Cannabinoid Interactions With Central and Peripheral Pain Mechanisms in Osteoarthritis of the Knee

NCT04992624 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: HUM0001809861R01AT010381-01A11K01DA049219-01A1
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is being done to better understand how daily treatment with Tetrahydrocannabinol (THC), Cannabidiol (CBD), or the combination of CBD plus THC affects knee osteoarthritis pain and other related symptoms. Consented participants will have a screening period and visit (up to 30 days to treatment start). If participants pass the screening phase, they will be randomly assigned to take one of the investigational study drugs. For this study, participants will not know when or if they are taking CBD, THC, THC plus CBD, and when or if taking placebo. Clinical pain will be assessed at multiple times throughout the study, and eligibility will be re-assessed at two weeks into the treatment period. It is possible that subjects will not be able to participate in the study after 14 days of of treatment. The treatment period will take approximately 16 weeks and then a follow-up period for approximately 2 weeks. In addition to treatment, participants will have clinical assessments, blood draws, questionnaires, daily pain diaries, sensory testing, as well as have functional connectivity magnetic resonance imaging (fcMRI).

Conditions

Osteoarthritis, Knee; Osteoarthritis of the Knee

Keywords

Cannabidiol; Tetrahydrocannabinol

Outcome Measures

Primary Outcomes (2)

• Default mode network (DMN) to insula connectivity via functional connectivity magnetic resonance imaging (fcMRI)

  Functional connectivity difference maps of insula to DMN connectivity using Independent Component Analysis and seed based connectivity. A reduction in the Z-score as a result of treatment will serve as the primary outcome measure.

  Day 15, and approximately day 99 of treatment

• Change in pre-post measurements of inflammatory marker IL-6.

  Serum IL-6

  Day 15, and approximately day 99 of treatment

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Cannabidiol (CBD)

EXPERIMENTAL

Up to 150 mg/day.

Drug: Cannabidiol (CBD)

Tetrahydrocannabinol (THC)

EXPERIMENTAL

Up to 10 mg/day.

Drug: Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol)

CBD plus THC

EXPERIMENTAL

Up to 150 mg/day CBD plus up to 10 mg/day THC.

Drug: Cannabidiol (CBD); Drug: Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol)

Interventions

Placebo DRUG

Placebo drug will be taken similarly to the THC and CBD and be matched to keep the trial blinded. In the event that 2.5 mg capsules of dronabinal capsules become unavailable, an equivalent product will be issued to participants and the comparator and placebo arms will be correspondingly adjusted to preserve blinding. If a participant's dose is not well-tolerated, the participant may initiate dose reductions with the study team. Participants will be instructed to eat a meal or snack greater than one hour after taking study drug.

Placebo

Cannabidiol (CBD) DRUG

Epidiolex doses will be 0.37 milliliter (mL) for seven days of treatment and then 0.75 mL two times a day (b.i.d) for the remaining days of this treatment. In the event that 2.5 mg capsules of dronabinal capsules become unavailable, an equivalent product will be issued to participants and the comparator and placebo arms will be correspondingly adjusted to preserve blinding. If a participant's dose is not well-tolerated, the participant may initiate dose reductions with the study team. Participants will be instructed to eat a meal or snack greater than one hour after taking study drug.

Also known as: Epidiolex

CBD plus THC; Cannabidiol (CBD)

Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol) DRUG

Dronabinol Capsules doses will be 2.5 mg b.i.d. for seven days of treatment and then 5 mg b.i.d. for the remaining days of this treatment. In the event that 2.5 mg capsules of dronabinal capsules become unavailable, an equivalent product will be issued to participants and the comparator and placebo arms will be correspondingly adjusted to preserve blinding. If a participant's dose is not well-tolerated, the participant may initiate dose reductions with the study team. Participants will be instructed to eat a meal or snack greater than one hour after taking study drug.

Also known as: Dronabinol

CBD plus THC; Tetrahydrocannabinol (THC)

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to read and speak English to allow for written informed consent, phenotyping, and patient-reported outcomes measures
• Willingness to participate in a drug intervention trial
• Diagnosis of osteoarthritis (OA) of the knee by a medical provider (confirmed by checking medical records)
• Chronic knee pain, defined as moderate to severe knee pain for ≥ 6-month duration
• No use of cannabis or CBD in the past in the month prior to study enrollment as per self-report
• Fibromyalgia (FM) Survey Criteria score available. The questionnaire will be assessed by the research team for scoring. We will recruit enough patients to satisfy the spectrum of FM scores in four quartiles based on our previously existing data. Once a quartile is filled (approximately 40 patients enrolled), then we will not include more people from that quartile.
• Self-reported normal visual acuity or correctable (with corrective lenses- glasses or contacts) to at least 20/40 for reading instructions in the MRI and visual sensitivity testing
• No contraindications to magnetic resonance imaging (MRI) (for example (e.g.), metal implants)
• Able to lie still on their back for 1-1.5 hours during MRI
• Willingness to refrain from pain medications such as non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for 12 hours prior to neuroimaging and Quantitative Sensory Testing (QST)
• Willingness to refrain from alcohol and nicotine before QST and neuroimaging (alcohol and nicotine consumption is allowed after testing is completed)
• Willingness to refrain from physical activity or exercise that would cause significant muscle and/or joint soreness for 48 hours prior to testing (routine exercise or activity that does not lead to soreness is acceptable)
• Willingness to maintain a stable treatment regimen for chronic knee OA pain during the clinical trial (e.g., not initiating a new course of physical therapy)
• No use of adjunctive pain medications or stable chronic daily use of adjunctive pain medications (excluding opioids)
• Willingness to avoid grapefruit juice or food products for the duration of the study;

You may not qualify if:

• Individuals who are actively applying for or in litigation for compensation or disability and other aspects associated with potential secondary gain per self-report
• Inability to provide written informed consent
• Previous total knee arthroplasty
• Planned total knee arthroplasty within the time frame of the study
• Severe physical impairment (e.g., blindness, deafness, paraplegia)
• Co-morbid medical conditions that may significantly impair physical functional status (e.g., history of non-skin malignancy, or autoimmune disorder)
• Use of cannabis or CBD in the past month per self-report and/or drug screen
• Current opioid use (excepting tramadol) per self-report and/or drug screen
• Current valproate, clobazam, or warfarin use per self-report or medical records
• Current use of moderate or strong inhibitors of cytochrome p450 (CYP) enzymes CYP3A4 and CYP2C19, strong inducers of CYP3A4 or CYP2C19, moderate or strong inhibitors/inducers of CYP2C9, and narrow therapeutic index drugs (e.g., cyclosporine, amphotericin B). Participants will also not be allowed to start using these drugs during the study period if they wish to stay in the study
• Self-reported allergies to sesame oil or cannabis/cannabinoids
• Pregnant or nursing
• Liver failure
• Self-reported liver cirrhosis
• Active diagnosis or current symptoms of hepatitis by self-report

Sponsors & Collaborators

• Steven E Harte, PhD: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Cannabidiol; Dronabinol

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Steve Harte, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jaye Minghine

CONTACT

734-998-7020; mjaye@umich.edu

Steven Harte, PhD

CONTACT

734-998-6996; seharte@umich.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Some of the treatment phase will be blinded by the study team.
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology and Internal Medicine Associate Director, Chronic Pain and Fatigue Research Center

Model Details: This is a single-site, 2x2 factorial double-blind, randomized clinical trial with 200 participants (160 completers).

Study Record Dates

• First Submitted: July 28, 2021
• First Posted: August 5, 2021
• Study Start: February 22, 2022
• Primary Completion (Estimated): October 22, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)