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 randomised, double-blind, placebo-controlled trial (n=40) will study the safety, tolerability, pharmacokinetics, pharmacodynamics, and effects of intravenous (IV) and intramuscular (IM) dosing of SPL028 (deuterated DMT fumarate) in healthy volunteers and participants with major depressive disorder (MDD).

The study, conducted by MAC Clinical Research Unit in Manchester, UK, aims to investigate a modified version of N,N-dimethyltryptamine (DMT) called SPL028, which is predicted to have a longer duration of effect compared to standard DMT. The trial is divided into multiple cohorts, with Cohorts 1 and 2 involving experienced psychedelic users (healthy volunteers), and Cohorts 3-5 involving participants with limited psychedelic experience, including those with MDD.

Participants in Cohorts 1 and 2 will receive two doses of the study medication over approximately 15 weeks, while those in Cohorts 3-5 will receive one dose over about 8 weeks. The study involves inpatient stays, follow-up video calls, and various assessments including questionnaires on attitudes, moods, and relationships. The primary objectives are to assess the safety and tolerability of SPL028 administered via IV and IM routes, evaluate its pharmacokinetics and pharmacodynamics, and assess its effects on mood, feelings, thoughts, and beliefs.

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.

NCT Number ISRCTN42293056

Data attribution

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