Science‑based data on adaptogens

Adaptogens are bioactive substances from plants that increase the body’s nonspecific resistance to stress and help return physiological functions toward homeostasis when exposed to physical, chemical or psychological stressors. Research emphasises that adaptogens act through multiple pathways: modulation of the hypothalamic–pituitary–adrenal (HPA) axis, anti‑inflammatory and antioxidant effects, interaction with neurotransmitter systems (serotonin, dopamine, GABA), regulation of immune function and energy metabolism, and in some cases stimulation of protein synthesis. The table at the end summarises key compounds, doses and evidence for each adaptogen.

Ashwagandha (Withania somnifera)

Active compounds – Roots and leaves contain withanolide steroidal lactones such as withanolide A and withanone. These molecules are the most biologically active constituents and are thought to interact with glucocorticoid receptors and enhance γ‑aminobutyric acid (GABA) signalling. pmc.ncbi.nlm.nih.gov.

Mechanisms – Pre‑clinical studies show that ashwagandha extracts or purified withanolides reduce pro‑inflammatory cytokines (TNF‑α, IL‑1β and IL‑6) and improve cognitive performance in animal models with neurotoxicity pmc.ncbi.nlm.nih.gov. A narrative review notes that ashwagandha decreases morning cortisol by interacting with glucocorticoid receptors and modulates GABAergic activity nutritionandmetabolism.biomedcentral.com. The plant is therefore classified as an adaptogen because it dampens stress responses and promotes homeostasis.

Clinical evidence – A 2025 meta‑analysis of 15 trials (873 participants) concluded that ashwagandha supplementation significantly reduces anxiety and stress scores and lowers cortisol levels at eight weeks, although improvements in quality of life were not statistically significant pmc.ncbi.nlm.nih.gov. Typical doses in these trials ranged from 250–600 mg/day of root extract for 4–13 weeks nutritionandmetabolism.biomedcentral.com. Small trials of 330–1000 mg/day for 2–12 weeks suggest that ashwagandha may improve cardiorespiratory fitness, strength and VO₂max in athletes nutritionandmetabolism.biomedcentral.com.

Safety – Generally well tolerated; mild adverse effects such as gastrointestinal upset and somnolence occur. Ashwagandha may interact with sedatives and thyroid medications.

Passiflora incarnata (passionflower)

Active compounds – The aerial parts contain C‑glycoside flavonoids—vitexin, isovitexin, schaftoside, isoschaftoside, orientin, iso‑orientin and swertisin—and free flavonoids like apigenin, luteolin, quercetin, kaempferol and chrysin pmc.ncbi.nlm.nih.gov. β‑carboline alkaloids (harmine, harmol, harmaline, harmalol and harman) are present in small amounts pmc.ncbi.nlm.nih.gov.

Mechanisms – Passiflora flavonoids act as partial agonists at the benzodiazepine‑binding site of the GABA\u00a0A receptor. They inhibit uptake of [³H]‑GABA into synaptosomes, modulate chloride flow and produce anxiolytic effects without sedation pmc.ncbi.nlm.nih.gov. Chrysin and apigenin bind to benzodiazepine receptors and increase pentobarbital‑induced hypnosis in mice pmc.ncbi.nlm.nih.gov.

Dosage – The European Medicines Agency’s assessment report recommends that hydroalcoholic extracts of P. incarnata contain at least 2 % flavonoids (expressed as vitexin), and typical herbal medicines provide 20–30 mg/day of total flavonoids pmc.ncbi.nlm.nih.gov. Some products contain 30–120 mg of total flavonoids per daypmc.ncbi.nlm.nih.gov.

Clinical evidence – A 2024 randomized double‑blind trial in stressed adults reported that passiflora extract significantly decreased perceived stress scores and increased total sleep time compared with placebo and improved general psychological well‑being without adverse effects pmc.ncbi.nlm.nih.gov. In a 2023 real‑world study, patients who received passiflora extract while tapering benzodiazepines reduced their dose by 36.6 % after eight weeks compared with 20.4 % in controls and experienced greater improvements in anxiety and depression scores pmc.ncbi.nlm.nih.gov.

Safety – Well tolerated in trials; mild sleepiness may occur. The plant’s β‑carboline alkaloids can potentiate sedatives.

Lemon balm (Melissa officinalis)

Active compounds – Lemon balm contains essential oils (geranial, neral, citronellal and geraniol), triterpenes (ursolic and oleanolic acids), phenolic acids such as rosmarinic, caffeic and chlorogenic acids, and flavonoids (quercetin, rhamnocitrin and luteolin) pmc.ncbi.nlm.nih.gov. Rosmarinic acid is considered the main phenolic constituent.

Clinical evidence – A double‑blind trial found that 1000 mg/day of lemon balm extract for two weeks significantly reduced episodes of heart palpitations and improved anxiety, sleep and depression compared with placebo pmc.ncbi.nlm.nih.gov. Another eight‑week trial using 2000 mg/day produced antidepressant effects comparable to fluoxetine pmc.ncbi.nlm.nih.gov. Combined with valerian or fennel, lemon balm improved sleep quality in menopausal women; however, other trials using 80–400 mg/day showed mixed results, with some reporting improvements in sleep quality and mood and others finding little or only subjective benefit pmc.ncbi.nlm.nih.gov.

Mechanisms – Rosmarinic acid inhibits GABA transaminase and increases GABA levels; essential oils may modulate cholinergic and serotonergic systems. The plant’s antioxidant and anti‑inflammatory effects contribute to its adaptogenic properties.

Panax ginseng

Active compounds – Ginseng roots contain ginsenosides (triterpene saponins), including Rb₁, Rb₂, Rc, Rd, Re, Rg₁ and Rg₃; polysaccharides and polyphenols are also present. Hydroponically grown red ginseng with 24 mg ginsenosides per 200 mg dose has been used in clinical trials pmc.ncbi.nlm.nih.gov.

Mechanisms – Ginseng exerts adaptogenic effects by modulating the HPA axis, regulating neurotransmitters (serotonin, dopamine and GABA), enhancing antioxidant defences and inhibiting pro‑inflammatory mediators. Ginsenosides reduce nitric oxide and cytokine production (TNF‑α, IL‑6, IL‑1β) in LPS‑stimulated cells and increase anti‑inflammatory IL‑10 pmc.ncbi.nlm.nih.gov. The plant also improves immune function and energy metabolism pmc.ncbi.nlm.nih.gov.

Clinical evidence – In a 2025 double‑blind trial involving 149 moderately stressed adults, supplementation with 200 mg/day hydroponic red ginseng for three weeks resulted in significantly greater reductions in Perceived Stress Scale scores and negative affect, and faster reaction times compared with placebo pmc.ncbi.nlm.nih.gov. Mechanistic analysis in the same article noted that ginseng influences the HPA axis, neurotransmitters and inflammatory pathways pmc.ncbi.nlm.nih.gov. Earlier clinical trials summarised in reviews report improvements in fatigue, cognitive function and immunity, though results vary and many studies are small or short‑term pmc.ncbi.nlm.nih.gov.

Rhodiola rosea

Active compounds – Rhodiola roots contain phenylpropanoids such as salidroside, rosavin, rosin and rosarin, along with flavonoids and phenolic acids.

Mechanisms – Extracts inhibit NF‑κB translocation and reduce interleukin‑6 in stress‑model cell lines, improving cytokine balance pmc.ncbi.nlm.nih.gov. Pre‑clinical studies show that rhodiola modulates energy metabolism, increases glycogen stores, enhances antioxidant capacity and delays fatigue pmc.ncbi.nlm.nih.gov.

Clinical evidence – Human trials are limited and small. A 20‑day study of 100 mg/day rhodiola extract reduced self‑reported mental fatigue by ~30 % compared with an increase in the placebo group; a 28‑day study of 600 mg/day improved reaction times; and a 30‑day trial of 600 mg/day improved viral resistance in marathon runners pmc.ncbi.nlm.nih.gov. Overall, rhodiola may enhance mental performance and reduce fatigue, but evidence quality is modest.

Rhaponticum carthamoides (Leuzea, maral root)

Active compounds – The roots of leuzea contain phytoecdysteroids, principally 20‑hydroxyecdysone, and phenolic acids. Ecdysteroids are structurally similar to insect molting hormones and may stimulate protein synthesis.

Mechanisms and evidence – A 2020 rat study evaluated acute and chronic supplementation of Rhaponticum carthamoides (Rha) extract alone or in combination with Rhodiola rosea after resistance exercise. Doses were scaled from human equivalents: Rha 500 mg/day (8.33 mg/kg) and combination doses 100–1000 mg/day d-nb.info. Supplementation immediately after exercise enhanced muscle protein synthesis more than exercise alone, and after four weeks the groups receiving Rha or Rha + Rhodiola showed higher mean power performance without changes in muscle mass d-nb.info. These findings suggest that leuzea has anabolic and adaptogenic properties, especially when combined with rhodiola. Robust human studies are lacking.

Key points

Adaptogens act through multiple mechanisms – They support stress resilience by modulating the HPA axis, neurotransmitter systems, inflammation, oxidative stress and energy metabolism. Many adaptogens also possess immunomodulatory and neuroprotective properties.

Evidence quality varies – Ashwagandha and ginseng have the most robust human data showing reductions in stress and anxiety and improvements in mental performance. Passiflora and lemon balm show promise for anxiety and sleep, though evidence is limited to a few trials and products vary in flavonoid content. Rhodiola shows modest benefits for fatigue and mental performance, while leuzea’s adaptogenic claims rely mainly on pre‑clinical data. Ginkgo biloba has mixed evidence for cognitive benefits and cannot be recommended to prevent dementia.

Safety – Most adaptogens are well tolerated when used in recommended doses, but interactions with medications (e.g., anticoagulants, sedatives) should be considered. High‑quality standardised extracts and guidance from healthcare professionals are advisable, especially for individuals with chronic diseases or those taking multiple medications.