Cannabis Abstinence for Cannabis Use Disorder

Overseen By Allison Corlett

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Must not be taking: Antipsychotics, Unstable psychotropics

Disqualifiers: Substance use disorders, Nicotine, Psychosis, others

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

Compensation: Varies

Number of Visits: 8

Duration: 6 weeks

64 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are taking psychotropic medications, you can continue them as long as they have been stable for 6 weeks and are expected to remain stable throughout the study.

What data supports the effectiveness of the treatment for cannabis use disorder?

Research shows that behavioral therapies, like cognitive-behavioral therapy and motivational interviewing, are effective for treating cannabis use disorder. These therapies help people reduce their cannabis use and improve their overall functioning. ^{1 2 3 4 5}

How is the CB-Abst treatment for cannabis use disorder different from other treatments?

The CB-Abst treatment for cannabis use disorder is unique because it focuses on achieving complete abstinence from cannabis, which is challenging in clinical trials. Unlike other treatments that may aim for reduction in use, CB-Abst emphasizes total cessation, which can lead to significant functional improvements. ^{1 2 6 7 8}

What is the purpose of this trial?

The goal of this study is to understand the changes in neural correlates of reward in adolescents with and without Cannabis Use Disorder (CUD). The study will collect functional magnetic resonance imaging (fMRI) data at 3 different timepoints with the primary goals of understanding striatal reward-based activation during a Monetary Incentive Delay Task and fronto-striatal fMRI resting-state functional connectivity. The study will also explore self-reported impulsivity. The long-term goal is to advance scientific understanding of neural changes associated with cannabis abstinence and inter-individual variability that cannot be otherwise measured in preexisting observational cohorts such as the Adolescent Brain Cognitive Development Study. This parallel intervention study will collect fMRI data in adolescents ages 15-18 years old with and without CUD at three different timepoints over the course of their intervention. Utilizing a validated paradigm, adolescents with CUD will be randomized to 6-weeks of either incentivized, biochemically verified abstinence via contingency management or monitoring with no required abstinence. Age- and sex-matched adolescents with no lifetime history of cannabis use will also complete the protocol. Participants will complete 8 study visits (3 with fMRI scans) involving urinalysis to confirm cannabis self-report and measures of impulsivity.

Research Team

Brenden Tervo-Clemmens, PhD

Principal Investigator

University of Minnesota

Eligibility Criteria

Adolescents aged 15-18 with Cannabis Use Disorder (CUD) who use cannabis at least 5 days a week and those without any history of cannabis use. Participants must be native English speakers, have stable psychotropic medication if applicable, and commit to 8 study visits over about two months. They cannot have other substance abuse disorders, daily nicotine use, MRI contraindications like metal implants or claustrophobia, or serious medical/psychiatric conditions.

Inclusion Criteria

You have never used cannabis before, and your urine test shows no signs of recent cannabis use. You do not plan to start using cannabis during the study.

A parent or legal guardian can give permission for you to be in the study by signing a form.

I am a native English speaker.

Exclusion Criteria

I haven't had a substance use disorder, except for cannabis, in the past year.

Contraindications for MRI (ascertained via participant and parent report), including but not limited to: metal implants such as surgical clips or pacemakers, or history of working with metal, unless the possibility of a metal fragment can be ruled out by recent orbital scans; prior head trauma with neurological sequelae; claustrophobia; weight incompatible with MRI safety; pregnancy; previous or current diagnosis of psychosis, cognitive disability, or bipolar disorder; active suicidality; taking a psychotropic medication that has not reached stability criterion (same medication type and dose for 6 weeks with no planned changes over the study period); any other medical or psychiatric condition deemed serious or contraindicated for any study procedures by Dr. Tervo-Clemmens

Current daily nicotine use (e.g., via electronic and/or combustible cigarettes)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 6 weeks of either incentivized, biochemically verified abstinence or monitoring with no required abstinence, with fMRI data collection at baseline, week 3, and week 6

6 weeks

8 visits (3 with fMRI scans)

Follow-up

Participants are monitored for changes in neural correlates of reward and self-reported impulsivity

4 weeks

Treatment Details

Interventions

• CB-Abst
• CB-Mon

Trial Overview The trial is testing the effects of a six-week period where adolescents with CUD either abstain from cannabis use under supervision (CB-Abst group) or continue their usual consumption without abstinence requirements (CB-Mon group). The control group has no history of cannabis use. Brain function will be measured using fMRI scans during tasks related to reward processing and impulsivity.

Participant Groups

Group I: CB-MON Experimental Treatment 1 Intervention

adolescents ages 15-18 years old with CUD use randomized to CB-Mon

Group II: CB-Abst Experimental Treatment 1 Intervention

adolescents ages 15-18 years old with CUD use randomized to CB-Abst

Group III: control Active Control 1 Intervention

Age- and sex-matched adolescents with no lifetime history of cannabis use will also complete the protocol.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

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]

In a 12-week clinical trial involving 225 adults with cannabis use disorder, reductions in cannabis use frequency and quantity were linked to significant improvements in depression, anxiety, and cannabis-related problems.

The study suggests that measuring changes in cannabis use risk levels can serve as a meaningful endpoint for assessing the efficacy of treatments for cannabis use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating cannabis use risk reduction as an alternative clinical outcome for cannabis use disorder. Sherman, BJ., Sofis, MJ., Borodovsky, JT., et al.[2023]

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]

Only about 20% of individuals undergoing treatment for cannabis dependence achieve long-term abstinence, highlighting the need for more effective and accessible treatment options.

Psychotherapeutic strategies, especially combination therapies that include motivational interventions and behavioral skills training, have shown larger effect sizes for cannabis dependence compared to other substance use disorders, indicating their potential effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

State of the art treatments for cannabis dependence. Danovitch, I., Gorelick, DA.[2021]

A study involving 186 adults with problematic cannabis use found that a self-directed treatment workbook combined with a single motivational interviewing session significantly reduced cannabis use frequency and increased abstinence rates at the 3-month follow-up compared to a workbook alone or a delayed treatment control.

The results suggest that this low-intensity intervention can effectively support individuals seeking recovery with minimal professional help, addressing a gap in treatment options for cannabis use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promoting self-change in cannabis use disorder: Findings from a randomized trial. Schluter, MG., Hodgins, DC., Stea, JN., et al.[2022]

Marijuana dependence is characterized by three key elements: preoccupation with obtaining marijuana, compulsive use, and relapse, which are essential for diagnosing addiction.

The consequences of marijuana addiction can lead to various medical, psychiatric, and social issues, and these effects are driven by the drug's reinforcing properties rather than external stressors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The diagnosis of marijuana (cannabis) dependence. Miller, NS., Gold, MS.[2019]

The pilot study involved four male veterans with cannabis use disorder and sleep problems, testing a mobile app for Cognitive Behavioral Therapy for Insomnia (CBT-I) over two weeks.

Participants using the CBT-I app reported daily use, found it helpful, and experienced decreased cannabis use and improved sleep efficiency, suggesting that mobile CBT-I could be a promising intervention for cannabis dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mobile App-Delivered Cognitive Behavioral Therapy for Insomnia: Feasibility and Initial Efficacy Among Veterans With Cannabis Use Disorders. Babson, KA., Ramo, DE., Baldini, L., et al.[2020]

In a study involving 206 cannabis users and 999 abstainers from cannabis during Alcohol Use Disorder (AUD) treatment, frequent cannabis use (12 times/month or more) was linked to significantly more physical alcohol-related consequences one year after treatment.

The findings suggest that individuals in AUD treatment who frequently use cannabis may benefit from reducing or stopping cannabis use to minimize the risk of alcohol-related physical problems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis use during alcohol treatment is associated with alcohol-related problems one-year post-treatment. Subbaraman, MS., Metrik, J., Patterson, D., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Evaluating cannabis use risk reduction as an alternative clinical outcome for cannabis use disorder. [2023]

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

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

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

State of the art treatments for cannabis dependence. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Promoting self-change in cannabis use disorder: Findings from a randomized trial. [2022]

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

The diagnosis of marijuana (cannabis) dependence. [2019]

7. Canada pubmed.ncbi.nlm.nih.gov

Mobile App-Delivered Cognitive Behavioral Therapy for Insomnia: Feasibility and Initial Efficacy Among Veterans With Cannabis Use Disorders. [2020]

8. Ireland pubmed.ncbi.nlm.nih.gov

Cannabis use during alcohol treatment is associated with alcohol-related problems one-year post-treatment. [2023]