Extended Effects of Cannabis Abstinence on Clinical Symptoms and Cognition in Depression

Effects of Extended Cannabis Abstinence on Clinical and Cognitive Outcomes in Patients with Co-Morbid Major Depressive and Cannabis Use Disorders

The prevalence of major depressive disorder (MDD) is ~5.0%, and rates of co-occurring SUDs in these patients approach 40-50%. Specifically, rates of co-morbid cannabis use disorder (CUD) in patients with MDD are elevated 2-3 fold compared to 2.9% in the general population, and is associated with poorer treatment outcomes and impaired cognitive and psychosocial functioning in comparison to MDD patients without CUD. Most studies of cannabis use in MDD are cross-sectional in design, and therefore causal relationships are unclear. This study investigates the effects of cannabis abstinence over a 28-day period in patients with MDD with co-occurring CUD using a randomized controlled design, namely contingent reinforcement.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Impairment; Major Depressive Disorder; Cannabis Use
• Intervention / Treatment: Behavioral: Non-Contingency Reinforcement; Behavioral: Contingency Reinforcement

Detailed Description

The prevalence of major depressive disorder (MDD) is ~5.0%, and rates of co-occurring SUDs in these patients approach 40-50%. Specifically, rates of co-morbid cannabis use disorder (CUD) in patients with MDD are elevated 2-3 fold compared to 2.9% in the general population, and is associated with poorer treatment outcomes and impaired cognitive and psychosocial functioning in comparison to MDD patients without CUD. To date, most studies of cannabis use in MDD were cross-sectional in design, and therefore causal relationships are unclear. The investigators previous studies in cannabis dependent patients with schizophrenia suggest that extended cannabis abstinence (up to 28 days) using contingent reinforcement is associated with improvements in specific areas of cognition (e.g. verbal learning and memory) and depressive symptoms. A more recent study using an open-label design demonstrated that 28 days of cannabis abstinence improves depressive symptoms and anhedonia in participants (N=11) with co-occurring MDD and CUD.

The investigators propose a controlled cannabis abstinence paradigm in patients with co-morbid MDD and CUD (N=52) to further investigate these findings. Stabilized MDD patients with moderate to severe CUD will be randomly assigned to one of two groups: 1) A contingent reinforcement (CR) intervention (n=26); 2) a non-contingent reinforcement (NCR) intervention (n=26), which will serve as a time and non-abstinence control. In the CR group, subjects achieving biochemically-verified cannabis abstinence at study endpoint (Day 28) will receive a $300 contingent payment; participants in the NCR group will not receive this contingent payment. The primary outcomes are: 1) cannabis abstinence rates at Day 28 in CR versus NCR groups; 2) changes in mood (depressive), anxiety and sleep symptoms over the 28-day assessment period. Secondary outcomes include cognition.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maryam Sorkhou, HBSc; Phone Number: 36225 4165358501; Email: maryam.sorkhou@mail.utoronto.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 1R8
      • Recruiting
      • Centre for Addiction and Mental Health
      • Contact: Tony P George, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All participants must be between the ages 18-55
• Meet SCID for DSM-5 diagnostic criteria for cannabis use disorder, moderate to severe
• Meet SCID for DSM-5 diagnostic criteria for Major Depressive Disorder
• Be an outpatient receiving a stable dose of antidepressant medication for at least three months (to ensure stability of depressive symptoms
• Have a Hamilton Depression Rating Scale (HDRS-17) at baseline assessment in the range of 12-25..
• Have a Full-Scale IQ ≥ 80 as determined by the WTAR
• Be a non-treatment seeking cannabis user
• Evidence of sufficient motivation and effort as measured by a Test of Memory Malingering (TOMM) score ≥ 45.

Exclusion Criteria:

• Meets criteria for substance use disorder of alcohol or other illicit substances within the past 6 months (with the exception of cannabis, nicotine, or caffeine)
• Positive urine screen for illicit substances other than cannabis, nicotine, or caffeine
• Current suicidal or homicidal ideation
• Psychotic disorder diagnosis (e.g. schizoaffective disorder, major depression with psychotic features) as determined by the SCID
• Treatment seeking for cannabis use
• Meet SCID for DSM-5 diagnostic criteria for Bipolar Disorder
• Head Injury> 5 minutes LOC
• Exceed upper and lower cut-offs on HSRD-17 (See Inclusion Criteria)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Non-Contingency Reinforcement Group; Subjects assigned to the NCR group with self-reported abstinence verified by urinary THC-COOH level <20 ng/ml will not receive contingency monetary reinforcement at Day 28 of the study.	Behavioral: Non-Contingency Reinforcement; Subjects will be randomly assigned on a 1:1 ratio to either the Contingency Reinforcement or Non-Contingency Reinforcement Intervention prior to their in-person screening visit.
Experimental: Contingency Reinforcement Group; Subjects assigned to the CR group with self-reported abstinence verified by urinary THC-COOH level <20 ng/ml will receive contingency monetary reinforcement at Day 28 of the study.	Behavioral: Contingency Reinforcement; Subjects will be randomly assigned on a 1:1 ratio to either the Contingency Reinforcement or Non-Contingency Reinforcement Intervention prior to their in-person screening visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Depressive Symptomology from Baseline to Week 4	The Hamilton Depression Rating Scale will be administered to assess severity of depressive symptoms. [Min score = 0, Max score = 52; Higher scores evince more severe symptomology]	[Time Frame: Weekly (Day 0, Day 7, Day 14, Day 21, Day 28)]
Changes in Anxious Symptomology from Baseline to Week 4	The Beck Anxiety Inventory will be administered to assess severity of anxiety symptoms [Min score = 0, Max score = 63; Higher scores evince more severe symptomology].	[Time Frame: Weekly (Day 0, Day 7, Day 14, Day 21, Day 28)]
Changes in Sleep Symptomology from Baseline to Week 4	The Pittsburgh Sleep Quality Index will be administered weekly to examine quality of sleep and other sleep disturbances [Min score = 0, Max score = 21; Higher scores evince more severe symptomology].	[Time Frame: Weekly (Day 0, Day 7, Day 14, Day 21, Day 28)]
Changes in Anhedonia from Baseline to Week 4	The Snaith-Hamilton Pleasure Scale will be administered weekly to measure changes in anhedonia [Min score = 0, Max score = 14; Higher scores evince more severe symptomology].	[Time Frame: Weekly (Day 0, Day 7, Day 14, Day 21, Day 28)]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Verbal Learning and Memory	The Hopkins Verbal Learning Test will be administered to investigate this cognitive domain.	Day 0 and Day 28
Changes in Attention and Visual Search	The Trail Making Test will be administered to investigate these cognitive domains	Day 0 and Day 28
Changes in Working Memory	The Digit Span test will be administered to investigate this cognitive domain.	Day 0 and Day 28
Changes in Sustained Attention	The Continuous Performance Test will be administered to investigate this cognitive domain	Day 0 and Day 28

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Investigators: Principal Investigator: Tony P George, MD., FRCPC, CAMH

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2021
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: June 1, 2021
• First Submitted That Met QC Criteria: June 15, 2021
• First Posted (Actual): June 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: depression; substance abuse; anxiety; cannabis; contingency reinforcement
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Marijuana Abuse
• Other Study ID Numbers: 125-2020

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No