Antidepressant Response of DMT Masked With Propofol

Официальное название

Investigating the Role of the Psychedelic Experience in the Antidepressant Response in Patients With Major Depression: a Placebo-controlled Factorial Trial With DMT Masked With Propofol (DMT4D-Study)

Обзор

The aim of this study is to elucidate if the anti-depressive effect of N,N-dimethyltryptamine (DMT) is based on a biological mechanisms including neuroplasticity and anti-inflammatory effect or due to the subjective psychedelic experience.

Подробное описание

Major depressive disorder (MDD) affects nearly 20% of people, but current treatments-both pharmacological and psychotherapeutic-have limited efficacy, especially for mild to severe cases. Psychedelics like LSD, psilocybin, and DMT are being explored as alternative therapies, with studies showing promising antidepressant effects. However, it is unclear whether these benefits stem from their acute subjective (psychedelic) experience or from biological mechanisms like neuroplasticity and anti-inflammatory effects.

This study aims to determine if the antidepressant effects of DMT occur independently of its psychedelic experience. To test this, DMT will be administered under sedation (with propofol) to mask subjective effects, as well as without sedation.

Вмешательства

• Препарат N,N-Dimethyltryptamine
  administration of a 2mg/min DMT perfusion over 20 min
• Препарат Placebo
  administration of a placebo perfusion over 20 min
• Процедура Propofol
  30 min propofol sedation
• Процедура no sedation
  no sedation

Первичные конечные точки

• long term changes in depressive symptoms (MADRS) [Срок оценки: baseline (before intervention) and on day 14 post-intervention]

Вторичные конечные точки (12)

• Short term changes in depressive symptoms (MADRS) [Срок оценки: Baseline (before intervention) and on day 1, 3 and 7 post-intervention]
• Changes in depressive symptoms (BDI) [Срок оценки: Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention]
• Changes in anxiety (STAI) [Срок оценки: Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention]
• Changes of clinical global impression (CGI-S) [Срок оценки: Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention]
• Changes of clinical global impression (CGI-I) [Срок оценки: Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention]
• Changes in quality of life (WHOQOL-bref) [Срок оценки: Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention]
• Persisting positive and negative effects (PEQ) [Срок оценки: On day 14 post-intervention]
• Acute subjective effects (5D-ASC) [Срок оценки: On day 0 post-intervention]
• Subjective Effects Rating (SES) [Срок оценки: On day 0 pre- and post-intervention]
• Psychedelic Experience Scale (PES) [Срок оценки: On day 0 post-intervention]
• Emotional breakthrough inventory (EBI) [Срок оценки: On day 0 post-intervention]
• Acute adverse effects [Срок оценки: On day 0 and 1 post-intervention]

Критерии участия

Критерии включения

• Participants must meet DSM-5 criteria for MDD of at least moderate severity (MADRS≥20).
• Participants either currently do not use antidepressants or are treated with a stable dose for at least 4 weeks prior to randomization.
• Age ≥ 21 years old.
• Sufficient understanding of the German language.
• Able to understand the study procedures and risks and willing to adhere to the protocol and sign the consent form.
• Willing not to drive or operate heavy machinery on the treatment day.
• Willing to refrain from more than 7 standard alcoholic drinks a week, more than 10 cigarettes a day, more than 2 cups of coffee a day, and any illicit substances during study participation.
• Willing to use effective contraceptive measures throughout study participation.

Критерии исключения

• Past or present bipolar or psychotic disorder, including depressive disorder with psychotic features.
• First-degree relative with a psychotic or bipolar disorder.
• Significant prodromal psychotic symptoms (Prodromal Questionnaire-16 symptoms ≥ 6).
• Psychiatric condition judged to be incompatible with establishment of rapport with study team members and/or safe exposure to DMT, e.g. diagnosed or suspected borderline personality disorder.
• Current post-traumatic stress disorder or acute stress reaction due to a traumatic event.
• Post-partum depression.
• Pregnant or breastfeeding women.
• Current or recent history of significant suicide ideation or suicide behavior within the past 6 months.
• Current severe substance use disorder other than nicotine.
• Planned ketamine, other psychedelic, or electroconvulsive treatment or any such treatment within the past 3 months.
• Any lifetime use of DMT, use of any other psychedelics within last 3 month or lifetime use of any other psychedelics more than 15 times.
• Patients who are treated with neuroleptics or known antagonists of 5-HT2 receptors or monoamine oxidase inhibitors (MAOI) and are not able/willing to pause.
• Increased risk for adverse reactions to propofol or soja products.
• Increased risk for aspiration.
• Increased risk for difficult mask ventilation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Швейцария · 1 центр

• University Hospital Basel — Basel

Идентификаторы

NCT: NCT06927076 · 2024-02312;am24Liechti6

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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