Cannabis Dependence, Marijuana Dependence
Conditions
Keywords
Cannabis Dependence, Marijuana Dependence, Cannabis Use Disorders, Cannabis Withdrawal, Dronabinol, Clonidine, Schizophrenia
Brief summary
Cannabis use disorders are an important public health problem in the United States, but no effective pharmacotherapies are available to treat these disorders. People with schizophrenia are more likely than healthy people to abuse cannabis. Cannabis use may worsen clinical outcomes in this group, making the identification of pharmacotherapy to treat cannabis dependence in those with schizophrenia important. The investigators intend to test the combination of dronabinol, a cannabinoid agonist, and the α2-adrenergic agonist clonidine, for cannabis dependence in subjects with schizophrenia. The combination of dronabinol and clonidine may alleviate cannabis withdrawal symptoms while allowing treatment-seeking outpatients to benefit from medical management (MM) sessions when they are trying to stop using cannabis. The investigators propose to assess the relationship of dronabinol and clonidine, when added to MM, on cannabis use patterns in cannabis-dependent patients with schizophrenia. Hypothesis: The investigators predict that combination pharmacotherapy of dronabinol and clonidine will significantly reduce cannabis use compared to those receiving placebo.
Detailed description
Subjects will receive either the combination of dronabinol and clonidine or placebo in addition to medical management (MM) over a 10-week treatment period. Following treatment completion, subjects will have follow-up visits until 14 weeks after treatment initiation. This pilot study will evaluate the feasibility of the combination of dronabinol and clonidine for cannabis dependence and will establish effect sizes for a larger trial. Cannabis use disorders are highly prevalent in the United States and rising among high school seniors, making the identification of efficacious treatments for cannabis dependence of critical clinical and public health significance. Schizophrenia is overrepresented among those with cannabis dependence. At the completion of this study, the investigators hope to have improved our understanding of the relationship of the pharmacotherapy combination of dronabinol and clondine on cannabis use.
Interventions
DRUGDronabinol
Dronabinol titrated to 5 mg three times daily
DRUGClonidine
Clonidine 0.1 mg twice daily
DRUGPlacebo
One placebo capsule by mouth twice daily
Sponsors
Brain & Behavior Research Foundation
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Age range 18-45 years 2. DSM-IV diagnosis of cannabis dependence, based on the Structured Clinical Interview for DSM-IV (SCID) 3. DSM-IV diagnosis of schizophrenia or schizoaffective disorder, based on the Structured Clinical Interview for DSM-IV (SCID) 4. express a desire to quit cannabis use within the next 30 days 5. have used cannabis on ≥20 days within the past 30 days (i.e., an average of ≥5 day per week) 6. identify cannabis as their primary drug of abuse; 6) stable on antipsychotic medication for ≥1 month 7. for women of childbearing age, a negative pregnancy test at screening with agreement to use adequate contraception to prevent pregnancy and monthly pregnancy tests 8. consent for us to communicate with their prescribing clinician if one exists 9. furnish the names of 2 locators, who would assist study staff in locating them during the study period 10. live close enough to McLean Hospital to attend study visits 11. plan to stay in the Boston area for the next 3 months 12. are willing and able to sign informed consent.
Exclusion criteria
1. Current diagnosis of other drug or alcohol dependence (excluding nicotine) 2. significant cardiac disease as indicated by history or suspected by abnormal ECG or history of cardiac symptoms 3. Positive and Negative Syndrome Scale (PANSS) subscale for positive symptoms of psychosis item \> 3 (moderate) at baseline evaluation 4. current medical condition that could prevent regular study attendance 5. liver function tests \>3 times the upper limit of normal range 6. history of seizure disorder or history of head trauma or CNS insult that could predispose the subject to seizures 7. taking clozapine 8. current suicidal risk 9. bradycardia less than or equal to 50 bpm, supine blood pressure of less than or equal to 100/65, a seated blood pressure of less than or equal to 90/60, or orthostatic change of \>20 systolic or \>10 diastolic on standing, at screening or any pre-dose assessment, or symptoms attributable to low BP (i.e. lightheadedness or dizziness on standing) 10. mental retardation or organic mental disorder 11. currently in a residential treatment setting in which substance use is monitored and restricted, since the restricted access to drugs could represent an important confounding variable 12. pregnant, nursing, or, if a woman of childbearing potential, not using a form of birth control judged by the investigator to be effective 13. concomitant treatment with opioid analgesics, sedative hypnotics, or other known CNS depressants 14. known hypersensitivity to cannabinoids or sesame oil or clonidine 15. disease of the gastrointestinal system, liver, or kidneys that may impede metabolism or excretion of dronabinol 16. inability to read or write in English that would hinder their ability to follow study procedures 17. history of seizures or a family history of seizures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Cannabis Use at 10 Weeks | At 10 weeks | Subject self-report hits of marijuana per day at week 10 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Craving Symptoms From Baseline at 10 Weeks | At 10 weeks | Scores on the Marijuana Craving Questionnaire (MCQ) (Heishman et al. 2009) - The 4 Factor Total Score. Maximum Score = 84 Minimum Score = 12 The higher the score, the more severe marijuana craving symptoms endorsed by the subject. |
| Change From Baseline in Cannabis Use at 14 Weeks | At 14 weeks | Self-report cannabis use at 14 weeks after initiating the study. |
| Change in Craving Symptoms From Baseline at 14 Weeks | At 14 weeks | Scores on the Marijuana Craving Questionnaire (Heishman et al. 2009) - The 4 Factor Total Score Maximum Score = 84 Minimum Score = 12 The higher the score, the more severe marijuana craving symptoms endorsed by the subject. |
Countries
United States
Participant flow
Recruitment details
7 subjects were randomized for this study out of 12 subjects who were screened for this DCCS study at McLean Hospital
Pre-assignment details
5 subjects that were screened were not randomized. 1 subject stopped using MJ between the screening visit and baseline visit and was thus withdrawn, 2 subjects were no longer interested in the study after screening visit, 1 subject entered in-patient treatment before randomization and 1 screened subject did not meet DSM criteria for MJ dependence
Participants by arm
| Arm | Count |
|---|---|
| Dronabinol + Clonidine Dronabinol titrated to 5 mg three times daily, Clonidine 0.1 mg twice daily
Dronabinol: Dronabinol titrated to 5 mg three times daily
Clonidine: Clonidine 0.1 mg twice daily | 3 |
| Placebo Placebo
Placebo: One placebo capsule by mouth twice daily | 4 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Dronabinol + Clonidine |
|---|---|---|---|
| Age, Continuous | 30.75 years STANDARD_DEVIATION 5.91 | 32.86 years STANDARD_DEVIATION 9.26 | 35.67 years STANDARD_DEVIATION 13.58 |
| Baseline Self-Report MJ Use | 37.4 hits/day STANDARD_DEVIATION 19.32 | 37.3 hits/day STANDARD_DEVIATION 18.63 | 37.16 hits/day STANDARD_DEVIATION 21.92 |
| Marijuana Craving | 55.5 Score on MCQ 4 Factor Total scale STANDARD_DEVIATION 13.33 | 59.57 Score on MCQ 4 Factor Total scale STANDARD_DEVIATION 12.2 | 65 Score on MCQ 4 Factor Total scale STANDARD_DEVIATION 10.15 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 0 / 3 | 1 / 4 |
| serious Total, serious adverse events | 0 / 3 | 0 / 4 |
Outcome results
Primary
Change From Baseline in Cannabis Use at 10 Weeks
Subject self-report hits of marijuana per day at week 10
Time frame: At 10 weeks
Population: Only 2 of the 4 placebo subjects had Week 10 data due to dropping out of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dronabinol + Clonidine | Change From Baseline in Cannabis Use at 10 Weeks | 16.91 hits/day | Standard Deviation 14.57 |
| Placebo | Change From Baseline in Cannabis Use at 10 Weeks | 22.35 hits/day | Standard Deviation 17.47 |
Secondary
Change From Baseline in Cannabis Use at 14 Weeks
Self-report cannabis use at 14 weeks after initiating the study.
Time frame: At 14 weeks
Population: Only 1 of the placebo subjects had week 14 data due to the other week 10 completer not attending the follow-up visit at week 14.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dronabinol + Clonidine | Change From Baseline in Cannabis Use at 14 Weeks | 18.95 hits/day | Standard Deviation 6.69 |
| Placebo | Change From Baseline in Cannabis Use at 14 Weeks | 16.29 hits/day | Standard Deviation 0 |
Secondary
Change in Craving Symptoms From Baseline at 10 Weeks
Scores on the Marijuana Craving Questionnaire (MCQ) (Heishman et al. 2009) - The 4 Factor Total Score. Maximum Score = 84 Minimum Score = 12 The higher the score, the more severe marijuana craving symptoms endorsed by the subject.
Time frame: At 10 weeks
Population: Only 2 of the placebo subjects completed week 10 and had MCQ scores for Week 10.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dronabinol + Clonidine | Change in Craving Symptoms From Baseline at 10 Weeks | 51 score on a MCQ 4 Factor Total scale | Standard Deviation 15.71 |
| Placebo | Change in Craving Symptoms From Baseline at 10 Weeks | 52.33 score on a MCQ 4 Factor Total scale | Standard Deviation 15.04 |
Secondary
Change in Craving Symptoms From Baseline at 14 Weeks
Scores on the Marijuana Craving Questionnaire (Heishman et al. 2009) - The 4 Factor Total Score Maximum Score = 84 Minimum Score = 12 The higher the score, the more severe marijuana craving symptoms endorsed by the subject.
Time frame: At 14 weeks
Population: Only 1 placebo subject completed Week 14 of the study and had Week 14 MCQ Total Score data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dronabinol + Clonidine | Change in Craving Symptoms From Baseline at 14 Weeks | 54.33 score on MCQ Total 4 Factor scale | Standard Deviation 9.29 |
| Placebo | Change in Craving Symptoms From Baseline at 14 Weeks | 56 score on MCQ Total 4 Factor scale | Standard Deviation 0 |