Clinical trial NCT05885542: SCORE Emerging Adult Cannabis Use & Stress
Official title: Sex Differences in the Interface Between Cannabis Use and Stress Among Emerging Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cannabis Use Disorder
Keywords: cannabis
stress
sex
withdrawal
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2023-06-02
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Maximum age (years): 25
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Cannabis withdrawal symptoms
timeFrame: Assessed after 3-day cannabis abstinence period
measure: Stress reactivity
timeFrame: Measured 5 minutes after laboratory-administered Trier Social Stress Task
measure: Time to resumption of cannabis use
timeFrame: Measured as the time span from laboratory session to time of resumption of ad lib cannabis use (maximum of 10 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Kevin M Gray, M.D.
role: PRINCIPAL_INVESTIGATOR
References: