Kratom

Kratom is a plant from Southeast Asia (Mitragyna speciosa) whose leaves contain compounds that act on the same brain receptors as opioids, but more weakly and in a more complicated way. At low doses it tends to feel like a mild stimulant, similar to a strong coffee. At higher doses it shifts toward pain relief, calm, and sedation. Most people in the West use it for chronic pain, anxiety, low mood, energy, or to taper off prescription or illicit opioids.

It is not a gentle herbal supplement. It is a real psychoactive drug with real risks, including physical dependence and a withdrawal syndrome that looks a lot like opioid withdrawal. Used carefully and intermittently it can be useful. Used daily for months, it tends to cause problems. The other thing worth knowing up front: most "7-OH" or "7-hydroxymitragynine" products now sold in US smoke shops and gas stations are not kratom in any traditional sense. They are concentrated or semi-synthetic opioid agonists that have caused overdose deaths and should be treated as a different drug entirely.

Deep-dive

Kratom leaves contain over 40 alkaloids. The two that matter most are mitragynine, which makes up the bulk of the alkaloid content in dried leaf, and 7-hydroxymitragynine (7-OH), which is present at trace levels (typically under 2% of total alkaloids in raw leaf) but is far more potent. Mitragynine itself is a partial agonist at the mu-opioid receptor with relatively modest affinity, and it also acts on delta and kappa opioid receptors, alpha-2 adrenergic receptors, and serotonin receptors (5-HT2C and 5-HT7). This multi-receptor profile is why kratom doesn't behave like a clean opioid, and why low doses can feel stimulating while high doses feel sedating. A comprehensive pharmacology review walks through the receptor binding in detail.

7-OH is the part that more closely resembles classical opioids. It binds the mu-opioid receptor with nanomolar affinity and in some assays exceeds the potency of morphine. In whole-leaf kratom, 7-OH exposure is small. In concentrated extracts and semi-synthetic products, it dominates the effect, and that is where the serious overdose risk lives.

Mitragynine is metabolised in the liver primarily by CYP3A4, with secondary involvement of CYP2D6. Half-life in chronic users is roughly 24 hours, longer than most people assume, which matters for accumulation and for next-day effects.

Pain. The strongest controlled human data comes from a randomised, placebo-controlled, double-blind study in 26 regular kratom users in Malaysia. A traditional kratom decoction significantly increased cold-pressor pain tolerance compared with placebo, with the effect peaking around an hour after dosing. Outside of that single trial, evidence for analgesic effect comes from large self-report surveys and ecological momentary assessment studies in US users, where pain relief is consistently the most commonly reported benefit and most users do not report escalating doses.

Mood, anxiety, depression. No controlled trials. The best evidence is observational. In a survey of nearly 2,800 US users, 67% used kratom for anxiety and 65% for depression, with most rating it effective. Mechanistically, mitragynine's activity at alpha-2 adrenergic and serotonergic receptors is plausibly relevant here, but plausible mechanism is not the same as proven effect.

Opioid withdrawal and substitution. Kratom is widely used for this and many users report success. In the same large survey, around 41% used kratom to reduce or stop prescription or illicit opioid use, with many reporting more than a year of opioid abstinence attributed to kratom. The catch is that some of these users then become dependent on kratom itself.

Tolerance, dependence, and withdrawal. This is the part most casual users underestimate. Regular daily use produces tolerance and physical dependence. A study of 293 regular kratom users in Malaysia found clear evidence of dependence, withdrawal symptoms, and craving, with severity tracking duration and frequency of use. In a US sample, about 30% of people who had ever used regularly met past-year criteria for kratom use disorder. Withdrawal symptoms are qualitatively similar to opioid withdrawal but generally milder: gastrointestinal upset, restlessness, anxiety, irritability, fatigue, low mood, muscle aches, runny nose, sweating, and craving. The frequency of dosing matters more than the size of any single dose for predicting how rough cessation will be, according to a 2024 analysis. In severe cases, doctors have used buprenorphine to manage kratom withdrawal, the same drug used for opioid use disorder. That should tell you something about how the body categorises kratom.

Liver injury. Rare but real. The US Drug-Induced Liver Injury Network identified 11 cases of kratom-attributed liver injury between 2003 and 2019, mostly in men, with a median latency of 14 days from first use to symptom onset. The pattern is usually cholestatic (jaundice, dark urine, itching, abdominal pain), and most cases resolve once kratom is stopped. The actual rate is unknown but appears low relative to how many people use kratom. Anyone with existing liver disease, heavy alcohol use, or other hepatotoxic medications should be more cautious.

Drug interactions. Mitragynine inhibits CYP3A4 (time-dependent, mostly intestinal) and CYP2D6. A clinical study in healthy adults found that even a single 2g dose of kratom tea increased exposure to midazolam (a CYP3A substrate) by about 40%. In real-world fatalities, kratom is rarely the sole cause; it usually appears alongside benzodiazepines, alcohol, opioids, or antidepressants, and the interaction is part of the mechanism. If you take any prescription drug metabolised by CYP3A4 or CYP2D6, which is a long list including many antidepressants, antipsychotics, statins, and benzodiazepines, treat kratom as a real interaction risk.

Strains, vein colours, and what's actually in your bag. Vendors sell red, white, green, and yellow vein kratom and assign distinct effects to each. Red is sold for relaxation and pain, white for energy, green as balanced. Independent chemical analyses, most notably this 2023 analysis, find that the alkaloid differences between vein colours are smaller and less consistent than marketing implies, though users do report consistent subjective differences. The bigger source of variability is product format. Powdered leaf typically runs 1 to 1.8% mitragynine. Extracts and tinctures concentrate this many-fold. Switching from powder to extract without recalculating dose is one of the most common ways people get into trouble.

The other category to be specific about is concentrated or semi-synthetic 7-OH products. These started appearing in US retail around 2023 and now include tablets, gummies, liquid shots, and nasal sprays containing 14-25 mg of 7-OH per labeled dose, sometimes up to 98% pure 7-OH. Recent reviews describe them as pharmacologically distinct from traditional kratom, with a much higher overdose and addiction risk. The Los Angeles County Medical Examiner identified three fatal 7-OH overdoses in otherwise healthy young adults in 2025. If a product is sold in a smoke shop, has a flashy brand name, lists 7-OH or "7" or "MIT" prominently, comes as a tablet or nasal spray, or claims a single-dose effect comparable to a strong opioid, it is not the same thing as traditional kratom and the dosing guidance below does not apply.

Women. Women appear to be a slight majority of US kratom users. In the largest US survey, 61% of nearly 2,800 respondents were women, with most using it for chronic pain, anxiety, and depression. Women report similar patterns of efficacy to men, but a 2024 analysis found men report more acute effects and more withdrawal symptoms than women at comparable doses, suggesting some sex-related difference in pharmacokinetics or response. Women also tend to use lower doses on average. There is no evidence of unique benefits or unique harms for women outside pregnancy and lactation. Pregnancy is a clear no. Kratom alkaloids cross the placenta, and systematic reviews of prenatal kratom exposure have documented neonatal abstinence syndrome (opioid-style withdrawal in the newborn) requiring pharmacological treatment of the infant. This holds even when the mother used kratom for what she considered therapeutic reasons. Breastfeeding while using kratom is also discouraged.

Older adults. No good data. Older adults are more likely to be on multiple medications, more likely to have reduced liver and kidney function, and more sensitive to sedation and respiratory depression. Drug interaction risk via CYP3A4 and CYP2D6 inhibition is the main concern. If you are over 60 and taking prescription medications, the bar for using kratom should be higher.

Limitations of the evidence. Most human research on kratom is observational, cross-sectional, and based on self-selected online samples that skew toward people who have positive things to say about it. There is exactly one randomised controlled trial of kratom for pain, in 26 people, in Malaysia. Long-term safety data is thin. Dosing standards are non-existent because product alkaloid content varies widely between vendors and even between batches from the same vendor. Take any precise-sounding claim about kratom with that context in mind.

Dosage:

Kratom dosing is non-standardised and varies significantly by product, alkaloid content, individual sensitivity, and goal. The figures below refer to dried, powdered leaf. Extracts, tinctures, and 7-OH products are different drugs and these doses do not apply.

Low dose (1-5 g): stimulant-like effects, mild energy, focus, sociability. This is where most regular users in Southeast Asia and most low-dose Western users sit

Moderate dose (5-10 g): shift toward analgesia, calm, mild euphoria, and sedation. This is where most US users self-managing pain or anxiety land

High dose (over 10-12 g): strong sedation, nausea, dizziness, full opioid-like effect. Higher overdose risk, especially with other depressants

Onset and duration: 20-40 minutes orally, peak at 1-2 hours, total duration 4-6 hours. Half-life is around 24 hours in chronic users, so daily dosing accumulates

Frequency drives dependence more than dose size. Daily use, especially multiple times per day, is the strongest predictor of withdrawal severity. Intermittent use (a few times a week or less) carries far lower dependence risk

Women tend to need lower doses than men for equivalent effect and tend to report fewer withdrawal symptoms at equivalent use patterns. Start at the low end

Tolerance builds quickly with daily use. If you find yourself needing to escalate dose to get the same effect, that is the signal to stop, not to increase

Avoid combining with alcohol, benzodiazepines, opioids, or sedating antidepressants. Most kratom-related deaths involve a second depressant

Hard contraindications: pregnancy, breastfeeding, liver disease, heavy alcohol use, or prescription medications metabolised by CYP3A4 or CYP2D6 (most antidepressants, antipsychotics, statins, benzodiazepines, many others)

Treat 7-OH and concentrated extract products as a separate category. They are not interchangeable with leaf kratom and have a much higher overdose risk

Here's what you can expect:

At low doses, most people feel a clean, slightly warm energy that resembles a strong coffee plus a mild mood lift, lasting a few hours. At moderate doses, a shift toward calm and physical pain relief, often with a sense of sociability or wellbeing. The taste is famously bad and most people use capsules, tea, or the toss-and-wash method.

Effects build over 30-90 minutes and last 4-6 hours. Hangover is uncommon at low doses. Used a few times a week, most users report it as a useful tool with mild side effects. Used daily for several months, most users find it harder to stop than they expected. The transition from "this is helpful" to "I need this to feel normal" tends to be gradual and is mostly predicted by frequency, not by any single high dose.

For pain specifically, expect partial relief, not full opioid-equivalent analgesia. For anxiety and low mood, expect short-term improvement that does not necessarily translate to long-term mental health gains.

Side effects & risks:

Common short-term effects: nausea (especially at first use or higher doses), constipation, dry mouth, sweating, itching, dizziness, and reduced appetite. Higher doses cause vomiting, sedation, and impaired coordination

Tolerance and physical dependence with regular use. Withdrawal on cessation includes anxiety, irritability, restlessness, GI upset, muscle aches, sweating, runny nose, insomnia, and craving. Acute phase 3-7 days, with mood and sleep effects persisting longer. Generally milder than full opioid withdrawal but still miserable

Cholestatic liver injury is rare but documented, usually reversible on stopping, presenting as jaundice, dark urine, itching, or abdominal pain 1-8 weeks after starting. Stop immediately and see a doctor if these appear

Seizures mostly at very high doses or in combination with other drugs

Respiratory depression mostly with concentrated 7-OH products or in combination with other depressants. Most kratom-related fatalities involve polysubstance use, not kratom alone

Drug interactions through CYP3A4 and CYP2D6 inhibition are real and clinically meaningful. Be cautious with antidepressants (SSRIs, SNRIs, tricyclics), antipsychotics, benzodiazepines, statins, certain blood thinners, and many other prescription medications. Avoid stacking with serotonergic drugs (risk of serotonin syndrome at high doses)

Pregnancy and breastfeeding are contraindicated. Neonatal abstinence syndrome is well documented in infants exposed in utero

Product contamination is a real risk. Unregulated kratom has tested positive for heavy metals and bacterial contamination. Buy from vendors who publish current third-party certificates of analysis

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Blood markers

Liver panel (ALT, AST, ALP, GGT, total bilirubin), baseline before starting regular use. Kratom-induced liver injury is rare but typically shows up within 1-8 weeks of starting, so a reference point matters.

Recheck at 6-8 weeks after starting daily or near-daily use, then every 6-12 months while continuing. Sooner if you notice fatigue, jaundice, dark urine, abdominal pain, or itching, all of which can be early signs of cholestatic injury.

Who actually needs what: intermittent users (a few times a week or less) probably don't need routine liver monitoring beyond a sensible baseline. Daily users, especially those over 40, drinking alcohol regularly, or on other hepatotoxic medications, should monitor more carefully. Anyone using concentrated extracts or 7-OH products should treat themselves as taking a real opioid and discuss monitoring with a clinician.

Kratom is unregulated in most jurisdictions and product quality varies widely. None of this is medical advice.