Real-world Evidence of Cannabinoid for Observed Pain Relief

BACKGROUND:

Chronic muscle pain affects up to 70% of amateur and professional athletes over 12 months, with 7-day prevalence rates of approximately 32.8%. Conventional pharmacological therapies (NSAIDs, muscle relaxants, opioids) frequently provide inadequate relief and are associated with limiting systemic adverse effects. The endocannabinoid system (ECS) has emerged as a promising therapeutic target, with CB1 and CB2 receptors playing key roles in nociceptive modulation and neuroinflammation attenuation.

Topical cannabinoid administration offers the advantage of delivering high concentrations directly to peripheral receptors (CB1, CB2, and TRPV1) in nerve endings and immune cells of the skin and underlying muscle tissue, while minimizing systemic absorption. The combination of CBD and THC in a 3:1 ratio may maximize synergistic therapeutic effects (entourage effect) while mitigating psychotropic adverse effects.

STUDY DESIGN:

This is a prospective, comparative, non-randomized observational study with 90 days of follow-up per participant. Treatment allocation is based exclusively on the principal investigator's clinical decision, reflecting routine medical practice.

POPULATION:

60 adult athletes (amateur or professional) practicing structured physical activity (≥3 sessions/week) for at least 6 months, with clinically confirmed chronic muscle pain (≥3 months duration), including myofascial pain syndrome, recurrent persistent DOMS, or pain from overtraining/repetitive microtrauma.

INTERVENTIONS OBSERVED:

Cohort A (Control, n=30): Full spectrum CBD oil, 60 mg/day, oral/sublingual, once daily at bedtime, for 90 days.

Cohort B (Intervention, n=30): Full spectrum CBD oil (same as Cohort A) PLUS Papa & Barkley Topical Balm (450 mg CBD + 150 mg THC per 50 mL bottle; 9 mg CBD + 3 mg THC per mL), applied twice daily (every 12 hours) to the affected muscle area for 90 days.

ASSESSMENTS:

Evaluations at D0 (baseline), D7, D14, D30, D60, and D90 using validated instruments including BPI, NRS (0-10), PSQI, SF-36, TQR scale, LEFS/UEFI, rescue analgesic quantification, and structured adverse event reporting.

STATISTICAL ANALYSIS:

Mixed-effects models for repeated measures (MMRM) or Generalized Estimating Equations (GEE) will be used. Propensity score matching may be employed to mitigate confounding bias. Pre-specified subgroup analyses by sport modality, pain location, competitive level, and training volume.

ETHICS:

The protocol will be submitted to the Research Ethics Committee (CEP) via Plataforma Brasil, following CNS Resolutions 466⁄2012 and 510⁄2016.

Results will be reportedfollowing STROBE guidelines for observational studies.

Inclusion criteria

• Predominantly articular, bone, or non-muscular pain (e.g., fractures, degenerative arthropathies)
• Presence of open skin lesions, infections, or active dermatoses at the topical application site
• Current use of WADA-prohibited substances that may interfere with outcome assessment
• Athletes in official competition during the study period using THC-containing formulations (due to WADA in-competition prohibition)
• Severe acute musculoskeletal injury (complete muscle rupture, fracture) within the last 30 days
• Cognitive or technological inability to use the follow-up platform

Exclusion criteria

• Predominantly articular, bone, or non-muscular pain (e.g., fractures, degenerative arthropathies)
• Presence of open skin lesions, infections, or active dermatoses at the topical application site
• Current use of WADA-prohibited substances that may interfere with outcome assessment
• Athletes in official competition during the study period using THC-containing formulations (due to WADA in-competition prohibition)
• Severe acute musculoskeletal injury (complete muscle rupture, fracture) within the last 30 days
• Cognitive or technological inability to use the follow-up platform