Herb-Drug Interactions: Hops

Humulus lupulus L. (Cannabaceae)

Synonym(s) and related species

Humulus, Lupulus.

Pharmacopoeias

Hop Strobile (British Ph 2009, Eur Ph 6.4).

Constituents

The flowers (strobiles) of hops contain a volatile oil composed mainly of humulene (alpha-caryophyllene), with beta-caryophyllene, myrcene, famesene and others. There is also an oleo-resin fraction composed of bitter acids. Flavonoids present include glycosides of kaempferol and quercetin, and a series of prenylated flavonoids (including 6-prenylnaringenin) and prenylated chalcones. A number of hop proanthocyanidins, based on gallocatechin, afzelechin and epicatechin derivatives, and the trans isomer of the stilbenoid resveratrol and its glucoside, piceid, have also been isolated. Note that a large variety of hops genotypes exist, and the relative content of these constituents may vary between genotype.

Use and indications

Hops are used mainly as a sedative, anxiolytic, hypnotic and tranquilliser. These properties have been demonstrated pharmacologically but there is little clinical evidence to date. Hops also contain a number of compounds with oestrogenic activity such as 6-prenylnaringenin. Many products include hops as one of several ingredients rather than as a single extract. There are also many varieties of hops, normally produced for their flavour and other characteristics useful for beer production. The variety used medicinally is usually not stated.

Pharmacokinetics

Most of the investigations carried out into the metabolism of hops have concerned the metabolism of isoxanthohumol to the more potent phytoestrogen 8-prenylnaringenin by human liver microsomes, and by intestinal microflora, particularly in the colon. These studies suggest that the levels of active constituents vary between individuals, and may be altered by antibacterial treatment, which suggests that the activity (particularly the oestrogenic activity) of hops, and its potential to interact, is also likely to vary between individuals. The cytochrome P450 isoenzymes CYP1A2, CYP2C19 and CYP2C8 may be involved, but information is too sparse to be able to comment further on the potential for conventional drugs to diminish the effects of hops.

See under flavonoids, for information on the individual flavonoids present in hops, and see under resveratrol, for the pharmacokinetics of resveratrol.

Interactions overview

Animal studies suggest that hops extracts potentiate the analgesic effects of paracetamol, suppress the stimulant effects of cocaine, suppress the effects of diazepam and potentially alter the sedative effects of pentobarbital. For information on the interactions of flavonoids, see under flavonoids, and for the interactions of resveratrol, see under resveratrol.

Hops + Cocaine

The interaction between hops and cocaine is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

In a study of the interactions of various genotypes of hops, mice were given cocaine 25 mg/kg after they had received four intraperitoneal doses of a 0.5% alcoholic extract of hops. Three hops genotypes were used: Aroma, Magnum and wild hops. The study found that the Magnum hops extracts almost completely suppressed the excitatory effects of cocaine (measured by spontaneous motility), when compared with controls. Extracts of the wild genotype also decreased the excitatory effects of cocaine, but to a lesser extent than the Magnum genotype, whereas the Aroma genotype did not alter the effects of cocaine.

Mechanism

It has been suggested that hops may alter the effects of cocaine on the central nervous system, but it is not known how this occurs.

Importance and management

Evidence appears to be limited to this one study in mice, the clinical relevance of which is unclear. What is known suggests that any interaction may be advantageous or, more likely, not clinically important. Of more interest is the variability in the interaction between the different hops genotypes, which suggests that the exact source of the hops used in any preparation is likely to be of importance in establishing their potential for interactions.

Hops + Diazepam

The interaction between hops and diazepam is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

In study of the interactions of various genotypes of hops, mice were given diazepam 3 mg/kg after they had received four intraperitoneal doses of a 0.5% alcoholic extract of hops. Three hops genotypes were used: Aroma, Magnum and wild hops. The study found that the hops extracts suppressed the effects of diazepam (assessed by coordination of movements). The most pronounced effect occurred with the extracts of Magnum and Aroma genotypes whereas the wild genotype had no significant effect.

Mechanism

It has been suggested that hops may prevent diazepam exerting its effect on GABA receptors in the central nervous system, thereby diminishing its effects.

Importance and management

Evidence appears to be limited to this one study in mice, the clinical relevance of which is unclear. What is known suggests that hops may diminish the effects of diazepam, which is in contrast to what would be expected, given that hops is given for similar reasons to diazepam. It is difficult to extrapolate these findings to humans, but there appears to be no good reason to avoid concurrent use. Of more interest is the variability in the interaction between the different hops genotypes, which suggests that the exact source of the hops used in any preparation is likely to be of importance in establishing their potential for interactions.

Hops + Food

No interactions found.

Hops + Herbal medicines

No interactions found.

Hops + Oestrogens or Oestrogen antagonists

Hops contains oestrogenic compounds. This may result in additive effects with oestrogens or it may oppose the effects of oestrogens. Similarly, hops may have additive effects with oestrogen antagonists or oppose the effects of oestrogen antagonists (e.g. tamoxifen). See Chinese angelica + Oestrogens or Oestrogen antagonists for more information.

Hops + Paracetamol (Acetaminophen)

The interaction between hops and paracetamol is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

In a study of the interactions of various genotypes of hops, mice were given paracetamol 80 mg/kg after they had received four intraperitoneal doses of a 0.5% alcoholic extract of hops. Three hops genotypes were used: Aroma, Magnum and wild hops. The study found that the hops extracts alone did not possess an analgesic effect, but each of the extracts increased the analgesic effect of paracetamol 80 mg/kg, with the most pronounced effect occurring with the extracts of Aroma and wild genotypes hops.

Mechanism

Unknown.

Importance and management

Evidence appears to be limited to this one study in mice, the clinical relevance of which is unclear. What is known suggests that any interaction may be advantageous. Of more interest is the variability in the interaction between the different hops genotypes, which suggests that the exact source of the hops used in any preparation is likely to be of importance in establishing their potential for interactions.

Hops + Pentobarbital

The interaction between hops and pentobarbital is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

In a study of the interactions of various genotypes of hops, mice were given pentobarbital 40 mg/kg after they had received four intraperitoneal doses of 0.5% alcoholic extract of hops. Three hops genotypes were used: Aroma, Magnum and wild hops. The study found that the hops extracts suppressed the hypnotic effects of pentobarbital (measured by a decrease in the sleeping time of the mice). The most pronounced effect occurred with the extracts of Magnum and Aroma genotypes whereas the wild genotype had no significant effect. However, the effects varied greatly between individual mice, with some sleeping for a longer time.

Mechanism

It has been suggested that hops may alter the effects of phenobarbital on the central nervous system, but it is not known how this occurs.

Importance and management

Evidence appears to be limited to this one study in mice, the clinical relevance of which is unclear. What is known suggests that hops may slightly decrease the sedative effects of pentobarbital in some individuals, or increase them in others. It is difficult to extrapolate these findings to humans, but there appears to be no good reason to avoid concurrent use, although patients should be aware that there is a possibility that they may be more or less sedated than with either medicine alone. Of more interest is the variability in the interaction between the different hops genotypes, which suggests that the exact source of the hops used in any preparation is likely to be of importance in establishing their potential for interactions.