Cannabinoids and Biological Reactivity to Stress

NCT06430580 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: STUDY00006376R21DA058780-01A1
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to test the impact of two drugs that produce temporary stress-like symptoms, both in isolation and together, on cannabis use motivation in individuals with Cannabis Use Disorder. The main questions it will answer are:

1. 1.How do different forms of stress affect cannabis use motivation?
2. 2.How do different forms of stress affect the body's natural cannabinoids?

Conditions

Cannabis Use Disorder

Outcome Measures

Primary Outcomes (7)

• Amplitude of neurophysiological response to cannabis cues (μV)

  Change in electroencephalography-recorded (EEG) late positive potential amplitude to cannabis cue images after hydrocortisone (with or without yohimbine) compared to placebo+placebo and yohimbine+placebo conditions (higher amplitudes indicate worse outcome)

  Late positive potential amplitude outcome is assessed at each of the four lab visits, which take place over the study period (10-22 days)

• Amplitude of Demand Intensity for Cannabis (# of hits at $0)

  Marijuana purchase task-derived Intensity after hydrocortisone administration (with or without yohimbine) compared to placebo+placebo and yohimbine+placebo (increased Intensity indicates worse outcome)

  Intensity is assessed at each of the four lab visits, which take place over the study period (10-22 days)

• Peak Total Monetary Expenditure for Cannabis (total amount of money spent on hits)

  Marijuana purchase task-derived OMax after hydrocortisone administration (with or without yohimbine) compared to placebo+placebo and yohimbine+placebo (increased OMax indicates worse outcome)

  OMax is assessed at each of the four lab visits, which take place over the study period (10-22 days)

• Breakpoint of Monetary Expenditure for Cannabis (price at which no hits are purchased)

  Marijuana purchase task-derived Breakpoint after hydrocortisone administration (with or without yohimbine) compared to placebo+placebo and yohimbine+placebo (increased Breakpoint indicates worse outcome)

  Breakpoint is assessed at each of the four lab visits, which take place over the study period (10-22 days)

• Sensitivity of Cannabis Hit Purchasing Behavior to Price Increases

  Marijuana purchase task-derived Elasticity after hydrocortisone administration (with or without yohimbine) compared to placebo+placebo and yohimbine+placebo (decreased Elasticity indicates worse outcome)

  Elasticity is assessed at each of the four lab visits, which take place over the study period (10-22 days)

• Frequency of implicit cannabis image choice

  Change in cannabis image selections on the Implicit Image Choice Task (computerized behavioral task; range 0-30; higher scores indicate worse outcome) after hydrocortisone administration (with and without yohimbine) compared to placebo+placebo and yohimbine+placebo

  Implicit choice task # of cannabis image selections outcome is assessed at each of the four lab visits, which take place over the study period (10-22 days)

• Frequency of explicit cannabis image choice

  Change in cannabis image selections on the Explicit Image Choice Task (computerized behavioral task; range 0-30; higher scores indicate worse outcome) after hydrocortisone administration (with and without yohimbine) compared to placebo+placebo and yohimbine+placebo

  Explicit choice task # of cannabis image selections outcome is assessed at each of the four lab visits, which take place over the study period (10-22 days)

Study Arms (4)

20mg hydrocortisone + 54mg yohimbine hcl

EXPERIMENTAL

20mg hydrocortisone, single oral dose 54mg yohimbine hcl, single oral dose

Drug: Hydrocortisone Oral; Drug: Yohimbine Hydrochloride

20mg hydrocortisone + 54mg placebo

EXPERIMENTAL

20mg hydrocortisone, single oral dose 54mg cornstarch placebo, single oral dose

Drug: Hydrocortisone Oral; Drug: Cornstarch Placebo 54mg

20mg placebo + 54mg yohimbine hcl

ACTIVE COMPARATOR

20mg cornstarch placebo, single oral dose 54mg yohimbine hcl, single oral dose

Drug: Yohimbine Hydrochloride; Drug: Cornstarch Placebo 20mg

20mg placebo + 54mg placebo

PLACEBO COMPARATOR

20mg cornstarch placebo, single oral dose 54mg cornstarch placebo, single oral dose

Drug: Cornstarch Placebo 20mg; Drug: Cornstarch Placebo 54mg

Interventions

Hydrocortisone Oral DRUG

20mg hydrocortisone, single oral dose

20mg hydrocortisone + 54mg placebo; 20mg hydrocortisone + 54mg yohimbine hcl

Yohimbine Hydrochloride DRUG

54mg yohimbine hcl, single oral dose

20mg hydrocortisone + 54mg yohimbine hcl; 20mg placebo + 54mg yohimbine hcl

Cornstarch Placebo 20mg DRUG

20mg cornstarch placebo, single oral dose

20mg placebo + 54mg placebo; 20mg placebo + 54mg yohimbine hcl

Cornstarch Placebo 54mg DRUG

54mg cornstarch placebo, single oral dose

20mg hydrocortisone + 54mg placebo; 20mg placebo + 54mg placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Meets criteria for current, moderate to severe Cannabis Use Disorder (CUD) as assessed by the Structured Clinical Interview (SCID) for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) during the screening interview.
• Reports engagement in near-daily/daily cannabis use.
• Provide a urine sample positive for THC.
• Must be in generally good health as determined by a physical exam, EKG, and blood tests
• Must be adequately informed of the nature and risks of the study and given written informed consent prior to screening.
• Able to read and write in English.

You may not qualify if:

• Has a history of serious psychiatric problems (i.e., psychosis, Bipolar Disorder I) or meets criteria for a current Major Depressive Episode, as assessed by the SCID-V-RV.
• Reports current suicidal ideation.
• Meets DSM-5 criteria for any other current, moderate to severe substance use disorder (other than CUD or Tobacco Use Disorder
• Has a positive result urine drug screen for all other drugs aside from THC (i.e., amphetamine, methamphetamine, benzodiazepine, cocaine, MDMA, morphine, oxycodone, methadone, buprenorphine) at screening or at any lab visit.
• Has structural brain abnormalities (e.g., neoplasms), stroke, seizures, infectious disease, a history of other neurological diseases, or a history of head trauma resulting in unconsciousness.
• Has a history of cardiovascular disease, myocardial infarction, chest pain, or palpitations on exertion or drug use, edema, hypertension, resting heart rate \<50 BPM or \>100 BPM. Cardiovascular diseases include:
• a. Benign prostatic hyperplasia (BPH) b. Post-myocardial infarction
• Demonstrates systolic BP outside of acceptable range (80-140mmHG), or diastolic BP outside of acceptable range (50-90 mmHG)
• Has a history of cor pulmonale, dyspnea, orthopnea, tachypnea (\>24 breaths per minute), or uncontrolled chronic obstructive pulmonary disease or asthma.
• Currently taking any daily psychotropic medication
• Currently taking any of the following medications:
• Angiotensin-Converting Enzyme (ACE) inhibitors including Lisinopril, Enalapril, Benazepril, and Bamipril
• Angiotensin II Receptor Blockers (ARB) including Losartan, Valsartan, and Olmesartan
• Thiazide Diuretics including Hydrochlorothiazide (HCTZ), Chlorthalidone
• Calcium Channel Blockers including Amlodipine, Diltiazem, and Verapamil

Sponsors & Collaborators

• Florida State University: lead
• Wayne State University: collaborator
• National Institute on Drug Abuse (NIDA): collaborator
• Auburn University: collaborator

Study Sites (1)

The BRAINS Lab at Florida State University

Tallahassee, Florida, 32306-4301, United States

RECRUITING

MeSH Terms

Interventions

Hydrocortisone; Yohimbine

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Richard J Macatee, PhD

  Florida State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mallory Cannon, MS

CONTACT

850-644-2445; brains@psy.fsu.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 2x2 randomized double-blind within-subject crossover

Study Record Dates

• First Submitted: May 13, 2024
• First Posted: May 28, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: September 16, 2025

Record last verified: 2025-07

Locations

US (1)