Osteoarthritis, KneePhase 2NCT04992624
Cannabinoid Interactions With Central and Peripheral Pain Mechanisms in Osteoarthritis of the Knee
A Phase 2 study testing Cannabidiol (CBD) and Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol) in people with Osteoarthritis, Knee and Osteoarthritis of the Knee, run by Steven E Harte, PhD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Osteoarthritis, Knee, Osteoarthritis of the Knee
- What is being tested?
- Cannabidiol (CBD) and Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Feb 2022to 30 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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;
- Females of reproductive potential must agree to use acceptable birth control from the screening visit and until the completion study drug administration. Sexually active male participants and/or their female partners must agree to use effective contraception during study drug treatment of the male participant. Male participants may also agree not to donate sperm during study drug treatment
Who cannot join
- 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)
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- 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
- Self-reported medical or psychiatric conditions that in the judgment of study personnel would preclude participation in this study (e.g., schizophrenia, malignancy, psychosis, suicidal ideation, history of substance abuse; note that stable anxiety and depression are not exclusions)
- Pregnant or nursing
- Liver failure
- Self-reported liver cirrhosis
- Active diagnosis or current symptoms of hepatitis by self-report
- Self-reported uncontrolled diabetes
- Blood pressure at screening above 180 systolic and/or 120 diastolic
- Resting heart rate at screening less than 50 beats per minute (bpm) or greater than 100 bpm;
- Elevated liver enzymes and bilirubin (measured via blood test at screening):
- Serum total bilirubin ≥ 2.5 milligrams per deciliter (mg/dL); or,
- Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 3x upper limit normal (ULN); or,
- Alkaline phosphatase ≥ 2 times ULN
- Severe cardiovascular disease (examples: history of myocardial infarction, unstable angina, severe coronary artery disease, congestive heart failure, or severe valvular abnormalities) that is self-reported by patient or by medical record
- Severe claustrophobia precluding MRI
- Unable to fit in or lie comfortably in MRI
- Diagnosed peripheral neuropathy
- Diagnosed or self-reported epilepsy or history of seizures
- Current head injury or history of head injury (e.g., traumatic brain injury)
- Any impairment, activity, behavior, or situation that in the judgment of the study team would prevent satisfactory completion of the study protocol
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Katherine Scott, 734-998-7022, jrsj@umich.edu
Steven Harte, PhD
About this study
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).
Read the detailed description
The study hypothesizes that:
- CBD alone will exert a peripheral anti-inflammatory effect by decreasing levels of Interleukin (IL)-6
- THC alone will modify central nervous system (CNS) pain via decreasing insula to Default Mode Network (DMN) connectivity
- CBD plus THC will do both.
- Conditions
- Osteoarthritis, Knee, Osteoarthritis of the Knee
- Being tested
- Placebo, Cannabidiol (CBD), Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol)
- Keywords
- Cannabidiol, Tetrahydrocannabinol
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
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.
Cannabidiol (CBD)Drug
Also called Epidiolex
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.
Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol)Drug
Also called Dronabinol
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Cannabidiol (CBD) | Experimental | Up to 150 mg/day. Receives: Drug: Cannabidiol (CBD) |
| Tetrahydrocannabinol (THC) | Experimental | Up to 10 mg/day. Receives: 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. Receives: Drug: Cannabidiol (CBD); Drug: Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 15, and approximately day 99 of treatment
Change in pre-post measurements of inflammatory marker IL-6.
Serum IL-6
Measured: Day 15, and approximately day 99 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2021
- Study start22 Feb 2022
- Primary completion22 Mar 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- This is a single-site, 2x2 factorial double-blind, randomized clinical trial with 200 participants (160 completers).
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Steven E Harte, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH), National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor-investigator, Steven E Harte, PhD, University of Michigan
- Investigators
- Steve Harte, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04992624
- Sponsor's protocol ID
- HUM000180986
- Other IDs
- 1R01AT010381-01A1, 1K01DA049219-01A1
- Status last verified
- Jul 2026
- First submitted
- 28 Jul 2021
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cannabinoid Interactions With Central and Peripheral Pain Mechanisms in Osteoarthritis of the Knee
- ClinicalTrials.gov ID
- NCT04992624
- Acronym / sponsor ID
- HUM000180986
- Conditions
- Osteoarthritis, Knee, Osteoarthritis of the Knee
- Keywords
- Cannabidiol, Tetrahydrocannabinol
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Steven E Harte, PhDUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH), National Institute on Drug Abuse (NIDA)
- Study start
- 22 Feb 2022 (actual)
- Primary completion
- 22 Mar 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 5 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The study hypothesizes that:
- CBD alone will exert a peripheral anti-inflammatory effect by decreasing levels of Interleukin (IL)-6
- THC alone will modify central nervous system (CNS) pain via decreasing insula to Default Mode Network (DMN) connectivity
- CBD plus THC will do both.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- This is a single-site, 2x2 factorial double-blind, randomized clinical trial with 200 participants (160 completers).
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| Cannabidiol (CBD) | Experimental | Drug: Cannabidiol (CBD)Up to 150 mg/day. |
| Tetrahydrocannabinol (THC) | Experimental | Drug: Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol)Up to 10 mg/day. |
| CBD plus THC | Experimental | Drug: Cannabidiol (CBD), Drug: Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol)Up to 150 mg/day CBD plus up to 10 mg/day THC. |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (30 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo 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. | Drug | Placebo |
| Cannabidiol (CBD)Also: EpidiolexEpidiolex 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. | Drug | CBD plus THC, Cannabidiol (CBD) |
| Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol)Also: DronabinolDronabinol 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. | Drug | CBD plus THC, Tetrahydrocannabinol (THC) |
Primary outcome
Default mode network (DMN) to insula connectivity via functional connectivity magnetic resonance imaging (fcMRI)
Time frame: Day 15, and approximately day 99 of treatment
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.
Change in pre-post measurements of inflammatory marker IL-6.
Time frame: Day 15, and approximately day 99 of treatment
Serum IL-6
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Steve Harte, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cannabidiol (CBD) and Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol) in people with Osteoarthritis, Knee and Osteoarthritis of the Knee, run by Steven E Harte, PhD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Katherine Scott (734-998-7022, jrsj@umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Default mode network (DMN) to insula connectivity via functional connectivity magnetic resonance imaging (fcMRI) (time frame: Day 15, and approximately day 99 of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.