NIH Advances Clinical Trial of Kratom Compound for Opioid Use Disorder

Could a compound found in kratom change the future of opioid addiction treatment? A new National Institute of Health clinical trial is exploring that question, drawing attention to kratom for opioid use disorder during an ongoing opioid epidemic. Here’s what the research is studying, why it matters, and what it could mean for treating addiction while balancing safety, evidence, and the risks of addiction and withdrawal symptoms.

What Is Kratom?

Kratom is an herbal substance made from the leaves of Mitragyna speciosa, a tropical tree native to Southeast Asia. People may consume it as a powder, capsule, tea, or extract. Its main compounds, including mitragynine and 7-hydroxymitragynine, interact with opioid receptors; lower amounts may cause mild stimulant effects, while mitragynine is about 25% as potent as morphine and 7-hydroxymitragynine is about 10 times more potent than morphine, helping explain opioid-like effects at higher doses. Kratom is not FDA-approved to treat opioid use disorder, withdrawal, pain, or any other medical condition.

Why Researchers Are Studying Kratom for Opioid Use Disorder

Some kratom users are taking kratom to manage opioid cravings and withdrawal symptoms without medical supervision. Among people with substance use disorders, reported kratom use has ranged from 10% to 21%. Researchers want to determine whether isolated kratom compounds could serve as a potential treatment for opioid use disorder under controlled study. Current research does not establish whole-leaf kratom or retail kratom products as safe or effective treatments, and evidence suggests they are not established options.

What Is the Kratom Compound Being Tested?

The NIH clinical trial is evaluating MG001, an oral formulation of mitragynine, which is the primary active compound found in kratom. Unlike whole-leaf kratom products, MG001 is a purified compound produced under controlled conditions and is one of the kratom derived products being examined in a pharmaceutical form rather than as an unregulated retail item. The phase 1 study will evaluate its safety, tolerability, and how it is absorbed and processed in the body.

How the NIH Clinical Trial May Advance Opioid Use Disorder Research

The Food and Drug Administration recently cleared the NIH Investigational New Drug application for MG001, allowing researchers to begin a phase 1 clinical trial. Outside this investigational pathway, kratom products are classified by the FDA as new dietary ingredients. This study is the first to evaluate purified mitragynine in humans under FDA oversight. If the results are positive, larger studies could determine whether it has a future role in treating opioid use disorder.

How Kratom Compounds Affect Opioid Receptors

Mitragynine and related kratom compounds act at the mu opioid receptor and also interact with kappa opioid receptors in the brain that influence pain, reward, cravings, and withdrawal, a focus of preclinical investigations and medicinal chemistry research. Researchers believe these interactions may explain why some users report relief from opioid withdrawal symptoms. However, these same effects may also contribute to tolerance, dependence, and addiction with repeated use.

Potential Benefits of Kratom for Opioid Use Disorder

Researchers are investigating whether purified kratom compounds may:

• Reduce opioid withdrawal symptoms
• Decrease opioid cravings
• Lower illicit opioid use
• Provide a new medication option for opioid use disorder
• Offer an alternative approach for people who do not respond to existing medications
• Improve understanding of opioid receptor biology

These potential benefits remain under investigation, and kratom is not an FDA-approved treatment for opioid use disorder.

Can Kratom Reduce Opioid Cravings or Withdrawal Symptoms?

Some people use kratom leaves, lyophilized kratom tea, or another herbal extract sold as a dietary supplement to relieve pain, reduce anxiety, reduce tiredness, ease opioid withdrawal, or treat opium addiction. However, evidence is limited, and the FDA warns people that kratom may cause dependence, respiratory depression, unpleasant physical symptoms during the process called withdrawal, or a need for medical attention. Drugs prescribed for opioid use disorder, including buprenorphine, methadone, and naltrexone, remain the recommended options, while Drug Enforcement Administration drug fact sheet and Substance Abuse and Mental Health Services Administration guidance link kratom-related drug abuse to broader concerns about unintentional drug overdose deaths.

Prevalence of Kratom Use in the United States

About 1.7 million people in the United States reported using kratom in the past year. In 2021, opioid overdose caused more than 80,000 deaths, which may help explain interest in alternatives for pain, mental health symptoms, opioid withdrawal, or recreational use. Researchers have also tracked rising concern because 65% of kratom-related reports occurred between 2016 and 2017.

Effects and Risks of Kratom Use

Short-Term:

• Increased energy and alertness
• Relaxation or sedation
• Pain relief
• Euphoria
• Nausea and vomiting
• Constipation
• Dizziness
• Drowsiness
• Increased heart rate
• Increased blood pressure
• Dry mouth
• Confusion

Long-Term:

• Tolerance
• Physical dependence
• Kratom withdrawal
• Kratom addiction
• Sleep disturbances
• Anxiety or depression
• Liver injury
• Seizures
• Memory or concentration problems
• Financial, work, or relationship problems
• Increased overdose risk when combined with opioids, alcohol, benzodiazepines, or other sedatives

Kratom overdose can occur, and kratom-related fatal overdose involvement increased from 0.5% in 2016 to 2% in 2022. Risk is higher when kratom is taken with other drugs.

Side Effects of Kratom Compounds

Kratom compounds can cause nausea, constipation, dizziness, dry mouth, sweating, drowsiness, agitation, increased heart rate, and higher blood pressure. Strong doses or concentrated products may cause confusion, seizures, liver injury, breathing problems, or loss of consciousness. Product strength and purity can vary, and some products may contain dangerous contaminants such as heavy metals or harmful bacteria, making reactions difficult to predict and increasing the risk of adverse health effects.

Kratom Dependence, Addiction, and Withdrawal

Regular kratom use can cause tolerance, physical dependence, cravings, and loss of control. Withdrawal symptoms may include irritability, anxiety, insomnia, muscle aches, nausea, diarrhea, sweating, and restlessness. Kratom contains addictive substances, and some commercial preparations may include very addictive substances in concentrated amounts. A person may need professional support if they cannot stop despite health, work, or relationship problems.

Risks of Mixing Kratom With Opioids, Alcohol, or Benzodiazepines

Mixing kratom with fentanyl, heroin, morphine, oxycodone, hydrocodone, methadone, or other opioids may increase sedation and breathing risks. Combining it with alcohol or benzodiazepines such as Xanax, Valium, Klonopin, or Ativan can further slow the central nervous system. Sleep medications, gabapentin, and muscle relaxants may also increase the risk of overdose or a medical emergency. In an overdose emergency, the same medicines used for opioid exposure, including naloxone, a medication sometimes called opioid overdose reversal treatment, may also be used when kratom exposure is suspected.

Why People With Opioid Use Disorder May Turn to Kratom

People may use kratom as part of broader drug use patterns to reduce cravings, avoid opioid withdrawal, manage chronic pain, or replace fentanyl, heroin, prescription opioids, or pain medicines. Some may view kratom as a natural or more accessible option because it is sold online and in stores, and some turn to it instead of recreational drugs or prescribed pain medicines, but this can still lead to dependence. However, self-treatment can delay proven care and may lead to kratom dependence.

Co-Occurring Mental Health Conditions, Kratom Use, and Opioid Use Disorder

People may use kratom or opioids to cope with depression, generalized anxiety disorder, panic disorder, PTSD, insomnia, attention problems, nightmares, or intrusive memories. Bipolar disorder, schizophrenia, and other serious mental health conditions may also increase the risk of agitation, unstable mood, paranoia, cravings, and unsafe substance use. Integrated treatment should address substance use, mental health symptoms, trauma responses, and relapse triggers together.

How Kratom Research Compares With Approved Opioid Use Disorder Medications

Mitragynine remains experimental and is not approved to treat opioid use disorder. Buprenorphine, methadone, and naltrexone have established dosing standards, safety guidance, and stronger evidence. Current research has not established kratom in clinical practice as an effective or safer substitute for approved medications. These medications can reduce cravings, withdrawal symptoms, illicit opioid use, and overdose risk when used as part of a treatment plan.

What the NIH Trial Could Mean for Future Addiction Treatment

The NIH trial could provide early information about the safety and tolerability of purified mitragynine in humans, which is why kratom is sometimes described as a promising medicinal plant in drug development from isolated compounds, not as evidence that retail products are therapeutic. Positive findings could support larger studies involving people with opioid use disorder, but they would not prove that retail kratom products are safe or effective. Several stages of research would be needed before a kratom-derived medication could receive approval and to better understand abuse potential.

Evidence-Based Residential and Outpatient Treatment for Opioid Use Disorder

Effective treatment may include buprenorphine, methadone, or naltrexone with medical care, therapy, peer support, naloxone access, overdose education, and relapse prevention. Residential treatment provides 24-hour structure, while PHP, IOP, and standard outpatient programs offer different levels of care for people living at home. The right program should match the person’s withdrawal risk, mental health, substance use, and home environment.

Dual Diagnosis Treatment for Opioid Use Disorder and Mental Health Conditions

Dual diagnosis treatment addresses opioid or kratom use alongside anxiety, depression, PTSD, bipolar disorder, or other mental health conditions. Care may include psychiatric support, medication management, individual therapy, group counseling, and relapse prevention. Treating both conditions can reduce self-medication and support long-term stability.

What Patients and Families Should Know About Kratom Research

Research on purified mitragynine is different from research on kratom powders, gummies, highly concentrated extracts, and concentrated 7-hydroxymitragynine products sold at retail. FDA and kratom policy has included a proposal to schedule kratom derivatives with high 7-OH concentration, while the DEA proposed scheduling kratom in 2016 and later rescinded that proposal. An NIH clinical trial does not mean kratom is approved or proven safe for opioid withdrawal. Patients should speak with a qualified clinician before replacing approved treatment with an unregulated product.

When to Seek Help

Call emergency services if someone has slow or stopped breathing, blue or gray lips, severe confusion, a seizure, chest pain, or cannot be awakened. Give naloxone when opioid exposure is known or suspected. Immediate help is also important after kratom is mixed with fentanyl, heroin, prescription opioids, alcohol, benzodiazepines, or other sedatives.

Kratom Addiction Treatment Options

• Medical Assessment: Reviews substance use, withdrawal, medications, and health risks.
• Withdrawal Management: Reduces discomfort and monitors symptoms.
• Medication Treatment: Buprenorphine, methadone, or naltrexone may treat opioid use disorder.
• Residential Treatment: Provides structured live-in care for severe addiction.
• PHP and IOP: Offer frequent treatment without overnight residence.
• Outpatient Care: Includes therapy, medication visits, and recovery support.
• Dual Diagnosis Care: Treats substance use and mental health conditions together.
• Aftercare: Supports relapse prevention and long-term recovery.

Does Insurance Cover Treatment?

Many insurance plans cover assessments, medications, therapy, residential care, and outpatient treatment when medically necessary. Coverage depends on the plan, network, deductible, and authorization rules.

Conclusion

The NIH clinical trial marks an important step in understanding whether a purified kratom compound has a role in future opioid use disorder treatment. While the findings are promising, kratom is not FDA-approved to treat opioid addiction, ease withdrawal symptoms, or replace medications such as buprenorphine-naloxone, and commercially available kratom products may carry serious health risks. As research continues, people experiencing opioid addiction, drug and alcohol dependence, or withdrawal should seek evidence-based treatment and medical guidance rather than relying on unregulated products.