Psilocybin AsSisted pSychotherapy for the treatmENt of Gambling disordER : a Pilot Study (PASSENGER)

The PASSENGER project aims to conduct a pilot feasibility study of the implementation of a randomized clinical trial on psilocybin-assisted psychotherapy for the treatment of gambling disorder. Feasibility will be assessed by estimating the ability to retain participants until the end of the protocol. Other objectives of the study will be to generate preliminary efficacy data, identify clinical factors potentially associated with the intensity of the psychedelic experience (which determines the expected therapeutic effect), and conduct a preliminary assessment of the safety of the treatment under study.

Study Overview

• Status: Not yet recruiting
• Conditions: Gambling Disorder
• Intervention / Treatment: Drug: Psychotherapy assisted by high-dose psilocybin (25mg or 40mg where appropriate); Drug: Psychotherapy assisted by low-dose psilocybin (1 mg)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Benoit SCHRECK; Phone Number: +33.2.40.84.76.20; Email: benoit.schreck@chu-nantes.fr

Study Locations

• France
  • Nantes, France
    • Nantes University Hospital
    • Contact: Benoit SCHRECK; Phone Number: +33.2.40.84.76.20; Email: benoit.schreck@chu-nantes.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Men and women aged 18 years or older
• With a confirmed diagnosis of current gambling disorder (diagnostic criteria according to DSM-5), regardless of severity.
• Able to complete self-assessment questionnaires
• Willing to start addiction treatment, or for whom treatment already undertaken is not sufficient
• Willing to undergo a blood test and ECG
• Written and oral comprehension of French
• Having signed an informed consent form before any procedure under study
• Affiliated with a French social security system
• Women of childbearing age with a negative pregnancy test and highly effective contraception (according to version 1.2 of March 2024 of the CTCG recommendations in Appendix 7)
• Men of childbearing age using effective contraception (according to version 1.2 of March 2024 of the CTCG recommendations).
• Negative result on urinary toxicology screening
• In the case of psychotropic treatment (excluding nicotine replacement therapy): stabilization of dosage or initiation for more than 1 month.

Exclusion Criteria:

• Medical conditions that would prevent safe participation in the trial (epilepsy, significantly impaired liver function (TP<50%), significantly impaired kidney function (GFR<90 mL/min), coronary artery disease, history of arrhythmia, heart failure, uncontrolled hypertension, history of stroke, severe asthma, hyperthyroidism, narrow-angle glaucoma, symptomatic prostatic hypertrophy, or bladder neck obstruction).
• Serious ECG abnormalities (including QTc prolongation = corrected QT)
• Current or past psychotic or bipolar disorder
• Other unstable psychiatric disorder
• Family history (first-degree relatives) of psychotic disorder or type 1 bipolar disorder
• Current high risk of suicide (according to the MINI 5.0 suicide risk module)
• History of hallucinogen use disorder or any use in the past year
• Current alcohol use disorder with a history of withdrawal symptoms
• Extreme thinness (BMI < 16.5) or obesity (BMI > 30)
• Major cognitive impairment (Mini-Mental State Examination score < 26)
• Allergy or hypersensitivity to psilocybin or any of the excipients contained in the investigational drug
• Taking UGT1A9, UGT1A10, ALDH, or ADH inhibitors
• Pregnancy or breastfeeding
• Current protective measures (guardianship and legal protection)
• Participation in another interventional research protocol involving another psychotherapeutic or pharmacological intervention that may have an impact on clinical progression

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psychotherapy assisted by high-dose psilocybin (25mg or 40mg where appropriate)	Drug: Psychotherapy assisted by high-dose psilocybin (25mg or 40mg where appropriate); The first session of psilocybin PEX010 administration will use a moderately high dose of psilocybin, i.e., 25 mg. The dose may be increased to 40 mg during the second administration session in the experimental group, depending on the response during the previous session, as assessed by the Mystical Experience Questionnaire-30 (MEQ-30).
Active Comparator: Psychotherapy assisted by low-dose psilocybin (1 mg)	Drug: Psychotherapy assisted by low-dose psilocybin (1 mg); The first session of psilocybin PEX010 administration will use a very low dose of 1 mg in the control group. During the second administration session, the dose will be maintained at 1 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protocol completion rate	Proportion of randomized participants who completed all scheduled visits and procedures, including all PAP sessions/control sessions and follow-up assessments until the end of study participation.	End of study (33 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of recruitment and the proposed experimental protocol.	Goal of recruiting 30 participants within the planned inclusion period achieved	End of study (33 months)
Assessement of the acceptability of the proposed experimental treatment by patients and caregivers.	Self-reported acceptability by patients and caregivers	Month 1
Assessment of personal self-efficacy (General Self-Efficacy Scale: GSES)	Changes in each arm, between baseline assessment (V0) and post-treatment assessment (V1) of personal self-efficacy (General Self-Efficacy Scale: GSES)	Month 1
Correlation between the intensity of the psychedelic experience, measured by the Mystical Experience Questionnaire (MEQ-30) score, and the WHOQOL-SRPB spirituality score	Correlation between the intensity of the psychedelic experience, measured by the Mystical Experience Questionnaire (MEQ-30) score obtained post-administration, and the spirituality WHOQOL-SRPB at baseline	Month 1
Correlation between the intensity of the psychedelic experience, measured by the Mystical Experience Questionnaire (MEQ-30) score, and the Self-Compassion Scale	Correlation between the intensity of the psychedelic experience, measured by the Mystical Experience Questionnaire (MEQ-30) score obtained post-administration, and the self-compassion score (Self-Compassion Scale: SCS)	Month 1
Correlation between the intensity of the psychedelic experience, measured by the Mystical Experience Questionnaire (MEQ-30) score, and treatment expectations (Credibility/Expectancy Questionnaire: CEQ)	Correlation between the intensity of the psychedelic experience, measured by the Mystical Experience Questionnaire (MEQ-30) score obtained post-administration, and treatment expectations based on the Credibility/Expectancy Questionnaire (CEQ)	Month 1
Correlation between the intensity of the psychedelic experience, measured by the Mystical Experience Questionnaire (MEQ-30) score, and personal self-efficacy (General Self-Efficacy Scale: GSES)	Correlation between the intensity of the psychedelic experience, measured by the Mystical Experience Questionnaire (MEQ-30) score obtained post-administration, and the personal self-efficacy based on General Self-Efficacy Scale (GSES)	Month 1
Correlation between the intensity of the psychedelic experience, measured by the Mystical Experience Questionnaire (MEQ-30) score, and average dose of psilocybin administered during the two sessions	Correlation between the intensity of the psychedelic experience, measured by the Mystical Experience Questionnaire (MEQ-30) score obtained post-administration, and average dose of psilocybin administered during the two sessions	Month 1
Correlation between the intensity of the psychedelic experience, measured by the Mystical Experience Questionnaire (MEQ-30) score, and measurement of blind maintenance	Correlation between the intensity of the psychedelic experience, measured by the Mystical Experience Questionnaire (MEQ-30) score obtained post-administration, and the measurement of blind maintenance.	Month 1
Clinical global impression of severity (Clinical Global Impression-Severity: CGI-S)	Changes between baseline assessment (Visit 0) and post-treatment assessment (Visit 1) of clinical global impression of severity (Clinical Global Impression-Severity: CGI-S)	Month 1
Self-Compassion Scale (SCS)	Changes between baseline assessment (Visit 0) and post-treatment assessment (Visit 1) of Self-Compassion Scale (SCS)	Month 1
Spirituality assessment (World Health Organization Quality of Life Spirituality, Religiousness and Personal Beliefs Instrument: WHOQOL-SRPB)	Changes between baseline assessment (Visit 0) and post-treatment assessment (Visit 1) of World Health Organization Quality of Life Spirituality, Religiousness and Personal Beliefs Instrument (WHOQOL-SRPB)	Month 1
Analysis of daily diary	Changes between baseline assessment (Visit 0) and post-treatment assessment (Visit 1) of gambling behavior using daily diary.	Month 1
Heart rate	Average scores in each arm of heart rate assessed during administration sessions	Month 1
Blood pressure	Average scores in each arm of blood pressure assessed during administration sessions	Month 1
Expected acute effects assessment	Average scores in each arm of expected acute effects (17-item behavior and mood observation grid), assessed during administration sessions	Month 1
Assessment of Adverse Effects	Assessment of AEs (excluding expected acute effects), assessed during administration sessions in particular, but also throughout the duration of participation in the study;	Month 3
Mini International Neuropsychiatric Interview (MINI 5.0)	Average scores in each arm of an increase in the level of suicide risk assessed by the Mini International Neuropsychiatric Interview (MINI 5.0)	Month 3
Clinical Global Impression-Efficacy Index: CGI-IE	Average scores in each arm of the therapeutic index (Clinical Global Impression-Efficacy Index: CGI-IE) and clinical improvement (Clinical Global Impression-Improvement: CGI-I), assessed at post-treatment evaluation.	Month 3

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: January 22, 2026
• First Submitted That Met QC Criteria: January 29, 2026
• First Posted (Actual): February 5, 2026

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Disruptive, Impulse Control, and Conduct Disorders; Behavior; Risk-Taking; Gambling; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Psilocybin
• Other Study ID Numbers: RC25_0105; 2025-522743-18-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No