Potential interactions of popular adaptogens (Withania somnifera, Rhodiola rosea) with psychotropic drugs

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Abstract
Purpose: The aim of this review is to synthesize existing literature regarding the neuropharmacological effects and potential drug interactions of the most commonly used adaptogens: Withania somnifera and Rhodiola rosea; and develop practical guidelines for the safe use of these supplements with psychotropic medications. Methods: This narrative review examined clinical, observational, and mechanistic studies regarding Ashwagandha and Rhodiola that were identified through a search of PubMed, Cochrane and ScienceDirect between 2013 and 2024. Results: Ashwagandha has been shown to have significant anxiolytic and stress reducing effects, and has a relatively favorable pharmacokinetic profile. However, it has GABAergic activity which can lead to pharmacodynamic interactions with benzodiazepines, z-drugs, and other central nervous system depressants. Rhodiola, on the other hand, has been shown to have activating and antidepressant-like effects, and has been found to modulate monoaminergic transmission, as well as inhibit the activity of cytochrome P450 enzymes CYP2D6 and CYP3A4. These findings suggest that Rhodiola may increase the risk of serotonin toxicity when combined with certain psychotropic medications, and potentially increase the plasma concentrations of co-administered psychotropics due to decreased metabolic clearance. Conclusions: Based on the findings of this review, both Ashwagandha and Rhodiola cannot be viewed as pharmacologically inert supplements that can be safely used in conjunction with prescription medications for the treatment of psychiatric disorders. Therefore, they should be carefully assessed prior to initiating therapy, with consideration of the individual's concurrent prescription medications and comorbid medical conditions. Furthermore, they should be initiated at low doses and monitored closely for symptoms of sedation, serotonergic effects, and signs of drug accumulation.