Insomnia, restlessness, and anxiety.
Mechanism of Action
The pharmacological activity of Humulus is principally due to resin (lupulin) from the dried, female-flowering parts (strobiles). It is believed that the constituents in Humulus resin contribute to increasing levels of the neurotransmitter γ-aminobutyric acid (GABA), the chief inhibitory neurotransmitter of the CNS.1
Its sedating effects may be a result of three different categories of constituents acting synergistically: alpha acids, beta acids, and essential oils. 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. Bitter beta acids (lupulones) and essential oils also contribute to the sedating activity of Humulus lupulus.2
Data from in vivo studies in rats have shown that Humulus extracts containing alpha bitter acids exert significant sedative and antidepressant effects, whereas beta acids seem to exhibit antidepressant activity but with fewer sedative effects, probably by affecting GABA neurotransmission activity.3
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.4
In an animal study using female NMRI mice, alcohol/water and CO2 extracts from H. lupulus were tested for sedative qualities. In both types of extracts, spontaneous locomotor activity was reduced, ketamine-induced sleeping time was increased, and body temperature was reduced. These actions indicate a sedating effect on the CNS; however, anxiolytic activity was not observed in the elevated plus maze test for either type of extract. It was found that the sedating activity of Humulus could be attributed to the bitter alpha and beta acids and its essential oil. The most active of three groups of constituents were the alpha acids; however, the beta acids and the essential oil clearly contributed to the sedating activity of lipophilic H. lupulus extracts.2
A randomized, placebo-controlled, double-blind crossover study examined the effects of a Humulus dry extract on self-reported mild depression, anxiety, and stress levels of young healthy adults. The study used two 4-week intervention periods (Humulus or placebo; two 0.2-g capsules once daily) separated by a 2-week interval period. Anthropometric measurements, assessments, and morning cortisol plasma levels were performed at the beginning and the end of the 4-week treatment periods. The authors found no changes in morning cortisol, but they did find significant decreases in anxiety, depression, and stress scores with Humulus compared with placebo.3
Humulus and valerian are traditionally combined together in a formula to promote sleep. A study focused on the question of whether a single dose of the combo can be an effective sleep inducer. Two parallel groups of human participants with chronic insomnia were tested. Of 42 participants, 20 were given a hops/valerian combo and 22 were given placebo. Each subject spent two consecutive nights in the lab, consisting of a reference night and a medication night (herbs or placebo). The poor sleepers in the study were identified by a validated sleep questionnaire (Schlaffragebogen SF-B). The medication consisted of 2 mL of a hops/valerian liquid extract or a similar smelling and tasting placebo. An EEG recording was started 15 minutes after the administration of medication. The data analysis is based on the electrohypnogram—a method of charting sleep over time. It is a validated computer-assisted analysis for depth of sleep. Differences between the reference nights and medication nights were evaluated and tested for significance. Time spent in sleep was significantly higher for the hops/valerian group compared with the placebo group. The time spent in deeper sleep between reference and medication night was also statistically significant. Overall, this study showed that a single administration of hops/valerian combination can have a significant impact on the duration and the depth of sleep compared with placebo.5
There are two notable studies on the sedative effects of nonalcoholic beer made from Humulus. The first study was conducted to analyze sedatives effect of Humulus on the sleep–wake rhythm in a work-stressed population. Test subjects included 17 healthy, but work-stressed, female nurses working rotating shifts, night shifts, or both. Overnight sleep and chronobiological parameters were assessed by actigraphy (a measure of gross motor activity) after moderate ingestion (333 mL) of a nonalcoholic beer containing hops with dinner for 14 days after a 2-week baseline (without Humulus). Results showed improvement of night sleep quality by using parameters of sleep latency and total activity, with both showing a statistically significant reduction in the treatment versus the control group. In addition, the beverage also had reported anxiolytic effects within the treatment group, as assessed by the State-Trait Anxiety Inventory questionnaire. The study authors concluded that the nighttime drinking of hoppy nonalcoholic beer has a significant positive effect on sleep and anxiety in human subjects.1
The second study of the sedative effects of nonalcoholic hoppy beer involved 30 college students. The study took place for 21 days, and The Pittsburgh Sleep Quality Index was used to determine whether there was an improvement in subjective sleep quality. The first 7 days were used for the control, during which no beer was ingested. During the following 14 days the students ingested one nonalcoholic hoppy beer every evening with dinner. Subjective sleep quality improved for the students in the beer-drinking period compared with the control, whereas sleep latency was found to decrease. The Global Score of Quality of Sleep also improved in a statistically significantly manner. This study also concluded that the consumption of nonalcoholic hoppy beer at dinnertime can help to improve the quality of nighttime sleep.6
Safety in Pregnancy and Breastfeeding
Humulus contains the compound 8-prenylnaringenin, a phytoestrogenic compound shown to have selective estrogen receptor–modulating activity both in animals and in vitro studies. No studies have been identified that test the safety of hops in either pregnancy or breastfeeding.7
In the United States, hops and hops oil have generally regarded as safe statuses and have been consumed widely (mainly in beer) with very few adverse reactions (from the hops portion). Farm and brewery workers are the most likely to report allergic reactions to fresh or dried hops.7
Humulus is often combined with other soporific herbs such as valerian, chamomile, and passionflower. The combination is usually taken in 300–1000-mg doses. Alone, Humulus is generally considered safe and can be taken at doses of 600 mg and up to 1200 mg/day. In a concentrated extract form, lower doses are recommended, such as 50–300 mg.
By the end of the 1800s, hops were commonly used in mainstream medicine in the United States to treat insomnia and as bitter to aid digestive upset. In the early 1900s, eclectic physicians in the United States are reported to have used hops as a hypnotic specifically for insomnia because of worry or nerve weakness. A pillow filled with hops is a centuries-old popular folk remedy for sleeplessness.
In North America, several Native American tribes independently discovered the medicinal properties of Humulus for indigestion, as a sedative and sleep aid, and to relieve toothache.
Other traditional uses include the treatment of women’s symptoms associated with menopause such as hot flashes and osteoporosis because of its phytoestrogen content.
PLoS One. 2012;7(7):e37290. doi: 10.1371/journal.pone.0037290. Epub 2012 Jul 18. The sedative effect of non-alcoholic beer in healthy female nurses. Franco L, Sánchez C, Bravo R, Rodríguez AB, Barriga C, Romero E, Cubero J.
3 Hormones (Athens). 2017;16(2):171–80. Effects of a hops (Humulus lupulus L.) dry extract supplement on self-reported depression, anxiety and stress levels in apparently healthy young adults: a randomized, placebo-controlled, double-blind, crossover pilot study. Kyrou I, Christou A, Panagiotakos D, Stefanaki C, Skenderi K, Katsana K, Tsigos C.
5 Eur J Med Res. 2008;13(5):200–4. Sleep improving effects of a single dose administration of a valerian/hops fluid extract – a double blind, randomized, placebo-controlled sleep-EEG study in a parallel design using electrohypnograms. Dimpfel W, Suter A.
6 Acta Physiol Hung. 2014;101(3):353–61. doi: 10.1556/APhysiol.101.2014.3.10. Effect of non-alcoholic beer on subjective sleep quality in a university stressed population. Franco L, Bravo R, Galán C, Rodríguez AB, Barriga C, Cubero J.
7 American Herbal Products Association's Botanical Safety Handbook. 2nd edn., Boca Raton, FL: CRC Press, LLC; 2013. McGuffin, Gardner, eds.