Efficacy and Tolerance of Cannabidiol in Patients with Severe Pruritus: a Multicenter, Double-blind, Randomized, Placebo-controlled Study (CANNABITCH)

Regional University Hospital Center (CHRU)

Status and phase: Not yet enrolling; Phase 3

Conditions: Pruritus

Treatments: Drug: Placebo; Drug: Cannabis oil

Study type: Interventional

Funder types: Other

Identifiers

NCT06435299

29BRC23.0164

Details and patient eligibility

About

Pruritus is defined as an unpleasant sensation leading to the need to scratch. Medications for pruritus are much less effective than those used for pain and it is imperative to find new therapeutic options.

Over the last 20 years, the understanding of the pathophysiology of pruritus has progressed significantly, opening new possible therapeutic fields. Among these, cannabinoids seem very promising because the physiological inhibitory role of endocannabinoids, mainly produced by neurons, has been well demonstrated. Data from the literature suggest that the antipruritic effects of cannabinoids are due to a combination of effects on neuronal activation, transmission along the afferent pathway, and local modulation of keratinocytes and mast cells. The antipruritic effect is peripheral and central, through modulation of CB1, CB2 or TRPV1 channels. CB1 and CB2 receptors are specific cannabinoid receptors, CB1 being present at the central and peripheral level while CB2 is only peripheral and very present in the skin. Cannabinoids can also bind to TRPV1, and thus inhibit neurogenic inflammation by antagonizing or stabilizing this ion channel, which prevents neuronal activation by pruritogenic mediators. Phytocannabinoids are derived from cannabis and are used for a variety of purposes, with their development for medical purposes expanding rapidly. The two best known are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC binds to TRPV1, CB2 and CB1, the activation of the latter being at the origin of parallel psychotropic effects. CBD binds mainly to TRPV1, which allows us to expect very favorable effects on pruritus, neurogenic inflammation and skin pain, without fearing side effects of this type.

A limited number of studies suggest that cannabinoids may be useful topically or systemically, in humans or animals, but no comparative study with placebo has been performed. These encouraging results have been observed in cases of induced pruritus, idiopathic pruritus, eczema, uremic pruritus, cholestatic pruritus, prurigo, sensitive skin or even epidermolysis bullosa.

Currently, the ANSM is conducting an evaluation of the effects of medical cannabis on severe pain. We propose to evaluate the effects on severe pruritus in a randomized placebo-controlled study one of the products chosen by the ANSM in this context, the oil LITTLE GREEN PHARMA, which we choose for its dominant CBD ratio (THC < 5 mg/ml, CBD > 5 mg/ml).

Enrollment: 218 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 <50% or with predictive biological impairment.
• Moderate to severe renal impairment, with an estimated glomerular filtration rate ≤ 44 mL/min/1.73 m².
• Severe cardiovascular or cerebrovascular disease, including history of myocardial infarction or stroke.
• Pregnant or breastfeeding women.
• Lack of understanding of questionnaires or inability to follow up.
• Women of childbearing potential unwilling to use appropriate contraception.
• Cannabinoid use outside the clinical trial
• Use of cannabis or its derivatives less than one week before inclusion
• History of hypersensitivity or allergy to any cannabinoid product.
• Allergy to nuts.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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218 participants in 2 patient groups, including a placebo group

Cannabis oil

Experimental group

Description:

Cannabis oil 50mg/mL arm : An auto-titration phase will take place during the first 14 days of treatment: 0.2 ml on the first day then increase of 0.2 ml every 2 days in 2 daily doses, that is to say 1.4 ml/day maximum. If any tolerable side-effects occurred, patients were advised not to increase the dose; if intolerable side-effects occurred, dose reduction was advised. After initial titration, the dose will then be maintained for 4 consecutive weeks.

Treatment:

Drug: Cannabis oil

PLACEBO

Placebo Comparator group

Description:

Placebo arm : An auto-titration phase will take place during the first 14 days of treatment: 0.2 ml on the first day then increase of 0.2 ml every 2 days in 2 daily doses, that is to say 1.4 ml/day maximum. If any tolerable side-effects occurred, patients were advised not to increase the dose; if intolerable side-effects occurred, dose reduction was advised. After initial titration, the dose will then be maintained for 4 consecutive weeks.

Treatment:

Drug: Placebo