Effect of Clonazepam on Cannabis Withdrawal and Relapse in Treatment-seeking Patients

Effect of Clonazepam on Cannabis Withdrawal and Relapse in Treatment-seeking Patients: Combined Inpatient/Outpatient Study

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.

Study Overview

• Status: Completed
• Conditions: Cannabis Use Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Clonazepam

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.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Substance Treatment Research Service (STARS) of Columbia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Clonazepam; fixed-flexible daily dose to a maximum of 2 mg (1 mg twice per day) for the first 8 weeks of the trial; Other Names: Klonopin
Placebo Comparator: 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.	Drug: Placebo; Other Names: Matched Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Number of days during 12 weeks of study participation
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	the 7 weeks of study participation or length of participants participation during the medication maintenance phase

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: john mariani, MD, New York Psychiatric Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: September 22, 2016
• First Submitted That Met QC Criteria: September 22, 2016
• First Posted (Estimate): September 26, 2016

Study Record Updates

• Last Update Posted (Actual): August 6, 2021
• Last Update Submitted That Met QC Criteria: July 15, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Treatment; Marijuana
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Modulators; GABA Agents; Anticonvulsants; Clonazepam
• Other Study ID Numbers: 7343; U54DA037842-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No