Kratom in Psychiatric Practice: The Gas-Station Opioid Your Drug Screen Can't See

📇 The Index Card — Key Takeaways

Kratom (Mitragyna speciosa)

Why this hides in plain sight. A patient is not improving — or arrives agitated, paranoid and not sleeping — and the medication list looks clean. Nobody asked about the $1–2 gas-station capsule or the $10–20 bag of powder bought for energy, pain or mood, because patients do not count a “natural supplement” as a medication. Ask by name, or you will never hear it.

1. Ask by name or you will never hear it. Patients do not volunteer a gas-station capsule when asked about “medications,” so ask directly about kratom and other herbal supplements used for energy, pain, or mood. It is not FDA-approved for any use and the FDA has warned against it. State law is a moving patchwork — it is banned outright in a growing list of states (including Alabama, Arkansas, Connecticut, Indiana, Louisiana, Tennessee, Vermont, and Wisconsin) — so check current state law rather than assuming it is legal because it is on a shelf.
2. Dose flips its personality. At low doses kratom is stimulant-like — energy, alertness, talkativeness — with minimal opioid activity. At roughly 5–15 grams the opioid activity dominates: analgesia, sedation, euphoria. Above that, stupor and, rarely, coma. The same product is two different drugs depending on the dose, and US products are often concentrated extracts, not the chewed leaf of traditional Southeast Asian use.
3. The chemistry: two alkaloids run the show. Kratom carries 40+ alkaloids; the two that matter are mitragynine (the most abundant) and 7-hydroxymitragynine — cited in the pharmacology literature at about 13 times morphine's potency at the mu receptor. Both are partial mu-opioid agonists with added kappa, delta, 5-HT2A and alpha-2 activity, which makes buprenorphine kratom's closest pharmacologic cousin.
4. It will not show up on the drug screen. Kratom is absent from standard 5-panel, extended 10- and 12-panel screens, and even expanded opioid immunoassays — a clean urine proves nothing. If you suspect it, order the specific mitragynine urine test (available through Quest and LabCorp).
5. The silent interactions are the lethal part. Kratom inhibits CYP2D6, raising levels of aripiprazole (think akathisia, and a patient who quits a drug that was working), risperidone, paroxetine, fluoxetine and venlafaxine — with QT-prolongation and serotonin-syndrome stakes. It also inhibits CYP3A4, raising quetiapine sedation and benzodiazepine levels; combined with kratom's own opioid effect, respiratory depression is the pairing that kills.
6. Withdrawal mimics psychosis — treat it as a substance question first. Kratom withdrawal arrives 1–3 days after stopping and goes beyond classic opioid withdrawal (joint pain, diarrhea, yawning, tearing, insomnia) into hallucinations, paranoia, persecutory delusions, confusion and hostility. New “psychosis” with dilated pupils and diarrhea is a substance question first, not an automatic antipsychotic — and do not compound it by raising an SSRI whose clearance kratom is already inhibiting.

The call: When the story stops making sense — a clean drug screen, a failing medication, a sudden “psychosis” — ask about kratom by name. Kratom is a partial mu-opioid agonist hiding in gas stations — invisible on standard drug screens, a CYP2D6 and 3A4 inhibitor, and capable of a withdrawal syndrome that mimics new psychosis.