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
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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.
Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2026-09-08
What this record can show
Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.
Registry facts
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.
Linked local records
Local links use governed condition terms or exact source-reported intervention names. They are navigation candidates, not efficacy claims.
Interventions
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 is Medium-chain triglycerides oil with identical features (in appearance, flavour, and odour) to the MPL-001 oil.
Source-reported results
Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.
Proportion of patients experiencing moderate to severe PPSP (average of pain over last week of ≥4 out of 10 on a numeric rating scale \[NRS\])
Population: Of the 37 included participants, only 30 completed their 6 month post-op visit
| Group | N | Value | Spread / interval |
|---|---|---|---|
| MPL-001 (CBD: THC 25:1) | 14 | 2 | - |
| Placebo | 16 | 3 | - |
Time from discharge to opioid discontinuation (days).
Population: Of the 37 included participants, only 30 completed their 6 month post-op visit
| Group | N | Value | Spread / interval |
|---|---|---|---|
| MPL-001 (CBD: THC 25:1) | 14 | 32 | 14 to 64 |
| Placebo | 16 | 16 | 12 to 37 |
Average pain over the past 24 hours measured on a 0-10 numeric rating scale (higher scores indicate worse pain).
Population: Of the 37 included participants, only 30 completed their 6 month post-op visit.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| MPL-001 (CBD: THC 25:1) | 19 | 5.9 | 1.6 |
| Placebo | 18 | 5.9 | 2.2 |
| MPL-001 (CBD: THC 25:1) | 19 | 3.5 | 1.5 |
| Placebo | 18 | 2.6 | 2.0 |
Pain interference with daily activities measured on a 0-10 numeric rating scale (higher scores indicate greater interference).
Population: Of the 37 included participants, only 30 completed their 6 month post-op visit.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| MPL-001 (CBD: THC 25:1) | 19 | 5.9 | 1.9 |
| Placebo | 18 | 6.0 | 2.6 |
| MPL-001 (CBD: THC 25:1) | 19 | 2.1 | 2.3 |
| Placebo | 18 | 2.1 | 2.4 |
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.
Population: Of the 37 included participants, only 30 completed their 6 month post-op visit.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| MPL-001 (CBD: THC 25:1) | 19 | 6 | - |
| Placebo | 18 | 3 | - |
| MPL-001 (CBD: THC 25:1) | 19 | 2 | - |
| Placebo | 18 | 0 | - |
| MPL-001 (CBD: THC 25:1) | 19 | 9 | - |
| Placebo | 18 | 7 | - |
| MPL-001 (CBD: THC 25:1) | 19 | 2 | - |
| Placebo | 18 | 3 | - |
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.
Population: Of the 37 included participants, only 30 completed their 6 month post-op visit.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| MPL-001 (CBD: THC 25:1) | 19 | 59.4 | 19.2 |
| Placebo | 18 | 68.9 | 19.2 |
| MPL-001 (CBD: THC 25:1) | 19 | 79.5 | 14.8 |
| Placebo | 18 | 80.7 | 11.7 |
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.
Population: Of the 37 included participants, only 30 completed their 6 month post-op visit.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| MPL-001 (CBD: THC 25:1) | 19 | 0.555 | 0.242 |
| Placebo | 18 | 0.573 | 0.138 |
| MPL-001 (CBD: THC 25:1) | 19 | 0.780 | 0.138 |
| Placebo | 18 | 0.797 | 0.097 |
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).
| Group | N | Value | Spread / interval |
|---|---|---|---|
| Overall Study Population | 37 | 2.9 | - |
Proportion of participants who took at least 75% of prescribed study medication doses prior to surgery.
Population: Of 37 randomized participants, 36 initiated study medication. Two participants discontinued prior to surgery. Therefore, 34 participants contributed to the preoperative adherence analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| MPL-001 (CBD: THC 25:1) | 17 | 13 | - |
| Placebo | 17 | 11 | - |
Proportion of participants who took at least 75% of prescribed study medication doses after surgery.
Population: Of 37 randomized participants, 36 initiated study medication. Two participants discontinued prior to surgery. One patient discontinued after surgery. Therefore, 33 participants contributed to the postoperative adherence analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| MPL-001 (CBD: THC 25:1) | 16 | 10 | 25.7 |
| Placebo | 17 | 6 | - |
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.
Population: Of the 37 included participants, only 30 completed their 6 month post-op visit
| Group | N | Value | Spread / interval |
|---|---|---|---|
| MPL-001 (CBD: THC 25:1) | 19 | 9 | - |
| Placebo | 18 | 10 | - |
| MPL-001 (CBD: THC 25:1) | 19 | 2 | - |
| Placebo | 18 | 3 | - |
Return to function assessed as the percentage of preoperative function regained following surgery. Higher percentages indicate greater recovery of function.
Population: Of 37 included participants, 30 completed the 6-month postoperative assessment and were included in the 6-month analysis.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| MPL-001 (CBD: THC 25:1) | 18 | 51.7 | 20.6 |
| Placebo | 19 | 61.9 | 17.7 |
| MPL-001 (CBD: THC 25:1) | 18 | 75.0 | 18.7 |
| Placebo | 19 | 78.3 | 21.9 |
Number of patients completing the 6 month follow-up visit.
Population: All participants randomized except two post-randomization exclusions who were deemed ineligible.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| MPL-001 (CBD: THC 25:1) | 19 | 14 | - |
| Placebo | 18 | 16 | - |
| Milestone | MPL-001 (CBD: THC 25:1) | Placebo |
|---|---|---|
| STARTED | 19 | 18 |
| COMPLETED | 14 | 16 |
| NOT COMPLETED | 5 | 2 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Enteritis | Gastrointestinal disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 0 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Bradycardia | Cardiac disorders | MPL-001 (CBD: THC 25:1): 0 / 19 · Placebo: 0 / 18 · Enrolled, But Discontinued Study Participants: 1 / 2 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Small bowel obstruction | Gastrointestinal disorders | MPL-001 (CBD: THC 25:1): 0 / 19 · Placebo: 1 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Nausea/upset stomach | Gastrointestinal disorders | MPL-001 (CBD: THC 25:1): 7 / 19 · Placebo: 2 / 18 · Enrolled, But Discontinued Study Participants: 2 / 2 |
| Diarrhea | Gastrointestinal disorders | MPL-001 (CBD: THC 25:1): 2 / 19 · Placebo: 2 / 18 · Enrolled, But Discontinued Study Participants: 1 / 2 |
| Vomiting | Gastrointestinal disorders | MPL-001 (CBD: THC 25:1): 0 / 19 · Placebo: 1 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Constipation | Gastrointestinal disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 0 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Enteritis | Gastrointestinal disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 0 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Indigestion | Gastrointestinal disorders | MPL-001 (CBD: THC 25:1): 0 / 19 · Placebo: 1 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Throat irritation | Gastrointestinal disorders | MPL-001 (CBD: THC 25:1): 0 / 19 · Placebo: 2 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
Eligibility
primary outcomes
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).
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.
Time frame: From surgery to 6 weeks post-op
Proportion of participants who took at least 75% of prescribed study medication doses after surgery.
Time frame: 6 months post-op
Number of patients completing the 6 month follow-up visit.
secondary outcomes
Time frame: 6 months postop
Proportion of patients experiencing moderate to severe PPSP (average of pain over last week of ≥4 out of 10 on a numeric rating scale \[NRS\])
Time frame: Up to 6 months post-op
Time from discharge to opioid discontinuation (days).
Time frame: Preoperative and 6 months postop
Average pain over the past 24 hours measured on a 0-10 numeric rating scale (higher scores indicate worse pain).
Time frame: Preoperative and 6 months postop
Pain interference with daily activities measured on a 0-10 numeric rating scale (higher scores indicate greater interference).
Time frame: Preoperative and 6 months post-op
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.
Time frame: Preoperative and 6 months post-op
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.
Time frame: Preoperative and 6 months post-op
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.
Time frame: Preoperative and 6 months post-op
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.
Time frame: Post-op (2 weeks, 6 months)
Return to function assessed as the percentage of preoperative function regained following surgery. Higher percentages indicate greater recovery of function.
Publications
No exact PMID-linked public article is currently readable locally.
| Mouth sores | Gastrointestinal disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 0 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Erythema | General disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 0 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Abdomial pain | General disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 0 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Fatigue | General disorders | MPL-001 (CBD: THC 25:1): 2 / 19 · Placebo: 2 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Dry mouth | General disorders | MPL-001 (CBD: THC 25:1): 0 / 19 · Placebo: 2 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Drowsiness | General disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 0 / 18 · Enrolled, But Discontinued Study Participants: 1 / 2 |
| Dizziness | General disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 1 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Mood changes | General disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 0 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Feeling flush | General disorders | MPL-001 (CBD: THC 25:1): 0 / 19 · Placebo: 1 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Superficial infection | Infections and infestations | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 0 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Knee stiffness | Musculoskeletal and connective tissue disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 4 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| AE in non-study joint | Musculoskeletal and connective tissue disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 2 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Back Pain | Musculoskeletal and connective tissue disorders | MPL-001 (CBD: THC 25:1): 0 / 19 · Placebo: 2 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Restless leg | Musculoskeletal and connective tissue disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 0 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Headache | Nervous system disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 2 / 18 · Enrolled, But Discontinued Study Participants: 2 / 2 |
| Insomnia | Nervous system disorders | MPL-001 (CBD: THC 25:1): 0 / 19 · Placebo: 2 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |
| Impaired concentration | Nervous system disorders | MPL-001 (CBD: THC 25:1): 1 / 19 · Placebo: 0 / 18 · Enrolled, But Discontinued Study Participants: 0 / 2 |