Buspirone and Grapefruit

Yes — there is a documented interaction between these two, and it has a named mechanism. CYP3A4 inhibition.

Major Grapefruit inhibits CYP3A4; Buspirone is cleared by it

Mechanism: CYP3A4 inhibition

Grapefruit slows the enzyme that clears Buspirone, so Buspirone reaches higher blood levels than its dose implies. A CYP3A4 substrate taken with a CYP3A4 inhibitor reaches higher blood levels than its dose implies.

Mechanism-based (irreversible) inactivation of enterocyte CYP3A4. A single 200–300 mL glass is enough. Recovery of CYP3A activity takes roughly 3 days, and separating the juice from the dose by a few hours does NOT avoid it — which is the part almost every patient gets wrong.

A textbook CYP3A4 victim: grapefruit juice raises buspirone exposure severalfold.

What to watch for. The exaggerated version of that drug's own dose-related effects.

Sources: Bailey DG 2013, Bailey DG 1991, Paine MF 2006, Lown KS 1997, Lundahl J 1995, Greenblatt DJ 2003, Edwards DJ 1996, Flockhart DA 2021

The mechanism, generalised

Read the mechanism page and you can apply this to substances that are not on it: CYP3A4 inhibition.

Substance pages: Buspirone · Grapefruit.

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

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.
  • Additive sedation, respiratory depression, bleeding risk, hypoglycaemia and most other pharmacodynamic axes beyond the ones listed above.
  • 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.

72 substances, 20 mechanisms, 64 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. Bailey DG, Dresser G, Arnold JMO (2013). Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?. CMAJ (published online 2012-11-26). doi:10.1503/cmaj.120951
  2. Bailey DG, Spence JD, Munoz C, Arnold JMO (1991). Interaction of citrus juices with felodipine and nifedipine. The Lancet. doi:10.1016/0140-6736(91)90872-M
  3. Paine MF, Widmer WW, Hart HL, et al. (2006). A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction. The American Journal of Clinical Nutrition. doi:10.1093/ajcn/83.5.1097
  4. Lown KS, Bailey DG, Fontana RJ, et al. (1997). Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. Journal of Clinical Investigation. doi:10.1172/JCI119439
  5. Lundahl J, Regårdh CG, Edgar B, Johnsson G (1995). Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. European Journal of Clinical Pharmacology. doi:10.1007/BF00192360
  6. Greenblatt DJ, von Moltke LL, Harmatz JS, et al. (2003). Time course of recovery of cytochrome p450 3A function after single doses of grapefruit juice. Clinical Pharmacology & Therapeutics. doi:10.1016/S0009-9236(03)00118-8
  7. Edwards DJ, Bellevue FH 3rd, Woster PM (1996). Identification of 6',7'-dihydroxybergamottin, a cytochrome P450 inhibitor, in grapefruit juice. Drug Metabolism and Disposition. doi:10.1016/s0090-9556(25)08464-8
  8. 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

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.