Study: NCT06746441

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Psilocybin
Description: Psilocybin is a naturally occurring serotonergic psychedelic compound found in Psilocybe mushrooms. It is metabolized in the body into its active form, psilocin, which has a high affinity for serotonin 5-HT2A receptors. This enables psilocin to bypass the default serotonin pathway, producing antidepressant effects.~For this study:~Psilocybin will be administered orally in a dose of 5-6 grams per session. Each participant in the Psilocybin and Psilocybin-assisted CBT arms will receive two sessions spaced six weeks apart.~The therapy will be conducted in a controlled hospital setting with medical monitoring during the session to ensure safety until the hallucination phase subsides.~Psilocybin will be added to routine antidepressant medication.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Psilocybin
Description: Psilocybin is a naturally occurring serotonergic psychedelic compound found in Psilocybe mushrooms. It is metabolized in the body into its active form, psilocin, which has a high affinity for serotonin 5-HT2A receptors. This enables psilocin to bypass the default serotonin pathway, producing antidepressant effects.~For this study:~Psilocybin will be administered orally in a dose of 5-6 grams per session. Each participant in the Psilocybin and Psilocybin-assisted CBT arms will receive two sessions spaced six weeks apart.~The therapy will be conducted in a controlled hospital setting with medical monitoring during the session to ensure safety until the hallucination phase subsides.~Psilocybin will be added to routine antidepressant medication.

Intervention type: BEHAVIORAL
Group type: ACTIVE_COMPARATOR
Intervention: Cognitive Behavioral Therapy (CBT)
Description: Cognitive Behavioral Therapy (CBT) is a structured, time-limited psychotherapy aimed at alleviating symptoms of depression. It involves addressing negative thoughts and behavioral patterns through the following steps:~Identifying troubling life situations. Recognizing thoughts, emotions, and beliefs about those situations. Identifying negative or inaccurate thinking patterns. Restructuring those thoughts into positive and realistic perspectives.~In this study:~CBT will consist of 8-10 structured sessions, each lasting approximately 90 minutes.~Participants will attend therapy sessions twice weekly over a six-week period. The intervention will be delivered by trained psychotherapists in a controlled hospital setting.~Routine antidepressant medications will be continued alongside CBT.

Intervention type: BEHAVIORAL
Group type: ACTIVE_COMPARATOR
Intervention: Cognitive Behavioral Therapy (CBT)
Description: Cognitive Behavioral Therapy (CBT) is a structured, time-limited psychotherapy aimed at alleviating symptoms of depression. It involves addressing negative thoughts and behavioral patterns through the following steps:~Identifying troubling life situations. Recognizing thoughts, emotions, and beliefs about those situations. Identifying negative or inaccurate thinking patterns. Restructuring those thoughts into positive and realistic perspectives.~In this study:~CBT will consist of 8-10 structured sessions, each lasting approximately 90 minutes.~Participants will attend therapy sessions twice weekly over a six-week period. The intervention will be delivered by trained psychotherapists in a controlled hospital setting.~Routine antidepressant medications will be continued alongside CBT.