Efficacy and Tolerance of THC 25: CBD 25 in Patients With Severe Pruritus: a Multicenter, Double-blind, Randomized, Placebo-controlled Study

Chronic pruritus affects 10-20% of the population and causes a major reduction in quality of life, comparable to pain, with significant psychological, social, and functional consequences. Current treatments are often insufficient, highlighting the urgent need for new therapeutic options. Recent advances in the pathophysiology of itch have shown the involvement of the endocannabinoid system (CB1, CB2, and TRPV1 receptors) in modulating itch signal transmission and cutaneous inflammation. Cannabinoids, particularly the balanced CBD:THC combination, appear promising as they provide both central and peripheral antipruritic effects, while CBD helps mitigate the psychotropic side effects of THC. Preclinical studies and limited clinical data suggest efficacy across various forms of pruritus (dermatological, uremic, cholestatic), though robust controlled trials are still lacking. Evidence from nabiximols (1:1 CBD:THC spray) in other conditions such as neuropathic pain and spasticity further supports the rationale for this approach. Therefore, sublingual LGP THC25:CBD25 oil has been selected for its balanced ratio, simple administration route, and expected tolerability, to evaluate its efficacy and safety in the treatment of chronic pruritus.

Inclusion Criteria: * Age ≥ 18 years * Severe pruritus, defined by a mean WI-NRS score ≥7/10 (evaluated on one week before inclusion, regardless of the cause of the pruritus * Insufficient relief (WI-NRS ≥7/10 ) or poor tolerance (adverse effects) of accessible drug and non-drug therapies * Stable treatment (for treatment of the prurit) for at least 6 weeks * Affiliated or benefiting of a social security * Informed consent (personally dated and) signed by the participant or any representatives (impartial witness/trusted person) Exclusion Criteria: * Patients unable to consent. * Patients refusing to participate in research. * Patients under guardianship or conservatorship. * Personal history of psychotic disorders. * Severe hepatic impairment, defined as prothrombin level \