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.

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.

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.