8-Prenylnaringenin

8-Prenylnaringenin (8-PN) is a prenylflavonoid from hops (Humulus lupulus). It holds two distinctions that are rarely mentioned together, and both matter to anyone taking it:

It is the most potent natural MAGL inhibitor identified, with an IC50 of 9.5 μM — the enzyme that clears roughly 85% of brain 2-AG.
It is among the most potent phytoestrogens known, with oestrogenic activity exceeding that of the soy isoflavones and of coumestrol.

It is also reported to promote neurogenesis.

The two activities are not separable

This is the point of the page. 8-PN is usually encountered in one of two literatures — the endocannabinoid one, where it is an MAGL inhibitor, or the menopause and hormone one, where it is the reason hops preparations are studied for hot flushes. A person taking it for the first reason receives the second as well. Its oestrogenic potency is not a side note; on a molar basis it is the strongest activity the molecule has.

The historical observation usually cited is "hop-pickers' amenorrhoea" — menstrual disruption reported among women handling large volumes of hops — which is the field observation that eventually led to 8-PN's identification.

In hops

8-PN occurs at low levels in hops directly. Larger amounts are formed by demethylation of isoxanthohumol, which is the abundant precursor — and that conversion is carried out substantially by gut microbiota, specifically Eubacterium limosum. Consequently the dose someone actually receives from a hops preparation is determined by their gut flora, and varies severalfold between individuals. This is an unusually clean example of a compound whose effective dose is not a property of the product.

Beer contains 8-PN, at concentrations far below any of the levels discussed above.

Related hop compounds

Xanthohumol — the parent prenylchalcone; studied for antioxidant and metabolic effects, not appreciably oestrogenic.
Isoxanthohumol — the direct precursor described above.
β-Caryophyllene — also present in hops; CB2 agonist.
Myrcene and α-humulene — the major hop terpenes, shared with cannabis.

Cautions

Hormone-sensitive conditions. Oestrogen-receptor-positive breast cancer, endometrial conditions and any hormone-modulating therapy are the obvious contraindications, and the potency here is high enough that this is not a formality.
Interaction with hormonal contraception and HRT is plausible on mechanism.
Sedation. Hops preparations are traditionally sedative; combined with alcohol or other sedatives the effect is additive.
Dose is not what the label says, for the microbiota reason above.
The MAGL and neurogenesis findings are preclinical. The oestrogenic activity is the best-established thing about this molecule.