Cannabis UseNCT04935619
Extended Effects of Cannabis Abstinence on Clinical Symptoms and Cognition in Depression
A study testing Contingency Reinforcement and Non-Contingency Reinforcement in people with Cannabis Use and Major Depressive Disorder, run by Centre for Addiction and Mental Health at 1 site in Canada.
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… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Cannabis Use, Major Depressive Disorder, Cognitive Impairment
- What is being tested?
- Contingency Reinforcement and Non-Contingency Reinforcement
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteCanada
- Study dates
- 21 Jul 2021to 31 Aug 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Centre for Addiction and Mental Health
Toronto, Ontario, M5T 1R8
Tony P George, M.D.
About this study
Official title: 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.
Read the 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.
- Being tested
- Contingency Reinforcement, Non-Contingency Reinforcement
- Keywords
- cannabis, substance abuse, depression, anxiety, contingency reinforcement
- Medical subject headings
- Depressive Disorder, Major, Cognitive Dysfunction, Marijuana Abuse, Substance-Related Disorders, Depression, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Contingency ReinforcementBehavioural
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 ReinforcementBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Non-Contingency Reinforcement Group | Other | 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. Receives: Behavioral: Non-Contingency Reinforcement |
| Contingency Reinforcement Group | Experimental | 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. Receives: Behavioral: Contingency Reinforcement |
What is being measured
The primary outcome is the main question the study is designed to answer.
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]
Measured: [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].
Measured: [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].
Measured: [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].
Measured: [Time Frame: Weekly (Day 0, Day 7, Day 14, Day 21, Day 28)]
Secondary outcomes (4)
Changes in Verbal Learning and Memory
The Hopkins Verbal Learning Test will be administered to investigate this cognitive domain.
Measured: Day 0 and Day 28
Changes in Attention and Visual Search
The Trail Making Test will be administered to investigate these cognitive domains
Measured: Day 0 and Day 28
Changes in Working Memory
The Digit Span test will be administered to investigate this cognitive domain.
Measured: Day 0 and Day 28
Changes in Sustained Attention
The Continuous Performance Test will be administered to investigate this cognitive domain
Measured: Day 0 and Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2021
- Study start21 Jul 2021
- Primary completion30 Jun 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cannabis UseStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tony P George, MD., FRCPC, Principal investigator, CAMH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04935619
- Sponsor's protocol ID
- 125-2020
- Status last verified
- Feb 2025
- First submitted
- 1 Jun 2021
- Last updated
- 24 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Extended Cannabis Abstinence on Clinical and Cognitive Outcomes in Patients With Co-Morbid Major Depressive and Cannabis Use Disorders
- ClinicalTrials.gov ID
- NCT04935619
- Acronym / sponsor ID
- 125-2020
- Keywords
- cannabis, substance abuse, depression, anxiety, contingency reinforcement
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- 21 Jul 2021 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 23 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-Contingency Reinforcement Group | Other | Behavioral: Non-Contingency ReinforcementSubjects 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. |
| Contingency Reinforcement Group | Experimental | Behavioral: Contingency ReinforcementSubjects 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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..
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Contingency ReinforcementSubjects 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. | Behavioural | Contingency Reinforcement Group |
| Non-Contingency ReinforcementSubjects 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. | Behavioural | Non-Contingency Reinforcement Group |
Primary outcome
Changes in Depressive Symptomology from Baseline to Week 4
Time frame: [Time Frame: Weekly (Day 0, Day 7, Day 14, Day 21, Day 28)]
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]
Changes in Anxious Symptomology from Baseline to Week 4
Time frame: [Time Frame: Weekly (Day 0, Day 7, Day 14, Day 21, Day 28)]
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].
Changes in Sleep Symptomology from Baseline to Week 4
Time frame: [Time Frame: Weekly (Day 0, Day 7, Day 14, Day 21, Day 28)]
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].
Changes in Anhedonia from Baseline to Week 4
Time frame: [Time Frame: Weekly (Day 0, Day 7, Day 14, Day 21, Day 28)]
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].
4 secondary outcomes
Changes in Verbal Learning and Memory
Time frame: Day 0 and Day 28
Changes in Attention and Visual Search
Time frame: Day 0 and Day 28
Changes in Working Memory
Time frame: Day 0 and Day 28
Changes in Sustained Attention
Time frame: Day 0 and Day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tony P George, MD., FRCPC principal investigator
CAMH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Contingency Reinforcement and Non-Contingency Reinforcement in people with Cannabis Use and Major Depressive Disorder, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maryam Sorkhou, HBSc (4165358501 ext. 36225, maryam.sorkhou@mail.utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Depressive Symptomology from Baseline to Week 4 (time frame: [Time Frame: Weekly (Day 0, Day 7, Day 14, Day 21, Day 28)]). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025.