NCT05269628 · Tiffany J. Braley, MD, MS
Mechanisms of Cannabidiol in Persons With MS: the Role of Sleep and Pain Phenotype
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Cannabidiol (CBD)
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.
DRUG
Tetrahydrocannabinol (THC)
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.
DRUG
Placebo CBD
Placebo solution will be taken twice per day, using the same dosing regimen as described for Epidiolex®.
DRUG
Placebo THC
Placebo capsules will be taken twice per day in the same schedule and manner as active dronabinol.
Primary outcome measures
Mean change in sleep bout length
Time frame: Baseline, 12 weeks
Measured with in-laboratory polysomnography, reported as average length of continuous bouts of sleep, for each sleep stage and total sleep (in minutes).
Change in Walsh Spectral Entropy
Time frame: Baseline, 12 weeks
Measured with in-laboratory polysomnography, computed from EEG sleep stage data to quantify hypnogram regularity (dimensionless, values range from 0-1)
Change in Transition Entropy
Time frame: Baseline, 12 weeks
Measured with in-laboratory polysomnography. Entropy measure computed from sleep stage transition matrix that quantifies hypnogram regularity (dimensionless, values range from 0-1)
Change of center of activity
Time frame: Baseline, 12 weeks
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
Change in sleep rhythmicity
Time frame: Baseline, 12 weeks
Measured by actigraphy. Probability of being in the same sleep/wake state 24h apart
Change in sleep regularity
Time frame: Baseline, 12 weeks
Measured by actigraphy in hours.
Change in sleep continuity and duration
Time frame: Baseline, 12 weeks
Measured by actigraphy in minutes to obtain time in wakefulness after sleep onset (WASO) and total sleep time.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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;
Exclusion criteria
- 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;
- Current cannabinoid use (participants may be reconsidered for inclusion after 30-day washout) and/or unwillingness to abstain from cannabinoids in any form from 30 days prior to the study of the study drugs and until the last follow up phone call at the end of the study (30 - 37 days after taking the last dose of the study drug).
- 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.
- Current use of known moderate or strong inhibitors of CYP3A4 \[topical ketoconazole, and temporary (\<= 4 week) oral courses of clarithromycin, fluconazole and itraconazole will be allowed\].
- Current use of strong inducers of CYP3A4 or CYP2C19 (does not include glucocorticoids or modafinil/armodafinil, which are permitted),
- Current use of moderate or strong inhibitors/inducers of CYP2C9, and narrow therapeutic index drugs (e.g., cyclosporine, amphotericin B).
- Current use of known non-minor Sensitive CYP2C19 Substrates, with the exception of some proton pump inhibitors (e.g., esoprazole, omeprazole)), periodic self-limited courses of diazepam (e.g., for MRI sedation) and submaximal doses of some antidepressant class medications (e.g., citalopram, and escitalopram), which will be permitted by the discretion of the treating neurologist PI.
- Refusal to avoid grapefruit or grapefruit products during the study treatment interval.
- Current use of opioids (tramadol permitted).
- Employed as a commercial driver or employed in an occupation that involves extreme heights or use of heavy machinery.
- History of car crashes or near-crashes due to untreated sleepiness that has led to near-misses in the past 6 months.
- Cognitive dysfunction as indicated by \>=3 errors on the six-item cognitive screener
- Expanded Disability Status Scale (EDSS) score \>=8.0.
- Blood pressure at screening above 180 mmHg systolic and/or 120 mmHg diastolic, or below 90 mmHg systolic and or 60 mmHg diastolic, or history of syncope related to orthostatic hypotension;
- Resting heart rate at screening less than 50 bpm or greater than 100 bpm;
- Any other treatment or medical, neurological, sleep, or psychiatric condition that, in the opinion of the investigators, could affect participant safety or eligibility.
Where
- Ann Arbor, Michigan
Collaborators
National Center for Complementary and Integrative Health (NCCIH)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 17, 2026 · Source of record for eligibility and locations