Knee OsteoarthritisPhase 3NCT03825965
Cannabinoids vs. Placebo on Persistent Post-surgical Pain Following TKA: A Pilot RCT
A Phase 3 study testing MPL-001 (CBD: THC 25:1) in people with Knee Osteoarthritis, run by McMaster University at 2 sites in Canada.
Trial summary
Each year, approximately 75,000 Canadians undergo knee replacement surgery, and up to 25% develop persistent post-surgical pain. Persistent post-surgical pain is associated with depression, anxiety, unemployment, and reduced quality of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- MPL-001 (CBD: THC 25:1)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 2 sitesCanada
- Study dates
- 3 May 2023to 25 Feb 2025
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing TKA aged 18 or older
- Cognitive ability and English-language skills required to complete outcome measures
- Provision of informed consent
- Successful completion of the run-in period
Who cannot join
- Severe cardio-respiratory disease (For operationalizing: ASA 4/NYHA 4)
- Substance use disorder based on DSM-V criteria
- Allergy or intolerance to cannabis, cannabis derivatives, or other ingredients of the study drug
- Patients who are pregnant, planning to be pregnant, or breastfeeding
- Revision TKA
- Bilateral TKA
Show all 9Show fewer
- Presenting for their pre-surgical consultation less than 4 weeks before surgery
- Patients with a chronic pain condition affecting the knee (other than osteoarthritis) (e.g.: patients with knee pain due to fibromyalgia or chronic pain syndrome will be excluded)
- Unwilling or unable to follow the study protocol
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
About this study
Official title: The Effect of Cannabinoids vs. Placebo on Persistent Post-surgical Pain Following Total Knee Arthroplasty: A Multicenter, Randomized Pilot Trial
Each year, approximately 75,000 Canadians undergo knee replacement surgery, and up to 25% develop persistent post-surgical pain. Persistent post-surgical pain is associated with depression, anxiety, unemployment, and reduced quality of life. Chronic pain after surgery is often managed with opioid therapy, which typically provides only modest benefits and is associated with rare but serious adverse events, such as overdose and death. A number of studies have found that greater pain just before and after knee replacement surgery is associated with the development of chronic pain, suggesting that reducing peri-operative pain may help prevent persistent post-surgical pain.
Medicinal cannabis has begun to emerge as a potential therapy for pain reduction, and produces effects largely due to 2 active components: (1) cannabidiol (CBD), and (2) tetrahydrocannabinol (THC). Studies of CBD have shown analgesic, anti-inflammatory, and anti-anxiety properties, but without the psychoactive effects (feeling 'high') that THC produces. This study will assess the feasibility of a definitive trial to explore whether adding CBD dominant vs. placebo to usual care before and after surgery can reduce the rate of persistent post-surgical pain after total knee replacement. This study will randomize 40 patients to receive either CBD dominant or placebo, and follow them for six months to confirm our ability to recruit patients, adhere to protocol, and capture full outcome data for at least 85% of patients.
Read the detailed description
Approximately 25% of patients develop persistent post-surgical pain (PPSP) after undergoing total knee arthroplasty (TKA), and higher pre-surgery and acute post-operative pain are associated with this outcome. Medicinal cannabis has anti-inflammatory and analgesic properties and may reduce peri-operative pain and the rate of PPSP following TKA. Cannabidiol (CBD) is the active ingredient of interest because of its anti-inflammatory effects and lack of psychoactive effects seen with tetrahydrocannabinol (THC). The primary objective of this pilot trial is to assess the feasibility of a definitive trial to determine the effect of medicinal cannabis, versus placebo, on the proportion of patients experiencing PPSP following TKA. The primary objective of the definitive trial is to determine if medicinal cannabis add-on therapy, versus placebo, reduces the proportion of patients experiencing PPSP at 6 months following TKA. The secondary objectives of the definitive trial are to determine if medicinal cannabis, versus placebo, reduces opioid use, reduces peri-operative pain interference, improves physical functioning, mental functioning, return to function, anxiety and depression, and sleep. The effect of medicinal cannabis, versus placebo, on the incidence of adverse events at 6 months post-surgery will also be examined. In this blinded multi-centre pilot trial, 40 patients will be randomized to receive either oral capsules of CBD oil or visually identical placebo in addition to standard of care pain medications. Participants will be followed for 6 months.
- Conditions
- Knee Osteoarthritis
- Being tested
- MPL-001 (CBD: THC 25:1), Placebo oil for oral use
- Keywords
- Total knee arthroplasty, Cannabis, Pilot trial, Persistent post-surgical pain
- Medical subject headings
- Osteoarthritis, Knee, Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MPL-001 (CBD: THC 25:1)Drug
25:1 cannabidiol (CBD): tetrahydrocannabinol (THC) oral formulation, with a concentration of 50 mg/mL CBD and 2 mg/mL THC, oil- Liquid for oral use
Placebo oil for oral useDrug
Placebo is Medium-chain triglycerides oil with identical features (in appearance, flavour, and odour) to the MPL-001 oil.
| Study group | Role | What they receive |
|---|---|---|
| MPL-001 (CBD: THC 25:1) | Experimental | 125mg CBD/5 mg THC oil for oral use Receives: Drug: MPL-001 (CBD: THC 25:1) |
| Placebo | Placebo comparator | Visually identical placebo (medium chain triglyceride oil) Receives: Drug: Placebo oil for oral use |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility - Recruitment Rate (Participants/Month)
Average number of participants enrolled per month. Feasibility predefined as achieving a recruitment rate of ≥6.7 participants/month (equivalent to enrolling 40 participants within 6 months).
Measured: From study start to end of recruitment
Feasibility - Proportion of Participants Achieving ≥75% Preoperative Adherence
Proportion of participants who took at least 75% of prescribed study medication doses prior to surgery.
Measured: From treatment initiation to surgery, average of 4 weeks
Feasibility - Proportion of Participants Achieving ≥75% Postoperative Adherence
Proportion of participants who took at least 75% of prescribed study medication doses after surgery.
Measured: From surgery to 6 weeks post-op
Feasibility - Follow-up Completion
Number of patients completing the 6 month follow-up visit.
Measured: 6 months post-op
Secondary outcomes (9)
Persistent Post-surgical Pain (PPSP)
Proportion of patients experiencing moderate to severe PPSP (average of pain over last week of ≥4 out of 10 on a numeric rating scale [NRS])
Measured: 6 months postop
Time to Opioid Discontinuation
Time from discharge to opioid discontinuation (days).
Measured: Up to 6 months post-op
Pain Intensity (Numeric Rating Scale)
Average pain over the past 24 hours measured on a 0-10 numeric rating scale (higher scores indicate worse pain).
Measured: Preoperative and 6 months postop
Pain Interference (Numeric Rating Scale)
Pain interference with daily activities measured on a 0-10 numeric rating scale (higher scores indicate greater interference).
Measured: Preoperative and 6 months postop
Anxiety and Depression (HADS)
Count of participants with borderline or clinically significant anxiety and depression, assessed using the Hospital Anxiety and Depression Scale (HADS). Scores of 0-7 in each subscale are considered normal, with 8-10 borderline and ≥11 indicating clinically important anxiety or depression.
Measured: Preoperative and 6 months post-op
EQ-5D Visual Analogue Scale (VAS)
Health-related quality of life assessed using the EQ-5D instrument. Self-reported overall health measured on a 0-100 scale, where higher scores indicate better health.
Measured: Preoperative and 6 months post-op
EuroQol-5 Dimensions (EQ-5D) Index Value
Health utility index derived from EuroQol-5 Dimensions (EQ-5D) responses. Index values typically range from 0 (death) to 1 (full health) but it is also possible to have negative values (worse than death). To calculate index values, we used the Canadian time trade-off (TTO) value set.
Measured: Preoperative and 6 months post-op
Insomnia Severity (Insomnia Severity Index)
Proportion of participants meeting criteria for moderate to severe insomnia, assessed using the Insomnia Severity Index (ISI). Standard ISI cutoff scores were used to classify insomnia severity.
Measured: Preoperative and 6 months post-op
Return to Function
Return to function assessed as the percentage of preoperative function regained following surgery. Higher percentages indicate greater recovery of function.
Measured: Post-op (2 weeks, 6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2019
- Study start3 May 2023
- Primary completion25 Feb 2025
- Study completion25 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- St. Joseph's Healthcare Hamilton, Hamilton Health Sciences Corporation
- Responsible party
- Sponsor
- Investigators
- Anthony Adili, MD, P.Eng, Principal investigator, McMaster UniversityJason W Busse, DC, PhD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03825965
- Sponsor's protocol ID
- Cannabis TKA Pilot Trial
- Status last verified
- May 2026
- First submitted
- 30 Jan 2019
- Last updated
- 22 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will share IPD upon reasonable request with a data sharing agreement and ethical approval.
Publications
Busse JW, Flood B, Madden K, Ashoorion V, Olaonipekun E, Atrey A, Khanna V, Adili A; Cannabis-TKA Investigators. Cannabidiol to reduce persistent post-surgical pain following total knee arthroplasty: protocol for a multi-centre, randomized, controlled pilot trial. Pilot Feasibility Stud. 2026 Apr 25;12(1):84. doi: 10.1186/s40814-026-01822-w.
PubMed 42032682
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Cannabinoids vs. Placebo on Persistent Post-surgical Pain Following Total Knee Arthroplasty: A Multicenter, Randomized Pilot Trial
- ClinicalTrials.gov ID
- NCT03825965
- Acronym / sponsor ID
- Cannabis TKA Pilot Trial
- Conditions
- Knee Osteoarthritis
- Keywords
- Total knee arthroplasty, Cannabis, Pilot trial, Persistent post-surgical pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- St. Joseph's Healthcare Hamilton, Hamilton Health Sciences Corporation
- Study start
- 3 May 2023 (actual)
- Primary completion
- 25 Feb 2025 (actual)
- Study completion
- 25 Feb 2025 (actual)
- First posted
- 1 Feb 2019 (actual)
- Results
- Posted 8 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Each year, approximately 75,000 Canadians undergo knee replacement surgery, and up to 25% develop persistent post-surgical pain. Persistent post-surgical pain is associated with depression, anxiety, unemployment, and reduced quality of life. Chronic pain after surgery is often managed with opioid therapy, which typically provides only modest benefits and is associated with rare but serious adverse events, such as overdose and death. A number of studies have found that greater pain just before and after knee replacement surgery is associated with the development of chronic pain, suggesting that reducing peri-operative pain may help prevent persistent post-surgical pain.
Medicinal cannabis has begun to emerge as a potential therapy for pain reduction, and produces effects largely due to 2 active components: (1) cannabidiol (CBD), and (2) tetrahydrocannabinol (THC). Studies of CBD have shown analgesic, anti-inflammatory, and anti-anxiety properties, but without the psychoactive effects (feeling 'high') that THC produces. This study will assess the feasibility of a definitive trial to explore whether adding CBD dominant vs. placebo to usual care before and after surgery can reduce the rate of persistent post-surgical pain after total knee replacement. This study will randomize 40 patients to receive either CBD dominant or placebo, and follow them for six months to confirm our ability to recruit patients, adhere to protocol, and capture full outcome data for at least 85% of patients.
Detailed description
Approximately 25% of patients develop persistent post-surgical pain (PPSP) after undergoing total knee arthroplasty (TKA), and higher pre-surgery and acute post-operative pain are associated with this outcome. Medicinal cannabis has anti-inflammatory and analgesic properties and may reduce peri-operative pain and the rate of PPSP following TKA. Cannabidiol (CBD) is the active ingredient of interest because of its anti-inflammatory effects and lack of psychoactive effects seen with tetrahydrocannabinol (THC). The primary objective of this pilot trial is to assess the feasibility of a definitive trial to determine the effect of medicinal cannabis, versus placebo, on the proportion of patients experiencing PPSP following TKA. The primary objective of the definitive trial is to determine if medicinal cannabis add-on therapy, versus placebo, reduces the proportion of patients experiencing PPSP at 6 months following TKA. The secondary objectives of the definitive trial are to determine if medicinal cannabis, versus placebo, reduces opioid use, reduces peri-operative pain interference, improves physical functioning, mental functioning, return to function, anxiety and depression, and sleep. The effect of medicinal cannabis, versus placebo, on the incidence of adverse events at 6 months post-surgery will also be examined. In this blinded multi-centre pilot trial, 40 patients will be randomized to receive either oral capsules of CBD oil or visually identical placebo in addition to standard of care pain medications. Participants will be followed for 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MPL-001 (CBD: THC 25:1) | Experimental | Drug: MPL-001 (CBD: THC 25:1)125mg CBD/5 mg THC oil for oral use |
| Placebo | Placebo comparator | Drug: Placebo oil for oral useVisually identical placebo (medium chain triglyceride oil) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients undergoing TKA aged 18 or older
- Cognitive ability and English-language skills required to complete outcome measures
- Provision of informed consent
- Successful completion of the run-in period
Key exclusion criteria (9 listed)
- Severe cardio-respiratory disease (For operationalizing: ASA 4/NYHA 4)
- Substance use disorder based on DSM-V criteria
- Allergy or intolerance to cannabis, cannabis derivatives, or other ingredients of the study drug
- Patients who are pregnant, planning to be pregnant, or breastfeeding
- Revision TKA
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 |
|---|---|---|
| MPL-001 (CBD: THC 25:1)25:1 cannabidiol (CBD): tetrahydrocannabinol (THC) oral formulation, with a concentration of 50 mg/mL CBD and 2 mg/mL THC, oil- Liquid for oral use | Drug | MPL-001 (CBD: THC 25:1) |
| Placebo oil for oral usePlacebo is Medium-chain triglycerides oil with identical features (in appearance, flavour, and odour) to the MPL-001 oil. | Drug | Placebo |
Primary outcome
Feasibility - Recruitment Rate (Participants/Month)
Time frame: From study start to end of recruitment
Average number of participants enrolled per month. Feasibility predefined as achieving a recruitment rate of ≥6.7 participants/month (equivalent to enrolling 40 participants within 6 months).
Feasibility - Proportion of Participants Achieving ≥75% Preoperative Adherence
Time frame: From treatment initiation to surgery, average of 4 weeks
Proportion of participants who took at least 75% of prescribed study medication doses prior to surgery.
Feasibility - Proportion of Participants Achieving ≥75% Postoperative Adherence
Time frame: From surgery to 6 weeks post-op
Proportion of participants who took at least 75% of prescribed study medication doses after surgery.
Feasibility - Follow-up Completion
Time frame: 6 months post-op
Number of patients completing the 6 month follow-up visit.
9 secondary outcomes
Persistent Post-surgical Pain (PPSP)
Time frame: 6 months postop
Time to Opioid Discontinuation
Time frame: Up to 6 months post-op
Pain Intensity (Numeric Rating Scale)
Time frame: Preoperative and 6 months postop
Pain Interference (Numeric Rating Scale)
Time frame: Preoperative and 6 months postop
Anxiety and Depression (HADS)
Time frame: Preoperative and 6 months post-op
EQ-5D Visual Analogue Scale (VAS)
Time frame: Preoperative and 6 months post-op
EuroQol-5 Dimensions (EQ-5D) Index Value
Time frame: Preoperative and 6 months post-op
Insomnia Severity (Insomnia Severity Index)
Time frame: Preoperative and 6 months post-op
Return to Function
Time frame: Post-op (2 weeks, 6 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 42032682Busse JW, Flood B, Madden K, Ashoorion V, Olaonipekun E, Atrey A, Khanna V, Adili A; Cannabis-TKA Investigators. Cannabidiol to reduce persistent post-surgical pain following total knee arthroplasty: protocol for a multi-centre, randomized, controlled pilot trial. Pilot Feasibility Stud. 2026 Apr 25;12(1):84. doi: 10.1186/s40814-026-01822-w.
- Individual participant dataSharing planned: Yes. We will share IPD upon reasonable request with a data sharing agreement and ethical approval.
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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. This study is not recruiting at the moment.
Anthony Adili, MD, P.Eng principal investigator
McMaster University
Jason W Busse, DC, PhD principal investigator
McMaster University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing MPL-001 (CBD: THC 25:1) in people with Knee Osteoarthritis, run by McMaster University at 2 sites in Canada.
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 4 inclusion and 9 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: finished, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility - Recruitment Rate (Participants/Month) (time frame: From study start to end of recruitment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03825965, which also lists 1 linked publication.
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 22 Oct 2026.