Seizure-threshold lowering

Seizure-threshold lowering. Agents that make a seizure more likely, additively. A CYP interaction that raises the blood level of a seizure-threshold-lowering drug converts a pharmacokinetic problem into a neurological one.

What acts on it

What is affected by it

What a clean result means here

A clean result means NO DOCUMENTED INTERACTION IN THIS DATASET. It does not mean safe, and it is not a clearance. Most substances are not in this dataset at all, and for many pairs that are, nobody has ever studied the combination.

In this dataset

  • Monoamine oxidase inhibition (prescription MAOIs, RIMAs, linezolid, methylene blue, harmala alkaloids)
  • Serotonergic drugs and the serotonin-toxicity mechanism
  • Dietary tyramine and L-dopa loads
  • The major cytochrome P450 pathways: CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C19 — inhibition and induction
  • P-glycoprotein inhibition and induction
  • 11β-HSD2 inhibition (the licorice mechanism) and the potassium consequences that follow it
  • QT prolongation as an additive pharmacodynamic axis
  • Culinary seasonings and common foods with documented pharmacological activity
  • A selected set of narrow-therapeutic-index drugs where those shifts matter most
  • The endocannabinoid enzymes and transport: FAAH, MAGL, endocannabinoid membrane transport, CB1 and CB2
  • Additive CNS depression and GABA-A positive modulation — the alcohol / benzodiazepine / opioid / kava axis
  • The phytocannabinoids delta-9-THC, cannabidiol and the converted cannabinoids, as both substrates and inhibitors
  • Synthetic full CB1 agonists as a class, and why they are pharmacologically unlike cannabis
  • CYP2E1, and phase-2 glucuronidation and sulfation where a specific entry names them
  • The sedative and potentiator botanicals of the kava literature, and dietary L-dopa from Mucuna

Not in this dataset

  • Any substance not named in this dataset — which is most substances. There are tens of thousands of marketed drugs and this table holds fewer than a hundred entries.
  • Phase-2 conjugation (UGT, SULT, NAT2, COMT) except where a specific entry names it. The oilahuasca corpus turns heavily on phase 2 and this engine models it only in passing.
  • Pharmacogenomics. CYP2D6 and CYP2C19 are strongly polymorphic; a poor metaboliser and an ultra-rapid metaboliser can have opposite outcomes from the same pair, and this engine does not know your genotype.
  • Dose, timing, duration, formulation and route — all of which change whether a documented interaction is clinically real for you.
  • Renal and hepatic impairment, age, pregnancy, and body composition.
  • Bleeding and antiplatelet risk, hypoglycaemia, anticholinergic load, and most other pharmacodynamic axes beyond the ones listed above. Additive CNS depression and GABA-A modulation ARE now modelled — see the covers list — but the absence of a sedation finding still only means the agents you named are not on that axis in this dataset.
  • Herb–herb interactions outside the named entries, and essentially the whole botanical world: most plants have no interaction literature at all.
  • Allergy, intolerance, and contamination or adulteration of unregulated products.
  • Anything published after the last-reviewed date below.
  • Bleeding and antiplatelet risk, which is the mechanism that matters most for garlic, ginkgo and several other common supplements. It is not modelled at all, so a clean result says nothing about it.
  • Whether any of the natural FAAH, MAGL or transport inhibition reported in vitro occurs at all at a dose a person would take. For most of these compounds nobody has measured it.
  • The actual contents of an unregulated cannabinoid product. This engine models named compounds; an unidentified isomer or side-product in a converted-cannabinoid product is outside it by construction.
  • Dose. Every cannabinoid interaction here scales with dose, and consumer product labelling for this category is repeatedly found inaccurate in published surveys.
  • Inhalation-specific hazards — thermal degradation products, diluents chosen for rheology rather than for inhalation toxicology, and carrier and adulterant contamination.

101 substances, 33 mechanisms, 101 citations. Last reviewed . Primary literature (every DOI resolved against the Crossref API) and FDA drug labelling. There is no free, openly-licensed, comprehensive drug-interaction dataset to draw on; NLM retired its Drug Interaction API on 2024-01-02 and DrugBank's interaction set is a commercial licence.

References

  1. Beakley BD, Kaye AM, Kaye AD (2015). Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain Physician. doi:10.36076/ppj.2015/18/395
  2. U.S. Food and Drug Administration (2023). Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. FDA. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers
  3. Ize-Ludlow D, Ragone S, Bruck IS, Bernstein JN, Duchowny M, Peña BM (2004). Neurotoxicities in Infants Seen With the Consumption of Star Anise Tea. Pediatrics. doi:10.1542/peds.2004-0058
  4. Flockhart DA, Thacker D, McDonald C, Desta Z (2021). The Flockhart Cytochrome P450 Drug-Drug Interaction Table. Division of Clinical Pharmacology, Indiana University School of Medicine. https://drug-interactions.medicine.iu.edu
  5. Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S (2016). A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clinical Toxicology. doi:10.3109/15563650.2015.1110590
  6. Adams AJ, Banister SD, Irizarry L, Trecki J, Schwartz M, Gerona R (2017). "Zombie" Outbreak Caused by the Synthetic Cannabinoid AMB-FUBINACA in New York. New England Journal of Medicine. doi:10.1056/NEJMoa1610300

Every DOI above was resolved against the Crossref API on 2026-09-09 and the returned title checked against the one printed here. Three DOIs in the first draft resolved to real but different papers and were corrected before publication.

Last reviewed . All interaction pages.