Safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and effects of intravenous (IV) and intramuscular (IM) dosing of SPL028 (deuterated DMT fumarate [a serotonergic psychedelic]) in healthy volunteers and participants with major depressive disorder (MDD)

This interventional trial (n=38) assessed the safety, tolerability, pharmacokinetics (how the drug is absorbed and processed by the body), and pharmacodynamics (how the drug affects the body) of SPL028 (a modified form of DMT) when given intravenously (IV) or intramuscularly (IM) in healthy volunteers.

SPL028 is a deuterated form of DMT, designed to have a longer-lasting effect compared to standard DMT, which is the main psychedelic compound in ayahuasca. The study aims to evaluate the safety and psychological effects of SPL028, particularly its impact on mood, thoughts, and beliefs. It includes multiple cohorts, with healthy volunteers who have prior psychedelic experience receiving two doses over 15 weeks, while MDD patients with little to no prior psychedelic use receive a single dose over an 8-week period. Participants will stay in a clinic under medical supervision, with follow-up assessments including psychotherapy sessions.

The study was conducted at the MAC Clinical Research Unit in Manchester, UK, and has now been completed. The planned second (B) part with MDD patients didn’t take place.

Trial Details

This is a study investigating a modified version of N, N-dimethyltryptamine (DMT) – DMT is a psychedelic substance that occurs naturally in many plants and animals. Psychedelic substances, also known as hallucinogens, act on the brain causing temporary changes to perception, sensations, and emotions, which can be intense. DMT is best known for being the main psychedelic substance in ayahuasca (a hallucinogenic brew that has been used for centuries in religious ceremonies in some South American countries). DMT is a Class A illegal drug – we have a special licence to be able to give this modified version of DMT to participants in this study. The modified version of DMT being investigated in this study is called SPL028 (also known as the ‘study drug’). The modification that has been made to the DMT molecule is predicted to cause SPL028 to have a longer duration of effect compared to standard DMT; other than the predicted longer duration of effect, SPL028 is very similar to standard DMT. We’re testing the study drug as an experimental treatment for Major Depressive Disorder (MDD) in combination with therapy sessions. In Part A of this study, we’re investigating how safe and tolerated SPL028 is in healthy volunteers.

Trial Number ISRCTN42293056

Data attribution

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