Achieving Cannabis Cessation-Evaluating N-Acetylcysteine Treatment (ACCENT)

Achieving Cannabis Cessation: Evaluating N-Acetylcysteine Treatment (ACCENT)

The primary objective of this study is to evaluate the impact of N-acetylcysteine (NAC) 1200 mg versus matched placebo (PBO) twice daily, added to contingency management (CM), on cannabis use among treatment-seeking cannabis-dependent adults (ages 18-50).

Study Overview

• Status: Completed
• Conditions: Cannabis Dependence
• Intervention / Treatment: Drug: N-Acetylcysteine; Drug: Placebo

Detailed Description

The primary objective of this Phase 3 study is to evaluate the impact of NAC 1200 mg versus matched placebo (PBO) twice daily, added to contingency management (CM), on cannabis use among treatment-seeking cannabis-dependent adults (ages 18-50). After assessment and inclusion into the study, participants will be randomized to receive a 12-week course of NAC 1200 mg or matched placebo twice daily. All participants will concurrently participate in a twice-weekly contingency management (CM) intervention. Medication management will be conducted weekly throughout treatment by the medical clinician. Urine cannabinoid testing will occur at all visits, and will be used as the primary determinant of cannabis use. Participants will return approximately four weeks after treatment conclusion for evaluation of adverse events with medication discontinuation and sustained treatment effects.

• Study Type: Interventional
• Enrollment (Actual): 302
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • UCLA Integrated Substance Abuse Programs
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • APT Foundation, Inc.
  • Kentucky
    • Lexington, Kentucky, United States, 40502
      • University Of Kentucky
  • Oregon
    • Portland, Oregon, United States, 97214
      • CODA, Inc.
  • South Carolina
    • Pickens, South Carolina, United States, 29671
      • Behavioral Health Services of Pickens County
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-50 years
• Must be able to understand the study and provide written informed consent
• Must meet current DSM-IV criteria for cannabis dependence in the last 30 days
• Must express interest in treatment for cannabis dependence
• Must submit a positive urine cannabinoid test during screening
• Women of child bearing potential must agree to use appropriate birth control methods during study participation: oral contraceptives, contraceptive patch, barrier (diaphragm or condom), levonorgestrel implant, medroxyprogesterone acetate, complete abstinence from sexual intercourse, or hormonal contraceptive vaginal ring

Exclusion Criteria:

• Allergy or intolerance to N-Acetylcysteine
• Women who are pregnant or lactating
• Current use of NAC or any supplement containing N-Acetylcysteine (must agree not to take any such supplement throughout study participation)
• Use of carbamazepine or nitroglycerin within 14 days of randomization
• Current enrollment in treatment for cannabis dependence
• Any use of synthetic cannabinoids (such as K2/Spice) in the 30 days prior to screening or during the period between screening and randomization
• Current substance dependence, other than cannabis or nicotine
• Urine drug screen positive for any drug of abuse other than cannabis or amphetamines at the randomization visit (Only participants who have a valid prescription for amphetamines (e.g., for ADHD) may be included)
• Urine drug screen positive for amphetamines at the randomization visit without having a valid prescription for it
• Maintenance treatment with buprenorphine or methadone
• Recent history of asthma (within the last 3 years)
• History of seizure disorder, bipolar disorder, schizophrenia, or other significant or unstable medical or psychiatric illness that may place the participant at increased risk in the judgment of the medical clinician
• Significant risk of homicide or suicide

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NAC plus CM; N-acetylcysteine (NAC) plus Contingency Management (CM)	Drug: N-Acetylcysteine; Study participants randomly assigned to the NAC arm will receive a 12-week course of N-Acetylcysteine (1200mg) twice daily. All participants will concurrently participate in weekly medication management sessions and twice-weekly contingency management interventions.; Other Names: NAC
Placebo Comparator: Placebo plus CM; Placebo plus Contingency Management (CM)	Drug: Placebo; Study participants randomly assigned to the placebo arm will receive a matched placebo twice daily. All participants will concurrently participate in weekly medication management sessions and twice-weekly contingency management interventions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Odds of Negative Urine Cannabinoid Tests During Treatment.	The primary outcome is the abstinence rate over the 12 weeks of treatment. Abstinence is based on a weekly urine drug screen confirmed by central laboratory testing and defined as a negative cannabinoid result.	study weeks 2-13

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Kevin M Gray, MD, Associate Professor, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina

Publications and helpful links

General Publications

• McClure EA, Sonne SC, Winhusen T, Carroll KM, Ghitza UE, McRae-Clark AL, Matthews AG, Sharma G, Van Veldhuisen P, Vandrey RG, Levin FR, Weiss RD, Lindblad R, Allen C, Mooney LJ, Haynes L, Brigham GS, Sparenborg S, Hasson AL, Gray KM. Achieving cannabis cessation -- evaluating N-acetylcysteine treatment (ACCENT): design and implementation of a multi-site, randomized controlled study in the National Institute on Drug Abuse Clinical Trials Network. Contemp Clin Trials. 2014 Nov;39(2):211-23. doi: 10.1016/j.cct.2014.08.011. Epub 2014 Aug 30.
• Borodovsky JT, Sofis MJ, Sherman BJ, Gray KM, Budney AJ. Characterizing cannabis use reduction and change in functioning during treatment: Initial steps on the path to new clinical endpoints. Psychol Addict Behav. 2022 Aug;36(5):515-525. doi: 10.1037/adb0000817. Epub 2022 Jan 27.
• Sherman BJ, Sofis MJ, Borodovsky JT, Gray KM, McRae-Clark AL, Budney AJ. Evaluating cannabis use risk reduction as an alternative clinical outcome for cannabis use disorder. Psychol Addict Behav. 2022 Aug;36(5):505-514. doi: 10.1037/adb0000760. Epub 2021 Jul 1.
• Tomko RL, Baker NL, Hood CO, Gilmore AK, McClure EA, Squeglia LM, McRae-Clark AL, Sonne SC, Gray KM. Depressive symptoms and cannabis use in a placebo-controlled trial of N-Acetylcysteine for adult cannabis use disorder. Psychopharmacology (Berl). 2020 Feb;237(2):479-490. doi: 10.1007/s00213-019-05384-z. Epub 2019 Nov 11.
• Hser YI, Mooney LJ, Huang D, Zhu Y, Tomko RL, McClure E, Chou CP, Gray KM. Reductions in cannabis use are associated with improvements in anxiety, depression, and sleep quality, but not quality of life. J Subst Abuse Treat. 2017 Oct;81:53-58. doi: 10.1016/j.jsat.2017.07.012. Epub 2017 Jul 29.
• Gray KM, Sonne SC, McClure EA, Ghitza UE, Matthews AG, McRae-Clark AL, Carroll KM, Potter JS, Wiest K, Mooney LJ, Hasson A, Walsh SL, Lofwall MR, Babalonis S, Lindblad RW, Sparenborg S, Wahle A, King JS, Baker NL, Tomko RL, Haynes LF, Vandrey RG, Levin FR. A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults. Drug Alcohol Depend. 2017 Aug 1;177:249-257. doi: 10.1016/j.drugalcdep.2017.04.020. Epub 2017 Jun 10.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: August 19, 2012
• First Submitted That Met QC Criteria: August 27, 2012
• First Posted (Estimate): August 30, 2012

Study Record Updates

• Last Update Posted (Actual): May 24, 2018
• Last Update Submitted That Met QC Criteria: April 23, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: CTN-0053; U10DA013732 (U.S. NIH Grant/Contract); UG1DA013727 (U.S. NIH Grant/Contract); U10DA013727 (U.S. NIH Grant/Contract); U10DA013045 (U.S. NIH Grant/Contract); U10DA015815 (U.S. NIH Grant/Contract); U10DA015831 (U.S. NIH Grant/Contract); U10DA020024 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The lead investigator will submit coded individual level data on Clinical Trials Network (CTN) study participants to the Data Management Center contracted by NIDA Center for CTN. These data may include but are not limited to: demographic information, date of birth, medical history, substance use history, psychiatric history, objective measures of substance use and psychiatric status, HIV status and genetic information. Data will be submitted without information that could readily identify the study participant (i.e. We will not share medical record numbers, social security numbers or participant names or phone numbers with the Data Management Center). De-identified data will be made publicly available per the CTN's policies.