SPL028 (deuterated DMT fumarate) in healthy subjects
Research type
Research Study
Full title
A Phase 1, Double-Blind Study Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous and Intramuscular Dosing of SPL028 (Deuterated DMT Fumarate [A Serotonergic Psychedelic]) in Healthy Volunteers (Part A); Followed by an Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Exploratory Efficacy of SPL028 in Patients with Major Depressive Disorder (Part B)
IRAS ID
1006153
Contact name
Zelah Joel
Contact email
Sponsor organisation
Small Pharma Ltd
Eudract number
2022-002618-17
ISRCTN Number
ISRCTN42293056
Research summary
Research Summary
In this study we’re testing the safety of SPL028 (a new compound that is very similar to DMT, a psychedelic substance, that occurs naturally in plants and animals) alongside therapy as a potential treatment for Major Depressive Disorder (MDD).\nMDD, or ‘depression’, is a common mental illness that affects about 280 million people worldwide. There are existing treatments for depression, but they don’t work well in all patients and more treatment options are needed.\nSPL028 acts at sites in the brain (called serotonin receptors) related to mood and mental health. We’ll test single doses, given by slow injection into a vein, or as an injection into a muscle to assess its safety; how well it’s tolerated; its blood levels; psychedelic effects; and effects on mood, feelings and thoughts.\nThe study is in 2 parts. In Part A, we’ll recruit up to 32 healthy volunteers who will be split into 4 groups. The first 2 groups will receive 2 doses of SPL028 about 3 weeks apart, and the second 2 groups will receive 1 dose. Each group will likely receive a different dose. Any increase in dose level will be based on the safety and tolerability data from the previous group. Dosing will take place with psychological support from a therapist team. Healthy volunteers will take up to 12 weeks finish the study. They’ll stay at the clinical research unit for 2 nights/3 days for each dosing session and have 1 follow-up video call.\nIn Part B we will give up to 8 MDD patients a single dose of SPL028. These patients may be taking ineffective medication (a selective serotonin reuptake inhibitor) for their depression, or they may not be taking any medication. The dose given will be decided based on data from Part A of the study. Patients will take up to 17 weeks to finish the study. They’ll stay at the clinical research units for 2 nights/3 days and have 3 follow-up video calls.\nA pharmaceutical company (Small Pharma, UK) is funding the study.\nThe study will take place at 2 centres in the UK.
Summary of Results
The study was organised and funded by Small Pharma Ltd (the ‘Sponsor’) and was run
by MAC Clinical Research’s clinic in the UK from January 2023 to December 2023. Only Part A of this study was completed.
Why was this study conducted?
The purpose of this study was to test a drug called SPL028 in healthy participants when given as a slow injection into a vein (intravenous [IV]) or given as a quick injection into the gluteal muscle (intramuscular [IM]). It was thought that this drug may help in treating depression, also known as major depressive disorder
Depression is a common mental health condition. In the UK around 1 in 4 people experience depression at some stage in their life. There are a number of medicines available to treat depression, but for around 1 in 3 people, they do not work well or cause unpleasant side effects resulting in people not taking them.
It was hoped that this study may lead to new treatments for people with depression. The study drug contains DMT (N, N-dimethyltryptamine), a psychedelic or mood-altering chemical
found naturally in many plants and animals. DMT is the main ingredient in ayahuasca, a hallucinogenic drink used for centuries in religious ceremonies in some South American countries. Substances like DMT act on the brain, causing temporary changes in awareness,
sensation, and emotions.
The aims of the study were to assess:
• how safe and tolerable SPL028 is when given as slow IV injection into a vein or a quick IM injection.
• how the body absorbs and removes SPL028.
• how SPL028 affected the psychological and mental well-being of the study participants.
Who took part in the study?
Altogether, 38 healthy participants took part in this study. Participants were divided into 5 groups. In each group, 2 participants received a placebo and up to 6 participants received SPL028 either via quick IM injection (Group 4) or slow IV infusion (Groups 3 and 5), or both
(Group 1 and Group 2, only). A placebo is a substance that looks like SPL028 but does not contain the active ingredient. In this document, the term ‘study medication’ refers to receiving either SPL028 or placebo.
Each group received a different dose of SPL028 or placebo (see diagram below). Participantsin Group 1 and Group 2 had past experience with psychedelic drugs, but Group 3, Group 4 and
Group 5 did not. In Group 1, 1 participant did not receive a full dose SPL028 because of technical issues. In Group 4, 2 participants stopped the slow IV infusion before having the full dose.
What happened during the study?
During this study, participants in Groups 3, 4 and 5 visited the clinic twice while participants in Groups 1 and 2 visited the clinic 3 times. During the first visit, all participants underwent a range of health checks and filled in questionnaires to confirm that it was safe for them to take part in the study. The second visit included 2 overnight stays. Participants checked into the clinic 1 day before they were due to receive the study medication. After receiving the study medication, participants completed additional health checks, a range of questionnaires asking about their psychedelic experience and stayed for another night. Around 2 weeks after being discharged from the clinic, participants received a follow-up video call to complete
questionnaires to assess psychological well-being.
In Group 1 and Group 2 only, participants returned to the clinic for their second dose of the study medication, which included another 2 overnight stays and a second follow-up video-call around 2 weeks after being discharged from the clinic. All assessments completed for their first and second dose (within the clinic and for follow up) were the same , only they occurred approximately 3 to 6 weeks apart.
The maximum length of participation in this study for Group 3, Group 4 and Group 5 was
approximately 8 weeks. The maximum duration of the study for Group 1 and Group 2 was approximately 15 weeks.
What were the overall results of the study?
There were no serious safety concerns associated with the administration of SPL028, although some participants reported side effects. One participant in Group 4 experienced a bad side effect including restlessness, back arching and leg kicking, which resulted in their slow IV infusion being stopped. This participant experienced a noticeable side effect of facial spasms. These side effects returned to normal within 75 minutes after the slow IV infusion ended. The
day after the slow IV infusion, the participant reported muscle twitching without any pain, and after discharge they reported spontaneous contortions of their legs, shoulders and neck during
their sleep for two consecutive nights. All side effects returned to normal by the follow-up call.
Another participant in Group 4 experienced noticeable side effects. They reported anxiety and requested to have the slow IV infusion stopped. This participant also reported paranoia during
the slow IV infusion. The day after the slow IV infusion the participant reported anxiety and flashbacks, which were not negative. All side effects returned to normal by follow-up call.
The most common side effects thought to be related to the SPL028 slow IV infusion were nausea, which was reported by 2 participants in Group 1 and anxiety, which was reported by 2 participants in Group 4. All other study medication related side effects were reported by 1
participant only.
Side effects related to SPL028 IM injection were each reported by 1 participant only.
The study medication seemed to be well tolerated by most participants. Across the study, two
participants in Group 4 responded ‘Yes’ to the question ‘Do you wish you had not gone through that experience?’. Of these, 1 participant had received SPL028 and 1 participant had received placebo.
The participants subjective experience was measured with several questionnaires assessing the intensity of the experience, sensations and challenges, among others. SPL028 affected participants’ mood, feelings, thoughts and beliefs, but the effects varied a lot between
participants in all groups.
Participants’ well-being was measured with questionnaires assessing anxiety, attitudes and psychological well-being. There were no clear negative or positive effects of SPL028 on participants psychological well-being, although it seemed that the “ability to feel compassion”
and “feel intense emotions” increased. This finding needs to be taken with caution as larger studies are needed to confirm the result.
How has this study helped the researchers?
This study was in healthy women and men aged 25 or older, in order to establish the safety and tolerability of the SPL028. The results apply to the particular people studied and may not betrue for everybody. Not all participants in the study had the same results.
This research helps us to understand more about the medicine being studied.
Are there any plans for further studies?
No further studies are planned with the study drug. However, the Sponsor will use information learnt from this study for their research into other similar drugs.
Where can I find more information about this study?
To learn more about this study, visit: https://www.isrctn.com/ISRCTN42293056
This summary was written on 26 November 2024 and includes only results from one study.
Other studies may find different results and newer information may exist.REC name
Wales REC 1
REC reference
22/WA/0220
Date of REC Opinion
27 Oct 2022
REC opinion
Further Information Favourable Opinion