TABLE 2.

Side effects and possible interaction mechanisms of the analyzed adaptogens. ↑ indicating induction and ↓ indicating inhibition.

		Side effect		Interactions with cytochrome	Interactions with p-glycoprotein
Withania somnifera		Somnolence, epigastric pain/discomfort, diarrhea, giddiness, drowsiness, hallucinations, vertigo, rhinitis, cough, cold, decreased appetite, nausea, constipation, dry mouth, hyperactivity, nocturnal cramps, blurring of vision, hyperacidity, skin rash, and weight gain (Tandon and Yadav, 2020)		↑ ↓/none CYP3A4	↓ (Hassan et al., 2021)
				↓/none CYP2D6
				↓ CYP2B6
				↑ CYP1A2
				(Brinker (2010); Savai et al. (2013); Savai et al. (2015); Sultana and Sultan (2018); Kumar et al. (2021b); Haron et al. (2022))
Eleutherococcus senticosus		Insomnia, shifts in heart rhythm, tachycardia, extrasystoles, palpitations, headache, pericardial pain, elevated blood pressure, irritability, melancholy, anxiety, and bleeding (European Medicine’s Agency, 2008)		↓ CYP2C9	↓ (Takahashi et al., 2010)
				↓ CYP2E1
				(Guo et al., 2014)
Schisandra chinensis		Dyspepsia, anorexia, urticaria, restlessness, insomnia, and dyspnea (Bove et al., 2010; St. John, 2018)		↓ CYP3A4	↓ (F. Zhang et al., 2022)
				↓ CYP2B6
				↓ CYP2C8
				↓ CYP2C9
				↓ CYP2C19
				↓ CYP2E1
				(Jiang et al., 2010; Seo et al., 2021b)
Tribulus terrestris		Abdominal pain/distension/discomfort, diarrhea, gastric upset, halitosis, headache, insomnia, irritability, nausea, and priapism (Gama et al., 2014; Campanelli et al., 2016)		↓ CYP3A4	—
				(Wang et al., 2022)
Coptis chinensis		—		↓ CYP3A4	↑ (Yu et al., 2018)
				↓ CYP2C9
				↓ CYP2D6
				(Guo et al., 2012; Yu et al., 2018)
Cimcifuga racemosa		Stiffening of extremities, gastric pain, allergic reactions, gastrointestinal symptoms (dyspeptic disorders and diarrhea), facial edema, and peripheral edema (EMA, 2017)		↓ CYP3A4,	Not significant (Gurley et al., 2006)
				↓ CYP2D6
				(J. Li et al., 2011; Tsukamoto et al., 2005)
Bacopa monnieri		Gastrointestinal symptoms (increased stool frequency, nausea, and abdominal cramps) (Walker and Pellegrini, 2023)		↓ CYP2C9	↓ (Singh et al., 2013)
				↓ CYP2C19
				↓ CYP1A2
				↓ CYP2D6
				↓ CYP3A4
				(Ramasamy et al., 2014)
Gynostema pentaphyllum		Nausea and increased bowel movements (Chen and Su, 1989)		↓ CYP2D6	↓ (Zhu et al., 2012)
				↓ CYP2C8
				↓ CYP3A4
				↓ CYP2C9
				(He et al., 2013)
Cordyceps sinensis		Bleeding, dry mouth, abdominal distension, throat discomfort, and headache (Hatton et al., 2018; X. Yu et al., 2019)		—	—
Lepidium meyenii		—		↓/none CYP3A4	—
				(Brinker, 2010; Ibrahim et al., 2022; Y. Zhang et al., 2019)
Scutellaria baicalensis		Skin allergy, platelet count reduction, pneumonia, and liver damage (Kiguchi et al., 2000; Takeshita et al., 2001; Dhanasekaran et al., 2013; Lin et al., 2016)		↓ CYP2C9	↓ (Miao et al., 2016)
				↑ CYP2E1
				↓ CYP2C19
				↓CYP4F2
				↓/↑ CYP3A4
				↓/↑ CYP2B6
				↓ CYP1A2
				(Zhou et al., 2021)