Pharmacokinetics, Safety, and Tolerability of Intramuscular 5-MeO-DMT in Healthy Volunteers

A Phase 1, First-in-human, Double-blind, Placebo-controlled, Randomized, Single- and Multiple-ascending-dose Study to Determine the Safety, Tolerability, and Pharmacokinetics of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) Administered by Intramuscular Injection in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics; Tolerability; Safety
• Intervention / Treatment: Drug: 5-methoxy-N,N-dimethyltryptamine succinate salt; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Altasciences Clinical Kansas, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

9

Arms and Interventions

Participant Group / 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: 5-MeO-DMT; 5-MeO-DMT succinate salt; 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: 0.9% sodium chloride solution (USP)
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: 5-MeO-DMT; 5-MeO-DMT succinate salt; 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: 0.9% sodium chloride solution (USP)
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: 5-MeO-DMT; 5-MeO-DMT succinate salt; 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: 0.9% sodium chloride solution (USP)
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: 5-MeO-DMT; 5-MeO-DMT succinate salt; 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: 0.9% sodium chloride solution (USP)
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: 5-MeO-DMT; 5-MeO-DMT succinate salt; 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: 0.9% sodium chloride solution (USP)
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: 5-MeO-DMT; 5-MeO-DMT succinate salt; 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: 0.9% sodium chloride solution (USP)
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: 5-MeO-DMT; 5-MeO-DMT succinate salt; 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: 0.9% sodium chloride solution (USP)
Experimental: Cohort 6 - 13 mg single-dose; A single 5-MeO-DMT 13 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: 5-MeO-DMT; 5-MeO-DMT succinate salt; 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: 0.9% sodium chloride solution (USP)
Experimental: Cohort 9 - multiple-dose, 3 hour interval; Administration of up to two 5-MeO-DMT (2.5 mg followed by 10.5 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: 5-MeO-DMT; 5-MeO-DMT succinate salt; 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: 0.9% sodium chloride solution (USP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Treatment Emergent Adverse Events as coded by MedDRA and assessed by CTCAE v4.0	Number of participants with TEAEs following administration of 5-MeO-DMT.	Up to 30 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetic parameters of 5-MeO-DMT and bufotenine following a single-dose and multiple-doses of 5-MeO-DMT	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.	Up to 24 hours
Urine pharmacokinetic parameters of 5-MeO-DMT and bufotenine following a single-dose and multiple-doses of 5-MeO-DMT	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.	Up to 24 hours

Collaborators and Investigators

• Sponsor: Usona Institute

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2022
• Primary Completion (Actual): September 7, 2023
• Study Completion (Actual): September 7, 2023

Study Registration Dates

• First Submitted: January 5, 2023
• First Submitted That Met QC Criteria: January 13, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; First-in-human; Psychedelics; 5-MeO-DMT; 5-methoxy-N,N-dimethyltryptamine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Serotonin Antagonists; Hallucinogens; N,N-Dimethyltryptamine
• Other Study ID Numbers: MEO101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No