# Cannabis and Waking Cortisol: What the Study Did Not Prove

> **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637)
> **Publisher:** CED Clinic (https://cedclinic.com)
> **Canonical URL:** https://cedclinic.com/cannabis-waking-cortisol-study-evidence-check/
> **Published:** 2026-07-24T20:45:42-04:00 | **Last Modified / Clinically Audited:** 2026-09-28T10:48:25-04:00
> **Clinical Summary:** cannabis waking cortisol study: frequent users had higher waking cortisol, but no different awakening response and no proof of causation.

---

CED Clinical Relevance #75 Evidence Check The study addresses a clinically familiar question about frequent [cannabis use](https://cedclinic.com/cannabis-cardiovascular-health-insights-2024/) and stress physiology, while offering a useful correction to causal or diagnostic interpretations of a small observational finding.

Clinical Insight | CED Clinic
The most useful clinical contribution of this paper is precision. Researchers compared 39 adults with frequent [cannabis use](https://cedclinic.com/cannabis-cardiovascular-health-insights-2024/) and 43 controls using salivary cortisol samples collected at waking, 30 minutes later, and in the evening on two consecutive weekdays. The groups did not differ significantly in the cortisol awakening response, the rise from waking to 30 minutes later. The frequent-use group did have higher cortisol at the waking sample, and higher waking cortisol was associated with more cannabis-related consequences. Because cannabis exposure was not assigned and the groups were observed rather than followed through a controlled change in use, the study cannot determine whether cannabis raised cortisol, whether people under greater stress used cannabis more frequently, or whether sleep, withdrawal, psychiatric symptoms, or other factors contributed to both.

StressCortisolFrequent [Cannabis Use](https://cedclinic.com/cannabis-cardiovascular-health-insights-2024/)Mental HealthEvidence Check

Audience
Patients, clinicians, and readers trying to understand what a cortisol association can and cannot say about frequent cannabis use.

Primary Topic
Frequent cannabis use, waking cortisol, and the cortisol awakening response.

Source
[Read the peer-reviewed primary paper](https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/390)

A small observational study found that 39 frequent cannabis users had higher cortisol at waking than 43 controls, but the groups did not differ in the cortisol awakening response. The result does not show that cannabis caused stress-system dysregulation or that waking cortisol can diagnose problematic use. A careful reading keeps the positive finding, the negative replication result, and the study’s limits together.

Earlier context
[Frequent cannabis users wake with higher cortisol levels, study finds](https://cedclinic.com/frequent-cannabis-users-wake-with-higher-cortisol-levels-study-finds/)

The earlier article summarized the same study as evidence that frequent cannabis use may dysregulate the HPA axis and potentially worsen long-term stress resilience.

**What this perspective adds:** This primary-source evidence check corrects the emphasis by centering the unchanged cortisol awakening response, the small observational sample, the borderline waking-cortisol group difference, and the inability to determine whether cannabis use, underlying stress, sleep, withdrawal, or another factor explains the association.

What This Study Teaches Us
The paper teaches that waking cortisol and the cortisol awakening response are not interchangeable. A modest group difference at the first morning sample can coexist with no detectable group difference in the subsequent awakening response.

Why This Matters
Many patients use cannabis in the context of stress, anxiety, or sleep difficulty. A headline implying that frequent cannabis use damages the stress system can therefore affect clinical counseling. The study deserves attention, but the appropriate lesson is to ask more carefully about use patterns and consequences while resisting causal, diagnostic, and treatment claims the design cannot support.

Study Snapshot

Study Type
Peer-reviewed observational group comparison

Population
39 adults with frequent cannabis use and 43 healthy controls

Sampling
Saliva at awakening, 30 minutes later, and in the evening

Duration
Two consecutive weekdays

Primary Comparison
Cortisol awakening response between frequent-use and control groups

Main Negative Finding
No significant group difference in cortisol awakening response, p = 0.23

Main Positive Finding
Higher cortisol at awakening in the frequent-use group, p = 0.047

Within-Group Association
Waking cortisol was associated with cannabis-related consequences, p = 0.007

Major Limitation
Observational design cannot establish directionality or causation

Journal
Cannabis

Published
June 9, 2026

DOI
10.26828/cannabis/2026/000390

Clinical Bottom Line
Frequent users in this small study woke with modestly higher cortisol, but they did not have a significantly different cortisol awakening response. The paper supports further study of stress physiology and cannabis-related consequences, not a conclusion that cannabis caused endocrine dysregulation.

What the Researchers Actually Measured

Participants reported subjective stress and collected saliva at waking, 30 minutes later, and in the evening on two consecutive weekdays.

The investigators compared the cortisol awakening response between groups and examined relationships among subjective stress, cortisol, cannabis-use status, and cannabis-related consequences.

The Result That Did Not Replicate

The groups did not differ significantly in the cortisol awakening response. This matters because earlier work had suggested a blunted response among chronic users.

A negative replication result should remain visible in the interpretation. It narrows any claim that frequent use produces a consistent alteration in the morning cortisol rise.

The Positive Finding Worth Following

At the first waking sample, the frequent-use group had higher cortisol than controls. Within the study, higher waking cortisol was also associated with greater cannabis-related consequences.

This is a potentially useful signal for future research, but it is not yet a validated biomarker and should not be used as a diagnostic shortcut.

Why Directionality Remains Unknown

The study cannot determine whether frequent cannabis use altered waking cortisol, whether people experiencing more stress were more likely to use frequently, or whether shared factors influenced both.

Sleep timing, withdrawal, psychiatric symptoms, other substance use, collection adherence, product potency, and cannabinoid composition are among the factors that larger longitudinal work should characterize more fully.

A Better Clinical Conversation

The practical response is neither dismissal nor alarm. Clinicians can ask why a person uses cannabis, how often, at what time, with what products, and whether use is accompanied by withdrawal, sleep disruption, anxiety, or unwanted consequences.

Those questions are clinically useful now. Ordering cortisol tests or declaring chronic endocrine harm on the basis of this paper is not supported.

How Strong Is This Evidence?
This is peer-reviewed human research with a defined control group, repeated daily saliva sampling, and explicit statistical comparisons. Its evidentiary strength remains limited by the small sample, short observation window, self-collected samples, observational design, and inability to establish temporal direction.

Where This Paper Deserves Skepticism
The waking-cortisol group difference had a p value of 0.047, close to the conventional significance boundary, while the named cortisol awakening response comparison was negative. A careful interpretation therefore emphasizes replication, effect stability, adherence to collection timing, and adjustment for possible confounders.

What This Paper Does Not Show
The paper does not show that cannabis caused higher cortisol, that frequent use permanently damages the HPA axis, that cannabis worsens anxiety, that waking cortisol diagnoses [cannabis use disorder](https://cedclinic.com/sex-differences-cannabis-stress-reactivity-oxytocin/), or that a patient should stop or start a treatment based on this result.

How This Fits With the Broader Clinical Conversation

Stress and cannabis use can plausibly influence one another in both directions. People may use cannabis in response to stress, while frequent use, withdrawal, sleep disruption, and use-related consequences may also shape stress experience.

That bidirectional possibility is exactly why cross-sectional biomarker findings require restraint. A plausible mechanism is not the same as demonstrated causation.

Dr. Caplan’s Take

*The detail I would protect from the headline is that the cortisol awakening response itself did not differ between groups. The positive finding was narrower: a higher first morning value in frequent users.*

*That is worth studying, particularly because it tracked with use-related consequences, but it is not enough to tell a patient that cannabis caused endocrine dysfunction. Better counseling starts with patterns, context, symptoms, and consequences rather than a dramatic biomarker story.*

What a Careful Reader Should Take Away
A careful reader should keep three facts together: the study was small and observational, the cortisol awakening response did not differ between groups, and waking cortisol was modestly higher among frequent users. Together, those findings justify longitudinal research and more precise clinical questions, not causal certainty.

Evidence Interpretation Guide

Table of Contents

- [How to Read a Cortisol Association Without Turning It Into Causation](#How_to_Read_a_Cortisol_Association_Without_Turning_It_Into_Causation)[Four questions that keep the result in proportion](#Four_questions_that_keep_the_result_in_proportion)
- [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)[A Marker Is Not a Diagnosis](#A_Marker_Is_Not_a_Diagnosis)
- [The Use Pattern and the Reason for Use Both Matter](#The_Use_Pattern_and_the_Reason_for_Use_Both_Matter)
- [The Main Replication Result Was Negative](#The_Main_Replication_Result_Was_Negative)
- [Two Weekdays and Three Daily Samples Define the Boundary](#Two_Weekdays_and_Three_Daily_Samples_Define_the_Boundary)
- [Stress Relief and Stress Biology Are Different Questions](#Stress_Relief_and_Stress_Biology_Are_Different_Questions)
- [Consequences Deserve Attention Without Overreach](#Consequences_Deserve_Attention_Without_Overreach)
- [Headlines Can Reverse the Weight of the Findings](#Headlines_Can_Reverse_the_Weight_of_the_Findings)
- [Longitudinal Replication Is the Next Useful Step](#Longitudinal_Replication_Is_the_Next_Useful_Step)
- [Frequently Asked Questions](#Frequently_Asked_Questions)[Related](#Related)

## How to Read a Cortisol Association Without Turning It Into Causation

Biomarker studies can sound more definitive than their designs allow.

The right interpretation separates the exact measure that changed from the one that did not, then asks whether the design can establish direction.

### Four questions that keep the result in proportion

**What changed?**Cortisol at awakening was higher in the frequent-use group.

**What did not change?**The rise from waking to 30 minutes later did not differ significantly between groups.

**Can the study establish cause?**No. Cannabis use was observed, not assigned, and temporal direction was not established.

**What is clinically justified?**Ask about use patterns, stress, sleep, withdrawal, and consequences while awaiting longitudinal replication.

The Research Question
Do adults with frequent cannabis use differ from controls in morning cortisol patterns and relationships between stress and cortisol?

The Patient Question
Does this mean my cannabis use is damaging my stress hormones?

The Bottom Line
No causal conclusion can be drawn from this study. It identifies a waking-cortisol association that needs replication and longitudinal testing.

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
The study becomes most useful when its positive, negative, and uncertain findings remain together. These eight perspectives translate the paper without converting an association into a diagnosis or treatment rule.

#### A Marker Is Not a Diagnosis

A higher waking cortisol value in one small group comparison does not diagnose a stress disorder or prove that cannabis damaged the stress system.

The finding is a reason for better questions about sleep, stress, withdrawal, use patterns, and symptoms, not a reason for self-diagnosis.

Lens takeaway
Treat the result as a research signal, not a personal verdict.

#### The Use Pattern and the Reason for Use Both Matter

Frequent use can be both an exposure and a response to pre-existing stress. Cross-sectional data cannot cleanly separate those directions.

A useful history includes frequency, timing, product type, sleep, anxiety symptoms, withdrawal, and the consequences that the patient associates with use.

Lens takeaway
Clinical context is more informative than one biomarker.

#### The Main Replication Result Was Negative

The study was designed in part to examine the cortisol awakening response, the change from waking to 30 minutes later. That response did not differ significantly between groups.

The positive finding concerned the waking baseline, and it should not be expanded into a claim that the entire daily stress rhythm was proven to be dysregulated.

Lens takeaway
The unchanged awakening response is central, not a footnote.

#### Two Weekdays and Three Daily Samples Define the Boundary

Participants collected saliva at waking, 30 minutes later, and in the evening on two consecutive weekdays.

That design can detect group associations, but it cannot establish long-term trajectories, eliminate all timing error, or determine which factor came first.

Lens takeaway
Measurement structure limits causal interpretation.

#### Stress Relief and Stress Biology Are Different Questions

A person can report short-term relief while also having a complicated relationship among chronic stress, sleep, dependence, and use consequences.

This paper did not test cannabis as an [anxiety treatment](https://cedclinic.com/benzodiazepine-discontinuation-rates-medical-cannabis/) and did not compare clinical therapies.

Lens takeaway
Do not convert a biomarker association into treatment advice.

#### Consequences Deserve Attention Without Overreach

Within the frequent-use group, higher waking cortisol was associated with more cannabis-related consequences.

That association can support screening and conversation, but it still does not show that lowering cannabis use will necessarily normalize cortisol or improve a specific condition.

Lens takeaway
Screen thoughtfully and preserve uncertainty.

#### Headlines Can Reverse the Weight of the Findings

A headline about higher cortisol can sound causal and alarming even when the study found no group difference in its named awakening-response measure.

Accurate communication keeps the negative and positive findings together and identifies the study as observational.

Lens takeaway
Lead with the full result, not the most dramatic fragment.

#### Longitudinal Replication Is the Next Useful Step

Larger studies should track people over time, standardize collection adherence, characterize THC and CBD exposure, and measure sleep, withdrawal, psychiatric symptoms, and other substance use.

Those designs would better test whether waking cortisol predicts problematic use, follows it, or reflects shared underlying stress.

Lens takeaway
Directionality is the unanswered clinical question.

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/forum/cannabis-industry/)

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Source: [Subjective Stress and Diurnal Salivary Cortisol in Adults with Frequent Cannabis Use](https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/390)

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Earlier context
[Frequent cannabis users wake with higher cortisol levels, study finds](https://cedclinic.com/frequent-cannabis-users-wake-with-higher-cortisol-levels-study-finds/)

The earlier article summarized the same study as evidence that frequent cannabis use may dysregulate the HPA axis and potentially worsen long-term stress resilience.

This primary-source evidence check corrects the emphasis by centering the unchanged cortisol awakening response, the small observational sample, the borderline waking-cortisol group difference, and the inability to determine whether cannabis use, underlying stress, sleep, withdrawal, or another factor explains the association.

[Read the related background](https://cedclinic.com/frequent-cannabis-users-wake-with-higher-cortisol-levels-study-finds/)

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## Frequently Asked Questions

What did the cannabis waking cortisol study investigate?

It compared subjective stress and salivary cortisol patterns in 39 adults with frequent cannabis use and 43 healthy controls.

Did frequent cannabis users have a different cortisol awakening response?

No. The change from waking to 30 minutes later did not differ significantly between the groups.

What cortisol result did differ between groups?

The frequent-use group had higher cortisol at the waking sample, and that measure was associated with cannabis-related consequences within the study.

Does the study prove cannabis caused higher waking cortisol?

No. The observational comparison cannot determine whether cannabis use caused the difference, whether stress contributed to frequent use, or whether another factor influenced both.

Was this a cannabis treatment trial?

No. Researchers did not assign cannabis, test a therapeutic product, or compare treatments for anxiety or stress.

How were cortisol samples collected?

Participants collected saliva at awakening, 30 minutes after awakening, and in the evening on two consecutive weekdays.

Can a waking cortisol value diagnose problematic cannabis use?

No. The authors described it as a possible research marker that requires further investigation, not a validated diagnostic test.

Does the result mean frequent cannabis use worsens anxiety?

No. The study did not establish a causal effect on anxiety symptoms or show that cannabis worsened a psychiatric condition.

What should clinicians take from the paper?

It supports careful discussion of use frequency, stress, sleep, withdrawal, and cannabis-related consequences while avoiding causal claims from a single biomarker study.

What research would clarify the finding?

Larger longitudinal studies with detailed cannabinoid exposure, collection-adherence checks, and measurement of sleep, psychiatric symptoms, withdrawal, and other substance use would help establish directionality.

 

### Related

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### Verification & Medical Governance

- **Lead Clinical Author:** Benjamin Caplan, MD
- **Credentials:** Board Certified in Family Medicine (ABFM), 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).
