Safety, PK and PD of DMT Intramuscular and intravenous doses
Research type
Research Study
Full title
An open-label, cross-over study of intramuscular (IM) and intravenous (IV) doses of SPL026 drug product (DMT fumarate [a serotonergic psychedelic]), in healthy, psychedelic experienced participants (Part A: IM and IV doses) and participants with little to no psychedelic experience (Part B: IM dose only)
IRAS ID
1006227
Contact name
Zelah Joel
Contact email
Sponsor organisation
Small Pharma Ltd
Eudract number
2022-002775-10
Clinicaltrials.gov Identifier
Research summary
Research Summary
In this study, we’re testing DMT– a psychedelic substance that occurs naturally in plants and animals – as an experimental treatment for mental health conditions, including Major Depressive Disorder (MDD). MDD, 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. DMT acts at sites in the brain (called serotonin receptors) related to mood and mental health. We hope DMT will give patients with depression more treatment options.
We’ll test single doses of DMT, by injection into a muscle (intramuscular injection) and by slow injection into a vein (intravenous infusion), to assess: its safety; how well it’s tolerated; its blood levels; psychedelic effects; and its effects on mood, feelings and thoughts.
The study has 2 parts. In Part A, we’ll give 6 healthy volunteers (HVs) (with previous experience of psychedelic substances) up to 2 single doses of DMT. The first dose will be by injection into a muscle and the second dose will be by slow injection into a vein. Participants will take up to 5 weeks to finish the study, and have 2 study sessions. They’ll stay on the ward for up to 2 nights in each session, and have up to 5 follow-up video calls.
In Part B, we’ll give up to 8 HVs (with little to no experience with psychedelic substances) a single dose of DMT by injection into a muscle. The dose in Part B will be decided after reviewing results from Part A. Participants will take up to 3 weeks to finish the study and have 1 study session. They’ll stay on the ward for up to 2 nights and have up to 3 follow-up video calls.
Participants will attend a screening visit during the 4 weeks before the study.
A pharmaceutical company (Small Pharma, UK) is funding the study. The study will take place at 1 centre in London.Summary of Results
Why did we do the study?
Major Depressive Disorder (MDD), known as ‘depression’, is a common mental illness affecting about 322 million people worldwide. Depression affects people in different ways and causes a wide range of symptoms, such as feelings of unhappiness and hopelessness, losing interest in things they used to enjoy, and anxiety, as well as physical symptoms (tiredness, problems with sleep, etc). There are existing treatments for depression, but they don’t work well in all patients.
SPL026 (the study medicine, also known as DMT) is an experimental new treatment for depression. It is a psychedelic substance that acts at sites in the brain (called serotonin receptors) related to mood and mental health. We hope SPL026 will give patients with depression more treatment options.
We tested single doses of the study medicine in healthy volunteers and compared the effects when these doses were given to healthy volunteers in different ways. This included giving SPL026 by a slow injection into the blood stream, also known as intravenous administration, and giving SPL026 by injection into the muscle at the top of the buttock (ventrogluteal muscle), otherwise known as intramuscular injection. SPL026 has previously been studied in healthy volunteers and patients with MDD but it has not been administered by the intramuscular route and therefore we started at a low intramuscular dose and increased the dose as the study progressed. We wanted to find out what people experienced after a dose of SPL026, and its side effects, blood levels, and effects on mood, feelings, thoughts, and beliefs and we wanted to compare if this is different when SPL026 is given to people intravenously compared to intramuscularly. Some people were given two doses of SPL026, one by intravenous administration and one by intramuscular administration, to better compare the differences between these two routes. These two doses were given two-three weeks apart.
Who organised the study and when did it take place?
The doctors and support staff of Hammersmith Medicines Research (HMR) in London organised the study. A pharmaceutical company – Small Pharma, London, UK (the ‘sponsor’) – paid for the study and provided SPL026.
The study took place at HMR (London) from 03 January 2023 until 05 April 2023. The study was completed as planned.
Who took part in the study and what treatments did they take?
This study was set up with 2 parts, Part A and Part B.
6 healthy volunteers aged 25–65 years, completed Part A of the study. They had taken a psychedelic drug before (such as DMT, LSD, or magic mushrooms and they received two single doses of the study medicine (SPL026) with the doses (or study sessions) separated by two-three weeks. One dose of SPL026 was given intravenously (slow injection into the vein) and one dose was given intramuscularly (injection into the top of the buttock).
8 healthy volunteers aged 25-65 years, completed Part B of the study. They had not taken psychedelic drugs before. They had just one study session where they received a dose of SPL026 by intramuscular injection. Volunteers received psychological support before and after their doses.
What were the results of the study?
Side effects
Side effects are unwanted medical events (such as headache) that happen during the study and are reported because the study doctor believes they may have been related to the study medicine. In this study, we found out the following.
• There were no serious side effects – those are side effects, for instance, that are life threatening or required someone to stay in hospital.
• Not all people in the study had side effects. Overall, side effects were reported by 5 out of 6 healthy volunteers (83%) in Part A, and 3 out of 8 healthy volunteers (37.5%) in Part B.
• The most common side effects – reported by 5 out of 6 people (83%) in Part A, and 1 out of 8 people (12.5%) in Part B) – were pain or reactions at the study medicine injection site.
• Other people had one or more of the following side effects:
• effects on mood (vivid dreams or anxiety), reduction in blood pressure, and palpitations (reported by 1 person each) in Part A.
• anxiety (reported by 2 people), sweating (reported by 1 person), sleep disturbance including sleep hallucinations (reported by 2 people) and abdominal discomfort (reported in 1 person) in Part B.
• Generally, more side effects were seen at the higher doses.
• Because of what we know about SPL026 and DMT, we expected some of these side effects.
• All participants handled their psychedelic experience well.
Other results
• The study medicine was safe and well tolerated at the doses tested and when given into the vein and into the muscle.
• All participants tolerated the psychedelic experience, and no participant who was asked said they wished they had not gone through it. It was observed that participants who had both IM and IV doses felt that their experience after the IV dose was more intense or challenging than the IM dose, though acute endpoint results were similar between participants who received 27.5 mg SPL026 IV and 50 mg SPL026 IM. How participants felt may in part be because of the rapid rise in plasma DMT to time to peak drug concentration (Tmax) – the time it takes for a drug to reach the maximum concentration and the maximum concentration (Cmax) – the highest (peak) concentration of a drug in the bloodstream that occurred after IV dosing; however, it may also be a result of the low IM dose tested in Part A.
• The psychedelic experience caused by the study medicine affected participants’ mood, feelings, thoughts, and beliefs, but the effects varied a lot.
• Blood levels of the study medicine were generally as expected but varied a lot between participants. In most participants, the body got rid of the study medicine quickly (within about 1–2 hours after the start of dosing).
How has the study helped patients and researchers?
In this study, the results of Part A and Part B will be used to determine which route SPL026 will be administered to patients when it is progressed into further trials, it will also be used to help design later clinical trials of the study medicine in patients. This study has also helped to inform the safety of Small Pharma’s follow-on molecule SPL028 and will be used to help design later clinical trials of SPL028 in patients. The results of Part A and B will also inform the research field generally on the safety and other effects of DMT.
Are there plans for further studies?
Other studies of SPL026 (the study medicine) and SPL028 (the follow-on medicine) have been completed or are ongoing, and further trials are planned in people with MDD.
Where can I find more information about the study?
You can find out more detailed information about this study at https://www.isrctn.com/ISRCTN63723571 (for results) and https://classic.clinicaltrials.gov/ct2/show/NCT05644093?term=SPL026&draw=2&rank=3 (for trial description).If you would like more general information about clinical trials, the UK Clinical Research Collaboration (UKCRC) booklet ‘Understanding Clinical Trials’ has information about medical research, and questions you might want to ask. If you’d like to read it, please visit www.ukcrc.org/wp-content/uploads/2014/03/iCT_Booklet.pdf
REC name
Wales REC 1
REC reference
22/WA/0216
Date of REC Opinion
12 Oct 2022
REC opinion
Further Information Favourable Opinion