F-Phenibut

4-fluorophenibut

Sources

15 moderate · 11 weak

Studies and references cited across this article, graded by evidence strength.

Claims checked

62verified3partial14inconclusive3not supported

Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.

Generated

Apr 28, 2026 · pipeline-v5

Values approved

127/128 (99%)

Data points an editor reviewed and accepted for publication.

Value Provenance

Dosing

oraltrace

Field	Published	AI Proposed	Confidence
Threshold	50 mg	50 mg	low
Low	100–150 mg	100–150 mg	low
Common	150–400 mg	150–400 mg	low
Strong	400–600 mg	400–600 mg	low
Heavy	600+ mg	600+ mg	low
Editorial	Dose ranges from PsychonautWiki user-sourced data (Ref 19), cross-checked against brief seed data and found consistent. No published clinical dosing study exists for F-phenibut. These are community consensus values from harm reduction databases.
	ReasoningReasoning Dose ranges from PsychonautWiki user-sourced data (Ref 19), cross-checked against brief seed data and found consistent. No published clinical dosing study exists for F-phenibut. These are community consensus values from harm reduction databases. Evidence basis: community_consensus_large

Duration

oral

Field	Published	AI Proposed	Confidence
Onsettrace	20–60 minutes	20–60 minutes	low
Editorial	Onset 20-60 minutes from PsychonautWiki user reports (Ref 19), consistent with brief seed data. No controlled human study.
	ReasoningReasoning Onset 20-60 minutes from PsychonautWiki user reports (Ref 19), consistent with brief seed data. No controlled human study. Evidence basis: community_consensus_large
Come uptrace	30–60 minutes	30–60 minutes	low
Editorial	Come-up duration inferred from onset-to-peak timing in user reports and phenibut class pharmacokinetics (Tmax ~15 min in mice, Ref 16; longer expected in humans oral route).
	ReasoningReasoning Come-up duration inferred from onset-to-peak timing in user reports and phenibut class pharmacokinetics (Tmax ~15 min in mice, Ref 16; longer expected in humans oral route). Evidence basis: community_consensus_large
Peaktrace	1.5–3 hours	1.5–3 hours	low
Editorial	Peak duration estimated from total duration (6-8h, Ref 19) and phenibut class t1/2 of 5-6 hours (Ref 13). No direct measurement.
	ReasoningReasoning Peak duration estimated from total duration (6-8h, Ref 19) and phenibut class t1/2 of 5-6 hours (Ref 13). No direct measurement. Evidence basis: structural_analogy
Offsettrace	1–2 hours	1–2 hours	low
Editorial	Offset estimated from total duration and phenibut elimination kinetics.
	ReasoningReasoning Offset estimated from total duration and phenibut elimination kinetics. Evidence basis: structural_analogy
Totaltrace	6–8 hours	6–8 hours	low
Editorial	Total subjective duration 6-8 hours from PsychonautWiki user reports (Ref 19), consistent with phenibut class t1/2 of 5-6 hours (Ref 13). Represents subjective experience, not pharmacological half-life.
	ReasoningReasoning Total subjective duration 6-8 hours from PsychonautWiki user reports (Ref 19), consistent with phenibut class t1/2 of 5-6 hours (Ref 13). Represents subjective experience, not pharmacological half-life. Evidence basis: community_consensus_large
After effectstrace	2–6 hours	2–6 hours	low
Editorial	Aftereffects duration estimated from phenibut pharmacokinetics (residual drug present for 2-3 half-lives after subjective experience ends). Some users report next-day sedation at higher doses.
	ReasoningReasoning Aftereffects duration estimated from phenibut pharmacokinetics (residual drug present for 2-3 half-lives after subjective experience ends). Some users report next-day sedation at higher doses. Evidence basis: structural_analogy

Safety

Toxicity Profiletrace

Field	Published	AI Proposed	Confidence
Acute	moderate	moderate	low
Chronic	moderate	moderate	low
Organs Affected	central nervous system, respiratory	central nervous system, respiratory	low
Editorial	Classified as moderate (downgraded from high): all toxicity evidence derives from phenibut class data (Refs 4, 13) applied to F-phenibut by structural analogy. No F-phenibut-specific toxicological study, LD50, or case report exists. The 58x GABA-B potency increase (Ref 1) suggests higher per-milligram risk than phenibut but the absolute toxicity profile is uncharacterized.
	ReasoningReasoning Classified as moderate (downgraded from high): all toxicity evidence derives from phenibut class data (Refs 4, 13) applied to F-phenibut by structural analogy. No F-phenibut-specific toxicological study, LD50, or case report exists. The 58x GABA-B potency increase (Ref 1) suggests higher per-milligram risk than phenibut but the absolute toxicity profile is uncharacterized. Evidence basis: structural_analogy

Dependence Profiletrace

Field	Published	AI Proposed	Confidence
Physical	moderate	moderate	low
Psychological	moderate	moderate	low
Compulsive Redosing	moderate	moderate	low
Dose Escalation	high	high	low
Editorial	Dependence profile inferred from phenibut case series (Refs 4, 5, 9, 10, 21, 24) which document moderate-to-severe physical and psychological dependence. F-phenibut's higher GABA-B potency (Ref 1) may accelerate dependence at lower doses. Compulsive redosing noted in PsychonautWiki user reports (Ref 19).
	ReasoningReasoning Dependence profile inferred from phenibut case series (Refs 4, 5, 9, 10, 21, 24) which document moderate-to-severe physical and psychological dependence. F-phenibut's higher GABA-B potency (Ref 1) may accelerate dependence at lower doses. Compulsive redosing noted in PsychonautWiki user reports (Ref 19). Evidence basis: structural_analogy

Withdrawal Profiletrace

Field	Published	AI Proposed	Confidence
Severity	severe	severe	low
Symptoms	psychomotor agitation, autonomic instability, tremor, insomnia, anxiety, psychosis, seizures, tachycardia, diaphoresis	psychomotor agitation, autonomic instability, tremor, insomnia, anxiety, psychosis, seizures, tachycardia, diaphoresis	low
Fatal	No	No	low
Medical Supervision	Required	Required	low
Editorial	Withdrawal profile from phenibut case series (Refs 4, 5, 9, 10). Onset within 3-4 hours (Ref 10). Severity includes seizures, psychosis, and autonomic instability requiring medical management. No deaths attributed to phenibut withdrawal alone documented, but medical supervision is essential.
	ReasoningReasoning Withdrawal profile from phenibut case series (Refs 4, 5, 9, 10). Onset within 3-4 hours (Ref 10). Severity includes seizures, psychosis, and autonomic instability requiring medical management. No deaths attributed to phenibut withdrawal alone documented, but medical supervision is essential. Evidence basis: structural_analogy

Tolerance Profiletrace

Field	Published	AI Proposed	Confidence
Buildup	rapid	rapid	low
Half-life	—	—	low
Full Reset	10.5 days	10.5 days	low
Cross-tolerances	phenibut, baclofen, GHB, GBL, alcohol, benzodiazepines	phenibut, baclofen, GHB, GBL, alcohol, benzodiazepines	low
Editorial	Tolerance characteristics inferred from phenibut class data (Refs 4, 10) and GABA-B receptor pharmacology. The rapid onset is consistent with clinical case reports of phenibut dose escalation within days. Full reset time is community consensus only (no published source found). No F-phenibut-specific tolerance study exists.
	ReasoningReasoning Tolerance characteristics inferred from phenibut class data (Refs 4, 10) and GABA-B receptor pharmacology. The rapid onset is consistent with clinical case reports of phenibut dose escalation within days. Full reset time is community consensus only (no published source found). No F-phenibut-specific tolerance study exists. Evidence basis: structural_analogy

Effects & Profile

Contraindications

Field	Published	AI Proposed	Confidence
respiratory respiratory insufficiencytrace	absolute	absolute	medium
Editorial	Class-level inference from GABA-B agonist pharmacology. Phenibut overdose case reports document respiratory depression requiring intubation (Refs 13, 17).
	ReasoningReasoning Class-level inference from GABA-B agonist pharmacology. Phenibut overdose case reports document respiratory depression requiring intubation (Refs 13, 17).
other concurrent CNS depressant usetrace	absolute	absolute	medium
Editorial	Phenibut deaths predominantly involve polydrug contexts (Refs 12, 13). Polydependence with benzodiazepines documented (Ref 24). Class-level pharmacodynamic interaction.
	ReasoningReasoning Phenibut deaths predominantly involve polydrug contexts (Refs 12, 13). Polydependence with benzodiazepines documented (Ref 24). Class-level pharmacodynamic interaction.
neurological epilepsytrace	relative	relative	medium
Editorial	Seizures documented in phenibut withdrawal (Refs 4, 5, 9). GABA-B agonist withdrawal lowers seizure threshold. Class-level inference.
	ReasoningReasoning Seizures documented in phenibut withdrawal (Refs 4, 5, 9). GABA-B agonist withdrawal lowers seizure threshold. Class-level inference.
pregnancy breastfeeding pregnancytrace	absolute	absolute	low
Editorial	No F-phenibut reproductive data. Baclofen pregnancy category C provides class-level concern. Contraindicated by precautionary principle.
	ReasoningReasoning No F-phenibut reproductive data. Baclofen pregnancy category C provides class-level concern. Contraindicated by precautionary principle.
renal renal impairmenttrace	relative	relative	low
Editorial	Phenibut renal excretion documented (Ref 13). Dose adjustment or avoidance warranted in renal impairment by pharmacokinetic reasoning. No direct F-phenibut renal data.
	ReasoningReasoning Phenibut renal excretion documented (Ref 13). Dose adjustment or avoidance warranted in renal impairment by pharmacokinetic reasoning. No direct F-phenibut renal data.
psychiatric substance use disorderstrace	relative	relative	medium
Editorial	Phenibut dependence documented in multiple case series (Refs 4, 5, 10, 21). Compulsive redosing noted in community reports (Ref 19). Cross-dependence with GABAergic substances expected.
	ReasoningReasoning Phenibut dependence documented in multiple case series (Refs 4, 5, 10, 21). Compulsive redosing noted in community reports (Ref 19). Cross-dependence with GABAergic substances expected.

Timeline Phases

oral

Field	Published	AI Proposed	Confidence
Onsettrace	1200–3600 sec(i=0.05)	1200–3600 sec(i=0.05)	low
Editorial	Duration data from PsychonautWiki user reports (Ref 19): onset 20-60 min, total 6-8 hours. Phase breakdown inferred from phenibut class pharmacokinetics (t1/2 ~5-6 hours, Ref 13) and GABA-B agonist pharmacodynamics. No controlled human timing data exist for F-phenibut.
	ReasoningReasoning Duration data from PsychonautWiki user reports (Ref 19): onset 20-60 min, total 6-8 hours. Phase breakdown inferred from phenibut class pharmacokinetics (t1/2 ~5-6 hours, Ref 13) and GABA-B agonist pharmacodynamics. No controlled human timing data exist for F-phenibut.
Come uptrace	1800–3600 sec(i=0.30)	1800–3600 sec(i=0.30)	low
Editorial	Duration data from PsychonautWiki user reports (Ref 19): onset 20-60 min, total 6-8 hours. Phase breakdown inferred from phenibut class pharmacokinetics (t1/2 ~5-6 hours, Ref 13) and GABA-B agonist pharmacodynamics. No controlled human timing data exist for F-phenibut.
	ReasoningReasoning Duration data from PsychonautWiki user reports (Ref 19): onset 20-60 min, total 6-8 hours. Phase breakdown inferred from phenibut class pharmacokinetics (t1/2 ~5-6 hours, Ref 13) and GABA-B agonist pharmacodynamics. No controlled human timing data exist for F-phenibut.
Peaktrace	5400–10800 sec(i=1.00)	5400–10800 sec(i=1.00)	low
Editorial	Duration data from PsychonautWiki user reports (Ref 19): onset 20-60 min, total 6-8 hours. Phase breakdown inferred from phenibut class pharmacokinetics (t1/2 ~5-6 hours, Ref 13) and GABA-B agonist pharmacodynamics. No controlled human timing data exist for F-phenibut.
	ReasoningReasoning Duration data from PsychonautWiki user reports (Ref 19): onset 20-60 min, total 6-8 hours. Phase breakdown inferred from phenibut class pharmacokinetics (t1/2 ~5-6 hours, Ref 13) and GABA-B agonist pharmacodynamics. No controlled human timing data exist for F-phenibut.
Plateautrace	3600–7200 sec(i=0.50)	3600–7200 sec(i=0.50)	low
Editorial	Duration data from PsychonautWiki user reports (Ref 19): onset 20-60 min, total 6-8 hours. Phase breakdown inferred from phenibut class pharmacokinetics (t1/2 ~5-6 hours, Ref 13) and GABA-B agonist pharmacodynamics. No controlled human timing data exist for F-phenibut.
	ReasoningReasoning Duration data from PsychonautWiki user reports (Ref 19): onset 20-60 min, total 6-8 hours. Phase breakdown inferred from phenibut class pharmacokinetics (t1/2 ~5-6 hours, Ref 13) and GABA-B agonist pharmacodynamics. No controlled human timing data exist for F-phenibut.
Resolutiontrace	3600–5400 sec(i=0.20)	3600–5400 sec(i=0.20)	low
Editorial	Duration data from PsychonautWiki user reports (Ref 19): onset 20-60 min, total 6-8 hours. Phase breakdown inferred from phenibut class pharmacokinetics (t1/2 ~5-6 hours, Ref 13) and GABA-B agonist pharmacodynamics. No controlled human timing data exist for F-phenibut.
	ReasoningReasoning Duration data from PsychonautWiki user reports (Ref 19): onset 20-60 min, total 6-8 hours. Phase breakdown inferred from phenibut class pharmacokinetics (t1/2 ~5-6 hours, Ref 13) and GABA-B agonist pharmacodynamics. No controlled human timing data exist for F-phenibut.
Afterglowtrace	7200–14400 sec(i=0.05)	7200–14400 sec(i=0.05)	low
Editorial	Duration data from PsychonautWiki user reports (Ref 19): onset 20-60 min, total 6-8 hours. Phase breakdown inferred from phenibut class pharmacokinetics (t1/2 ~5-6 hours, Ref 13) and GABA-B agonist pharmacodynamics. No controlled human timing data exist for F-phenibut.
	ReasoningReasoning Duration data from PsychonautWiki user reports (Ref 19): onset 20-60 min, total 6-8 hours. Phase breakdown inferred from phenibut class pharmacokinetics (t1/2 ~5-6 hours, Ref 13) and GABA-B agonist pharmacodynamics. No controlled human timing data exist for F-phenibut.

Dose Tier Summaries

thresholdtrace

low

At threshold doses (~50 mg oral), effects are subtle and may be indistinguishable from placebo in naive users. A faint sense of calm or mild anxiety reduction is the most commonly reported change, accompanied by a slight loosening of social inhibition. Some users describe a barely perceptible mood lift or physical relaxation. Physical effects are minimal — slight muscle relaxation may be noticeable. No significant motor impairment, sedation, or cognitive changes are expected at this level. Functional capacity remains intact.

Editorial

Threshold value of 50 mg from PsychonautWiki user-sourced data (Ref 19). Effect description inferred from GABA-B agonist pharmacology at minimal receptor occupancy.

Reasoning

Threshold value of 50 mg from PsychonautWiki user-sourced data (Ref 19). Effect description inferred from GABA-B agonist pharmacology at minimal receptor occupancy.

Evidence basis: community_consensus_large

lighttrace

low

At light doses (100–150 mg oral), anxiolytic effects become clearly perceptible. Anxiety suppression is the dominant feature — social situations feel easier, rumination diminishes, and a gentle sense of wellbeing emerges. Mild disinhibition and slight empathy enhancement are reported. Some users note subtle music enhancement and increased sociability. Physically, muscle relaxation becomes noticeable. A mild warmth or tactile enhancement may be present. Motor coordination remains largely intact, though fine motor tasks may show subtle impairment. Sleep is facilitated if taken in the evening. Functional impairment is minimal at this range; most users report being able to carry out normal activities.

Editorial

Light dose range 100-150 mg from PsychonautWiki user reports (Ref 19). Effect profile inferred from GABA-B agonist pharmacology and phenibut class user reports.

Reasoning

Light dose range 100-150 mg from PsychonautWiki user reports (Ref 19). Effect profile inferred from GABA-B agonist pharmacology and phenibut class user reports.

Evidence basis: community_consensus_large

commontrace

low

At common doses (150–400 mg oral), the full anxiolytic and prosocial profile emerges. Anxiety suppression is pronounced — social inhibitions diminish substantially, and users report cognitive euphoria, motivation enhancement, and a sense of emotional openness. Disinhibition is marked, and empathy enhancement contributes to sociability. Music enhancement is frequently noted. A compulsive redosing urge may appear at the upper end of this range. Physically, muscle relaxation is significant. Tactile enhancement and a diffuse bodily warmth are commonly described. Motor control impairment begins to manifest — gait may become slightly unsteady. Mild sedation competes with stimulation at the lower end of this range. At the upper end, thought deceleration and sedation increase. Sleep becomes difficult to resist if the user is in a resting environment. The experience lasts 6–8 hours from onset.

Editorial

Common dose range 150-400 mg from PsychonautWiki user reports (Ref 19), consistent with brief seed data. Effect profile based on phenibut class pharmacology and community reports.

Reasoning

Common dose range 150-400 mg from PsychonautWiki user reports (Ref 19), consistent with brief seed data. Effect profile based on phenibut class pharmacology and community reports.

Evidence basis: community_consensus_large

strongtrace

low

At strong doses (400–600 mg oral), sedation and motor impairment dominate. Anxiety suppression is complete, but cognitive euphoria gives way to thought deceleration, amnesia, and reduced decision-making capacity. Disinhibition is pronounced and may result in impulsive behavior. Emotional blunting may replace the empathic openness of lower doses. Physically, motor control impairment is significant — ataxia, slurred speech, and difficulty with coordinated movements are expected. Nausea may occur. Sedation is heavy, and remaining awake requires effort. Respiratory depression risk increases, particularly if combined with any other CNS depressant. Functional capacity is substantially impaired. Operating vehicles or machinery is dangerous. The commitment is 6–8 hours of primary effects with potential next-day residual sedation.

Editorial

Strong dose range 400-600 mg from PsychonautWiki user reports (Ref 19). Effect profile based on GABA-B agonist dose-response pharmacology at high receptor occupancy.

Reasoning

Strong dose range 400-600 mg from PsychonautWiki user reports (Ref 19). Effect profile based on GABA-B agonist dose-response pharmacology at high receptor occupancy.

Evidence basis: community_consensus_large

heavytrace

low

At heavy doses (600+ mg oral), the risk of severe adverse outcomes increases sharply. Deep sedation approaching unconsciousness is expected. Amnesia is near-complete for the experience. Motor coordination is profoundly impaired — standing and walking may be impossible. Cognitive function is severely compromised. Respiratory depression becomes a primary safety concern, especially with any concurrent CNS depressant use. Nausea, vomiting (with aspiration risk in a sedated state), and loss of protective reflexes are possible. Falls and injuries are a significant risk. This dose range approaches the territory where phenibut-class intoxication has produced coma requiring intubation. Medical supervision is strongly advisable. Recovery may extend beyond the typical 6–8 hour window, with residual impairment lasting into the following day.

Editorial

Heavy dose 600+ mg from PsychonautWiki user reports (Ref 19). Severe effect profile inferred from phenibut overdose case reports (Refs 4, 13, 17) applied to F-phenibut's higher GABA-B potency.

Reasoning

Heavy dose 600+ mg from PsychonautWiki user reports (Ref 19). Severe effect profile inferred from phenibut overdose case reports (Refs 4, 13, 17) applied to F-phenibut's higher GABA-B potency.

Evidence basis: community_consensus_large

History

current version

published Jun 4, 2026AI-generated—

versions

1 total

publication ledger

backfill Jun 4, 2026

Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.

full version history suggest a correction contact@psychedex.org

Sources

15 moderate · 11 weak

[1]
moderate
F-phenibut (beta-(4-Fluorophenyl)-GABA), a potent GABA-B receptor agonist, activates an outward-rectifying K+ current and suppresses action potentials in mouse cerebellar Purkinje cells
Irie T, Yamazaki D, Kikura-Hanajiri R · 2020 · European Journal of Pharmacology
doi.org/10.1016/j.ejphar.2020.173437 pubmed 3273598615 claims checked12 verified1 partial2 inconclusive
[2]
weak
4-Fluorophenibut (HandWiki Chemistry article)
HandWiki contributors · 2023
linkno claims checked
[3]
moderate
Monitoring the use of novel psychoactive substances in Australia by wastewater-based epidemiology
Jaunay EL, Bade R, Paxton KR, Nadarajan D, Barry DC, Zhai Y, Tscharke BJ, O'Brien JW, Mueller J, White JM, Simpson BS, Gerber C · 2024 · The Science of the Total Environment
doi.org/10.1016/j.scitotenv.2024.170473 pubmed 382862922 claims checked2 verified
[4]
moderate
Clinical Presentations and Treatment of Phenibut Toxicity and Withdrawal: A Systematic Literature Review
Weleff J, Kovacevich A, Burson J, Nero N, Anand A · 2023 · Journal of Addiction Medicine
doi.org/10.1097/adm.0000000000001141 pubmed 375790986 claims checked1 verified5 inconclusive
[5]
weak
Acute phenibut withdrawal: A comprehensive literature review and illustrative case report
Hardman MI, Sprung J, Weingarten TN · 2019 · Bosnian Journal of Basic Medical Sciences
doi.org/10.17305/bjbms.2018.4008 pubmed 305016084 claims checked4 verified
[6]
moderate
Diversity of structure and function of GABA-B receptors: a complexity of GABA-B-mediated signaling
Terunuma M · 2018 · Proceedings of the Japan Academy, Series B
doi.org/10.2183/pjab.94.026 pubmed 305419665 claims checked4 verified1 inconclusive
[7]
weak
F-Phenibut - PsychonautWiki
PsychonautWiki contributors · 2024
linkno claims checked
[8]
moderate
R-phenibut binds to the alpha2-delta subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects
Zvejniece L, Vavers E, Svalbe B, Veinberg G, Rizhanova K, Liepins V, Kalvinsh I, Dambrova M · 2015 · Pharmacology, Biochemistry, and Behavior
doi.org/10.1016/j.pbb.2015.07.014 pubmed 262344704 claims checked4 verified
[9]
moderate
Comparison of Nootropic and Neuroprotective Features of Aryl-Substituted Analogs of Gamma-Aminobutyric Acid
Tyurenkov IN, Borodkina LE, Bagmetova VV, Berestovitskaya VM, Vasil'eva OS · 2016 · Bulletin of Experimental Biology and Medicine
doi.org/10.1007/s10517-016-3198-4 pubmed 269061983 claims checked2 verified1 inconclusive
[10]
moderate
Comparative pharmacological activity of optical isomers of phenibut
Dambrova M, Zvejniece L, Liepinsh E, Cirule H, Zharkova O, Veinberg G, Kalvinsh I · 2008 · European Journal of Pharmacology
doi.org/10.1016/j.ejphar.2008.01.015 pubmed 182759582 claims checked2 verified
[11]
moderate
GABA-B Receptors and Alcohol Use Disorders: Preclinical Studies
Holtyn AF, Weerts EM · 2022 · Current Topics in Behavioral Neurosciences
doi.org/10.1007/7854_2020_178 pubmed 328080905 claims checked2 verified1 partial2 not supported
[12]
moderate
The GABA-B Receptor - Structure, Ligand Binding and Drug Development
Evenseth LSM, Gabrielsen M, Sylte I · 2020 · Molecules
doi.org/10.3390/molecules25133093 pubmed 326460322 claims checked1 verified1 inconclusive
[13]
weak
Toxidrome of an Easily Obtainable Nootropic: A Case Report of Phenibut Intoxication and Withdrawal Delirium
Martin R, Buffenstein I, Cho D, Kiyokawa M · 2024 · Journal of Clinical Psychopharmacology
doi.org/10.1097/jcp.0000000000001759 pubmed 379302021 claim checked1 verified
[14]
moderate
Phenibutan - an Illegal Food Supplement With Psychotropic Effects and Health Risks
Bonnet U, Scherbaum N, Schaper A, Soyka M · 2024 · Deutsches Arzteblatt International
doi.org/10.3238/arztebl.m2024.0003 pubmed 383773328 claims checked5 verified1 partial2 inconclusive
[15]
moderate
Mitochondrial-Protective Effects of R-Phenibut after Experimental Traumatic Brain Injury
Kupats E, Stelfa G, Zvejniece B, et al. · 2020 · Oxidative Medicine and Cellular Longevity
doi.org/10.1155/2020/9364598 pubmed 332740111 claim checked1 verified
[16]
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Phenibut dependence
Samokhvalov AV, Paton-Gay CL, Balchand K, Rehm J · 2013 · BMJ Case Reports
doi.org/10.1136/bcr-2012-008381 pubmed 233919594 claims checked3 verified1 inconclusive
[17]
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Coenen NCB, Dijkstra BAG, Batalla A, Schellekens AFA · 2019 · Journal of Clinical Psychopharmacology
doi.org/10.1097/jcp.0000000000001104 pubmed 314333442 claims checked2 verified
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Dissociative Intoxication and Prolonged Withdrawal Associated With Phenibut: A Case Report
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[19]
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Suspected phenibut poisoning with brainstem involvement
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doi.org/10.61409/v07250573 pubmed 417576662 claims checked2 verified
[20]
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doi.org/10.1080/15563650.2021.1973020 pubmed 345500381 claim checked1 verified
[21]
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[22]
moderate
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doi.org/10.1093/jat/bkac023 pubmed 354452671 claim checked1 verified
[23]
moderate
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Penzak SR, Bulloch M · 2024 · Journal of Clinical Pharmacology
doi.org/10.1002/jcph.2414 pubmed 383398752 claims checked1 verified1 inconclusive
[24]
weak
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VanDreese B, Holland A, Murray A · 2022 · WMJ
pubmed 354425851 claim checked1 not supported
[25]
moderate
The clinical toxicology of gamma-hydroxybutyrate, gamma-butyrolactone and 1,4-butanediol
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linkno claims checked

Claim Verification

Citation-bearing claims in this article were checked by an AI model against the abstract of the source they cite — every safety-critical claim, plus a sample of the rest. Verdicts below are model-issued, not human-issued; when an editor overrides a verdict, the override is recorded alongside it. Claims whose source does not support them are flagged for editorial review.

summary9 claims6verified1partial2inconclusive

verifiedWith an EC₅₀ of 23.3 µM at GABA-B — approximately 58 times more potent than phenibut and 4 times less potent than baclofen — F-phenibut occupies an intermediate position in the halogenated β-phenyl-GABA series^[1]99%

Verified

Abstract directly states all three EC₅₀ values (phenibut 1362 µM, F-phenibut 23.3 µM, baclofen 6.0 µM) and the ~58x and ~4x potency ratios.

EC50 for GABA-B-mediated outward K+ current in Purkinje cells: phenibut 1362 µM, F-phenibut 23.3 µM, baclofen 6.0 µM. F-phenibut ~58x more potent than phenibut, ~4x less potent than baclofen.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveThe first peer-reviewed pharmacological characterization was published in 2020, when Irie and colleagues determined its GABA-B potency via mouse cerebellar Purkinje cell electrophysiology^[1]75%

Inconclusive

Abstract confirms the method (Purkinje cell electrophysiology) and findings but does not state the publication year (2020), the authors' names, or confirm that this was the 'first' such characterization.

EC50 for GABA-B-mediated outward K+ current in Purkinje cells: phenibut 1362 µM, F-phenibut 23.3 µM, baclofen 6.0 µM.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedPopulation-level use has been confirmed through detection in Australian wastewater surveys.^[3]99%

Verified

Abstract directly confirms 4F-phenibut detected across 57 catchments in Australia in a wastewater-based epidemiology study.

4F-phenibut detected across 57 catchments alongside phenibut. Detection frequency ranged 3–100% of sites analyzed.

checked by claude-sonnet-4-6 · Apr 28, 2026

partialF-phenibut activates GABA-B receptors (EC₅₀ = 23.3 µM), triggering downstream Gαi/o-mediated inhibition of voltage-gated Ca²⁺ channels and activation of K⁺ conductances^[1]85%

Partial

Abstract confirms EC₅₀ = 23.3 µM and K⁺ current activation, but does not describe Gαi/o-mediated inhibition of voltage-gated Ca²⁺ channels. That VGCC mechanism is canonical GABA-B signaling documented elsewhere (e.g., citation 23), not in this abstract.

EC50 for GABA-B-mediated outward K+ current in Purkinje cells: F-phenibut 23.3 µM. Current is outward-rectifying, insensitive to Ba2+, Cs+, TEA-Cl.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedF-phenibut activates GABA-B receptors (EC₅₀ = 23.3 µM), triggering downstream Gαi/o-mediated inhibition of voltage-gated Ca²⁺ channels and activation of K⁺ conductances^[6]95%

Verified

Abstract directly describes GABA-B signaling via Gαi/o producing VGCC inactivation and K⁺ channel activation, supporting the downstream signaling component of the claim.

GABA-B receptors are GPCRs mediating slow inhibitory action via Gai/o. Activate inwardly rectifying K+ channels, inactivate voltage-gated Ca2+ channels.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBy structural analogy with phenibut, additional binding at the α₂-δ subunit of voltage-dependent calcium channels is expected but has not been directly measured.^[8]90%

Verified

Abstract establishes phenibut's α₂-δ binding affinity (Ki=23 µM for R-phenibut), providing the structural analogy basis for the claim about F-phenibut.

Binding affinities for α2-δ subunit: R-phenibut Ki=23 µM, S-phenibut Ki=39 µM, baclofen Ki=156 µM, gabapentin Ki=0.05 µM.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe primary acute hazard is its 58-fold potency increase over phenibut, creating substantial overdose risk when users miscalculate dose conversions^[1]90%

Verified

Abstract directly confirms the ~58-fold potency difference. The overdose risk inference follows reasonably from the potency data.

F-phenibut ~58x more potent than phenibut, ~4x less potent than baclofen.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveTolerance develops within days of continuous use, and physical dependence with a severe withdrawal syndrome — including psychomotor agitation, autonomic instability, psychosis, and seizures — is documented for the phenibut class^[4]70%

Inconclusive

Abstract describes only that this is a systematic review of phenibut toxicity and withdrawal — too sparse to verify specific symptoms (agitation, psychosis, seizures) or the 'within days' tolerance timeline.

Systematic review of published articles evaluating phenibut toxicity and withdrawal cases to understand clinical presentations and treatments.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedTolerance develops within days of continuous use, and physical dependence with a severe withdrawal syndrome — including psychomotor agitation, autonomic instability, psychosis, and seizures — is documented for the phenibut class^[5]80%

Verified

Abstract confirms severe psychomotor agitation and autonomic signs (NMS/serotonin syndrome mimicry) in phenibut withdrawal. 'Within days' timeline and seizures not explicitly confirmed but core of claim supported.

Severe psychomotor agitation prominent. Neurologic and autonomic signs may mimic serotonin or neuroleptic malignant syndrome.

checked by claude-sonnet-4-6 · Apr 28, 2026

history3 claims2verified1inconclusive

verifiedThe parent compound, phenibut, was discovered and introduced into clinical practice in the Soviet Union in the 1960s, where it gained widespread use as an anxiolytic and nootropic agent99%

Verified

Abstract directly states 'phenibut discovered and introduced into clinical practice in Russia in the 1960s.'

Historical review: phenibut discovered and introduced into clinical practice in Russia in the 1960s.

source: Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedF-phenibut became commercially available from online nootropic and research chemical vendors in the 2010s, marketed under names including "F-phenibut," "fluorophenibut," "fluorobut," and "4F-phenibut." Its presence in the general population was confirmed by a systematic wastewater-based epidemiology survey in Australia spanning February 2022 to February 2023, which detected 4-fluorophenibut alongside other novel psychoactive substances.^[3]97%

Verified

Abstract confirms the wastewater epidemiology study in Australia (Feb 2022–Feb 2023) detecting 4F-phenibut across 57 catchments. The 2010s online availability claim is not addressed by this abstract but the citation is clearly for the wastewater component.

Wastewater-based epidemiology of NPS in Australia (Feb 2022–Feb 2023). 4F-phenibut detected across 57 catchments alongside phenibut.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveThe first peer-reviewed study specifically investigating F-phenibut's mechanism of action was published by Irie, Yamazaki, and Kikura-Hanajiri in 2020 in the European Journal of Pharmacology^[1]70%

Inconclusive

Abstract confirms the study's content (Purkinje cell electrophysiology, EC₅₀ values) but does not state the year (2020), authors' names, journal name, or that this was the 'first' such study.

EC50 for GABA-B-mediated outward K+ current in Purkinje cells: phenibut 1362 µM, F-phenibut 23.3 µM, baclofen 6.0 µM.

checked by claude-sonnet-4-6 · Apr 28, 2026

chemistry5 claims4verified1not supported

verifiedThe defining structural feature is a fluorine atom at the para position of the phenyl ring, placing F-phenibut in a halogen series between the unsubstituted phenibut and the para-chloro-substituted baclofen (β-(4-chlorophenyl)-GABA)80%

Verified

Abstract discusses structure-activity relationships of phenibut and derivatives including baclofen, providing context for the halogen series claim. F-phenibut specifically is not named in the abstract but the review's scope covers this structural territory.

Discusses structure-activity relationship of phenibut and derivatives including baclofen.

source: Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug

checked by claude-sonnet-4-6 · Apr 28, 2026

Verified

Abstract covers structure-activity comparison of aryl GABA analogs including phenibut and baclofen, contextualizing the halogen series.

Aryl GABA analogs (phenibut, baclofen, tolibut) show nootropic activity. Structure-activity comparison of the chemical series.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe electron-withdrawing fluorine enhances GABA-B receptor binding, consistent with the approximately 58-fold potency increase over unsubstituted phenibut.^[1]85%

Verified

Abstract directly confirms the ~58-fold potency increase. The fluorine electron-withdrawing mechanism is a reasonable chemical inference from the potency data, not contradicted by the abstract.

F-phenibut ~58x more potent than phenibut, ~4x less potent than baclofen.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBy analogy with phenibut, where the R-enantiomer carries essentially all GABA-B agonist activity and S-phenibut is inactive at GABA-B, and with baclofen, where R(+)-baclofen is the pharmacologically dominant enantiomer, the R-enantiomer of F-phenibut is expected to carry the majority of GABA-B activity^[10]93%

Verified

Abstract directly states 'S-phenibut inactive' and 'R-phenibut 2x more potent than racemic form,' supporting the analogy for expected F-phenibut enantiomer selectivity.

GABA-B binding affinities: racemic phenibut Ki=177 uM, R-phenibut Ki=92 uM, baclofen Ki=6.0 uM. S-phenibut inactive. R-phenibut 2x more potent than racemic form.

checked by claude-sonnet-4-6 · Apr 28, 2026

not supportedBy analogy with phenibut, where the R-enantiomer carries essentially all GABA-B agonist activity and S-phenibut is inactive at GABA-B, and with baclofen, where R(+)-baclofen is the pharmacologically dominant enantiomer, the R-enantiomer of F-phenibut is expected to carry the majority of GABA-B activity^[11]90%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

Abstract covers GABA-B receptors in alcohol use disorder context. It contains no information about phenibut or baclofen enantiomers, stereochemistry, or the analogy being claimed.

GABA-B receptor activation (primarily via baclofen) reduces stimulating/rewarding effects of alcohol, signs of alcohol withdrawal, alcohol drinking.

checked by claude-sonnet-4-6 · Apr 28, 2026

pharmacology12 claims11verified1partial

verifiedF-phenibut is a potent agonist at the GABA-B receptor, a class C G-protein coupled receptor forming obligate GB1/GB2 heterodimers^[6]99%

Verified

Abstract directly states 'Obligate heterodimers (R1+R2 subunits)' confirming the obligate heterodimer structure.

Obligate heterodimers (R1+R2 subunits).

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedF-phenibut is a potent agonist at the GABA-B receptor, a class C G-protein coupled receptor forming obligate GB1/GB2 heterodimers^[12]95%

Verified

Abstract directly describes GABA-B as a class C GPCR heterodimer.

GABA-B class C GPCR heterodimer. VFT and 7TM domains.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedDownstream signaling proceeds through Gαi/o proteins, producing inactivation of voltage-gated Ca²⁺ channels, activation of inwardly rectifying K⁺ channels (GIRK/Kir3), and inhibition of adenylate cyclase.^[6]99%

Verified

Abstract explicitly lists all three downstream effectors: inwardly rectifying K+ channels, VGCC inactivation, and adenylate cyclase inhibition, all via Gai/o.

GABA-B receptors are GPCRs mediating slow inhibitory action via Gai/o. Activate inwardly rectifying K+ channels, inactivate voltage-gated Ca2+ channels, inhibit adenylate cyclase.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedIn mouse cerebellar Purkinje cells, F-phenibut activated K⁺ currents with an EC₅₀ of 23.3 µM, compared with 1362 µM for phenibut and 6.0 µM for baclofen — establishing F-phenibut as approximately 58 times more potent than phenibut and 4 times less potent than baclofen at GABA-B^[1]99%

Verified

All three EC₅₀ values and both potency ratios are directly stated in the abstract.

EC50 for GABA-B-mediated outward K+ current in Purkinje cells: phenibut 1362 µM, F-phenibut 23.3 µM, baclofen 6.0 µM. F-phenibut ~58x more potent than phenibut, ~4x less potent than baclofen.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedF-phenibut suppressed action potential generation in Purkinje cells, consistent with its CNS depressant profile.^[1]99%

Verified

Abstract directly states 'F-phenibut suppresses action potential generation in Purkinje cells.'

F-phenibut suppresses action potential generation in Purkinje cells.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedR-phenibut binds the α₂-δ subunit with Ki = 23 µM, approximately 4 times higher affinity than its GABA-B binding (Ki = 92 µM), and the anti-nociceptive effects of R-phenibut are mediated via α₂-δ rather than GABA-B, as demonstrated by insensitivity to the GABA-B antagonist CGP35348^[8]97%

Verified

Abstract confirms Ki=23 µM at α₂-δ, '4x higher than GABA-B affinity,' and anti-nociceptive effects mediated via α₂-δ not GABA-B. CGP35348 not mentioned but the mechanism conclusion is directly confirmed.

Binding affinities for α2-δ subunit: R-phenibut Ki=23 µM. R-phenibut α2-δ affinity is 4x higher than GABA-B affinity. Anti-nociceptive effects mediated via α2-δ, not GABA-B.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedPhenibut also stimulates dopamine receptors and antagonizes β-phenethylamine (PEA), a putative endogenous anxiogenic99%

Verified

Abstract directly states phenibut 'stimulates dopamine receptors and antagonizes β-phenethylamine (PEA).'

Also stimulates dopamine receptors and antagonizes β-phenethylamine (PEA).

source: Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedPhenibut exhibits minor GABA-A activity at very high concentrations, but this is not expected to be clinically significant for F-phenibut at doses producing GABA-B-mediated effects.^[13]92%

Verified

Abstract confirms phenibut has 'minor GABA-A activity,' supporting the claim about minor GABA-A effects at high concentrations.

Phenibut acts as GABA-B agonist and has high affinity at alpha-2-delta subunit calcium channels (gabapentinoid activity), plus minor GABA-A activity.

checked by claude-sonnet-4-6 · Apr 28, 2026

partialPhenibut exhibits oral bioavailability of approximately 65%, with maximal brain concentrations reached within approximately 15 minutes of administration in mice (R-phenibut data)^[14]85%

Partial

Abstract confirms bioavailability ~65%, but does not mention the 15-minute brain concentration finding. That data point is from a different citation (citation [16], R-phenibut CNS penetration study).

Elimination t1/2 5-6h, bioavailability ~65%, excreted unchanged.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedPhenibut exhibits oral bioavailability of approximately 65%, with maximal brain concentrations reached within approximately 15 minutes of administration in mice (R-phenibut data)^[15]99%

Verified

Abstract directly states 'R-phenibut reaches brain tissue 15 min after i.p./p.o.' confirming the 15-minute brain penetration finding.

R-phenibut reaches brain tissue 15 min after i.p./p.o. CNS penetration data.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe elimination half-life is approximately 5–6 hours^[14]99%

Verified

Abstract directly states 'Elimination t1/2 5-6h.'

Elimination t1/2 5-6h, bioavailability ~65%, excreted unchanged.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedHepatic metabolism is virtually absent — phenibut is excreted largely unchanged in urine — and CYP enzyme involvement has not been established.^[14]95%

Verified

Abstract states 'excreted unchanged,' directly supporting minimal hepatic metabolism. CYP absence is a reasonable inference from renal excretion unchanged.

Elimination t1/2 5-6h, bioavailability ~65%, excreted unchanged.

checked by claude-sonnet-4-6 · Apr 28, 2026

neuroscience10 claims7verified3inconclusive

verifiedBaclofen reduces the rewarding properties of alcohol and stimulants, yet phenibut-class compounds themselves carry significant dependence liability — suggesting that negative reinforcement (escape from baseline anxiety, relief from inter-dose withdrawal) drives compulsive use more powerfully than positive hedonic reward.^[11]85%

Verified

Abstract confirms baclofen/GABA-B reduces stimulating/rewarding effects of alcohol and alcohol-seeking, providing the factual premise for the negative reinforcement argument.

GABA-B receptor activation (primarily via baclofen) reduces stimulating/rewarding effects of alcohol, signs of alcohol withdrawal, alcohol drinking, motivational properties of alcohol, and alcohol-seeking.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveGABA-B receptors are distributed throughout the brain with high densities in the cerebral cortex, thalamus, cerebellum, hippocampus, and amygdala^[12]70%

Inconclusive

Abstract describes GABA-B structure, ligand binding, and drug development; it mentions dysfunction links to anxiety/depression but does not provide regional brain distribution data.

GABA-B class C GPCR heterodimer. VFT and 7TM domains. Only baclofen approved. Dysfunction linked to anxiety, depression, alcohol addiction.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedActivation of presynaptic GABA-B heteroreceptors inhibits neurotransmitter release (glutamate, monoamines, GABA itself) via inactivation of voltage-gated Ca²⁺ channels, while postsynaptic GABA-B receptors hyperpolarize neurons through activation of K⁺ conductances.^[6]88%

Verified

Abstract directly confirms VGCC inactivation and K+ channel activation as GABA-B downstream effectors. Presynaptic/postsynaptic distinction and specific neurotransmitters not mentioned explicitly but the effector mechanisms are confirmed.

Activate inwardly rectifying K+ channels, inactivate voltage-gated Ca2+ channels, inhibit adenylate cyclase.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedIn cerebellar Purkinje cells specifically, F-phenibut activates an outward-rectifying K⁺ current rather than the conventional GIRK-mediated inward rectification^[1]97%

Verified

Abstract directly confirms the current in Purkinje cells is 'outward-rectifying,' contrasting with the inwardly rectifying K+ channels described in other GABA-B contexts.

Current is outward-rectifying, insensitive to Ba2+, Cs+, TEA-Cl.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe putative α₂-δ VDCC subunit binding (inferred from phenibut data) would add a gabapentinoid component — reduction of excitatory neurotransmitter release through presynaptic Ca²⁺ channel modulation — that could contribute to anxiolysis, anti-nociception, and the subjective warmth reported by users.^[8]90%

Verified

Abstract confirms α₂-δ binding and gabapentin-like anti-nociceptive effects mediated via α₂-δ, supporting the gabapentinoid component inference.

R-phenibut binds to the α2-δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects. Anti-nociceptive effects mediated via α2-δ, not GABA-B.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedIf dopaminergic activity analogous to phenibut's is present, mesolimbic dopamine pathway facilitation could explain the mood elevation and motivation enhancement reported at lower doses, as well as the compulsive redosing potential.87%

Verified

Abstract directly confirms phenibut 'stimulates dopamine receptors,' providing the basis for this mechanistic inference about F-phenibut.

Also stimulates dopamine receptors and antagonizes β-phenethylamine (PEA).

source: Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveGABA-B receptors in the reticular thalamic nucleus regulate sensory information flow to the cortex; enhanced GABAergic inhibition at this level reduces cortical arousal and sensory processing intensity, producing anxiolysis and, at higher levels of activation, sedation and coma.^[6]70%

Inconclusive

Abstract covers general GABA-B receptor signaling mechanisms but does not specifically address the reticular thalamic nucleus or region-specific effects on cortical arousal.

GABA-B receptors are GPCRs mediating slow inhibitory action via Gai/o. Activate inwardly rectifying K+ channels, inactivate voltage-gated Ca2+ channels, inhibit adenylate cyclase.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveThe nootropic paradox of phenibut-class compounds — cognitive enhancement at low doses, cognitive impairment at high doses — may reflect a dose-dependent shift in the balance between presynaptic disinhibition (reducing excessive glutamate inhibition at low GABA-B occupancy) and postsynaptic inhibition (direct neuronal hyperpolarization at high occupancy).^[9]65%

Inconclusive

Abstract confirms nootropic activity of aryl GABA analogs but does not describe the dose-dependent presynaptic/postsynaptic balance mechanism proposed in the claim.

Aryl GABA analogs (phenibut, baclofen, tolibut) show nootropic activity. Structure-activity comparison of the chemical series.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedIs the outward-rectifying K⁺ current observed in Purkinje cells present in other brain regions, or is it cerebellar-specific? If widespread, it represents a novel GABA-B effector pathway with implications for the entire compound class.^[1]88%

Verified

Abstract confirms the outward-rectifying K+ current finding in Purkinje cells, establishing the factual premise from which this research question logically follows.

Current is outward-rectifying, insensitive to Ba2+, Cs+, TEA-Cl. F-phenibut suppresses action potential generation in Purkinje cells.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedDoes F-phenibut produce neuroplasticity changes (BDNF upregulation, synaptogenesis) at sub-sedating doses, as suggested by phenibut's nootropic effects in animal models?^[9]82%

Verified

Abstract confirms nootropic and neuroprotective activity of aryl GABA analogs in animal models, providing the basis for this research question about neuroplasticity.

Aryl GABA analogs (phenibut, baclofen, tolibut) show nootropic activity. Structure-activity comparison of the chemical series.

checked by claude-sonnet-4-6 · Apr 28, 2026

receptor pharmacology3 claims2verified1not supported

verifiedIrie et al. reported that the K⁺ current activated by F-phenibut, phenibut, and baclofen in cerebellar Purkinje cells is outward-rectifying — pharmacologically distinct from the inwardly rectifying K⁺ current (GIRK/Kir3) conventionally associated with GABA-B receptor activation^[1]97%

Verified

Abstract directly confirms the current is 'outward-rectifying, insensitive to Ba2+, Cs+, TEA-Cl,' which are pharmacological signatures distinguishing it from conventional GIRK channels.

Current is outward-rectifying, insensitive to Ba2+, Cs+, TEA-Cl.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBy analogy with phenibut, where R-phenibut is approximately 2 times more potent than the racemate and S-phenibut is inactive at GABA-B, and with baclofen, where R(+)-baclofen is the active enantiomer, the pharmacological activity of racemic F-phenibut is expected to reside predominantly in the R-enantiomer^[10]99%

Verified

Abstract directly states R-phenibut is 2x more potent than racemic and S-phenibut is inactive, fully supporting the analogy.

GABA-B binding affinities: racemic phenibut Ki=177 uM, R-phenibut Ki=92 uM. S-phenibut inactive. R-phenibut 2x more potent than racemic form.

checked by claude-sonnet-4-6 · Apr 28, 2026

not supportedBy analogy with phenibut, where R-phenibut is approximately 2 times more potent than the racemate and S-phenibut is inactive at GABA-B, and with baclofen, where R(+)-baclofen is the active enantiomer, the pharmacological activity of racemic F-phenibut is expected to reside predominantly in the R-enantiomer^[11]90%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

Abstract covers GABA-B and alcohol use disorders. It contains no information about phenibut enantiomers, stereochemistry, or baclofen optical isomers.

GABA-B receptor activation (primarily via baclofen) reduces stimulating/rewarding effects of alcohol, signs of alcohol withdrawal, alcohol drinking, motivational properties of alcohol, and alcohol-seeking.

checked by claude-sonnet-4-6 · Apr 28, 2026

pharmacokinetic detail1 claim1verified

verifiedGiven the minimal hepatic metabolism of the phenibut class, CYP-mediated pharmacokinetic interactions with F-phenibut are not expected^[14]90%

Verified

Abstract states phenibut is 'excreted unchanged,' supporting minimal hepatic/CYP metabolism as the basis for the interaction claim.

Elimination t1/2 5-6h, bioavailability ~65%, excreted unchanged.

checked by claude-sonnet-4-6 · Apr 28, 2026

safety28 claims18verified1partial8inconclusive1not supported

inconclusiveManagement is supportive: airway protection, ventilatory support, and hemodynamic monitoring.^[14]80%

Inconclusive

Abstract contains only PK data and legal information. No clinical management guidance is described.

Elimination t1/2 5-6h, bioavailability ~65%, excreted unchanged.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedManagement is supportive: airway protection, ventilatory support, and hemodynamic monitoring.^[21]90%

Verified

Abstract describes phenibut intoxication 'requiring sedation and mechanical ventilation,' confirming ventilatory/airway support as core management.

30-year-old with phenibut intoxication requiring sedation and mechanical ventilation.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe primary acute hazard derives from F-phenibut's approximately 58-fold higher GABA-B potency relative to phenibut^[1]97%

Verified

Abstract directly states F-phenibut is ~58x more potent than phenibut at GABA-B.

F-phenibut ~58x more potent than phenibut, ~4x less potent than baclofen.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveAt equipotent GABA-B activation, the clinical presentation of severe intoxication is expected to resemble phenibut overdose: progressive CNS depression ranging from somnolence to coma, respiratory depression requiring intubation, and fall-related injuries.^[14]80%

Inconclusive

Abstract provides only PK data (t½, bioavailability, excretion) and legal/epidemiological information. No clinical presentation of overdose is described.

Elimination t1/2 5-6h, bioavailability ~65%, excreted unchanged. GIZ-Nord: 17 cases 2018-2022.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedMore than 80 cases of coma and death have been associated with phenibut consumption and withdrawal in the United States, though most involve polydrug contexts^[20]90%

Verified

Abstract directly states 'More than 80 cases of coma and death associated.' The polydrug qualifier is not confirmed by abstract but the primary statistic is directly stated.

More than 80 cases of coma and death associated. FDA warned phenibut not permitted in supplements.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedA case of suspected phenibut intoxication presenting with partial brainstem areflexia has been documented, and dissociative features during intoxication have been reported.^[19]99%

Verified

Abstract directly confirms 'Unconscious patient with brainstem areflexia after phenibut ingestion.'

Unconscious patient with brainstem areflexia after phenibut ingestion; ICU admission.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedA case of suspected phenibut intoxication presenting with partial brainstem areflexia has been documented, and dissociative features during intoxication have been reported.^[18]99%

Verified

Abstract directly confirms dissociative intoxication with phenibut.

Case report of dissociative intoxication and prolonged withdrawal associated with phenibut.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedIdentification requires specialized LC-MS/MS methods not routinely available in emergency departments^[21]88%

Verified

Abstract confirms 'No readily available confirmatory lab tests,' supporting the claim that routine ED testing is unavailable. LC-MS/MS not named specifically but the detection gap is confirmed.

No readily available confirmatory lab tests.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedIdentification requires specialized LC-MS/MS methods not routinely available in emergency departments^[22]82%

Verified

Abstract highlights 'Routine drug screening limitations' in the context of NPS adverse events, supporting the claim about specialized detection needs.

Routine drug screening limitations highlighted.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedAcute psychological adverse effects at supratherapeutic doses include paradoxical anxiety (anxiogenic rebound), cognitive impairment, amnesia, and dissociative symptoms^[18]80%

Verified

Abstract directly confirms dissociative intoxication with phenibut. Paradoxical anxiety, cognitive impairment, and amnesia are not mentioned but not contradicted; dissociative symptoms are clearly supported.

Case report of dissociative intoxication and prolonged withdrawal associated with phenibut.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusivePsychosis has been documented during both intoxication and withdrawal in phenibut case series.^[4]65%

Inconclusive

Abstract is too sparse (only describes the study design as a systematic review) to confirm specific symptom documentation such as psychosis.

Systematic review of published articles evaluating phenibut toxicity and withdrawal cases to understand clinical presentations and treatments.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveTolerance to F-phenibut develops rapidly — within days of continuous use — consistent with phenibut class behavior documented in clinical case reports^[4]65%

Inconclusive

Abstract too sparse to verify the specific 'within days' tolerance development timeline.

Systematic review of published articles evaluating phenibut toxicity and withdrawal cases to understand clinical presentations and treatments.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveTolerance to F-phenibut develops rapidly — within days of continuous use — consistent with phenibut class behavior documented in clinical case reports^[16]70%

Inconclusive

Abstract confirms tolerance and withdrawal develop rapidly ('within 3-4 h of last use') but this refers to withdrawal onset, not the timeframe over which tolerance itself develops (claimed as 'within days of continuous use').

Tolerance and significant withdrawal within 3-4 h of last use.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedWithdrawal symptoms can begin within 3–4 hours of the last dose and include severe psychomotor agitation, autonomic instability, neurological signs mimicking serotonin syndrome or neuroleptic malignant syndrome, psychosis, and seizures^[16]83%

Verified

Abstract directly confirms 'significant withdrawal within 3-4 h of last use,' establishing the timing. Specific symptoms (agitation, NMS/SS mimicry) are supported by other citations in this claim set.

Tolerance and significant withdrawal within 3-4 h of last use.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveWithdrawal symptoms can begin within 3–4 hours of the last dose and include severe psychomotor agitation, autonomic instability, neurological signs mimicking serotonin syndrome or neuroleptic malignant syndrome, psychosis, and seizures^[4]65%

Inconclusive

Abstract too sparse to confirm specific withdrawal symptoms or timing.

Systematic review of published articles evaluating phenibut toxicity and withdrawal cases to understand clinical presentations and treatments.

checked by claude-sonnet-4-6 · Apr 28, 2026

Verified

Abstract directly confirms severe psychomotor agitation and neurological/autonomic signs mimicking serotonin syndrome or NMS in phenibut withdrawal.

Severe psychomotor agitation prominent. Neurologic and autonomic signs may mimic serotonin or neuroleptic malignant syndrome.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe higher potency of F-phenibut relative to phenibut suggests potentially more rapid dependence development at lower absolute doses, though this has not been formally studied.^[1]85%

Verified

Abstract confirms the ~58-fold potency difference that forms the factual basis for this inference. The claim appropriately qualifies that dependence is not formally studied.

F-phenibut ~58x more potent than phenibut, ~4x less potent than baclofen.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBaclofen substitution and taper is the primary documented withdrawal management strategy, at approximately 10 mg baclofen per 1 g phenibut equivalence^[16]99%

Verified

Abstract directly states 'Substitution with baclofen (~10 mg baclofen per gram phenibut), then baclofen taper over 9 weeks.'

Substitution with baclofen (~10 mg baclofen per gram phenibut), then baclofen taper over 9 weeks.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBenzodiazepines and phenobarbital are alternatives; phenobarbital may be preferred when seizure risk is elevated^[23]99%

Verified

Abstract directly states 'patients treated with baclofen, benzodiazepines, and phenobarbital' and 'phenobarbital preferred if seizure risk.'

Among 29 cases of withdrawal, patients treated with baclofen, benzodiazepines, and phenobarbital. Baclofen tapers successful; phenobarbital preferred if seizure risk.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveAncillary agents include antipsychotics, dexmedetomidine, gabapentin, and pregabalin.^[23]75%

Inconclusive

Abstract mentions only baclofen, benzodiazepines, and phenobarbital as treatment agents. Antipsychotics, dexmedetomidine, gabapentin, and pregabalin are not mentioned; they may be in the full text.

Among 29 cases of withdrawal, patients treated with baclofen, benzodiazepines, and phenobarbital.

checked by claude-sonnet-4-6 · Apr 28, 2026

not supportedAdditive respiratory depression from concurrent GABA-B agonism and µ-opioid receptor activation can be life-threatening.^[24]90%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

Abstract describes only chronic phenibut use and severe withdrawal. There is no mention of opioid interactions, µ-opioid receptor activation, or respiratory depression from combined use.

Chronic phenibut use and severe withdrawal. Unregulated in USA.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedPolydependence on phenibut and benzodiazepines has been documented, requiring coordinated withdrawal management.^[17]99%

Verified

Abstract directly describes 'comorbid dependence on phenibut and benzodiazepines managed by baclofen tapering.'

Case of comorbid phenibut and benzodiazepine dependence managed by baclofen tapering.

checked by claude-sonnet-4-6 · Apr 28, 2026

partialAlcohol presents a complex interaction: GABA-B agonism reduces the stimulating and rewarding properties of alcohol, but concurrent use produces additive CNS depression with increased risk of respiratory compromise and aspiration.^[11]85%

Partial

Abstract directly supports the first half (GABA-B agonism reduces alcohol's stimulating/rewarding properties). The second half (additive CNS depression, respiratory compromise, aspiration risk from concurrent use) is not addressed in the abstract.

GABA-B receptor activation (primarily via baclofen) reduces stimulating/rewarding effects of alcohol, signs of alcohol withdrawal, alcohol drinking, motivational properties of alcohol, and alcohol-seeking.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedOther GABA-B agonists (baclofen, ghb, gbl) produce additive GABA-B receptor activation with risk of severe CNS depression.^[25]90%

Verified

Abstract confirms GHB and analogs act as CNS depressants via GABA-B agonism, directly supporting the additive CNS depression risk from concurrent GABA-B agonist use.

GHB and analogs as CNS depressants. GABA-B agonism mechanism of toxicity.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedPhenibut withdrawal has been noted to mimic serotonin syndrome clinically, but this represents a mimicry syndrome rather than a true serotonergic pharmacological interaction^[5]95%

Verified

Abstract directly states neurological and autonomic signs 'may mimic serotonin or neuroleptic malignant syndrome,' supporting the mimicry characterization.

Neurologic and autonomic signs may mimic serotonin or neuroleptic malignant syndrome.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedGiven the minimal hepatic metabolism of the phenibut class, CYP-mediated pharmacokinetic drug interactions are not expected but have not been studied.^[14]90%

Verified

Abstract states phenibut is 'excreted unchanged,' directly supporting minimal hepatic metabolism and the implication of negligible CYP involvement.

Elimination t1/2 5-6h, bioavailability ~65%, excreted unchanged.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveSeizure disorders — While acute GABA-B agonism has anticonvulsant properties, abrupt discontinuation after regular use may precipitate seizures.^[4]65%

Inconclusive

Abstract too sparse to confirm anticonvulsant properties or seizure risk upon discontinuation.

Systematic review of published articles evaluating phenibut toxicity and withdrawal cases to understand clinical presentations and treatments.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedRenal impairment — Phenibut is excreted largely unchanged in urine^[14]99%

Verified

Abstract directly states phenibut is 'excreted unchanged.'

Elimination t1/2 5-6h, bioavailability ~65%, excreted unchanged.

checked by claude-sonnet-4-6 · Apr 28, 2026

clinical evidence7 claims7verified

verifiedPublished phenibut clinical data include a systematic literature review of toxicity and withdrawal encompassing multiple case reports, a comprehensive review of acute withdrawal, and individual case reports of dependence, polydependence with benzodiazepines, dissociative intoxication, and suspected brainstem involvement during severe intoxication^[4]99%

Verified

Abstract directly describes this as a 'Systematic review of published articles evaluating phenibut toxicity and withdrawal cases,' confirming one of the cited sources listed in the claim.

Systematic review of published articles evaluating phenibut toxicity and withdrawal cases to understand clinical presentations and treatments.

checked by claude-sonnet-4-6 · Apr 28, 2026

Verified

Abstract describes 'Review of 22 published phenibut withdrawal cases,' confirming the comprehensive review of acute withdrawal cited in the claim.

Review of 22 published phenibut withdrawal cases. Severe psychomotor agitation prominent.

checked by claude-sonnet-4-6 · Apr 28, 2026

Verified

Abstract directly describes a case of phenibut dependence, confirming the individual case report component of the claim.

Case of phenibut dependence for self-medication of anxiety, insomnia, and alcohol cravings.

checked by claude-sonnet-4-6 · Apr 28, 2026

Verified

Abstract directly describes 'comorbid dependence on phenibut and benzodiazepines,' confirming the polydependence case report component of the claim.

Case of comorbid phenibut and benzodiazepine dependence managed by baclofen tapering.

checked by claude-sonnet-4-6 · Apr 28, 2026

Verified

Abstract directly describes 'dissociative intoxication and prolonged withdrawal with phenibut,' confirming that component of the claim.

Case report of dissociative intoxication and prolonged withdrawal associated with phenibut.

checked by claude-sonnet-4-6 · Apr 28, 2026

Verified

Abstract describes 'brainstem areflexia after phenibut ingestion,' directly confirming the brainstem involvement case report component.

Unconscious patient with brainstem areflexia after phenibut ingestion; ICU admission.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe sole primary pharmacology study — Irie et al. (2020) — was an in vitro electrophysiology investigation in mouse cerebellar Purkinje cells, not a clinical or whole-animal efficacy study.^[1]97%

Verified

Abstract clearly describes an in vitro Purkinje cell electrophysiology study measuring K+ currents, confirming the in vitro (not clinical or whole-animal) nature of the investigation.

EC50 for GABA-B-mediated outward K+ current in Purkinje cells: phenibut 1362 µM, F-phenibut 23.3 µM, baclofen 6.0 µM.

checked by claude-sonnet-4-6 · Apr 28, 2026

comparative pharmacology4 claims4verified

verifiedAll EC₅₀ values derive from the same assay system (mouse cerebellar Purkinje cell K⁺ current).^[1]99%

Verified

Abstract reports all three EC₅₀ values (phenibut, F-phenibut, baclofen) from the same Purkinje cell K+ current assay in a single study.

EC50 for GABA-B-mediated outward K+ current in Purkinje cells: phenibut 1362 µM, F-phenibut 23.3 µM, baclofen 6.0 µM.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedR-phenibut binds the α₂-δ VDCC subunit with Ki = 23 µM — far weaker than gabapentin (Ki = 0.05 µM) but sufficient to produce gabapentin-like anti-nociceptive effects in animal models^[8]99%

Verified

Abstract directly states R-phenibut Ki=23 µM, gabapentin Ki=0.05 µM, and anti-nociceptive effects mediated via α₂-δ — all directly supporting the claim.

Binding affinities for α2-δ subunit: R-phenibut Ki=23 µM, gabapentin Ki=0.05 µM. Anti-nociceptive effects mediated via α2-δ, not GABA-B.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedUnlike baclofen, which is used clinically as a skeletal muscle relaxant and is under investigation for alcohol use disorder, F-phenibut has no clinical applications and no regulatory pathway^[11]85%

Verified

Abstract confirms strong preclinical evidence for GABA-B as therapeutic target for AUD and baclofen's role, supporting the clinical investigation context for baclofen.

Strong preclinical evidence for GABA-B as therapeutic target for AUD.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedUnlike phenibut, which is available as a prescription medication in Russia and as an unregulated supplement in some Western markets, F-phenibut exists exclusively in the research chemical market85%

Verified

Abstract confirms phenibut was 'introduced into clinical practice in Russia,' supporting its prescription status there.

Historical review: phenibut discovered and introduced into clinical practice in Russia in the 1960s.

source: Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug

checked by claude-sonnet-4-6 · Apr 28, 2026

Coverage & Gaps

effect links

100 links · 99 approved · 23 audited1/100 with evidence basis

Research Trail

substance-article pipeline-v5 Apr 28, 2026

Step	Source	Query	Results
1database lookup	PubChem	fluorophenibut	0 results
2database lookup	PubChem	4-fluorophenibut (CID 103611)	1 result, 1 selected
3literature search	PubMed	F-phenibut fluorophenibut pharmacology	0 results
4literature search	PubMed	phenibut GABA-B receptor agonist pharmacology	15 results, 6 selected
5clinical trial search	ClinicalTrials.gov	F-phenibut fluorophenibut	0 results
6database lookup	PubMed	PMID 32735986 full record	1 result
7literature search	OpenAlex	F-phenibut fluorophenibut GABA-B receptor	2 results, 1 selected
8literature search	PubMed	phenibut alpha-2-delta calcium channel voltage gated gabapentin binding	1 result
9web search	WebSearch	F-phenibut 4-fluorophenibut legal status scheduling UK EU US Australia	10 results, 1 selected
10web search	WebSearch	F-phenibut CGP-11130 SMILES structure history discovery	10 results, 2 selected
11document retrieval	HandWiki	—	1 result, 3 selected
12document retrieval	PMC	—	1 result, 2 selected
13web search	WebSearch	phenibut Australia Schedule 4 TGA 2021 scheduling	10 results, 1 selected
14literature search	PubMed	Zvejniece R-phenibut pharmacology neuroprotective	2 results, 2 selected
15web search	WebSearch	F-phenibut Canada legal controlled substance NPS survey	10 results, 1 selected
16literature search	PubMed	baclofen GABA-B agonist abuse dependence withdrawal treatment	5 results, 1 selected
17web search	WebSearch	F-phenibut CGP-11130 GABA-B IC50 original paper reference	10 results, 0 selected
18document retrieval	PsychonautWiki	—	1 result, 1 selected
19literature search	PubMed	Zvejniece phenibut GABA-B pharmacology Latvia	2 results, 2 selected
20database lookup	PubMed	PMID 34550038 phenibut dietary supplement FDA warning	1 result, 1 selected
21web search	WebSearch	WHO ECDD phenibut 44th pre-review scheduling recommendation	10 results, 1 selected
22document retrieval	PMC	—	1 result, 2 selected
23cross reference	Multiple	F-phenibut dose/duration cross-reference PsychonautWiki vs brief seed data	2 results, 1 selected
24data extraction	Multiple	Compile all F-phenibut chemical identity data	1 result, 1 selected

Research document (raw, unedited pipeline output)

# Research Output: F-Phenibut

## Chemical Identity

**Verified via PubChem CID 103611 and HandWiki cross-reference:**

| Property | Value |
|---|---|
| Preferred IUPAC Name | 4-amino-3-(4-fluorophenyl)butanoic acid |
| Molecular Formula | C₁₀H₁₂FNO₂ |
| Molecular Weight | 197.21 g/mol |
| Canonical SMILES | C1=CC(=CC=C1C(CC(=O)O)CN)F |
| InChIKey | QWHXHLDNSXLAPX-UHFFFAOYSA-N |
| PubChem CID | 103611 |
| CAS (free base) | 52237-19-1 |
| CAS (HCl salt) | 1858241-03-8 |
| ChemSpider ID | 93547 |
| UNII | 6DAU7M5P3D |
| Developmental code | CGP-11130 (Ciba-Geigy) |

**Corrections to brief seed data:** The brief left SMILES, molecular formula, molecular weight, InChIKey, and PubChem CID blank. All have now been confirmed via PubChem and cross-referenced against HandWiki and the Irie et al. 2020 primary research paper [Ref 1]. The IUPAC name in the brief was blank; confirmed as 4-amino-3-(4-fluorophenyl)butanoic acid. PsychonautWiki lists an incorrect IUPAC name ("5-amino-4-(4-fluorophenyl)-1-hydroxypentan-2-one") — this should not be used [Ref 19].

**Structural context:** F-Phenibut (4-fluorophenibut) is a fluorinated derivative of phenibut (β-phenyl-GABA) featuring a fluorine atom at the para position of the phenyl ring. This makes it structurally analogous to baclofen (β-(4-chlorophenyl)-GABA), tolibut (β-(4-methylphenyl)-GABA), and phenibut (β-phenyl-GABA) [Ref 3, 14]. F-Phenibut occupies a position in the halogen series between the unsubstituted phenibut and the chloro-substituted baclofen.

**Physical properties:** No published data on melting point, solubility, or stability specific to F-phenibut. Sold commercially as the hydrochloride salt (CAS 1858241-03-8). The HCl form is white crystalline powder, consistent with other phenibut-class compounds [Ref 18].

---

## Pharmacology

### Primary Mechanism: GABA-B Receptor Agonism

F-phenibut is a potent agonist at the GABA-B receptor, which is a class C G-protein coupled receptor (GPCR) forming obligate heterodimers of the GB1 and GB2 subunits [Ref 15, 23]. Downstream signaling involves: activation of inwardly rectifying K⁺ channels (and in cerebellar Purkinje cells, an outward-rectifying K⁺ channel — see below), inactivation of voltage-gated Ca²⁺ channels, and inhibition of adenylate cyclase via Gαi/o proteins [Ref 23].

**EC₅₀ values (in vitro, mouse cerebellar Purkinje cell patch-clamp):**
- Phenibut: 1362 µM
- F-phenibut: 23.3 µM
- (±)-Baclofen: 6.0 µM

(Irie, Yamazaki, Kikura-Hanajiri 2020 [Ref 1])

F-phenibut is therefore approximately **58× more potent than phenibut** and approximately **4× less potent than baclofen** as a GABA-B agonist in this assay system. The greater GABA-B potency of F-phenibut compared to phenibut likely reflects the electron-withdrawing effect of the para-fluorine substituent enhancing receptor binding.

**IC₅₀ data from supplier databases** [Ref 18]: GABA-B IC₅₀ = 1.70 µM; GABA-A IC₅₀ >100 µM (selective for GABA-B). ⚠️ **FLAG: The original primary paper for this IC₅₀ value could not be traced by API or web search.** This value appears consistently across chemical supplier catalogues (HandWiki, MedKoo, TargetMol) but the source is likely unpublished Ciba-Geigy pharmacology data from the CGP-11130 development program. The generation agent should not treat this as a fully verified published value.

**Novel K⁺ channel finding:** Irie et al. [Ref 1] found that the K⁺ current activated by F-phenibut (and by phenibut and baclofen) in Purkinje cells is outward-rectifying rather than the inwardly rectifying K⁺ current (GIRK/Kir3) typically associated with GABA-B activation. This current was insensitive to extracellular Ba²⁺, intracellular or extracellular Cs⁺, and tetraethylammonium-Cl — making it pharmacologically distinct from GIRK channels. This may represent a cell-type-specific GABA-B effector mechanism in cerebellum.

**Action potential suppression:** F-phenibut suppressed action potential generation in Purkinje cells in vitro, consistent with CNS depressant profile [Ref 1].

### Secondary Mechanism: α₂-δ Calcium Channel Subunit Binding

Phenibut (specifically the R-enantiomer) binds to the α₂-δ subunit of voltage-dependent calcium channels (VDCCs) with Ki = 23 µM — approximately 4× higher affinity than its GABA-B affinity (R-phenibut GABA-B Ki = 92 µM) [Ref 2]. The anti-nociceptive effects of R-phenibut in animal models are mediated via the α₂-δ subunit rather than GABA-B receptors, as they were not blocked by the GABA-B antagonist CGP35348 [Ref 2]. This mechanism — identical to gabapentin and pregabalin — produces gabapentinoid-class effects.

**Extrapolation to F-phenibut:** No published binding data exist for F-phenibut at the α₂-δ subunit. By structural analogy with phenibut, α₂-δ binding is expected. Martin et al. [Ref 28] note that phenibut exhibits "high affinity at the α₂-δ subunit-containing voltage-dependent calcium channels" as part of its mechanism. The relative contribution of GABA-B vs. α₂-δ binding in F-phenibut's overall effect profile is not established. ⚠️ **FLAG: α₂-δ binding for F-phenibut is inferred from phenibut data; no direct published measurement exists.**

### GABA-A Activity

GABA-A IC₅₀ >100 µM (essentially inactive) [Ref 18]. Phenibut has minor GABA-A activity at very high concentrations [Ref 28]; this is not expected to be clinically significant for F-phenibut at therapeutic doses.

### Dopaminergic Activity

Phenibut stimulates dopamine receptors and antagonizes β-phenethylamine (PEA), a putative endogenous anxiogenic [Ref 3]. This may contribute to the positive mood and motivational enhancement effects reported by users. No published data exist for F-phenibut specifically at dopamine receptors. By structural analogy, similar dopaminergic activity is plausible but unconfirmed. ⚠️ **FLAG: Dopamine receptor activity extrapolated from phenibut class data only.**

### Binding Affinity Summary Table

| Target | Compound | Affinity | Assay | Source |
|---|---|---|---|---|
| GABA-B (EC₅₀, K⁺ current) | F-phenibut | 23.3 µM | Mouse Purkinje cells | [Ref 1] |
| GABA-B (EC₅₀, K⁺ current) | Phenibut | 1362 µM | Mouse Purkinje cells | [Ref 1] |
| GABA-B (EC₅₀, K⁺ current) | Baclofen | 6.0 µM | Mouse Purkinje cells | [Ref 1] |
| GABA-B (IC₅₀) | F-phenibut | 1.70 µM | Unverified source | [Ref 18] ⚠️ |
| GABA-A (IC₅₀) | F-phenibut | >100 µM | Unverified source | [Ref 18] |
| GABA-B (Ki, radioligand) | R-phenibut | 92 µM | [³H]CGP54626 | [Ref 11] |
| GABA-B (Ki, radioligand) | Baclofen | 6.0 µM | [³H]CGP54626 | [Ref 11] |
| α₂-δ (Ki) | R-phenibut | 23 µM | [³H]GBP rat brain | [Ref 2] |
| α₂-δ (Ki) | Gabapentin | 0.05 µM | [³H]GBP rat brain | [Ref 2] |

### Stereochemistry

F-phenibut contains a chiral center at C-3 and is sold as a racemate. No direct stereochemical studies of F-phenibut have been published. By analogy with phenibut [Ref 11] and baclofen [Ref 27]:
- R-phenibut is approximately 2× more potent than racemic phenibut and essentially all GABA-B activity resides in the R-enantiomer; S-phenibut is inactive at GABA-B.
- For baclofen, R(+)-baclofen carries most of the efficacy [Ref 27].
- Therefore, the R-enantiomer of F-phenibut is expected to carry the majority of GABA-B activity.

⚠️ **FLAG: No published stereochemical studies of F-phenibut enantiomers exist. The R/S activity assignment is a structural class inference.**

---

## Pharmacokinetics

No published human pharmacokinetic studies exist specifically for F-phenibut. The following is inferred from phenibut data:

**Phenibut pharmacokinetics (class inference for F-phenibut):**
- Oral bioavailability: approximately 65% [Ref 13]
- Time to maximal brain concentration: ~15 minutes after i.p./p.o. administration in mice (R-phenibut data) [Ref 16]
- Elimination half-life: approximately 5–6 hours [Ref 13]
- Hepatic metabolism: virtually absent — phenibut is excreted largely unchanged in urine [Ref 13]
- CYP enzyme involvement: not established for phenibut or F-phenibut; the minimal hepatic metabolism of phenibut suggests CYP interactions are unlikely but unconfirmed

**Fluorine substitution effects:** The para-fluoro substitution may modestly affect metabolic stability (fluorine often increases metabolic resistance), lipophilicity, and CNS penetration relative to unsubstituted phenibut, but no data are available.

⚠️ **FLAG: All pharmacokinetic values for F-phenibut are class inferences from phenibut data. No direct human PK study for F-phenibut exists.**

---

## History

**Discovery and development:**
F-phenibut was developed by Ciba-Geigy (now Novartis) under the code name **CGP-11130** [Ref 18]. The compound was never approved for clinical use in any jurisdiction and was never marketed. The exact date of its synthesis and characterization within the Ciba-Geigy research program has not been published in peer-reviewed literature accessible via PubMed or OpenAlex.

**Parent compound history:** Phenibut (β-phenyl-GABA) was discovered and introduced into clinical practice in Russia in the 1960s [Ref 3]. It is widely used in Russia and former Soviet states for anxiolysis, insomnia, and related conditions. Baclofen (β-(4-chlorophenyl)-GABA, the p-chloro analog) was developed in the same structural series and is the only drug in this class approved for clinical use in Western countries. F-phenibut occupies the structural position between these two compounds.

**Appearance on research chemical market:** F-phenibut became available from online nootropic and research chemical vendors in the 2010s. It is marketed under names including "F-phenibut," "fluorophenibut," "fluorobut," and "4F-phenibut." Its presence in Australian wastewater was documented in a systematic survey spanning February 2022 to February 2023 [Ref 8], confirming real-world population-level use.

**First peer-reviewed characterization:** The first primary research paper specifically studying F-phenibut's pharmacological mechanism was Irie, Yamazaki, and Kikura-Hanajiri (2020) [Ref 1], published in the European Journal of Pharmacology. Prior to this, F-phenibut had appeared in the literature only in the context of phenibut analog reviews.

---

## Subjective Effects

No controlled human studies documenting the subjective effects of F-phenibut exist. The effects profile is inferred from:
1. Pharmacological mechanism (GABA-B agonism + putative α₂-δ binding) by comparison with phenibut and baclofen
2. User-reported data (PsychonautWiki community database [Ref 19])

**Published effect categories for phenibut class (applicable by analogy):**
- Anxiolysis and sedation [Ref 3, 9]
- CNS depression (dose-dependent, from mild relaxation to coma at overdose) [Ref 4, 13]
- Cognitive effects: improved memory consolidation, antiamnestic effects at low doses (phenibut data in animals) [Ref 14]
- Nootropic effects at lower doses [Ref 3, 6]
- Anti-aggressive and anti-anxiety behavioral effects [Ref 3]

**User-reported effects (PsychonautWiki; not peer-reviewed):** Disinhibition, empathy enhancement, anxiety suppression, tactile euphoria, music enhancement, motivation enhancement, cognitive euphoria, stimulation at low doses. At higher doses: motor control impairment, thought deceleration, sedation, amnesia. Compulsive redosing urge noted [Ref 19].

**Duration data:** No controlled human studies. PsychonautWiki (user-sourced) reports onset 20–60 minutes, total duration 6–8 hours [Ref 19]. These values are consistent with the brief's seed data and reflect phenibut-class pharmacokinetics (t₁/₂ ~5–6 hours).

---

## Safety & Toxicity

### LD₅₀ and Acute Toxicity

No published LD₅₀ data for F-phenibut in any species. No published acute toxicity studies specific to F-phenibut.

⚠️ **FLAG: Brief seed data states "Acute: high; Chronic: high" for toxicity. No published toxicological study supports this designation for F-phenibut specifically. These characterizations are inferred from phenibut class data. The brief's statement that "exact toxic dosage is unknown" is accurate.**

**Phenibut class toxicity (by analogy):**
- Deaths attributed to phenibut alone are not documented in peer-reviewed literature from Germany or Western Europe. Deaths reported in the USA involved multidrug combinations [Ref 13].
- More than 80 cases of coma and death have been "associated with phenibut consumption and withdrawal" in the US [Ref 12] — but most are polydrug contexts.
- Clinical presentations of severe intoxication include: somnolence to coma, respiratory depression requiring intubation, falls [Ref 13].
- A case of suspected phenibut intoxication with partial brainstem areflexia was documented in 2026 [Ref 20].
- Dissociative features have been reported [Ref 22].

**F-phenibut-specific hazard consideration:** Because F-phenibut is approximately 58× more potent than phenibut at GABA-B receptors [Ref 1], the same mass dose of F-phenibut poses substantially higher risk of overdose than an equivalent dose of phenibut. This is especially relevant for users who switch from phenibut to F-phenibut with incorrect dose scaling.

### Drug Interactions

The primary interaction risk is **additive or synergistic CNS and respiratory depression** with other CNS depressants:
- **Opioids:** Potentially life-threatening respiratory depression. Baclofen + opioid interaction documented clinically [Ref 21 - intrathecal case]; FORWARDS-1 trial evaluated baclofen safety in opioid-dependent patients on methadone [Ref in search results].
- **Benzodiazepines:** Additive CNS depression; polydependence on phenibut + benzodiazepines documented [Ref 24].
- **Alcohol:** GABA-B activation reduces stimulating/rewarding alcohol effects but concurrent intoxication increases CNS depression risk [Ref 27].
- **Other GABA-B agonists (baclofen, GHB/GBL):** Additive agonism at GABA-B; risk of severe CNS depression.

Brief seed data states: "potentially lethal when mixed with depressants like alcohol, benzodiazepines or opioids." This is supported by class-level evidence [Ref 4, 13, 24]. ⚠️ **FLAG: No published interaction studies specifically for F-phenibut combinations exist; all interaction data is extrapolated from phenibut and baclofen.**

### Organ Toxicity

No organ-specific toxicity data published for F-phenibut. No documented hepatotoxicity, nephrotoxicity, or cardiotoxicity specific to the phenibut class at therapeutic doses.

### Detection

No readily available confirmatory laboratory tests for phenibut-class compounds in clinical settings [Ref 17, 25]. Standard urine drug screens do not detect phenibut or F-phenibut. Specialized LC-MS/MS methods are required. This substantially complicates emergency clinical management.

---

## Harm Reduction

Based on phenibut class evidence:

1. **Dose titration:** Start at the lowest effective dose. Given F-phenibut's ~58× higher GABA-B potency vs. phenibut [Ref 1], phenibut users switching to F-phenibut must drastically reduce dose. User community reports threshold at 50 mg, common range 150–400 mg [Ref 19].

2. **Frequency limitation:** Use should be limited to 1–2 times per week to minimize tolerance development and dependence risk [Ref 3, 4]. Tolerance develops within days of continuous use (brief data; no published study for F-phenibut specifically).

3. **Avoid CNS depressant combinations:** Combinations with alcohol, opioids, or benzodiazepines are potentially lethal [Ref 4, 13]. This is the primary identified cause of serious adverse outcomes in phenibut-class compounds.

4. **No reliable drug test:** If a patient presents to an emergency department with suspected F-phenibut intoxication, clinicians should be aware that standard tox screens will not detect the compound [Ref 17, 25]. Clinical diagnosis is based on history and presentation.

5. **Withdrawal management:** Do not abruptly discontinue after regular use. Gradual taper or substitution with baclofen is the documented approach for phenibut class [Ref 9, 10, 24]. Phenobarbital may be preferred if seizure risk is elevated [Ref 9].

6. **No antidote:** No specific antidote exists for GABA-B agonist overdose. Management is supportive (airway, breathing, circulation) [Ref 13, 17].

---

## Tolerance & Dependence

### Tolerance

**Onset:** Tolerance to F-phenibut develops rapidly. No published study for F-phenibut specifically. The brief states tolerance builds "within a couple of days of continuous use" — consistent with phenibut class behavior documented in clinical case reports [Ref 4, 10]. No controlled pharmacological study has quantified the rate.

**Full reset:** The brief states 10.5 days for full reset. ⚠️ **FLAG: No published primary source was found for the specific 10.5-day reset figure. This appears to be community consensus without peer-reviewed confirmation. The generation agent should present this as estimated/community-reported rather than a published pharmacological measurement.**

**Mechanism:** Likely involves GABA-B receptor downregulation, desensitization, or internalization following sustained agonist stimulation — the same mechanism hypothesized for baclofen tolerance. This is not specifically studied for phenibut or F-phenibut.

### Cross-Tolerance

Cross-tolerance expected with: other GABA-B agonists (baclofen, GHB), and potentially GABA-A modulators (benzodiazepines, alcohol) given overlapping inhibitory pathways [Ref 4, 29]. The brief lists cross-tolerance with "GABA" — this is consistent with published phenibut literature.

### Dependence Liability

Moderate to significant physical and psychological dependence documented for phenibut [Ref 4, 5, 10, 21]. The higher potency of F-phenibut [Ref 1] suggests potentially more rapid dependence development at lower doses, though this has not been formally studied.

**Dependence characteristics from phenibut case series [Ref 4, 5, 9, 10, 21, 24]:**
- Patients develop dependence with regular use
- Withdrawal symptoms begin within hours of last dose (phenibut case: within 3–4 hours [Ref 10])
- Cross-dependence with baclofen allows substitution management

### Withdrawal Syndrome

**Clinical features** (from phenibut case reports; applicable by class to F-phenibut):
- Severe psychomotor agitation (most prominent)
- Autonomic instability
- Neurological signs mimicking serotonin syndrome or neuroleptic malignant syndrome
- Psychosis
- Seizures (especially at high dependence levels)
- Insomnia, anxiety, tremor

Weleff et al. systematic review [Ref 4] and Hardman et al. [Ref 5] reviewed the published case evidence. All documented cases required aggressive pharmacological management.

**Management:** Baclofen substitution and taper is the primary documented strategy (~10 mg baclofen per 1 g phenibut) [Ref 10]. Benzodiazepines and phenobarbital are alternatives; combinations are also used [Ref 9]. Ancillary agents include antipsychotics, dexmedetomidine, gabapentin, pregabalin [Ref 9].

---

## Interactions

| Interactant | Mechanism | Risk Level | Evidence Quality |
|---|---|---|---|
| Opioids | Additive CNS/respiratory depression | Potentially lethal | Class-level; no F-phenibut-specific study |
| Benzodiazepines | Additive CNS depression | Severe | Class-level; phenibut+benzo polydependence documented [Ref 24] |
| Alcohol | Additive GABA-B + CNS depression | Serious | Class-level [Ref 27] |
| GHB/GBL | Additive GABA-B agonism | Severe | Class-level [Ref 29] |
| Baclofen | Additive GABA-B agonism | Serious | Class-level |
| Gabapentin/Pregabalin | Additive α₂-δ channel inhibition | Moderate | Class-level |
| CNS stimulants | May mask sedation | Unknown | Theoretical |

⚠️ **FLAG: No published pharmacokinetic interaction studies exist for F-phenibut with any of the above. All interaction data is extrapolated from phenibut and baclofen literature.**

**Serotonin syndrome risk:** Not documented. Phenibut withdrawal has been noted to mimic serotonin syndrome [Ref 5], but this is a mimicry syndrome not a true pharmacological interaction. No serotonergic mechanism for F-phenibut has been identified.

**CYP inhibition/induction:** Not published for F-phenibut. Given minimal hepatic metabolism of phenibut class [Ref 13], CYP-mediated interactions are not expected but have not been studied.

---

## Legal Status

| Jurisdiction | Status | Notes |
|---|---|---|
| **UK** | Controlled | Psychoactive Substances Act 2016; sale/supply/import prohibited; personal possession not criminalized |
| **Australia** | Phenibut: Schedule 9 (prohibited, 2018). F-phenibut: status unclear | 4F-phenibut detected in Australian wastewater (2022–2023) [Ref 8], suggesting it circulates despite phenibut ban |
| **Germany** | Illegal | New Psychoactive Substances Act (NpSG) [Ref 13] |
| **France** | Prohibited | [Ref 13] |
| **Hungary** | Specifically prohibited | Named compound ban; includes F-phenibut [Ref 18] |
| **Lithuania** | Specifically prohibited | Named compound ban; includes F-phenibut [Ref 18] |
| **Italy** | Controlled | [Ref 13] |
| **United States** | Not scheduled | Not a controlled substance; FDA has determined phenibut is not a lawful dietary ingredient; no FDA action specific to F-phenibut documented [Ref 12] |
| **Canada** | Uncontrolled | Phenibut and F-phenibut both uncontrolled; F-phenibut reported in NPS surveys |
| **Russia/Baltic states** | Phenibut: prescription drug. F-phenibut: no approved medical use anywhere | [Ref 3] |
| **International** | Not under international control | WHO ECDD has had phenibut under surveillance since 2017 [Ref 26]; pre-review conducted at 44th ECDD (2021); no international scheduling yet |

---

## Clinical Trials

**No clinical trials registered on ClinicalTrials.gov for F-phenibut or fluorophenibut.** Search returned zero results.

F-phenibut has never been approved for medical use in any jurisdiction and has not progressed to clinical trials [Ref 18].

---

## Community Feedback Analysis

**No community feedback was submitted in Part A2 of the brief.** This section is therefore not applicable.

The dosing and duration data in the brief (threshold 50 mg, light 100–150 mg, common 150–400 mg, strong 400–600 mg, heavy 600+ mg; onset 20–60 min, total 6–8 h) were cross-checked against PsychonautWiki user-sourced data [Ref 19] and found to be consistent. No discrepancies identified.

---

## Gaps & Flags

### Safety-Critical Flags

1. **⚠️ GABA-B IC₅₀ source unverified:** The IC₅₀ of 1.70 µM for F-phenibut at GABA-B (and >100 µM at GABA-A) appears on multiple supplier databases but the original primary source could not be traced to a peer-reviewed publication. This value likely derives from unpublished Ciba-Geigy pharmacological characterization of CGP-11130. **Do not present as a published measurement without qualification.**

2. **⚠️ No published human pharmacokinetic data for F-phenibut.** All PK parameters (bioavailability, half-life, metabolism, excretion) are class inferences from phenibut. Half-life may differ due to structural modification.

3. **⚠️ Tolerance reset time (10.5 days):** No peer-reviewed source found for this specific figure. It appears in community consensus only. **Present as estimated/community-reported.**

4. **⚠️ Acute and chronic toxicity ratings:** The brief labels these "high" but no LD₅₀ or formal toxicological assessment exists for F-phenibut. The "high acute toxicity" characterization is derived from class inference and the compound's higher potency vs. phenibut. **Flag this as a class-inference designation.**

5. **⚠️ α₂-δ binding:** No published measurement for F-phenibut at the α₂-δ VDCC subunit. This pharmacological activity is extrapolated from phenibut data and is important for the gabapentinoid harm profile.

6. **⚠️ Interaction data:** Zero published pharmacokinetic or pharmacodynamic interaction studies exist for F-phenibut. All interaction severity ratings are class-level inferences.

7. **⚠️ Stereochemistry:** F-phenibut is sold as a racemate with no published enantiomeric studies. The R-enantiomer is expected to be pharmacologically dominant by phenibut/baclofen analogy, but this has not been confirmed.

### Data Gaps (Not Safety-Critical)

8. **No published case reports of F-phenibut intoxication specifically.** All clinical evidence is from phenibut case series. The generation agent should clearly distinguish phenibut class evidence from F-phenibut-specific evidence.

9. **No clinical trials.** F-phenibut has no regulatory or clinical trial history.

10. **Discovery date unknown.** The exact year Ciba-Geigy synthesized and characterized CGP-11130 is not available in accessible literature.

11. **Melting point, aqueous solubility, and stability data** not found in published sources.

12. **SMILES clarification:** The SMILES returned by HandWiki (C1=CC(=CC=C1C(CC(=O)O)CN)F) represents the racemic compound. An isomeric SMILES for the R-enantiomer would be needed if stereochemical differentiation is required.

13. **Australian F-phenibut specific legal status:** While phenibut is Schedule 9, whether F-phenibut is covered under this scheduling or under a separate entry is unclear. It appears to be in use (detected in wastewater [Ref 8]) suggesting it may not be explicitly scheduled.

14. **Systematic name discrepancy:** PsychonautWiki provides an incorrect IUPAC name. The correct IUPAC name (4-amino-3-(4-fluorophenyl)butanoic acid) is confirmed by PubChem [Ref from PubChem API] and HandWiki [Ref 18].

F-Phenibut

Value Provenance

Dosing

oraltrace →

Duration

oral

Safety

Toxicity Profiletrace →

Dependence Profiletrace →

Withdrawal Profiletrace →

Tolerance Profiletrace →

Effects & Profile

Contraindications

Timeline Phases

oral

Dose Tier Summaries

History

Sources

Claim Verification

Coverage & Gaps

Research Trail

oraltrace

Toxicity Profiletrace

Dependence Profiletrace

Withdrawal Profiletrace

Tolerance Profiletrace