Cannabis Use Disorder
Conditions
Keywords
Marijuana, Treatment
Brief summary
The proposed protocol is a double-blind, placebo-controlled inpatient and outpatient study,looking at the clinical treatment of cannabis use disorder. The treatment study is a total of 12 weeks. There will be two options offered to participants for week 1 of the treatment study. 1) Patient will go inpatient for 5 nights and after discharge from the inpatient phase will complete the 11-weeks of outpatient treatment or 2) patients who cannot complete the inpatient phase due to work or other obligations will complete the treatment 12-week study outpatient. 80 patients seeking treatment for cannabis use disorder will be enrolled into either the inpatient/outpatient or only outpatient study. This combined design will provide a comprehensive understanding of clonazepam's effects on individuals with cannabis use disorder across a range of outcome measures while also testing the medication's ability to prevent relapse in cannabis-abstinent patients.
Detailed description
Patients seeking treatment for Cannabis Use Disorder (CUD) will be enrolled into an inpatient laboratory for 5 nights, where they will be initiated on medication and be assessed for the influence of clonazepam (or placebo) on (1) cannabis withdrawal (mood, sleep, cannabis craving, food intake), ratings associated with medication abuse liability, cognitive performance, and (2) relapse to cannabis use after patients (now abstinent from cannabis) leave the inpatient setting maintained on clonazepam (or placebo) for 8 weeks (with a 4-week, medication-free follow up). This combined design will provide a comprehensive understanding of clonazepam's effects on individuals with cannabis use disorder across a range of outcome measures (safety, abuse liability, withdrawal symptoms) while also testing the medication's ability to prevent relapse in cannabis-abstinent patients. Patient's who are unable to complete the inpatient approach will complete the 12 week trial as an outpatient only.
Interventions
DRUGClonazepam
fixed-flexible daily dose to a maximum of 2 mg (1 mg twice per day) for the first 8 weeks of the trial
DRUGPlacebo
Sponsors
National Institute on Drug Abuse (NIDA)
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Meets DSM 5 criteria for CUD of at least moderate severity (≥ 4 symptoms) and is seeking treatment for cannabis use. * Reports using cannabis a minimum of 5 days per week over the past 28 days and have positive urine test for THC on the day of study entry * 18-65 years of age
Exclusion criteria
* Individuals with a lifetime DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder * Individuals meeting current DSM-5 criteria for any other psychiatric disorder that may, according to the investigator's judgment, require either pharmacological or non-pharmacological intervention over the course of the study. Individuals who are currently stable on a psychotropic medication for at least 3 months may be included if in the investigator's opinion the psychotropic medication is compatible with the study medication (clonazepam). CNS depressants (e.g., benzodiazepines, opioids, adrenergic agonists) and cyp3A4 inhibitors (ketoconazole, some antipsychotics & anticonvulsants) will be exclusionary. * Known history of allergy, intolerance or hypersensitivity to benzodiazepines * Episodic or chronic use of benzodiazepines * Pregnancy, lactation, or failure to use adequate contraceptive methods (condoms, diaphragm, birth control pill, IUD) in female patients who are currently engaging in sexual activity with men. * Unstable medical conditions, such as poorly controlled hypertension, which might make participation hazardous * Participants with a current DSM-5 diagnosis of an alcohol of substance use disorder (abuse or dependence) other than cannabis or nicotine use disorder * Are legally mandated to participate in a substance use disorder treatment program * Increased risk for suicide * Current parole or probation * Recent history of significant violent behavior * History of current of past diagnosis of glaucoma * History of benzodiazepine or other sedative hypnotic use disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Cannabis Use Relapse | Number of days during 12 weeks of study participation | for inpatient participants the number of days till relapse to cannabis use, post inpatient discharge, as recorded on the time line follow-back and confirmed by urine toxicology. |
| Proportion of Cannabis Use Days Per Week | the 7 weeks of study participation or length of participants participation during the medication maintenance phase | for outpatient participants the proportion of cannabis use days per week as recorded by the Timeline Followback method |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clonazepam Clonazepam will be taken twice per day in the morning and in the evening. Clonazepam is given in a fixed flexible dose schedule with the dose titrated to 2mg per day or the maximum tolerated dose. Clonazepam will be taken for the first 8 weeks of the trial.
Clonazepam: fixed-flexible daily dose to a maximum of 2 mg (1 mg twice per day) for the first 8 weeks of the trial | 34 |
| Placebo Placebo will be taken twice per day in the morning and in the evening. Placebo will be taken for the first 8 weeks of the trial.
Placebo | 34 |
| Total | 68 |
Baseline characteristics
| Characteristic | Clonazepam | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 34.9 years STANDARD_DEVIATION 10.4 | 35.9 years STANDARD_DEVIATION 12 | 35.4 years STANDARD_DEVIATION 11.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 3 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 31 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Marijuana Using days in prior 28 days at study start | 27.4 days STANDARD_DEVIATION 1.5 | 27.2 days STANDARD_DEVIATION 1.5 | 27.3 days STANDARD_DEVIATION 1.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 16 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 11 Participants | 16 Participants | 27 Participants |
| Region of Enrollment United States | 34 participants | 34 participants | 68 participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 26 Participants | 28 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 34 |
| other Total, other adverse events | 27 / 34 | 20 / 34 |
| serious Total, serious adverse events | 1 / 34 | 1 / 34 |
Outcome results
Primary
Proportion of Cannabis Use Days Per Week
for outpatient participants the proportion of cannabis use days per week as recorded by the Timeline Followback method
Time frame: the 7 weeks of study participation or length of participants participation during the medication maintenance phase
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clonazepam | Proportion of Cannabis Use Days Per Week | week 3 | 0.71 proportion of use days | Standard Deviation 0.45 |
| Clonazepam | Proportion of Cannabis Use Days Per Week | week 5 | 0.67 proportion of use days | Standard Deviation 0.47 |
| Clonazepam | Proportion of Cannabis Use Days Per Week | week 2 | 0.78 proportion of use days | Standard Deviation 0.41 |
| Clonazepam | Proportion of Cannabis Use Days Per Week | week 6 | 0.58 proportion of use days | Standard Deviation 0.5 |
| Clonazepam | Proportion of Cannabis Use Days Per Week | week 4 | 0.67 proportion of use days | Standard Deviation 0.47 |
| Clonazepam | Proportion of Cannabis Use Days Per Week | week 7 | 0.58 proportion of use days | Standard Deviation 0.5 |
| Clonazepam | Proportion of Cannabis Use Days Per Week | week 1 | 0.74 proportion of use days | Standard Deviation 0.44 |
| Placebo | Proportion of Cannabis Use Days Per Week | week 7 | 0.67 proportion of use days | Standard Deviation 0.47 |
| Placebo | Proportion of Cannabis Use Days Per Week | week 1 | 0.79 proportion of use days | Standard Deviation 0.41 |
| Placebo | Proportion of Cannabis Use Days Per Week | week 2 | 0.75 proportion of use days | Standard Deviation 0.44 |
| Placebo | Proportion of Cannabis Use Days Per Week | week 3 | 0.70 proportion of use days | Standard Deviation 0.46 |
| Placebo | Proportion of Cannabis Use Days Per Week | week 4 | 0.64 proportion of use days | Standard Deviation 0.48 |
| Placebo | Proportion of Cannabis Use Days Per Week | week 5 | 0.64 proportion of use days | Standard Deviation 0.48 |
| Placebo | Proportion of Cannabis Use Days Per Week | week 6 | 0.65 proportion of use days | Standard Deviation 0.48 |
Primary
Time to Cannabis Use Relapse
for inpatient participants the number of days till relapse to cannabis use, post inpatient discharge, as recorded on the time line follow-back and confirmed by urine toxicology.
Time frame: Number of days during 12 weeks of study participation
Population: 11 participants started the study utilizing the inpatient approach
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clonazepam | Time to Cannabis Use Relapse | 1 days |
| Placebo | Time to Cannabis Use Relapse | 1 days |