Methamphetamine Isomer Pharmacology in Humans

University of Wisconsin (UW)

Status and phase: Not yet enrolling; Phase 1

Conditions: Methamphetamine

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

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT06746831

2024-1164

Protocol Version 2/12/25 (Other Identifier)

A523000 (Other Identifier)

Details and patient eligibility

About

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.

Full description

Double-blind crossover study design. Healthy volunteers will attend three study drug administration visits, at least 7 days apart, in which methamphetamine isomer pharmacology will be assessed following intravenous administration of (1) S-(+)-methamphetamine, (2) R(-)-methamphetamine, or (3) a (1:1) racemic mixture of R-(-)- and S-(+)-methamphetamine. The order of these interventions will be counterbalanced across participants. Serial blood samples will be drawn during each dosing visit and compared with concurrent dried blood spots from a finger stick, oral fluid collections, and pooled urine specimens.

Primary Objective

• Characterize the pharmacokinetics of acute S-(+)-methamphetamine administration.
• Characterize the pharmacokinetics of acute R-(-)-methamphetamine administration.
• Characterize the pharmacokinetics of acute racemic (1:1) R-(-)- and S-(+)-methamphetamine administration.

Secondary Objectives

• Assess for evidence of stereo-selective metabolic pathways.
• Assess for evidence of subjective, cognitive, or physiological effects from acute R-(-)-methamphetamine administration.
• Assess for evidence of more than additive effects when administering racemic methamphetamine.

Correlative Objectives

• Compare biological methamphetamine and metabolite concentrations in surveyed biological matrices (i.e., plasma, whole blood, oral fluid, dried capillary blood spots, and urine) over time.
• Compare cognitive and subjective effects of acute S-(+)-methamphetamine, R-(-)-methamphetamine, and racemic methamphetamine administration.

Enrollment: 17 estimated patients

Sex: All

Ages: 21 to 64 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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17 participants in 3 patient groups

S-Meth, R-Meth, Racemic Isomer

Experimental group

Description:

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

Treatment:

Drug: S-(+)-methamphetamine

Drug: 1:1 racemic mixture of two isomers

Drug: R-(-)-methamphetamine

R-Meth, Racemic Isomer, S-Meth

Experimental group

Description:

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

Treatment:

Drug: S-(+)-methamphetamine

Drug: 1:1 racemic mixture of two isomers

Drug: R-(-)-methamphetamine

Racemic Isomer, S-Meth, R-Meth

Experimental group

Description:

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

Treatment:

Drug: S-(+)-methamphetamine

Drug: 1:1 racemic mixture of two isomers

Drug: R-(-)-methamphetamine