Investigation of the Role of Psychedelic Experiences in the Antidepressant Effect in Patients with Depression: A Placebo-Controlled Study with DMT (Administered with Propofol)
Summary description of the study
In this study, we investigate whether DMT as our investigational substance (DMT) has an antidepressant effect and whether this antidepressant effect is associated with the acute psychedelic experience or whether there is also an antidepressant effect when the acute psychedelic effects are absent due to a short anesthesia. Additionally, we examine the neuroplastic and anti-inflammatory potential of a single treatment with DMT through certain biological markers.
(BASEC)
Intervention under investigation
In our study, participants are randomly assigned to one of the groups. This is important to obtain reliable results from the study. This is called randomization. Each group receives a different treatment.
In our study, there are four groups:
• Group 1 (experimental group) receives the investigational substance administered intravenously at a dosage of 2 mg per minute for a total of 20 minutes. Moderate to strong psychedelic effects occur.
• Group 2 (experimental group) receives the investigational substance administered intravenously at a dosage of 2 mg per minute for a total of 20 minutes. Simultaneously, a standard short anesthesia (with Propofol) of 30 minutes takes place, preventing the perception of psychedelic effects.
• Group 3 (control group) receives a placebo administered intravenously for a total of 20 minutes. No psychedelic effects occur.
• Group 4 (control group) receives a placebo administered intravenously for a total of 20 minutes. Simultaneously, a standard short anesthesia (with Propofol) of 30 minutes takes place.
The study is a so-called double-blind study regarding the investigational substance. However, participants will be informed before their test session whether they will receive a standard short anesthesia with Propofol or not. "Double-blind" means that no one involved in the conduct knows whether a person is receiving the investigational substance or not: the participants themselves do not know which group they are in. The examiners and physicians also do not know which group individual participants belong to. In this sense, all participants are "blind." The idea is to minimize influence on the results. Through randomization and double-blinding, we can objectively assess how well the investigational substance works and whether specific biological markers are released.
(BASEC)
Disease under investigation
Depression
(BASEC)
1. Participants must meet the DSM-5 criteria for moderate to severe Major Depression (MDD) (MADRS > 20). 2. Participants are not currently using antidepressants or have been on a stable dose for at least 4 weeks prior to randomization. 3. Age ≥ 21 years. 4. Sufficient understanding of the German language. 5. Ability to understand the study procedures and risks and willing to adhere to the protocol and sign the informed consent. 6. Willing to refrain from driving or operating heavy machinery on the treatment day. 7. Willing to abstain from more than 7 alcoholic drinks per week, more than 10 cigarettes per day, more than 2 cups of coffee per day, and the use of illegal drugs during the study participation. 8. Willing to use effective contraceptive measures throughout the study participation. (BASEC)
Exclusion criteria
1. Previous or current bipolar or psychotic disorder, including depressive disorders with psychotic features. 2. First-degree relatives with a psychotic or bipolar disorder. 3. Significant prodromal psychotic symptoms (Prodromal Questionnaire-16 symptoms ≥ 6). 4. Borderline personality disorder. 5. Current post-traumatic stress disorder. 6. Postpartum depression. 7. Pregnant or breastfeeding women. 8. Current or recently significant suicidal thoughts or suicidal behavior in the last 6 months. 9. Current severe substance use disorder other than nicotine. 10. Planned ketamine, other psychedelic, or electroconvulsive treatments or such treatment in the last 3 months. 11. Any use of DMT in life, use of other psychedelics in the last 3 months, or lifetime use of psychedelics more than 15 times. 12. Patients treated with neuroleptics or known antagonists of 5-HT2 receptors or monoamine oxidase inhibitors (MAOIs) and not willing to pause these. 13. Increased risk of adverse reactions to Propofol or soy products. 14. Increased risk of aspiration. 15. Increased risk of difficult mask ventilation. (BASEC)
Trial sites
Basel
(BASEC)
Sponsor
Prof. Dr. med. Matthias E. Liechti Universitätsspital Basel
(BASEC)
Contact
Contact Person Switzerland
Joyce Santos de Jesus
+ 41 61 556 56 02
DMT4D@clutterusb.chUniversity Hospital Basel Klinische Pharmakologie & Toxikologie
(BASEC)
General Information
University Hospital, Basel, SwitzerlandUniversity Hospital, Basel, Switzerland
+41 61 556 65 02+41 61 325 53 94
DMT4D@clutterusb.chfelix.mueller@upk.ch(ICTRP)
General Information
University Hospital, Basel, SwitzerlandUniversity Hospital, Basel, Switzerland
+41 61 325 53 94+41 61 556 65 02
felix.mueller@upk.chDMT4D@clutterusb.ch(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee northwest/central Switzerland EKNZ
(BASEC)
Date of authorisation
17.12.2024
(BASEC)
ICTRP Trial ID
NCT06927076 (ICTRP)
Official title (approved by ethics committee)
Investigating the role of the psychedelic experience in the antidepressant response in patients with major depression: a placebo-controlled factorial trial with DMT masked with propofol (DMT4D-Study) (BASEC)
Academic title
Investigating the Role of the Psychedelic Experience in the Antidepressant Response in Patients With Major Depression: a Placebo-controlled Factorial Trial With DMT Masked With Propofol (DMT4D-Study) (ICTRP)
Public title
Antidepressant Response of DMT Masked With Propofol (ICTRP)
Disease under investigation
Major Depressive DisorderPsychedelic Experiences (ICTRP)
Intervention under investigation
Drug: N,N-DimethyltryptamineDrug: PlaceboProcedure: PropofolProcedure: no sedation (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Inclusion/Exclusion criteria
Inclusion Criteria:
1. Participants must meet DSM-5 criteria for MDD of at least moderate severity
(MADRS=20).
2. Participants either currently do not use antidepressants or are treated with a
stable dose for at least 4 weeks prior to randomization.
3. Age = 21 years old.
4. Sufficient understanding of the German language.
5. Able to understand the study procedures and risks and willing to adhere to the
protocol and sign the consent form.
6. Willing not to drive or operate heavy machinery on the treatment day.
7. Willing to refrain from more than 7 standard alcoholic drinks a week, more than 10
cigarettes a day, more than 2 cups of coffee a day, and any illicit substances
during study participation.
8. Willing to use effective contraceptive measures throughout study participation.
Exclusion Criteria:
1. Past or present bipolar or psychotic disorder, including depressive disorder with
psychotic features.
2. First-degree relative with a psychotic or bipolar disorder.
3. Significant prodromal psychotic symptoms (Prodromal Questionnaire-16 symptoms = 6).
4. Psychiatric condition judged to be incompatible with establishment of rapport with
study team members and/or safe exposure to DMT, e.g. diagnosed or suspected
borderline personality disorder.
5. Current post-traumatic stress disorder or acute stress reaction due to a traumatic
event.
6. Post-partum depression.
7. Pregnant or breastfeeding women.
8. Current or recent history of significant suicide ideation or suicide behavior within
the past 6 months.
9. Current severe substance use disorder other than nicotine.
10. Planned ketamine, other psychedelic, or electroconvulsive treatment or any such
treatment within the past 3 months.
11. Any lifetime use of DMT, use of any other psychedelics within last 3 month or
lifetime use of any other psychedelics more than 15 times.
12. Patients who are treated with neuroleptics or known antagonists of 5-HT2 receptors
or monoamine oxidase inhibitors (MAOI) and are not able/willing to pause.
13. Increased risk for adverse reactions to propofol or soja products.
14. Increased risk for aspiration.
15. Increased risk for difficult mask ventilation. (ICTRP)
not available
Primary and secondary end points
long term changes in depressive symptoms (MADRS) (ICTRP)
Short term changes in depressive symptoms (MADRS);Changes in depressive symptoms (BDI);Changes in anxiety (STAI);Changes of clinical global impression (CGI-S);Changes of clinical global impression (CGI-I);Changes in quality of life (WHOQOL-bref);Persisting positive and negative effects (PEQ);Acute subjective effects (5D-ASC);Subjective Effects Rating (SES);Psychedelic Experience Scale (PES);Emotional breakthrough inventory (EBI);Acute adverse effects;Safety events;Neuroplasticity;Inflammation;DMT plasma concentration;Expectancy (CEQ);Expectancy;Mood;Personality (NEO-FFI);Personality (TAS);Sedation Level (RASS) (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Matthias Liechti, Prof. Dr. med.Felix Mller, PD Dr. med.Joyce Santos de JesusFelix Mueller, PD Dr. med., DMT4D@usb.chfelix.mueller@upk.ch, +41 61 556 65 02+41 61 325 53 94, University Hospital, Basel, SwitzerlandUniversity Hospital, Basel, Switzerland (ICTRP)
Secondary trial IDs
2024-02312, am24Liechti6 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/study/NCT06927076 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available