# Insights on Cannabis Craving and Cross-Substance Use from Pooled Trial Data

> **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637)
> **Publisher:** CED Clinic (https://cedclinic.com)
> **Canonical URL:** https://cedclinic.com/cannabis-craving-cross-substance-use-analysis/
> **Published:** 2026-08-15T10:24:59-04:00 | **Last Modified / Clinically Audited:** 2026-09-27T22:00:31-04:00
> **Clinical Summary:** Explore cannabis craving and cross-substance use in a pooled analysis of 829 patients, revealing modest links with alcohol and cigarette use during treatment.

---

CED Clinical Relevance #80 Clinical Evidence Update [Cannabis use disorder](https://cedclinic.com/sex-differences-cannabis-stress-reactivity-oxytocin/) trials rarely examine what happens to a patient’s alcohol and tobacco use during treatment. This pooled, longitudinal analysis of 829 participants across seven pharmacologic CUD trials, published in a peer-reviewed addiction journal, is the first to systematically test whether cannabis craving and use predict next-week shifts in other substance use, which clears the bar for a Clinical Evidence Update even though the findings are exploratory and statistically modest.

Clinical Insight | CED Clinic
Researchers pooled data from 829 adults enrolled across seven pharmacologic [clinical trials](https://cedclinic.com/endocannabinoid-system-emotional-memory-ptsd-treatment/) for [cannabis use](https://cedclinic.com/cannabis-cardiovascular-health-insights-2024/) disorder, drawing on a sample with a mean age of 27.1 years, 31 percent female, 63 percent White, and 13 percent Latine or Hispanic participants. Each trial tracked weekly [cannabis use](https://cedclinic.com/cannabis-cardiovascular-health-insights-2024/), alcohol use, and cigarette use, with cigarette data available in six of the seven trials. The team used longitudinal mixed-effects models to test whether a given week’s [cannabis use](https://cedclinic.com/cannabis-cardiovascular-health-insights-2024/) or craving predicted the following week’s alcohol and cigarette use, and whether assignment to active pharmacotherapy changed that relationship. No treatment condition significantly altered the overall pattern across all three substances. Cannabis craving combined with heavier cannabis use in a given week predicted a small increase in the following week’s alcohol quantity, though not in how often participants drank. Heavier cannabis use in a given week predicted slightly lower cigarette quantity the following week. Among participants randomized to active medication, higher cannabis craving was linked to fewer smoking days, a treatment-specific signal not seen broadly across the sample.

[Cannabis Use Disorder](https://cedclinic.com/sex-differences-cannabis-stress-reactivity-oxytocin/)CravingSubstance SubstitutionAlcoholTobacco

Audience
[Addiction medicine](https://cedclinic.com/cognitive-flexibility-alcohol-cocaine-misuse-effects/) clinicians, primary care physicians treating patients with [cannabis use disorder](https://cedclinic.com/sex-differences-cannabis-stress-reactivity-oxytocin/), and patients considering or undergoing cannabis cessation treatment

Primary Topic
A pooled secondary analysis of 829 participants across seven pharmacologic cannabis use disorder [clinical trials](https://cedclinic.com/endocannabinoid-system-emotional-memory-ptsd-treatment/), examining whether cannabis craving and use predict cross-substance alcohol and tobacco use, published in Addictive Behaviors, August 2026

Source
[Read the study on PubMed](https://pubmed.ncbi.nlm.nih.gov/42594823/)

Table of Contents

- [Cannabis Craving and Cross-Substance Use: What Pooled Trial Data From 829 Patients Show](#Cannabis_Craving_and_Cross-Substance_Use_What_Pooled_Trial_Data_From_829_Patients_Show)
- [How to Read a Borderline-Significant, Pooled Secondary Analysis](#How_to_Read_a_Borderline-Significant_Pooled_Secondary_Analysis)[A Four-Step Reading Frame](#A_Four-Step_Reading_Frame)
- [The Same Study Can Mean Different Things Depending on the Question Being Asked](#The_Same_Study_Can_Mean_Different_Things_Depending_on_the_Question_Being_Asked)[What This Means If You Are Cutting Back on Cannabis](#What_This_Means_If_You_Are_Cutting_Back_on_Cannabis)
- [A Reason to Ask, Not Yet a Reason to Predict](#A_Reason_to_Ask_Not_Yet_a_Reason_to_Predict)
- [Borderline P-Values Deserve a Second Look](#Borderline_P-Values_Deserve_a_Second_Look)
- [Polysubstance Patterns Are the Clinical Norm](#Polysubstance_Patterns_Are_the_Clinical_Norm)
- [Seven Trials, One Analysis, Many Assumptions](#Seven_Trials_One_Analysis_Many_Assumptions)
- [A Template for Mining Existing Trial Data](#A_Template_for_Mining_Existing_Trial_Data)
- [Framing Substitution Claims Carefully Matters](#Framing_Substitution_Claims_Carefully_Matters)
- [The Right Question, an Early-Stage Answer](#The_Right_Question_an_Early-Stage_Answer)
- [Frequently Asked Questions](#Frequently_Asked_Questions)[Related](#Related)

## Cannabis Craving and Cross-Substance Use: What Pooled Trial Data From 829 Patients Show

A pooled analysis of 829 participants across seven cannabis use disorder trials found that cannabis craving and heavier use predicted small, next-week shifts in alcohol and cigarette use, with one treatment-specific signal: patients on active medication who craved cannabis more smoked fewer cigarettes the following week.

What This Study Teaches Us
This analysis suggests that reducing cannabis use does not uniformly reduce use of other substances. Alcohol use tended to rise modestly alongside cannabis craving, consistent with a complementary use pattern, while cigarette use showed signs of both co-use and substitution depending on treatment assignment. The findings support monitoring alcohol and tobacco use as part of cannabis use disorder treatment rather than assuming other substance use will passively improve.

Why This Matters
Clinicians treating cannabis use disorder often focus monitoring on cannabis itself, but patients rarely use only one substance. This pooled analysis, though exploratory, offers early evidence that alcohol and tobacco use can shift in different directions during cannabis cessation efforts, information that could shape how closely clinicians track polysubstance use during treatment.

Study Snapshot

Study Type
Pooled, exploratory secondary analysis of longitudinal data from seven pharmacologic [clinical trials](https://cedclinic.com/endocannabinoid-system-emotional-memory-ptsd-treatment/) for cannabis use disorder

Population
829 participants (mean age 27.1 years, SD 9.1; 31% female; 63% White; 13% Latine or Hispanic)

Data Source
Seven pharmacotherapy trials for cannabis use disorder; cigarette data available in six of the seven

Measures
Weekly self-reported cannabis, alcohol, and cigarette use, and cannabis craving

Analysis
Longitudinal mixed-effects models testing whether cannabis use or craving predicted next-week alcohol and cigarette outcomes, with treatment condition as a moderator

Alcohol Finding
Cannabis craving combined with higher cannabis frequency predicted a small increase in next-week alcohol quantity (b=0.009, p=0.0497), not drinking frequency

Cigarette Finding
Higher cannabis quantity predicted lower next-week cigarette quantity (b=-0.009, p=0.042)

Treatment-Specific Signal
Among participants on active pharmacotherapy, higher cannabis craving predicted fewer smoking days the following week (b=-0.008, p=0.0499)

Treatment Effect Overall
No significant three-way interactions between treatment, cannabis measures, and substance outcomes emerged

Journal
Addictive Behaviors

Published
August 12, 2026

DOI
10.1016/j.addbeh.2026.108834

PMID
42594823

Clinical Bottom Line
In a pooled analysis of 829 patients across seven cannabis use disorder trials, cannabis craving and use predicted small, next-week shifts in alcohol and cigarette use rather than a uniform decline across substances, with statistical signals close to the significance threshold that support monitoring polysubstance use during treatment but do not establish a reliable substitution effect.

What the Analysis Tested

Researchers pooled longitudinal data from 829 participants originally enrolled in seven separate pharmacologic clinical trials for cannabis use disorder, each of which independently tracked weekly cannabis, alcohol, and cigarette use as part of its own study design.

The team used mixed-effects models to ask whether a given week’s cannabis use or craving predicted the following week’s alcohol and cigarette use, and whether being randomized to active medication changed that relationship, an approach that lets a single analysis draw on trial data never originally designed together for this specific question.

Alcohol Use Rose Modestly When Cannabis Craving Was High

Weeks with both higher cannabis craving and higher cannabis use frequency predicted a small increase in the following week’s alcohol quantity, a pattern the authors describe as consistent with complementary use, where cannabis and alcohol use rise and fall together rather than substituting for each other.

This effect did not extend to how often participants drank, only to how much, and the statistical signal was modest, with a p-value of 0.0497, just inside the conventional threshold for significance.

Cigarette Use Told a More Complicated Story

Higher cannabis quantity in a given week predicted slightly lower cigarette quantity the following week across the full sample, a pattern more consistent with substitution than complementary use.

Among participants specifically assigned to active pharmacotherapy, higher cannabis craving was linked to fewer smoking days the following week, a treatment-specific signal that the authors flag as an initial, exploratory finding rather than an established effect.

No Broad Effect of Medication on Substitution Patterns

Across the pooled analysis, no significant three-way interactions between treatment assignment, cannabis measures, and substance outcomes emerged, meaning active pharmacotherapy did not broadly reshape how cannabis use related to alcohol or tobacco use.

The one treatment-specific finding, for cigarette frequency and craving, was described by the authors as limited evidence, a signal worth following up rather than a confirmed treatment effect.

What This Analysis Cannot Tell Us

This was an exploratory secondary analysis of data collected for other purposes, pooled across seven pharmacologically distinct trials rather than a single study designed to test substitution effects, and it relied on self-reported substance use rather than biological verification.

The p-values for the key findings sat close to the conventional 0.05 threshold, and the analysis does not describe correction for the number of comparisons tested, both of which mean these results should be read as hypothesis-generating rather than confirmatory.

How Strong Is This Evidence?
This analysis draws on a relatively large pooled sample, 829 participants, and applies longitudinal mixed-effects modeling capable of testing whether earlier cannabis measures predict later substance use, an approach well suited to detecting real behavioral patterns over time rather than a single cross-sectional snapshot. Pooling seven separate trials also gives the analysis more statistical power than any one trial alone could offer.

Where This Paper Deserves Skepticism
The trials pooled here were not designed together and used different pharmacotherapies, different enrollment criteria, and different original research questions, which introduces heterogeneity that a pooled secondary analysis cannot fully account for. Substance use was self-reported rather than biologically verified, and the key statistical findings had p-values clustered just under 0.05 (0.0497, 0.042, 0.0499), a pattern that, combined with testing multiple outcomes without described correction for multiple comparisons, warrants real caution before treating these associations as robust effects rather than exploratory signals.

What This Paper Does Not Show
This analysis does not show that reducing cannabis use causes people to drink more alcohol or smoke fewer cigarettes; it identifies statistical associations in observational, self-reported data, not causal treatment effects. It does not establish a reliable, clinically actionable substitution or complementary-use pattern strong enough to guide specific treatment decisions, and it does not include outcomes beyond the original trials’ follow-up windows.

How This Fits With the Broader Clinical Conversation

This analysis adds to a mixed and long-running literature on substance substitution during [addiction treatment](https://cedclinic.com/cannabis-based-therapies-smoking-cessation/), where some studies find that reducing one substance leads patients to increase use of another, and others find no such relationship or even simultaneous declines across substances.

The authors frame their findings as initial insights meant to prompt closer monitoring of alcohol and tobacco use during cannabis use disorder treatment, not as a settled account of how cannabis cessation affects other substance use.

Dr. Caplan’s Take

*This is exactly the kind of study I want to see more of: a real attempt to look past the single substance a trial was designed to treat and ask what happens to a patient’s broader substance use pattern. Addiction rarely stays confined to one substance, and treatment research that ignores that misses something clinically important.*

*That said, I would not change how I counsel patients based on p-values this close to the 0.05 line in an exploratory, pooled analysis of trials that were not designed to test this question. What I take from this is a reminder to ask patients in cannabis use disorder treatment about their alcohol and tobacco use directly, rather than assuming one will improve as the other does. The signal here is worth watching, not yet worth building a clinical protocol around.*

What a Careful Reader Should Take Away
A pooled, exploratory analysis of 829 patients across seven cannabis use disorder trials found modest, statistically borderline signals that cannabis craving and use track with small next-week shifts in alcohol and cigarette use, supporting closer clinical attention to polysubstance use during treatment without establishing a reliable substitution effect.

Evidence Interpretation Guide

## How to Read a Borderline-Significant, Pooled Secondary Analysis

Pooled analyses of trial data not originally designed together can surface genuinely useful patterns, but they also carry a specific set of caveats that are easy to skip past in a headline.

Four checks keep this analysis’s real contribution, an early signal worth monitoring, from being read as a confirmed clinical effect.

### A Four-Step Reading Frame

**Confirm what was pooled**Seven separate trials with different medications and designs, not one study built to test substitution.

**Check the p-values**Key findings sat at 0.0497, 0.042, and 0.0499, just inside significance and worth treating cautiously.

**Separate association from cause**Self-reported, observational data can show a pattern without proving cannabis changes drinking or smoking.

**Note what the authors call it**The authors themselves describe these as initial insights, not confirmed treatment effects.

The Research Question
Do cannabis use and craving during cannabis use disorder treatment predict changes in alcohol and cigarette use the following week, and does pharmacotherapy change that relationship?

The Patient Question
If I cut back on cannabis, will I end up drinking more or smoking more instead?

The Bottom Line
The pooled data suggest a possible, modest link between cannabis craving or use and small next-week shifts in alcohol and cigarette use, but the evidence is exploratory and not strong enough to predict what will happen for any individual patient.

CED Perspective Lens

## The Same Study Can Mean Different Things Depending on the Question Being Asked

Scientific papers rarely answer a single question. Patients, clinicians, researchers, policymakers, and critics often read the same data differently. The perspectives below explore how this study looks through several evidence-based lenses.

Lens Overview
Eight perspectives keep an exploratory but genuinely useful pooled analysis from being overstated as a confirmed substitution effect or dismissed as clinically irrelevant.

#### What This Means If You Are Cutting Back on Cannabis

This analysis found only modest, borderline statistical signals linking cannabis craving and use to small shifts in alcohol and cigarette use the following week, not a reliable rule that cutting back on cannabis will make you drink or smoke more or less.

If you are working on reducing cannabis use, it is reasonable to pay attention to your alcohol and tobacco use during that process and mention any changes to your treating clinician.

Lens takeaway
Watch your alcohol and tobacco use during cannabis cessation, but do not expect a predictable trade-off.

#### A Reason to Ask, Not Yet a Reason to Predict

This pooled analysis supports actively asking patients in cannabis use disorder treatment about alcohol and tobacco use rather than assuming those will passively track cannabis outcomes.

The statistical signals were weak and the trials pooled were heterogeneous, so this should inform monitoring practice, not specific predictions about how an individual patient’s other substance use will change.

Lens takeaway
Use this as a prompt to monitor polysubstance use, not a predictive tool.

#### Borderline P-Values Deserve a Second Look

All three key findings had p-values clustered just under the conventional 0.05 threshold (0.0497, 0.042, 0.0499), a pattern that raises the question of how many outcomes were tested and whether correction for multiple comparisons was applied.

Findings this close to the significance threshold, in an exploratory analysis, are more appropriately treated as hypothesis-generating than as confirmed effects.

Lens takeaway
Borderline p-values in an exploratory analysis call for replication before confidence.

#### Polysubstance Patterns Are the Clinical Norm

Most patients in cannabis use disorder treatment are not using cannabis in isolation, and this analysis is a useful reminder that treatment monitoring should reflect that reality rather than focusing on a single substance.

The differing patterns for alcohol (possible complementary use) and cigarettes (possible substitution, but only in the active treatment arm) suggest that a one-size-fits-all assumption about substitution is not supported by this data.

Lens takeaway
Different substances may move in different directions during cannabis cessation; monitor each separately.

#### Seven Trials, One Analysis, Many Assumptions

Pooling data from seven trials that were designed independently, with different medications, populations, and endpoints, introduces heterogeneity that statistical modeling can adjust for but not eliminate.

Self-reported substance use, without biological verification, is a real limitation for an analysis built specifically around detecting small week-to-week changes in use.

Lens takeaway
Heterogeneous, self-reported, pooled data support caution before generalizing these findings.

#### A Template for Mining Existing Trial Data

This analysis illustrates a resource-efficient way to ask new questions of data already collected in completed trials, rather than requiring an entirely new, purpose-built study to explore substitution patterns.

The authors’ own framing suggests the logical next step would be a study designed from the outset to test substitution and complementary-use hypotheses, ideally with biologically verified substance use measures.

Lens takeaway
This is a hypothesis-generating reanalysis, best followed by a purpose-built confirmatory study.

#### Framing Substitution Claims Carefully Matters

Overstating this analysis as proof that cannabis cessation causes increased drinking, or that cannabis treatment reliably reduces smoking, would misrepresent findings that the authors themselves describe as initial and exploratory.

Accurate public communication about polysubstance use during [addiction treatment](https://cedclinic.com/cannabis-based-therapies-smoking-cessation/) supports better-informed patients and clinicians without inflating the certainty of early, borderline findings.

Lens takeaway
Communicate this as an early signal, not a settled substitution effect.

#### The Right Question, an Early-Stage Answer

The research question, whether cannabis treatment reshapes use of other substances, is clinically important and underexplored, which makes this analysis worth attention despite its limitations.

But the combination of pooled heterogeneous trials, self-report data, and borderline statistical significance means this study answers that question only provisionally, and a confirmatory, purpose-built trial is the necessary next step.

Lens takeaway
An important question with a provisional, not final, answer.

Join the Conversation

Have a question about how this applies to your situation? [Ask Dr. Caplan](https://benjamincaplan.com/ask-dr-caplan)

Want to discuss this topic with other patients and caregivers? [Join the forum discussion](https://cedclinic.com/interact/discussion-forums/)

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Source: [Douglass MA, Fronk GE, Baker N, McRae-Clark AL, Gray KM, Santa Ana EJ, Tomko RL, Neelon B, McClure EA. Cannabis craving and cross-substance substitution during cannabis treatment: Initial insights across seven cannabis use disorder clinical trials. Addict Behav. 2026 Aug 12;183:108834. DOI: 10.1016/j.addbeh.2026.108834. PMID: 42594823.](https://pubmed.ncbi.nlm.nih.gov/42594823/)

Related Reading at CED Clinic
Continue exploring the evidence

[Cannabinoid Effects on Substance Use Disorders: Evidence and Insights](https://cedclinic.com/cannabinoid-effects-substance-use-disorders-review/)

CED’s earlier coverage of a large systematic review examining whether cannabinoids themselves help treat substance use disorders, useful context for how cannabis use disorder treatment evidence has been evolving.

[Read the cannabinoids and substance use disorders review](https://cedclinic.com/cannabinoid-effects-substance-use-disorders-review/)

[Virtual Program Reduces Cannabis and Alcohol Use in Native American Emerging Adults](https://cedclinic.com/culturally-grounded-virtual-substance-use-intervention-native-american/)
A randomized trial of a culturally grounded virtual intervention that reduced both cannabis and alcohol use together, offering a contrasting example of co-occurring substance use responding to a single treatment.

[Read the Native American emerging adults trial coverage](https://cedclinic.com/culturally-grounded-virtual-substance-use-intervention-native-american/)

[Understanding Mental Health Risks of Cannabis Use Disorder in Youth](https://cedclinic.com/cannabis-use-disorder-mental-health-risks-young-adults/)
Background on cannabis use disorder’s broader clinical risks in younger patients, useful context for clinicians managing polysubstance use during treatment.

[Read about cannabis use disorder risks in young adults](https://cedclinic.com/cannabis-use-disorder-mental-health-risks-young-adults/)

Similar Studies on CEDClinic.com
Earlier coverage on closely related evidence
When a new paper overlaps with earlier CED Clinic coverage, we preserve the chain instead of hiding the overlap. These links point to older related posts so readers can compare what is new, what is repeated, and how the evidence has moved.

Related digest item
[Cannabinoid Effects on Substance Use Disorders: Evidence and Insights](https://cedclinic.com/cannabinoid-effects-substance-use-disorders-review/)

A tier-weighted systematic review of 97 studies found short-term symptom relief from cannabinoids in substance use disorder treatment but no durable evidence for abstinence or relapse prevention.

Related topic area (cannabis and substance use disorder treatment), but examines cannabinoids as a treatment rather than cross-substance substitution during cannabis cessation.

[Compare earlier coverage](https://cedclinic.com/cannabinoid-effects-substance-use-disorders-review/)

Related digest item
[Virtual Program Reduces Cannabis and Alcohol Use in Native American Emerging Adults](https://cedclinic.com/culturally-grounded-virtual-substance-use-intervention-native-american/)
A randomized trial found a culturally grounded virtual intervention reduced both cannabis and alcohol use simultaneously among urban Native American emerging adults.

Related topic (co-occurring cannabis and alcohol use), but tests a behavioral intervention rather than analyzing substitution patterns during pharmacologic CUD trials.

[Compare earlier coverage](https://cedclinic.com/culturally-grounded-virtual-substance-use-intervention-native-american/)

## Frequently Asked Questions

What did this analysis look at?

Researchers pooled longitudinal data from 829 participants across seven pharmacologic clinical trials for cannabis use disorder, using mixed-effects models to test whether weekly cannabis use or craving predicted the following week’s alcohol and cigarette use, and whether treatment assignment changed that relationship.

Did cutting back on cannabis make people drink more alcohol?

Weeks with both higher cannabis craving and higher cannabis use frequency predicted a small increase in the following week’s alcohol quantity, not how often people drank, and this signal was statistically borderline (p=0.0497).

Did cannabis use affect cigarette smoking?

Higher cannabis quantity in a given week predicted slightly lower cigarette quantity the following week across the full sample, and among participants on active pharmacotherapy, higher cannabis craving was linked to fewer smoking days.

Did the medication being tested change these patterns?

No significant three-way interactions between treatment assignment, cannabis measures, and substance outcomes emerged overall. The one treatment-specific signal, for cigarette frequency and craving, was described by the study authors as limited evidence.

How many people were studied, and where did the data come from?

The analysis pooled 829 participants (mean age 27.1 years, 31% female, 63% White, 13% Latine or Hispanic) from seven separate pharmacologic clinical trials for cannabis use disorder, which were not originally designed to study substitution.

Is this strong evidence that cannabis treatment causes changes in drinking or smoking?

No. This is an exploratory, observational secondary analysis of self-reported data, not a study designed to test causation, and the key statistical findings had p-values clustered just under the conventional 0.05 threshold.

What does cross-substance substitution mean in this study?

It refers to the idea that reducing use of one substance, cannabis, might lead a person to use more of another substance, such as alcohol or tobacco, to compensate. This analysis found mixed evidence: alcohol use showed a pattern more consistent with complementary use, while cigarette use showed signs of both co-use and substitution.

Should clinicians change how they treat cannabis use disorder based on this study?

The authors frame their findings as initial insights supporting closer monitoring of alcohol and tobacco use during cannabis use disorder treatment, not as evidence strong enough to change specific treatment protocols.

What are the main limitations of this analysis?

The seven pooled trials used different medications, populations, and original research questions; substance use was self-reported rather than biologically verified; and the key p-values were close to the significance threshold without described correction for multiple comparisons.

What should someone in cannabis use disorder treatment take from this study?

It is reasonable to pay attention to your own alcohol and tobacco use while working on cannabis cessation and to mention any changes to your treating clinician, though this study does not predict a specific or reliable trade-off for any individual patient.

 

### Related

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### Verification & Medical Governance

- **Lead Clinical Author:** Benjamin Caplan, MD
- **Credentials:** Board Certified in Family Medicine (ABFM), Former CMO Canna Care Docs (250,000+ patients supervised), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House).
- **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`).
- **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/).
- **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637).
- **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).