Cannabis UseCLR2NCT05833230
Investigating Real-world Stress-related Mechanisms in Heavy Cannabis Users
A study testing Intensive Day Monitoring in people with Cannabis Use and Cannabis, run by Yale University at 1 site in United States.
Trial summary
This research project proposes a novel approach to elucidate the biological adaptations associated with heavy cannabis use and to assess whether such adaptations are predictive of higher cannabis craving in response to both cannabis cues and stressors. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cannabis Use, Cannabis, Cannabis Abuse
- What is being tested?
- Intensive Day Monitoring
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2023to 26 Feb 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Cannabis-using men and women who:
- have a past-year pattern of 1 or more cannabis use episodes per week
- do not meet criteria for any other substance use disorders other than mild Cannabis and Alcohol Use Disorder
- are at least 18 years old
- are fluent in English
- can provide negative alcohol breathalyzer and only positive for cannabis at all visits.
- can provide written informed consent.
Who cannot join
- Individuals will be excluded if they:
- meeting current or past for major psychiatric disorders, other than depression or anxiety disorder;
- meeting criteria for a current Substance Use Disorder other than mild Cannabis Use Disorder and Alcohol Use Disorder;
- any significant current medical conditions requiring medication, including neurological, renal, thyroid, cardiovascular, liver, endocrine, or immune conditions
- current use of medications that interfere with hypothalamic-pituitary-adrenal axis response
- women who are pregnant, lactating, peri-/post-menopausal, or with hysterectomies
- current use of psychotropic drugs other than antidepressants.
Trial locations and contacts
1 site in 1 country.
About this study
This research project proposes a novel approach to elucidate the biological adaptations associated with heavy cannabis use and to assess whether such adaptations are predictive of higher cannabis craving in response to both cannabis cues and stressors.
Read the detailed description
As more states in the US have legalized recreational cannabis use, the number of individuals who use cannabis has also increased. Individuals are also using cannabis more frequently and in larger amounts as it has become more available and less challenging to purchase. These statistics are alarming because heavy use of cannabis has been linked to several societal and public health concerns, such as poorer mental health outcomes, higher rates of unemployment, and poorer life satisfaction. Many of these associations are associated with increased burden and stress; however, cannabis may alter how individuals cope biologically, such as the stress hormone cortisol, and psychologically with these stressors. For example, heavy use of alcohol and other drugs, such as cocaine or nicotine, change overall cortisol levels and how cortisol is released in response to stress. In laboratory studies, healthy individuals show a peak in cortisol following a stressor, whereas individuals who use alcohol and substances heavily have a less robust response. However, it is not known if this phenomenon occurs in individuals who use cannabis heavily in real-world stressful situations. Heavier use of alcohol or drugs is associated with wanting or craving drugs or alcohol more when in stressful situations. In this proposal, the team will use smartphone-delivered surveys combined with regular saliva sampling to examine the associations between psychological and biological stress responses and cannabis use. Individuals who use cannabis at least once weekly will be recruited to complete two weeks of smartphone surveys. The participants will also provide regular saliva samples and wear a heart rate monitor on three consecutive days within those two weeks. These saliva samples will be analyzed for the hormone cortisol and salivary alpha amylase. The team will examine if self-reported cannabis use predicts how an individual responds, both biological and psychological, to a stressor when they encounter it their daily life. The team will also investigate if individuals who use more cannabis are more likely to want to use cannabis when they encounter daily life stress. Results from this study can help us develop treatments that help individuals who use cannabis heavily better cope with stress.
- Conditions
- Cannabis Use, Cannabis, Cannabis Abuse
- Being tested
- Intensive Day Monitoring
- Keywords
- Cannabis, Marijuana, Smartphone, Cortisol, Heart rate variability, Ecological Momentary Assessment, Saliva
- Medical subject headings
- Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intensive Day MonitoringOther
During intake, a research assistant will demonstrate how to place the Heart Rate Variability monitor and provide instructions on completing the saliva samples at home. Participants will wear the Heart Rate Variability monitor for three consecutive, randomly selected days twice (72 hours each). Participants will be provided with six saliva sample collection tubes per day with explicit directions on when the saliva sampling should occur (hours since waking: +0, +1, +2, +4, +6, +10 hours, and before going to sleep). Participants will also complete a subjective report using similar questions included in the survey prompts at the same scheduled time as the saliva sample. All participants will complete a total of 6 such days during the study.
| Study group | Role | What they receive |
|---|---|---|
| Individuals who use cannabis | Experimental | Participants who are non-treatment seeking cannabis users (30 men, 30 women) ranging from once weekly use to multiple times daily. All participants will be recruited from the greater New Haven community and will complete four weeks of smartphone monitoring. During this monitoring period, they will also complete two three-consecutive days of intensive monitoring including more frequent smartphone surveys, saliva samples, heart rate monitoring, and an alcohol use monitor. Receives: Other: Intensive Day Monitoring |
What is being measured
The primary outcome is the main question the study is designed to answer.
Averaged cortisol response to stress and cannabis cues in the real world
Saliva samples for cortisol levels will be collected throughout the day on a randomly selected three-day period during week 1 of the study. The data will be averaged on all three days and not treated as separate time points.
Measured: 3 days in Week 1
Ratings of subjective craving in the real world
Participants will report using ecological momentary assessment (EMA) their current levels of craving. These reports will be generated in three different ways: at 8 am and 8 pm at night, at four random times during waking hours, and while drinking alcohol. Craving will be assessed using a 100-point visual analog scale (VAS) in which 0="Not at all" and 100="Extremely High."
Measured: 48 days
Ratings of subjective subjective stress in the real world
Participants will report using ecological momentary assessment (EMA) their current levels of stress. These reports will be generated in three different ways: at 8 am and 8 pm at night, at four random times during waking hours, and while drinking alcohol. Stress will be assessed using a 100-point visual analog scale (VAS) in which 0="Not at all" and 100="Extremely High."
Measured: 48 days
Secondary outcomes (1)
Self-reported cannabis use
Participants will report how recently they've used cannabis. Self-reports of stress, stress biology, and craving will be used to predict next-moment self-reported cannabis use (use since last assessment = 1, no use since last assessment = 0) from the smartphone assessments.
Measured: 48 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2023
- Study start1 Jun 2023
- Primary completion26 Feb 2025
- Study completion26 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cannabis UseStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Robert E. Leet and Clara Guthrie Patterson Trust Mentored Research Award
- Responsible party
- Sponsor
- Investigators
- Stephanie Wemm, PhD, Principal investigator, Associate Research Scientist, Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05833230
- Sponsor's protocol ID
- 2000034321
- Acronym
- CLR2
- Status last verified
- Feb 2025
- First submitted
- 17 Mar 2023
- Last updated
- 4 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Real-world Stress-related Mechanisms in Heavy Cannabis Users
- ClinicalTrials.gov ID
- NCT05833230
- Acronym / sponsor ID
- CLR2 / 2000034321
- Conditions
- Cannabis Use, Cannabis, Cannabis Abuse
- Keywords
- Cannabis, Marijuana, Smartphone, Cortisol, Heart rate variability, Ecological Momentary Assessment, Saliva
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Robert E. Leet and Clara Guthrie Patterson Trust Mentored Research Award
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 26 Feb 2025 (actual)
- Study completion
- 26 Feb 2025 (actual)
- First posted
- 27 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research project proposes a novel approach to elucidate the biological adaptations associated with heavy cannabis use and to assess whether such adaptations are predictive of higher cannabis craving in response to both cannabis cues and stressors.
Detailed description
As more states in the US have legalized recreational cannabis use, the number of individuals who use cannabis has also increased. Individuals are also using cannabis more frequently and in larger amounts as it has become more available and less challenging to purchase. These statistics are alarming because heavy use of cannabis has been linked to several societal and public health concerns, such as poorer mental health outcomes, higher rates of unemployment, and poorer life satisfaction. Many of these associations are associated with increased burden and stress; however, cannabis may alter how individuals cope biologically, such as the stress hormone cortisol, and psychologically with these stressors. For example, heavy use of alcohol and other drugs, such as cocaine or nicotine, change overall cortisol levels and how cortisol is released in response to stress. In laboratory studies, healthy individuals show a peak in cortisol following a stressor, whereas individuals who use alcohol and substances heavily have a less robust response. However, it is not known if this phenomenon occurs in individuals who use cannabis heavily in real-world stressful situations. Heavier use of alcohol or drugs is associated with wanting or craving drugs or alcohol more when in stressful situations. In this proposal, the team will use smartphone-delivered surveys combined with regular saliva sampling to examine the associations between psychological and biological stress responses and cannabis use. Individuals who use cannabis at least once weekly will be recruited to complete two weeks of smartphone surveys. The participants will also provide regular saliva samples and wear a heart rate monitor on three consecutive days within those two weeks. These saliva samples will be analyzed for the hormone cortisol and salivary alpha amylase. The team will examine if self-reported cannabis use predicts how an individual responds, both biological and psychological, to a stressor when they encounter it their daily life. The team will also investigate if individuals who use more cannabis are more likely to want to use cannabis when they encounter daily life stress. Results from this study can help us develop treatments that help individuals who use cannabis heavily better cope with stress.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Individuals who use cannabis | Experimental | Other: Intensive Day MonitoringParticipants who are non-treatment seeking cannabis users (30 men, 30 women) ranging from once weekly use to multiple times daily. All participants will be recruited from the greater New Haven community and will complete four weeks of smartphone monitoring. During this monitoring period, they will also complete two three-consecutive days of intensive monitoring including more frequent smartphone surveys, saliva samples, heart rate monitoring, and an alcohol use monitor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- have a past-year pattern of 1 or more cannabis use episodes per week
- do not meet criteria for any other substance use disorders other than mild Cannabis and Alcohol Use Disorder
- are at least 18 years old
- are fluent in English
- can provide negative alcohol breathalyzer and only positive for cannabis at all visits.
Key exclusion criteria (7 listed)
- meeting current or past for major psychiatric disorders, other than depression or anxiety disorder;
- meeting criteria for a current Substance Use Disorder other than mild Cannabis Use Disorder and Alcohol Use Disorder;
- any significant current medical conditions requiring medication, including neurological, renal, thyroid, cardiovascular, liver, endocrine, or immune conditions
- current use of medications that interfere with hypothalamic-pituitary-adrenal axis response
- women who are pregnant, lactating, peri-/post-menopausal, or with hysterectomies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intensive Day MonitoringDuring intake, a research assistant will demonstrate how to place the Heart Rate Variability monitor and provide instructions on completing the saliva samples at home. Participants will wear the Heart Rate Variability monitor for three consecutive, randomly selected days twice (72 hours each). Participants will be provided with six saliva sample collection tubes per day with explicit directions on when the saliva sampling should occur (hours since waking: +0, +1, +2, +4, +6, +10 hours, and before going to sleep). Participants will also complete a subjective report using similar questions included in the survey prompts at the same scheduled time as the saliva sample. All participants will complete a total of 6 such days during the study. | Other | Individuals who use cannabis |
Primary outcome
Averaged cortisol response to stress and cannabis cues in the real world
Time frame: 3 days in Week 1
Saliva samples for cortisol levels will be collected throughout the day on a randomly selected three-day period during week 1 of the study. The data will be averaged on all three days and not treated as separate time points.
Ratings of subjective craving in the real world
Time frame: 48 days
Participants will report using ecological momentary assessment (EMA) their current levels of craving. These reports will be generated in three different ways: at 8 am and 8 pm at night, at four random times during waking hours, and while drinking alcohol. Craving will be assessed using a 100-point visual analog scale (VAS) in which 0="Not at all" and 100="Extremely High."
Ratings of subjective subjective stress in the real world
Time frame: 48 days
Participants will report using ecological momentary assessment (EMA) their current levels of stress. These reports will be generated in three different ways: at 8 am and 8 pm at night, at four random times during waking hours, and while drinking alcohol. Stress will be assessed using a 100-point visual analog scale (VAS) in which 0="Not at all" and 100="Extremely High."
1 secondary outcome
Self-reported cannabis use
Time frame: 48 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephanie Wemm, PhD principal investigator
Associate Research Scientist, Psychiatry
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intensive Day Monitoring in people with Cannabis Use and Cannabis, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Averaged cortisol response to stress and cannabis cues in the real world (time frame: 3 days in Week 1). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2025.