Methamphetamine for Methamphetamine Use

Overseen By Heather Barkholtz, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Wisconsin, Madison

Must not be taking: Mood stabilizers, sedatives

Disqualifiers: Substance use disorder, pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 3 weeks

17 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, especially those that affect cognition or metabolism, like mood stabilizers or sedatives. If you're dependent on a medication that can't be stopped for 48 hours before and during study visits, you might not be eligible to participate.

Is methamphetamine safe for human use?

Methamphetamine has different forms, and the S-(+)-methamphetamine is known to have strong effects and is often associated with health risks. The R-(-)-methamphetamine is used in some over-the-counter drugs in the U.S., suggesting it may have a safer profile, but overall, methamphetamine can have toxic effects and should be used with caution. ^{1 2 3 4 5}

How is the drug in the Methamphetamine for Methamphetamine Use trial different from other treatments?

This drug uses a 1:1 mixture of two forms of methamphetamine, R-(-)-methamphetamine and S-(+)-methamphetamine, which is unique because most illicit methamphetamine is either a racemic mixture or predominantly the S-(+)-isomer. The R-(-)-isomer is less potent and often not detected in standard drug tests, making this combination novel for treating methamphetamine use. ^{1 2 3 6 7}

Research Team

Heather K Barkholtz, PhD

Principal Investigator

University of Wisconsin, Madison

David Leinweber, MD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for healthy individuals who want to help understand how different forms of methamphetamine work in the body. Participants will be involved in three study visits over a maximum of 12 weeks.

Inclusion Criteria

Good mental health as determined by self-reported responses to the Psychopathology Screener

I don't have major heart, brain, mental health, cancer, hormone, metabolism, kidney, or liver diseases.

English-speaking (able to provide consent and complete questionnaires)

Exclusion Criteria

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)

I cannot stop my current medication for 2 days for study visits.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous administration of methamphetamine isomers in a double-blind crossover design over three visits

3 weeks

3 visits (in-person), each at least 7 days apart

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

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

Trial Overview The study is testing two mirror-image chemical structures of methamphetamine: R-meth, found in nasal decongestants, and S-meth, used to treat ADD. It aims to compare their effects on metabolism and impairment.

Participant Groups

Group I: S-Meth, R-Meth, Racemic Isomer Experimental Treatment 3 Interventions

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

Group II: Racemic Isomer, S-Meth, R-Meth Experimental Treatment 3 Interventions

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

Group III: R-Meth, Racemic Isomer, S-Meth Experimental Treatment 3 Interventions

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

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

U.S. Department of Justice

Collaborator

Trials

23

Recruited

86,700+

Findings from Research

Recent studies suggest that (±)-MDMA can be effective as an adjunct to psychotherapy for treating psychiatric disorders, but it also has a range of adverse effects that may limit its clinical use.

Preclinical research indicates that the R(-)-MDMA enantiomer may offer a better therapeutic profile than the racemic (±)-MDMA, potentially maintaining therapeutic benefits while reducing side effects, warranting further investigation in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(±)-MDMA and its enantiomers: potential therapeutic advantages of R(-)-MDMA. Pitts, EG., Curry, DW., Hampshire, KN., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Forensic toxicologic analysis of methamphetamine and amphetamine optical isomers by high performance liquid chromatography. [2019]

2. China pubmed.ncbi.nlm.nih.gov

Research Progress on Chiral Separation Methods and Toxic Effects of Methamphetamine Enantiomers. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

Chromatographic separation of R/S-enantiomers of amphetamine and methamphetamine: Pathways of methamphetamine synthesis and detection in blood samples by qualitative enantioselective LC-MS/MS analysis. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Determination of methamphetamine enantiomer composition in human hair by non-chiral liquid chromatography-tandem mass spectrometry method. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

(±)-MDMA and its enantiomers: potential therapeutic advantages of R(-)-MDMA. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Enantiomeric separation and quantitation of (+/-)-amphetamine, (+/-)-methamphetamine, (+/-)-MDA, (+/-)-MDMA, and (+/-)-MDEA in urine specimens by GC-EI-MS after derivatization with (R)-(-)- or (S)-(+)-alpha-methoxy-alpha-(trifluoromethy)phenylacetyl chloride (MTPA). [2019]

7. England pubmed.ncbi.nlm.nih.gov

Be aware of (R)-methamphetamine: Negative immunoassay versus positive confirmation analysis. [2023]