Table 5. Drug interactions of Lupuli flos.

ATC therapeutic subgroup	ATC pharmacological/chemical subgroup	Drugs	Pharmacokinetic basis of interaction	Pharmacodynamic basis of interaction	Manifestation of interaction
Endocrine therapy (L02)	Anti-estrogens	Tamoxifen	CYP2C9	Humulus has estrogenic effects (prenylated flavonoids).	antagonistic effect	Harrigan et al. (2021), Yoshimaru et al. (2014)
Analgesics (N02)	Other analgesics and antipyretics, anilides	Paracetamol	CYP1A2 CYP3A4 CYP2E1	β-Caryophyllene affects CB2 receptor	↑ analgetic effect	Horvat et al. (2007), Jakovljevic et al. (2009)
Antiepileptics (N03)	Antiepileptics, barbiturates and derivatives	Phenobarbital	CYP3A4 CYP2C9	Humulus has an α2-agonistic effect (β-myrcene), affects CB2 (β-caryophyllene) and opioid receptors. Humulone is a positive allosteric modulator of GABAA receptors.	additive effect ↑ adverse reactions	Raskovic et al. (2007), Raskovic et al. (2016)
Psycholeptics (N05)	Anxiolytics, benzodiazepine derivatives	Diazepam	CYP1A2 CYP2C19 CYP3A4	Humulus has an α2-agonistic effect (β-myrcene), affects CB2 (β-caryophyllene) and opioid receptors. Humulone is a positive allosteric modulator of GABAA receptors.	additive effect ↑ adverse reactions	Raskovic et al. (2007, 2016)

Note:

ATC, Anatomical Therapeutic Chemical Classification System (WHO, 2023); ↑, increase (of); ↓, decrease (of); !, warning; CB₂, cannabinoid receptor type 2; GABA_A, γ-aminobutyric acid A receptor.