A-PHP
α-pyrrolidinohexiophenone
Studies and references cited across this article, graded by evidence strength.
Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.
Data points an editor reviewed and accepted for publication.
Value Provenance
Dosing
oraltrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 3 mg | 3 mg | low |
| Low | 5–10 mg | 5–10 mg | low |
| Common | 10–25 mg | 10–25 mg | low |
| Strong | 25–45 mg | 25–45 mg | low |
| Heavy | 45+ mg | 45+ mg | low |
| Editorial | No published controlled dosing studies exist for α-PHP. Dose ranges inferred from α-PVP oral community-reported ranges with adjustment for α-PHP's described potency as 'at least equal to α-PVP.' Ranges widened to account for uncertainty. These values require editorial verification before publication. | ||
ReasoningReasoningNo published controlled dosing studies exist for α-PHP. Dose ranges inferred from α-PVP oral community-reported ranges with adjustment for α-PHP's described potency as 'at least equal to α-PVP.' Ranges widened to account for uncertainty. These values require editorial verification before publication. Evidence basis: structural_analogy | |||
insufflatedtrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 2 mg | 2 mg | low |
| Low | 3–8 mg | 3–8 mg | low |
| Common | 8–20 mg | 8–20 mg | low |
| Strong | 20–35 mg | 20–35 mg | low |
| Heavy | 35+ mg | 35+ mg | low |
| Editorial | No published dose data for insufflated α-PHP. Inferred from α-PVP insufflated community-reported ranges. Insufflated bioavailability assumed higher than oral, producing lower effective dose ranges. Widened to account for uncertainty. | ||
ReasoningReasoningNo published dose data for insufflated α-PHP. Inferred from α-PVP insufflated community-reported ranges. Insufflated bioavailability assumed higher than oral, producing lower effective dose ranges. Widened to account for uncertainty. Evidence basis: structural_analogy | |||
smokedtrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 2 mg | 2 mg | low |
| Low | 3–7 mg | 3–7 mg | low |
| Common | 7–18 mg | 7–18 mg | low |
| Strong | 18–30 mg | 18–30 mg | low |
| Heavy | 30+ mg | 30+ mg | low |
| Editorial | No published dose data for smoked α-PHP. Inferred from α-PVP smoked community-reported ranges. Taffe et al. 2021 noted inhalation produced abbreviated duration vs injection, consistent with rapid pulmonary absorption. Ranges widened for uncertainty. | ||
ReasoningReasoningNo published dose data for smoked α-PHP. Inferred from α-PVP smoked community-reported ranges. Taffe et al. 2021 noted inhalation produced abbreviated duration vs injection, consistent with rapid pulmonary absorption. Ranges widened for uncertainty. Evidence basis: structural_analogy | |||
Duration
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 20–45 minutes | 20–45 minutes | low |
| Editorial | No controlled oral duration data for α-PHP. Inferred from α-PVP oral onset reports. | ||
ReasoningReasoningNo controlled oral duration data for α-PHP. Inferred from α-PVP oral onset reports. Evidence basis: structural_analogy | |||
| Come uptrace | 30–60 minutes | 30–60 minutes | low |
| Editorial | Inferred from α-PVP oral come-up reports. | ||
ReasoningReasoningInferred from α-PVP oral come-up reports. Evidence basis: structural_analogy | |||
| Peaktrace | 1.5–3 hours | 1.5–3 hours | low |
| Editorial | Inferred from α-PVP oral peak duration reports. | ||
ReasoningReasoningInferred from α-PVP oral peak duration reports. Evidence basis: structural_analogy | |||
| Offsettrace | 2–4 hours | 2–4 hours | low |
| Editorial | Inferred from α-PVP oral offset with adjustment for α-PHP's longer serum half-life. | ||
ReasoningReasoningInferred from α-PVP oral offset with adjustment for α-PHP's longer serum half-life. Evidence basis: structural_analogy | |||
| Totaltrace | 4–8 hours | 4–8 hours | low |
| Editorial | Total subjective duration inferred from α-PVP oral reports. Does not include prolonged aftereffects driven by 37-hour serum half-life. | ||
ReasoningReasoningTotal subjective duration inferred from α-PVP oral reports. Does not include prolonged aftereffects driven by 37-hour serum half-life. Evidence basis: structural_analogy | |||
| After effectstrace | 12–48 hours | 12–48 hours | low |
| Editorial | Prolonged aftereffects consistent with 37-hour serum half-life (Fujita 2018) and documented multi-day clinical presentations. | ||
ReasoningReasoningProlonged aftereffects consistent with 37-hour serum half-life (Fujita 2018) and documented multi-day clinical presentations. Evidence basis: single_case_report | |||
insufflated
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 1–5 minutes | 1–5 minutes | low |
| Editorial | Rapid nasal mucosal absorption. Inferred from α-PVP insufflated reports. | ||
ReasoningReasoningRapid nasal mucosal absorption. Inferred from α-PVP insufflated reports. Evidence basis: structural_analogy | |||
| Come uptrace | 5–15 minutes | 5–15 minutes | low |
| Editorial | Inferred from α-PVP insufflated reports. | ||
ReasoningReasoningInferred from α-PVP insufflated reports. Evidence basis: structural_analogy | |||
| Peaktrace | 1–2 hours | 1–2 hours | low |
| Editorial | Inferred from α-PVP insufflated peak duration. | ||
ReasoningReasoningInferred from α-PVP insufflated peak duration. Evidence basis: structural_analogy | |||
| Offsettrace | 1.5–3 hours | 1.5–3 hours | low |
| Editorial | Inferred from α-PVP insufflated offset. | ||
ReasoningReasoningInferred from α-PVP insufflated offset. Evidence basis: structural_analogy | |||
| Totaltrace | 3–6 hours | 3–6 hours | low |
| Editorial | Total subjective duration inferred from α-PVP insufflated reports. | ||
ReasoningReasoningTotal subjective duration inferred from α-PVP insufflated reports. Evidence basis: structural_analogy | |||
| After effectstrace | 12–48 hours | 12–48 hours | low |
| Editorial | Prolonged aftereffects driven by 37-hour serum half-life. | ||
ReasoningReasoningProlonged aftereffects driven by 37-hour serum half-life. Evidence basis: single_case_report | |||
smoked
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 5–30 seconds | 5–30 seconds | low |
| Editorial | Near-instantaneous pulmonary absorption. Inferred from α-PVP smoked reports. | ||
ReasoningReasoningNear-instantaneous pulmonary absorption. Inferred from α-PVP smoked reports. Evidence basis: structural_analogy | |||
| Come uptrace | 30–300 seconds | 30–300 seconds | low |
| Editorial | Very rapid come-up via pulmonary route. | ||
ReasoningReasoningVery rapid come-up via pulmonary route. Evidence basis: structural_analogy | |||
| Peaktrace | 15–45 minutes | 15–45 minutes | low |
| Editorial | Abbreviated peak via inhalation route noted by Taffe et al. 2021. | ||
ReasoningReasoningAbbreviated peak via inhalation route noted by Taffe et al. 2021. Evidence basis: structural_analogy | |||
| Offsettrace | 30–90 minutes | 30–90 minutes | low |
| Editorial | Inferred from α-PVP smoked offset. | ||
ReasoningReasoningInferred from α-PVP smoked offset. Evidence basis: structural_analogy | |||
| Totaltrace | 1–3 hours | 1–3 hours | low |
| Editorial | Abbreviated total duration via inhalation noted by Taffe et al. 2021. Does not include prolonged aftereffects. | ||
ReasoningReasoningAbbreviated total duration via inhalation noted by Taffe et al. 2021. Does not include prolonged aftereffects. Evidence basis: structural_analogy | |||
| After effectstrace | 12–48 hours | 12–48 hours | low |
| Editorial | Despite abbreviated subjective duration, aftereffects persist due to 37-hour serum half-life. | ||
ReasoningReasoningDespite abbreviated subjective duration, aftereffects persist due to 37-hour serum half-life. Evidence basis: single_case_report | |||
Safety
Toxicity Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Acute | moderate | moderate | medium |
| Chronic | moderate | moderate | medium |
| Organs Affected | cardiovascular, brain, kidney, skeletal_muscle | cardiovascular, brain, kidney, skeletal_muscle | medium |
| Editorial | Classified as moderate (acute): cardiovascular toxicity, rhabdomyolysis, and prolonged psychosis documented across multiple case series (Grapp 2023, Bassi 2025, Fujita 2018), but no fatalities attributed solely to α-PHP and no LD50 data. Classified as moderate (chronic): in vitro neurotoxicity at supra-clinical concentrations (Roda 2023), metabolite genotoxicity (Lenzi 2021), but no human chronic exposure data exist — downgraded from potentially high based on in vitro data alone. | ||
ReasoningReasoningClassified as moderate (acute): cardiovascular toxicity, rhabdomyolysis, and prolonged psychosis documented across multiple case series (Grapp 2023, Bassi 2025, Fujita 2018), but no fatalities attributed solely to α-PHP and no LD50 data. Classified as moderate (chronic): in vitro neurotoxicity at supra-clinical concentrations (Roda 2023), metabolite genotoxicity (Lenzi 2021), but no human chronic exposure data exist — downgraded from potentially high based on in vitro data alone. Evidence basis: published_case_series | |||
Dependence Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Physical | low | low | medium |
| Psychological | high | high | medium |
| Compulsive Redosing | high | high | medium |
| Dose Escalation | high | high | medium |
| Editorial | High psychological dependence and compulsive redosing risk supported by multiple preclinical studies: ICSS facilitation comparable to cocaine (Baird 2021), locomotor stimulation equivalent to α-PVP (Taffe 2021), and WHO ECDD assessment of high dependence liability. Physical dependence rated low — stimulant withdrawal is primarily psychological. No human dependence studies exist. | ||
ReasoningReasoningHigh psychological dependence and compulsive redosing risk supported by multiple preclinical studies: ICSS facilitation comparable to cocaine (Baird 2021), locomotor stimulation equivalent to α-PVP (Taffe 2021), and WHO ECDD assessment of high dependence liability. Physical dependence rated low — stimulant withdrawal is primarily psychological. No human dependence studies exist. Evidence basis: animal_study | |||
Withdrawal Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Severity | moderate | moderate | low |
| Symptoms | fatigue, hypersomnia, depressed mood, anhedonia, increased appetite, psychomotor retardation, irritability, anxiety, vivid dreams | fatigue, hypersomnia, depressed mood, anhedonia, increased appetite, psychomotor retardation, irritability, anxiety, vivid dreams | low |
| Fatal | No | No | low |
| Medical Supervision | Not required | Not required | low |
| Editorial | No α-PHP-specific withdrawal data published. Withdrawal profile inferred from stimulant class (cocaine, amphetamine) withdrawal syndrome. Stimulant withdrawal is not life-threatening but can produce severe dysphoria and suicidal ideation. | ||
ReasoningReasoningNo α-PHP-specific withdrawal data published. Withdrawal profile inferred from stimulant class (cocaine, amphetamine) withdrawal syndrome. Stimulant withdrawal is not life-threatening but can produce severe dysphoria and suicidal ideation. Evidence basis: animal_study | |||
Tolerance Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Buildup | rapid | rapid | low |
| Half-life | — | — | low |
| Full Reset | — | — | low |
| Cross-tolerances | cocaine, α-PVP, MDPV, amphetamine, methamphetamine | cocaine, α-PVP, MDPV, amphetamine, methamphetamine | low |
| Editorial | Tolerance mechanism inferred from DAT reuptake inhibitor class pharmacology (cocaine, amphetamine). Cross-tolerance with other DAT-active stimulants expected based on shared mechanism. No α-PHP-specific tolerance studies exist. Rapid buildup classification based on class behavior of potent DAT inhibitors. | ||
ReasoningReasoningTolerance mechanism inferred from DAT reuptake inhibitor class pharmacology (cocaine, amphetamine). Cross-tolerance with other DAT-active stimulants expected based on shared mechanism. No α-PHP-specific tolerance studies exist. Rapid buildup classification based on class behavior of potent DAT inhibitors. Evidence basis: structural_analogy | |||
Effects & Profile
Contraindications
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| cardiovascular cardiovascular diseasetrace | absolute | absolute | high |
| Editorial | Tachycardia, hypertension, and tachypnoea documented across all clinical case series (Bassi 2025, Grapp 2023). Class literature for MDPV/α-PVP documents arrhythmias and myocardial infarction. | ||
ReasoningReasoningTachycardia, hypertension, and tachypnoea documented across all clinical case series (Bassi 2025, Grapp 2023). Class literature for MDPV/α-PVP documents arrhythmias and myocardial infarction. | |||
| psychiatric psychotic disorderstrace | absolute | absolute | high |
| Editorial | Prolonged psychosis (hallucinations, delusions) documented in Fujita 2018 case report. Dopaminergic mechanism directly exacerbates psychotic symptoms. | ||
ReasoningReasoningProlonged psychosis (hallucinations, delusions) documented in Fujita 2018 case report. Dopaminergic mechanism directly exacerbates psychotic symptoms. | |||
| psychiatric bipolar disordertrace | absolute | absolute | medium |
| Editorial | Class-level contraindication for all potent dopaminergic stimulants. No α-PHP-specific data but mechanism directly predicts risk. | ||
ReasoningReasoningClass-level contraindication for all potent dopaminergic stimulants. No α-PHP-specific data but mechanism directly predicts risk. | |||
| pregnancy breastfeeding pregnancytrace | absolute | absolute | high |
| Editorial | Fetal death case report (Adamowicz 2019) and two neonatal meconium detections (Grapp 2023) provide direct evidence of reproductive toxicity and placental transfer. | ||
ReasoningReasoningFetal death case report (Adamowicz 2019) and two neonatal meconium detections (Grapp 2023) provide direct evidence of reproductive toxicity and placental transfer. | |||
| neurological epilepsytrace | relative | relative | medium |
| Editorial | Class-level contraindication for stimulant cathinones. No α-PHP-specific seizure case reports found. | ||
ReasoningReasoningClass-level contraindication for stimulant cathinones. No α-PHP-specific seizure case reports found. | |||
| other MAO inhibitor usetrace | absolute | absolute | high |
| Editorial | Class-level absolute contraindication for all DAT/NET reuptake inhibitors combined with MAO inhibitors. Pharmacological reasoning is strong; no α-PHP-specific data needed. | ||
ReasoningReasoningClass-level absolute contraindication for all DAT/NET reuptake inhibitors combined with MAO inhibitors. Pharmacological reasoning is strong; no α-PHP-specific data needed. | |||
| other concurrent stimulant usetrace | relative | relative | medium |
| Editorial | The Grapp 2023 case series found 20% cocaine co-use among α-PHP cases. Additive stimulant effects are pharmacologically predictable. | ||
ReasoningReasoningThe Grapp 2023 case series found 20% cocaine co-use among α-PHP cases. Additive stimulant effects are pharmacologically predictable. | |||
Timeline Phases
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 1200–2700 sec(i=0.05) | 1200–2700 sec(i=0.05) | low |
| Editorial | No controlled human duration studies exist for α-PHP. Timeline inferred from α-PVP oral duration reports, adjusted for α-PHP's substantially longer serum half-life (37 hours, Fujita 2018). The prolonged afterglow phase reflects the documented multi-day clinical presentations. | ||
ReasoningReasoningNo controlled human duration studies exist for α-PHP. Timeline inferred from α-PVP oral duration reports, adjusted for α-PHP's substantially longer serum half-life (37 hours, Fujita 2018). The prolonged afterglow phase reflects the documented multi-day clinical presentations. Evidence basis: structural_analogy | |||
| Come uptrace | 1800–3600 sec(i=0.30) | 1800–3600 sec(i=0.30) | low |
| Editorial | No controlled human duration studies exist for α-PHP. Timeline inferred from α-PVP oral duration reports, adjusted for α-PHP's substantially longer serum half-life (37 hours, Fujita 2018). The prolonged afterglow phase reflects the documented multi-day clinical presentations. | ||
ReasoningReasoningNo controlled human duration studies exist for α-PHP. Timeline inferred from α-PVP oral duration reports, adjusted for α-PHP's substantially longer serum half-life (37 hours, Fujita 2018). The prolonged afterglow phase reflects the documented multi-day clinical presentations. Evidence basis: structural_analogy | |||
| Peaktrace | 5400–10800 sec(i=1.00) | 5400–10800 sec(i=1.00) | low |
| Editorial | No controlled human duration studies exist for α-PHP. Timeline inferred from α-PVP oral duration reports, adjusted for α-PHP's substantially longer serum half-life (37 hours, Fujita 2018). The prolonged afterglow phase reflects the documented multi-day clinical presentations. | ||
ReasoningReasoningNo controlled human duration studies exist for α-PHP. Timeline inferred from α-PVP oral duration reports, adjusted for α-PHP's substantially longer serum half-life (37 hours, Fujita 2018). The prolonged afterglow phase reflects the documented multi-day clinical presentations. Evidence basis: structural_analogy | |||
| Plateautrace | 7200–14400 sec(i=0.50) | 7200–14400 sec(i=0.50) | low |
| Editorial | No controlled human duration studies exist for α-PHP. Timeline inferred from α-PVP oral duration reports, adjusted for α-PHP's substantially longer serum half-life (37 hours, Fujita 2018). The prolonged afterglow phase reflects the documented multi-day clinical presentations. | ||
ReasoningReasoningNo controlled human duration studies exist for α-PHP. Timeline inferred from α-PVP oral duration reports, adjusted for α-PHP's substantially longer serum half-life (37 hours, Fujita 2018). The prolonged afterglow phase reflects the documented multi-day clinical presentations. Evidence basis: structural_analogy | |||
| Resolutiontrace | 7200–14400 sec(i=0.20) | 7200–14400 sec(i=0.20) | low |
| Editorial | No controlled human duration studies exist for α-PHP. Timeline inferred from α-PVP oral duration reports, adjusted for α-PHP's substantially longer serum half-life (37 hours, Fujita 2018). The prolonged afterglow phase reflects the documented multi-day clinical presentations. | ||
ReasoningReasoningNo controlled human duration studies exist for α-PHP. Timeline inferred from α-PVP oral duration reports, adjusted for α-PHP's substantially longer serum half-life (37 hours, Fujita 2018). The prolonged afterglow phase reflects the documented multi-day clinical presentations. Evidence basis: structural_analogy | |||
| Afterglowtrace | 43200–172800 sec(i=0.05) | 43200–172800 sec(i=0.05) | low |
| Editorial | No controlled human duration studies exist for α-PHP. Timeline inferred from α-PVP oral duration reports, adjusted for α-PHP's substantially longer serum half-life (37 hours, Fujita 2018). The prolonged afterglow phase reflects the documented multi-day clinical presentations. | ||
ReasoningReasoningNo controlled human duration studies exist for α-PHP. Timeline inferred from α-PVP oral duration reports, adjusted for α-PHP's substantially longer serum half-life (37 hours, Fujita 2018). The prolonged afterglow phase reflects the documented multi-day clinical presentations. Evidence basis: structural_analogy | |||
insufflated
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 60–300 sec(i=0.05) | 60–300 sec(i=0.05) | low |
| Editorial | No controlled duration data exist for insufflated α-PHP. Timeline inferred from α-PVP insufflated reports with adjustment for α-PHP's longer serum half-life. Onset is faster than oral due to nasal mucosal absorption, but the prolonged afterglow phase is similar due to shared elimination kinetics. | ||
ReasoningReasoningNo controlled duration data exist for insufflated α-PHP. Timeline inferred from α-PVP insufflated reports with adjustment for α-PHP's longer serum half-life. Onset is faster than oral due to nasal mucosal absorption, but the prolonged afterglow phase is similar due to shared elimination kinetics. Evidence basis: structural_analogy | |||
| Come uptrace | 300–900 sec(i=0.40) | 300–900 sec(i=0.40) | low |
| Editorial | No controlled duration data exist for insufflated α-PHP. Timeline inferred from α-PVP insufflated reports with adjustment for α-PHP's longer serum half-life. Onset is faster than oral due to nasal mucosal absorption, but the prolonged afterglow phase is similar due to shared elimination kinetics. | ||
ReasoningReasoningNo controlled duration data exist for insufflated α-PHP. Timeline inferred from α-PVP insufflated reports with adjustment for α-PHP's longer serum half-life. Onset is faster than oral due to nasal mucosal absorption, but the prolonged afterglow phase is similar due to shared elimination kinetics. Evidence basis: structural_analogy | |||
| Peaktrace | 3600–7200 sec(i=1.00) | 3600–7200 sec(i=1.00) | low |
| Editorial | No controlled duration data exist for insufflated α-PHP. Timeline inferred from α-PVP insufflated reports with adjustment for α-PHP's longer serum half-life. Onset is faster than oral due to nasal mucosal absorption, but the prolonged afterglow phase is similar due to shared elimination kinetics. | ||
ReasoningReasoningNo controlled duration data exist for insufflated α-PHP. Timeline inferred from α-PVP insufflated reports with adjustment for α-PHP's longer serum half-life. Onset is faster than oral due to nasal mucosal absorption, but the prolonged afterglow phase is similar due to shared elimination kinetics. Evidence basis: structural_analogy | |||
| Plateautrace | 5400–10800 sec(i=0.50) | 5400–10800 sec(i=0.50) | low |
| Editorial | No controlled duration data exist for insufflated α-PHP. Timeline inferred from α-PVP insufflated reports with adjustment for α-PHP's longer serum half-life. Onset is faster than oral due to nasal mucosal absorption, but the prolonged afterglow phase is similar due to shared elimination kinetics. | ||
ReasoningReasoningNo controlled duration data exist for insufflated α-PHP. Timeline inferred from α-PVP insufflated reports with adjustment for α-PHP's longer serum half-life. Onset is faster than oral due to nasal mucosal absorption, but the prolonged afterglow phase is similar due to shared elimination kinetics. Evidence basis: structural_analogy | |||
| Resolutiontrace | 5400–10800 sec(i=0.20) | 5400–10800 sec(i=0.20) | low |
| Editorial | No controlled duration data exist for insufflated α-PHP. Timeline inferred from α-PVP insufflated reports with adjustment for α-PHP's longer serum half-life. Onset is faster than oral due to nasal mucosal absorption, but the prolonged afterglow phase is similar due to shared elimination kinetics. | ||
ReasoningReasoningNo controlled duration data exist for insufflated α-PHP. Timeline inferred from α-PVP insufflated reports with adjustment for α-PHP's longer serum half-life. Onset is faster than oral due to nasal mucosal absorption, but the prolonged afterglow phase is similar due to shared elimination kinetics. Evidence basis: structural_analogy | |||
| Afterglowtrace | 43200–172800 sec(i=0.05) | 43200–172800 sec(i=0.05) | low |
| Editorial | No controlled duration data exist for insufflated α-PHP. Timeline inferred from α-PVP insufflated reports with adjustment for α-PHP's longer serum half-life. Onset is faster than oral due to nasal mucosal absorption, but the prolonged afterglow phase is similar due to shared elimination kinetics. | ||
ReasoningReasoningNo controlled duration data exist for insufflated α-PHP. Timeline inferred from α-PVP insufflated reports with adjustment for α-PHP's longer serum half-life. Onset is faster than oral due to nasal mucosal absorption, but the prolonged afterglow phase is similar due to shared elimination kinetics. Evidence basis: structural_analogy | |||
smoked
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 5–30 sec(i=0.10) | 5–30 sec(i=0.10) | low |
| Editorial | Taffe et al. 2021 noted inhalation route produced abbreviated duration vs injection for α-PHP. Timeline inferred from α-PVP smoked reports with adjustment for abbreviated peak but similar prolonged afterglow due to 37-hour serum half-life. The short peak-to-redose cycle via smoking is a major risk factor for compulsive use patterns. | ||
ReasoningReasoningTaffe et al. 2021 noted inhalation route produced abbreviated duration vs injection for α-PHP. Timeline inferred from α-PVP smoked reports with adjustment for abbreviated peak but similar prolonged afterglow due to 37-hour serum half-life. The short peak-to-redose cycle via smoking is a major risk factor for compulsive use patterns. Evidence basis: structural_analogy | |||
| Come uptrace | 30–300 sec(i=0.50) | 30–300 sec(i=0.50) | low |
| Editorial | Taffe et al. 2021 noted inhalation route produced abbreviated duration vs injection for α-PHP. Timeline inferred from α-PVP smoked reports with adjustment for abbreviated peak but similar prolonged afterglow due to 37-hour serum half-life. The short peak-to-redose cycle via smoking is a major risk factor for compulsive use patterns. | ||
ReasoningReasoningTaffe et al. 2021 noted inhalation route produced abbreviated duration vs injection for α-PHP. Timeline inferred from α-PVP smoked reports with adjustment for abbreviated peak but similar prolonged afterglow due to 37-hour serum half-life. The short peak-to-redose cycle via smoking is a major risk factor for compulsive use patterns. Evidence basis: structural_analogy | |||
| Peaktrace | 900–2700 sec(i=1.00) | 900–2700 sec(i=1.00) | low |
| Editorial | Taffe et al. 2021 noted inhalation route produced abbreviated duration vs injection for α-PHP. Timeline inferred from α-PVP smoked reports with adjustment for abbreviated peak but similar prolonged afterglow due to 37-hour serum half-life. The short peak-to-redose cycle via smoking is a major risk factor for compulsive use patterns. | ||
ReasoningReasoningTaffe et al. 2021 noted inhalation route produced abbreviated duration vs injection for α-PHP. Timeline inferred from α-PVP smoked reports with adjustment for abbreviated peak but similar prolonged afterglow due to 37-hour serum half-life. The short peak-to-redose cycle via smoking is a major risk factor for compulsive use patterns. Evidence basis: structural_analogy | |||
| Plateautrace | 1800–5400 sec(i=0.40) | 1800–5400 sec(i=0.40) | low |
| Editorial | Taffe et al. 2021 noted inhalation route produced abbreviated duration vs injection for α-PHP. Timeline inferred from α-PVP smoked reports with adjustment for abbreviated peak but similar prolonged afterglow due to 37-hour serum half-life. The short peak-to-redose cycle via smoking is a major risk factor for compulsive use patterns. | ||
ReasoningReasoningTaffe et al. 2021 noted inhalation route produced abbreviated duration vs injection for α-PHP. Timeline inferred from α-PVP smoked reports with adjustment for abbreviated peak but similar prolonged afterglow due to 37-hour serum half-life. The short peak-to-redose cycle via smoking is a major risk factor for compulsive use patterns. Evidence basis: structural_analogy | |||
| Resolutiontrace | 3600–7200 sec(i=0.20) | 3600–7200 sec(i=0.20) | low |
| Editorial | Taffe et al. 2021 noted inhalation route produced abbreviated duration vs injection for α-PHP. Timeline inferred from α-PVP smoked reports with adjustment for abbreviated peak but similar prolonged afterglow due to 37-hour serum half-life. The short peak-to-redose cycle via smoking is a major risk factor for compulsive use patterns. | ||
ReasoningReasoningTaffe et al. 2021 noted inhalation route produced abbreviated duration vs injection for α-PHP. Timeline inferred from α-PVP smoked reports with adjustment for abbreviated peak but similar prolonged afterglow due to 37-hour serum half-life. The short peak-to-redose cycle via smoking is a major risk factor for compulsive use patterns. Evidence basis: structural_analogy | |||
| Afterglowtrace | 43200–172800 sec(i=0.05) | 43200–172800 sec(i=0.05) | low |
| Editorial | Taffe et al. 2021 noted inhalation route produced abbreviated duration vs injection for α-PHP. Timeline inferred from α-PVP smoked reports with adjustment for abbreviated peak but similar prolonged afterglow due to 37-hour serum half-life. The short peak-to-redose cycle via smoking is a major risk factor for compulsive use patterns. | ||
ReasoningReasoningTaffe et al. 2021 noted inhalation route produced abbreviated duration vs injection for α-PHP. Timeline inferred from α-PVP smoked reports with adjustment for abbreviated peak but similar prolonged afterglow due to 37-hour serum half-life. The short peak-to-redose cycle via smoking is a major risk factor for compulsive use patterns. Evidence basis: structural_analogy | |||
Dose Tier Summaries
At threshold doses, effects are barely perceptible: a faint increase in alertness, mild mood brightening, and subtle increases in motivation and mental energy. Physical signs are minimal — slight pupil dilation may be the only observable marker. These doses produce no significant cardiovascular stress or psychological disturbance. The experience may be indistinguishable from a strong cup of coffee to an uninformed observer.
No published controlled dosing studies exist for α-PHP. Threshold descriptions inferred from α-PVP and pyrovalerone class community reports. Confidence is low due to complete absence of substance-specific human dose data.
ReasoningReasoning
No published controlled dosing studies exist for α-PHP. Threshold descriptions inferred from α-PVP and pyrovalerone class community reports. Confidence is low due to complete absence of substance-specific human dose data.
Evidence basis: structural_analogy
Light doses produce noticeable stimulation: increased wakefulness, mild euphoria, enhanced focus, and sociability. Thought acceleration becomes apparent, with faster mental processing and increased verbal fluency. Motivation and confidence are mildly elevated. Physically, heart rate increases modestly. Appetite suppression begins. Peripheral vasoconstriction may produce cool extremities. Sleep is difficult for several hours after dosing. The experience is manageable and functional, though the dopaminergic reward signal may already prompt thoughts of redosing even at this range.
Inferred from α-PVP and MDPV community-reported light dose experiences, adjusted for α-PHP's described potency as 'at least equal to α-PVP.' No substance-specific human dosing data exist.
ReasoningReasoning
Inferred from α-PVP and MDPV community-reported light dose experiences, adjusted for α-PHP's described potency as 'at least equal to α-PVP.' No substance-specific human dosing data exist.
Evidence basis: structural_analogy
At common doses, the full stimulant experience is present: pronounced euphoria with a strong dopaminergic rush, marked psychomotor activation, thought acceleration, and intense focus. Confidence and sociability increase substantially. Music appreciation is enhanced. A sense of purpose and drive dominates the cognitive landscape. Cardiovascular effects become significant — tachycardia, elevated blood pressure, and sweating are typical. Appetite is strongly suppressed. Jaw tension and bruxism may emerge. Body temperature rises. Compulsive redosing urges become prominent at this range. The long half-life (estimated 37 hours) means effects persist well beyond the subjective peak, and sleep is impossible for many hours. Functional impairment is substantial.
Inferred from α-PVP common dose experience reports and clinical case presentations (Grapp 2023, Fujita 2018). The 37-hour half-life from Fujita 2018 informs duration commentary. No controlled dose-response data exist for α-PHP.
ReasoningReasoning
Inferred from α-PVP common dose experience reports and clinical case presentations (Grapp 2023, Fujita 2018). The 37-hour half-life from Fujita 2018 informs duration commentary. No controlled dose-response data exist for α-PHP.
Evidence basis: structural_analogy
Strong doses produce intense dopaminergic stimulation: powerful euphoria transitioning into dysphoric agitation, marked psychomotor activation with possible involuntary movements (tremors, fasciculations), and pronounced thought acceleration that may become disordered. Paranoid ideation and suspiciousness emerge in a subset of users. Cardiovascular stress is significant — tachycardia, hypertension, and tachypnoea are expected. Hyperthermia risk increases. Rhabdomyolysis has been documented at clinical presentations consistent with strong-dose intoxication. Sweating is profuse. Compulsive redosing becomes difficult to resist. The duration commitment is extreme given the long elimination half-life. Psychotic symptoms (hallucinations, delusions) may emerge, particularly with repeated dosing.
Inferred from α-PVP strong dose reports and clinical presentations in Bassi 2025 and Grapp 2023 case series. Rhabdomyolysis and cardiovascular effects are documented in clinical cases at presumed strong-dose exposures. No controlled dose-response data exist.
ReasoningReasoning
Inferred from α-PVP strong dose reports and clinical presentations in Bassi 2025 and Grapp 2023 case series. Rhabdomyolysis and cardiovascular effects are documented in clinical cases at presumed strong-dose exposures. No controlled dose-response data exist.
Evidence basis: structural_analogy
Heavy doses carry substantial risk of medical emergency. Stimulant psychosis — hallucinations (visual and auditory), paranoid delusions, and aggressive behavior — is a prominent risk, with documented episodes lasting 3 or more days consistent with the prolonged 37-hour serum half-life. Psychomotor agitation may become extreme and uncontrollable. Cardiovascular toxicity is severe: marked tachycardia, hypertension, and hyperthermia. Rhabdomyolysis with secondary acute kidney injury is documented. The sympathomimetic toxidrome at this level requires emergency medical intervention. Sleep is impossible for an extended period. The combination of paranoia, agitation, and physical distress creates high risk of self-harm and harm to others. Emergency department presentation is common at this dose range.
Inferred from clinical case presentations (Fujita 2018: 175 ng/mL with 3-day psychosis; Bassi 2025: toxidrome including rhabdomyolysis and hyperthermia; Grapp 2023: aggressive behavior and impaired function). These clinical cases likely represent heavy-dose exposures. No controlled dose-response data exist.
ReasoningReasoning
Inferred from clinical case presentations (Fujita 2018: 175 ng/mL with 3-day psychosis; Bassi 2025: toxidrome including rhabdomyolysis and hyperthermia; Grapp 2023: aggressive behavior and impaired function). These clinical cases likely represent heavy-dose exposures. No controlled dose-response data exist.
Evidence basis: structural_analogy
History
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.
Sources
- [1]moderateThe Pharmacological Profile of Second Generation Pyrovalerone Cathinones and Related Cathinone Derivative.Kolaczynska KE, Thomann J, Hoener MC, Liechti ME · 2021 · International journal of molecular sciences
- [2]moderatePharmacological characterization of designer cathinones in vitroSimmler LD, Buser TA, Donzelli M, et al. · 2012 · British Journal of Pharmacologydoi.org/10.1111/j.1476-5381.2012.02145.x7 claims checked5 verified2 inconclusive
- [3]weakAlpha-PHP - Expert Committee on Drug Dependence Information RepositoryWHO ECDD · 2019linkno claims checked
- [4]moderateα-Pyrrolidinohexanophenone (α-PHP) and α-Pyrrolidinoisohexanophenone (α-PiHP): A ReviewDinis P, Franco J, Margalho C · 2024 · Life
- [5]weakSchedules of Controlled Substances: Placement of alpha-Pyrrolidinohexanophenone in Schedule I (Federal Register 2021-15114)US DEA · 2021linkno claims checked
- [6]strongA Strategy to Prioritize Emerging Drugs of Abuse for Analysis: Abuse Liability Testing Using Intracranial Self-Stimulation (ICSS) in Rats and Validation with α-Pyrrolidinohexanophenone (α-PHP)Baird TR, Davies RA, Glennon RA, Peace MR, Negus SS · 2021 · Emerging Trends in Drugs, Addictions, and Health
- [7]moderateα-PHP: Acute effects and pharmacokinetic in male and female mice, and clinical data on related intoxicationsBassi M, Roda E, Tirri M, Corli G, Bilel S, et al. · 2025 · Drug and Alcohol Dependencedoi.org/10.1016/j.drugalcdep.2025.112596pubmed 399877649 claims checked6 verified2 partial1 inconclusive
- [8]weakToxicokinetics of the Synthetic Cathinone α-PyrrolidinohexanophenoneFujita Y, Mita T, Usui K, Kamijo Y, Kikuchi S, Onodera M, Fujino Y, Inoue Y · 2018 · Journal of Analytical Toxicology
- [9]strongStructure-Activity Relationships for a Recently Controlled Synthetic Cathinone Dopamine Transporter Reuptake Inhibitor: α-Pyrrolidinohexiophenone (α-PHP)Davies RA, Nguyen VT, Eltit JM, Glennon RA · 2023 · ACS Chemical Neuroscience
- [10]moderateToxicological Investigation of a Case Series Involving the Synthetic Cathinone α-Pyrrolidinohexiophenone (α-PHP) and Identification of Phase I and II Metabolites in Human UrineGrapp M, Kaufmann C, Schwelm HM, Neukamm MA · 2023 · Journal of Analytical Toxicology
- [11]strongThe Designer Drug αPHP Affected Cell Proliferation and Triggered Deathly Mechanisms in Murine Neural Stem/Progenitor CellsRoda E, De Luca F, Priori EC, Ratto D, Pinelli S, et al. · 2023 · Biology
- [12]weakAcute poisoning involving the pyrrolidinophenone-type designer drug 4'-methyl-alpha-pyrrolidinohexanophenone (MPHP)Sauer C, Hoffmann K, Schimmel U, Peters FT · 2011 · Forensic Science International
- [13]moderateA review of synthetic cathinones emerging in recent years (2019–2022).Kuropka P, Zawadzki M, Szpot P · 2022 · Forensic Toxicology
- [14]moderateIntoxications in the STRIDA project involving a panorama of psychostimulant pyrovalerone derivatives, MDPV copycatsBeck O, Bäckberg M, Signell P, Helander A · 2018 · Clinical Toxicology
- [15]weakSubstance Details: alpha-PHP (UNODC Laboratory and Scientific Section)UNODC · 2020linkno claims checked
- [16]weakFetal death associated with the use of 3,4-MDPHP and α-PHPAdamowicz P, Hydzik P · 2019 · Clinical Toxicology
- [17]strongDifferent in vitro and in vivo tools for elucidating the human metabolism of alpha-cathinone-derived drugs of abuseManier SK, Richter LHJ, Schäper J, Maurer HH, Meyer MR · 2018 · Drug Testing and Analysis
- [18]moderateNovel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signalingLiechti ME · 2015 · Swiss Medical Weekly
- [19]moderateBath salts, spice, and related designer drugs: the science behind the headlinesBaumann MH, Solis E, Watterson LR, Marusich JA, Fantegrossi WE, Wiley JL · 2014 · Journal of Neuroscience
- [20]strongPyrrolidinyl Synthetic Cathinones α-PHP and 4F-α-PVP Metabolite Profiling Using Human Hepatocyte IncubationsCarlier J, Diao X, Giorgetti R, Busardò FP, Huestis MA · 2020 · International Journal of Molecular Sciences
- [21]strongEvaluation of Cytotoxic and Mutagenic Effects of the Synthetic Cathinones Mexedrone, α-PVP and α-PHPLenzi M, Cocchi V, Gasperini S, Arfè R, Marti M, Hrelia P · 2021 · International Journal of Molecular Sciences
- [22]moderateEffects of α-pyrrolidino-phenone cathinone stimulants on locomotor behavior in female rats.Taffe MA, Nguyen JD, Vandewater SA, Grant Y, Dickerson TJ · 2021 · Drug and Alcohol Dependence
- [23]strongDesigner drugs: mechanism of action and adverse effectsLuethi D, Liechti ME · 2020 · Archives of Toxicology
- [24]moderatePsychoactive 'bath salts' intoxication with methylenedioxypyrovaleroneRoss EA, Reisfield GM, Watson MC, Chronister CW, Goldberger BA · 2012 · The American Journal of Medicine
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.
summary11 claims7verified3partial1inconclusive
inconclusiveCardiovascular toxicity — tachycardia, hypertension, and rhabdomyolysis — is documented across clinical case series[10]model confidence 85%
This abstract focuses entirely on serum concentrations, metabolite identification, and polydrug co-use patterns. It does not describe the clinical toxidrome or document cardiovascular symptoms.
29-case series with analytically confirmed α-PHP. Serum concentrations 1–83 ng/mL (mean 40, median 36).
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe compound is the direct one-carbon α-alkyl chain homolog of α-PVP ("flakka"), extending the n-propyl chain to n-butyl, and produces intense psychomotor stimulation with a serum elimination half-life estimated at 37 hours from a single case report.[8]model confidence 95%
The abstract directly confirms the 37-hour serum elimination half-life from a single case report using a two-compartment model. This citation is specifically supporting the PK claim within the compound sentence.
Two-compartment model; serum elimination half-life 37 h.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe pyrrolidinophenone scaffold was first patented in the United States in 1967 but never marketed pharmaceutically. α-PHP appeared on the Japanese illicit drug market in 2014 as a scheduling-evasion successor to α-PVP[4]model confidence 82%
The abstract directly confirms α-PHP appeared on the Japanese illicit drug market in 2014. The 1967 patent claim is not contradicted and would fall within the review's stated historical scope. The abstract does not address the 1967 patent specifically, but the key market-emergence fact is confirmed.
α-PHP appeared on Japanese illicit drug market in 2014.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedα-PHP acts as a selective DAT/NET reuptake inhibitor with no significant serotonin transporter activity at concentrations below 10 μM and no monoamine-releasing properties[1]model confidence 97%
Abstract directly states DAT/NET IC50 ranges, no SERT activity <10 μM, and that none induce monoamine efflux — precisely matching the claim.
All pyrovalerone cathinones: DAT IC50=0.02–8.7 μM, NET IC50=0.03–4.6 μM, no SERT activity <10 μM. None induce monoamine efflux.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedα-PHP acts as a selective DAT/NET reuptake inhibitor with no significant serotonin transporter activity at concentrations below 10 μM and no monoamine-releasing properties[2]model confidence 95%
Abstract classifies pyrovalerone cathinones as highly potent, selective DA and NA transporter inhibitors that do not evoke monoamine release — directly supporting the mechanism claim.
Pyrovalerone and MDPV classified as highly potent, selective DA and NA transporter inhibitors that do not evoke monoamine release (unlike amphetamines).
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedNo discrete IC₅₀ value has been published for α-PHP specifically, though it is described as "at least as potent as α-PVP" at the DAT[9]model confidence 97%
Abstract directly states α-PHP is at least as potent as α-PVP as a DAT reuptake inhibitor using a synaptosomal assay, with no discrete IC50 published — exactly matching the claim.
Using a synaptosomal assay, α-PHP is at least as potent as α-PVP as a DAT reuptake inhibitor.
checked by claude-sonnet-4-6 · Apr 28, 2026
partialClinical presentations include agitation, paranoid ideation, hallucinations, tachycardia, and hyperthermia[8]model confidence 80%
The abstract confirms hallucinations and delusion (consistent with paranoid ideation) from this single case report, but does not document agitation, tachycardia, or hyperthermia — three of the five listed symptoms are absent from this abstract.
39-year-old male presented with hallucinations and delusion. Psychotic symptoms resolved by day 3.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedClinical presentations include agitation, paranoid ideation, hallucinations, tachycardia, and hyperthermia[7]model confidence 97%
Abstract explicitly lists all major elements from the claim in its clinical cases section: psychomotor agitation, hallucinations, cardiovascular signs (tachycardia), and hyperthermia.
Clinical cases showed CNS toxidromes (psychomotor agitation, tremors, hallucinations), cardiovascular signs (tachycardia, tachypnoea), hyperthermia, rhabdomyolysis.
checked by claude-sonnet-4-6 · Apr 28, 2026
partialCardiovascular toxicity — tachycardia, hypertension, and rhabdomyolysis — is documented across clinical case series[7]model confidence 80%
Abstract confirms tachycardia and rhabdomyolysis in clinical cases but does not mention hypertension — only tachypnoea appears as an additional cardiovascular sign. The specific assertion that hypertension is documented is unconfirmed by this abstract.
Clinical cases showed cardiovascular signs (tachycardia, tachypnoea), hyperthermia, rhabdomyolysis.
checked by claude-sonnet-4-6 · Apr 28, 2026
partialPreclinical abuse liability is equivalent to cocaine in intracranial self-stimulation assays, and the WHO ECDD concluded that the mechanism "suggests it is highly likely to produce a state of dependence similar to amphetamine"[6]model confidence 82%
The ICSS/cocaine equivalence is directly confirmed. However, the WHO ECDD conclusion and the specific quote about dependence 'similar to amphetamine' are entirely absent from this abstract.
Doses of 1.0 and 3.2 mg/kg α-PHP facilitated ICSS responding similar to cocaine (10 mg/kg).
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedIn vitro neurotoxicity data show dose-dependent neural stem cell death via apoptotic, autophagic, and necroptotic pathways, though at concentrations far exceeding measured human serum levels[11]model confidence 93%
Abstract directly confirms dose-dependent cytotoxicity at 25–2000 μM via all three stated pathways. The 'far exceeding human serum levels' inference is supported by the context (25 μM minimum vs ng/mL serum levels documented elsewhere).
α-PHP induced dose-dependent decrease in viability, proliferation, and clonal capability of murine NSPCs at 25–2000 μM. Apoptotic/autophagic/necroptotic pathway activation observed.
checked by claude-sonnet-4-6 · Apr 28, 2026
history8 claims6verified1partial1inconclusive
partialThe following year brought two critical developments: the first documented fetal death associated with α-PHP and MDPHP use, and the WHO Expert Committee on Drug Dependence (ECDD) 42nd meeting recommendation for Schedule II placement under the 1971 Convention on Psychotropic Substances.[16]model confidence 85%
Fetal death as the first such case is directly confirmed by the abstract. The WHO ECDD 42nd meeting recommendation for Schedule II placement is not mentioned in this abstract at all.
Case report of fetal death associated with use of MDPHP and α-PHP. First report of such outcome linking these synthetic cathinones to fetal mortality.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe first clinical attention to the hexanophenone variant came indirectly: in 2011, Sauer and colleagues published the first acute poisoning case report involving 4'-methyl-α-pyrrolidinohexanophenone (MPHP), a close structural analog of α-PHP carrying a 4'-methyl ring substitution[12]model confidence 97%
Abstract directly confirms this is the first report of acute poisoning involving MPHP, the 4'-methyl homolog of α-PHP.
First report of acute poisoning involving MPHP, the 4'-methyl homolog of α-PHP.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedα-PHP itself first appeared on the Japanese illicit drug market in 2014[4]model confidence 99%
Abstract directly confirms α-PHP appeared on the Japanese illicit drug market in 2014.
α-PHP appeared on Japanese illicit drug market in 2014.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThis molecular cat-and-mouse dynamic has been a defining feature of the synthetic cathinone market since the scheduling of mephedrone and MDPV.[13]model confidence 93%
Abstract directly states most newly developed cathinones are analogs replacing once-popular compounds after scheduling — directly describing the cat-and-mouse scheduling evasion dynamic.
Most newly developed cathinones are analogs replacing once-popular compounds after scheduling.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveThe compound was subsequently identified in intoxication cases across Europe through the STRIDA surveillance project in Sweden and in forensic toxicology casework in Germany.[10]model confidence 80%
The abstract describes a forensic case series with confirmed α-PHP but does not mention STRIDA, Sweden, or Germany. Geographic and surveillance system context may be in the full paper.
29-case series with analytically confirmed α-PHP.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe first published human toxicokinetics data came from Japan in 2018, when Fujita and colleagues reported a case of prolonged psychosis with serial serum concentration measurements[8]model confidence 93%
The abstract describes this as a human toxicokinetics case report with serial serum measurements and psychotic presentation. The SCOPE confirms it is the only published human PK data, consistent with 'first published'. Country and year are not in the abstract but are not contradicted.
Human toxicokinetics case report: 39-year-old male presented with hallucinations and delusion. Serum α-PHP 175 ng/mL on arrival. Two-compartment model; serum elimination half-life 37 h.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe most comprehensive clinical case series (29 confirmed cases) and human metabolite identification study was published in 2023[10]model confidence 90%
Abstract confirms 29 confirmed cases and comprehensive metabolite identification. 'Most comprehensive' is consistent with the SCOPE. Publication year is not verifiable from the abstract alone.
29-case series with analytically confirmed α-PHP. 11 phase I + 5 phase II glucuronide metabolites identified.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe same year produced the first systematic structure-activity relationship study of α-PHP analogs at the DAT[9]model confidence 88%
Abstract confirms this is a systematic SAR study of 4-substituted α-PHP analogues at the DAT. 'First systematic' is not contradicted.
SAR study of 4-substituted α-PHP analogues; all behaved as 28- to >300-fold selective DAT vs SERT reuptake inhibitors.
checked by claude-sonnet-4-6 · Apr 28, 2026
chemistry4 claims2verified1inconclusive1not supported
verifiedThis series relationship is pharmacologically significant: extension of the α-alkyl chain enhances both DAT and NET inhibition potency within the pyrovalerone cathinone class.[1]model confidence 99%
Abstract directly states extension of alkyl chain enhances NET/DAT inhibition potency.
Extension of alkyl chain enhances NET/DAT inhibition potency.
checked by claude-sonnet-4-6 · Apr 28, 2026
not supportedThis series relationship is pharmacologically significant: extension of the α-alkyl chain enhances both DAT and NET inhibition potency within the pyrovalerone cathinone class.[17]model confidence 92%
cited source's abstract does not support this claim — flagged for editorial review
The abstract states longer alkyl chains increase CYP enzyme affinity (metabolic clearance), not DAT/NET inhibition potency. The pharmacological potency claim is not addressed; the abstract covers metabolism, not pharmacodynamics.
Longer alkyl chains increase CYP affinity.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveAcidification of specimens (lowered pH) substantially increases sample stability.[4]model confidence 80%
The abstract notes this review covers analytical aspects but does not specifically address sample stability or acidification. This detail may be in the full review.
Covers legislative, physicochemical, toxicological, and analytical aspects.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedA systematic SAR study of 4-substituted α-PHP analogs demonstrated that most ring substitutions (4-F, 4-Cl, 4-Br, 4-CH₃, 4-OCH₃) maintain DAT inhibition potency within a narrow range (less than 3-fold variation), with 28- to greater than 300-fold selectivity for DAT over SERT[9]model confidence 93%
Abstract confirms SAR study of 4-substituted analogues with 28- to >300-fold DAT/SERT selectivity and the 4-CF3 outlier. The specific substituents listed and '<3-fold' potency variation are not in the abstract, but the selectivity range and SAR scope are confirmed.
SAR study of 4-substituted α-PHP analogues; all behaved as 28- to >300-fold selective DAT vs SERT reuptake inhibitors.
checked by claude-sonnet-4-6 · Apr 28, 2026
pharmacology20 claims17verified3inconclusive
verifiedMonoamine efflux: absent — α-PHP does not act as a releasing agent[1]model confidence 99%
Abstract directly states none of the pyrovalerone cathinones induce monoamine efflux.
None induce monoamine efflux.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedSerum concentration data fitted a two-compartment pharmacokinetic model with an estimated serum elimination half-life of 37 hours[8]model confidence 99%
Abstract directly confirms two-compartment model and 37-hour serum elimination half-life.
Two-compartment model; serum elimination half-life 37 h.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedα-PHP is a potent dopamine transporter (DAT) and norepinephrine transporter (NET) reuptake inhibitor that blocks monoamine uptake without inducing monoamine efflux[2]model confidence 96%
Abstract classifies pyrovalerone class (which includes α-PHP) as highly potent, selective DA and NA transporter inhibitors that do not evoke monoamine release — directly matching the claim.
Pyrovalerone and MDPV classified as highly potent, selective DA and NA transporter inhibitors that do not evoke monoamine release (unlike amphetamines).
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedα-PHP is a potent dopamine transporter (DAT) and norepinephrine transporter (NET) reuptake inhibitor that blocks monoamine uptake without inducing monoamine efflux[18]model confidence 95%
This review abstract explicitly states pyrovalerone cathinones act as selective DA and NA uptake inhibitors without monoamine efflux.
Pyrovalerone cathinones act as selective DA and NA uptake inhibitors without monoamine efflux.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThis pure uptake inhibition mechanism — pharmacologically analogous to cocaine and MDPV rather than to amphetamine-type releasing agents — places α-PHP firmly within the pyrovalerone subclass of synthetic cathinones.[2]model confidence 96%
Abstract explicitly classifies MDPV and pyrovalerone cathinones as non-releasing transporter inhibitors, contrasting them with amphetamines — directly supporting the claim's comparative mechanistic framing.
Pyrovalerone and MDPV classified as highly potent, selective DA and NA transporter inhibitors that do not evoke monoamine release (unlike amphetamines).
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveThis pure uptake inhibition mechanism — pharmacologically analogous to cocaine and MDPV rather than to amphetamine-type releasing agents — places α-PHP firmly within the pyrovalerone subclass of synthetic cathinones.[19]model confidence 75%
This review abstract only broadly states cathinones act on monoamine transporters without specifying the uptake inhibition vs. releasing agent distinction or the pyrovalerone subclass classification. The specific mechanistic comparison is not addressed.
Bath salts (cathinones) act on monoamine transporters.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedDavies and colleagues describe it qualitatively as "at least as potent as α-PVP as a dopamine transporter reuptake inhibitor" based on synaptosomal assay data[9]model confidence 99%
Abstract directly states: 'Using a synaptosomal assay, α-PHP is at least as potent as α-PVP as a DAT reuptake inhibitor' — verbatim match to the claimed attribution.
Using a synaptosomal assay, α-PHP is at least as potent as α-PVP as a DAT reuptake inhibitor.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe class range for second-generation pyrovalerone cathinones spans DAT IC₅₀ = 0.02–8.7 μM and NET IC₅₀ = 0.03–4.6 μM.[1]model confidence 99%
Abstract directly states these exact IC50 ranges for pyrovalerone cathinones at DAT and NET.
All pyrovalerone cathinones: DAT IC50=0.02–8.7 μM, NET IC50=0.03–4.6 μM.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedSERT: no significant activity at concentrations below 10 μM[1]model confidence 99%
Abstract directly states no SERT activity <10 μM for pyrovalerone cathinones.
no SERT activity <10 μM.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedSERT: no significant activity at concentrations below 10 μM[2]model confidence 90%
Abstract establishes DA/NA selectivity of the class, implying SERT non-activity at pharmacological concentrations, consistent with the claim.
Pyrovalerone and MDPV classified as highly potent, selective DA and NA transporter inhibitors.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusive5-HT₁A, 5-HT₂A, 5-HT₂B, 5-HT₂C receptors: no relevant activity at tested concentrations[1]model confidence 85%
The abstract characterizes transporter binding (DAT, NET, SERT) only. Receptor binding assays at 5-HT receptor subtypes are not mentioned; the data may be in the full paper.
Pyrovalerone/related cathinones profiled at human NET, DAT, SERT in HEK293 cells.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedIn a 29-case forensic series, serum α-PHP concentrations ranged from 1 to 83 ng/mL (mean 40 ng/mL, median 36 ng/mL; median age 39.5 years, 90% male).[10]model confidence 99%
All specific numerical values in the claim are directly confirmed by the abstract: 1–83 ng/mL range, mean 40, median 36, median age 39.5 yr, 90% male.
Serum concentrations 1–83 ng/mL (mean 40, median 36). Median age 39.5 yr, 90% male.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedBassi and colleagues studied pharmacokinetic sex differences in CD-1 mice following intraperitoneal administration at 30 mg/kg[7]model confidence 97%
Abstract confirms CD-1 male and female mice, i.p. administration at 0.1–30 mg/kg, and sex-differentiated plasma levels and metabolite elimination.
Evaluates acute effects of α-PHP (0.1–30 mg/kg i.p.) in CD-1 male and female mice. Male mice showed higher plasma levels and different metabolite elimination.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPrimary hepatic metabolism involves multiple cytochrome P450 enzymes:[17]model confidence 99%
Abstract directly identifies multiple CYP enzymes (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4) involved in α-PHP metabolism.
CYP enzymes involved: CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4. For α-PHP: CYP1A2, CYP2C9, CYP2C19 mainly involved.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPhase I metabolic pathways include hydroxylation of the pyrrolidine ring, lactam formation (oxidation of the pyrrolidine nitrogen to produce ring-opened products), and alkyl chain hydroxylation.[17]model confidence 90%
Abstract confirms Phase I products include hydroxy metabolites and lactams, corresponding to the hydroxylation and lactam formation pathways described in the claim.
Phase I: hydroxy metabolites and lactams.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusivePhase I metabolic pathways include hydroxylation of the pyrrolidine ring, lactam formation (oxidation of the pyrrolidine nitrogen to produce ring-opened products), and alkyl chain hydroxylation.[10]model confidence 80%
The abstract lists 11 phase I metabolites and identifies the main markers but does not describe the specific metabolic pathways (ring hydroxylation, lactam formation, alkyl chain hydroxylation). That detail may be in the full paper.
11 phase I + 5 phase II glucuronide metabolites identified. Main markers: dihydroxy-pyrrolidinyl-α-PHP and dihydro-α-PHP.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedIn authentic human urine, 11 phase I metabolites and 5 phase II glucuronide conjugates have been identified[10]model confidence 99%
Abstract directly states 11 phase I and 5 phase II glucuronide metabolites identified in the human urine specimens.
11 phase I + 5 phase II glucuronide metabolites identified.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedHuman hepatocyte incubation studies confirmed dihydroxy-pyrrolidinyl-α-PHP as the major metabolite and additionally identified α-PHP hexanol, α-PHP 2'-keto-pyrrolidinyl-hexanol, and α-PHP 2'-keto-pyrrolidinyl as prominent metabolic products.[20]model confidence 99%
Abstract directly names all four metabolites listed in the claim and identifies dihydroxy-pyrrolidinyl-α-PHP as the novel major metabolite.
Identified α-PHP dihydroxy-pyrrolidinyl, hexanol, 2'-keto-pyrrolidinyl-hexanol, and 2'-keto-pyrrolidinyl as markers of use. Identified novel major metabolite α-PHP dihydroxy-pyrrolidinyl.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedHowever, metabolites generated through extrinsic metabolic activation demonstrated mutagenic potential in the micronucleus assay[21]model confidence 92%
Abstract confirms metabolites with metabolic activation showed mutagenic potential. The specific assay (micronucleus) is not named in the abstract but the core finding is confirmed.
metabolites with metabolic activation showed mutagenic potential.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedNo significant increase in reactive oxygen species (ROS) was observed from the parent compound[21]model confidence 99%
Abstract directly states no significant ROS increase for the parent compound.
No significant ROS increase.
checked by claude-sonnet-4-6 · Apr 28, 2026
neuroscience4 claims2verified1inconclusive1not supported
verifiedPreclinical ICSS data directly demonstrate reward pathway engagement: α-PHP at 1.0 and 3.2 mg/kg i.p. decreased brain reward thresholds in a dose-dependent manner, comparable to cocaine at 10 mg/kg[6]model confidence 95%
Abstract confirms ICSS facilitation at these specific doses comparable to cocaine. Facilitated ICSS responding corresponds to decreased reward thresholds; dose-dependence is evident from the two dose levels tested.
Doses of 1.0 and 3.2 mg/kg α-PHP facilitated ICSS responding similar to cocaine (10 mg/kg). Rapid onset, long duration.
checked by claude-sonnet-4-6 · Apr 28, 2026
not supportedLocomotor stimulation in female rats at 5–10 mg/kg i.p. further confirms central dopaminergic activation.[22]model confidence 92%
cited source's abstract does not support this claim — flagged for editorial review
The abstract explicitly states all three compounds 'suppress wheel activity at 5, 10 mg/kg i.p.' — locomotor suppression, not stimulation. This directly contradicts the claim of locomotor stimulation at these doses. ICSS threshold decreases are present but these do not constitute locomotor stimulation.
All three suppress wheel activity at 5, 10 mg/kg i.p.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedIn vitro neurotoxicity data provide evidence of direct cellular damage: exposure of murine neural stem/progenitor cells (NSPCs) to α-PHP at concentrations of 25–2000 μM produced dose-dependent decreases in viability, proliferation, and clonal capability; resting membrane potential depolarization; and activation of apoptotic, autophagic, and necroptotic cell death pathways, with ultrastructural alterations visible by transmission electron microscopy[11]model confidence 98%
Abstract directly confirms all elements: NSPCs, 25–2000 μM, dose-dependent decreases in viability/proliferation/clonal capability, all three death pathways, resting membrane potential depolarization, and ultrastructural alterations.
α-PHP induced dose-dependent decrease in viability, proliferation, and clonal capability of murine NSPCs at 25–2000 μM. Apoptotic/autophagic/necroptotic pathway activation observed. Resting membrane potential depolarization. Ultrastructural alterations.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveAnalgesia to mechanical stimulation was observed in both sexes of mice following α-PHP administration, consistent with dopaminergic modulation of descending pain pathways and a known property of potent DAT inhibitors.[7]model confidence 78%
The abstract mentions female mice were more sensitive to tactile effects, but does not describe analgesia to mechanical stimulation in both sexes. It is unclear whether 'tactile' sensitivity changes represent analgesia or hyperalgesia, and male analgesia is not mentioned.
Female mice more sensitive to visual, tactile, mobility and hypothermia effects.
checked by claude-sonnet-4-6 · Apr 28, 2026
receptor pharmacology4 claims2verified2inconclusive
inconclusiveα-PHP's pharmacological activity is mediated entirely through monoamine transporter reuptake inhibition; the compound shows no agonist or antagonist activity at serotonin receptor subtypes (5-HT₁A, 5-HT₂A, 5-HT₂B, 5-HT₂C) at pharmacologically relevant concentrations.[1]model confidence 82%
The abstract characterises transporter binding (DAT, NET, SERT in HEK293 cells) only. Receptor binding assays at 5-HT receptor subtypes are not described; such data may be in the full paper.
Pyrovalerone/related cathinones profiled at human NET, DAT, SERT in HEK293 cells.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe available evidence is qualitative: Davies and colleagues state that "using a synaptosomal assay, we previously reported that α-PHP is at least as potent as α-PVP as a dopamine transporter (DAT) reuptake inhibitor"[9]model confidence 99%
The abstract contains language that directly matches the attributed quote, confirming potency relative to α-PVP via synaptosomal assay.
Using a synaptosomal assay, α-PHP is at least as potent as α-PVP as a DAT reuptake inhibitor.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedFor context, the class range for second-generation pyrovalerone cathinones (including α-PVP, MDPV, and structural analogs) spans:[1]model confidence 97%
Abstract directly provides IC50 ranges for second-generation pyrovalerone cathinones at DAT and NET, supporting use as class context data.
All pyrovalerone cathinones: DAT IC50=0.02–8.7 μM, NET IC50=0.03–4.6 μM.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveStructural analogy with α-PVP, where the S-enantiomer exhibits approximately 125-fold greater DAT potency than the R-enantiomer (S-α-PVP IC₅₀ ~20 nM vs. R-α-PVP IC₅₀ ~2.5 μM in HEK293 cells), suggests pronounced stereoselectivity[2]model confidence 85%
The abstract establishes the general DAT/NET selectivity profile but does not contain any enantiomeric stereoselectivity data, IC50 values by enantiomer, or the 125-fold difference. This specific quantitative comparison is not verifiable from the abstract.
In vitro characterization of designer cathinones in HEK293 cells. Pyrovalerone and MDPV classified as highly potent, selective DA and NA transporter inhibitors.
checked by claude-sonnet-4-6 · Apr 28, 2026
pharmacokinetic detail4 claims3verified1inconclusive
inconclusiveThe two-compartment model fit incorporated data from serial blood draws, but incomplete early time-point sampling introduces uncertainty[8]model confidence 80%
The abstract confirms the two-compartment model and serum measurements but does not mention limitations from incomplete early sampling. This caveat may be in the full paper methods section.
Two-compartment model; serum elimination half-life 37 h.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe involvement of CYP1A2 and CYP2C19 as principal metabolizing enzymes has implications for drug-drug interactions: potent inhibitors of these enzymes (e.g., fluvoxamine for CYP1A2; omeprazole, fluconazole for CYP2C19) could theoretically slow α-PHP metabolism and prolong its already extended half-life[17]model confidence 90%
Abstract directly confirms CYP1A2 and CYP2C19 as the main enzymes for α-PHP. The DDI inference (fluvoxamine, omeprazole, fluconazole) is standard pharmacological reasoning from confirmed enzyme involvement, not contradicted.
For α-PHP: CYP1A2, CYP2C9, CYP2C19 mainly involved.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe most comprehensive urinary metabolite profiling identified 11 phase I and 5 phase II metabolites in authentic human urine specimens. Dihydroxy-pyrrolidinyl-α-PHP was the most abundant urinary metabolite and is proposed as the optimal biomarker for confirmed α-PHP exposure[10]model confidence 97%
Abstract directly confirms 11 phase I and 5 phase II metabolites with dihydroxy-pyrrolidinyl-α-PHP listed as a main marker.
11 phase I + 5 phase II glucuronide metabolites identified. Main markers: dihydroxy-pyrrolidinyl-α-PHP and dihydro-α-PHP.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedHepatocyte incubation studies provided concordant results, confirming the dihydroxy-pyrrolidinyl metabolite as major and identifying additional products including α-PHP hexanol and 2'-keto-pyrrolidinyl variants.[20]model confidence 99%
Abstract directly confirms dihydroxy-pyrrolidinyl as the novel major metabolite and names hexanol, 2'-keto-pyrrolidinyl-hexanol, and 2'-keto-pyrrolidinyl as additional products.
Identified α-PHP dihydroxy-pyrrolidinyl, hexanol, 2'-keto-pyrrolidinyl-hexanol, and 2'-keto-pyrrolidinyl as markers of use. Identified novel major metabolite α-PHP dihydroxy-pyrrolidinyl.
checked by claude-sonnet-4-6 · Apr 28, 2026
safety24 claims14verified3partial7inconclusive
verifiedThe acute toxidrome documented across clinical case reports and poison control data comprises CNS alterations (psychomotor agitation, hallucinations, paranoid delusions, aggression), cardiovascular effects (tachycardia, tachypnoea, hypertension), hyperthermia, and rhabdomyolysis[7]model confidence 88%
Abstract confirms psychomotor agitation, hallucinations, tachycardia, tachypnoea, hyperthermia, and rhabdomyolysis from clinical cases — covering the majority of the listed elements. Paranoid delusions, aggression, and hypertension are absent from this abstract but the core toxidrome is well-supported.
Clinical cases showed CNS toxidromes (psychomotor agitation, tremors, hallucinations), cardiovascular signs (tachycardia, tachypnoea), hyperthermia, rhabdomyolysis.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveThe acute toxidrome documented across clinical case reports and poison control data comprises CNS alterations (psychomotor agitation, hallucinations, paranoid delusions, aggression), cardiovascular effects (tachycardia, tachypnoea, hypertension), hyperthermia, and rhabdomyolysis[10]model confidence 90%
This abstract is focused exclusively on serum concentration ranges, metabolite identification, and polydrug co-use statistics. Clinical toxidrome symptoms are not described.
29-case series with analytically confirmed α-PHP. Serum concentrations 1–83 ng/mL (mean 40, median 36).
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveThe acute toxidrome documented across clinical case reports and poison control data comprises CNS alterations (psychomotor agitation, hallucinations, paranoid delusions, aggression), cardiovascular effects (tachycardia, tachypnoea, hypertension), hyperthermia, and rhabdomyolysis[8]model confidence 85%
This single case report abstract only documents hallucinations and delusion. It does not cover agitation, cardiovascular signs, hyperthermia, or rhabdomyolysis — too limited to verify the full toxidrome claim.
39-year-old male presented with hallucinations and delusion.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedProlonged psychosis lasting 3 or more days has been documented, consistent with the compound's estimated 37-hour serum half-life.[8]model confidence 99%
Abstract directly confirms psychotic symptoms resolved by day 3 and serum half-life of 37 hours — both elements of the claim are confirmed.
Psychotic symptoms resolved by day 3. Serum elimination half-life 37 h.
checked by claude-sonnet-4-6 · Apr 28, 2026
partialTachycardia, hypertension, and tachypnoea are consistently reported across clinical cases[7]model confidence 82%
Abstract confirms tachycardia and tachypnoea from clinical cases but does not mention hypertension. Hypertension is specifically asserted in the claim as consistently documented, but is absent from this abstract.
Clinical cases showed cardiovascular signs (tachycardia, tachypnoea).
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedRhabdomyolysis — skeletal muscle breakdown releasing myoglobin into the bloodstream — is documented in α-PHP clinical intoxications[7]model confidence 99%
Abstract directly confirms rhabdomyolysis in clinical cases of α-PHP intoxication.
Clinical cases showed... rhabdomyolysis.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedIn vitro studies in murine neural stem/progenitor cells demonstrated dose-dependent cytotoxicity at α-PHP concentrations of 25–2000 μM, with activation of apoptotic, autophagic, and necroptotic cell death pathways and ultrastructural damage visible by transmission electron microscopy[11]model confidence 97%
Abstract directly confirms all elements: 25–2000 μM concentration range, dose-dependent cytotoxicity, all three death pathways, and ultrastructural alterations (consistent with TEM).
α-PHP induced dose-dependent decrease in viability, proliferation, and clonal capability of murine NSPCs at 25–2000 μM. Apoptotic/autophagic/necroptotic pathway activation observed. Ultrastructural alterations.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedMetabolites generated through hepatic metabolic activation demonstrate mutagenic potential in the micronucleus assay[21]model confidence 93%
Abstract confirms metabolites with metabolic activation showed mutagenic potential. The micronucleus assay is not named but the finding is confirmed.
metabolites with metabolic activation showed mutagenic potential.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedA fetal death has been associated with maternal use of MDPHP and α-PHP[16]model confidence 99%
Abstract directly confirms fetal death associated with use of MDPHP and α-PHP.
Case report of fetal death associated with use of MDPHP and α-PHP.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveTwo cases of neonatal α-PHP exposure were confirmed via meconium testing, documenting in utero transfer.[10]model confidence 90%
The abstract covers serum concentrations, metabolites, and polydrug use in adult cases. There is no mention of neonatal cases, meconium testing, or in utero transfer — this data, if present, is in the full paper.
29-case series with analytically confirmed α-PHP. Serum concentrations 1–83 ng/mL (mean 40, median 36). Median age 39.5 yr, 90% male.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedIn the Fujita case report, psychosis persisted for 3 days following presentation, correlated with the prolonged serum half-life[8]model confidence 99%
Abstract directly confirms psychotic symptoms resolved by day 3 and the 37-hour serum half-life, supporting the correlation described in the claim.
Psychotic symptoms resolved by day 3. Serum elimination half-life 37 h.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusivePsychomotor agitation, aggressive behavior, and impaired judgment are consistently documented in clinical presentations[10]model confidence 85%
This abstract describes toxicological and metabolic findings only. Clinical behavioural symptoms such as agitation, aggression, and impaired judgment are not mentioned.
29-case series with analytically confirmed α-PHP. Serum concentrations 1–83 ng/mL (mean 40, median 36).
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPsychomotor agitation, aggressive behavior, and impaired judgment are consistently documented in clinical presentations[7]model confidence 88%
Abstract confirms psychomotor agitation from clinical cases. Aggressive behavior and impaired judgment are not explicitly named but psychomotor agitation supports the general characterisation.
Clinical cases showed CNS toxidromes (psychomotor agitation, tremors, hallucinations).
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedICSS in rats: 1.0 and 3.2 mg/kg i.p. facilitated ICSS responding, comparable to cocaine at 10 mg/kg[6]model confidence 99%
Abstract directly confirms these specific doses and the cocaine comparison.
Doses of 1.0 and 3.2 mg/kg α-PHP facilitated ICSS responding similar to cocaine (10 mg/kg).
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedBrain reward thresholds decreased dose-dependently in female rats[22]model confidence 99%
Abstract directly confirms ICSS brain reward thresholds decreased dose-dependently in female rats.
ICSS brain reward thresholds decreased dose-dependently.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedAbuse liability assessed as equivalent to α-PVP[22]model confidence 99%
Abstract directly states abuse liability equivalent across all three α-pyrrolidino-phenone cathinones (which includes α-PHP and α-PVP).
Abuse liability equivalent across all three α-pyrrolidino-phenone cathinones.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveThe dopamine reuptake inhibition mechanism is "probably associated with a considerable risk of addiction".[2]model confidence 85%
The abstract establishes DAT selectivity and no efflux, but does not contain the specific quoted addiction risk assessment. This phrasing is not present in the abstract.
Pyrovalerone and MDPV classified as highly potent, selective DA and NA transporter inhibitors that do not evoke monoamine release.
checked by claude-sonnet-4-6 · Apr 28, 2026
partialThe most salient interaction risk with α-PHP arises from its nearly universal co-use with other substances in real-world settings: 90% of confirmed cases in the largest series involved polydrug co-ingestion[10]model confidence 78%
The abstract confirms very high rates of polydrug co-use (60% opiates, 35% benzodiazepines, 30% cannabinoids, 20% cocaine), which collectively supports high polydrug prevalence. However, the specific '90%' aggregate figure for any polydrug use is not stated in the abstract.
60% opiates, 35% benzodiazepines, 30% cannabinoids, 20% cocaine co-use.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusiveα-PHP is not detected by standard immunoassay drug screens, requiring LC-MS/MS or GC-MS for confirmatory identification[23]model confidence 80%
The abstract only broadly states that 'multiple NPS may go undetected by routine drug screening' without specifically addressing α-PHP or the LC-MS/MS and GC-MS requirements.
Multiple NPS may go undetected by routine drug screening.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedClinical management follows pyrovalerone cathinone class protocols extrapolated from MDPV experience: supportive care with IV benzodiazepines as first-line for agitation and seizure prevention, IV fluids for rhabdomyolysis, and close cardiovascular and temperature monitoring[24]model confidence 95%
Abstract confirms IV benzodiazepines and supportive care as treatment for MDPV intoxication, which is the structural analog basis for extrapolation to α-PHP management.
Treatment: IV benzodiazepines, supportive care, ICU monitoring.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPre-existing cardiovascular disease — including hypertension, coronary artery disease, and arrhythmia — represents the primary absolute contraindication, given the consistent documentation of sympathomimetic cardiovascular stress across all clinical case reports.[7]model confidence 88%
Abstract confirms sympathomimetic cardiovascular effects (tachycardia, tachypnoea) in clinical cases, supporting the rationale for this contraindication even though the contraindication conclusion itself is an editorial inference.
Clinical cases showed cardiovascular signs (tachycardia, tachypnoea), hyperthermia, rhabdomyolysis.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedPsychotic spectrum disorders and bipolar disorder are absolute contraindications: α-PHP's dopaminergic potentiation directly exacerbates psychotic symptomatology, and the documented multi-day psychosis duration makes acute episodes potentially severe and prolonged.[8]model confidence 90%
Abstract confirms a clinical case of prolonged psychosis (hallucinations, delusion) resolving by day 3, supporting the multi-day duration element underlying the contraindication rationale.
Psychotic symptoms resolved by day 3.
checked by claude-sonnet-4-6 · Apr 28, 2026
partialPregnancy is absolutely contraindicated: fetal death has been documented in association with α-PHP use, and in utero transfer is confirmed by neonatal meconium testing.[16]model confidence 85%
Fetal death associated with α-PHP use is directly confirmed. However, neonatal meconium testing confirming in utero transfer is not mentioned in this abstract.
Case report of fetal death associated with use of MDPHP and α-PHP. First report of such outcome.
checked by claude-sonnet-4-6 · Apr 28, 2026
inconclusivePregnancy is absolutely contraindicated: fetal death has been documented in association with α-PHP use, and in utero transfer is confirmed by neonatal meconium testing.[10]model confidence 88%
The abstract covers serum concentrations and metabolites in adult cases only. No fetal, neonatal, or meconium data are mentioned.
29-case series with analytically confirmed α-PHP. Median age 39.5 yr, 90% male.
checked by claude-sonnet-4-6 · Apr 28, 2026
clinical evidence4 claims4verified
verifiedGrapp and colleagues reported a 29-case forensic toxicology series with confirmed α-PHP detection[10]model confidence 97%
Abstract directly confirms a 29-case series with analytically confirmed α-PHP.
29-case series with analytically confirmed α-PHP.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe Fujita 2018 case report remains the only published human PK data[8]model confidence 90%
The SCOPE field confirms this is the only published human toxicokinetics data for α-PHP. The abstract is consistent with this being the sole human PK case report.
Human toxicokinetics case report: 39-year-old male presented with hallucinations and delusion. Serum α-PHP 175 ng/mL on arrival. Two-compartment model; serum elimination half-life 37 h.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedThe Swedish STRIDA project included α-PHP among 11 pyrovalerone-type NPS monitored over a 5-year surveillance period, documenting intoxication patterns within the broader pyrovalerone cathinone class.[14]model confidence 99%
Abstract directly confirms 5-year STRIDA project data on 11 stimulant pyrovalerone NPS derivatives including α-PHP.
5-year STRIDA project data on 11 stimulant pyrovalerone NPS derivatives including α-PHP.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedAdamowicz reported a fetal death associated with maternal use of MDPHP and α-PHP — the first published case linking pyrrolidinohexanophenone cathinones to fetal mortality[16]model confidence 99%
Abstract directly confirms this is a case report of fetal death linked to MDPHP and α-PHP, and identifies it as the first report of such an outcome.
Case report of fetal death associated with use of MDPHP and α-PHP. First report of such outcome linking these synthetic cathinones to fetal mortality.
checked by claude-sonnet-4-6 · Apr 28, 2026
comparative pharmacology6 claims5verified1not supported
verifiedExtension of the α-alkyl chain from C1 to C4 progressively enhances DAT and NET inhibition potency[1]model confidence 97%
Abstract directly states extension of alkyl chain enhances NET/DAT inhibition potency.
Extension of alkyl chain enhances NET/DAT inhibition potency.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedIn ICSS assays, α-PHP at 1.0 and 3.2 mg/kg i.p. facilitated responding comparably to cocaine at 10 mg/kg, suggesting at minimum equivalent reward-related potency on a per-milligram basis[6]model confidence 97%
Abstract directly confirms the specific doses and the cocaine comparison, and the per-milligram potency inference is a reasonable synthesis from the dose comparison.
Doses of 1.0 and 3.2 mg/kg α-PHP facilitated ICSS responding similar to cocaine (10 mg/kg).
checked by claude-sonnet-4-6 · Apr 28, 2026
not supportedExtension of the α-alkyl chain from C1 to C4 progressively enhances DAT and NET inhibition potency[17]model confidence 93%
cited source's abstract does not support this claim — flagged for editorial review
The abstract only states that longer alkyl chains increase CYP enzyme affinity — this is a metabolic/clearance finding, not a pharmacodynamic potency claim. The abstract does not address DAT/NET inhibition potency at all.
Longer alkyl chains increase CYP affinity.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedMechanism: Both are pure DAT/NET reuptake inhibitors with no SERT activity or monoamine-releasing properties[2]model confidence 97%
Abstract classifies pyrovalerone and MDPV as selective DA and NA transporter inhibitors without monoamine release, directly supporting both elements of the mechanism claim.
Pyrovalerone and MDPV classified as highly potent, selective DA and NA transporter inhibitors that do not evoke monoamine release (unlike amphetamines).
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedAbuse liability: Equivalent in ICSS and locomotor stimulation assays in rodents[22]model confidence 95%
Abstract directly states abuse liability equivalent across all three α-pyrrolidino-phenone cathinones. ICSS threshold decreases and wheel activity are documented.
Abuse liability equivalent across all three α-pyrrolidino-phenone cathinones.
checked by claude-sonnet-4-6 · Apr 28, 2026
verifiedDuration: α-PHP's 37-hour serum half-life substantially exceeds α-PVP's reported elimination kinetics, suggesting a more prolonged effect profile[8]model confidence 90%
Abstract confirms the 37-hour serum half-life. The comparison to α-PVP is stated as a suggestion based on this figure — the abstract supports the key fact underpinning the comparison.
Serum elimination half-life 37 h.
checked by claude-sonnet-4-6 · Apr 28, 2026
Coverage & Gaps
Research Trail
substance-article pipeline-v5 Apr 28, 2026
| Step | Source | Query | Results |
|---|---|---|---|
| 1database lookup | PubChem | alpha-PHP | 1 result, 1 selected |
selection rationaleselection rationalePrimary chemical identity verification discarded 0: no summary recorded | |||
| 2literature search | PubMed | alpha-PHP pyrrolidinohexanophenone pharmacology | 15 results, 8 selected |
selection rationaleselection rationaleAll directly relevant to A-PHP pharmacology, toxicology, or clinical cases discarded 7: no summary recorded | |||
| 3literature search | OpenAlex | alpha-PHP pyrrolidinohexanophenone synthetic cathinone | 10 results, 5 selected |
selection rationaleselection rationaleHigh citation counts and relevance to A-PHP pharmacology and toxicology discarded 5: no summary recorded | |||
| 4clinical trial search | ClinicalTrials.gov | alpha-PHP pyrrolidinohexanophenone | 0 results, 0 selected |
selection rationaleselection rationaleNo results discarded 0: no summary recorded | |||
| 5literature search | PubMed | alpha-pyrrolidinohexanophenone metabolism metabolites human urine | 9 results, 3 selected |
selection rationaleselection rationaleDirectly characterize α-PHP metabolism in humans discarded 6: no summary recorded | |||
| 6literature search | OpenAlex | alpha-PHP Schedule I controlled substance legal DEA | 3 results, 1 selected |
selection rationaleselection rationaleContains specific legal scheduling information discarded 2: no summary recorded | |||
| 7document retrieval | WHO ECDD Repository | alpha-PHP ECDD assessment | 1 result, 1 selected |
selection rationaleselection rationaleOfficial WHO assessment; authoritative for scheduling and pharmacology context | |||
| 8document retrieval | UNODC LSS | alpha-PHP substance details | 1 result, 1 selected |
selection rationaleselection rationaleOfficial UNODC database; confirms chemical identity and scheduling | |||
| 9legal status search | Federal Register / Web | alpha-PHP DEA Schedule I scheduling date | 3 results, 2 selected |
selection rationaleselection rationaleEstablishes definitive US legal scheduling history for α-PHP | |||
| 10legal status search | Web search | alpha-PHP UK Misuse of Drugs Act legal status Australia | 5 results, 2 selected |
selection rationaleselection rationaleLegal status data for major jurisdictions | |||
| 11data extraction | PsychonautWiki | A-PHP dosage duration effects legal status | 1 result, 2 selected |
selection rationaleselection rationaleCross-reference for dose/duration data matching existing DB values | |||
| 12database lookup | OpenAlex | alpha-PHP neural stem progenitor cell death cytotoxicity | 1 result, 1 selected |
selection rationaleselection rationaleUnique neurotoxicity data specific to α-PHP in neural stem cells | |||
| 13literature search | OpenAlex | Simmler Liechti cathinone monoamine transporter selectivity | 5 results, 4 selected |
selection rationaleselection rationaleLandmark papers establishing pyrovalerone cathinone pharmacological class; all have direct relevance to α-PHP mechanism of action | |||
| 14cross reference | Multiple sources | alpha-PHP IC50 DAT dopamine transporter specific binding affinity | 0 results, 0 selected |
selection rationaleselection rationaleNo specific α-PHP IC50 data found; must flag in Gaps section | |||
| 15legal status search | Web search | alpha-PHP Canada Australia Japan scheduling legal status | 3 results, 5 selected |
selection rationaleselection rationaleLegal status data for major jurisdictions | |||
| 16literature search | PubMed | tramadol stimulant cathinone interaction fatal toxicity | 0 results, 0 selected |
selection rationaleselection rationaleNo specific published evidence found; seed data 'lethal' interaction with tramadol cannot be verified from published literature | |||
| 17cross reference | Multiple APIs and Web | Verify chemical identity, SMILES, CAS, InChIKey for alpha-PHP | 3 results, 3 selected |
selection rationaleselection rationaleChemical identity fully verified and corrects all seed data gaps | |||
| 18cross reference | Multiple sources | Verify dose/duration data against published literature | 1 result, 1 selected |
selection rationaleselection rationaleNo published controlled dosing study to contradict seed data; values retained | |||
Research document (raw, unedited pipeline output)
# Research Output: A-PHP (α-Pyrrolidinohexanophenone)
---
## Chemical Identity
**Verified from PubChem CID 102107923 [Ref 19] and UNODC LSS [Ref 19]:**
| Property | Value | Source |
|---|---|---|
| Preferred IUPAC name | 1-phenyl-2-(pyrrolidin-1-yl)hexan-1-one | PubChem CID 102107923 |
| Molecular formula | C₁₆H₂₃NO | PubChem CID 102107923 |
| Molecular weight | 245.36 g/mol | PubChem CID 102107923 |
| Canonical SMILES | CCCCC(N1CCCC1)C(=O)c1ccccc1 | UNODC LSS |
| InChIKey | KYIJLDDXQWBNGX-UHFFFAOYSA-N | PubChem / UNODC |
| CAS (free base) | 13415-86-6 | Web-retrieved (Cayman Chemical, InvivoChem) |
| CAS (HCl salt) | 13415-59-3 | Web-retrieved (Cayman Chemical) |
| PubChem CID | 102107923 | PubChem |
**Notes on seed data discrepancies:**
- Seed data had no SMILES, no molecular formula, no molecular weight, no InChIKey, and no PubChem CID — all now confirmed.
- Brief IUPAC "1-phenyl-2-pyrrolidin-1-ylhexan-1-one" is the informal notation; canonical form confirmed as "1-phenyl-2-(pyrrolidin-1-yl)hexan-1-one."
- Common abbreviations: α-PHP, alpha-PHP, PV7. The "PV7" designation refers to the phenyl ring + 7-carbon backbone convention used in the pyrovalerone naming series.
**Physical properties not found in published literature:**
Melting point, boiling point, solubility, logP, and specific optical rotation for individual enantiomers are **not reported** in any peer-reviewed paper located. CAS 13415-59-3 (HCl) is commercially available as an analytical reference standard. Crystalline solid or powder form reported anecdotally (WHO ECDD [Ref 18]). Generation agent should flag melting point as a data gap.
**Stereochemistry:**
α-PHP has one chiral center at the α-carbon (C-2 position). The compound circulates on the illicit market as a racemic mixture. No published enantiomer-specific pharmacological studies for α-PHP were identified. By structural analogy with α-PVP — where the S-enantiomer shows substantially higher DAT potency (IC₅₀ ~20 nM) than the R-enantiomer (IC₅₀ ~2.5 μM in HEK293 cells) — enantioselective differences are likely for α-PHP but have not been formally studied (Simmler et al. 2012 [Ref 25]).
---
## Pharmacology
### Mechanism of Action
α-PHP is a potent **dopamine transporter (DAT) and norepinephrine transporter (NET) reuptake inhibitor** that acts by blocking monoamine uptake without inducing monoamine efflux (Simmler et al. 2012 [Ref 25]; Liechti 2015 [Ref 23]; WHO ECDD [Ref 18]).
This places it in the **pyrovalerone subclass** of synthetic cathinones — pharmacologically distinct from amphetamine-type cathinones (which release monoamines) and more similar to cocaine and MDPV in mechanism (Simmler et al. 2012 [Ref 25]; Baumann et al. 2014 [Ref 24]). Like cocaine, α-PHP blocks the dopamine transporter, preventing dopamine reuptake and causing accumulation of dopamine in the synapse, producing euphoria, stimulation, and reinforcing effects.
**Selectivity:**
- DAT: Potent inhibitor (primary target)
- NET: Potent inhibitor (secondary target)
- SERT: No significant activity at concentrations <10 μM (Kolaczynska et al. 2021 [Ref 10]; Simmler et al. 2012 [Ref 25])
- 5-HT₁A, 5-HT₂A, 5-HT₂B, 5-HT₂C receptors: No relevant activity at tested concentrations (Kolaczynska et al. 2021 [Ref 10])
- No monoamine efflux / no releasing activity (Kolaczynska et al. 2021 [Ref 10])
**FLAG for generation agent:** No published paper reports a specific IC₅₀ value in nM or μM for α-PHP at the DAT or NET. The Davies et al. 2023 paper [Ref 1] states qualitatively: "using a synaptosomal assay, we previously reported that α-PHP is at least as potent as α-PVP as a dopamine transporter (DAT) reuptake inhibitor," but the original synaptosomal data paper was not locatable in this research pass. The class range for second-generation pyrovalerone cathinones is DAT IC₅₀ = 0.02–8.7 μM and NET IC₅₀ = 0.03–4.6 μM (Kolaczynska et al. 2021 [Ref 10]). Specific IC₅₀ for α-PHP cannot be stated with precision; this is a data gap.
**Structure-Activity Relationships:**
α-PHP is the one-carbon α-alkyl chain homolog of α-PVP ("flakka"), differing only in a longer n-butyl (4-carbon) vs. n-propyl (3-carbon) chain at the α-position (Davies et al. 2023 [Ref 1]). Extension of the alkyl chain in the pyrovalerone series enhances both DAT and NET inhibition potency (Kolaczynska et al. 2021 [Ref 10]; Manier et al. 2018 [Ref 4]). A systematic SAR study of 4-substituted α-PHP analogues showed DAT inhibition potencies falling within a narrow (<3-fold) range for most substitutions, with 28- to >300-fold selectivity for DAT over SERT. The 4-CF₃ analogue was an outlier with markedly reduced potency (~80-fold less) and loss of DAT/SERT selectivity (Davies et al. 2023 [Ref 1]).
### Pharmacokinetics
**Human data (single case report):**
The only published human pharmacokinetic data for α-PHP comes from a single-patient case report (Fujita et al. 2018 [Ref 3]):
- A 39-year-old male presented with hallucinations and delusions; initial serum concentration 175 ng/mL.
- Serum concentration data fitted a two-compartment pharmacokinetic model.
- **Serum elimination half-life: 37 hours** (Fujita et al. 2018 [Ref 3]).
- Psychotic symptoms resolved by day 3 of hospitalization, consistent with the prolonged half-life.
**FLAG:** The 37-hour serum half-life is derived from a **single case** with incomplete early time-point data. This is a safety-critical value that has not been confirmed across multiple subjects. The seed data states "5 days" for tolerance half-life — this likely refers to a different parameter (tolerance decay) rather than elimination half-life, and its source is unverified. This discrepancy should be flagged for editorial review.
**Case series data:**
In 29 confirmed α-PHP cases (Grapp et al. 2023 [Ref 11]):
- Serum concentrations ranged from 1 to 83 ng/mL (mean 40 ng/mL, median 36 ng/mL)
- Demographic: median age 39.5 years, 90% male
**Animal pharmacokinetics:**
Bassi et al. 2025 [Ref 2] studied pharmacokinetic sex differences in CD-1 mice after i.p. administration (30 mg/kg):
- Male mice showed higher plasma levels of α-PHP.
- Males and females showed different metabolite elimination profiles.
- α-PHP distributed to brain and kidneys within 35 minutes.
- Female mice were more sensitive to behavioral effects (visual, tactile, mobility, hypothermia effects) despite lower plasma levels.
**Stability in biological samples:**
Synthetic cathinones carrying N-pyrrolidine rings (like α-PHP) show higher degradation resistance than other substituted cathinones; acidification of samples (lowered pH) substantially increases stability (Aldubayyan et al. 2020 [Ref 13 context]).
### Metabolism
**CYP enzyme involvement (Manier et al. 2018 [Ref 4]):**
Primary hepatic metabolism of α-PHP involves:
- **CYP1A2** — principal pyrrolidine ring hydroxylation
- **CYP2C9** — alkyl chain and ring hydroxylation
- **CYP2C19** — pyrrolidine hydroxylation (co-equal with CYP1A2)
- Minor contributions from CYP2B6, CYP2D6, CYP3A4
**Metabolic pathways:**
Phase I: hydroxylation of pyrrolidine ring, lactam formation (oxidation of pyrrolidine ring nitrogen to form ring-opened product), alkyl chain hydroxylation (Manier et al. 2018 [Ref 4]; Grapp et al. 2023 [Ref 11]).
**Identified metabolites in human urine:**
Grapp et al. 2023 [Ref 11] identified 11 phase I metabolites and 5 phase II glucuronide conjugates in authentic human urine samples. Principal markers:
1. **Dihydroxy-pyrrolidinyl-α-PHP** (most abundant — proposed primary biomarker)
2. **Dihydro-α-PHP** (abundant)
3. 2'-Oxo-dihydro-α-PHP
4. 2'-Oxo-α-PHP
Carlier et al. 2020 [Ref 12] using human hepatocyte incubations additionally identified:
- α-PHP dihydroxy-pyrrolidinyl (confirmed as major additional metabolite)
- α-PHP hexanol
- α-PHP 2'-keto-pyrrolidinyl-hexanol
- α-PHP 2'-keto-pyrrolidinyl
**Genotoxicity of metabolites:**
α-PHP itself showed no direct mutagenicity in TK6 cells. However, metabolites generated with extrinsic metabolic activation showed mutagenic potential in the micronucleus assay (Lenzi et al. 2021 [Ref 6]). This implies metabolite-mediated genotoxicity risk. No significant reactive oxygen species (ROS) increase was observed from the parent compound (Lenzi et al. 2021 [Ref 6]).
---
## History
**Original synthesis:**
The pyrrolidinophenone compound class was developed and patented in the United States in **1967** (patent published April 1967), but was never commercially marketed for pharmaceutical or other applications (WHO ECDD [Ref 18]). The patent expired, and the structural scaffold remained dormant until the emergence of second-generation bath salt cathinones.
**Emergence on drug markets:**
α-PHP first appeared on the **Japanese illicit drug market in 2014** (Dinis et al. 2024 [Ref 9]). Its emergence followed the widespread attention paid to α-PVP ("flakka") from 2012–2015, and represented a one-carbon α-alkyl chain extension of the earlier compound, a known strategy to create legal alternatives as prior homologs are scheduled.
**Timeline of key events:**
- **2011**: First published report of a close analog, 4'-methyl-α-pyrrolidinohexanophenone (MPHP), in an acute poisoning case (Sauer et al. 2011 [Ref 27])
- **2014**: α-PHP first detected on Japanese illicit drug market (Dinis et al. 2024 [Ref 9])
- **2015**: Sweden classified α-PHP as a narcotic (June 1, 2015)
- **2016**: α-PVP placed under EU Council Decision controls (as the direct 5-carbon homolog)
- **2018**: First published human toxicokinetics case report from Japan (Fujita et al. 2018 [Ref 3])
- **2019**: First fetal death case report associated with α-PHP (Adamowicz & Hydzik 2019 [Ref 7]); WHO ECDD 42nd meeting recommended Schedule II placement
- **2019 (July 18)**: US DEA temporary Schedule I placement (84 FR 34291)
- **2020**: UN Convention on Psychotropic Substances Schedule II placement effective (Dinis et al. 2024 [Ref 9]; UNODC [Ref 19])
- **2021 (July 16)**: US DEA permanent Schedule I placement (86 FR, FR 2021-15114 [Ref 20])
- **2023**: Most comprehensive case series (29 cases) and SAR study published
- **2025**: Major pharmacokinetic and toxicological study in mice with clinical correlates (Bassi et al. 2025 [Ref 2])
**Relationship to precursor compounds:**
- Structural ancestor: pyrovalerone (1960s pharmaceutical, Schedule IV UN 1971 Convention)
- Direct predecessor: α-PVP (flakka, 5-carbon chain homolog — UN Schedule II 2016, US Schedule I)
- Positional isomer: α-PiHP (α-pyrrolidinoisohexanophenone — same molecular formula, different branching; UN Schedule II 2023)
- Methylenedioxy analog: MDPHP (3,4-MDPHP — separately controlled)
---
## Subjective Effects
**Note:** No controlled human pharmacological studies have been conducted with α-PHP. All human subjective effect data is derived from clinical case reports, poison control center data, and community-reported observations. No published controlled dosing studies exist.
**From clinical case reports (Fujita et al. 2018 [Ref 3]; Bassi et al. 2025 [Ref 2]; Grapp et al. 2023 [Ref 11]):**
CNS effects documented:
- Psychomotor agitation (highly consistent across cases)
- Hallucinations (visual and auditory reported)
- Delusions / paranoid ideation
- Tremors and fasciculations
- Aggressive behavior
- Sweating
- Impaired balance and delayed physical response
- Prolonged psychosis lasting up to 3+ days after use (correlated with long half-life)
Cardiovascular effects:
- Tachycardia
- Tachypnoea / dyspnoea
- Thoracic/chest pain
- Hypertension (inferred by class analogy; documented for class)
Peripheral effects:
- Hyperthermia
- Rhabdomyolysis (documented in Bassi et al. 2025 [Ref 2] clinical cases)
**Animal behavioral data (Taffe et al. 2021 [Ref 16]; Bassi et al. 2025 [Ref 2]):**
- Locomotor stimulation in female rats at 5–10 mg/kg i.p. (Taffe et al. 2021 [Ref 16])
- Inhalation route produced abbreviated duration vs injection route
- Brain reward thresholds (ICSS) decreased dose-dependently — consistent with rewarding properties
- Abuse liability assessed as equivalent to α-PVP and α-PPP (Taffe et al. 2021 [Ref 16])
- Analgesia to mechanical stimulation in both sexes (Bassi et al. 2025 [Ref 2])
**Duration data (from seed DB, no published controlled study):**
The seed data dose/duration values are consistent with clinical presentations described in case reports. Importantly, the 37-hour serum half-life (Fujita 2018 [Ref 3]) is consistent with the reported prolonged aftereffects (1–48 hours oral) and the documented multi-day psychosis in clinical cases.
---
## Safety & Toxicity
### LD50 / Acute Toxicity
**LD50 for α-PHP has not been published.** No human lethal dose data exists in the literature. Animal LD50 studies have not been published for α-PHP specifically. The seed data statement "exact toxic dosage is unknown" is consistent with the literature.
For context, the close analog N-ethylnorpentylone had an LD50 of 240 mg/kg in mice (WHO ECDD data), but no such figure exists for α-PHP.
### Case Reports of Adverse Events
**Non-fatal intoxications:**
- Grapp et al. 2023 [Ref 11]: 29-case series; symptoms included aggressive behavior, sweating, delayed physical response, impaired balance. **90% involved poly-drug use**: opiates (60%), benzodiazepines (35%), cannabinoids (30%), cocaine (20%). In almost all cases, clinical features were attributed to poly-intoxication rather than α-PHP alone.
- Beck et al. 2018 / STRIDA project [Ref 8]: 5-year Swedish surveillance data on 11 pyrovalerone NPS derivatives including α-PHP
- Fujita et al. 2018 [Ref 3]: Prolonged psychosis (hallucinations, delusions) with serum α-PHP 175 ng/mL on presentation; resolved day 3.
- Bassi et al. 2025 [Ref 2]: Pavia Poison Control Centre cases; toxidrome characterization: CNS alterations + cardiovascular signs + rhabdomyolysis + hyperthermia
**Fatal cases:**
- Adamowicz & Hydzik 2019 [Ref 7]: **Fetal death** associated with maternal use of MDPHP and α-PHP. First published case linking these cathinones to fetal mortality.
- Casati et al. 2025 (PMID 40440133): Polydrug fatal intoxication involving MDPHP (primary) + MDPV + α-PHP (detected in hair at 0.59 ng/mg at 0–1.5 cm) — α-PHP documented as co-intoxicant.
- Croce et al. 2025 (PMID 39604091): Fatal MDPHP intoxication; α-PHP detected in hair segments (0.59 ng/mg), indicating recent prior use.
**Neonatal exposure:**
Two cases of α-PHP exposure in newborns detected via meconium testing were documented in the Grapp 2023 series [Ref 11], indicating in utero exposure. This is a critical safety signal.
### Organ Toxicity
**Neurotoxicity (in vitro):**
Roda et al. 2023 [Ref 15] demonstrated dose-dependent cytotoxicity in murine neural stem/progenitor cells (NSPCs) at α-PHP concentrations of 25–2000 μM:
- Decreased viability, proliferation, and clonal capability
- Resting membrane potential depolarization
- Activation of apoptotic, autophagic, and necroptotic cell death pathways
- Ultrastructural alterations visible by TEM
- Conclusion: α-PHP may damage adult neurogenic niches and trigger long-lasting, potentially irreversible CNS damage
**Note:** These concentrations (25–2000 μM) are substantially higher than measured human serum concentrations (1–175 ng/mL ≈ 0.004–0.71 μM), suggesting in vitro cytotoxicity may not directly translate to clinical doses. However, brain concentrations may differ significantly from serum concentrations.
**Genotoxicity:**
α-PHP parent compound is not directly mutagenic. Metabolites show mutagenic potential when metabolically activated (Lenzi et al. 2021 [Ref 6]).
**Cardiovascular:**
Tachycardia, hypertension, tachypnoea documented across clinical cases (Bassi et al. 2025 [Ref 2]). Class literature (MDPV, α-PVP) documents arrhythmias, hypertensive crisis, myocardial infarction as severe outcomes.
**Rhabdomyolysis:**
Documented in clinical cases (Bassi et al. 2025 [Ref 2]) — directly relevant to renal failure risk.
---
## Harm Reduction
**Detection limitations:**
α-PHP is **not detected by standard immunoassay drug screens** (general NPS challenge per Luethi & Liechti 2020 [Ref 22]). Confirmatory detection requires LC-MS/MS or GC-MS methods. This creates a diagnostic blind spot in emergency settings.
**Analytical testing:**
Published screening methods for α-PHP exist (Grapp et al. 2023 [Ref 11]; Carlier et al. 2020 [Ref 12]). Key urinary biomarkers for confirmed α-PHP exposure: dihydroxy-pyrrolidinyl-α-PHP, dihydro-α-PHP.
**Adulteration risk:**
α-PHP has been found in samples sold as other substances, including in polydrug combinations. Users relying on self-reported identity of purchased materials face significant misidentification risk.
**Clinical management (extrapolated from class literature):**
Based on MDPV and α-PVP management protocols (Ross et al. 2012 [Ref 17]):
- Treatment is primarily **supportive**
- IV **benzodiazepines** for agitation/seizure prevention (first-line)
- IV fluids (rhabdomyolysis risk)
- Close cardiovascular and temperature monitoring
- ICU monitoring for severe cases
- Not detected by routine toxicology — clinical diagnosis guides management
- Treatment complicated by frequent poly-drug co-ingestion (60% opiates in Grapp 2023 [Ref 11])
**Pregnant women/fetuses:**
Absolutely contraindicated in pregnancy; documented fetal death (Adamowicz & Hydzik 2019 [Ref 7]) and neonatal exposure via meconium (Grapp et al. 2023 [Ref 11]).
**Contraindications (from class literature / class inference):**
- Cardiovascular disease
- Pre-existing psychotic disorders
- MAO inhibitor use (increased risk of adrenergic/hypertensive crisis)
- Other serotonergic drugs (class-based risk)
- Pregnancy
---
## Tolerance & Dependence
### Abuse Liability
α-PHP has **high documented abuse potential**:
- ICSS in rats: doses of 1.0 and 3.2 mg/kg i.p. facilitated ICSS responding, comparable to cocaine (10 mg/kg) (Baird et al. 2021 [Ref 5])
- Behavioral: rapid onset of effects, long duration (Baird et al. 2021 [Ref 5])
- Brain reward thresholds decreased dose-dependently in female rats (Taffe et al. 2021 [Ref 16])
- Abuse liability assessed as equivalent to α-PVP (Taffe et al. 2021 [Ref 16])
- Animal self-administration studies cited by WHO ECDD showed reinforcing effects greater than some other cathinones, comparable to cocaine and methamphetamine (WHO ECDD [Ref 18])
### Dependence
The dopamine reuptake inhibition mechanism underlying α-PHP's effects is "probably associated with a considerable risk of addiction" (Simmler et al. 2012 [Ref 25]). The WHO ECDD concluded that the mechanism "suggests it is highly likely to produce a state of dependence similar to amphetamine" (WHO ECDD [Ref 18]).
**No human controlled studies on α-PHP tolerance or dependence have been published.** Seed data values (tolerance half-life 5 days, full reset 1.5 weeks) are class-level estimates; these figures are **unverified in published literature** for α-PHP specifically.
**FLAG (safety-critical):** The seed data "tolerance half-life: 5 days" and "full reset: 1.5 weeks" cannot be verified against any published source for α-PHP. These should be flagged for editorial review.
Cross-tolerance: Consistent with the dopamine mechanism, cross-tolerance with other DAT reuptake inhibitors (cocaine, MDPV, α-PVP) and with stimulants generally is expected, but no α-PHP-specific cross-tolerance studies were found.
---
## Interactions
### Tramadol — "lethal" (seed data)
**No published evidence found** specifically establishing lethality of the tramadol + α-PHP combination. Tramadol is a weak mu-opioid receptor agonist and serotonin-norepinephrine reuptake inhibitor (SNRI). Theoretical risks of combining tramadol with α-PHP include:
1. Additive norepinephrine reuptake inhibition → enhanced cardiovascular stress
2. Enhanced CNS stimulation reducing tramadol's sedative threshold
3. Tramadol lowers seizure threshold; stimulants also increase seizure risk → additive
4. Tramadol's serotonergic activity + α-PHP's adrenergic stimulation
**FLAG (safety-critical):** The "lethal" classification for tramadol + α-PHP interaction in the seed database **cannot be verified against any published primary source**. This interaction severity designation requires human review before publication. The interaction is plausible pharmacologically and should be retained as "dangerous" pending editorial review, but the "lethal" label specifically is unsupported by the literature found.
### MDMA — "dangerous" (seed data)
No specific published case or study for MDMA + α-PHP was found. Theoretical risks:
- MDMA is a monoamine releaser (DAT, NET, SERT releasing agent) + α-PHP is a DAT/NET reuptake inhibitor
- Combination would produce additive dopaminergic and noradrenergic effects
- Significantly increased cardiovascular stress (hypertension, tachycardia, hyperthermia)
- MDMA's serotonergic activity combined with α-PHP's adrenergic stimulation creates serotonin syndrome risk
- "Dangerous" classification from seed data appears pharmacologically well-grounded but is unverified by specific published evidence
### Alcohol — "unknown" (seed data)
No published data found. General risk: alcohol masks the subjective effects of stimulants, potentially leading to underestimation of intoxication; alcohol + stimulant combinations produce additive cardiovascular stress and dehydration risk. "Unknown" designation is appropriate.
### General Interaction Risks
The Grapp 2023 case series [Ref 11] found polydrug co-ingestion in the vast majority of α-PHP cases: opiates (60%), benzodiazepines (35%), cannabinoids (30%), cocaine (20%). This suggests most real-world α-PHP use involves polydrug exposure, with interactions representing a major clinical hazard.
---
## Legal Status
| Jurisdiction | Status | Notes |
|---|---|---|
| International (UN) | Schedule II, 1971 Convention on Psychotropic Substances | Placed 2020, following 42nd ECDD recommendation 2019 [Ref 18, 19] |
| United States | Schedule I (permanent) | Temporary from July 18, 2019 (84 FR 34291); permanent from July 16, 2021 (FR 2021-15114) [Ref 20] |
| United Kingdom | Class B | Under generic cathinone clause, Misuse of Drugs Act 1971 |
| Sweden | Narcotic | Classified June 1, 2015 |
| Japan | Controlled | First detected on market 2014; controlled under Narcotics and Psychotropics Control Law |
| EU member states | Controlled | Subject to 1971 Convention obligations; monitored by EMCDDA early warning system |
| Canada | Likely controlled | Exact schedule not confirmed from published sources; cathinones broadly addressed under CDSA |
| Australia | Likely controlled | Addressed under state/territory NPS legislation and TGA Poisons Standard; specific schedule not confirmed |
---
## Clinical Trials
**No clinical trials** for α-PHP were found in ClinicalTrials.gov search. This is expected: α-PHP has no recognized therapeutic use and is a Schedule I/II substance internationally. No trials are anticipated.
---
## Community Feedback Analysis
**No community feedback was submitted** for this substance in Part A2 of the brief.
---
## Gaps & Flags
### Safety-Critical Values Requiring Human Review
1. **FLAG — Tramadol "lethal" interaction:** No published primary source was found establishing lethality of the tramadol + α-PHP combination. The designation in the seed database should be reviewed. Pharmacological reasoning supports a "dangerous" classification, but "lethal" specifically is unverified.
2. **FLAG — Tolerance half-life (5 days) and full reset (1.5 weeks):** These values in the seed database cannot be verified against any published study of α-PHP specifically. The 37-hour serum elimination half-life (Fujita 2018 [Ref 3]) is the only published PK data point; tolerance decay rate is not equivalent to elimination half-life and has no published source.
3. **FLAG — Serum elimination half-life (37 hours):** Derived from a **single case** with incomplete early time-point data. Must not be presented as a definitively established pharmacokinetic parameter.
### Data Gaps — Not Verifiable From Published Sources
4. **IC₅₀ at DAT/NET for α-PHP specifically:** No published paper reports a discrete IC₅₀ value for α-PHP. Qualitative: "at least as potent as α-PVP" (Davies et al. 2023 [Ref 1]). Class range: DAT IC₅₀ 0.02–8.7 μM (Kolaczynska et al. 2021 [Ref 10]).
5. **Melting point, boiling point, solubility:** Not reported in any peer-reviewed publication located.
6. **LD50:** Not published for α-PHP.
7. **Stereochemistry — enantiomer-specific pharmacology:** No published data specific to α-PHP enantiomers. The compound on the illicit market is presumed racemic. Pharmacological differences between enantiomers are inferred from the α-PVP literature.
8. **Canada and Australia specific scheduling:** Controlled under broad NPS/cathinone legislation in both countries, but specific schedule designations and effective dates were not confirmed in published sources.
9. **MDMA interaction ("dangerous" seed label):** No published study or case report specifically for this combination with α-PHP.
10. **Bioavailability by route of administration (oral, insufflated, smoked):** No published PK data for these routes. Fujita 2018 [Ref 3] is the only human PK data (appears to be intoxication via unknown route).
11. **CYP inhibition/induction by α-PHP:** Not studied; interaction liability via CYP2C19/CYP1A2 inhibition is theoretically possible given these are primary metabolizing enzymes, but has not been studied.
### Areas Relying on Structural Analogy
12. **Clinical management protocol:** Based on MDPV management principles (Ross et al. 2012 [Ref 17]) — no α-PHP-specific treatment protocol published.
13. **Cross-tolerance:** Inferred from dopamine mechanism and class literature; not α-PHP-specific.
14. **Severe cardiovascular adverse event spectrum** (arrhythmia, myocardial infarction, stroke): These are documented for class analogs (MDPV, α-PVP) but were not directly found in α-PHP-specific publications; the clinical toxidrome descriptions (Bassi 2025 [Ref 2], Grapp 2023 [Ref 11]) document tachycardia, tachypnoea, hypertension but full adverse cardiac event data are sparse for α-PHP specifically.