Antidepressant Response of DMT Masked With Propofol (DMT4D)

This randomised, placebo-controlled, quadruple-masked trial (n=112) will investigate whether the antidepressant effects of DMT (2 mg/min over 20 minutes) in patients with major depressive disorder (MDD) depend on the subjective psychedelic experience, by comparing DMT with and without sedation using propofol.

Conducted by University Hospital Basel, this 2×2 factorial Phase II study will assess the biological versus experiential contributions to DMT’s antidepressant effects. Participants will be randomly assigned to receive either DMT or placebo, with or without concurrent sedation using propofol. Propofol is used here to mask the psychedelic experience, enabling researchers to isolate DMT’s potential neurobiological effects—such as those linked to neuroplasticity or anti-inflammatory pathways—independent of the altered state of consciousness it typically produces.

All participants must have moderate to severe MDD (defined as MADRS score >20) and no history of psychotic or bipolar disorders. The primary outcome is the change in depressive symptoms from baseline to 14 days after treatment, measured using the Montgomery–Åsberg Depression Rating Scale (MADRS). This innovative trial could clarify whether psychedelics exert their therapeutic effects through subjective experience or underlying biological mechanisms.

Trial Details

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.

Trial Number NCT06927076

Data attribution

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