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

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04935619
• Other study ID #: 125-2020
• Status: Recruiting
• Phase: N/A
• Start date: July 21, 2021
• Est. completion date: August 31, 2025

Study information

• Verified date: August 2023
• Source: Centre for Addiction and Mental Health
• Contact: Maryam Sorkhou, HBSc
• Phone: 4165358501
• Email: maryam.sorkhou[@]mail.utoronto.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: August 31, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cannabis Use
• Cognitive Impairment
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• Marijuana Abuse

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)]
Primary	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)]
Primary	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)]
Primary	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	Changes in Verbal Learning and Memory	The Hopkins Verbal Learning Test will be administered to investigate this cognitive domain.	Day 0 and Day 28
Secondary	Changes in Attention and Visual Search	The Trail Making Test will be administered to investigate these cognitive domains	Day 0 and Day 28
Secondary	Changes in Working Memory	The Digit Span test will be administered to investigate this cognitive domain.	Day 0 and Day 28
Secondary	Changes in Sustained Attention	The Continuous Performance Test will be administered to investigate this cognitive domain	Day 0 and Day 28