Major Depressive DisorderPhase 1/2NCT04673383
SPL026 (DMT Fumarate) in Healthy Subjects and MDD Patients
A Phase 1/2 study testing SPL026 in people with Major Depressive Disorder, run by Small Pharma Ltd at 2 sites in United Kingdom.
Trial summary
SPL026 (N,N-dimethyltryptamine [DMT] fumarate) is a psychedelic tryptamine being developed as a therapy for patients with major depressive disorder (MDD). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- SPL026
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 4 Feb 2021to 22 Dec 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Normotensive male or female, deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, laboratory tests of blood and urine, Mini-International Neuropsychiatric Interview (MINI) and Beck Scale for Suicidal Ideation (BSS); willing to follow the contraception requirements of the trial; willing to refrain from psychedelic drug use (excluding the study drug) during the trial and ≥ 3 months afterwards; willing to be contacted by email and video call, and have online access; able to give fully informed written consent. Part A only: psychedelic-naïve, ie have never taken a serotonergic psychedelic drug, in any form. Must be 25 years or older. Part B only: MDD diagnosis (as per DSM-V); not on antidepressant medication or willing to discontinue antidepressant medication (eg selective serotonin reuptake inhibitor [SSRI] treatment) for a sufficient time before and during the study; no psychedelic drug use in the 6 months before dosing.
Who cannot join
- Pre-menopausal females who are pregnant or lactating, or who are sexually active and not using a reliable method of contraception; clinically relevant abnormal findings at the screening assessment; acute or chronic illness (other than MDD [Part B only]) or infection; clinically relevant abnormal medical history or concurrent medical condition (other than MDD [Part B only]); positive tests for hepatitis B \& C, or HIV; severe adverse reaction to any drug; use of over-the-counter or prescribed medication (excluding oral contraceptives) within previous 28 days (paracetamol [acetaminophen] permitted up to 7 days, and antidepressant medication must have ceased for at least 14 days; 28 days for MOAIs) before first dose of trial medication; drug or alcohol abuse; use of cannabis in the 24 h before each study visit; heavy smokers (> 10 [Part A] or > 20 cigarettes [Part B] daily); supine blood pressure, heart rate, or QTcF outside the acceptable ranges; participation in other clinical trials of unlicensed medicines, or loss of more than 400 mL blood, within the previous 3 months; phobia of needles or blood; possibility that volunteer will not cooperate with the study.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
MAC Clinical Research
Liverpool, L34 1BH
Hammersmith Medicines Research
London
About this study
Official title: A Double-blind, Randomised, Placebo-controlled Study of Intravenous Doses of SPL026 (DMT Fumarate), a Serotonergic Psychedelic, in Healthy Subjects (Part A) and Patients With Major Depressive Disorder (Part B)
SPL026 (N,N-dimethyltryptamine [DMT] fumarate) is a psychedelic tryptamine being developed as a therapy for patients with major depressive disorder (MDD).
Read the detailed description
2-part study. Part A in psychedelic-naïve healthy volunteers. Part B in patients with MDD who score moderate-severe on Ham-D.
Healthy volunteers will receive a single dose of SPL026 in a dose-escalation parallel group study.
Patients will receive up to 2 single doses of SPL026, 2 weeks apart. Dose 1 will be randomised double-blind with placebo. Dose 2 will be open label, active SPL026.
SPL026 will be administered by IV injection. Safety and tolerability, PK, PD and efficacy will be measured.
- Conditions
- Major Depressive Disorder
- Being tested
- SPL026, Placebo
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SPL026Drug
Also called DMT, dimethyltryptamine, n,n-dimethytryptaimine
Intravenous solution
PlaceboDrug
Also called Dummy, SPL026-matched placebo
SPL026-matched placebo
| Study group | Role | What they receive |
|---|---|---|
| Healthy volunteers (active) | Experimental | SPL026 to be administered by IV injection Receives: Drug: SPL026 |
| Healthy volunteers (placebo) | Experimental | SPL026-matched placebo to be administered by IV injection Receives: Drug: Placebo |
| Patients (active) | Experimental | SPL026 to be administered by IV injection Receives: Drug: SPL026 |
| Patients (placebo) | Experimental | SPL026-matched placebo to be administered by IV injection Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability in healthy volunteers
Safety and tolerability measured by lab biochemistry, adverse events and intensity rating scale to measure tolerability of the psychedelic experience
Measured: Up to three months after a single dose
Efficacy of SPL026 in MDD patients with moderate to severe depression
Montgomery-Åsberg Depression Rating Scale (MADRS) score (where 7 - 19 is mild depression, 20 - 34 is moderate depression, and >34 is severe depression) change from baseline at 2 weeks after the first dose (± 2 days)
Measured: 2 weeks after a single dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2020
- Study start4 Feb 2021
- Primary completion1 Oct 2022
- Study completion22 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Small Pharma Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Erritzoe, MD, Principal investigator, Imperial College LondonMalcolm Boyce, MD, Principal investigator, Hammersmith Medicines ResearchFabian Devlin, MD, Principal investigator, MAC Clinical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04673383
- Sponsor's protocol ID
- CT026_001
- Status last verified
- Mar 2024
- First submitted
- 10 Dec 2020
- Last updated
- 27 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan for this yet.
Publications
Good M, Joel Z, Benway T, Routledge C, Timmermann C, Erritzoe D, Weaver R, Allen G, Hughes C, Topping H, Bowman A, James E. Pharmacokinetics of N,N-dimethyltryptamine in Humans. Eur J Drug Metab Pharmacokinet. 2023 May;48(3):311-327. doi: 10.1007/s13318-023-00822-y. Epub 2023 Apr 22.
PubMed 37086340James E, Erritzoe D, Benway T, Joel Z, Timmermann C, Good M, Agnorelli C, Weiss BM, Barba T, Campbell G, Baker Jones M, Hughes C, Topping H, Boyce M, Routledge C. Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial. Front Psychiatry. 2024 Jan 11;14:1305796. doi: 10.3389/fpsyt.2023.1305796. eCollection 2023.
PubMed 38274414Erritzoe D, Barba T, Benway T, Joel Z, Good M, Layzell M, Jones MB, Campbell G, Murphy-Beiner A, Rands P, Boyce M, Topping H, Weiss B, Timmermann C, Nutt D, Carhart-Harris R, Routledge C, James E. A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial. Nat Med. 2026 Feb;32(2):591-598. doi: 10.1038/s41591-025-04154-z. Epub 2026 Feb 16.
PubMed 41699126Swieczkowski D, Kwasny A, Cubala WJ. Safety and tolerability of NN-dimethyltryptamine (DMT) in healthy volunteers and Major Depressive Disorder (MDD) patients: A systematic review of early-phase clinical trials. Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jul 13;140:111419. doi: 10.1016/j.pnpbp.2025.111419. Epub 2025 Jun 7.
PubMed 40484114
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomised, Placebo-controlled Study of Intravenous Doses of SPL026 (DMT Fumarate), a Serotonergic Psychedelic, in Healthy Subjects (Part A) and Patients With Major Depressive Disorder (Part B)
- ClinicalTrials.gov ID
- NCT04673383
- Acronym / sponsor ID
- CT026_001
- Conditions
- Major Depressive Disorder
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Small Pharma LtdIndustry (pharma, biotech, devices)
- Study start
- 4 Feb 2021 (actual)
- Primary completion
- 1 Oct 2022 (actual)
- Study completion
- 22 Dec 2022 (actual)
- First posted
- 17 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
SPL026 (N,N-dimethyltryptamine [DMT] fumarate) is a psychedelic tryptamine being developed as a therapy for patients with major depressive disorder (MDD).
Detailed description
2-part study. Part A in psychedelic-naïve healthy volunteers. Part B in patients with MDD who score moderate-severe on Ham-D.
Healthy volunteers will receive a single dose of SPL026 in a dose-escalation parallel group study.
Patients will receive up to 2 single doses of SPL026, 2 weeks apart. Dose 1 will be randomised double-blind with placebo. Dose 2 will be open label, active SPL026.
SPL026 will be administered by IV injection. Safety and tolerability, PK, PD and efficacy will be measured.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers (active) | Experimental | Drug: SPL026SPL026 to be administered by IV injection |
| Healthy volunteers (placebo) | Experimental | Drug: PlaceboSPL026-matched placebo to be administered by IV injection |
| Patients (active) | Experimental | Drug: SPL026SPL026 to be administered by IV injection |
| Patients (placebo) | Experimental | Drug: PlaceboSPL026-matched placebo to be administered by IV injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Normotensive male or female, deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, laboratory tests of blood and urine, Mini-International Neuropsychiatric Interview (MINI) and Beck Scale for Suicidal Ideation (BSS); willing to follow the contraception requirements of the trial; willing to refrain from psychedelic drug use (excluding the study drug) during the trial and ≥ 3 months afterwards; willing to be contacted by email and video call, and have online access; able to give fully informed written consent. Part A only: psychedelic-naïve, ie have never taken a serotonergic psychedelic drug, in any form. Must be 25 years or older. Part B only: MDD diagnosis (as per DSM-V); not on antidepressant medication or willing to discontinue antidepressant medication (eg selective serotonin reuptake inhibitor [SSRI] treatment) for a sufficient time before and during the study; no psychedelic drug use in the 6 months before dosing.
Key exclusion criteria (1 listed)
- Pre-menopausal females who are pregnant or lactating, or who are sexually active and not using a reliable method of contraception; clinically relevant abnormal findings at the screening assessment; acute or chronic illness (other than MDD [Part B only]) or infection; clinically relevant abnormal medical history or concurrent medical condition (other than MDD [Part B only]); positive tests for hepatitis B \& C, or HIV; severe adverse reaction to any drug; use of over-the-counter or prescribed medication (excluding oral contraceptives) within previous 28 days (paracetamol [acetaminophen] permitted up to 7 days, and antidepressant medication must have ceased for at least 14 days; 28 days for MOAIs) before first dose of trial medication; drug or alcohol abuse; use of cannabis in the 24 h before each study visit; heavy smokers (> 10 [Part A] or > 20 cigarettes [Part B] daily); supine blood pressure, heart rate, or QTcF outside the acceptable ranges; participation in other clinical trials of unlicensed medicines, or loss of more than 400 mL blood, within the previous 3 months; phobia of needles or blood; possibility that volunteer will not cooperate with the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SPL026Also: DMT, dimethyltryptamine, n,n-dimethytryptaimineIntravenous solution | Drug | Healthy volunteers (active), Patients (active) |
| PlaceboAlso: Dummy, SPL026-matched placeboSPL026-matched placebo | Drug | Healthy volunteers (placebo), Patients (placebo) |
Primary outcome
Safety and tolerability in healthy volunteers
Time frame: Up to three months after a single dose
Safety and tolerability measured by lab biochemistry, adverse events and intensity rating scale to measure tolerability of the psychedelic experience
Efficacy of SPL026 in MDD patients with moderate to severe depression
Time frame: 2 weeks after a single dose
Montgomery-Åsberg Depression Rating Scale (MADRS) score (where 7 - 19 is mild depression, 20 - 34 is moderate depression, and >34 is severe depression) change from baseline at 2 weeks after the first dose (± 2 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2024.
- Results publication: PubMed 37086340Good M, Joel Z, Benway T, Routledge C, Timmermann C, Erritzoe D, Weaver R, Allen G, Hughes C, Topping H, Bowman A, James E. Pharmacokinetics of N,N-dimethyltryptamine in Humans. Eur J Drug Metab Pharmacokinet. 2023 May;48(3):311-327. doi: 10.1007/s13318-023-00822-y. Epub 2023 Apr 22.
- Results publication: PubMed 38274414James E, Erritzoe D, Benway T, Joel Z, Timmermann C, Good M, Agnorelli C, Weiss BM, Barba T, Campbell G, Baker Jones M, Hughes C, Topping H, Boyce M, Routledge C. Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial. Front Psychiatry. 2024 Jan 11;14:1305796. doi: 10.3389/fpsyt.2023.1305796. eCollection 2023.
- Derived from this study: PubMed 41699126Erritzoe D, Barba T, Benway T, Joel Z, Good M, Layzell M, Jones MB, Campbell G, Murphy-Beiner A, Rands P, Boyce M, Topping H, Weiss B, Timmermann C, Nutt D, Carhart-Harris R, Routledge C, James E. A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial. Nat Med. 2026 Feb;32(2):591-598. doi: 10.1038/s41591-025-04154-z. Epub 2026 Feb 16.
- Derived from this study: PubMed 40484114Swieczkowski D, Kwasny A, Cubala WJ. Safety and tolerability of NN-dimethyltryptamine (DMT) in healthy volunteers and Major Depressive Disorder (MDD) patients: A systematic review of early-phase clinical trials. Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jul 13;140:111419. doi: 10.1016/j.pnpbp.2025.111419. Epub 2025 Jun 7.
- Clinical Trial Report Synopsis Available HereLink provided by the sponsor.
- Individual participant dataSharing planned: No. No plan for this yet.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Erritzoe, MD principal investigator
Imperial College London
Malcolm Boyce, MD principal investigator
Hammersmith Medicines Research
Fabian Devlin, MD principal investigator
MAC Clinical Research
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SPL026 in people with Major Depressive Disorder, run by Small Pharma Ltd at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability in healthy volunteers (time frame: Up to three months after a single dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04673383, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2024.