Carries the most potent natural MAGL inhibitor reported, 8-prenylnaringenin — which is simultaneously one of the most potent phytoestrogens known. Both facts belong to the same molecule and only one of them is usually mentioned.
Also known as: Humulus lupulus, 8-prenylnaringenin, 8-PN, xanthohumol, isoxanthohumol. Category: plant.
What it does, mechanism by mechanism
MAGL inhibition — inhibits, weak
Slows monoacylglycerol lipase, which performs the large majority of 2-AG hydrolysis in brain. Raises 2-AG and simultaneously diverts it away from the arachidonic-acid pool. Sustained complete blockade produces CB1 desensitisation in animals, so more inhibition is not simply more effect.
8-prenylnaringenin is reported to inhibit MAGL with an IC50 in the low micromolar range. A specific figure is not quoted here because the number was not confirmed against the paper text. Reported from in-vitro enzyme assays. A micromolar IC50 in a dish does not establish that a dietary, tea or capsule dose reaches that concentration at the enzyme in a person, and for most of these compounds no human pharmacokinetic study exists. Treated here as a mechanism worth knowing about, not as an established clinical effect.
Activates the peripheral and immune-cell cannabinoid receptor. Not psychoactive. Relevant here because several very common dietary constituents do it, so it is a real pharmacology hiding in the spice rack rather than an exotic one.
Via beta-caryophyllene and humulene in the volatile fraction.
Sedation, impaired coordination, and at sufficient combined load impaired airway protection and breathing. The most common serious harm in this whole corpus and the least exotic. It does not need a metabolic interaction to happen: the agents simply add.
The traditional sedative use has modest human support, usually in combination products with valerian, which makes attribution to hops alone difficult.
The estrogenic activity of 8-prenylnaringenin is well characterised and is a genuine pharmacological consequence, not a curiosity. Exposure is also person-dependent in a way most botanicals are not: isoxanthohumol is converted to 8-prenylnaringenin by gut microbiota in some individuals and not others, so the same preparation delivers different amounts of the active compound to different people.
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.
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
Tung C-W, Fung K-M, Hsu C-C, Tseng T-S (2021). Discovery of 8-prenylnaringenin from hop (Humulus lupulus L.) as a potent monoacylglycerol lipase inhibitor for treatments of neuroinflammation and Alzheimer's disease. RSC Advances. doi:10.1039/d1ra05311f
Gertsch J, Leonti M, Raduner S, et al. (2008). Beta-caryophyllene is a dietary cannabinoid. PNAS. doi:10.1073/pnas.0803601105
Benke D, Barberis A, Kopp S, et al. (2009). GABA-A receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts. Neuropharmacology. doi:10.1016/j.neuropharm.2008.07.041
Milligan SR, Kalita JC, Heyerick A, Rong H, De Cooman L, De Keukeleire D (1999). Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. The Journal of Clinical Endocrinology & Metabolism. doi:10.1210/jcem.84.6.5887
Possemiers S, Bolca S, Verstraete W, Heyerick A (2011). The intestinal microbiome: A separate organ inside the body with the metabolic potential to influence the bioactivity of xenobiotics. Fitoterapia. doi:10.1016/j.fitote.2010.07.012
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.