Mechanisms of Cannabidiol and Sleep in the Context of Alcohol Use (CALM)

The goal of this clinical trial is to learn if cannabidiol helps to improve sleep and decrease alcohol use. It will also learn about the safety of cannabidiol. The main questions it aims to answer are:

Does 4 weeks of nightly cannabdiol use:

1. improve sleep quality and time spent in REM sleep?
2. decrease alcohol use and alcohol craving?
3. pose any safety risks?

Researchers will compare cannabidiol to a placebo (a look-alike substance that contains no drug).

Participants will:

Take cannabidiol every night for 4 weeks Visit the clinic once at the beginning and once at the end of the study Wear an activity monitoring watch while in the study Complete an at-home sleep test both at the beginning and the end of the study Check in once a week with researchers via video conference

Study Overview

• Status: Not yet recruiting
• Conditions: Sleep; Alcohol Misuse
• Intervention / Treatment: Drug: Cannabidiol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ellie Sundali; Phone Number: 720-378-8532; Email: CALM.custudy@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able to provide informed consent
• Self reported poor sleep quality (PSQI score >5)
• Hazardous or harmful levels of alcohol consumption (MINI AUD score ≧2)
• No current moderate or severe alcohol withdrawal symptoms (CIWA-Ar)
• For female participants of childbearing potential: Not pregnant or lactating at the time of study enrollment or trying to become pregnant as confirmed by urine preg. Lack of childbearing potential confirmed by a history of amenorrhea for at least 12 consecutive months and serum FSH level within the laboratory's reference range for postmenopausal females OR documented bilateral oophorectomy and/or hysterectomy
• For female participants of childbearing potential: Agree to use a highly effective contraception method (i.e., a method with a failure rate of less than 1 percent per year when used consistently and correctly) starting at least five days before you begin the study and continuing for full participation.
• No current use of sleep medications including CBD in the last 90 days
• No history of complicated alcohol withdrawal (i.e., seizure, delirium tremens, or alcohol hallucinosis).
• No current or past 6 months active suicidal ideation or suicidal behavior
• No current diagnosis, or family history of diagnosis, of psychosis; current major psychiatric illness, such as bipolar disorder, major depression, or schizophrenia
• No current cannabis use disorder (MINI SUD for cannabis score ≧2)
• History of previous exposure to guaiol through CBD or other cannabis product

Exclusion Criteria:

• Current use of anti-epileptic medications (e.g., clobazam, sodium valproate, lamotrigine)
• Greater than low risk for obstructive sleep apnea (STOP-BANG <=4 or Moderate or greater risk as calculated by Nox Noxturnal Software from baseline PSG data)
• Current use of medications known to have major interactions with Epidiolex (e.g., brexanolone, buprenorphine, colchicine, esketamine, fezolinetant, ketamine, leflunomide, levoketoconazole, levomethadyl acetate, lomitapide, mipomersen, morphine, pexidartinib, pralsetinib, propoxyphene, relugolix, sodium oxybate, teriflunomide, and venetoclax)
• Current use of anti-psychotic medications
• Current use of potent CYP2C19 or CYP3A4 inducers (e.g., Rifampin, apalutamide, carbamazepine, enzalutamide, ivosidenib9, lumacaftor, ivacaftor, phenytoin, St. John's wort, Fosphenytoin, Mitotane, Phenobarbital, Primidone)
• History of hypersensitivity reactions to cannabidiol
• Liver function test (Alanine transaminase [ALT] and Aspartate transaminase [AST]) levels ≥2x the upper normal limits at baseline
• Moderate or severe liver disease
• Allergy or aversion to gelatin (softgels contain porcine gelatin)
• Report of illegal drug use (e.g., cocaine, methamphetamine) in the past 90 days or positive screening on urine toxicology test at Baseline visit.
• Uncontrolled hypertension
• Blood pressure findings concerning for moderate or severe alcohol withdrawal at baseline
• Abnormal resting heart rate, defined as <60 bpm or >100 bpm at baseline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Placebo	Drug: Placebo; Taste and appearance matched softgel with hemp seed oil, glycerin, and gelatin
Experimental: 300mg oral cannabidiol	Drug: Cannabidiol; 300mg broad spectrum hemp extract in 50mg softgels

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol Use Frequency	Measure of frequency of alcohol use using the Timeline Followback	4 weeks
Sleep Efficiency	A calculation of objective quality of sleep as measured by a continuously worn actigraphy watch	4 weeks
Total Sleep Time	An average of total time spent asleep each night as measured by a continuously worn actigraphy watch	4 weeks
Time Spent in REM	Amount of time spent in the rapid eye movement sleep stage as measured by polysomnography	4 weeks
Subjective Sleep Quality	Self reported sleep quality using the Patient Reported Outcomes Measurement Information Scale (PROMIS) Sleep Disturbance Subscale. The scale consists of eight items with a minimum score of eight and a maximum score of 40. Higher scores correspond to worse sleep quality.	4 weeks
Alcohol Craving	Subjective report of alcohol craving using the Penn Alcohol Craving Scale. Scores range from 0 to 35, with higher scores corresponding to greater alcohol craving.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mood and Stress	Subjective report of symptoms of anxiety, depression, and stress using the Depression Anxiety Stress Scale (DASS). The DASS is a 21-item short-form measuring three related negative emotional states of depression, anxiety, and tension/stress. Scores for the entire measure range from 0 to 63, with higher scores corresponding to worse mood and stress outcomes. Subscales can also be scored individually (0-21).	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol Withdrawal	Safety monitoring of alcohol withdrawal symptoms using the Combine Systematic Assessment for the Treatment of Emergent Effects	4 weeks
Alcohol Withdrawal	Safety monitoring of alcohol withdrawal symptoms using the Revised Clinical Institute Withdrawal Assessment of Alcohol Scale	4 weeks
Risk for Self-Injurious Behaviors	Safety monitoring of risk for behaviors related to self-injury or suicide as measured by the Columbia Suicide Severity Rating Scale (C-SSRS). It includes five 'yes/no' items and follow-up interview items examining ideation intensity and characterization of suicidal behaviors. Research is mixed on whether a combined score (ideation and behavior) is meaningful on the C-SSRS. For the purposes of this study, any score greater than 0 is considered clinically significant. Suicidal ideation is defined by a scores of 'yes' on any items 1-5 and suicidal behavioral correspondents to 'yes' on any items 6-10.	4 weeks
Blood levels of alanine transaminase and aspartate transaminase	Safety monitoring of liver functioning for as determined by levels of alanine transaminase (ALT) and aspartate transaminase (AST) in blood samples. The upper limit of normal functioning typical for both AST and ALT for men is 35-40 units per liter (U/L) and 25-30 U/L for women.	4 weeks

Collaborators and Investigators

• Sponsor: University of Colorado, Boulder

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): February 1, 2031

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Cannabidiol
• Other Study ID Numbers: 25-0483

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No