Alcohol Use Disorder, Depressive Sympotoms, Psilocybin
Conditions
Brief summary
Up to 40% of individuals with alcohol use disorder (AUD) experience depression, which increases the risk of early relapse. Depression can cause relapse to occur 3 times faster in individuals with AUD who experience depressive symptoms at discharge. No treatments have been approved for individuals with both AUD and depression. Psilocybin, a psychedelic, shows promising results in treating both depression and addiction. It may be particularly effective for preventing relapse in people with AUD who also have depressive symptoms after detoxification, offering quicker action than traditional antidepressants. The Psilocybin Alcohol Depression (PAD) pilot study, launched in February 2024, has provided critical insights for avoiding methodological flaws and demonstrated that psilocybin-assisted psychotherapy (PAP) is both feasible and acceptable. Preliminary efficacy analyses were conducted: at 12 weeks, the 25 mg group showed significantly greater reductions in drinking days (p = 0.038) and craving frequency (p = 0.045). Relapse rates were 35% in the 25 mg group and 50% in the control group (HR = 0.52 \[0.16-1.65\]). In the ERPPAD trial, the study authors will compare high-dose PAP with low-dose PAP in preventing relapse in individuals with AUD and depressive symptoms. The hypothesis is that high-dose PAP will be more effective than low-dose in preventing relapse over 6 months.
Interventions
2 administrations of high-dose psilocybin (25 mg) 3 weeks apart
2 administrations of low-dose psilocybin (3 mg) 3 weeks apart
Sponsors
Centre Hospitalier Universitaire de Nīmes
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed DSM-5 diagnosis of severe AUD. * Scale BDI-II ((Beck Depression Inventory) ≥14 * The last drink must have been consumed between day(D) -60 and D -10 at the inclusion visit. The patient must have had at least 1 HDD during the last drinking period NB: The last drinking period before inclusion is defined by the last 4 weeks counted from the last drink. * The patient must have given their free and informed consent and signed the consent form * The patient must be a member or beneficiary of a health insurance plan
Exclusion criteria
* The subject is participating in an interventional study, a clinical trial, or a clinical investigation or is in a period of exclusion determined by a previous study * The subject refuses to sign the consent * It is impossible to give the subject informed information * The patient is under safeguard of justice or state guardianship * Patient unable to give informed consent. * Participants planning to donate sperm within three months of psilocybin administration * Positive pregnancy test at inclusion for participants of childbearing age. * Patient who is pregnant, breastfeeding, or wishing to become pregnant during participation in the study. * Any use of classical psychedelic in the last year * Other current substance use disorder (except tobacco) * Diagnosed schizophrenic or bipolar disorder * High emotional lability (clinician-judged) * On antipsychotics treatment that may interfere with psilocybin. * Need for monoamine oxidase inhibitor (MAOI) treatment, which may interfere with psilocybin. * Severe suicidal ideation (high risk on the Columbia scale) * 1st degree family member with a diagnosed psychotic disorder * Severe cognitive impairment (clinician-judged) * CIWA-AR \> 8 * Medical conditions that would preclude safe participation in the trial, for example: seizure disorders; significant impairment of hepatic function; coronary artery disease; history of arrhythmia; Abnormal QT interval prolongation (QTc \> 470 ms for women and \>450 ms for men); heart failure; uncontrolled hypertension (greater than 165/95 mmHg at screening); history of stroke; severe asthma; hyperthyroidism; narrow-angle glaucoma; stenosing gastroduodenal ulcer; pyloroduodenal obstruction; symptomatic prostatic hypertrophy or bladder neck obstruction; uncontrolled type I or type II diabetes, or a history of ketoacidosis, hyperglycemic coma, or severe hypoglycemia with loss of consciousness.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of relapse between groups | Month 6 | Relapse Yes/no, where relapse is defined as the 1st heavy drinking day, assessed using the Timeline Follow-Back (TLFB) method |
| Time to relapse between groups | Month 6 | Days until relapse, where relapse is defined as the 1st heavy drinking day, assessed using the Timeline Follow-Back (TLFB) method |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in relapse rate between groups | At weeks 3, 9, 15, 21, 27 compared to baseline | Assessed using the Timeline Follow-Back (TLFB) method |
| Change in rate of heavy drinking days between groups | At weeks 3, 9, 15, 21, 27 compared to baseline | Percent; Assessed using the Timeline Follow-Back (TLFB) method |
| Change in total alcohol consumption between groups | At weeks 3, 9, 15, 21, 27 compared to baseline | Grams, assessed using the Timeline Follow-Back (TLFB) method |
| Change in number of drinking days between groups | At weeks 3, 9, 15, 21, 27 compared to baseline | Days, assessed using the Timeline Follow-Back (TLFB) method |
| Change in craving between groups | At weeks 3, 9, 15, 21, 27 compared to baseline | Assessed using the Craving Experience Questionnaire (CEQ), measuring strength and frequency of craving with a score ranging from 0 to 110, whereby a higher score denotes more craving. |
| Change in alcohol-related quality of life between groups | At weeks 3, 15, 21, 27 compared to baseline | Alcohol Quality of Life Scale- brief, a 7-item questionnaire assessing the negative impact of alcohol across 7 dimensions: social relationships, activities, living conditions, self-care, negative emotions, sleep, and loss of control. |
| Change in anxiety between groups | At weeks 3, 9, 15, 21, 27 compared to baseline | Beck Anxiety Inventory (BAI) |
| Change in emotional dysregulation between groups | At weeks 3, 9, 15, 21, 27 compared to baseline | Difficulties in Emotion Regulation Scale (DERS), a 36-item questionnaire |
| Change in rejection sensitivity between groups | At weeks 3, 9, 15, 21, 27 compared to baseline | Adult Rejection Sensitivity Questionnaire (A-RSQ) |
| Change in post-Traumatic Stress Disorder between groups | At weeks 3, 9, 15, 21, 27 compared to baseline | Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5), where a score of 44 is highly sensitive to diagnose PTSD |
| Visual Perspective task (VPT) | Day 0 | This task allows calculation of the egocentric bias index, the altercentric bias index and the egocentric egocentric bias |
| Visual Perspective task (VPT) for participants opting for a third dose | Week 28 | This task allows calculation of the egocentric bias index, the altercentric bias index and the egocentric egocentric bias |
| Request for a 3rd dose of psilocybin between groups | Week 27 | Yes/no |
| Reason for 3rd dose request | Week 27 | Relapse in AUD/ risk of relapse in AUD/low self-efficacy/ relapse in depression/ personal development/ other |
| Administration of 3rd dose | Week 28 | Yes/no |
| Relapse rate in relapsers between groups | At weeks 33, 39, 45, 51 compared to week 27 | Assessed using the Timeline Follow-Back (TLFB) method |
| Rate of heavy drinking days in relapsers between groups | At weeks 33, 39, 45, 51 compared to week 27 | Percent; Assessed using the Timeline Follow-Back (TLFB) method |
| Total alcohol consumption in relapsers between groups | At weeks 33, 39, 45, 51 compared to week 27 | Grams, assessed using the Timeline Follow-Back (TLFB) method |
| Change in number of drinking days in relapsers between groups | At weeks 33, 39, 45, 51 compared to week 27 | Days, assessed using the Timeline Follow-Back (TLFB) method |
| Change in craving in relapsers between groups | At weeks 33, 39, 45, 51 compared to week 27 | Assessed using the Craving Experience Questionnaire (CEQ), measuring strength and frequency of craving with a score ranging from 0 to 110, whereby a higher score denotes more craving. |
| Change in alcohol-related quality of life in relapsers between groups | At weeks 33, 39, 45, 51 compared to week 27 | Alcohol Quality of Life Scale- brief, a 7-item questionnaire assessing the negative impact of alcohol across 7 dimensions: social relationships, activities, living conditions, self-care, negative emotions, sleep, and loss of control. |
| Change in depressive symptoms in relapsers between groups | At weeks 33, 39, 45, 51 compared to week 27 | Beck Depression Inventory-II (BDI-II). The total score is the sum of the 21 item scores, ranging from 0 to 39. Higher scores indicate greater severity of depression. |
| Change in anxiety in relapsers between groups | At weeks 33, 39, 45, 51 compared to week 27 | Beck Anxiety Inventory (BAI) |
| Change in emotional dysregulation in relapsers between groups | At weeks 33, 39, 45, 51 compared to week 27 | Difficulties in Emotion Regulation Scale (DERS), a 36-item questionnaire |
| Change in rejection sensitivity in relapsers between groups | At weeks 33, 39, 45, 51 compared to week 27 | Adult Rejection Sensitivity Questionnaire (A-RSQ) |
| Adverse Childhood Experiences | Day 0 | The Adverse Childhood Experiences (ACE) Questionnaire |
| Attachment style | Day 0 | The Relationship Scale Questionnaire (RSQ) for attachment style (secure, fearful, preoccupied, dismissing) |
| Severity of aocohol use disorder | Day 0 | The Clinical Global Impression- Severity (CGI-S) |
| Cognitive impairments | Day 0 | Montreal Cognitive Assessment (MoCA) |
| Features of the psychedelic experience | Prior to integration session in Week 0 | Acceptance/Avoidance Promoting Experience Questionnaire (APEQ) |
| Age | Day 0 | years |
| Sex | Day 0 | — |
| Currently under antidepressant at the inclusion | Day 0 | Yes/no |
| Diagnosed with ADHD | Day 0 | Yes/no |
| In menstruating participants, point of the menstruation cycle at psilocybin administration | Dosing session in week 0 | — |
| Safety and tolerance of psilocybin | End of study, week 51 | List of adverse events |
| Change in gamma-glutamyl transferase (GGT) between groups and subgroups | At week 28 compared to baseline | fL |
| Change in carbohydrate-deficient transferrin (CDT) between groups and subgroups | At week 28 compared to baseline | U/L |
| Change in mean corpuscular volume (MCV) between groups and subgroups | At week 28 compared to baseline | Percentage |
| Guess the group | After dosing session Week 0 | Two-item questionnaire developed from the EPIsoDE framework |
Countries
France
Contacts
CONTACTAmandine Luquiens
PRINCIPAL_INVESTIGATORAmandine Luquiens
Centre Hospitalier Universitaire de Nīmes
Outcome results
None listed