Pharmacokinetics, Safety, and Tolerability of Intramuscular 5-MeO-DMT in Healthy Volunteers
Study Details
Study Description
Brief Summary
The primary objective of the study is to assess the pharmacokinetics, safety, and tolerability of a single-dose and multiple-doses of 5-MeO-DMT administered by intramuscular (IM) injections in healthy subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This study is a phase 1, first-in-human, double-blind, placebo-controlled, randomized, single-dose and multiple-ascending-dose study of 5-MeO-DMT administered by intramuscular injection in 54 healthy subjects (adult male and/or females, 18-65 years of age). Subjects will be randomized 6:1 to receive 5-MeO-DMT or placebo.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 - 0.5 mg single-dose A single 0.5 mg 5-MeO-DMT or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject). |
Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt
The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.
Other Names:
Drug: Placebo
The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.
Other Names:
|
| Experimental: Cohort 2 - 2.5 mg single-dose A single 2.5 mg 5-MeO-DMT or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject). |
Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt
The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.
Other Names:
Drug: Placebo
The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.
Other Names:
|
| Experimental: Cohort 3 - 4.5 mg single-dose A single 4.5 mg 5-MeO-DMT or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject). |
Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt
The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.
Other Names:
Drug: Placebo
The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.
Other Names:
|
| Experimental: Cohort 4 - 7 mg single-dose A single 7 mg 5-MeO-DMT or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject). |
Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt
The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.
Other Names:
Drug: Placebo
The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.
Other Names:
|
| Experimental: Cohort 5 - 10 mg single-dose A single 10 mg 5-MeO-DMT or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject). |
Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt
The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.
Other Names:
Drug: Placebo
The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.
Other Names:
|
| Experimental: Cohort 6 - 16 mg single-dose A single 5-MeO-DMT 16 mg or placebo dose administered intramuscularly (randomized as 5 active and 1 placebo subject). |
Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt
The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.
Other Names:
Drug: Placebo
The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.
Other Names:
|
| Experimental: Cohort 7 - multiple-dose, 3 hour interval Administration of up to two 5-MeO-DMT (2.5 mg followed by 4.5 mg) or placebo doses administered intramuscularly within a single day with a 3 hour dose interval (randomized as 5 active and 1 placebo subject). |
Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt
The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.
Other Names:
Drug: Placebo
The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.
Other Names:
|
| Experimental: Cohort 8 - multiple-dose, 3 hour interval Administration of up to two 5-MeO-DMT (2.5 mg followed by 7 mg) or placebo doses administered intramuscularly within a single day with a 3 hour dose interval (randomized as 5 active and 1 placebo subject). |
Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt
The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.
Other Names:
Drug: Placebo
The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.
Other Names:
|
| Experimental: Cohort 9 - multiple-dose, 3 hour interval Administration of up to two 5-MeO-DMT (4.5 mg followed by 11.5 mg) or placebo doses administered intramuscularly within a single day with a 3 hour dose interval (randomized as 5 active and 1 placebo subject). |
Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt
The 5-MeO-DMT drug product is comprised of the appropriate concentration of 5-MeO-DMT succinate salt drug substance in solution with 0.9% sodium chloride injection solution (USP) in a 5 mL glass vial, and is administered intramuscularly.
Other Names:
Drug: Placebo
The placebo is commercially available 0.9% sodium chloride solution (USP) for injection. The placebo is provided by the pharmacy in single-use sterile syringes of the appropriate dose.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of participants with Treatment Emergent Adverse Events as coded by MedDRA and assessed by CTCAE v4.0 [Up to 30 Days]
Number of participants with TEAEs following administration of 5-MeO-DMT.
Secondary Outcome Measures
- Plasma pharmacokinetic parameters of 5-MeO-DMT and bufotenine following a single-dose and multiple-doses of 5-MeO-DMT [Up to 24 hours]
For PK analysis, blood samples will be collected before and up to 24 hours after the intramuscular administration of 5-MeO-DMT to determine 5-MeO-DMT and bufotenine serum concentrations.
- Urine pharmacokinetic parameters of 5-MeO-DMT and bufotenine following a single-dose and multiple-doses of 5-MeO-DMT [Up to 24 hours]
For PK analysis, urine samples will be collected before and up to 24 hours after the intramuscular administration of 5-MeO-DMT to determine 5-MeO-DMT and bufotenine urine concentrations.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy adult male or female.
-
Aged at least 18 years but not older than 65 years, inclusive.
-
Body mass index (BMI) within 18.0 kg/m2 to 32.0 kg/m2, inclusive.
Exclusion Criteria:
-
History of significant hypersensitivity to the IP or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
-
Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, or endocrine disorders, as determined by the investigator (or designee).
-
Participants who, in the opinion of the investigator (or designee), should not participate in this study.
-
Participant is participating in another study with a medical device or IP within the last 30 days prior to first study drug administration.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Altasciences Clinical Kansas, Inc | Overland Park | Kansas | United States | 66212 |
Sponsors and Collaborators
- Usona Institute
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Barsuglia J, Davis AK, Palmer R, Lancelotta R, Windham-Herman AM, Peterson K, Polanco M, Grant R, Griffiths RR. Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study. Front Psychol. 2018 Dec 6;9:2459. doi: 10.3389/fpsyg.2018.02459. eCollection 2018.
- Davis AK, Barsuglia JP, Lancelotta R, Grant RM, Renn E. The epidemiology of 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption. J Psychopharmacol. 2018 Jul;32(7):779-792. doi: 10.1177/0269881118769063. Epub 2018 Apr 30.
- Ermakova AO, Dunbar F, Rucker J, Johnson MW. A narrative synthesis of research with 5-MeO-DMT. J Psychopharmacol. 2022 Mar;36(3):273-294. doi: 10.1177/02698811211050543. Epub 2021 Oct 19.
- Reckweg J, Mason NL, van Leeuwen C, Toennes SW, Terwey TH, Ramaekers JG. A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N, N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers. Front Pharmacol. 2021 Nov 25;12:760671. doi: 10.3389/fphar.2021.760671. eCollection 2021.
- Shen HW, Jiang XL, Winter JC, Yu AM. Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Curr Drug Metab. 2010 Oct;11(8):659-66. doi: 10.2174/138920010794233495.
- Sherwood AM, Claveau R, Lancelotta R, Kaylo KW, Lenoch K. Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use. ACS Omega. 2020 Dec 2;5(49):32067-32075. doi: 10.1021/acsomega.0c05099. eCollection 2020 Dec 15.
- Uthaug MV, Lancelotta R, van Oorsouw K, Kuypers KPC, Mason N, Rak J, Sulakova A, Jurok R, Maryska M, Kuchar M, Palenicek T, Riba J, Ramaekers JG. A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology (Berl). 2019 Sep;236(9):2653-2666. doi: 10.1007/s00213-019-05236-w. Epub 2019 Apr 13.
- MEO101