Analgesic Effects of a Treatment With Cannabis Sativa Extract in Patients With Knee Osteoarthritis - CANOA (Cannabis for Osteoarthritis)

Osteoarthritis (OA) is the most prevalent joint disease in humans, often causing disability in affected individuals, especially the elderly. OA is characterized by mechanical joint pain, crepitus and short-term post-immobilization stiffness. OA pain has a variable pathophysiology and, despite the many pharmacological options available, its treatment is often ineffective and has significant side effects. The search for more effective and safer treatments is therefore essential in the field of OA. Among the possible treatments are substances derived from cannabis. Cannabis plants have been used for various purposes by humankind for thousands of years. Its best-known species, Cannabis sativa, has more than a hundred substances called cannabinoids or, more specifically, phytocannabinoids, the most important of which is cannabidiol (CBD). Although many pre-clinical studies indicate the usefulness of phytocannabinoids, clinical evidence for their application is currently scarce. Therefore, this project aims to investigate the effects of a CBD-rich extract of Cannabis sativa on the pain of patients with knee OA, as well as the possible adverse events of this treatment.

Study Overview

• Status: Completed
• Conditions: OSTEOARTHRITIS OF THE KNEE
• Intervention / Treatment: Dietary supplement: Medium Chain Triglyceride solution; Other: Cannabis Sativa

Detailed Description

Osteoarthritis (OA) is the most common osteoarticular pathology in humans. In Brazil, in 2004, its prevalence was estimated at 4.14% of the population , and is likely even higher today, given the country's accelerated aging and the increasing prevalence of obesity.

The pain of OA has variable pathophysiology, with nociceptive, inflammatory, and neuropathic mechanisms, along with central and peripheral sensitization, being the main cause of functional disability in patients.

Currently, the pharmacological therapeutic arsenal for treating OA pain includes non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and intra-articular corticosteroids. However, their use is associated with undesirable adverse effects, more common in the geriatric population, which is already exposed to polypharmacy. Due to the heterogeneity of pain pathophysiology in OA, no medication is fully effective in its control, and combinations of different classes of drugs with diverse mechanisms of action are generally employed, along with non-pharmacological measures such as patient education, rehabilitation, and, when necessary, surgical interventions .

Several studies demonstrate that cannabis has antiemetic, appetite-stimulating, analgesic, euphoric, anti-inflammatory, anticonvulsant, and sedative effects. Pain is the main cause of functional disability in patients affected by OA. Modulation of the endocannabinoid system through CB1 and CB2 receptor agonists, as well as FAAH inhibitors, has shown antinociceptive effects in animal models of OA induced by monosodium iodoacetate (MIA) , collagen , and adjuvants , as well as in models of natural OA in guinea pigs.

Other preclinical studies have shown potential effects of cannabinoids on OA progression, such as the inhibition of enzymes that produce local inflammatory mediators, such as nitric oxide and prostaglandin E2 , matrix metalloproteinases , and modulation of cortisol-mediated synovial fibroblast adhesion .

This will be a double-blind, randomized, placebo-controlled clinical trial. Patients who meet the inclusion criteria and agree to participate in the study will be randomized in a 1:1 ratio to three experimental groups, each with a sample size of 16 individuals, treated for 60 days as follows:

Group 1: placebo (Medium Chain Triglycerides solution, without any active principle); Group 2: C. sativa extract with a THC:CBD ratio of 1:10 (2mg:20mg/day); Group 3: C. sativa extract with a THC:CBD ratio of 1:10 (4mg:40mg/day). All patients selected for this study, if using any pharmacological or non-pharmacological therapy for OA, will have these therapies maintained throughout the clinical trial.

The experimental product acquired by LCP consists of a full spectrum extract of Cannabis sativa with a concentration of 20 mg/mL CBD and 2 mg/mL THC, diluted in the vehicle MCT (medium-chain triglycerides). All clinical evaluations will be conducted at three time points, T0, T30 and T60, while laboratory evaluations will be analyzed at T0 and T60.

Aim To evaluate the analgesic effect of a treatment with THC:CBD doses of a C. sativa extract in patients diagnosed with osteoarthritis.

Objectives:

To evaluate the analgesic effect of a THC:CBD treatment in C. sativa extract in patients diagnosed with osteoarthritis; To evaluate the anti-inflammatory effect of a THC:CBD treatment in C. sativa extract in patients diagnosed with osteoarthritis; To evaluate the symptomatic clinical safety profile of the treatment; To evaluate the renal, hepatic, and hemostatic safety profile of the treatment; To determine if there is an association between Lipoxin A4 levels and pain intensity levels in patients diagnosed with osteoarthritis.

Hypothesis:

The prescribed doses of THC:CBD/day induce analgesic and anti-inflammatory effects in patients diagnosed with osteoarthritis.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Paraná
    • Foz do Iguaçu, Paraná, Brazil, 85870-650
      • Federal University of Latin American Integration

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a diagnosis of knee osteoarthritis, according to the ACR classification criteria (ALTMAN, 1986);
• Have a moderate or high level of pain induced by osteoarthritis (visual analog scale scale equal to or greater than 5);
• Voluntarily agree to take part in the study by signing the Informed Consent Form (ICF);
• For women of reproductive age, a negative Beta-HCG test, and use of a contraceptive method throughout the study.
• For women of reproductive age, a negative Beta-HCG test, and use of a contraceptive method throughout the study and 3 months after its conclusion.
• Age range of thirty (30) to seventy (70) years.

Exclusion Criteria:

• People with heart failure, hypertension or any heart disease;
• People with chronic kidney disease or liver failure;
• Patients with chronic inflammatory diseases;
• Patients with severe psychiatric illnesses, such as severe mood disorders and psychotic disorders;
• Current use of cannabinoids by any route of administration.
• Pregnant women
• Lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 1; placebo (solution of Medium Chain Triglycerides, without any active ingredient)	Dietary supplement: Medium Chain Triglyceride solution; Placebo
Experimental: Group 2; Cannabis sativa extract with a CBD (45 mg/day)	Other: Cannabis Sativa; Group 2: Cannabis sativa extract with CBD (45mg/day).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain levels	Change in pain levels, according to the score in the "pain" domain of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), using the Likert scale to assign a value to the answers obtained from the participants. The pain levels according to the score are 0-8 mild, greater than 8-14 moderate, greater than 14- 20 high.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression	Changes in levels of depression using the Beck Depression scale. Changes in depression levels using the Beck depression scale. The disease level values range from 0-9 indicating that the individual is not depressed, 10-18 indicating mild to moderate depression, 19-29 indicating moderate to severe depression and 30-63 indicating severe depression.	2 months
Adverse events	presence of adverse events (AE) - proportion of patients with AE in the placebo and intervention groups;	2 months
Serious adverse events	presence of serious adverse events (AEs) - description of the serious AEs that may appear in each group.	2 months
Short Form Health Survey (SF-12)	Change in the Short Form Health Survey (SF-12) quality of life scores, according to the "maximal walking" and "activities of daily living" domains, where a score of 0 is the worst quality of life and 100 the best.	2 months
Change in sleep quality	The Pittsburgh scale was used to see if there was any change in the participants' quality of sleep. The scale used classifies sleep quality as follows: Good 0-4; Bad -10; Presence of sleep disturbance greater than 10	2 months
Renal Function Panel	Used as form to identify any renal impairment in pacientes that could result in any need of adjusting the dose or need to leave the study.	2 months
Visual Analogue Scale (VAS)	It is used in the healthcare field to measure the intensity of pain a person feels, usually on a scale from 0 to 10, where 0 means 'no pain' and 10 means 'the worst pain imaginable	2 month
Hepatic Panel	Used to monitor liver function in patients, as pacientes are receiving an oil-based medication that may overload the liver.	2 month

Collaborators and Investigators

• Sponsor: Federal University of Latin American Integration
• Investigators: Study Director: Francisney P Nascimento, 1, Federal University of Latin American Integration

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Actual): October 10, 2024
• Study Completion (Actual): October 12, 2024

Study Registration Dates

• First Submitted: April 12, 2024
• First Submitted That Met QC Criteria: September 5, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): July 2, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Osteoarthritis; Pain; Cannabidiol; Tetrahydrocannabinol; Cannabinoids; Cannabinoid safety
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Mental Disorders; Arthritis; Joint Diseases; Rheumatic Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Osteoarthritis; Osteoarthritis, Knee; Marijuana Abuse
• Other Study ID Numbers: CANOA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No