Safety, blood levels and effects of N,N-dimethyltryptamine [DMT (SPL026)] in healthy participants and participants with major depressive disorder
| ISRCTN | ISRCTN63465876 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN63465876 |
| EudraCT/CTIS number | 2020-000251-13 |
| IRAS number | 288450 |
| ClinicalTrials.gov number | NCT04673383 |
| Secondary identifying numbers | CT026_001, IRAS 288450, CPMS 52296 |
- Submission date
- 26/07/2023
- Registration date
- 30/08/2023
- Last edited
- 30/01/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English Summary
Background and study aims
This is a study of N, N-dimethyltryptamine (DMT) – 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). This study is testing DMT (the study medicine, also known as SPL026, which has been manufactured for this study) as an experimental treatment for major depressive disorder (MDD). The aim is to find out about the effects and blood levels of DMT in healthy volunteers (Part A) and patients with MDD (Part B).
This study aims to answer these questions.
1. Do single doses of DMT improve the symptoms of depression, when given by slow injection into a vein in the arm?
2. Are single doses of DMT safe and well tolerated, when given by slow injection into a vein in the arm?
3. How much DMT gets into the bloodstream, and how long does the body take to get rid of it?
4. What do people experience after a dose of DMT?
5. What are the effects of DMT on mood, feelings, thoughts and beliefs?
Who can participate?
Part A: healthy volunteers aged 25 years or older
Part B: patients aged 18 years or older with major depressive disorder (MDD), also known as ‘depression’
What does the study involve?
In Session 1, participants will receive a dose of DMT or dummy medicine by slow injection into a vein in their arm. In Session 2, they will receive a dose of DMT by slow injection into a vein in their arm. The injections will take 6–11 min. Participants will stay on the ward for 3 days and 2 nights in a row. The researchers will contact them by video call for a check-up at about 7 days after each dose. At about 2 weeks after the last dose, participants come to the ward for a follow-up visit. There will be follow-up phone or video calls at about 1 month and 3 months after the last dose. At follow-ups, participants complete questionnaires to rate their mood, feelings, thoughts and beliefs.
What are the possible risks and benefits of participating?
The highest dose of DMT in this study is predicted to give blood levels no higher than those in previous studies. The dose of DMT is likely to cause a psychedelic experience or ‘trip’, which is expected to last about 20 min. Participants may experience: visual imagery or hallucinations (seeing colourful patterns, or seeing or hearing things that aren’t real); a sense of being detached from their thoughts or feelings; changes in their sense of time and space; out-of-body experiences; disorientation or confusion; anxiety; intense emotions such as happiness or grief. Sometimes people experience unpleasant images and sounds, and may also ‘relive’ painful memories or traumas. In published research into psychedelic treatments for depression, difficult emotions and upsetting content experienced during the ‘trip’ are considered therapeutically beneficial, as they can lead to important insights. Participants will have the support and guidance of expert therapists to help them interpret and deal with any experiences they may have during their trip. As with any new medicine, its side effects are not yet known. In any clinical trial, there is a risk of an unexpected, serious reaction to the study medicine, which could be life-threatening.
Participants may get some medical benefit from DMT, but it’s not been tested in patients with MDD before, so the researchers can’t be sure they will benefit. Participants may benefit from regular conversations with the study psychiatrist and therapist. The screening tests might be of benefit if an important medical problem is found, but they could reveal something participants prefer not to know about.
Participants will be helping with medical research. They can’t carry on taking DMT after the study has finished, even if they get some unexpected benefit from it. DMT is a Class A illegal drug – the researchers have a special licence to be able to give it to volunteers in this study.
Where is the study run from?
1. Hammersmith Medicines Research Limited (UK)
2. MAC Clinical Research Liverpool (UK)
When is the study starting and how long is it expected to run for?
August 2020 to December 2022.
Who is funding the study?
Small Pharma Ltd (UK)
Who is the main contact?
Carol Routledge, carol.routledge@smallpharma.co.uk
Contact information
Principal Investigator
Centres for Neuropsychopharmacology and Psychedelic Research
Commonwealth Building
Hammersmith Campus
London
W12 0NN
United Kingdom
 ORCID ID |
0000-0002-7022-6211 |
|---|---|
| Phone | +44 (0)2075895111 |
| d.erritzoe@imperial.ac.uk |
Study information
| Study design | Part A: Single ascending dose placebo-controlled double-blinded trial; Part B: Stage 1: Single-dose placebo-controlled double-blinded trial; Stage 2: open-label but blinded to first dose trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Pharmaceutical testing facility |
| Study type | Safety, Efficacy |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A double-blind, randomized, 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) |
| Study hypothesis | SPL026 is safe and well tolerated and (in participants with MDD) reduces depression scores more than placebo |
| Ethics approval(s) |
Approved 10/12/2020, London - Brent REC (80 London Road, London, SE1 6LH, United Kingdom; +44 (0)20 7104 8137; brent.rec@hra.nhs.net), ref: 20/LO/1035 |
| Condition | Major depressive disorder |
| Intervention | Subject numbers will be allocated to treatments (active or placebo) according to a randomisation schedule prepared by an independent HMR statistician using a SAS program. SPL026 (dimethyltryptamine fumarate) by intravenous infusion or matched placebo. Single dose or two single doses, 2 weeks apart. Part A: 4 cohorts of 8 participants randomised to 6 active, 2 placebo. 3 months follow-up. Doses: 9 mg, 12 mg, 17 mg, 21.5 mg Part B: Stage 1: randomised 1:1 active: placebo. Stage 2: second active dose 2 weeks after the first dose, open-label but blinded to the first dose. 3 months follow-up following Stage 2. Doses: 21.5 mg |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic, Dose response |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | SPL026 (N,N-dimethyltryptamine fumarate; DMT) |
| Primary outcome measure | Part A: Safety and tolerability assessed using adverse events, laboratory values, and tolerability assessments over 3 months Part B: Efficacy (depression) assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) at 2 weeks post first dose |
| Secondary outcome measures | Part A: 1. Pharmacokinetics (PK) measured using frequent blood sampling from pre-dose to 2 hours post-dose. DMT will be analysed by LC-MS/MS after liquid-liquid extraction of the human plasma sample. 2. Pharmacodynamics (PD) - Wellbeing assessed using the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) from pre-dose to 3 months post-dose 3. PD - Subjective experience assessed using Multidimensional Emotion Questionnaire (MEQ) immediately post-dose Part B: 1. PK measured using frequent blood sampling from pre-dose to 2 hours post-dose. DMT will be analysed by LC-MS/MS after liquid-liquid extraction of the human plasma sample. 2. Wellbeing assessed using WEMWBS from pre-dose to 3 months post-dose 3. Subjective experience assessed using MEQ immediately post-dose Part B: 1. Safety and tolerability assessed using adverse events, laboratory values, and tolerability assessments from pre-dose to 3 months post second dose. 2. Efficacy assessed using MADRS from pre-dose to 3 months post second dose. 3. PK measured using frequent blood sampling from pre-dose to 2 hours post-dose. DMT will be analysed by LC-MS/MS after liquid-liquid extraction of the human plasma sample. 4. PD - Wellbeing assessed using WEMWBS from pre-dose to 3 months post-dose 5. PD - Subjective experience assessed using MEQ immediately post-dose Part B: 1. PK measured using frequent blood sampling from pre-dose to 2 hours post-dose. DMT will be analysed by LC-MS/MS after liquid-liquid extraction of the human plasma sample. 2. PD - Wellbeing assessed using WEMWBS from pre-dose to 3 months post-dose 3. PD - Subjective experience assessed using MEQ immediately post-dose |
| Overall study start date | 01/08/2020 |
| Overall study end date | 21/12/2022 |
Eligibility
| Participant type(s) | Healthy volunteer, Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 72 |
| Total final enrolment | 68 |
| Participant inclusion criteria | 1. 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) 2. 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 3. Willing to be contacted by email and video call, and have online access; able to give fully informed written consent 4. Part A only: psychedelic-naïve, ie have never taken a serotonergic psychedelic drug, in any form. Must be 25 years or older 5. Part B only: MDD diagnosis (as per DSM-V); not on antidepressant medication or willing to discontinue antidepressant medication (e.g. selective serotonin reuptake inhibitor [SSRI] treatment) for a sufficient time before and during the study 6. No psychedelic drug use in the 6 months before dosing |
| Participant exclusion criteria | 1. Pre-menopausal females who are pregnant or lactating, or who are sexually active and not using a reliable method of contraception 2. Clinically relevant abnormal findings at the screening assessment 3. 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]) 4. Positive tests for hepatitis B & C, or HIV 5. Severe adverse reaction to any drug 6. Use of over-the-counter or prescribed medication (excluding oral contraceptives) within the 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 the first dose of trial medication 7. Drug or alcohol abuse; use of cannabis in the 24 h before each study visit 8. Heavy smokers (>10 [Part A] or > 20 cigarettes [Part B] daily) 9. Supine blood pressure, heart rate, or QTcF outside the acceptable ranges 10. Participation in other clinical trials of unlicensed medicines, or loss of more than 400 ml blood, within the previous 3 months 11. Phobia of needles or blood 12. Possibility that the volunteer will not cooperate with the study |
| Recruitment start date | 10/12/2020 |
| Recruitment end date | 01/09/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
London
NW10 7EW
United Kingdom
King's Business Park
Liverpool
L34 1BH
United Kingdom
Sponsor information
Industry
6-8 Bonhill Street
London
EC3A 4BX
England
United Kingdom
| Phone | +44 (0)7878900470 |
|---|---|
| carol.routledge@smallpharma.com | |
| Website | https://smallpharma.com/ |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 01/09/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to commercial sensitivity. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Funder report results | version 1 | 20/06/2023 | 18/09/2023 | No | No |
| Results article | Part A results in healthy volunteers | 11/01/2024 | 30/01/2024 | Yes | No |
Additional files
Editorial Notes
30/01/2024: Publication reference added.
18/09/2023: Funder report added.
05/09/2023: Internal review.
04/09/2023: The sponsor email was updated.
28/07/2023: Study's existence confirmed by London - Brent Research Ethics Committee.
