Science
Interactions
How 7-OH-class compounds can combine with other substances, according to published sources. Severity grades are from the evidence summaries we track, not a clinical score.
Known interaction pairs
| Agents | Effect | Evidence | Grade |
|---|---|---|---|
| 7-Hydroxymitragynine (7-OH) + Benzodiazepines incl. designer analogs (bromazolam, etizolam) | Synergistic respiratory depression, sedation, hypoxia Opioid MOR + GABA-A: brainstem respiratory centres suppressed by both | Human data (class: opioid+benzo); kratom case reports Refs: FDA 2016 boxed warning; Hwang 2016; kratom-death toxicology (Olsen 2019 MMWR) | A · severity 5/5 |
| 7-Hydroxymitragynine (7-OH) + Alcohol | Additive-synergistic respiratory depression Opioid + GABA/NMDA depressant | Human data (opioid class); mechanistic for 7-OH Refs: Standard opioid labeling | A · severity 5/5 |
| 7-Hydroxymitragynine (7-OH) + Fentanyl and analogs | Additive respiratory depression; tolerance to 7-OH may not protect Two MOR agonists; adulteration | Mechanistic; overdose surveillance Refs: Olsen 2019 MMWR | B · severity 5/5 |
| 7-Hydroxymitragynine (7-OH) + Nitazenes (isotonitazene, protonitazene, metonitazene) | Profound respiratory depression Two MOR agonists | Mechanistic Refs: Vandeputte 2021 | D · severity 5/5 |
| Tianeptine + Benzodiazepines incl. designer analogs (bromazolam, etizolam) | Synergistic respiratory depression MOR + GABA-A | Case reports Refs: FDA 2023 | B · severity 5/5 |
| Benzodiazepines incl. designer analogs (bromazolam, etizolam) + Fentanyl and analogs | Prolonged sedation after naloxone GABA-A + MOR | Human surveillance Refs: CDC 2021 | A · severity 5/5 |
| O-desmethyltramadol + Benzodiazepines incl. designer analogs (bromazolam, etizolam) | Synergistic respiratory depression MOR + GABA-A | Human (opioid class); Krypton deaths Refs: Kronstrand 2011 | A · severity 5/5 |
| Vitamin E acetate + Propylene glycol / glycerol | Acute lung injury (EVALI) VEA in oil cartridges; heating produces ketene | Human outbreak data Refs: Blount 2020 | A · severity 5/5 |
| 7-Hydroxymitragynine (7-OH) + Phenibut | Additive respiratory depression; phenibut withdrawal compounds opioid withdrawal Opioid + GABA-B | Case reports; mechanistic Refs: Graves 2020 | B · severity 4/5 |
| 7-Hydroxymitragynine (7-OH) + Gabapentin / pregabalin | Increased overdose risk (opioid+gabapentin OR ~1.5-2) Opioid + alpha2delta | Human data (opioid class) Refs: Gomes 2017 | A · severity 4/5 |
| 7-Hydroxymitragynine (7-OH) + Xylazine | Sedation, bradycardia, hypotension; naloxone-resistant part MOR + alpha-2 | Mechanistic/human (fentanyl+xylazine) Refs: ONDCP 2023 | D · severity 4/5 |
| 7-Hydroxymitragynine (7-OH) + Mitragynine pseudoindoxyl (MGPI) | Additive opioid effect; MGPI may outlast/prolong Two MOR agonists, often co-formulated | Mechanistic; market data Refs: Hill 2025; Stanciu 2026 | D · severity 4/5 |
| 7-Hydroxymitragynine (7-OH) + Tianeptine | Additive respiratory depression, compounded withdrawal Two MOR agonists | Mechanistic; poison-center co-exposures Refs: El Zahran 2018 | D · severity 4/5 |
| Mitragynine + CYP3A4 inhibitors (azoles, macrolides, ritonavir, grapefruit) | Raise mitragynine exposure 1.5x; lower 7-OH formation from leaf, but RAISE exposure to preformed 7-OH from concentrates (rat ketoconazole +130%) CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit) | Human (itraconazole) + animal (ketoconazole) Refs: Mongar 2024; Kamble 2023 | A · severity 4/5 |
| Synthetic cannabinoids (MDMB-4en-PINACA, ADB-BUTINACA etc.) + Caffeine and other stimulants | Seizures, tachyarrhythmia CB1 full agonism + stimulant | Case series Refs: Tait 2016 | B · severity 4/5 |
| Synthetic cannabinoids (MDMB-4en-PINACA, ADB-BUTINACA etc.) + 7-Hydroxymitragynine (7-OH) | Seizures plus respiratory depression; confusing picture Seizure-prone CB1 agonist + opioid | Mechanistic Refs: EUDA | D · severity 4/5 |
| Phenibut + Alcohol | Profound sedation, respiratory depression GABA-B + GABA-A | Case reports Refs: Graves 2020 | B · severity 4/5 |
| Mitragynine + 7-Hydroxymitragynine (7-OH) | More 7-OH formed when CYP3A4 active; varies with inducers/inhibitors Mitragynine is converted to 7-OH by CYP3A4 | Human data (itraconazole study) Refs: Mongar 2024 | A · severity 3/5 |
| Mitragynine + O-desmethyltramadol | Could raise levels of co-taken 2D6/3A4 substrates (tramadol, dextromethorphan, some SSRIs, quetiapine); case of quetiapine+kratom death Mitragynine inhibits CYP2D6 (and CYP3A4) | In vitro; case reports Refs: Kamble 2020; Hughes 2019 | B · severity 3/5 |
| Mitragynine + Caffeine and other stimulants | Seizure risk at high kratom doses plus stimulants Stimulant + kratom (seizure threshold) | Case reports (kratom seizures); mechanistic Refs: Kratom seizure case series (Eggleston 2019) | B · severity 3/5 |
| Mitragynine + QT-prolonging medicines | QT prolongation, torsades hERG block by mitragynine + QT drugs (ondansetron, antipsychotics, methadone, loperamide) | In vitro; case reports Refs: Tay 2016; Leong Abdullah 2021 | B · severity 3/5 |
| Synthetic cannabinoids (MDMB-4en-PINACA, ADB-BUTINACA etc.) + Nicotine (salt form) | Seizures/tachycardia (nicotine e-liquid toxicity also convulsant) Both sympathomimetic; spice in vapes | Case series; mechanistic Refs: EUDA | B · severity 3/5 |
| O-desmethyltramadol + Caffeine and other stimulants | Seizures, serotonin toxicity with SSRIs ODT/tramadol lower seizure threshold; serotonergic | Human data (tramadol) Refs: Tramadol labeling | A · severity 3/5 |
| Nitrous oxide + Alcohol | Loss of consciousness, aspiration Hypoxia + depressant | Case reports Refs: FDA 2025 | B · severity 3/5 |
| Kavalactones (kawain, methysticin, yangonin) + 7-Hydroxymitragynine (7-OH) | Added sedation; possibly higher kratom levels; additive liver strain GABA-A modulation + opioid; kava CYP inhibition | Mechanistic Refs: Teschke 2011 | D · severity 3/5 |
| Thermal by-products (formaldehyde, acrolein, ketene) + 7-Hydroxymitragynine (7-OH) | Faster onset, more dose-stacking; airway irritation Vaping 7-OH adds airway irritants; inhaled route may raise speed/bioavailability (unknown) | Mechanistic Refs: - | D · severity 3/5 |
| Mitragynine + Nicotine (salt form) | Combined withdrawal irritability, sleep loss Both raise sympathetic tone; dual dependence | Mechanistic; survey Refs: Surveys of co-use | D · severity 2/5 |
| Nicotine (salt form) + Caffeine and other stimulants | Tachycardia, anxiety, sleep loss Sympathomimetic | Human data Refs: Standard | A · severity 2/5 |
| Coil metals (lead, nickel, chromium, manganese) + Propylene glycol / glycerol | Chronic lead/nickel exposure Coil leaching into aerosol | Measurement studies Refs: Olmedo 2018 | B · severity 2/5 |