Acute experiences and persisting psychological effects associated with an encapsulated DMT-harmala alkaloid combination: results of a phase 1 study

The introduction outlines the growing scientific interest in psychedelic substances as potential treatments for a range of mental health conditions. A central theme in this field is the importance of the “mystical experience”, a term used to describe a distinctive state often induced by psychedelics. This state typically involves profound feelings of unity, sacredness, emotional uplift, ineffability (that is, a sense that the experience is difficult or impossible to explain in words), and a perceived shift beyond normal time and space. Earlier research has suggested that this type of experience may be a key factor underpinning long-term therapeutic benefits, including improvements in depression, anxiety, addiction and even fundamental aspects of personality such as openness to new perspectives.

The authors explain that the strength or intensity of mystical-type experiences has repeatedly been linked to positive outcomes across clinical and naturalistic settings. For example, studies with psilocybin have shown that more intense sessions predict greater improvements in mental health, sometimes persisting for over a year. Similar findings appear in addiction research, where stronger mystical experiences have been associated with higher abstinence rates. In people taking psychedelics in non-clinical environments, mystical experiences have also been linked to reduced anxiety surrounding death, improved wellbeing and key lifestyle changes.

Within this context, the authors emphasise the importance of developing standardised psychedelic formulations that reliably elicit such experiences. They note unique challenges concerning ayahuasca-type products—traditionally a combination of DMT and harmala alkaloids—because natural preparations vary widely in chemical composition depending on plant species and preparation techniques. This variability makes it difficult to predict the strength or quality of experiences in a clinical environment. The present Phase I study therefore evaluates a standardised, encapsulated DMT-harmala formulation (containing precise amounts of DMT, harmine, tetrahydroharmine and harmaline) and examines whether it reliably produces mystical experiences in healthy volunteers, and whether these experiences are associated with persisting psychological effects.

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