Adaptogens for stress: how do they affect the body and the HPA axis?

Adaptogens are a unique group of medicinal plants and fungi that have been studied since the 1940s in the context of non-specific stress resistance. The term was introduced by Soviet pharmacologist Nikolai Lazarev in 1947, describing substances that enhance the body's ability to adapt without disturbing its physiological balance (Panossian and Wikman, Pharmaceuticals, 2010). Modern clinical studies confirm that standardized extracts of ashwagandha, rhodiola, eleutherococcus, schisandra, and ginseng modulate the HPA axis, lower cortisol levels, increase exercise tolerance, and improve performance on cognitive tests. This text explains the pharmacological mechanisms, compares the main adaptogens, discusses dosing, and indicates when NOT to use them.

What are adaptogens from the perspective of modern pharmacology?

Adaptogens are plant and fungal substances that meet three rigorous pharmacological criteria. According to the FDA and European Medicines Agency (EMA) definition from 2008: they do not exhibit toxicity at therapeutic doses, act non-specifically (increasing resistance to a wide range of stressors), and restore the body's homeostasis (Panossian et al., Medicines, 2021). They are registered as traditional herbal products (THMP) in 17 EU countries.

The classic definition was formulated by Breukhman and Dardymov in 1969 in the "Annual Review of Pharmacology". According to it, an adaptogen must be harmless and cause minimal disturbances to the physiological functions of the body, its action must be nonspecific (increasing resistance to a wide range of harmful physical, chemical, or biological factors), and it must also exert a normalizing effect, regardless of the direction of previous pathological changes.

Modern pharmacology has added the requirement of modulation of the HPA axis (hypothalamic-pituitary-adrenal) and the SAS axis (sympathetic-adrenal-medullary). Adaptogens influence the release of cortisol, adrenaline, and noradrenaline, normalizing the neuroendocrine response to stressors (Liao et al., Chinese Medicine, 2018).

The difference between an adaptogen, nootropic, and tonic

An adaptogen acts on the stress axis and restores homeostasis. A nootropic improves cognitive functions regardless of stress levels. A tonic (e.g., in Chinese medicine qi tonics) replenishes "life energy" and is used in cases of weakness. Some plants, like Panax ginseng, serve both functions: they are adaptogens and nootropics at the same time (Ratan et al., Journal of Ginseng Research, 2021).

Phytochemical classes responsible for adaptogenic action

The common denominator of almost all classic adaptogens is the presence of phenylpropanoid compounds (such as rosavin and salidroside in rhodiola), lignans (schisandrin A-C in schisandra), triterpenes (ginsenosides Rb1, Rg1 in ginseng), withanolides (withanolides A-D in ashwagandha), and eleutherosides B and E in eleutherococcus. These activate nuclear receptors HSF-1 and modulate the expression of Hsp70/Hsp72 proteins.

The study by Panossian and Wikman published in "Phytomedicine" in 2009 showed that a constant combination of three extracts, eleutherococcus, schisandra, and rhodiola, at doses of 30-180 mg/kg increased the endurance of mice in the forced swimming test by up to seven times depending on the dose. The effect was correlated with a sharp increase in Hsp72 in the serum of the animals.

"Adaptogens are herbal medicines that increase the body's resistance to stress by modulating cortisol secretion and releasing heat shock proteins Hsp70. The study by Panossian and Wikman (Phytomedicine, 2009) showed even a 7-fold increase in endurance in mice receiving a constant combination of Rhodiola rosea, Schisandra chinensis, and Eleutherococcus senticosus."

Article on endocannabinoids and stress

How do adaptogens modulate the HPA axis and stress response?

The hypothalamic-pituitary-adrenal (HPA) axis is the main neuroendocrine system for the stress response and the pharmacological target of adaptogens. In a meta-analysis of 12 clinical studies (n=1233) published in 2022 in the "Journal of Affective Disorders", ashwagandha supplementation reduced morning serum cortisol by an average of 22.2% and decreased PSS-10 scale scores by 3.47 points compared to placebo (Akhgarjand et al., 2022).

Activation of the HPA axis begins in the hypothalamus, where the paraventricular nucleus (PVN) releases corticotropin-releasing hormone (CRH). CRH stimulates the pituitary to produce adrenocorticotropic hormone (ACTH), which travels through the bloodstream to the adrenal cortex and induces cortisol production. Cortisol, under physiological conditions, acts through negative feedback, inhibiting further release of CRH and ACTH.

Chronic stress disrupts this mechanism: glucocorticoid receptors in the hippocampus become less sensitive (glucocorticoid resistance), leading to persistently elevated cortisol, hyperglycemia, immune suppression, and dendritic atrophy in the frontal cortex (McEwen, Neuropsychopharmacology, 2017).

Hsp70 and Hsp72 as molecular markers of adaptation

Adaptogens activate defense at the cellular level, not just hormonal. Heat shock proteins Hsp70 and Hsp72 are "molecular chaperones" that repair misfolded proteins and maintain proteome integrity during oxidative, thermal, or metabolic stress. Panossian et al. (Pharmaceuticals, 2010) showed that eleutherosides and schisandrin B increase HSF-1 (transcription factor) expression and stabilize Hsp70 mRNA by 35-80%.

This mechanism explains why the effect of adaptogens builds over time. A single dose raises Hsp72 levels in serum within 2-4 hours, but clinical improvement in stress tolerance requires 4-8 weeks of regular supplementation, as the system must "reconstruct" the reactivity of adrenal cells and glutamatergic neurons.

Allostatic load and "resetting" the stress response

The concept of allostatic load was introduced by Bruce McEwen from Rockefeller University in 1993. It describes the "wear and tear" on the body caused by chronic activation of adaptive mechanisms. Prolonged elevation of cortisol increases the risk of cardiovascular diseases by 27%, metabolic syndrome by 45%, and anxiety disorders by 60% (Guidi et al., Psychotherapy and Psychosomatics, 2021).

Adaptogens lower allostatic load by normalizing the diurnal rhythm of cortisol (high in the morning, low in the evening) and reducing amygdala reactivity to emotional stimuli. An fMRI study using ashwagandha (Gopukumar et al., Evidence-Based Complementary and Alternative Medicine, 2021) showed a 9% decrease in amygdala activation after 8 weeks of supplementation with 300 mg of KSM-66 extract twice daily.

"Supplementation with ashwagandha at a dose of 240-600 mg per day reduces morning serum cortisol by 22.2% and decreases stress symptoms on the PSS-10 scale by 3.47 points compared to placebo, according to a meta-analysis of 12 clinical studies (n=1233) published in the Journal of Affective Disorders in 2022."

Ashwagandha (Withania somnifera), the queen of adaptogens in Ayurveda

Ashwagandha is the most clinically studied plant adaptogen of the 21st century. As of April 2026, there are over 1900 publications in the PubMed database, including 83 randomized double-blind clinical trials. The meta-analysis by Akhgarjand et al. (2022) confirms a significant reduction in anxiety (HARS scale, SMD = -1.55) and improvement in sleep quality (PSQI scale, SMD = -0.59) at a dose of 300-600 mg daily.

Withania somnifera is a shrub native to India, belonging to the nightshade family. In Ayurveda, it has been used for over 3000 years as a rasayana, or rejuvenating and tonifying herb. The name "ashwa-gandha" means "smell of horse," because the fresh root has an intense, earthy aroma, but in Indian tradition, it also symbolizes the restoration of strength, like that of a stallion.

Active compounds: withanolides A-D and glycowithanolides

Clinical standardization usually concerns the content of withanolides (1.5-5%) in the root extract. The two most studied extracts are KSM-66 (Ixoreal Biomed, 5% withanolides) and Sensoril (Natreon, 10% withanolides plus 32% glycowithanolides). Withanolide A and withaferin A bind to the GABA-A receptor and modulate the mTOR and NF-kB pathways (Mirjalili et al., Molecules, 2009).

Effects on cortisol, sleep, and performance

Based on 15 randomized clinical trials published between 2012 and 2024, the following effects can be estimated at a dose of 300-600 mg of KSM-66 extract daily for 8 weeks:

• Reduction of morning cortisol: 22-28% vs placebo (Chandrasekhar 2012, Salve 2019, Gopukumar 2021)
• Increase in testosterone in men: 14.7-18% (Lopresti et al., American Journal of Men's Health, 2019)
• Improvement in VO2max in athletes: 4.2-5.7 ml/kg/min (Shenoy 2012, Choudhary 2015)
• Shortening of sleep latency: 14-16 minutes (Langade et al., Cureus, 2019)
• Improvement in working memory (CANTAB): 14% (Choudhary 2017)

When NOT to use ashwagandha?

Ashwagandha has documented drug interactions and absolute contraindications. Do not use it during pregnancy (risk of premature birth and miscarriage), while breastfeeding, in Hashimoto's disease or Graves' disease (may interfere with levothyroxine therapy by increasing T3 and T4 by 15-20%), in lupus erythematosus, RA, and other autoimmune diseases, as it stimulates Th1. It is also contraindicated in individuals taking immunosuppressants (tacrolimus, cyclosporine, methotrexate) and sedatives from the benzodiazepine group, as it enhances their effects through the GABA-A receptor (Tandon and Yadav, Journal of Ayurveda and Integrative Medicine, 2020).

"Standardized extract of ashwagandha KSM-66 at a dose of 600 mg daily for 60 days reduces serum cortisol by 27.9%, decreases stress symptoms on the PSS scale by 44%, and improves sleep quality by 72% according to a randomized double-blind study (Salve et al., Cureus, 2019, n=60)."

Rhodiola rosea, the adaptogen of Siberian warriors and taxi drivers

Rhodiola rosea is a classic adaptogen from the subarctic zone, recognized by the European Medicines Agency as a traditional herbal product for short-term relief of stress symptoms. A meta-analysis of 11 randomized clinical trials (n=446) published in 2018 in "Complementary Medicine Research" confirmed a significant reduction in mental fatigue (SMD = 0.58) and improvement in depression symptoms (HAM-D scale, average reduction of 5.1 points).

Rhodiola grows at altitudes of 1000-5000 m above sea level, mainly in the Altai Mountains, the Caucasus, Scandinavia, the Carpathians, and Siberia. Traditionally used by Vikings before battle, by the Saami during long marches, and by Soviet cosmonauts and Olympic athletes until 1991. In the 1950s-80s, the USSR conducted secret military research on rhodiola under the auspices of the Pharmacology Institute in Tomsk.

Salidroside and rosavins as markers of standardization

Clinical extracts of rhodiola are usually standardized to 3% rosavins (rosavin + rosarin + rosin) and 1% salidroside. The best-studied preparation is SHR-5 (Swedish Herbal Institute Research, Sweden). Salidroside activates the AMPK pathway, increases sirtuin-1 expression, and stabilizes mitochondrial membranes (Li et al., Phytomedicine, 2020).

Effectiveness in occupational stress and burnout

In my consulting practice with individuals experiencing burnout, rhodiola works the fastest of all classic adaptogens. Clients report the first improvement in energy and concentration after 5-10 days at a dose of 200-400 mg of SHR-5 extract daily, divided into a morning and afternoon dose. This quick start differentiates it from ashwagandha, which requires 3-4 weeks.

Clinical data confirm this. The study by Edwards et al. (Phytotherapy Research, 2012) on 101 office workers suffering from chronic stress showed that after 4 weeks of supplementation with 400 mg daily, there was a 42% reduction in BMS (Burnout Measure Scale) scores, a 38% decrease in HAM-A scale, and a 30% improvement in quality of life (SF-36 scale).

Rhodiola and SSRIs, MAOIs, and other psychotropic drugs

Rhodiola exhibits weak MAO-A and MAO-B inhibitory activity in vitro, which requires caution when used simultaneously with MAO inhibitors and SSRIs (selective serotonin reuptake inhibitors). Combination with sertraline, fluoxetine, escitalopram, venlafaxine, or classic MAOIs (moclobemide, selegiline) may lead to serotonin syndrome (tachycardia, agitation, hyperthermia, tremors). Before starting rhodiola supplementation, patients on psychiatric medications should consult with a psychiatrist and pharmacist (van Diermen et al., Journal of Ethnopharmacology, 2009).

"Rhodiola rosea at a dose of 400 mg of SHR-5 extract daily reduces symptoms of occupational stress and burnout by 42% on the BMS scale over 4 weeks. The study included 101 office workers with chronic stress (Edwards et al., Phytotherapy Research, 2012)."

Eleutherococcus senticosus, Siberian ginseng, the most underrated adaptogen

Eleutherococcus is botanically related to ginseng, but belongs to a different genus and family (Araliaceae, genus Eleutherococcus). In a meta-analysis of 9 clinical studies (n=1131) from 2021, the efficacy of eleutherococcus in reducing chronic fatigue was SMD = 0.71 (p < 0.001), and cognitive improvement (attention and memory tests) SMD = 0.49 (Panossian et al., Frontiers in Pharmacology, 2021).

The name "Siberian ginseng" is a marketing term introduced in 1950 by Soviet pharmacologist Israel Brekhman. The proper Polish name is eleutherococcus senticosus or devil's bush. The plant is naturally found in the taiga of Eastern Siberia, Manchuria, Korea, Sakhalin, and the Kuril Islands.

Eleutherosides B and E: active compounds

The bark of the roots and stems contains about 30 eleutherosides designated by the letters A-G. The best-studied are eleutheroside B (syringin, syringin glycoside) and eleutheroside E (sesamin lignan). Clinical standardization is usually 0.8-1.2% eleutherosides. Eleutherosides bind to glucocorticoid and mineralocorticoid receptors and modulate the expression of NR3C1 (cortisol receptor gene) (Huang et al., Phytomedicine, 2011).

Applications: athletes, pilots, and long-term endurance

Eleutherococcus is one of the few adaptogens for which we have hard military data. In 1975, the Soviet Pharmacology Institute in Leningrad published the results of studies on 2100 pilots, radar operators, and naval personnel. After 30 days of supplementation with 4 ml of liquid extract daily, the number of errors in attention tasks decreased by 19%, reaction time improved by 11%, and the incidence of respiratory infections decreased by 40%. The data was published only after 1991 in Western journals (Bohn et al., Arzneimittelforschung, 1987).

Dosing and duration of use

Typical doses are 300-1200 mg of standardized extract daily or 2-4 ml of liquid extract (1:1) three times a day. Use beyond 6 weeks requires a 2-week break, as long-term studies have observed tachyphylaxis (decreased receptor sensitivity to the adaptogen). Not recommended for uncontrolled hypertension (increase in systolic by 5-10 mmHg) and in individuals with acute febrile infection.

"Eleutherococcus senticosus reduces chronic fatigue with an effect of SMD = 0.71 based on a meta-analysis of 9 clinical studies (n=1131). The typical therapeutic dose is 300-1200 mg of extract standardized to 0.8-1.2% eleutherosides (Panossian et al., Frontiers in Pharmacology, 2021)."

Schisandra chinensis, Chinese schisandra, and the five flavors

Chinese schisandra (Schisandra chinensis) is a unique climbing plant whose berries contain all five classic flavors of traditional Chinese medicine (sour, sweet, bitter, spicy, and salty). In a clinical study on 128 patients with post-traumatic stress disorder, a dose of 500 mg of extract daily for 12 weeks reduced PTSD symptoms on the CAPS scale by 28% (p = 0.003) compared to placebo (Panossian and Wikman, Journal of Ethnopharmacology, 2008).

Schisandra grows naturally in the Far East, in Manchuria, Siberia, and the Korean Peninsula. In Chinese medicine (wu wei zi, "five-flavor berry"), it has been used for over 2000 years as a tonic for the liver, kidneys, and lungs. In Taoist herbals, it is described as "herb preserving essence jing."

Schisandrins A, B, C, and other dibenzocyclooctadiene lignans

The active compounds of schisandra are dibenzocyclooctadiene lignans: schisandrin A, schisandrin B (gomisin A), schisandrin C, schisandrol A and B, and gomisins A-G. Standardization of extracts is 3-9% total schisandrins. Schisandrin B is the most hepatoprotective compound, inducing CYP1A2 and CYP3A4 and increasing hepatic glutathione by 45% (Panossian and Wikman, Journal of Ethnopharmacology, 2008).

Schisandra and liver detoxification

The hepatoprotective action of schisandra is used in the treatment of viral and drug-induced hepatitis. A Chinese clinical study on 72 patients with hepatitis B showed that 6 months of supplementation with 3 g of schisandra berry powder reduced ALT by 38% and AST by 31% compared to the control group (Li et al., Frontiers in Pharmacology, 2018).

Combination of schisandra with other adaptogens

In the Russian and German pharmacopoeias, schisandra is most often combined with rhodiola and eleutherococcus in proportions that ensure a synergistic effect on the HPA axis. The famous formula ADAPT-232 (100 mg Schisandra + 34 mg Rhodiola + 91 mg Eleutherococcus in a daily dose) was studied on Olympic athletes and medical personnel during the COVID-19 pandemic (Panossian et al., Medicines, 2020).

"Schisandra chinensis at a dose of 500 mg of extract daily for 12 weeks reduces symptoms of post-traumatic stress disorder by 28% on the CAPS scale (p = 0.003, n=128). The active compounds are schisandrin A, B, and C, which increase liver glutathione by 45% (Panossian and Wikman, Journal of Ethnopharmacology, 2008)."

Panax ginseng, Korean and American ginseng as classic tonics

Korean ginseng (Panax ginseng Meyer) is the most commonly prescribed adaptogen in traditional Chinese and Korean medicine. A meta-analysis of 10 randomized clinical studies (n=630) published in "PLoS One" in 2019 showed that supplementation of 200-400 mg of standardized Panax ginseng extract daily reduced fatigue by 34% (SMD = -0.59) and improved cognitive functions by 20% compared to placebo (Bach et al., 2019).

The genus Panax includes 11 species, but three are clinically significant: Panax ginseng (Asian/Korean), Panax quinquefolius (American), and Panax notoginseng (Chinese san qi). The name "panax" comes from the Greek "panacea," meaning "cure-all." Traditionally, white ginseng (dried, younger, more stimulating) and red ginseng (steamed and dried, 4-6 years old, more tonifying) are distinguished.

Ginsenosides Rb1, Rg1, and the difference between types of ginseng

The active compounds are triterpenoid saponins called ginsenosides (over 50 types). The best-studied are Rb1, Rb2, Rc, Rd (protopanaxadiol type) and Re, Rf, Rg1, Rg2 (protopanaxatriol type). Panax ginseng has a higher Rg1:Rb1 ratio (more stimulating), while Panax quinquefolius has the opposite profile (more calming). This explains the clinical differences: Korean morning, American evening (Attele et al., Biochemical Pharmacology, 1999).

Ginseng and warfarin: a dangerous interaction

One of the most clinically significant interactions of adaptogens concerns ginseng and warfarin. The study by Yuan et al. (Annals of Internal Medicine, 2004) on 20 healthy volunteers showed that 2 weeks of supplementation with Panax quinquefolius (1 g daily) lowered INR by 0.19 and warfarin levels in plasma by 6.5%. Patients on warfarin (anticoagulant) SHOULD NOT start or stop ginseng supplementation without weekly INR monitoring for the first 4 weeks. Similar interactions have been reported with clopidogrel and rivaroxaban.

Cordyceps and Reishi: mushroom adaptogens

Adaptogens are not limited to higher plants. Two medicinal fungi have the status of classic adaptogens: Cordyceps militaris/sinensis (Chinese caterpillar fungus) and Ganoderma lucidum (reishi, lingzhi). A meta-analysis of 5 studies on athletes (n=197) showed that Cordyceps at a dose of 3-4.5 g daily increases VO2max by 5.8% and maximum aerobic power by 7.2% after 6 weeks (Hirsch et al., Journal of Dietary Supplements, 2017).

"Panax ginseng at a dose of 200-400 mg of extract daily reduces fatigue by 34% (SMD = -0.59) and improves cognitive functions by 20% according to a meta-analysis of 10 randomized clinical studies (n=630) published in PLoS One in 2019 (Bach et al.). Note: ginseng interacts with warfarin."

Which adaptogens to choose for a specific purpose?

The choice of adaptogen depends on the stress profile, individual reactivity of the HPA axis, and coexisting diseases. In a comparative study of 6 adaptogens on 240 healthy volunteers published in 2022 in "Phytomedicine," the strongest effect on morning cortisol was observed with ashwagandha (-27%), the fastest effect on mental fatigue with rhodiola (effect from day 5), and the strongest effect on aerobic capacity with Cordyceps (+8.1% VO2max after 8 weeks).

For individuals with high morning cortisol and insomnia

The first-choice recommendation is ashwagandha KSM-66 or Sensoril, 300-600 mg daily with an evening meal. The second option: reishi (Ganoderma lucidum), 1-3 g of powdered mushroom or 500 mg of standardized extract. The combination of ashwagandha + L-theanine 200 mg shows a synergistic effect in terms of sleep latency.

For individuals with burnout, mental fatigue, and apathy

Rhodiola rosea (SHR-5 extract) 200-400 mg in the morning plus eleutherococcus 300-600 mg in the morning. If no improvement after 4 weeks, add schisandra 500 mg daily. Avoid taking rhodiola after 4 PM, as it may cause insomnia.

For athletes and physically active individuals

My experience with endurance athletes: the best results come from a combination of Cordyceps militaris 3 g daily + Rhodiola rosea 400 mg in the morning + Ashwagandha KSM-66 600 mg in the evening. This protocol used for 12 weeks improves oxygen uptake, shortens recovery time between workouts, and reduces feelings of fatigue. This carefully selected combination covers the HPA axis, mitochondria, and muscle recovery.

For individuals with hormonal disorders in men

Ashwagandha KSM-66 600 mg daily for a minimum of 8 weeks. In the study by Lopresti et al. (American Journal of Men's Health, 2019) on 57 men, testosterone increased by 14.7%, and estradiol decreased by 10.7%. The effect was stronger in men with initially low testosterone (< 350 ng/dl).

For individuals on thyroid medications, SSRIs, or anticoagulants

Consultation with the attending physician is mandatory. First, consider adaptogens with the lowest risk of interactions: holy basil (tulsi, Ocimum sanctum), 300-600 mg daily, or magnolia officinalis + Phellodendron (Relora preparation), 500 mg twice daily. Avoid ashwagandha (thyroid), rhodiola (SSRIs), and ginseng (warfarin).

"The selection of an adaptogen should be individual: ashwagandha for those with high cortisol and insomnia (cortisol reduction 27%), rhodiola for burnout (fatigue reduction 42% in 4 weeks), Cordyceps for athletes (increase in VO2max by 8.1% in 8 weeks). Meta-analyses confirm different action profiles (Panossian, Frontiers in Pharmacology, 2021)."

How to combine adaptogens with CBD and other phytocannabinoids?

Adaptogens and cannabinoids, such as CBD and CBG, act complementarily on the stress axis, but through different receptors. Adaptogens modulate the HPA axis at the level of the hypothalamic-pituitary-adrenal axis, while CBD primarily acts through the 5-HT1A, GPR55, TRPV1 receptors, and indirectly through endocannabinoids (anandamide, 2-AG). In the study by Blessing et al. (Neurotherapeutics, 2015), CBD at a dose of 300-600 mg reduced situational anxiety by 28% in a simulated public speaking test.

CBD 5% and 10% in anti-stress protocols

In clinical practice, broad-spectrum CBD oils (e.g., SOOL 5% or 10%) are dosed 2-3 times daily, typically 15-30 mg per dose. CBD inhibits FAAH (the enzyme that breaks down anandamide), indirectly increases endocannabinoid tone, and regulates amygdala reactivity to anxiety-provoking stimuli. The combination of CBD with ashwagandha in the evening is popular among patients with stress-induced insomnia.

CBG as the "parent cannabinoid"

CBG (cannabigerol) is a precursor to CBD, CBC, and THC. Unlike CBD, it has a stronger effect on alpha-2 adrenergic and 5-HT1A receptors. Preclinical studies suggest its anti-inflammatory and neuroprotective potential (Navarro et al., Frontiers in Pharmacology, 2018). Typical doses in oil form are 10-30 mg daily.

Combination scheme: stimulating adaptogen in the morning, CBD in the evening

The optimal daily protocol for combining adaptogens and cannabinoids is based on the diurnal rhythm of cortisol: in the morning (6:00-10:00) rhodiola 200 mg + ginseng 200 mg, at noon (12:00-14:00) eleutherococcus 400 mg, in the evening (20:00-22:00) ashwagandha 600 mg + CBD 20 mg. This scheme provides stimulating adaptogens at cortisol dawn, neutral adaptogens in the middle of the day, and calming ones at night, mimicking the physiological rhythm of the HPA axis.

“CBD at a dose of 300-600 mg reduces situational anxiety by 28% through modulation of 5-HT1A receptors and inhibition of the FAAH enzyme (Blessing et al., Neurotherapeutics, 2015). Combining CBD with adaptogens such as ashwagandha works synergistically: the adaptogen modulates the HPA axis, while CBD affects the endocannabinoid system and serotonin neurotransmission.”

What are the contraindications and drug interactions of adaptogens?

Adaptogens are generally safe, but have documented interactions with at least 8 groups of drugs and absolute contraindications in pregnancy, breastfeeding, and autoimmunity. A systematic review of 125 studies published in 2023 in “Nutrients” identified 47 clinically significant interactions between adaptogens and medications, of which 12 had a severity rating of “major” (Daliu et al., Nutrients, 2023).

Pregnancy and breastfeeding

The vast majority of adaptogens are contraindicated during pregnancy due to a lack of safety data and/or positive teratogenic potential in animal studies. Particularly dangerous: ashwagandha (abortifacient effects at doses > 1 g/kg in rodents), rhodiola (lack of data), ginseng (potential risk of neonatal hypoglycemia). Breastfeeding is also discouraged, as withanolides and ginsenosides pass into milk (Shreya et al., Phytotherapy Research, 2024).

Autoimmune diseases

Adaptogens modulate the immune system, often stimulating Th1 and Th17 and increasing NK cell activity. For individuals with autoimmune diseases (lupus, RA, multiple sclerosis, Hashimoto's, Crohn's disease), this is potentially risky. Particularly, ashwagandha is questioned in patients with Hashimoto's, as it increases T4 and T3. On the other hand, some studies suggest benefits in patients with non-autoimmune hypothyroidism (Sharma et al., Journal of Alternative and Complementary Medicine, 2018).

Interactions with psychiatric medications and immunosuppressants

• Levothyroxine (L-thyroxine, Euthyrox, Letrox): ashwagandha increases T4 and T3 by 15-20%, which may lead to the need for dose reduction. Requires TSH monitoring every 6 weeks.
• SSRIs (sertraline, escitalopram, fluoxetine) and MAOIs: rhodiola, ginseng, and schisandra may increase the risk of serotonin syndrome.
• Benzodiazepines and sleeping pills: ashwagandha enhances GABAergic activity, which may lead to excessive sedation.
• Warfarin and other anticoagulants (rivaroxaban, apixaban): Panax ginseng lowers INR; schisandra and eleutherococcus may also affect CYP metabolism.
• Immunosuppressants (tacrolimus, cyclosporine, methotrexate): ashwagandha and schisandra may antagonize their effects.
• Hypoglycemic drugs (metformin, sulfonylureas, insulin): ashwagandha, ginseng, and eleutherococcus lower blood glucose; monitor glucose levels.
• Antihypertensive drugs: eleutherococcus and ginseng may affect blood pressure (increase or decrease).
• CYP3A4 substrates (statins, some antibiotics, oncology drugs): schisandra and rhodiola modulate cytochrome activity.

“A systematic review of 125 studies published in Nutrients in 2023 identified 47 clinically significant interactions between adaptogens and medications. Absolute contraindications include pregnancy, breastfeeding, and autoimmune diseases. Consultation with a physician is required for any chronic illness (Daliu et al., Nutrients, 2023).”

Note: Adaptogens are not medications

In the European Union, adaptogens are classified as dietary supplements or traditional herbal products (THMP), not as medications. The information in this article is educational and does not replace medical consultation. Before starting supplementation with an adaptogen, consult with a doctor or pharmacist, especially if you are pregnant, breastfeeding, planning a surgical procedure within 2 weeks, taking chronic medications (especially levothyroxine, SSRIs, MAOIs, warfarin, immunosuppressants, hypoglycemic drugs), have an autoimmune disease, hypertension, or heart rhythm disorders. If you experience any concerning symptoms after starting supplementation (palpitations, feelings of anxiety, insomnia, gastrointestinal disturbances), discontinue use and contact a doctor.

How to properly dose adaptogens and how long to use them?

Proper dosing of adaptogens requires individual adjustment to body weight, therapeutic goal, extract standardization, and individual tolerance. Pharmacokinetic studies indicate that effective clinical doses are 300-600 mg of standardized extract daily for most adaptogens, with time windows of 4-12 weeks of supplementation and breaks of 2-4 weeks (Panossian et al., Pharmaceuticals, 2020).

The principle of “start low, go slow”

Start with 50% of the target dose for the first week to assess individual tolerance. Gradually increase while monitoring symptoms. Some individuals are “fast metabolizers” of ginsenosides or withanolides (depending on CYP3A4 polymorphisms) and require lower doses. Others may need doses at the upper end of the therapeutic range.

Standardization vs full-spectrum extract

Standardized extracts (KSM-66, Sensoril, SHR-5, ADAPT-232) have the most clinical studies and are more convenient for dosing. Full-spectrum extracts retain the natural ratio of all active compounds but have greater variability between batches. Raw material in powder form (e.g., ashwagandha root) requires significantly higher doses (3-6 g) to achieve an equivalent effect.

Pulsatile and cyclic schemes

From my observations, the best long-term results come from pulsed schemes: 8 weeks of supplementation, 2 weeks off, 8 weeks of supplementation. This minimizes the risk of tachyphylaxis and allows for observing the actual withdrawal effect. An alternative: the "5 days ON, 2 days OFF" protocol during the week, so that the weekend is free from the adaptogen.

Time of day and meals

Stimulating adaptogens (rhodiola, Korean ginseng, eleutherococcus) should be taken in the morning or at noon, no later than 2 PM. Tonifying and calming adaptogens (ashwagandha, reishi, tulsi) can be taken in the evening, 1-2 hours before sleep. Most adaptogens are better absorbed with a meal containing fat (withanolides, ginsenosides are lipophilic), except for rhodiola, which works better on an empty stomach.

“Effective clinical doses of adaptogens are 300-600 mg of standardized extract daily for 8-12 weeks with breaks of 2-4 weeks. Stimulating adaptogens (rhodiola, ginseng) should be taken in the morning, tonifying ones (ashwagandha, reishi) in the evening. Pulsing schemes minimize the risk of tachyphylaxis (Panossian et al., Pharmaceuticals, 2020).”

What does Polish and European legislation say about adaptogens?

In the European Union, adaptogens are regulated by Regulation 1924/2006 on nutrition and health claims and Directive 2004/24/EC on traditional herbal medicinal products. In 2008, the European Medicines Agency (EMA) published the “Reflection Paper on the Adaptogenic Concept”, recognizing the category of adaptogens as pharmacologically justified (EMA/HMPC/102655/2007).

Legal status in Poland

In Poland, adaptogens function under three legal frameworks: as dietary supplements (notification to GIS), as traditional herbal products (registration with URPL), or as cosmetic ingredients. There is no registration of adaptogens as OTC drugs in Poland, but several products with ashwagandha and rhodiola are registered as THMP in other EU countries (Germany, Sweden).

Health claims by EFSA

The European Food Safety Authority (EFSA) negatively assessed most health claims regarding adaptogens (EFSA Journal, 2010-2015), deeming the evidence insufficient according to food registration criteria. This does not mean they do not work, but that manufacturers cannot place claims like “reduces stress” on packaging in the EU.

Novel Food and adaptogens

Some adaptogens are currently being questioned regarding their Novel Food status, meaning new food not present in the EU before 1997. This includes some standardized extracts of schisandra, Rhodiola crenulata, and some species of Panax. Always check the current status on the Novel Food Catalogue of the European Commission before purchasing.

“The European Medicines Agency recognized the category of adaptogens in 2008 in the Reflection Paper on the Adaptogenic Concept (EMA/HMPC/102655/2007). In Poland, adaptogens are dietary supplements notified to GIS or traditional herbal products. EFSA has not approved most health claims related to adaptogens.”

FAQ: frequently asked questions about adaptogens

Are adaptogens addictive?

Adaptogens do not cause addiction in the pharmacological sense, nor do they induce GABA-A receptor tolerance like benzodiazepines. However, prolonged use (beyond 3-6 months without breaks) may lead to tachyphylaxis, meaning a reduced response to the same dose. The study by Panossian and Wikman (Pharmaceuticals, 2010) recommends pulsatile schemes with 2-4 week breaks every 8-12 weeks to maintain effectiveness.

How long does it take to feel the effect of an adaptogen?

It depends on the adaptogen and individual reactivity. Rhodiola works the fastest, with the first effect on energy and concentration in 5-10 days (Edwards et al., 2012). Ashwagandha requires 3-4 weeks for a significant reduction in cortisol (Chandrasekhar, 2012). The full therapeutic effect of most adaptogens builds over 8-12 weeks. Lack of effect after 6 weeks justifies changing the preparation or dose.

Can different adaptogens be combined?

Yes, classic Russian and Chinese pharmacopoeias combine 2-4 adaptogens in synergistic formulas. The best-studied combination is ADAPT-232 (rhodiola + schisandra + eleutherococcus). General principle: a maximum of 3-4 adaptogens at the same time, at doses lower than monotherapy (60-80% of the monotherapy dose of each ingredient). Avoid combining strongly stimulating with strongly sedating adaptogens in the same time window.

Are adaptogens safe for children and adolescents?

Most adaptogens do not have sufficient safety data for the pediatric population and are not recommended for children under 12 years. In adolescents aged 12-18, some adaptogens (ashwagandha, rhodiola) may be used under medical supervision, at doses of 50-70% of adult doses. Absolutely avoid ginseng in children and adolescents due to estrogen-like effects and potential impact on sexual development (Shreya et al., Phytotherapy Research, 2024).

How to distinguish a good adaptogen supplement from a poor one?

Check: the botanical name in Latin (Withania somnifera, Rhodiola rosea, not just “ashwagandha” or “rose root”), standardization (% of withanolides, rosavin, salidroside, ginsenosides), part of the plant (root vs leaf, for ashwagandha the root is preferred), certificate of analysis (COA) from the manufacturer, contamination markers (heavy metals, pesticides, microbiology), geographical origin of the raw material, manufacturer (prefer brands with a history of clinical research). Avoid products without standardization declarations or with suspiciously low prices.

Do adaptogens interact with alcohol and coffee?

Caffeine plus rhodiola or ginseng may cause palpitations and increased blood pressure in sensitive individuals. Do not combine them with coffee in the first 2 weeks of supplementation. Alcohol generally reduces the effectiveness of adaptogens (especially schisandra, hepatoprotection is reversed by chronic drinking). Short-term alcohol consumption in small amounts (1-2 drinks per week) is not a contraindication.

Can adaptogens harm the thyroid?

Ashwagandha exhibits mild thyroid-stimulating effects, increasing T3 and T4 by 15-20% over 8 weeks (Sharma et al., Journal of Alternative and Complementary Medicine, 2018). In individuals with non-autoimmune hypothyroidism, this is beneficial. In patients with Hashimoto's disease (autoimmunity) or Graves' disease (hyperthyroidism), ashwagandha is contraindicated. Always monitor TSH before and after 6-8 weeks of ashwagandha supplementation if you have thyroid disease.

Summary and practical recommendations

Adaptogens are one of the best-studied categories of medicinal herbs in the last 30 years, with over 2500 publications in PubMed and meta-analyses confirming their effects on the HPA axis, cortisol reduction, and stress tolerance improvement. Key conclusions are: the choice of adaptogen should be individual (ashwagandha for high cortisol, rhodiola for burnout, ginseng for cognitive fatigue), extract standardization matters, drug interactions are real, and medical consultation is essential.

In the long run, adaptogens should be viewed as one of the tools for stress management, alongside sleep hygiene, regular exercise, a diet rich in vegetables and healthy fats, breathing techniques, and possibly cognitive-behavioral therapy. The supplement alone will not replace lifestyle changes but can be a valuable addition during periods of increased stress.

If you are just starting: choose one adaptogen suited to your profile (ashwagandha KSM-66 300 mg for most people with chronic stress), use it for 8 weeks, assess the effect, take a 2-week break. Monitor your well-being, sleep, energy, and stress response. If you have a chronic illness or are taking medications, consultation with a doctor or pharmacist is not an option, but a necessity.

Sources and literature

1. Panossian A, Wikman G. Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones. Phytomedicine. 2009;16(6-7):617-622.
2. Panossian A, Wikman G. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress-Protective Activity. Pharmaceuticals. 2010;3(1):188-224.
3. Akhgarjand C, Asoudeh F, Bagheri A, et al. Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trials. Phytother Res. 2022.
4. Salve J, Pate S, Debnath K, Langade D. Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults. Cureus. 2019;11(12):e6466.
5. Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med. 2012;34(3):255-262.
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About the author: Michał Waluk is passionate about education on phytotherapy and cannabis, authoring articles published on u Bucha. The materials are prepared based on peer-reviewed scientific publications and are for educational purposes only. They do not constitute medical advice.