Mechanisms of Cannabidiol in Persons With MS: the Role of Sleep and Pain Phenotype

NCT05269628 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: HUM001907341R01AT011341-01
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to compare the effects of cannabidiol (CBD), tetrahydrocannabinol (THC), or both, on sleep and pain in persons with multiple sclerosis (MS). Little is known about how CBD and/or THC may help sleep, reduce pain, or perhaps even treat pain through better sleep.

Conditions

Multiple Sclerosis; Sleep; Pain

Keywords

Cannabidiol

Outcome Measures

Primary Outcomes (7)

• Mean change in sleep bout length

  Measured with in-laboratory polysomnography, reported as average length of continuous bouts of sleep, for each sleep stage and total sleep (in minutes).

  Baseline, 12 weeks

• Change in Walsh Spectral Entropy

  Measured with in-laboratory polysomnography, computed from EEG sleep stage data to quantify hypnogram regularity (dimensionless, values range from 0-1)

  Baseline, 12 weeks

• Change in Transition Entropy

  Measured with in-laboratory polysomnography. Entropy measure computed from sleep stage transition matrix that quantifies hypnogram regularity (dimensionless, values range from 0-1)

  Baseline, 12 weeks

• Change of center of activity

  Measured with in-laboratory polysomnography. Weighted mean temporal location over the night of all 30 second epochs scored as N3 and Rapid eye movement (REM) sleep

  Baseline, 12 weeks

• Change in sleep rhythmicity

  Measured by actigraphy. Probability of being in the same sleep/wake state 24h apart

  Baseline, 12 weeks

• Change in sleep regularity

  Measured by actigraphy in hours.

  Baseline, 12 weeks

• Change in sleep continuity and duration

  Measured by actigraphy in minutes to obtain time in wakefulness after sleep onset (WASO) and total sleep time.

  Baseline, 12 weeks

Study Arms (4)

Cannabidiol (CBD)

EXPERIMENTAL

Cannabidiol (Epidiolex® 100 mg/mL solution) will initially be prescribed as 50 mg (0.5 mL) twice daily during the first seven days of active treatment (half of full anticipated dose), followed by 100 mg (1 mL) twice daily for the remainder of the treatment interval (full dose). PLUS Placebo Tetrahydrocannabinol (TCH) capsules which contain no active ingredients. Matching placebo capsules will be taken twice per day in the same schedule and manner as active dronabinol.

Drug: Cannabidiol (CBD); Drug: Placebo THC

Tetrahydrocannabinol (THC)

ACTIVE COMPARATOR

Tetrahydrocannabinol (Dronabinol capsules) will initially be prescribed as 2.5 mg twice daily during the first seven days of active treatment (half of full anticipated dose), followed by 5 mg twice daily for the following days of active treatment (full dose). PLUS Placebo CBD (A matching placebo oral solution to Epidiolex® will be used that consists of all of the excipients in the active solution without the cannabidiol component). The placebo will be dosed in the same schedule and manner as active Epidiolex®.

Drug: Tetrahydrocannabinol (THC); Drug: Placebo CBD

CBD + THC

ACTIVE COMPARATOR

Cannabidiol (Epidiolex® solution) will initially be prescribed as 50 mg (0.5 mL) twice daily during the first seven days of active treatment (half of full anticipated dose), followed by 100 mg (1 mL) twice daily for the remainder of the treatment interval (full dose). PLUS Tetrahydrocannabinol (Dronabinol capsules) will initially be prescribed as 2.5 mg twice daily during the first seven days of active treatment (half of full anticipated dose), followed by 5 mg twice daily for the following days of active treatment (full dose).

Drug: Cannabidiol (CBD); Drug: Tetrahydrocannabinol (THC)

Placebo CBD + Placebo THC

PLACEBO COMPARATOR

Placebo CBD (A matching placebo oral solution to Epidiolex® will be used that consists of all of the excipients in the active solution without the cannabidiol component). The placebo will be dosed in the same schedule and manner as the active CBD. PLUS Placebo Tetrahydrocannabinol (TCH) capsules which contain no active ingredients. Matching placebo capsules will be taken twice per day in the same schedule and manner as active drug.

Drug: Placebo CBD; Drug: Placebo THC

Interventions

Cannabidiol (CBD) DRUG

Epidiolex® dose will be 0.5 mL (50 mg) twice daily during the first seven days of active treatment (half of full anticipated dose), followed by 1 mL (100 mg) twice daily for the remainder of the treatment interval (full dose). If the full dose (100 mg twice daily) is not tolerated by participants, they will have the option of going down to the original half-dose (50 mg twice daily). Participants who go back to the half-dose of Cannabidiol (50 mg twice daily) also have the option to request once-per-day dosing with study drug taken at preferred time of day. Participants who request once-per-day dosing will not exceed a total daily dose 100 mg Cannabidiol per day. Participants who are tolerating the full-dose of medication (Cannabidiol 100 mg twice daily) will not be allowed to combine these doses into one daily dose.

Also known as: Epidiolex® 100 mg/mL solution

CBD + THC; Cannabidiol (CBD)

Tetrahydrocannabinol (THC) DRUG

Dronabinol dose will be 2.5 mg twice daily during the first seven days of active treatment (half of full anticipated dose), followed by 5 mg twice daily for the remainder of the treatment interval (full dose). If the full dose (5 mg twice daily) is not tolerated by participants, they will have the option of going down to the original half-dose (2.5 mg twice daily). Participants who go back to the half-dose of Dronabinol (2.5 mg twice daily) also have the option to request once-per-day dosing with study drug taken at preferred time of day. Participants who request once-per-day dosing will not exceed a total daily dose 5 mg Dronabinol per day. Participants who are tolerating the full-dose of medication (Dronabinol 5 mg BID) will not be allowed to combine these doses into one daily dose.

Also known as: Marinol®, dronabinol capsules

CBD + THC; Tetrahydrocannabinol (THC)

Placebo CBD DRUG

Placebo solution will be taken twice per day, using the same dosing regimen as described for Epidiolex®.

Placebo CBD + Placebo THC; Tetrahydrocannabinol (THC)

Placebo THC DRUG

Placebo capsules will be taken twice per day in the same schedule and manner as active dronabinol.

Cannabidiol (CBD); Placebo CBD + Placebo THC

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with clinically definite MS (those who are on a disease modifying therapy must be on a stable dose without evidence of liver toxicity for at least 3 months);
• Presence of chronic pain defined as moderate to severe pain for at least 3 months, based on a 0-10 numeric rating scale (NRS);
• Willingness to maintain stable analgesic regimen during study period;
• Recent serum aspartate transaminase, alanine transaminase, and bilirubin testing within 90 days of screening;

You may not qualify if:

• Current shift work sleep disorder, or narcolepsy diagnosed with polysomnography and multiple sleep latency test;
• History of MS relapse within the last 30 days prior to screening (participants will be considered eligible after the 30-day window);
• Pain due to cancer;
• Pregnancy or breastfeeding;
• Unwillingness to use contraception from screening until the end of drug treatment
• Current suicidal ideation (SI) with intent and/or plan; these individuals will be assessed by a study psychologist and referred for urgent mental health treatment as indicated;
• Current severe depression as indicated by a PHQ-9 score of ≥ 17 that includes indicators of significant depressed mood (sum of items #1 and #2 ≥ 5).
• History of mania or schizophrenia diagnosis
• Known hypersensitivity to cannabinoids in general, or Epidiolex® or Dronabinol specifically or its excipients (e.g., sesame oil)
• History of the following cardiovascular conditions: recent myocardial infarction or stroke (last 6 months prior to screening), unstable angina, left ventricular hypertrophy, mitral valve prolapses, severe coronary artery disease, NYHA class III or IV congestive heart failure.
• History severe hepatic impairment (must have blood AST ≤ 2.0x ULN, ALT ≤ 2,0x ULN, and bilirubin ≤ 1.5x ULN within the last 90 days (AST, ALT, bilirubin testing will be required within 90 days of screening);
• History of seizure disorder (recurrent, unprovoked seizures not explained by a known reversible cause) or history of certain types of head injury that could cause an increased risk of seizures;
• History of prescription or illicit drug abuse (such as cocaine, amphetamine, methamphetamine, heroin);
• Current risk for alcohol misuse as indicated by a score of ≥ 8 on the Alcohol Use Disorders Identification Test (AUDIT) self-report measure.
• Current warfarin, valproate or clobazam use.

Sponsors & Collaborators

• Tiffany J. Braley, MD, MS: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis; Pain

Interventions

Cannabidiol; Solutions; Dronabinol

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Pharmaceutical Preparations

Study Officials

• Tiffany Braley

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Johnson

CONTACT

734-615-9650; johnsodj@umich.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: February 13, 2022
• First Posted: March 8, 2022
• Study Start: March 25, 2022
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2027
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)