Meta Information
ID:ashwagandha
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ashwagandha has been traditionally associated with abortifacient properties and its safety during pregnancy has not been established.
Actionable advice:
This should be strictly avoided during pregnancy.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
Don’t use ashwagandha if you’re pregnant because it may increase your risk of miscarriage.
Label source:
Anecdotal: MSKCC
Action type:
avoid
Target id:
/procedure/surgery-anesthesia
Target name:
Surgery with General Anesthesia
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
336
Hours after target:
null
Description:
Ashwagandha's sedative effects can combine with anesthesia and other medications used during surgery, potentially causing excessive central nervous system depression.
Actionable advice:
Use should be discontinued at least 2 weeks before any scheduled surgery.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Only mild and mainly transient type adverse events of somnolence, epigastric pain/discomfort and loose stools were reported as most common (>5%); and giddiness, drowsiness, hallucinogenic, vertigo, nasal congestion (rhinitis), cough, cold, decreased appetite, nausea, constipation, dry mouth, hyperactivity, nocturnal cramps, blurring of vision, hyperacidity, skin rash and weight gain were reported as less common adverse events.
Label source:
PubMed: Journal of ethnopharmacology (2020)
Source url:
Exact phrase from label:
No mutagenicity or genotoxicity was reported for the root; only mild CNS depression and increase in thyroxine (T4) levels were reported with rootby some studies.
Label source:
PubMed: Journal of ethnopharmacology (2020)
Action type:
avoid
Target id:
/condition/hyperthyroidism
Target name:
Hyperthyroidism (Overactive Thyroid)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ashwagandha may increase thyroid hormone levels (T3 and T4), potentially worsening the symptoms and biochemical state of hyperthyroidism.
Actionable advice:
This should be strictly avoided with an overactive thyroid (hyperthyroidism).
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In turn, other studies prove that active substances from W. somnifera, acting on the body, cause an increase in the secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland and a subse
Label source:
PubMed: Can Ashwagandha Benefit the Endocrine System?-A Review. (PMID 38003702)
Action type:
avoid
Target id:
/intervention/levothyroxine
Target name:
Thyroid Hormone Medication (e.g., Levothyroxine)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ashwagandha may increase the production of thyroid hormones, which can lead to an excessive, additive effect when combined with thyroid replacement therapy, risking thyrotoxicosis.
Actionable advice:
This should not be taken with thyroid medication unless under strict medical supervision with regular thyroid function monitoring.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
To date, scant attention has been paid to thyrotoxicosis associated with Ashwagandha and it is rarely reported in the literature.
Label source:
PubMed: Ashwagandha as a Unique Cause of Thyrotoxicosis Presenting With Supraventricular Tachycardia. (PMID 35475098)
Action type:
avoid
Target id:
/class/cns-depressants
Target name:
CNS Depressants (e.g., Benzodiazepines, Barbiturates, Alcohol)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ashwagandha has calming and sedative properties which can be amplified when taken with other central nervous system depressants, leading to excessive drowsiness or respiratory depression.
Actionable advice:
This is best used with caution, and it is important to talk to a healthcare provider before combining it with sedative medications or alcohol.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Furthermore, the γ-aminobutyric acid (GABA) content in the brain and mRNA and protein expression of GABAA, GABAB1, and serotonin receptors were significantly increased by EA compared to the normal group. In particular, EA showed sleep-promoting activity by binding to various GABAA receptor sites.
Label source:
PubMed: Journal of food and drug analysis (2023)
Source url:
Exact phrase from label:
These results show that mWS has an inhibitory effects on SG neurons of the Vc through GABAA receptor-mediated activation of chloride ion channels, indicating that mWS contains compounds with sedative effects on the central nervous system.
Label source:
PubMed: The American journal of Chinese medicine (2013)
Source url:
Exact phrase from label:
Proposed mechanisms include modulation of monoaminergic and GABAergic pathways, serotonergic activity, regulation of the hypothalamic-pituitary-adrenal axis, and anti-inflammatory effects. However, clinically relevant risks were identified, including cytochrome P450-mediated drug interactions, excessive sedation, serotonin syndrome, and toxic effects associated with adulterated products, such as hepatotoxicity, cardiovascular events, and neurological disturbances.
Label source:
PubMed: Pharmaceuticals (Basel, Switzerland) (2026)
Action type:
informational_none
Target id:
/class/immunosuppressants
Target name:
Immunosuppressant Medications
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ashwagandha may enhance immune system activity, potentially counteracting the effects of medications designed to suppress the immune system, such as those used after organ transplants.
Actionable advice:
Use is best avoided when taking immunosuppressant medications.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The results of this study suggest that the population of stromal and tumorinfiltrating NK cells is increased by dietary Ashwagandha supplementation.
Label source:
PubMed: Dietary supplementation of Ashwagandha (Withania somnifera, Dunal) enhances NK cell function in ovarian tumors in the laying hen model of spontaneous ovarian cancer. (PMID 24188693)
Action type:
avoid
Target id:
/condition/autoimmune-disease
Target name:
Autoimmune Diseases (e.g., RA, Lupus, MS)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
By potentially increasing immune system activity, ashwagandha could exacerbate symptoms of autoimmune conditions where the immune system is already overactive.
Actionable advice:
This is best used with caution and under medical supervision in those with an autoimmune condition.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
These herbs were widely marketed for 'immune support' and shared proinflammatory mechanisms, including toll-like receptor activation, NF-κB/MAPK signalling and increased production of inflammatory cytokines including IL-1β, IL-6, TNF-α, IL-12 and IFN-γ.
Label source:
PubMed: Lupus science & medicine (2025)
Source url:
Exact phrase from label:
Significant increases were observed in the expression of CD4 on CD3+ T cells after 96 hours. CD56+ NK cells were also activated after 96 hours as evidenced by expression of the CD69 receptor.
Label source:
PubMed: Journal of alternative and complementary medicine (New York, N.Y.) (2009)
Source url:
Exact phrase from label:
Gastrointestinal side effects, immune hypersensitivity, liver toxicity, and endocrine disruption have been reported, particularly with prolonged or excessive usage.
Label source:
PubMed: Phytotherapy research : PTR (2026)
Action type:
informational_none
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ashwagandha can lower blood glucose levels, potentially causing an additive effect with diabetes medications that could lead to hypoglycemia (dangerously low blood sugar).
Actionable advice:
Blood sugar should be monitored closely, and it is important to talk to a doctor before combining with diabetes medications.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Decrease in blood glucose was comparable to that of an oral hypoglycemic drug.
Label source:
PubMed: Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root. (PMID 11116534)
Action type:
monitor
Target id:
/class/antihypertensives
Target name:
Antihypertensive Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ashwagandha may have a mild blood pressure-lowering effect, which could be amplified when taken with antihypertensive drugs, potentially causing hypotension (low blood pressure).
Actionable advice:
Blood pressure should be monitored, and it is important to talk to a doctor before combining with blood pressure medications.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The experimental literature indicates that WS has the potential for 1) maintaining immune homeostasis, 2) regulating inflammation, 3) suppressing pro-inflammatory cytokines, 4) organ protection (nervous system, heart, lung, liver, and kidney), and 5) anti-stress, antihypertensive, and antidiabetic activities.
Label source:
PubMed: Frontiers in pharmacology (2021)
Source url:
Exact phrase from label:
Withania somnifera has proved its potential for maintaining immune homeostasis of the body, inflammation regulation, pro-inflammatory cytokines suppression, protection of multiple organs, anti-viral, anti-stress, and anti-hypertensive properties.
Label source:
PubMed: Frontiers in cellular and infection microbiology (2022)
Action type:
monitor
Target id:
/condition/hepatic-impairment
Target name:
Hepatic Impairment (Liver Disease)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Rare cases of liver injury have been reported with ashwagandha use; individuals with pre-existing liver conditions may be at higher risk.
Actionable advice:
This is best used with caution and under medical supervision in those with liver disease.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Five patients had underlying chronic liver disease; 3 presented with acute-on-chronic liver failure, and all 3 died on follow-up.
Label source:
PubMed: Hepatology communications (2023)
Source url:
Exact phrase from label:
This case underscores the dangers of Ashwagandha, particularly for individuals with preexisting liver conditions, where it can lead to life-threatening acute-on-chronic liver failure.
Label source:
PubMed: Revista espanola de enfermedades digestivas (2025)
Source url:
Exact phrase from label:
These cases illustrate the hepatotoxic potential of ashwagandha. Liver injury is typically cholestatic or mixed with severe jaundice and pruritus, but self-limited with liver tests normalizing in 1-5 months.
Label source:
PubMed: Liver international : official journal of the International Association for the Study of the Liver (2020)
Action type:
informational_none
Target id:
/condition/hemochromatosis
Target name:
Hemochromatosis (Iron Overload)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ashwagandha root contains significant amounts of iron, which could contribute to iron overload in individuals with hemochromatosis.
Actionable advice:
Use is best avoided with hemochromatosis.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Exact phrase from label:
It is high in iron and has been shown to help increase hemoglobin levels
Label source:
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
There is insufficient reliable information about the safety of taking ashwagandha while breastfeeding; its components may pass into breast milk.
Actionable advice:
Use should be avoided while breastfeeding due to a lack of safety data.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Source url:
Exact phrase from label:
Ashwagandha should be avoided during pregnancy and should not be used while breastfeeding.
Label source:
Anecdotal: NCCIH
Action type:
avoid
Target id:
/intervention/digoxin
Target name:
Digoxin
Severity:
moderate
Interaction type:
assay_interference
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Components in ashwagandha may cross-react with the laboratory test (immunoassay) for digoxin, leading to a falsely high reading of the drug's level in the blood.
Actionable advice:
It is a good idea to let a healthcare provider know about ashwagandha use if on digoxin therapy.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
When Ashwagandha extract was added to a serum pool containing digoxin, falsely elevated digoxin value was observed with fluorescence polarization immunoassay, but values were falsely lowered when measured by the microparticle enzyme immunoassay.
Label source:
PubMed: Effect of Indian Ayurvedic medicine Ashwagandha on measurement of serum digoxin and 11 commonly monitored drugs using immunoassays: study of protein binding and interaction with Digibind. (PMID 17683192)
Action type:
informational_none
Target id:
/circadian/sleep
Target name:
Going to Sleep
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
null
Description:
Ashwagandha's anxiolytic and GABAergic properties may help improve sleep quality and reduce the time it takes to fall asleep when taken in the evening.
Actionable advice:
Consider taking your dose in the evening, about an hour before bedtime, to support sleep.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
WS may alleviate these conditions predominantly through modulation of the hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary axes, as well as through GABAergic and serotonergic pathways.
Label source:
PubMed: Effects of Withania somnifera (Ashwagandha) on Stress and the Stress- Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia. (PMID 34254920)
Action type:
separate
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
informational
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Taking ashwagandha with food can help prevent potential gastrointestinal upset, which may occur when taken on an empty stomach.
Actionable advice:
It is generally best taken with a meal to minimize the risk of stomach discomfort.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Gastrointestinal side effects, immune hypersensitivity, liver toxicity, and endocrine disruption have been reported, particularly with prolonged or excessive usage.
Label source:
PubMed: Phytotherapy research : PTR (2026)
Source url:
Exact phrase from label:
Withania somnifera: reboxetine (testicle pain and ejaculatory dysfunctions), sertraline (severe diarrhea), escitalopram (myalgia, epigastric pain, nausea, vomiting, restless legs syndrome, and severe cough), and paroxetine (generalized myalgia, ophthalmalgia, and ocular hypertension);
Label source:
PubMed: Frontiers in pharmacology (2023)
Source url:
Exact phrase from label:
The most common AEs include nausea (3.2% in PL vs. 2.0% in ARE), dry mouth (1.4% in both groups), and headache (2.2% in PL vs. 0.2% in ARE).
Label source:
PubMed: Phytotherapy research : PTR (2026)
Action type:
informational_none
Target id:
/class/cyp3a4-substrates
Target name:
Drugs Metabolized by CYP3A4
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Some evidence suggests ashwagandha may induce the CYP3A4 enzyme, potentially increasing the metabolism and reducing the effectiveness of drugs that are substrates for this enzyme.
Actionable advice:
Reduced efficacy may occur for CYP3A4 substrate drugs; consulting a pharmacist may help.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Our findings revealed that 70% ethanol ashwagandha root extracts (WSR-2) modulated CYP3A4 enzyme expression and activity.
Label source:
PubMed: Ashwagandha (Withania somnifera) Plant Extracts Affect the Cytochrome P450 System and Cytotoxicity of Primary Human Hepatocytes. (PMID 40551718)
Action type:
informational_none
Target id:
/class/cyp2c9-substrates
Target name:
Drugs Metabolized by CYP2C9 (e.g., Warfarin)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Some in-vitro evidence suggests ashwagandha may inhibit the CYP2C9 enzyme, potentially slowing the metabolism and increasing the levels of drugs like warfarin.
Actionable advice:
This is best used with caution when taking drugs metabolized by CYP2C9, especially those with a narrow therapeutic index.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The results of the study revealed that W. somnifera showed no significant interaction with both the isoforms of CYP.
Label source:
PubMed: Drug metabolism and personalized therapy (2015)
Source url:
Exact phrase from label:
Four extracts from ashwagandha root or leaf were evaluated for P450 inhibition, and no reversible inhibition was detected at IC50 > 100 μg/mL extract.
Label source:
PubMed: Drug metabolism and disposition: the biological fate of chemicals (2025)
Source url:
Exact phrase from label:
Metabolic transformation via cytochrome P450 enzymes can form reactive intermediates, leading to oxidative stress and hepatotoxicity.
Label source:
PubMed: Phytotherapy research : PTR (2026)
Action type:
informational_none