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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how the body processes and responds to different forms of methamphetamine, which include two chemical versions: R-meth and S-meth. S-meth, a potent stimulant, treats attention deficit disorder, while R-meth, a milder form, appears in some nasal sprays. Participants will receive these forms in different sequences to observe how each behaves in the body. The study seeks healthy individuals without a history of drug use, who can communicate in English and have no significant health issues affecting the heart, brain, or other major systems. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical research.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that methamphetamine, in its various forms, can seriously affect health. S-methamphetamine is a strong stimulant sometimes used to treat attention deficit disorder (ADD), but it can cause side effects like paranoia, anxiety, a fast heart rate, and even heart problems.

R-methamphetamine, a milder stimulant, is found in some nasal decongestant sprays. Although less potent, it still shares some risks with the stronger form. When combined, R- and S-methamphetamine can produce stronger effects than when used separately.

The treatment tested in this trial is in an early stage, meaning researchers are still studying its safety. This often means limited information is available on its safety for people. However, methamphetamine is approved for certain medical uses, suggesting it can be safe under specific conditions. Anyone considering joining the trial should understand these risks and discuss them with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for methamphetamine use because they explore the effects of different isomers of methamphetamine, which is a novel approach compared to current options. Unlike standard treatments, which often focus on behavioral therapy and medications like bupropion or naltrexone, these treatments directly examine the specific effects of R-(-)-methamphetamine, S-(+)-methamphetamine, and a racemic mixture of both. This innovative method could help pinpoint more precise ways to address methamphetamine use, potentially leading to more effective and tailored interventions. By understanding how each isomer impacts the brain and behavior, researchers hope to uncover new pathways for treatment that are currently untapped by existing therapies.

What evidence suggests that this trial's treatments could be effective for methamphetamine use?

This trial will examine the effects of different methamphetamine formulations on methamphetamine use disorder. Research has shown that S-meth, a component of the methamphetamine mixture, acts as a strong brain stimulant. It can increase brain activity and is already used to treat attention deficit disorder (ADD). Studies have found that methamphetamine use can reduce cravings and depressive symptoms, while improving speed and accuracy in tasks. In contrast, R-meth is a milder stimulant often found in nasal decongestants. This trial will study the combination of R-meth and S-meth, known as a racemic mixture, to understand how they interact in the body. Although early research suggests potential benefits in certain areas, further studies are necessary to confirm these effects for treating methamphetamine use disorder. Participants in this trial will receive these treatments in different sequences to evaluate their effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Heather K Barkholtz, PhD

Principal Investigator

University of Wisconsin, Madison

David Leinweber, MD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11043883/

Sociodemographic and patient reported outcomes by racial ... At baseline non-Hispanic Black participants reported less severe indicators of methamphetamine use than non-Hispanic White. Treatment effects ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2949916X25000167

Methamphetamine use among substance use disorder ... Recent data shows a sharp rise in methamphetamine use, particularly among specific racial and ethnic groups, with higher rates in males and certain age ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9097961/

Methamphetamine use in the United States - PubMed Central Methamphetamine is an addictive and potent stimulant, and its use is associated with a range of physical and mental health harms, overdose, and mortality.

4. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2774859

Methamphetamine Overdose Deaths in the US by Sex and ... US age-adjusted rates of drug overdose deaths involving methamphetamine increased nearly 5-fold during 2012-2018.

5. cdc.gov cdc.gov/mmwr/volumes/69/wr/mm6912a1.htm

Patterns and Characteristics of Methamphetamine Use ... Non-Hispanic black race/ethnicity was associated with lower odds of past-year methamphetamine use compared with non-Hispanic white race/ ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK535356/

Methamphetamine - StatPearls - NCBI Bookshelf - NIH Methamphetamine is one of the powerful stimulants of the central nervous system (CNS). It is sometimes used as a second-line treatment for attention deficit ...

7. pubs.acs.org pubs.acs.org/doi/10.1021/acsptsci.3c00019

Pharmacology of R-(−)-Methamphetamine in Humans Authors found that racemic methamphetamine has more than an additive effect when comparing results to equivalent doses of (+)-MAMP and (−)-MAMP.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4164186/

Methamphetamine: An Update on Epidemiology ... Methamphetamine use disorders are associated with differential brain activity during decision-making, as assessed via fMRI.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06746831?intr=METHAMPEX&aggFilters=studyType:int&viewType=Table&rank=9

Methamphetamine Isomer Pharmacology in Humans This study is being done to understand the metabolism and impairment profile of methamphetamine (meth). Meth exists as two chemical structures that are ...

10. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2009.02564.x

A review of the clinical pharmacology of methamphetamine At higher doses used typically by illicit users (≥50 mg), methamphetamine can produce psychosis. Its hypertensive effect can produce a number of ...