Cannabis Abstinence for Depression

Overseen By Maryam Sorkhou, HBSc

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must be taking: Antidepressants

Disqualifiers: Alcohol, Illicit substances, Suicidal, Psychotic, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

52 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that you have been on a stable dose of antidepressant medication for at least three months before joining.

What data supports the effectiveness of the treatment Contingency Management for cannabis abstinence in depression?

Research shows that Contingency Management (CM), which rewards people for staying off cannabis, can help reduce cannabis use and achieve abstinence, especially in those with mental health issues like depression. Studies found that CM was effective in improving outcomes for people with cannabis use disorder and co-occurring mental health disorders, suggesting it could be beneficial for those with depression. ^{1 2 3 4 5}

Is contingency management a safe treatment for cannabis abstinence in humans?

Contingency management, which involves providing rewards for abstaining from cannabis, has been used safely in various studies to help people reduce or stop cannabis use. While it is effective in promoting abstinence, the main concerns are related to its cost and the need for proper training to implement it effectively. ^{1 2 3 4 6}

How does cannabis abstinence differ from other treatments for depression?

Cannabis abstinence for depression is unique because it focuses on stopping cannabis use as a way to improve depressive symptoms, unlike traditional treatments that often involve medication or therapy directly targeting depression. This approach is based on the idea that reducing or eliminating cannabis use can lead to better mental health outcomes, especially for those with co-occurring cannabis use disorder and depression. ^{2 4 7 8 9}

What is the purpose of this trial?

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.

Research Team

Tony P George, MD., FRCPC

Principal Investigator

CAMH

Eligibility Criteria

This trial is for adults aged 18-55 with Major Depressive Disorder and co-occurring moderate to severe Cannabis Use Disorder. They must be on stable antidepressant medication for three months, have an IQ of 80 or above, and show motivation. Excluded are those with bipolar disorder, significant head injury, other substance abuse (except nicotine/caffeine), psychotic disorders, or current suicidal/homicidal thoughts.

Inclusion Criteria

Participants must have a Hamilton Depression Rating Scale (HDRS-17) at baseline assessment in the range of 12-25

Participants must meet SCID for DSM-5 diagnostic criteria for Major Depressive Disorder

I have been on a stable dose of antidepressants for at least three months.

Exclusion Criteria

Participants with a psychotic disorder diagnosis (e.g. schizoaffective disorder, major depression with psychotic features) as determined by the SCID

Participants who meet criteria for substance use disorder of alcohol or other illicit substances within the past 6 months (with the exception of cannabis, nicotine, or caffeine)

Participants who meet SCID for DSM-5 diagnostic criteria for Bipolar Disorder

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 28-day cannabis abstinence period with contingent or non-contingent reinforcement interventions

4 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for changes in depressive, anxiety, and sleep symptoms, as well as cognitive outcomes

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Contingency Reinforcement
• Non-Contingency Reinforcement

Trial Overview The study examines the impact of stopping cannabis use for 28 days in patients with depression who also frequently use cannabis. Participants will either receive rewards for abstaining from cannabis (Contingency Reinforcement) or not (Non-Contingency Reinforcement), to see if this affects their depression symptoms and cognitive function.

Participant Groups

Group I: Non-Contingency Reinforcement Group Experimental Treatment 1 Intervention

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.

Group II: Contingency Reinforcement Group Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Findings from Research

In a study involving 333 cocaine-negative patients, both attendance-based and abstinence-based contingency management (CM) were equally effective in enhancing the longest duration of abstinence, with attendance-based CM leading to higher participation and submission of negative samples.

For 109 cocaine-positive patients, a higher magnitude abstinence-based CM ($560Abs) significantly improved abstinence outcomes compared to standard care, indicating that greater rewards can enhance treatment effectiveness for those actively using cocaine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial adapting contingency management targets based on initial abstinence status of cocaine-dependent patients. Petry, NM., Barry, D., Alessi, SM., et al.[2021]

Contingency management (CM) has been shown to effectively reduce cannabis use and promote abstinence in individuals with comorbid cannabis use disorder and mental health disorders, particularly those with psychotic-spectrum or major depressive disorders.

The review included six studies, indicating a need for more extensive longitudinal research with larger sample sizes and diverse psychiatric populations to better understand the long-term effects of CM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contingency Management for Treatment of Cannabis Use Disorder in Co-Occurring Mental Health Disorders: A Systematic Review. Rodas, JD., Sorkhou, M., George, TP.[2023]

In a 12-week clinical trial with 127 young adults seeking treatment for cannabis dependence, combining contingency management (CM) with cognitive-behavioral therapy (CBT) did not improve treatment outcomes and actually worsened results when compared to CM alone.

The CM for abstinence condition was the most effective, showing the highest percentage of cannabis-free urine specimens, while the enhanced treatment groups experienced increased cannabis use during a 1-year follow-up, indicating that combining these therapies may not be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining cognitive behavioral therapy and contingency management to enhance their effects in treating cannabis dependence: less can be more, more or less. Carroll, KM., Nich, C., Lapaglia, DM., et al.[2021]

In a study involving 240 marijuana-dependent participants, adding contingency management (ContM) to motivational enhancement therapy plus cognitive behavioral therapy (MET+CBT) significantly improved abstinence rates compared to other treatment conditions.

The ContM-only group achieved the highest abstinence rates immediately after treatment, while the combination of MET+CBT and ContM showed the best outcomes at follow-up, highlighting the effectiveness of reinforcement strategies in treating marijuana dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abstinence rates following behavioral treatments for marijuana dependence. Kadden, RM., Litt, MD., Kabela-Cormier, E., et al.[2022]

A meta-analysis of 10 randomized controlled trials involving 2,027 participants found that behavioral therapies (BTs) significantly improve outcomes for cannabis use disorders compared to control conditions, with an effect size of 0.44, indicating that patients receiving BTs fared better than 66% of those in control groups.

Behavioral therapies were effective in reducing both the frequency and severity of cannabis use, as well as improving psychosocial functioning, with larger effect sizes observed in studies using waitlist controls compared to those with active control comparisons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral therapies for treatment-seeking cannabis users: a meta-analysis of randomized controlled trials. Davis, ML., Powers, MB., Handelsman, P., et al.[2022]

Contingency management (CM) is an effective behavioral intervention that can enhance the efficacy of pharmacotherapies for drug abuse by providing rewards for desired behaviors, such as drug-free urines, and can be applied in various contexts, including improving medication compliance and fostering abstinence before starting certain treatments.

Despite its potential, CM faces challenges such as high costs, short-term effects, and the need for specialized training, which limit its widespread use; addressing these issues is crucial for maximizing CM's benefits in drug abuse treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A perfect platform: combining contingency management with medications for drug abuse. Carroll, KM., Rounsaville, BJ.[2018]

Reducing the number of days individuals use cannabis is linked to improvements in their overall functioning, suggesting that this could be a valuable outcome measure in treatment trials for cannabis use disorder (CUD).

While reductions in the amount of cannabis used showed inconsistent links to functional improvements, biologically-confirmed reductions in usage frequency may serve as a reliable endpoint for future clinical trials, highlighting the need for further research on quantifying cannabis reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring Within-Individual Cannabis Reduction in Clinical Trials: A Review of the Methodological Challenges. Tomko, RL., Gray, KM., Huestis, MA., et al.[2022]

A twelve-week intervention targeting both cannabis use disorders (CUD) and tobacco smoking showed that all six participants completed the cannabis treatment, and five achieved abstinence from cannabis, indicating that simultaneous treatment can be effective for cannabis outcomes.

While participation in the tobacco intervention was high, with 50% of participants starting nicotine replacement therapy, the actual quit attempts for tobacco were lower than expected, suggesting that more effective strategies are needed to improve tobacco cessation rates alongside CUD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment models for targeting tobacco use during treatment for cannabis use disorder: case series. Lee, DC., Budney, AJ., Brunette, MF., et al.[2021]

In a study involving 106 participants over 13 weeks, neither nefazodone nor bupropion-sustained release significantly improved cannabis abstinence rates or reduced withdrawal symptoms, suggesting limited efficacy for these medications in treating cannabis dependence.

While participants did show some improvement in coping skills and a decrease in irritability, the medications did not have a meaningful impact on overall cannabis use or dependence severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preliminary trial: double-blind comparison of nefazodone, bupropion-SR, and placebo in the treatment of cannabis dependence. Carpenter, KM., McDowell, D., Brooks, DJ., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

A randomized trial adapting contingency management targets based on initial abstinence status of cocaine-dependent patients. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Contingency Management for Treatment of Cannabis Use Disorder in Co-Occurring Mental Health Disorders: A Systematic Review. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Combining cognitive behavioral therapy and contingency management to enhance their effects in treating cannabis dependence: less can be more, more or less. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Abstinence rates following behavioral treatments for marijuana dependence. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Behavioral therapies for treatment-seeking cannabis users: a meta-analysis of randomized controlled trials. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A perfect platform: combining contingency management with medications for drug abuse. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Measuring Within-Individual Cannabis Reduction in Clinical Trials: A Review of the Methodological Challenges. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Treatment models for targeting tobacco use during treatment for cannabis use disorder: case series. [2021]

9. England pubmed.ncbi.nlm.nih.gov

A preliminary trial: double-blind comparison of nefazodone, bupropion-SR, and placebo in the treatment of cannabis dependence. [2021]