SCORE Emerging Adult Cannabis Use & Stress

• ClinicalTrials.gov Identifier: NCT05885542
• Recruitment Status: Recruiting
• First Posted: June 2, 2023
• Last Update Posted: November 18, 2023
• Sponsor: Medical University of South Carolina
• Information provided by (Responsible Party): Kevin Gray, MD, Medical University of South Carolina

Tracking Information

• First Submitted Date: April 3, 2023
• First Posted Date: June 2, 2023
• Last Update Posted Date: November 18, 2023
• Actual Study Start Date: November 1, 2023
• Estimated Primary Completion Date: July 31, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 30, 2023)

• Cannabis withdrawal symptoms [ Time Frame: Assessed after 3-day cannabis abstinence period ]
  Cannabis Withdrawal Scale score (Allsop et al., 2011) [minimum score 0 and maximum score 190; higher score means a worse outcome]
• Stress reactivity [ Time Frame: Measured 5 minutes after laboratory-administered Trier Social Stress Task ]
  Within Session Rating Scale - Stress score (Childress et al., 1986) [minimum score 0 and maximum score 10; higher score means a worse outcome]
• Time to resumption of cannabis use [ Time Frame: Measured as the time span from laboratory session to time of resumption of ad lib cannabis use (maximum of 10 days) ]
  After 3-day abstinence phase and laboratory session, ecological momentary assessment will be conducted twice daily for a 10-day span. Participants may resume ad lib cannabis use, and will be prompted to self-report the day/time that they resume cannabis use [minimum score 0 and maximum score 10 days, with the possibility of no resumption at all; higher score means a better outcome, and no resumption at all by the end of the 10 days is the best possible outcome]

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: SCORE Emerging Adult Cannabis Use & Stress
• Official Title: Sex Differences in the Interface Between Cannabis Use and Stress Among Emerging Adults
• Brief Summary: The interface between cannabis use and stress is a particularly important focus for sex differences research in emerging adults. Given the dynamics at play in this critical stage when cannabis use is most prevalent, developmentally informed research is needed to guide tailored clinical interventions. This study will apply rigorous and innovative methods to elucidate sex differences in the nexus of cannabis use and stress among emerging adults with cannabis use disorder to guide the development of tailored treatments.
• Detailed Description: Among the physiological systems most important to brain development in emerging adulthood is the endocannabinoid system, which among other roles facilitates cognitive and behavioral processing, including the underpinnings of stress management and resiliency. Sex differences in endocannabinoid system development have been identified, and emerging evidence indicates a bidirectional relationship between stress exposure and the endocannabinoid system during emerging adulthood. Repeated exposure to exogenous cannabinoids, such as those administered via cannabis use, perturbates endocannabinoid system development, which may adversely affect the programming of future coping in a manner that differs by sex. Use of cannabis, which exerts its psychoactive effects via delta-9-tetrahydrocannabinol binding to endocannabinoid receptors, is more common among emerging adults than in any other age group. Many regular users develop a maladaptive, impairing pattern of use characterized as cannabis use disorder (CUD). A constellation of preliminary evidence suggests several factors disproportionately complicate CUD in females compared to males; the salience of these factors in emerging adulthood indicates that this developmental stage deserves focused sex differences research to inform clinical management. A central running thread is the importance of stress and stress-reactivity across endocannabinoid system development, cannabis use, CUD, cannabis withdrawal, and relapse to cannabis use. This study combines rigorous ecological momentary assessment (EMA), controlled human laboratory procedures, and innovative bioassay collection. Emerging adult cannabis users with CUD (ages 18-25, N=148, 1:1 female to male ratio) will undergo 3 days of reinforced abstinence with EMA monitoring of cannabis withdrawal and stress-related symptoms, followed by a standardized laboratory stress induction paradigm. Blood levels of endocannabinoid system markers will be assessed before and after the abstinence period; during the lab session, self-report measures and biomarkers of stress reactivity will be collected. Double-blind cannabidiol (CBD) versus placebo dosing before the laboratory stress paradigm will allow for examination of effects on stress response during withdrawal. Prior work indicates CBD administration reduces stress response in general populations and preliminary research suggests this effect may extend to cannabis users; this has not been rigorously applied to induced stress amid cannabis withdrawal in emerging adults with CUD, a context particularly important for females with CUD who often report using cannabis to cope with stress. Following the laboratory session, EMA monitoring will resume as participants return to ad libitum cannabis use, providing the opportunity to test associations between stress reactivity and time to resumption of use. The proposed study is designed to elucidate sex differences and guide the development of tailored treatments that address factors disproportionately affecting emerging adult females with CUD.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Participants will be randomized to receive either double-blind single-dose CBD 800 mg or matched placebo (1:1) utilizing a stratified random block design. Randomization will be stratified by biological sex (female, male) to facilitate analyses incorporating sex as a biological variable.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Randomization allocation will be completed by statisticians in the Biostatistics Resource Core and all other investigators, study personnel, and participants will be blinded to past and future study allocation.

Primary Purpose: Treatment

• Condition: Cannabis Use Disorder

Intervention

• Drug: Cannabidiol oral solution
  Double-blind cannabidiol oral solution 800 mg administered once
• Drug: Placebo
  Double-blind placebo oral solution administered once

Study Arms

• Experimental: cannabidiol 800 mg
  Cannabidiol 800 mg will be administered orally once in the laboratory prior to a stress induction paradigm.
  Intervention: Drug: Cannabidiol oral solution
• Placebo Comparator: placebo
  Placebo (formulated to appear identical to active condition) administered orally once in the laboratory prior to a stress induction paradigm.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 30, 2023): 148
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 31, 2028
• Estimated Primary Completion Date: July 31, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments
• Meet DSM-5 criteria for CUD and report using cannabis at least five times weekly over the past month. While individuals may also meet criteria for other mild substance use disorders, they must identify cannabis as their primary substance
• Age 18-25
• BMI between 18-30 (to decrease variability in CBD response and in endocannabinoid system measures)
• AST, ALT, and total bilirubin within the laboratory reference range of normal
• Consent to alcohol abstinence for 12 hours prior to study visits, three days of cannabis abstinence as part of study procedures, and abstinence from all substances aside from cannabis, alcohol, and nicotine for the duration of the study
• Sexually active females of childbearing potential must agree to utilize an effective means of birth control.
• Consent to random assignment to CBD versus placebo

Exclusion Criteria:

• Females who are pregnant, nursing, or planning to become pregnant during the study.
• Current moderate or severe substance use disorder other than cannabis
• Current medications or supplements with clinically significant interactions with cannabidiol (per Lexicomp, this list includes Blasting, Doxorubicin, Mavacamten, Pazopanib, Sirolimus, Topotecan, Vincristine, Afatinib, Berotraslstat, Cilostazol, Citalopram, Colchicine, Digoxin, Lefamulin, Relugolix, Relugolix+Estradiol+Norethindrone, Rimegepant, Tizanidine, Ubrogepant, and Venetoclax in the categories of "avoid combination" or "consider therapy modification")
• Current unstable psychiatric or medical disorder that would interfere with safety, compromise data integrity, or preclude reliable participation
• History of hypersensitivity to CBD, sesame, or sesame products
• Inability to comply with study procedures

Sex/Gender

• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: All

• Ages: 18 Years to 25 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Kevin Branson; 843-792-0493; bransonk@musc.edu

Contact: Ashlyn Summersett; 843-792-0484; summeash@musc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05885542
• Other Study ID Numbers: Pro00127995
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: A final de-identified data set will be made available for retrieval and analysis.

• Current Responsible Party: Kevin Gray, MD, Medical University of South Carolina
• Original Responsible Party: Same as current
• Current Study Sponsor: Medical University of South Carolina
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kevin M Gray, M.D.; Medical University of South Carolina

• PRS Account: Medical University of South Carolina
• Verification Date: November 2023