Quick Comparison
| Ashwagandha | Phenibut | |
|---|---|---|
| Half-Life | 6-12 hours (withanolides) | 5-6 hours |
| Typical Dosage | KSM-66 extract: 300-600 mg daily. Sensoril extract: 125-250 mg daily. Root powder: 3-6 g daily. Best taken with food. Can be taken morning or evening (does not cause drowsiness in most people). | Standard: 250-1000 mg on an empty stomach, no more than 1-2 times per week. NEVER use daily — tolerance and dependence develop within 3-5 days of consecutive use. Onset: 2-4 hours (slow). Do not exceed 2000 mg per occasion. |
| Administration | Oral (capsules, powder). Standardized extracts (KSM-66 or Sensoril) are preferred over raw root powder for consistent dosing. | Oral (powder, capsules). Take on an empty stomach — food significantly reduces absorption. Slow onset (2-4 hours). |
| Research Papers | 9 papers | 10 papers |
| Categories |
Mechanism of Action
Ashwagandha
Ashwagandha's withanolide compounds (withaferin A, withanolide A, withanone) modulate the hypothalamic-pituitary-adrenal (HPA) axis, reducing corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) signaling, thereby lowering cortisol production by 25-30% in stressed individuals. It acts as a GABA-A receptor positive allosteric modulator at the benzodiazepine site, producing anxiolytic effects without sedation. Ashwagandha inhibits acetylcholinesterase (AChE), raising acetylcholine levels in the hippocampus and cortex. The withanolides have anti-inflammatory properties via inhibition of NF-κB and COX-2, and antioxidant effects that reduce neuroinflammation and oxidative stress. It may support neurogenesis through upregulation of BDNF and its receptor TrkB, and modulation of the PI3K/Akt pathway.
Phenibut
Phenibut is a structural analog of GABA with a phenyl ring that confers lipophilicity and allows blood-brain barrier penetration (unlike GABA itself). It acts as a GABA-B receptor agonist, binding to the GABAB1/GABAB2 heterodimer and activating Gi/o-coupled signaling (similar to baclofen), producing anxiolytic, muscle relaxant, and sedative effects through inhibition of adenylyl cyclase and modulation of potassium and calcium channels. Phenibut also blocks the alpha-2-delta-1 and alpha-2-delta-2 subunits of voltage-gated calcium channels, reducing presynaptic calcium influx and neurotransmitter release (similar to gabapentin/pregabalin). The dual mechanism—GABA-B agonism dampening inhibitory interneurons and calcium channel blockade reducing excitatory transmission—produces potent anti-anxiety and sleep-promoting effects. Rapid tolerance develops due to receptor downregulation.
Risks & Safety
Ashwagandha
Common
Gastrointestinal discomfort, drowsiness at higher doses, thyroid hormone elevation.
Serious
Can cause hyperthyroidism in susceptible individuals — avoid with thyroid conditions without medical oversight. Rare liver injury reports.
Rare
Vertigo, nasal congestion, sexual dysfunction.
Phenibut
Common
Drowsiness, dizziness, nausea, tolerance with repeated use.
Serious
Physical dependence develops rapidly with daily use. Withdrawal can be severe and dangerous (anxiety, insomnia, psychosis, seizures). Respiratory depression when combined with alcohol or other CNS depressants.
Rare
Hallucinations, severe rebound anxiety, suicidal ideation during withdrawal.
Full Profiles
Ashwagandha →
An Ayurvedic adaptogen used for over 3,000 years that has become one of the most popular and well-studied supplements for stress, anxiety, and cognitive function. Ashwagandha (Withania somnifera) significantly reduces cortisol levels, improves stress resilience, and enhances memory and reaction time. KSM-66 and Sensoril are the two most studied standardized extracts.
Phenibut →
A GABA-B agonist and alpha-2-delta voltage-gated calcium channel blocker developed in Russia for anxiety, insomnia, and PTSD. It crosses the blood-brain barrier (unlike GABA supplements) and produces potent anxiolytic and social confidence effects. However, it carries significant addiction and withdrawal risks — tolerance develops within days of daily use, and withdrawal can be severe.