What are the mechanism of action (MOA) and side effects of ashwagandha?

Mechanism of Action and Side Effects of Ashwagandha

Ashwagandha (Withania somnifera) works primarily through modulating the hypothalamic-pituitary-adrenal (HPA) axis to reduce stress hormones and has potential side effects including thyroid disturbances, sedation, and drug interactions that require careful consideration before use.

Mechanism of Action

Ashwagandha exerts its therapeutic effects through several pathways:

1. HPA Axis Modulation

   • Reduces cortisol levels by regulating the hypothalamic-pituitary-adrenal axis 1
   • Affects DHEA-S levels, contributing to stress reduction 1

2. Hormonal Effects

   • Increases testosterone levels in males but not females 1
   • Affects thyroid function by increasing T3 and T4 hormone production 2
   • Influences reproductive hormones including LH and FSH 2

3. Neurological Effects

   • Improves cognitive function through enhancement of:
     • Episodic memory
     • Working memory
     • Attention accuracy 3
   • Reduces mental fatigue and improves executive functioning 3, 4

4. Adaptogenic Properties

   • Helps the body resist various stressors (physical, chemical, biological)
   • Stabilizes physiological processes during stress exposure 5

Side Effects and Safety Concerns

Common Side Effects

• Mild gastrointestinal disturbances (nausea, diarrhea)
• Drowsiness/sedation
• Headache
• Dizziness

Serious Concerns and Contraindications

1. Drug Interactions

   • MAOI medications: Contraindicated due to risk of severe hypertension and cerebrovascular accidents 6
   • Sedatives/benzodiazepines: Potentiates effects, increasing sedation risk 6
   • CYP450 enzyme substrates: May affect metabolism of other medications 6

2. Endocrine Effects

   • May exacerbate hyperthyroidism
   • Contraindicated in patients with personal or family history of thyroid disorders 6

3. Autoimmune Conditions

   • Contraindicated in autoimmune diseases due to potential immune-stimulating effects 6

4. Pregnancy and Breastfeeding

   • Contraindicated during pregnancy 6
   • Insufficient safety data for breastfeeding

5. Perioperative Considerations

   • Should be discontinued at least 2 weeks before scheduled surgery 6
   • May affect blood pressure, blood glucose, and immune function

Special Population Considerations

1. Liver Disease

   • Use with caution in patients with liver disease due to hepatic metabolism 6

2. Thyroid Disorders

   • May affect thyroid function by increasing T3 and T4 levels 2
   • Monitor thyroid function in patients with thyroid conditions

3. Psychiatric Conditions

   • May be beneficial for anxiety and stress-related disorders 5, 1
   • Effects on mood disorders require further research

Dosing Considerations

• Clinical studies have used doses ranging from 225-600 mg daily 3, 4
• Effects on cognitive function and stress reduction have been observed at 225 mg daily 4
• Higher doses (600 mg daily) have shown benefits for cognition, energy, and mood 3
• Duration of treatment in studies typically ranges from 4-8 weeks

Monitoring Recommendations

• Thyroid function tests in patients with thyroid conditions
• Blood pressure monitoring in hypertensive patients
• Assessment of potential drug interactions with concurrent medications
• Evaluation of sedation levels, especially when combined with other sedative medications

Ashwagandha shows promising benefits for stress reduction, cognitive enhancement, and mood improvement, but careful consideration of contraindications and potential drug interactions is essential before initiating treatment.