Real-world Evidence of Cannabinoid for Observed Pain Relief

Официальное название

Topical Use of Cannabinoids (CBD:THC 3:1) as Adjunctive Therapy for Chronic Muscle Pain in Athletes: A Comparative Prospective Observational Study

Обзор

Chronic muscle pain is one of the most prevalent clinical challenges in sports medicine, significantly affecting training capacity, competitive performance, and quality of life in athletes. The endocannabinoid system has emerged as a promising therapeutic target for pain modulation in the sports context. This prospective, comparative, non-randomized observational study aims to evaluate whether adjuvant topical application of a cannabinoid balm (CBD:THC 3:1 - Papa \& Barkley) provides additional reduction in chronic muscle pain intensity in athletes, compared to systemic CBD oil alone, over 90 days of follow-up in a real-world clinical practice setting. Sixty adult athletes (amateur or professional) with established chronic muscle pain (≥3 months) who receive clinical indication for cannabinoid therapy will be followed in two observational cohorts: Cohort A (n=30), receiving only systemic CBD oil (60 mg/day oral/sublingual), and Cohort B, (n=30) receiving systemic CBD oil plus the topical cannabinoid balm (CBD:THC 3:1, applied twice daily to the affected muscle area). Treatment allocation is based exclusively on the clinical decision of the principal investigator, reflecting routine medical practice. The primary outcome is the change in Brief Pain Inventory (BPI) scores from baseline (D0) to end of follow-up (D90). Secondary outcomes include pain intensity (NRS), sleep quality (PSQI), quality of life (SF-36), perceived muscle recovery (TQR scale), functional capacity (LEFS/UEFI), rescue analgesic use, and safety/tolerability of the topical formulation. The study aims to generate real-world evidence on the effectiveness and safety of adjuvant topical cannabinoid therapy in athletes with chronic muscle pain in the Brazilian clinical practice setting.

Подробное описание

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.

Первичные конечные точки

• Change in Chronic Muscle Pain Intensity and Interference (Brief Pain Inventory) [Срок оценки: From baseline (Day 0) to end of follow-up (Day 90)]

Вторичные конечные точки (6)

• Pain Intensity (Numeric Rating Scale) [Срок оценки: From baseline (Day 0) to Day 90, with assessments at Days 7, 14, 30, 60, and 90]
• Sleep Quality (Pittsburgh Sleep Quality Index - PSQI) [Срок оценки: From baseline (Day 0) to Day 90, with assessments at Days 30, 60, and 90]
• Quality of Life (SF-36) [Срок оценки: From baseline (Day 0) to Day 90, with assessments at Days 30, 60, and 90]
• Perceived Muscle Recovery (Total Quality Recovery - TQR Scale) [Срок оценки: From baseline (Day 0) to Day 90, with assessments at Days 7, 14, 30, 60, and 90]
• Sports Functional Capacity (LEFS/UEFI) [Срок оценки: From baseline (Day 0) to Day 90, with assessments at Days 30, 60, and 90]
• Safety and Tolerability (Adverse Events) [Срок оценки: From Day 7 to Day 90, with continuous monitoring and assessments at Days 7, 14, 30, 60, and 90]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Seevathee K, Kessomboon P, Manimmanakorn N, Luangphimai S, Thaneerat T, Wanaratna K, Plengphanich S, Thaenkham T, Sena W. Efficacy and Safety of Transdermal Medical Cannabis (THC:CBD:CBN formula) to Treat Painful Diabetic Peripheral Neuropathy of Lower Extremities. Med Cannabis Cannabinoids. 2024 Nov 14;8(1):1-14. doi: 10.1159/000542511. eCollection 2025 Jan-Dec. PMID 39720705
• Rojas-Valverde D, Fallas-Campos A. Cannabidiol in sports: insights on how CBD could improve performance and recovery. Front Pharmacol. 2023 Sep 22;14:1210202. doi: 10.3389/fphar.2023.1210202. eCollection 2023. No abstract available. PMID 37808192
• Hall N, James B, Bhuiyan MAN, Crane E, Falgout C, Murnane KS. Topical cannabidiol is well tolerated in individuals with a history of elite physical performance and chronic lower extremity pain. J Cannabis Res. 2023 Mar 30;5(1):11. doi: 10.1186/s42238-023-00179-8. PMID 36991501

Идентификаторы

NCT: NCT07733791 · APMCTOPICALCBD

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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