Methamphetamine use disorder remains difficult to treat. Behavioral approaches such as contingency management can be effective, but there are currently no medications approved specifically to treat the condition. This has led researchers to investigate new compounds that might reduce methamphetamine use without broadly interfering with motivation, appetite, or other healthy behaviors. 

A new preclinical study published in Psychopharmacology offers an early clue. Researchers found that mitragynine, the most abundant naturally occurring compound in the kratom plant, reduced methamphetamine-seeking behavior in rats without reducing their motivation to work for food. 

The study was conducted by researchers from Rutgers, Texas Tech University Health Sciences Center, and the University of Florida, including RARC researcher Dr. Jenny Wilkerson of the Department of Anesthesiology at Rutgers New Jersey Medical School. 

What Is Mitragynine? 

Kratom, or Mitragyna speciosa, is a plant native to Southeast Asia. Its leaves have traditionally been chewed or brewed as tea and are sometimes used to manage fatigue or pain. 

In the United States, kratom products are also marketed for mood, pain, opioid withdrawal, and substance use concerns. However, these products are not approved by the U.S. Food and Drug Administration to treat any medical condition, and their contents and potency can vary considerably. 

Mitragynine is the most abundant alkaloid, or active chemical compound, naturally found in kratom leaves. It interacts with several systems in the brain, including opioid, adrenergic, serotonin, and dopamine-related pathways. Many of these systems are also involved in reward, motivation, stress, and substance use. 

Importantly, mitragynine is not the same as concentrated 7-hydroxymitragynine, commonly called 7-OH. Concentrated or synthetic 7-OH products can produce much stronger opioid-like effects and have raised serious concerns related to dependence, respiratory depression, and overdose. 

Rather than studying commercially available kratom products, the researchers tested isolated mitragynine under carefully controlled laboratory conditions. 

Testing Motivation for Methamphetamine 

The researchers conducted two experiments involving adult male and female rates to test for motivation to receive methamphetamine. 

In two experiments, rats were trained to press a lever to receive methamphetamine. This self-administration model allows researchers to study drug-taking behavior and how strongly an animal is motivated to obtain a drug. 

The first experiment used a fixed-ratio schedule. Under this arrangement, rats had to complete a set number of lever presses to receive methamphetamine. 

The second methamphetamine experiment used a progressive-ratio schedule. Each time a rat received methamphetamine, it had to press the lever more times to earn the next dose. Eventually, the effort requiredbecomes too high and the animal stops responding. 

The highest amount of work completed is known as the “breakpoint.” Researchers use this measure to estimate how strongly an animal is motivated to obtain a particular reward. 

Before each test, the rats received either mitragynine or a control solution. The researchers then measured how often they pressed the active lever, how many methamphetamine infusions they received, and how much effort they were willing to make. 

Mitragynine Reduced Methamphetamine Responding 

Mitragynine reduced methamphetamine self-administration in a dose-dependent manner. At the higher doses tested, rats pressed the lever fewer times and received fewer methamphetamine infusions. 

Under the progressive-ratio schedule, mitragynine also lowered the rats’ breakpoints. In other words, the rats were less willing to continue working as the effort required to obtain methamphetamine increased. 

The effects were generally similar in male and female rats. However, the number of animals was too small to draw firm conclusions about possible sex differences. 

These findings suggest that mitragynine reduced both methamphetamine-taking behavior and motivation to obtain the drug under the conditions tested. 

Did It Simply Reduce All Motivation? 

One challenge in medication development is determining whether a potential treatment specifically reduces drug-related motivation or simply makes an animal tired, less active, or less interested in any reward. 

To explore that question, the researchers conducted a third experiment in which rats pressed a lever to receive food pellets instead of methamphetamine. 

Mitragynine did not reduce the number of food pellets earned or the rate at which the animals responded for food, even at doses that reduced methamphetamine self-administration. 

This distinction is important. It suggests that mitragynine did not merely suppress all motivated behavior. Under the study conditions, the compound appeared to affect methamphetamine-related reinforcement while leaving food-maintained responding intact. 

That does not yet prove that mitragynine would preserve all forms of healthy motivation, but it provides a useful reason to continue studying the compound. 

Why Might Mitragynine Have This Effect? 

Researchers do not yet know exactly how mitragynine reduced methamphetamine-seeking behavior. 

Unlike compounds that act on only one biological target, mitragynine interacts with several receptor systems involved in addiction. These include mu-opioid receptors, alpha-2 adrenergic receptors, serotonin receptors, and possibly dopamine-related pathways. 

This broader pharmacological profile may allow mitragynine to influence multiple processes connected to methamphetamine reinforcement, stress, reward, and motivation. 

However, acting on several systems can also create safety and tolerability concerns. Future studies will need to determine which mechanisms are responsible for the observed effects and whether they can be targeted safely. 

What the Study Does—and Does Not—Tell Us 

This was an early preclinical study conducted in rats. It does not show that kratom or mitragynine is a safe or effective treatment for methamphetamine use disorder in people. 

The study tested purified mitragynine at controlled doses, not commercial kratom powders, extracts, gummies, or shots. Those products can differ substantially in their chemical composition and may contain other compounds, contaminants, or unexpectedly high levels of 7-OH. 

The researchers also tested only one methamphetamine dose and examined the effects of short-term mitragynine administration. The study used relatively small groups of animals, and the food and methamphetamine experiments were conducted in separate groups rather than allowing the same animals to choose between the two rewards. 

Additional research will be needed to examine repeated dosing, safety, long-term effects, different methamphetamine doses, potential sex differences, and whether the results extend to humans. 

The findings should therefore not be interpreted as support for self-treating methamphetamine use with kratom. 

A Starting Point for Future Research 

Despite these limitations, the study addresses an important challenge in addiction treatment research: finding a compound that reduces motivation for a drug without broadly reducing motivation for everyday rewards. 

By reducing methamphetamine self-administration while leaving food-maintained responding unchanged, mitragynine showed a potentially meaningful degree of behavioral selectivity in this animal model. 

The findings provide a foundation for further investigation, not a ready-to-use treatment. Continued research may help scientists better understand how mitragynine affects reward-related brain systems and whether aspects of its pharmacology could eventually contribute to safer, evidence-based treatments for methamphetamine use disorder. 

At a time when effective medication options remain limited, carefully studying promising compounds under controlled conditions is an important step toward identifying new strategies for prevention, treatment, and recovery. 

Date: July 30, 2026
By: Ricki Arvesen