analysis in the future.
Secondary
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.
Time frame: 4 hours after oral drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Marijuana cigarette and placebo capsule SCZ-CUD | Cognitive Function, CPT-IP 2 Digit | 3.5 score on a scale | Standard Deviation 0.7 |
| Dronabinol and placebo cigarette. SCZ-CUD | Cognitive Function, CPT-IP 2 Digit | 3.3 score on a scale | Standard Deviation 0.9 |
| Placebo cigarette and placebo capsule. SCZ-CUD | Cognitive Function, CPT-IP 2 Digit | 3.7 score on a scale | Standard Deviation 0.7 |
| Marijuana cigarette and placebo capsule CUD only | Cognitive Function, CPT-IP 2 Digit | 4.1 score on a scale | Standard Deviation 0.4 |
| Dronabinol and placebo cigarette CUD only | Cognitive Function, CPT-IP 2 Digit | 3.8 score on a scale | Standard Deviation 0.5 |
| Placebo cigarette and placebo capsule. CUD only | Cognitive Function, CPT-IP 2 Digit | 3.9 score on a scale | Standard Deviation 0.4 |
| SCZ only | Cognitive Function, CPT-IP 2 Digit | 3.2 score on a scale | Standard Deviation 1 |
| Healthy Controls | Cognitive Function, CPT-IP 2 Digit | 4.0 score on a scale | Standard Deviation 0.3 |
p-value: 0.00295% CI: [-1, -0.23]Regression, Linear
Secondary
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.
Time frame: 4 hours after oral drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Marijuana cigarette and placebo capsule SCZ-CUD | Cognitive Functioning, Verbal Learning | 23.2 score on a scale | Standard Deviation 6.8 |
| Dronabinol and placebo cigarette. SCZ-CUD | Cognitive Functioning, Verbal Learning | 21.8 score on a scale | Standard Deviation 6.7 |
| Placebo cigarette and placebo capsule. SCZ-CUD | Cognitive Functioning, Verbal Learning | 25.0 score on a scale | Standard Deviation 5 |
| Marijuana cigarette and placebo capsule CUD only | Cognitive Functioning, Verbal Learning | 25.0 score on a scale | Standard Deviation 4.97 |
| Dronabinol and placebo cigarette CUD only | Cognitive Functioning, Verbal Learning | 25.3 score on a scale | Standard Deviation 6.1 |
| Placebo cigarette and placebo capsule. CUD only | Cognitive Functioning, Verbal Learning | 27.9 score on a scale | Standard Deviation 4.5 |
| SCZ only | Cognitive Functioning, Verbal Learning | 25.5 score on a scale | Standard Deviation 8.6 |
| Healthy Controls | Cognitive Functioning, Verbal Learning | 31.0 score on a scale | Standard Deviation 3.3 |
Comparison: This analysis tested whether the dronabinol group had different verbal learning scores compared to the placebo group adjusting for the SCZ only group. (The marijuana cigarette group was tested separately per our analytic plan.)p-value: 0.00495% CI: [-16.06, -3.18]Regression, Linear
Secondary
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.
Time frame: 3 hours after taking oral drug
Population: Only participants with Schizophrenia and CUD who were given study drug were analyzed for drug experiences, as specified in the Study Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Marijuana cigarette and placebo capsule SCZ-CUD | Drug Experience, Anxiety | 10.03 units on a scale | Standard Deviation 4.64 |
| Dronabinol and placebo cigarette. SCZ-CUD | Drug Experience, Anxiety | 3.88 units on a scale | Standard Deviation 2.06 |
| Placebo cigarette and placebo capsule. SCZ-CUD | Drug Experience, Anxiety | 3.96 units on a scale | Standard Deviation 2.3 |
| Marijuana cigarette and placebo capsule CUD only | Drug Experience, Anxiety | 14.31 units on a scale | Standard Deviation 4.72 |
Comparison: This analysis tested whether the marijuana cigarette group had different anxiety scores compared to the placebo group adjusting for the SCZ only group. (The dronabinol group was tested separately per our analytic plan.)p-value: 0.2295% CI: [-3.62, 15.75]Regression, Linear
Comparison: This analysis tested whether the dronabinol group had different anxiety scores compared to the placebo group adjusting for the SCZ only group. (The dronabinol group was tested separately per our analytic plan.)p-value: 0.9895% CI: [-5.87, 5.7]Regression, Linear
Secondary
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.
Time frame: 3 hours after taking oral drug
Population: Only participants with Schizophrenia and CUD who were given study drug were analyzed for drug experiences, as specified in the Study Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Marijuana cigarette and placebo capsule SCZ-CUD | Drug Experience Ratings of Drug Liking | 56.5 units on a scale | Standard Error 21.66 |
| Dronabinol and placebo cigarette. SCZ-CUD | Drug Experience Ratings of Drug Liking | 56.36 units on a scale | Standard Error 20.1 |
| Placebo cigarette and placebo capsule. SCZ-CUD | Drug Experience Ratings of Drug Liking | 5.54 units on a scale | Standard Error 3.49 |
Comparison: This analysis tested whether the dronabinol group had different drug experience ratings of liking scores compared to the placebo group. (The marijuana cigarette group was tested separately per our analytic plan.)p-value: 0.1395% CI: [10.9, 90.9]ANOVA
Comparison: This analysis tested whether the marijuana cigarette group had different drug liking scores compared to the placebo group. (The dronabinol group was tested separately per our analytic plan.)p-value: 0.00295% CI: [8.01, 94.07]Regression, Linear
Secondary
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.
Time frame: 3 hours after oral THC/placebo
Population: This analysis tested whether the marijuana cigarette group had different PANSS negative symptom scores compared to the placebo group adjusting for the SCZ only group. (The dronabinol group was tested separately per our analytic plan.). Only participants with Schizophrenia were assessed using the Positive and Negative Symptom Scale, as specified in the Study Protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Marijuana cigarette and placebo capsule SCZ-CUD | PANSS Negative Symptoms | 17.1 score on a scale | Standard Error 0.76 |
| Dronabinol and placebo cigarette. SCZ-CUD | PANSS Negative Symptoms | 16.4 score on a scale | Standard Error 0.67 |
| Placebo cigarette and placebo capsule. SCZ-CUD | PANSS Negative Symptoms | 15.8 score on a scale | Standard Error 0.81 |
| Marijuana cigarette and placebo capsule CUD only | PANSS Negative Symptoms | 15.2 score on a scale | Standard Error 0.56 |
Comparison: This analysis tested whether the marijuana cigarette group had different PANSS Negative symptom scores compared to the placebo group adjusting for the SCZ only group. (The dronabinol group was tested separately per our analytic plan.)p-value: 0.2895% CI: [-1, 3.45]ANOVA
Comparison: This analysis tested whether the dronabinol group had different PANSS Positive negative scores compared to the placebo group adjusting for the SCZ only group. (The dronabinol group was tested separately per our analytic plan.)p-value: 0.3995% CI: [-1.1, 2.85]ANOVA
Secondary
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.
Time frame: 3 hours after oral THC/placebo
Population: Only participants with Schizophrenia were assessed using the Positive and Negative Symptom Scale, as specified in the Study Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Marijuana cigarette and placebo capsule SCZ-CUD | PANSS Positive Symptoms | 11.0 score on a scale | Standard Error 0.54 |
| Dronabinol and placebo cigarette. SCZ-CUD | PANSS Positive Symptoms | 9.3 score on a scale | Standard Error 0.4 |
| Placebo cigarette and placebo capsule. SCZ-CUD | PANSS Positive Symptoms | 10.2 score on a scale | Standard Error 0.56 |
| Marijuana cigarette and placebo capsule CUD only | PANSS Positive Symptoms | 10.6 score on a scale | Standard Error 0.37 |
Comparison: This analysis tested whether the marijuana cigarette group had different PANSS Positive symptom scores compared to the placebo group adjusting for the SCZ only group. (The dronabinol group was tested separately per our analytic plan.)p-value: 0.3195% CI: [-0.77, 2.4]ANOVA
Comparison: This analysis tested whether the dronabinol group had different PANSS Positive symptom scores compared to the placebo group adjusting for the SCZ only group. (The marijuana cigarette group was tested separately per our analytic plan.)p-value: 0.6295% CI: [-2.4, 0.18]ANOVA