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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pruritus
• Intervention / Treatment: Drug: Cannabis oil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 218
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Laurent MISERY, PU-PH; Email: laurent.misery@chu-brest.fr

Study Locations

• France
  • France
    • Angers, France, France, 49000
      • CHU Angers
      • Contact: YANNICK LE CORRE, MD; Phone Number: 02 41 35 34 19; Email: yalecorre@chu-angers.fr
    • La Roche-sur-Yon, France, France, 85925
      • CHD Vendee
      • Contact: Carole POIRAUD, MD; Phone Number: 02 51 44 61 83; Email: Carole.poiraud@ght85.fr
    • La Rochelle, France, France, 17300
      • Groupe Hospitalier La Rochelle
      • Contact: Cécile FRENARD, MD; Phone Number: 05 45 45 51 83; Email: Cecile.frenard@ght-atlantique17.fr
    • Nantes, France, France, 44093
      • CHU de Nantes
      • Contact: Sebastien BARBAROT, MD-PHD; Phone Number: 02 40 08 40 86; Email: sebastien.barbarot@chu-nantes.fr
    • Poitiers, France, France, 86000
      • CHU de Poitiers
      • Contact: Ewa HAINAUT, MD; Phone Number: 05 49 44 44 59; Email: Ewa.HAINAUT@chu-poitiers.fr
    • Tours, France, France, 37044
      • CHRU de Tours
      • Contact: Laurent MACHET, MD-PHD; Phone Number: 02 47 47 87 73; Email: machet@univ-tours.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cannabis oil; CBD:THC 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 then only 0.1 per day , up to 1 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.	Drug: Cannabis oil; Patients in this arm will have to take Cannabis oil (50mg/mL) twice a day with the daily dose estimated during auto titration phase (from W0 to W2)
Placebo Comparator: PLACEBO; Placebo arm : An auto-titration phase will take place during the first 14 days of treatment with the same modalities as experimental group 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.	Drug: Placebo; Patients in this arm will have to take Placebo oil twice a day with the daily dose estimated during auto titration phase (from W0 to W2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WI-NRS change	Binary outcome (success or failure). Success is defined by a reduction of 30% in WINRS (Worst Itching Intensity Numerical Rating Scale - On a scale of 0 (no itch) to 10 (worst itch imaginable)) from the inclusion visit to week 6.	Week 0
WI-NRS change	Binary outcome (success or failure). Success is defined by a reduction of 30% in WINRS (Worst Itching Intensity Numerical Rating Scale - On a scale of 0 (no itch) to 10 (worst itch imaginable)) from the inclusion visit to week 6.	Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ItchyQoL change from W0 to W2	- Change in ItchyQoL score from inclusion (= Week 0) visit to week 2 (The ItchyQoL questionnaire contains 22 items, and each item is rated on a 5-point scale, ranging from 1 = never to 5 = all the time)	Week 0
ItchyQoL change from W0 to W2	- Change in ItchyQoL score from inclusion (= Week 0) visit to week 2 (The ItchyQoL questionnaire contains 22 items, and each item is rated on a 5-point scale, ranging from 1 = never to 5 = all the time)	Week 2
Chronic Itch Burden Scale change from W0 to W2	- Change in Chronic Itch Burden Scale - 10 from inclusion (= Week 0) visit to week 2 (10 questions rated from "Not at all" to "Very much" on patient itching)	Week 0
Chronic Itch Burden Scale change from W0 to W2	- Change in Chronic Itch Burden Scale - 10 from inclusion (= Week 0) visit to week 2 (10 questions rated from "Not at all" to "Very much" on patient itching)	Week 2
Treatment adverse events	- Incidence and severity of treatment-emergent adverse events.	Week 0
Treatment adverse events	- Incidence and severity of treatment-emergent adverse events.	Week 2
Treatment adverse events	- Incidence and severity of treatment-emergent adverse events.	Week 4
Treatment adverse events	- Incidence and severity of treatment-emergent adverse events.	Week 6
Treatment adverse events	- Incidence and severity of treatment-emergent adverse events.	Week 8
WI-NRS change from W0 to W2	- Proportion of patients achieving at least a weekly mean reduction of 4 points in WI-NRS (Worst Itching Intensity Numerical Rating Scale - On a scale of 0 (no itch) to 10 (worst itch imaginable)) score from inclusion visit to week 2	Week 0
WI-NRS change from W0 to W2	- Proportion of patients achieving at least a weekly mean reduction of 4 points in WI-NRS (Worst Itching Intensity Numerical Rating Scale - On a scale of 0 (no itch) to 10 (worst itch imaginable)) score from inclusion visit to week 2	Week 2
WI-NRS change from W2 to W6	Proportion of patients achieving at least a weekly mean reduction of 4 points in WI-NRS (Worst Itching Intensity Numerical Rating Scale - On a scale of 0 (no itch) to 10 (worst itch imaginable)) score from week 2 to week 6.	Week 2
WI-NRS change from W2 to W6	Proportion of patients achieving at least a weekly mean reduction of 4 points in WI-NRS (Worst Itching Intensity Numerical Rating Scale - On a scale of 0 (no itch) to 10 (worst itch imaginable)) score from week 2 to week 6.	Week 6
ItchyQoL change from W2 to W6	- Percent change in ItchyQoL score from Week 2 visit to week 6 (The ItchyQoL questionnaire contains 22 items, and each item is rated on a 5-point scale, ranging from 1 = never to 5 = all the time)	Week 2
ItchyQoL change from W2 to W6	- Change in ItchyQoL score from Week 2 visit to week 6.(The ItchyQoL questionnaire contains 22 items, and each item is rated on a 5-point scale, ranging from 1 = never to 5 = all the time)	Week 6
Chronic Itch Burden Scale change from W2 to W6	- Percent change in Chronic Itch Burden Scale - 10 from Week 2 visit to week 6 (10 questions rated from "Not at all" to "Very much" on patient itching)	Week 2
Chronic Itch Burden Scale change from W2 to W6	- Percent change in Chronic Itch Burden Scale - 10 from Week 2 visit to week 6 (10 questions rated from "Not at all" to "Very much" on patient itching)	Week 6
Treatment Observance Rate	- Number of observant patients (YES/NO) in both arms: Observance (defined as YES) is considered as taking at least one dose of treatment per day over the W0 - W6 period.	Week 6

Collaborators and Investigators

• Sponsor: University Hospital, Brest

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: March 27, 2024
• First Submitted That Met QC Criteria: May 29, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: CBD; THC; itching
• Additional Relevant MeSH Terms: Skin Manifestations; Skin Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Pruritus; nabiximols
• Other Study ID Numbers: 29BRC23.0164

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No