Cannabidiol After Multi-Trauma for Pain and Opioid Therapy (CAM-POT)

Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

Status and phase: Enrolling; Phase 2

Conditions: Fracture

Treatments: Drug: Cannabidiol; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06448923

2025-2105

Details and patient eligibility

About

The aim of this project is to investigate the therapeutic potential and safety of acute Cannabidiol (CBD) treatment on longitudinal pain symptoms, and to assess potential interactions with pain mediators including opioids and sex on CBD treatment response. To this end, this research protocol proposes a comprehensive translational approach including a placebo-controlled randomized clinical trial comparing two daily doses of CBD treatment administered for one month on pain relief. This study will also compare intervention conditions on inflammation markers, participant quality of life, sleep quality, depression, anxiety, cognition and orthopaedic function.

Full description

The level of pain in the acute phase after injury is a predictor of the development of chronic pain. Chronic pain is defined as pain that persists for more than 3 months post-accident and impairs functional recovery. Mechanistically, it has been shown that acute nonspecific inflammation triggered after peripheral injury results in the continuous release of proinflammatory cytokines that weaken the blood-brain barrier, facilitating the entry of toxins that can invade the central nervous system (CNS). The resulting sustained inflammation of the CNS plays an important role in establishing the maladaptive plasticity process underlying pain chronification. Cannabidiol (CBD), a component of cannabis devoid of addictive or psychotropic effects, stands out as a potential therapeutic agent given its analgesic and anti-inflammatory properties as well as its potential to enhance the biomechanical properties of bone healing. Given the excellent safety profile of CBD and its inhibitory effects on microglial activity, the primary mechanism of neuroinflammation and pain, CBD has the potential to promote acute pain relief while reducing reliance on addictive opioid treatments, hence facilitating recovery in trauma patients.

This study is a randomized, placebo controlled, human pilot clinical trial evaluating the effects of two doses (low and moderate) of CBD vs. placebo on pain after orthopaedic trauma.

Risks of adverse effects are considered low given the demonstrated excellent safety profile of CBD. CBD was also shown to accentuate opioid analgesic effects, thus reducing required opioid doses for patient comfort. The most likely adverse events associated with CBD in adult patients include somnolence, fatigue, drowsiness and decreased appetite. Access to on-duty emergency physicians at the recruiting site will be provided during the entire treatment duration.

A 30% relative pain intensity reduction on the VAS (expected response of 50% or more in the CBD group and expected 20% in the placebo group) has been used extensively to reflect clinically significant pain relief in clinical trials. Based on a Fisher's exact test, a sample size of 225 participants (3 groups of 75) will be required to reach a power of 80% to detect a statistically significant difference in the proportion of patients who reaches 30% pain reduction between the CBD groups and placebo at 1-month post-injury, assuming a dropout rate of 20% and a significance level of 5%. These parameters are taken from a successful randomised, placebo-controlled clinical trial using Sativex© in treating 125 neuropathic pain patients. Moreover, considering that the placebo group may ingest more opiates and that the anticipated inter-group effect at one month may be reduced to 20%, a total sample size of 225 subjects could be required to achieve 80% power, assuming a drop-out rate of 20% and a significance level of 5%.

Our group has ensured the feasibility of conducting such a pilot clinical trial in multi-trauma patients with the recruitment of 110 patients in less than 18 months to take part in a 10-session, outpatient treatment trial. A partnership with Canadian company EmpowerPharm will enable the use of pharmaceutical-grade synthetic CBD samples and identical placebos. The pharmacokinetic profile of the CBD product has been established.

Enrollment: 225 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with a long bone fracture of the lower limb (tibia, fibula, femur, metatarsals, and phalanges) or the upper limb (humerus, radius, ulna, metacarpals, and phalanges) treated to Sacre-Coeur Hospital in Montreal (HSCM) within one week of the accident
• Participants is between 18 and 70 years of age
• Patients with or without surgical procedures

Exclusion criteria

• Moderate/severe traumatic brain injury (TBI)
• Diagnosis of any of the following mental disorders as defined by the DSM-5: schizophrenia, intellectual disability, bipolar disorder, major depression, a diagnosed and untreated sleep disorders
• History of alcohol or opioid misuse/abuse, as defined by the DSM-5
• Evidence of severe renal (stage 4 or 5) or hepatic impairment (Child B or C)
• Pregnant or lactating women, women of childbearing potential who are not using medically accepted forms of contraception (e.g., condoms, oral contraceptive or intrauterine device), or women who are actively planning on becoming pregnant
• History of adverse reactions to cannabis
• Patients taking warfarin, sildenafil, valproate or under opioids treatment prior to the injury
• Patients experiencing on average mild-to-absent pain in the last 24h preceding recruitment (as per a score <30 on a 0-100mm Visual Analogue Scale (VAS))
• Transport business drivers and heavy machinery operators
• A diagnosis of chronic pain, bone pathology (e.g., osteoporosis) or chronic inflammatory disease (e.g., rheumatoid arthritis, arthritis, psoriasis)
• Not having French or English as a spoken language
• A weighted MoCA score of less than 24
• Regular cannabis use more than 5 times a week

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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225 participants in 3 patient groups, including a placebo group

Low CBD dose

Experimental group

Description:

Participants will receive 25 mg orally twice daily during a meal for a month

Treatment:

Drug: Cannabidiol

Drug: Cannabidiol

Moderate CBD dose

Experimental group

Description:

Participants will receive 50 mg orally twice daily during a meal for a month

Treatment:

Drug: Cannabidiol

Drug: Cannabidiol

Placebo

Placebo Comparator group

Description:

Participants will receive matching placebo orally twice daily during a meal for a month

Treatment:

Drug: Placebo