Part 1 covered the published reports of deaths and seizures, liver injury, and dependence and withdrawal. This part covers drug interactions, concentrated 7-OH products, who should not use kratom, and what researchers still do not know.
Two compounds come up again and again. Mitragynine is the main active compound (alkaloid) in kratom leaf. 7-hydroxymitragynine (7-OH) is a related compound that is much stronger. Fresh leaf contains little or none of it. Kratom: Botany, Alkaloids, and How It Actually Works explains how both act in the body.
This article gives no dosing guidance. Nothing in it encourages you to use kratom. Thailand regulates kratom under the Kratom Act B.E. 2565. Malaysia still controls it under its Poisons Act 1952, and Myanmar bans it under its Narcotic Drugs and Psychotropic Substances Law. Kratom Law in Thailand After 2021, and Across the Region gives the details. Nothing here encourages use anywhere kratom is banned.
This is Part 2. Part 1: Kratom Risks: What the Death Reports Show, Liver Injury, Dependence and Withdrawal (Part 1 of 2)
Drug interactions: the specific ones
Kratom’s drug interactions are more than a general warning. Researchers have documented several specific mechanisms, and each one has concrete effects.
The liver breaks down most medicines with enzymes. If something slows those enzymes, a medicine stays in the body longer and its blood level rises. Doctors call this a pharmacokinetic interaction.
Slowing the CYP2D6 and CYP3A4 enzymes
CYP2D6 and CYP3A4 are two liver enzymes from the cytochrome P450 (CYP) family. Together they break down a large share of prescription drugs. This is the most widely documented interaction mechanism for kratom.
In laboratory studies, mitragynine slows CYP2D6 and the CYP3A group, including CYP3A4. A 2023 review by Tanna and colleagues in Drug Metabolism and Disposition concludes that kratom can cause interactions through these enzymes. As a result, drugs taken with kratom can reach higher levels than expected.
Simple prediction models in the same review suggest a higher risk for drugs broken down by CYP3A than for drugs broken down by CYP2D6. Few studies have tested these interactions in people.
Slowing the UGT enzymes
UGT (UDP-glucuronosyltransferase) is another group of liver enzymes. They attach a small molecule to a drug so the body can flush it out. Mitragynine slows these enzymes too.
In theory, drugs cleared by UGT could then build up in the body. So far this has been shown only in laboratory tests, not in patients.
If you are treated with buprenorphine for kratom withdrawal (see Part 1), or take any other prescribed medicine, a doctor who knows about the kratom use should manage the prescribing. It is not a reason to avoid treatment.
Combining kratom with sedatives, opioids or antidepressants
Some substances slow the brain and breathing. Doctors call them central nervous system (CNS) depressants. The pattern in the deaths is clear. Benzodiazepines (sedatives), opioids (morphine-family painkillers) and SSRIs (a common group of antidepressants) appear again and again. Whatever risk kratom carries on its own, the risk is clearly higher when it is combined with any of these.
Alcohol and mixed drinks
Alcohol adds one more depressant to the mix. In southern Thailand, recent mixed drinks called “4x100” combine kratom with other substances. These drinks have been linked to harm.
Translator’s note: 4x100 is usually made by boiling kratom leaf and mixing it with cola, ice and cough syrup. Some cough, cold, allergy and sleep medicines sold in pharmacies contain sedating antihistamines such as diphenhydramine. Part 1 noted that the drug tests behind the kratom seizure reports did not check for antihistamines.
What you can do: Write one list of every medicine, supplement and herb you take, including kratom. Show it to your doctor or pharmacist before you start any new medicine. They can check two things: whether CYP or UGT enzymes break down the new medicine, and whether it adds to the sedative effect.
The risk that changed: concentrated 7-OH products
Everything above is about kratom leaf and products made from leaf. Recently, a different type of product has appeared on the market.
Fresh leaf contains little or no 7-OH. Some products are enriched with isolated 7-OH. They deliver it at concentrations the plant itself does not produce.
What forensic labs and US regulators have recorded
- The Center for Forensic Science Research and Education (CFSRE) is a US non-profit forensic science organisation. Its NPS Discovery programme tracks new psychoactive substances. It reported that in late 2024, 7-OH “emerged as the primary component in drug products being marketed and sold as ‘Kratom’ or ‘7OHM’”.
- The 2026 Current Addiction Reports review describes concentrated, misbranded 7-OH products that have prompted warnings from regulators.
- In 2025, the US Food and Drug Administration (FDA) sent warning letters to seven companies selling concentrated 7-OH products.
- The FDA’s parent department is the US Department of Health and Human Services (HHS). On 29 July 2025, HHS and the FDA formally recommended placing 7-OH in Schedule I. This is the strictest US drug category, for substances judged to have high abuse potential and no accepted medical use.
- US status as of October 2026: the US Drug Enforcement Administration (DEA) has not yet issued a temporary scheduling order for 7-OH itself. A notice of intent in July 2026 was not followed by an order. On 9 October 2026, the US Department of Justice (DOJ) announced that the DEA would issue a new notice. The DEA published it on 14 October 2026. It uses HHS’s updated thresholds for 7-OH concentration and ratio. On 26 August 2026, three related compounds were temporarily placed in Schedule I: mitragynine pseudoindoxyl, MGM-15 and MGM-16.
- 7-OH has been described as a partial mu-opioid agonist “potentially comparable to other full opioid agonists”. In plain words, it switches on the same brain receptor as morphine (the mu-opioid receptor). It does not switch the receptor fully on, but its effect may still come close to that of full opioids.
Why routine drug tests can miss it
Hospitals often use quick urine tests that detect common drugs with antibodies (immunoassay screens). These tests do not reliably detect 7-OH.
A patient may show the typical signs of opioid poisoning (opioid toxidrome), such as very slow breathing, pinpoint pupils and deep drowsiness. Yet the routine test can still come back negative.
What you can do: In an emergency, tell the medical staff clearly that the person used kratom or a 7-OH product. Otherwise the staff may never learn what caused the poisoning.
Translator’s note: This article could not confirm whether concentrated 7-OH products are sold in Thailand or elsewhere in Southeast Asia. It also could not confirm how Thai law classifies them. Treat any product as a different and stronger product than leaf if its label names 7-OH, 7-hydroxymitragynine or “7OHM”. The same applies to tablets, shots or gummies that claim high strength. If you grow or sell leaf, check the legal position before you stock or resell any such product. The kratom law topic linked above is the place to start.
Who should not use kratom
This list draws on the clinical reviews and on Thai law.
Thai law: who you may not sell to
The Kratom Act B.E. 2565 bans selling kratom to:
- anyone under 18
- pregnant women
- breastfeeding women
Thai rules for food products that contain kratom, including labelling, are covered in the kratom law topic linked above.
Translator’s note: If you sell leaf, check the buyer’s age on an ID card whenever you are unsure. You are responsible for meeting these restrictions.
Medical reasons: high risk or not suitable
- Existing liver disease. Liver injury is the best-documented harm.
- Heart, kidney, lung or nervous system disease.
- Taking benzodiazepines, opioids or SSRIs, or any medicine broken down by CYP2D6, CYP3A4 or UGT.
- A history of using several drugs together (polysubstance use).
- Pregnancy. Babies born to mothers who used kratom can go through withdrawal (neonatal abstinence syndrome), and this is documented. That is a much firmer finding than most of what is said about kratom.
What you can do: If you take any regular medicine, ask a pharmacist whether CYP2D6, CYP3A4 or UGT enzymes break it down. Ask before you use kratom, not afterwards.
What researchers still do not know
The evidence has clear gaps:
- Only a few controlled studies in people exist. Most measure pharmacokinetics (how the body absorbs, breaks down and removes a substance) or pain in a test setting. None shows that kratom works as a treatment. One example is a 2020 study from Malaysia by Vicknasingam and colleagues. Volunteers held a hand in cold water so researchers could measure pain tolerance (a cold-pressor test). It was double-blind, meaning neither the volunteers nor the researchers knew who had kratom and who had a dummy (placebo).
- Almost all other human data come from observing users, looking back at records, or case reports.
- Nobody knows how the risk changes with the amount taken (the dose–response relationship) in humans.
- Studies of long-term users in Thailand and Malaysia exist, but each looks at one point in time (cross-sectional). No study has followed a group of users forward over many years (a prospective cohort study).
- Nobody knows how much the minor alkaloids contribute. These are the leaf’s other active compounds, besides mitragynine and 7-OH.
The long-term gap matters most. Thailand has several generations of kratom users and a legal framework that allows research. It also has universities able to run the studies. Long-term studies that follow users forward in Thailand would be some of the most valuable kratom research anywhere.
What you can do: If you use kratom regularly, keep a simple record of how much you use, how often, and any symptoms. Also keep the results of any liver blood tests. Your doctor can use this record, and it is the kind of data long-term studies collect. If a Thai university study invites long-term users to take part, joining helps close this gap.
What it all adds up to
Kratom leaf is not the deadly substance its harshest critics describe. The published case reports do not support that claim. Kratom is also not the harmless herb its sellers describe:
- It probably causes liver injury, according to the LiverTox rating.
- It causes dependence and an opioid-like withdrawal.
- It has real, specific drug interactions through the CYP2D6, CYP3A4 and UGT enzymes.
- Seizures in surviving patients are a warning sign that needs more study.
Concentrated 7-OH products are different from leaf and more dangerous. Treating the two as the same thing is the biggest source of confusion in public discussion. It misleads people on both sides of the argument.
If you use kratom and cannot stop, you have a recognised medical condition with an established treatment. See a doctor and tell them what you have been taking.
Questions, corrections or experience from Thai clinics? Post them below this topic.
References (Part 2):
- “The acute adverse health effects of kratom: an evaluation of case reports”, Frontiers in Pharmacology, 2025
- “Kratom”, LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, NIH
- “Kratom”, StatPearls, NCBI Bookshelf
- Tanna et al., “Translating Kratom-Drug Interactions: From Bedside to Bench and Back”, Drug Metabolism and Disposition, 2023
- Vicknasingam et al., “Kratom and Pain Tolerance: A Randomized, Placebo-Controlled, Double-Blind Study”, Yale Journal of Biology and Medicine, 2020
- “7-Hydroxymitragynine (7-OH): Clinical Implications of a Potent, Unregulated Opioid Partial Agonist Derived from Kratom”, Current Addiction Reports, 2026
- “7-Hydroxy Mitragynine New Drug Monograph”, NPS Discovery / CFSRE, 2025
- US Department of Justice, “Department of Justice Announces Updates to Emergency Scheduling Actions for 7-OH and Related Opioid…”, 9 October 2026
- Kratom Act B.E. 2565 (Thailand)
Further reading on Asiannabis
The chemistry topic and the law topic are linked in the introduction above. Two more topics are related: