Hops

Hops (Humulus lupulus L.): A Comprehensive Reference

1. Identity and Botanical Description

Taxonomy and Nomenclature

Hops are scientifically known as Humulus lupulus L., a plant belonging to the Cannabaceae family. The most widely recognized names for the medicinal preparation of the strobiles include European hops, hoblon, hop vine, hopfen, and hops. In pharmacopeial literature, the dried female inflorescence is often referred to as Strobilus lupuli or Lupuli strobulus.

Plant Description and Cultivation

Humulus lupulus is a perennial plant used largely as a flavoring in the production of beer. The hop plant is cultivated as a vine that grows around a physical support and produces shoots, heart-shaped dark green leaves, fresh cones, and flowers that are borne on lateral branches. It is cultivated in Europe, Asia, and North America, occurring in the world's temperate areas.

Plant Part Used

Hops — the cone-like female structures called strobili — are the most frequently used part of the hop plant, but other tissues are of interest as well. The pharmacological activity of Humulus is principally due to resin (lupulin) from the dried, female-flowering parts (strobiles). The glandular resin, or lupulin, is concentrated in secretory trichomes on the cone bracts. H. lupulus owes its bitter taste and characteristic aroma to chemical compounds such as α-acids, primarily found in the bracts of pistillate flowers.

Commercial Role

Hop (Humulus lupulus) is best known for its use in beer brewing owing to its bittering flavor and floral aroma. Today, the brewing industry uses as much as 98% of the produced hop crop worldwide. It is also an important plant that contains metabolites used in the pharmaceutical field.

Common Forms and Preparations

Humulus lupulus strobiles are used in the form of herbal tea, infusions, powdered herbal substance, or alcoholic extracts for various indications. Most hop preparations used in combination products are dry extracts prepared with water, methanol 30–45%, or ethanol 70%. Hops are also used in herbal teas, as well as soft drinks including kvass and hop water. A dietary supplement extracted from hops, amarasate, is marketed to suppress appetite.

2. Traditional and Historical Use

Early History

In medicine, hops appears in the literature as early as the end of the 10th century — specifically in the manual of pharmaco-therapy traditionally identified in modern scholarly literature as the Old English Herbal. Hops also have a long history of use in herbal medicine dating back to at least the 9th century in Europe. They were traditionally used to treat a variety of ailments, ranging from indigestion to Hansen's disease (leprosy).

Brewing and Monastic Use

The first recorded use of hops for beer comes from a monastery in northern France in 822 CE. Some surmise that hops were a desired ingredient in monastery beer because of their ability to inhibit sexual desire. Several hundred years later, hops were being actively cultivated in Germany for beer. In time in Europe, it was declared that hops were a required ingredient in beer. In addition to adding flavor, hops also stabilize beer, giving it a much longer shelf life.

Traditional Medicinal Applications

The medicinal potential of hop (Humulus lupulus L.) is widely cited in ancient literature and is also allowed in several official pharmacopoeias for the treatment of a variety of ailments, mainly related to anxiety states. Strobilus lupuli was applied as a sedative agent for the treatment of nervous tension and insomnia, used in the treatment of dyspepsia and lack of appetite, and applied to treat anemia, bacterial infections, abdominal cramps, dysmenorrhoea, leukorrhoea, dermatitis, diarrhea, migraine, and edema.

Historically, menstrual disturbances were commonly reported among female hop pickers, and hop extract was reported to be efficient in reducing menopause-associated hot flushes in women. Moreover, hop baths were used for the treatment of gynecological disorders.

Hops pickers reported sedation during harvest, and hops flowers have been added to pillows for relief of nervous conditions. This observation — sometimes called "hop-picker fatigue" — contributed historically to the idea that hops possess genuine sedative properties.

Official Traditional Recognition

The German Commission E approved use of hops for mood disturbances such as restlessness and anxiety as well as sleep disturbances. Hops are mostly used in combination with other sedative herbs such as valerian, passion flower, and lemon balm for the treatment of sleep disturbances. The World Health Organization recognizes hop extract as a traditional treatment for abdominal cramps and diarrhea, and values it for its anthelmintic, carminative, and digestive properties.

3. Key Constituents and Active Compounds

Bitter Acids (Alpha- and Beta-Acids)

Analysis of strobili through chromatography showed the presence of bitter substances. The bitter substances in the resins are the major constituents of Strobulus lupuli, representing 15–25% of total strobili constituents. The most characteristic constituents of hops are the bitter principles, known as alpha- and beta-acids. In the plant, the alpha-acids occur as humulone, cohumulone, and adhumulone. During the brewing process, these compounds are isomerized to the iso-alpha-acid series of compounds that possess a bitter taste. The beta-acid series of compounds include lupulone and congeners; this series is destroyed during brewing.

Alpha-Acid Degradation Product: 2-Methyl-3-buten-2-ol

The pharmacological activity of hop resin is principally due to its bitter resins, in particular to the α-acid degradation product 2-methyl-3-buten-2-ol. The bitter alpha acids (humulones) seem to be the most active of the constituents, with the alpha acid degradation product 2-methyl-3-buten-2-ol being of particular interest. It has been shown that this degradation product, deriving from hop constituents during storage, reduced motility of rats when intraperitoneally injected.

Prenylflavonoids: Xanthohumol and 8-Prenylnaringenin

Xanthohumol (Xn; 3′-[3,3-dimethylallyl]-2′,4′,4-trihydroxy-6′-methoxychalcone), the most abundant prenylated flavonoid, represents 0.1–1% of dry weight in hops and can be isolated from the female inflorescences. 8-Prenylnaringenin (8-PN) is considered to be the most potent phytoestrogen thus far discovered. Xanthohumol, a metabolic precursor of 8-prenylnaringenin, was not itself estrogenic in functional assays. 8-Prenylnaringenin had nanomolar estrogenic potency without estrogen receptor selectivity, while xanthohumol did not bind estrogen receptors.

Essential Oils, Terpenes, and Polyphenols

Humulus lupulus contains a variety of sesquiterpenoids, diterpenoids, and triterpenoids, phytoestrogens, and the flavonoid xanthohumol, which has some in vitro anti-HIV activity. Research has focused on hop acids, essential oils, and flavonoids. Constituents identified include oleo-resins containing bitter substances (acylphloroglucides, humulone, lupulone, valerianic acid), volatile oil (humulene), tannins, an estrogenic substance, flavonoids (kaempferol, quercetin, rutin), chalcones, and aspargin.

Bioavailability Considerations

Xanthohumol is a major prenylated flavonoid in hops exhibiting a broad spectrum of health-promoting and therapeutic activities. However, due to its lipophilic nature, it is poorly soluble in water and barely absorbed from the gastrointestinal tract, which greatly limits its therapeutic potential.

4. Mechanisms of Action

GABAergic Modulation (Central Nervous System)

The mechanism of action of hop resin consists of raising the levels of the neurotransmitter γ-aminobutyric acid (GABA), an inhibitory neurotransmitter acting in the central nervous system (CNS). More specifically, the main mechanism of action of hops is to increase the activity of the neurotransmitter γ-aminobutyric acid (GABA) through modulation of brain GABA(A) receptors. The mechanism would principally be by modulating the GABAergic response through the effects of the hop components myrcenol, xanthohumol, and such α-acid derivatives as 2-methyl-3-buten-2-ol.

Certain components of hop essential oils, specifically terpenoids, have demonstrated modulatory enhancement of recombinant GABA-A receptors. However, these effects were detected at millimolar or high micromolar concentrations, which exceeded their natural presence in hops and may not be physiologically relevant. The constituents tested included myrcene (1 mM), β-caryophyllene (1 mM), linalool (300 μM), myrcenol (350 μM), geraniol (1 mM), and 2-methyl-3-buten-2-ol (600 μM).

With the potential to offer novel mechanisms distinct from those of benzodiazepines, xanthohumol has emerged as a noteworthy hop flavonoid. A preliminary study using fluorescence correlation spectroscopy reported a significant enhancement in the binding of muscimol to hippocampal neurons by xanthohumol at 75 nM.

Estrogenic Activity

Due to its estrogenic effects, administration of 8-PN represents a novel therapeutic approach to the treatment of menopausal and post-menopausal symptoms that occur as a consequence of a progressive decline in hormone levels in women. Apart from the estrogen receptor-activating pathway, phytoestrogens can also exhibit their effects through non-genomic mechanisms, via interactions with cell surface receptors.

Anti-inflammatory and Antioxidant Mechanisms

The plethora of phytoconstituents (e.g., bitter acids, polyphenols, prenyl flavonoids) present in the female inflorescences are endowed with anti-inflammatory, antioxidant, antimicrobial, and phytoestrogen activities. The beneficial pharmacological properties of xanthohumol were not widely appreciated until the 1990s, including antioxidant, anti-inflammatory, antibacterial, antiviral, antifungal, and antiplasmodial activity.

Cytochrome P450 Interactions

While studying cytochrome P450 enzymes involved in carcinogen activation, researchers reported that some hop prenylflavonoids can inhibit CYP1A1, CYP1B1, and CYP1A2. Hop-containing beers can inhibit CYP2C9, but no specific inhibitors were identified. Since hops have the potential to interfere with drug metabolism, more detailed studies of these drug-botanical interactions are needed.

5. Scientific Evidence by Area of Use

5.1 Sleep and Insomnia

Sleep promotion is the most studied application of hops. Animal studies suggest that hops has sedative effects, but there has been little clinical study of its efficacy in humans as a single agent.

Key clinical trials:

• Morin et al. (2005) conducted a randomized placebo-controlled clinical trial of a valerian-hops combination versus diphenhydramine versus placebo in 184 patients with mild insomnia and found a "modest hypnotic effect" for the herbal combination; there were no serious adverse events.
• A randomized, double-blind, placebo-controlled study evaluated a valerian and hops-based herbal medication (Ze 91019) on daytime cognitive performance and sleep measures in individuals with occasional sleep problems. Conducted in 40 participants over a 21-day run-in period and a 21-day treatment period, the valerian-hops extract combination significantly increased sleep duration in individuals with occasional sleep problems by 21.7 minutes per night and 48.7 minutes on the shortest night, compared to placebo, without impairing daytime cognitive or psychological functioning.
• A study investigated whether the hops content of alcohol-free beer may have a sedative action and affect the activity/sleep rhythm. The trial was conducted with a sample of 17 female volunteers on the nursing staff of a health service who had at least one night shift per working week and were subject to a high load of work and/or mood stress. Volunteers were in good health, had normal body weight, and did not take any medications that might have influenced or masked the results. The results suggested that, because of its hop content, beer may have a possible use as a sedative in humans.

Evidence assessment: Twelve studies found that the use of valerian, on its own or in combination with hops, is associated with improvements in some sleep parameters (e.g., sleep latency and quality of sleep). However, these results need to be interpreted cautiously as there were significant differences in design between the studies. Further randomized, double-blind, placebo-controlled trials are needed before such herbal treatments can be confidently recommended for the treatment of primary insomnia.

5.2 Anxiety, Stress, and Mood

The German Commission E approved use of hops for mood disturbances such as restlessness and anxiety. Some preclinical data suggest hops compounds modulate GABAergic pathways relevant to anxiety; however, clinical evidence specific to anxiety as an isolated outcome is limited.

In preclinical research investigating hop β-acids on central nervous system function, oral administration of β-acids (5–10 mg/kg) in rats produced an increased exploratory activity in the open field, a reduction in pentobarbital hypnotic activity, and a worsening of picrotoxin-induced seizures. When dosed at 10 mg/kg, β-acids increased open arm entries in the elevated plus maze. In the forced swimming test, a reduction in immobility time was observed that could suggest an antidepressant-like activity. These are animal findings and have not been directly replicated in adequately powered human trials for anxiety as a primary endpoint.

Hops may be used in herbal medicine in a way similar to valerian, as a treatment for anxiety, restlessness, and insomnia. A pillow filled with hops is a popular folk remedy for sleeplessness. These indications have limited evidence in man. Hops lack strong evidence supporting effectiveness for any specific medical condition, though they are generally considered safe.

5.3 Menopausal Symptoms

Hops are of interest for hormone replacement therapy and are under basic research for potential relief of menstruation-related problems.

8-Prenylnaringenin (8-PN) is a prenylated flavonoid occurring particularly in hops. It has proven to be one of the most potent phytoestrogens in vitro known to date, and in the past 20 years, research has unveiled new effects triggered by it in biological systems.

Animal evidence: Data from a rat model show that the hop-derived phytoestrogen 8-PN is capable of reducing the raised skin temperatures occurring in a rat model of menopausal hot flushes, when administered either subcutaneously or orally.

Human clinical evidence: A prospective, randomized, double-blind, placebo-controlled study over 12 weeks with 67 menopausal women administered a hop extract standardized on 8-PN (100 or 250 μg) to examine the efficacy on relief of menopausal discomforts. All groups, including placebo, showed a significant reduction of the Kupperman Index both after 6 weeks and after 12 weeks — limiting interpretation of efficacy. In an exhaustive review of the literature through 2003, only two clinical trials were identified that were designed to evaluate the effect of hops on symptoms related to menopause.

The majority of 8-PN effects require such high concentrations that they cannot be reached by normal dietary exposure, only pharmacologically; thus, adverse impacts may also emerge. The use of phytoestrogens is frequently questioned regarding possible adverse effects associated with long-term consumption. Further investigations are needed to define the safety risks related to its therapeutic use.

Branding hops as a "nutritional supplement" could provide an alternative route for hop-based remedies to the pharmaceutical market, but the claim that hop relieves menopausal symptoms was awaiting approval from the European Food Safety Authority at the time of publication.

5.4 Anticancer Activity (Preclinical)

Increasing evidence has suggested the anticancer activity of xanthohumol (Xn) against NSCLC, leukemia, HCC, breast cancer, prostate cancer, cholangiocarcinoma, glioblastoma, pancreatic cancer, colon cancer, cervical cancer, melanoma, thyroid cancer, laryngeal squamous cell carcinoma, and ovarian cancer. Numerous studies have demonstrated the anticancer activity of xanthohumol, a prenylated flavonoid isolated from hops.

Evidence assessment: Present studies are not sufficient to evaluate the anticancer activity of xanthohumol and more mechanistic and systematic in vivo studies must be conducted for better understanding of its efficacy for clinical development. Xanthohumol showed very promising bioactivities in both in vitro and in vivo examinations on various cancers, and it had the most prominent therapeutic effect on breast, colon, and prostate cancer. No human clinical trials for cancer treatment or prevention using hops constituents have been identified in the sources consulted. All anticancer evidence remains preclinical (in vitro and animal studies).

5.5 Digestive / Appetite and Metabolic Effects

Bitter-tasting plants have a long history of use as traditional foods and medicine. The use of bitter foods to suppress appetite and food cravings is reported in several cultures throughout history. The search for a commonly consumed bitter plant extract with a history of medicinal use that could be used for safe and effective appetite control led to Humulus lupulus (hops).

The structure of xanthohumol was first identified by Verzele in 1957, but only in the last decade has xanthohumol been rediscovered, focusing in particular on its multiple bioactivities, including anticancer, antidiabetic, antibacterial, and anti-inflammatory activities.

While the causes for metabolic diseases are complex, numerous studies have shown that hops have many beneficial effects for people with metabolic syndromes. About 1,000 polyphenolic substances have been found in hop strobiles. Many of those polyphenols have been shown to have a beneficial effect on cholesterol, reduce inflammation, and support heart health. This evidence remains largely preclinical.

5.6 Antimicrobial Activity

Constituents present in the female inflorescences are endowed with antimicrobial activity. The beneficial pharmacological properties of xanthohumol include antibacterial, antiviral, antifungal, and antiplasmodial activity. Studies of antimicrobial properties are predominantly in vitro and have not been evaluated in human clinical trials for infectious disease treatment.

6. Body Systems Associated With Hops

• Central Nervous System: Sedative, anxiolytic, and hypnotic actions via GABAergic modulation; primary area of traditional and regulatory recognition.
• Endocrine/Reproductive System: Phytoestrogenic activity via 8-PN; interest in menopausal symptom management.
• Gastrointestinal System: Traditional use as a bitter tonic for dyspepsia, appetite stimulation, antispasmodic effects, and anthelmintic use.
• Immune and Inflammatory System: Anti-inflammatory and antioxidant properties ascribed to xanthohumol and other polyphenols, primarily studied in preclinical models.
• Oncology (Investigational/Preclinical): Xanthohumol investigated across multiple cancer cell lines in vitro and in animal models.
• Metabolic System (Investigational): Preliminary interest in effects on blood glucose, cholesterol, and metabolic syndrome markers.

7. Dosage Forms and Reported Dosages

Traditional/Regulatory Dosages

For sleep and mood disturbances, single dosages of 0.5 g of cut or powdered strobile or dry extract powder for infusions and decoctions have been described by German regulatory sources. Infusion or decoction: 0.5 g hop strobiles (1 to 2 teaspoons) per preparation.

Dry extract: some traditional herbal monographs describe 125–250 mg of a dry extract before bedtime for sleep-related use. Powdered herbal substance: traditional use sources also describe 800–2,000 mg taken 30 to 60 minutes before bedtime.

Dosages Used in Clinical Studies

• In the menopausal symptoms trial, a hop extract standardized on 8-PN was administered at 100 μg or 250 μg doses over 12 weeks.
• In Morin et al. (2005), a valerian-hops combination was compared to diphenhydramine and placebo in 184 patients with mild insomnia, with the herbal combination found to have a "modest hypnotic effect."
• In the 2025 randomized controlled feasibility trial of Ze 91019 (a valerian-hops extract combination), the study was conducted in 40 participants over a 21-day run-in and 21-day treatment period.

Safety evaluations concluded that extracts and bitter acids are safe when used short-term and in adequate quantities, such as 300 mg/day for extracts for a period of 3 months, and 35 mg/day for bitter acids for the same duration.

Important Dosage Caveats

Most of the studies examining the efficacy of hops to aid sleep employ hops in combination with other compounds acting on various receptors known to be involved in sleep regulation. This makes it difficult to isolate dose-response relationships for hops alone. Most studies on hops use either supplements or non-alcoholic beer containing hops, not alcoholic beer, because alcohol independently disrupts sleep architecture.

8. Safety Considerations and Drug Interactions

General Safety Profile

Hop is an important agricultural plant that has been used to flavor beer for centuries and has been claimed to have sedative properties. Hops have not been implicated in causing serum enzyme elevations or clinically apparent liver injury. Hops lack strong evidence supporting effectiveness for any specific medical condition, though they are generally considered safe.

CNS Depression and Additive Sedation

Hops may add to the effects of alcohol, sleep aids, and other sedating products, which can increase drowsiness or reduce alertness.

Hormone-Sensitive Conditions

Hops may pose some risks of side effects, particularly for people with thyroid disease or estrogen-positive breast cancer. Researchers also speculate that hops-containing dietary supplements may raise the risk of postmenopausal bleeding. Some hop constituents have estrogen-like activity, which is one reason hops appears in some menopause supplements. That is also why people with hormone-sensitive conditions should be careful.

Cytochrome P450 Drug Interactions

As women are using hop-based supplements as alternatives to estrogen replacement therapy, it is important to understand the potential of these supplements to interact with clinically used drugs. Drug-botanical interactions include inhibition and induction of drug metabolizing enzymes, especially the cytochrome P450 enzymes, and induction or inhibition of drug transporters. Hop prenylflavonoids can inhibit CYP1A1, CYP1B1, and CYP1A2. Hops might decrease how quickly the liver breaks down some medications. Taking hops along with some medications that are changed by the liver might increase the effects and side effects of some medications.

Limitation of Evidence

Hops contains hundreds of phytochemicals, and some of the secondary metabolites have definite potential pharmacological and medicinal value, but further investigations are desirable. Although there have been a fair number of studies on this subject, there remains much more to learn about Humulus resin, all its active biochemical constituents, and their effects on the CNS. The predominance of combination studies with valerian makes it methodologically difficult to attribute specific effects exclusively to hops in most human clinical trials.

References

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• Chadwick LR et al. "Therapeutic Perspectives of 8-Prenylnaringenin, a Potent Phytoestrogen from Hops." International Journal of Molecular Sciences (2018) – PMC
• Bowe J et al. "The hop phytoestrogen, 8-prenylnaringenin, reverses the ovariectomy-induced rise in skin temperature in an animal model of menopausal hot flushes." – PMC
• Guo J et al. "Inhibition of human cytochrome P450 enzymes by hops (Humulus lupulus) and hop prenylphenols." – PMC
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• European Medicines Agency (EMA) – Final Assessment Report on Humulus lupulus L., flos (2014)
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• Zanoli P et al. "A first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts." Maturitas (2005)
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