HighlightsHops are ubiquitous in modern and ancient cul-ture, with recent research pointing towards efficacyin treatment of mild insomnia[2, 4, 6, 7].Hops are thought to work by modulating theGABAAreceptors.BackgroundHumulus lupulusL., known as Hops, is a memberof the Cannabaceae family and is perennial climbingplant which produces female inflorescences containingtrichomes, which are production sites for many sec-ondary metabolites. Hops have always been of eco-nomic and societal interest mainly due to its usage inbeer production, however, recent research has also re-newed interest in the volatile oils of hops for therapeuticuses[2, 4, 7].Three classes of secondary metabolites are mostprominent in hops – bitter acids, hop essential oils, andpolyphenols. These compounds have been found tohave pharmacological properties ranging from sedativeactivities to estrogenic and chemopreventive activities[2,4, 7].The main essential oils present in hops ared-Limonene,β-Myrcene,β-Ocimene,α-Pinene, Terpino-lene, Geraniol, and Linalool. Sesquiterpenes includeBergamotene, Bisavolene,β-Caryophyllene, and Humu-lene, among many others. Other compounds presentin hops which are known to have biological activity include Humulone and Lupulone, as well as isoxantho-humol (IXN) and 6-prenylnaringenin (6PN). All ofthe biologically active compounds in hops compromiseabout 30% by weight of the cones.In animals, hops have been found to produce seda-tive and hypnotic effects, however in humans, the lupulinand bitter acid compounds from hops do not so clearlyproduce these effects. Some studies which examinedthe effects of the combination of valerian and hops indi-cate that there were some improvements in certain sleepparameters[5, 6], although more research is warranted.Hop research in the last few decades has been largelydedicated to the biological activities of single hop compo-nentsin-vitroin animal models, rather than in clinical trials with humans.Mode of ActionAlthough not much is known about the exact mecha-nisms in which hop components yield sedative effects,recent research has elucidated that one of the mainmodes of action could be through modulation of GABAAreceptors.It was found, electrophysiologically in mice, that hu-mulone is a positive allosteric modulator of GABAAreceptors. Humulone was also found to inhibitcyclooxygenase-2 (COX-2) expression via interactionwith NFkappaB.It was also found that this specific modulation by hu-mulone caused sedative and hypnotic effects in mice.Additionally, it was found that additional hop flavanoidssuch as isoxanthohumol (IXN) and 6-prenylnaringenin(6PN) may also potentiate humulone’s effects via addi-tive mechanisms on the GABAAreceptors.Other prenylated polyphenols and derivatives with aphloroglucinol common substrate also exhibit interestingbiological activities, such as potential inhibition mecha-nisms on the conversion of procarcinogens to carcinogensand radical oxygen species scavenging.Pharmacological EffectsHops have been found to produce sedative and hypnoticeffects in animals, although lupulin and bitter acids didnot cause sleep-inducing effects in humans – however inhumans, valerian in combination with hops was associ-ated with improvements in sleep latency and quality ofsleep[4, 6]. However, not all studies point to improvements in sleep quality in humans, even in combinationwith other compounds.The Committee on Herbal Medicinal Products of theEuropean Medicines Agency (EMEA) report the tradi-tional use of hops for the relief of mild symptoms of men-tal stress and insomnia.As described previously, it is thought that the sleep-inducing effects of hops are related to modulation of theGABAAreceptors, although it is thought that someof the other pharmacological effects seen are also po-tentially due to interactions of the hop compounds withmelatonin and serotonin receptors.Other pharmacological effects of hops include its pro-estrogenic properties due to its flavanone compounds[2,7]. It was seen in somein-vivostudies that standard-ized hop extract was effective in managing menopausalsymptoms with a protective effect on bone loss.The bitter acids in hops also contribute to someantimicrobial activities, including the prevention ofbiofilms[2, 7].Lastly, some hop phenolic compounds such as xan-thohumol are considered cancer-preventive agents andare able to inhibit the progression and initiation of dif-ferent stages of carcinogenesisin-vitro[2, 7]. Addition-ally, oxidative stress and markers of cardiovascular riskand inflammation were also decreased in a fairly limitedstudy.Hops are considered largely safe, with the largest po-tential issue being allergies to the plant itself or largedoses of isolated compounds (such as humulone, whichwould not be present in sufficient quantities in the plantto be harmful).Potential UsesAs discussed above, the traditional use and use sup-ported by literature and various European Healthagencies is for the usage of hops in mild insomnia[4, 6],especially in combination with Valerian root.References A. Benkherouf, K. Eerola, S. Soini, and M. Uusi-Oukari. Humulone modulation of gabaa receptorsand its role in hops sleep-promoting activity.Fron-tiers in Neuroscience, 14:1100, 2020. L. Bocquet, S. Sahpaz, J. L. Hilbert, C. Rambaud,and C. Rivière. Humulus lupulus l., a very popularbeer ingredient and medicinal plant: overview of itsphytochemistry, its bioactivity, and its biotechnology.17(5):1047–1090, 2018.3] C. Cornu, L. Remontet, N. Florence, A. Nico-las, N. Feugier-Favier, P. Roy, B. Claustrat,M. Saadatian-Elahi, and B. Kassaï. A dietary supple-ment to improve the quality of sleep: a randomizedplacebo controlled trial. 10(1), 2010. D. De Keukeleire and A. Heyerick. Prenylflavonoidsaccount for intriguing biological activities of hops.ActaHortic., 668:175–190, 2005. S. Salter and S. Brownie.Australian Family Physi-cian, 39(6):433–437, 2010. C. Ulbricht, E. Basch, S. Basch, W. Chao, J. Con-quer, D. Costa, S. Culwell, C. Dacey, J. Guilford,P. Hammerness, E. Higdon, R. Isaac, M. Lynch,C. Orlando, E. Rusie, M. Varghese, M. Vora,R. Windsor, and J. Woods. Hops (humulus lupulus):An evidence-based systematic review by the natu-ral standard research collaboration.Alternative andComplementary Therapies, 18(2):98–108, 2012. P. Zanoli and M. Zavatti. Pharmacognostic and phar-macological profile of humulus lupulus l.Journal ofEthnopharmacology, 116(3):383–396, 2008.This document was created on November 11, 2021 and last up-dated on November 14, 2021.