Mechanism • α2δ + GABAΒ
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R-phenibut binds α2δ and shows gabapentin-like activity
Establishes α2δ engagement in addition to GABAΒ—explains gabapentinoid-like toxicity & withdrawal features.
Summary
Animal antinociception with receptor binding confirms α2δ targeting by R-phenibut; helps explain synergy/overlap with gabapentinoids.
Zvejniece L, et al. R-phenibut binds to the α2–δ subunit of voltage-dependent calcium channels and exerts gabapentin-like antinociception. Neurochem Int. 2015;89:41-47. PubMed
Mechanism • Enantiomers
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R-phenibut drives GABAΒ effects; S-phenibut largely inactive
Clarifies potency and expected effects by stereoisomer—important for product variability and dosing risk.
Summary
Compares optical isomers across assays; R-phenibut shows GABAΒ activity consistent with clinical effects.
Dambrova M, et al. Comparative pharmacological activity of optical isomers of phenibut. J Pharm Pharmacol. 2008;60(7):795-802. PubMed
Overview • Classic Review
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Foundational review of phenibut’s pharmacology & uses
Historic but influential review summarizing GABA-mimetic actions and early clinical experiences.
Summary
Frames Western literature with former-Soviet usage; useful for context when counseling on imported “nootropics.”
Lapin I. Phenibut (β-phenyl-GABA): a tranquilizer and nootropic drug. CNS Drug Rev. 2001;7(4):471-481. PubMed
Epidemiology • Regional Poison Center
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Five-year surge in phenibut calls (U.S. region)
CNS/respiratory depression common; some cases required intubation—front-line ED implications.
Summary
Describes exposure routes, symptoms, and outcomes; flags “supplement” source and polysubstance patterns.
McCabe DJ, et al. Phenibut exposures and clinical effects reported to a regional poison center. Am J Emerg Med. 2019;37(10):1937-1940. PubMed
Epidemiology • National (MMWR)
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Phenibut exposures reported to U.S. poison centers (2009–2019)
1,320 exposures; agitation, somnolence, coma, and pediatric cases—national scope across all 50 states.
Summary
Characterizes age distribution, clinical effects, and outcomes; establishes baseline for policy and public-health messaging.
Graves JM, et al. Phenibut Exposures Reported to Poison Centers — United States, 2009–2019. MMWR. 2020;69(35):1227-1232. CDC
Clinical • Toxicity & Withdrawal (Series)
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Clinical presentations & treatment of phenibut toxicity/withdrawal
Synthesizes intoxication (psychosis, movement disorders, respiratory depression) and withdrawal courses; many severe cases required intubation or ICU-level care.
Summary
Multi-case review outlines typical meds (benzodiazepines, baclofen, phenobarbital, gabapentinoids) and trajectories; emphasizes long, symptom-driven tapers for severe dependence.
Weleff J, Patel R, D’Souza R, et al. Clinical Presentations and Treatment of Phenibut Toxicity and Withdrawal: Case Series and Literature Review. Psychosomatics / Psychiatry. 2023. PMID: 37579098. PubMed
Dependence • Early Case
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Phenibut dependence with rapid tolerance and withdrawal
Early English-language case documenting dose escalation, short inter-dose withdrawal, and functional impairment.
Summary
Highlights availability via online “nootropic” vendors; charts classic withdrawal (anxiety, tremor, insomnia, autonomic symptoms) and urges regulatory attention.
Samokhvalov AV, Paton-Gay CL, Balchand K, Rehm J. Phenibut dependence. BMJ Case Rep. 2013;2013:bcr2012008389. PMC
Dependence • U.S. Case + Review
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Phenibut dependence and withdrawal (U.S. case)
Confirms GABAB agonist liability with significant withdrawal; discusses practical management with baclofen and benzodiazepines.
Summary
Case with escalating daily doses, anxiety/insomnia on cessation, and gradual stabilization; includes concise literature review useful for bedside counseling.
Ahuja T, Shah R, Siddiqui WJ. Phenibut (β-phenyl-γ-aminobutyric acid) dependence and withdrawal. Prim Care Companion CNS Disord. 2018;20(3):18l02219. PMC
Withdrawal • Protracted/Delirium
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Dissociative intoxication and prolonged withdrawal
Severe, protracted withdrawal with delirium; anticipate longer courses and higher-acuity management.
Summary
Describes dissociation, agitation, insomnia, and cognitive changes over weeks; supports need for slow tapering and close follow-up.
Joshi YB, MacKenzie EM, Narasimhan M. Dissociative intoxication and prolonged withdrawal associated with phenibut. Bosn J Basic Med Sci. 2017;17(3):253-256. PMC
Neuropsychiatry • Psychosis
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Acute psychosis associated with phenibut ingestion
Illustrates hallucinations/psychosis after phenibut with co-medications; important differential for agitated delirium in the ED.
Summary
Details time course, workup, and supportive/benzodiazepine management; recommends targeted history for imported “supplements.”
Acosta E, Kamboj A, Afzal A, et al. Acute Psychosis Associated with Phenibut Ingestion. Cureus. 2021;13(11):e19335. PMC
Emergency • Overdose
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Emergency-department overdose case
Describes delirium, autonomic instability, and supportive treatment; demonstrates unpredictable dosing of gray-market powders.
Summary
Case underscores importance of airway protection and serial neurologic exams; emphasizes unregulated supplement sourcing as a major risk factor.
Nedzlek CD, et al. A Case Report of Phenibut Overdose. Cureus. 2022;14(5):e24795. PMC
Withdrawal • Delirium
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Phenibut intoxication and withdrawal delirium
Highlights mixed receptor targets—GABAB, GABAA, gabapentinoid—and integrated management across these systems.
Summary
Provides a conceptual pharmacologic model for severe withdrawal; stresses early recognition and cross-titration strategies.
Martin R, et al. Phenibut Intoxication and Withdrawal Delirium: A Case Report. J Addict Med. 2023;17(6):e420-e423. PMID: 37930202. PubMed
Forensic • Fatality
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Phenibut detected in a death investigation
Confirms phenibut’s lethality at high levels and necessity of toxicologic screening in unexplained fatalities.
Arndt C, et al. Phenibut, a GABAB Agonist, Detected in a Fatality. J Anal Toxicol. 2022;46(2):e73-e79. PubMed
Treatment • Outpatient Baclofen Taper
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Outpatient withdrawal management using baclofen taper
Demonstrates a structured ambulatory taper strategy for patients refusing or unable to access inpatient detox.
Summary
Gradual baclofen substitution and taper minimized withdrawal; monitoring plan provided. Useful model for rural or outpatient care.
DiFiore E, et al. A Case of Phenibut Withdrawal Management and Outpatient Baclofen Taper. J Addict Med. 2024;XX(X):XX-XX. PMID: 38993282. PubMed
Systematic Review • Withdrawals
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Systematic review of phenibut withdrawal cases
Aggregates 15 cases (mean 13.6 g/day); most treated successfully with baclofen, benzodiazepines, or phenobarbital.
Summary
Provides dosing ranges and timeline benchmarks for symptom resolution; suggests cross-taper protocol similar to GABAB agonist withdrawals.
Stewart C, et al. A Systematic Review of Phenibut Withdrawals. Cureus. 2024;16(6):e60338. PMC
Informational only — not medical advice. Phenibut is not FDA-approved in the U.S.; advise patients to disclose use and avoid abrupt discontinuation.