Investigating Stress-related Mechanisms in the Laboratory and Real World in Individuals With Cannabis Use Disorder

• ClinicalTrials.gov Identifier: NCT04116619
• Recruitment Status: Recruiting
• First Posted: October 4, 2019
• Last Update Posted: February 25, 2021
• Sponsor: Yale University
• Collaborator: National Institutes of Health (NIH)
• Information provided by (Responsible Party): Stephanie Wemm, Yale University

Study Description

Brief Summary:

This research project proposes a novel approach to elucidate the biological adaptations associated with Cannabis Use Disorder and to assess whether such adaptations are predictive of higher drug craving in response to both drug cues and stressors in both the laboratory and real-world, and higher relapse risk and drug use in the real world.

Condition or disease	Intervention/treatment
Cannabis Use Disorder	Other: Guided Imagery Laboratory Session

Detailed Description:

The intent of this study is to recruit 25 treatment-seeking individuals with Cannabis Use Disorder (CUD) and 25 light users (<1 joint/week) to complete three guided imagery conditions (stress, cannabis, neutral) in inpatient research units. During the guided imagery, repeated measurements of subjective (i.e., craving, negative affect), neuroendocrine (i.e., cortisol), and physiological variables (i.e., heart rate variability [HRV]) will be collected. Thereafter, individuals with CUD will begin one-month of drug counseling treatment coupled with surveys delivered via smartphones daily in the morning, evening, and at four random times during the day.

Study Design

• Study Type: Observational
• Estimated Enrollment: 90 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Investigating Stress-related Mechanisms in the Laboratory and Real World in Individuals With Cannabis Use Disorder
• Actual Study Start Date: February 1, 2021
• Estimated Primary Completion Date: October 15, 2024
• Estimated Study Completion Date: April 15, 2025

Groups and Cohorts

Group/Cohort	Intervention/treatment
Individuals with Cannabis Use Disorder; Participants who meet criteria for Cannabis Use Disorder will complete three guided imagery conditions (stress, cannabis, neutral) in an inpatient research unit. During the guided imagery, repeated measurements of subjective (i.e., craving, negative affect), neuroendocrine (i.e., cortisol), and physiological variables (i.e., heart rate variability [HRV]) will be collected.	Other: Guided Imagery Laboratory Session; On days 1, 2 and 3 of the study, subjects will come to the research testing rooms and be provided with lunch before beginning the laboratory session. After a 40-minute adaptation period, two blood samples will be drawn before imagery (BASELINE). After the second blood draw, a 5-minute baseline period will follow to assess continuous pulse rate, BP, and HRV assessments. The subject and research staff conducting the sessions will be blinded to the order and content of the imagery condition. In each recording, the subjects will listen to the scripts over headphones and will vividly imagine the described situation, 'as if' it were happening right now," for 5 minutes. The research nurse will take a blood draw immediately after the imagery (IMAGERY). After that, three recovery blood draws will be performed at 15-minute intervals (RECOVERY). We will analyze the total of six blood samples for levels of cortisol.
Light Cannabis Users; Participants who are light cannabis users (<1 joint/week) will complete three guided imagery conditions (stress, cannabis, neutral) in an inpatient research unit. During the guided imagery, repeated measurements of subjective (i.e., craving, negative affect), neuroendocrine (i.e., cortisol), and physiological variables (i.e., heart rate variability [HRV]) will be collected.	Other: Guided Imagery Laboratory Session; On days 1, 2 and 3 of the study, subjects will come to the research testing rooms and be provided with lunch before beginning the laboratory session. After a 40-minute adaptation period, two blood samples will be drawn before imagery (BASELINE). After the second blood draw, a 5-minute baseline period will follow to assess continuous pulse rate, BP, and HRV assessments. The subject and research staff conducting the sessions will be blinded to the order and content of the imagery condition. In each recording, the subjects will listen to the scripts over headphones and will vividly imagine the described situation, 'as if' it were happening right now," for 5 minutes. The research nurse will take a blood draw immediately after the imagery (IMAGERY). After that, three recovery blood draws will be performed at 15-minute intervals (RECOVERY). We will analyze the total of six blood samples for levels of cortisol.

Outcome Measures

Primary Outcome Measures :

1. Rating of craving in the laboratory [ Time Frame: 3 days ]
   Participants will rate their level of stress and marijuana craving at five time points during the laboratory session, once at pre-baseline, baseline, immediately post-imagery procedures, and at three times point 15, 30, and 45 minutes post-imagery. Craving and stress will be assessed using a 100-point visual analog scale (VAS) in which 0="Not at all" and 100="Extremely High." Individuals with CUD will be compared to light marijuana users in their differences in slope in response to the imagery.
2. Rating of subjective stress in the laboratory [ Time Frame: 3 days ]
   Participants will rate their level of stress and marijuana craving at five time points during the laboratory session, once at pre-baseline, baseline, immediately post-imagery procedures, and at three times point 15, 30, and 45 minutes post-imagery. Craving and stress will be assessed using a 100-point visual analog scale (VAS) in which 0="Not at all" and 100="Extremely High." Individuals with CUD will be compared to light marijuana users in their differences in slope in response to the imagery.
3. Rating of subjective craving in the real world [ Time Frame: 28 days ]
   Participants will report using ecological momentary assessment (EMA) their current levels of stress and craving, if they have used marijuana, and if they experienced a stressor. 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 during marijuana use. Individuals with CUD will be compared to light marijuana users in their differences in real-world ratings of stress and craving. Craving and stress will be assessed using a 100-point visual analog scale (VAS) in which 0="Not at all" and 100="Extremely High."
4. Rating of subjective stress in the real world [ Time Frame: 28 days ]
   Participants will report using ecological momentary assessment (EMA) their current levels of stress and craving, if they have used marijuana, and if they experienced a stressor. 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 during marijuana use. Individuals with CUD will be compared to light marijuana users in their differences in real-world ratings of stress and craving. Craving and stress will be assessed using a 100-point visual analog scale (VAS) in which 0="Not at all" and 100="Extremely High."
5. Physiological response to stress and cannabis cues in the laboratory [ Time Frame: 3 days ]
   Plasma will be collected at each laboratory session to assess cortisol response to stress, drug cue, and neutral imagery exposure. Heart Rate Variability (HRV) measured via the Firstbeat Bodyguard 2 will be used to assess cardiovascular response to stress, drug, and neutral cue imagery exposure.
6. Heart rate response to stress and cannabis cues in the real world [ Time Frame: 2 weeks ]
   Heart Rate Variability (HRV) will be collected throughout the day on two separate three-day occasions during Weeks 1 and Week 2 via the Firstbeat Bodyguard.

Secondary Outcome Measures :

1. Blood pressure- diastolic [ Time Frame: 2 weeks ]
   A General Electric Dynamap will be used to place a blood pressure cuff on the subject's preferred arm to monitor blood pressure (BP) during the laboratory sessions in week 2 in order to assess change in BP responses to stress, drug cue and neutral provocation.
2. Blood pressure- systolic [ Time Frame: 2 weeks ]
   A General Electric Dynamap will be used to place a blood pressure cuff on the subject's preferred arm to monitor blood pressure (BP) during the laboratory sessions in week 2 in order to assess change in BP responses to stress, drug cue and neutral provocation.
3. Change in Cannabis use- Labs [ Time Frame: 4 weeks ]
   Cannabis use will be determined using a urine toxicology screen. Change in percent THCCOOH levels assessed via urine during the 4 week trial assessed by a weekly urine toxicology screen.
4. Change in Cannabis use- Self Report [ Time Frame: 4 weeks ]
   Change over time in daily reporting of cannabis use per day will be assessed by self-report on the Timeline Followback.

Biospecimen Retention:   Samples Without DNA

Saliva samples

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Individuals with Cannabis Use Disorder and individuals who use cannabis <1/week and do not meet criteria for Cannabis Use Disorder

Criteria

Inclusion Criteria:

• Cannabis using men and women who:
• 1. Are fluent in English;

• 2. Are using cannabis at levels to match either of the two groups:

  a) Light Users: i. Cannabis using levels of < 1 joint/week ii. Has never met DSM-5 criteria for CUD or other substance use disorders. b) Individuals with Cannabis Use Disorder: i. Meets criteria for CUD based on the SCID (≤ 2 symptoms in past year); ii. Has a past-year cannabis use pattern of ≤3 times per week; iii.Do not meet criteria for any other substance use disorders other than mild Alcohol Use Disorder.

• 3. Provide a negative breathalyzer for alcohol and only positive for cannabis use at all appointments;
• 4. Can provide written informed consent.

Exclusion Criteria:

• 1. Meets current or past DSM-5 criteria for Axis I for major psychiatric disorders, other than depression or anxiety disorder;
• 2. Meets criteria for a current Substance Use Disorder other than Cannabis or mild Alcohol Use Disorder;
• 3. Has any significant current medical conditions requiring medication, including neurological, renal, thyroid, cardiovascular, liver, endocrine, or immune conditions;
• 4. Reports current use of medications/drugs that interfere with HPA axis response,
• 5. Are women who are pregnant or lactating, are peri-/post-menopausal, or those with hysterectomies;
• 6. Report current use of psychotropic drugs other than antidepressants.

Contacts and Locations

Contacts

Contact: Stephanie Wemm, PhD; (203) 737-3436; stephanie.wemm@yale.edu

Locations

United States, Connecticut

Yale Stress Center; Recruiting

New Haven, Connecticut, United States, 06519

Contact: Rachel Hart 888-978-7377 stress@yale.edu

Sponsors and Collaborators

Yale University

National Institutes of Health (NIH)

Investigators

• Principal Investigator: Stephanie Wemm, PhD; Yale University

More Information

• Responsible Party: Stephanie Wemm, Associate Research Scientist, Yale University
• ClinicalTrials.gov Identifier: NCT04116619
• Other Study ID Numbers: 2000026364; KL2TR001862 ( U.S. NIH Grant/Contract )
• First Posted: October 4, 2019
• Last Update Posted: February 25, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Marijuana Abuse; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders