Methamphetamine Isomer Pharmacology in Humans

NCT06746831 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 2024-1164Protocol Version 2/12/25A523000
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to understand the metabolism and impairment profile of methamphetamine (meth). Meth exists as two chemical structures that are mirror images of each other: R-meth and S-meth. S-meth is a strong central nervous system stimulant and used to treat attention deficit disorder (ADD). R-meth is not a strong central nervous system stimulant and is available over-the-counter in nasal decongestant sprays.17 healthy participants will be enrolled for 3 study visits and on study for up to 12 weeks.

Conditions

Methamphetamine

Keywords

pharmacology; meth; isomers

Outcome Measures

Primary Outcomes (2)

• Peak concentration (Cmax)

  The pharmacokinetic analysis relies on observed drug and metabolite concentration measurements over time and across biological matrices (plasma, whole blood, dried capillary spots, oral fluid, urine) included in this study.

  pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 hours

• Area under the concentration versus time curve (AUC)

  The pharmacokinetic analysis relies on observed drug and metabolite concentration measurements over time and across biological matrices (plasma, whole blood, dried capillary spots, oral fluid, urine) included in this study.

  pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 hours

Secondary Outcomes (5)

• Cognitive Effects: Divided Attention Task (DAT)

  Visit 1 (baseline), Visit 2 (week 1), Visit 3 (week 2)

• Cognitive Effects: Digital Symbol Substitution Task (DSST)

  Visit 1 (baseline), Visit 2 (week 1), Visit 3 (week 2)

• Cognitive Effects: Paced Serial Addition Task (PASAT)

  Visit 1 (baseline), Visit 2 (week 1), Visit 3 (week 2)

• Subjective Effects: Drug Effect Questionnaire (DEQ)

  Visit 1 (baseline), Visit 2 (week 1), Visit 3 (week 2)

• Subjective Effects: Number of Participants Who Answer 'True' for Amphetamine-specific questions

  Visit 1 (baseline), Visit 2 (week 1), Visit 3 (week 2)

Study Arms (3)

S-Meth, R-Meth, Racemic Isomer

EXPERIMENTAL

First visit: Administer S-Meth, then at least 7 days later Second visit: Administer R-Meth, then at least 7 days later Third visit: Administer (1:1) racemic methamphetamine

Drug: S-(+)-methamphetamine; Drug: R-(-)-methamphetamine; Drug: 1:1 racemic mixture of two isomers

R-Meth, Racemic Isomer, S-Meth

EXPERIMENTAL

First visit: Administer R-Meth, then at least 7 days later Second visit: Administer (1:1) racemic methamphetamine, then at least 7 days later Third visit: Administer S-Meth

Drug: S-(+)-methamphetamine; Drug: R-(-)-methamphetamine; Drug: 1:1 racemic mixture of two isomers

Racemic Isomer, S-Meth, R-Meth

EXPERIMENTAL

First visit: Administer (1:1) racemic methamphetamine, then at least 7 days later Second visit: Administer S-Meth, then at least 7 days later Third visit: Administer R-Meth

Drug: S-(+)-methamphetamine; Drug: R-(-)-methamphetamine; Drug: 1:1 racemic mixture of two isomers

Interventions

1:1 racemic mixture of two isomers DRUG

15 mg R-Meth + 15 mg S-Meth

R-Meth, Racemic Isomer, S-Meth; Racemic Isomer, S-Meth, R-Meth; S-Meth, R-Meth, Racemic Isomer

S-(+)-methamphetamine DRUG

15 mg

Also known as: S-Meth

R-Meth, Racemic Isomer, S-Meth; Racemic Isomer, S-Meth, R-Meth; S-Meth, R-Meth, Racemic Isomer

R-(-)-methamphetamine DRUG

15 mg

Also known as: R-Meth

R-Meth, Racemic Isomer, S-Meth; Racemic Isomer, S-Meth, R-Meth; S-Meth, R-Meth, Racemic Isomer

Eligibility Criteria

• Age: 21 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Good mental health as determined by self-reported responses to the Psychopathology Screener
• Absence of any major cardiac, neurologic, psychiatric, oncologic, endocrine, metabolic, renal, or hepatic disease as determined by self-reported responses to the Medical History Screener
• English-speaking (able to provide consent and complete questionnaires)
• Written Informed Consent

You may not qualify if:

• Any serious prior adverse response to sympathomimetic agents or amphetamine analogs
• History of or current substance use disorder as determined by self-reported responses to the Internalizing, Externalizing, and Substance Use Disorder Screener
• Pregnancy or lactation (pregnancy test, if needed)
• Use of medications that may impact cognition or metabolism (e.g., mood stabilizers, sedatives)
• Dependent on prohibited concomitant therapy that cannot be withheld for 48 hours prior to and during study visits.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• U.S. Department of Justice: collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Study Officials

• Heather K Barkholtz, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• David Leinweber, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heather Barkholtz, PhD

CONTACT

608-890-1967; hbarkholtz@wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind crossover study design.

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: December 24, 2024
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)