Can Quitting Cannabis Reduce Depression and Suicide Risk in Teens? A Major RCT Protocol to Find Out

This protocol describes a 200-adolescent randomized trial testing whether 8 weeks of cannabis abstinence reduces depressive symptoms and suicidal ideation in daily-using teens — using real-time phone tracking to capture the moment-by-moment relationship.

Feibus, Isabella et al.·PloS one·2025·Preliminary EvidenceRandomized Controlled Trial·1 min read

Withdrawal (166)Addiction (1380)Depression (193)Youth (1291)

Quick Facts

Study Type

Randomized Controlled Trial

Evidence

Preliminary Evidence

Sample

N=200

Participants

N=200 adolescents aged 12-18, both male and female, with daily cannabis use and current depressive symptoms.

What This Study Found

Heavy cannabis use and depression frequently co-occur in adolescents, with cannabis users at increased risk of major depressive episodes and suicidal ideation. But the critical clinical question remains unanswered: does quitting cannabis improve depression, or does it temporarily worsen it due to withdrawal?

This study protocol describes an ambitious RCT designed to disentangle this relationship. Two hundred adolescents aged 12-18 with daily or near-daily cannabis use and current depressive symptoms will be randomized to either 8 weeks of abstinence (encouraged through contingency management — financial incentives for negative drug tests) or a monitoring control group that continues use as usual.

What makes this study particularly powerful is the ecological momentary assessment (EMA) design: participants will complete 8 surveys per day during data collection phases, capturing substance use, mood, and suicidal thoughts in near-real-time. This allows the researchers to observe what happens hour by hour during both cannabis use and withdrawal — when do depressive symptoms spike? When does suicidal ideation emerge? Does the timing correlate with acute use, acute withdrawal, or sustained abstinence?

The study spans 10 weeks with 12 visits, producing a granular temporal map of the cannabis-depression-suicide relationship that no previous study has achieved. The contingency management approach to motivating abstinence is evidence-based and addresses the practical challenge of getting teens to actually stop using during the study.

Key Numbers

200 adolescents (12-18 years). 8 weeks of abstinence vs. continued use. 8 EMA surveys per day during collection phases. 12 study visits over 10 weeks. 4 total weeks of EMA data collection. Contingency management for abstinence motivation. Funded and registered (protocol published in 2025).

How They Did This

Randomized controlled trial protocol. 200 adolescents aged 12-18 with daily/near-daily cannabis use and current depressive symptoms. Randomized 1:1 to 8 weeks of cannabis abstinence (contingency management) vs. monitoring control. 12 study visits over 10 weeks. Self-report and interview assessments of substance use and symptom severity. 3 phases of EMA data collection (4 total weeks, 8 daily surveys) assessing past-hour substance use, mood, and suicidal ideation.

Why This Research Matters

Adolescent depression and suicide are at crisis levels, and cannabis use is growing in this age group. Clinicians face a dilemma: they suspect cannabis may worsen depression, but withdrawal can also trigger mood symptoms, and telling a depressed teen to quit a substance they use to cope carries its own risks. This RCT will provide the first controlled evidence on whether abstinence helps or hurts — and the EMA design will capture the temporal dynamics that determine clinical recommendations.

The Bigger Picture

This study could resolve one of the most important open questions linking the cannabis-mental-health and adolescent-vulnerability clusters. RTHC-00125 (psychological inflexibility linking CUD and PTSD) showed a mechanism for how cannabis use worsens mental health symptoms. RTHC-00037 (Budney withdrawal timeline) documented that withdrawal itself produces mood symptoms. This RCT will determine which dominates in depressed adolescents: does the relief of sustained abstinence outweigh the withdrawal period, or does forcing abstinence make things worse?

What This Study Doesn't Tell Us

This is a protocol paper — no results yet. Contingency management may not achieve true abstinence in all participants (compliance varies). 8 weeks may not be long enough for full mood recovery after chronic use. The 12-18 age range includes very different developmental stages. Participants must have both daily cannabis use AND depressive symptoms, which is a specific population — results may not generalize to teens with one but not both conditions. EMA compliance in adolescents can be challenging.

Questions This Raises

?Will results show that abstinence improves depression, or that withdrawal temporarily worsens it before improvement?
?Is the timeline of mood improvement consistent with the CB1 receptor recovery timeline documented in adults (RTHC-00100)?
?Does suicidal ideation peak during withdrawal or during active use?
?Will the contingency management approach produce enough sustained abstinence to detect clinical differences?

Trust & Context

Key Stat:
Evidence Grade:: This is a published study protocol, not results. The design is rigorous (RCT, EMA, contingency management, registered trial), but no data exist yet. The value is in the methodology — this will be among the strongest studies ever conducted on this question when completed.
Study Age:: Published in 2025. Results are not yet available. This represents a study in progress.
Original Title:: Characterizing proximal risk for depressive symptoms and suicidal ideation with acute cannabis use and withdrawal among adolescents using ecological momentary assessment: Study protocol.
Published In:: PloS one, 20(12), e0338790 (2025) — PloS One is a reputable, peer-reviewed journal known for publishing interdisciplinary research.
Authors:: Feibus, Isabella, Mahiques, Marta Borrego, Costello, Meghan, Potter, Kevin, Bentley, Kate H, Hoeppner, Bettina B, Liu, Luwei, Evohr, Bryn, Yan, Lynn, Gilman, Jodi, Evins, A Eden, Kossowsky, Joe, Schuster, Randi M
Database ID:: RTHC-06443

Evidence Hierarchy

Meta-Analysis / Systematic Review

Randomized Controlled TrialGold standard for testing treatments

This study

Cohort / Case-Control

Cross-Sectional / Observational

Case Report / Animal Study

Participants are randomly assigned to treatment or placebo groups to test cause and effect.

What do these levels mean? →

Cite This Study

RTHC-06443·https://rethinkthc.com/research/RTHC-06443

APA

Feibus, Isabella; Mahiques, Marta Borrego; Costello, Meghan; Potter, Kevin; Bentley, Kate H; Hoeppner, Bettina B; Liu, Luwei; Evohr, Bryn; Yan, Lynn; Gilman, Jodi; Evins, A Eden; Kossowsky, Joe; Schuster, Randi M. (2025). Characterizing proximal risk for depressive symptoms and suicidal ideation with acute cannabis use and withdrawal among adolescents using ecological momentary assessment: Study protocol.. PloS one, 20(12), e0338790. https://doi.org/10.1371/journal.pone.0338790

MLA

Feibus, Isabella, et al. "Characterizing proximal risk for depressive symptoms and suicidal ideation with acute cannabis use and withdrawal among adolescents using ecological momentary assessment: Study protocol.." PloS one, 2025. https://doi.org/10.1371/journal.pone.0338790

RethinkTHC

RethinkTHC Research Database. "Characterizing proximal risk for depressive symptoms and sui..." RTHC-06443. Retrieved from https://rethinkthc.com/research/feibus-2025-characterizing-proximal-risk-for

Access the Original Study

View on PubMed View via DOI

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.

← Back to Research Database