Hops

Humulus lupulus L., the common hop, belongs to Cannabaceae, the same small family as hemp; NCBI Taxonomy files it as taxon 3486. Korpelainen and Pietiläinen (Economic Botany 2021) describe it as an herbaceous perennial climber, one of three Humulus species, all present in China, the likely region of origin of the genus; H. lupulus now grows in temperate regions around the world. The annual stems, called bines, twine clockwise around any support with the help of stout, downward-facing hairs and can reach 10–18 m. The leaves have three to five lobes. The species name lupulus is Latin for little wolf; Pliny the Elder linked it to the plant’s habit of climbing over and smothering neighbouring plants, often riverside willows.

Hops are dioecious: male and female flowers are usually on separate plants. The female plants bear cone-like strobiles, the hops of brewing and medicine, made of yellowish-green overlapping bracts on a central axis (Korpelainen and Pietiläinen). At the base of the bracts sit lupulin glands, tiny glandular hairs that secrete lupulin, a yellowish granular powder containing the bitter acids, essential oil, and polyphenols. The European Pharmacopoeia, quoted by EMA, defines the medicinal herb as the dried, generally whole female inflorescences. There are a few hundred cultivated varieties, grown mostly for bitterness and aroma in beer. Young hop shoots have been eaten as a vegetable in Europe since Roman times.

EMA lists the main constituents of the dried strobile. The bitter acids are alpha-acids or humulones (2–12%, chiefly humulone, PubChem CID 442911) and beta-acids or lupulones (1–10%, chiefly lupulone). The essential oil (0.5–1.5%) is mostly myrcene, beta-caryophyllene, humulene, and farnesene. Flavonoids (0.5–1.5%) include at least 22 prenylated compounds, notably xanthohumol (up to 1% of the strobile and 80–90% of total flavonoids), isoxanthohumol, and 8-prenylnaringenin (PubChem CID 480764, C20H20O5) at only 25–60 mg per kilogram. Storage changes the chemistry: 2-methyl-3-buten-2-ol, a volatile alcohol with sedative properties in animals, is present only in traces in fresh hops but rises to about 0.15% of dry weight after two years as the bitter acids break down. That is one reason EMA notes that different raw materials, storage, and extraction methods give contradictory pharmacological results.

Hops entered history through beer. Korpelainen and Pietiläinen, citing the brewing historian Ian Hornsey, date the first mention of hops in connection with brewing to a monastery document of 736 from the Hallertau region of Bavaria, and describe monasteries in France and Belgium demanding dues of hops and malt from their tenants within the following century. The abbess Hildegard of Bingen wrote about hops around 1150; she disliked them and preferred sweet gale for beer, but recognised their antibacterial, preservative value. Hop pollen found inside a tenth-century boat at Graveney in Kent suggests hops were traded early, but English hop gardens appeared only towards the end of the fourteenth century, and in the fifteenth century unhopped ale was still the preferred English drink.

Medicinal use grew from observation. EMA’s assessment report records that hop pickers tired easily, apparently from transferring hop resin from their hands to their mouths, and that the plant gained a reputation as a sedative and hypnotic; pillows filled with hops were used for sleeplessness and nervous conditions. A folk legend held that women who travelled to pick hops began to menstruate two days after arriving, and in 1953 two researchers following up the legend reported oestrogen-like activity in hops. Hops appear in the German, French, and British pharmacopoeias of the late twentieth century, and Germany’s Commission E approved hop strobiles as a sedative in 1984, for restlessness, anxiety, and sleep disturbances. In practice, EMA notes, hops have mostly been used in combination with other calming herbs such as valerian, passionflower, and lemon balm.

The modern era brought both regulation and chemistry. Milligan and colleagues identified 8-prenylnaringenin as the potent phytoestrogen in hops in 1999, offering an explanation for the reports about female hop workers, and noted that beer contains it at levels too low to cause concern. The EU herbal committee adopted its first hop monograph in May 2008 and revised it on 6 May 2014, granting only traditional use. EMA found that hop products met the criteria for traditional use in Denmark, France, Germany, and Poland, while in many other European countries hops were sold mainly in combinations with valerian. The committee’s separate monograph on valerian and hop combinations, revised on 25 September 2019, grants well-established use for sleep disorders.

How hops might calm or aid sleep is not settled. EMA’s assessment report summarises animal studies in which hop extracts reduced spontaneous activity, prolonged sleep induced by pentobarbital or ketamine, and lowered body temperature in mice and rats, consistent with a central sedative effect, with no clear anti-anxiety effect. The alpha-bitter acids appeared most active, with beta-acids and hop oil contributing. Candidate molecules such as myrcene and 2-methyl-3-buten-2-ol have been proposed but not confirmed. In laboratory work, xanthohumol influenced GABA-A receptors, the same receptor family targeted by benzodiazepines, without acting at the benzodiazepine binding site, and hop extracts produced melatonin-like drops in body temperature in mice that a melatonin receptor blocker prevented. EMA stresses that these findings still need confirmation in people, and that varying raw materials and extraction methods make results hard to compare.

The oestrogenic activity is better characterised. Milligan and colleagues used activity-guided fractionation and oestrogen receptor assays to identify 8-PN as the active compound, with activity greater than other plant oestrogens. EMA’s report cites work showing that 8-PN binds both oestrogen receptors, prefers ERα, and was described as the strongest plant-derived ERα agonist identified so far, yet its oestrogenic effect in reproductive tissue in animals was about 20,000-fold weaker than that of oestradiol. Xanthohumol and isoxanthohumol were inactive in those assays. EMA adds that 8-PN occurs in significant amounts in hop preparations only when old hops and special enrichment procedures are used, which matters both for efficacy claims and for safety worries.

On drug metabolism, MSKCC notes that laboratory studies suggest hop extracts may inhibit CYP1A2, 2C8, 2C9, and 2C19, but that a standardised hop extract did not cause clinically relevant interactions with CYP1A2, 2C9, 2D6, 3A4, or 3A5 in a human study.

Mild stress and sleep: EMA accepts hop strobile as a traditional herbal medicine for relief of mild symptoms of mental stress and to aid sleep, based on long-standing use rather than clinical trials. Its assessment report is blunt: no clinical studies had been conducted with hops as a single-ingredient product for restlessness or insomnia. The only study of hops alone that EMA could find gave 17 nurses on rotating or night shifts non-alcoholic beer with supper for 14 days; sleep latency measured by wrist actigraphy fell compared with controls, but EMA considered the study anecdotal because the hop content of the beer was assumed rather than measured. MSKCC likewise concludes that data on hop extracts for insomnia, pain, or menopausal symptoms are too limited to draw conclusions.

Valerian and hops together have more evidence. EMA lists four uncontrolled and three placebo- or reference-controlled trials of one fixed valerian-hops extract (Ze 91019) and further trials of related combinations. In the largest, Morin and colleagues (Sleep 2005) randomised 184 adults with mild insomnia at nine US sleep centres to two nightly tablets of a standardised valerian (187 mg) and hop (41.9 mg) extract combination for 28 days, placebo, or diphenhydramine. Improvements in sleep diaries were modest, few comparisons with placebo were statistically significant, and sleep laboratory recordings showed no differences, though quality of life improved more with the combination and there was no rebound insomnia on stopping. Koetter and colleagues (Phytotherapy Research 2007) found that Ze 91019, containing 500 mg of valerian extract and 120 mg of hop extract, shortened sleep latency compared with placebo over four weeks, while the same amount of valerian alone did not, suggesting the hops contribute; the first author was employed by Max Zeller Söhne AG, a Swiss herbal medicine company. See the valerian page for the broader valerian evidence.

Menopausal hot flashes: EMA describes three small placebo-controlled trials. A 1990 study in which 20 women received a hop extract and five a placebo reported lower hot flash scores with the extract, but the product was not standardised. Heyerick and colleagues (Maturitas 2006) randomised 67 women with menopausal discomfort to hop extract standardised to 100 or 250 micrograms of 8-PN daily or placebo for 12 weeks. All groups improved; the 100-microgram dose beat placebo at six weeks but not at 12, and the higher dose worked less well than the lower one, so there was no dose-response relationship. Erkkola and colleagues (Phytomedicine 2010) ran a 16-week crossover pilot in 36 women with the 100-microgram extract and found no significant overall effect, although some measures favoured the extract in the second period. EMA concluded that these studies fail to show clinical efficacy and that a larger trial is needed.

Other uses remain preliminary. MSKCC notes laboratory and animal research on antibacterial, anti-inflammatory, and anticancer activity of hop compounds, and small preliminary human studies of hop-containing products for osteoarthritis pain and blood sugar control, none of which supports a recommendation. Hop pillows are a traditional sleep aid with no clinical trial evidence.

EU traditional use, hop strobile (EMA/HMPC/682384/2013, adopted 6 May 2014), for adolescents and adults. For mild mental stress: tea made from 500 mg of dried hops in 150–200 ml of boiling water, up to four times a day; powdered hops 400 mg twice daily for adults or 200 mg twice daily for adolescents; liquid extract (1:1, 45% ethanol) 0.5–2.0 ml up to three times daily; tincture (1:5, 60% ethanol) 1–2 ml up to three times daily; or dry extract (4–5:1) 125 mg two or three times daily. To aid sleep: tea from 500–1,000 mg of dried hops, or 800–2,000 mg of powder, 30–60 minutes before bed, or 125–250 mg of dry extract an hour before bed. Not recommended under 12. See a doctor if symptoms last more than two weeks or worsen.

EU well-established use, valerian and hop combinations (EMA/HMPC/327107/2017, revision adopted 25 September 2019), for sleep disorders in adolescents and adults: fixed combinations of dry extracts containing 187–500 mg of valerian and 28–65 mg of hops, or 200–350 mg of valerian and 45–70 mg of hops, taken as one or two doses half an hour to an hour before bed, without exceeding 500 mg of valerian extract. EMA lists various traditional combination products for stress and sleep at other strengths. Because the effect builds gradually, EMA says these combinations are not suitable for acute use and recommends continuous use over four weeks for the best effect; if symptoms persist or worsen after four weeks, see a doctor.

Hop products vary widely. Extract strength, solvent, and the age of the hops change the content of bitter acids, volatile compounds, and 8-PN, so studies on one extract do not automatically apply to another. Menopause products standardised to 8-PN are a different proposition from a bedtime hop tea. Tinctures and some liquid extracts contain substantial alcohol, which EMA requires to be labelled. Beer is not a hop medicine: its alcohol may add to any sedative effect, as EMA notes for alcohol generally, and Milligan found 8-PN levels in beer to be low.