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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if stopping cannabis use for 28 days can improve depression and overall functioning in individuals with both major depressive disorder (MDD) and cannabis use disorder (CUD). Researchers will divide participants into two groups: one will receive a reward for abstaining from cannabis (Contingency Reinforcement), while the other will not (Non-Contingency Reinforcement). Individuals who experience depression, use cannabis regularly, and maintain stability on their depression medication might be suitable for this study. As an unphased trial, this study provides a unique opportunity to enhance understanding of the impact of cannabis abstinence on mental health.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that the reward system used in this trial, called contingency management, is safe. Research indicates that this approach can reduce mental health symptoms and lower the risk of psychiatric hospitalization. Tested in over 30 studies, this method effectively reduces the use of drugs like stimulants and alcohol. These findings suggest that contingency management is generally well-tolerated and safe for participants. No evidence from these studies indicates any major safety issues or harmful effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores two unique behavioral strategies to support cannabis abstinence and potentially alleviate depression. Unlike traditional treatments for depression, which often involve antidepressant medications or therapy, this trial focuses on the impact of abstaining from cannabis use through reinforcement techniques. The Contingency Reinforcement approach provides monetary incentives for verified cannabis abstinence, which could motivate behavior change more effectively. Meanwhile, the Non-Contingency Reinforcement approach evaluates the effects of abstinence without financial rewards, offering insights into the intrinsic benefits of quitting cannabis. This trial could reveal new, non-pharmacological ways to address depression, particularly for individuals whose symptoms are linked to cannabis use.

What evidence suggests that this trial's treatments could be effective for depression with co-occurring cannabis use disorder?

This trial will compare two approaches to support cannabis abstinence in individuals with depression. Research has shown that rewarding positive changes, such as stopping drug use, can help reduce substance use, including cannabis. Participants in the Contingency Reinforcement Group will receive monetary rewards for verified abstinence. Studies have found this method effective in reducing depression and anxiety symptoms in people trying to quit drugs like crack cocaine. Evidence suggests that this approach works well for those who might not succeed with other treatments. Overall, rewarding positive changes is considered one of the best strategies for helping people quit smoking and other substances, even when they face mental health challenges like depression or anxiety. ^{3 5 6 7 8}

Who Is on the Research Team?

Tony P George, MD., FRCPC

Principal Investigator

CAMH

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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 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]

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]

Citations

1. recoveryanswers.org recoveryanswers.org/research-post/contingency-management-response/

What types of individuals respond best to contingency ... On the whole, evidence suggests that contingency management may be especially beneficial in patients who might otherwise have poorer outcomes (for example, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4242089/

A randomized controlled trial of contingency management ... When added to treatment-as-usual, contingency management is associated with large reductions in stimulant, injection drug, and alcohol use.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29251975/

Contingency management targeting abstinence is effective ... This study provides evidence that an STCM intervention targeting crack cocaine abstinence also produces significant reductions in depressive and anxiety ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0376871621003033

Depression symptom profiles and long-term response to ... Contingency Management (CM) is now considered to be one of the most effective interventions for smoking cessation, including for those with ...

5. mdpi.com mdpi.com/2077-0383/10/4/616

Meta-Analysis on the Effect of Contingency Management ... Our meta-analysis shows a potential effect of CM on abstinence for patients with SUD and (severe) psychotic disorders, although the number of studies is ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7916027/

Meta-Analysis on the Effect of Contingency Management ... CM group lower levels of alcohol use, injection drug use, fewer psychiatric symptoms, less likely to be admitted for psychiatric hospitalization ...

7. psychiatryonline.org psychiatryonline.org/doi/full/10.1176/appi.ajp.20240261

A Call to Action: Evidence-Based Contingency Management Over 30 randomized controlled trials demonstrate that CM is an effective intervention to reduce stimulant use among individuals receiving ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2352853219301208

Implementation of a contingency approach for people with ... This study aims to assess the acceptability, the feasibility and the implementation of the CM in therapeutic groups in a COD integrated program.