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Psychedex
Sources
36
14 strong · 11 moderate · 11 weak

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

Claims checked
136
104verified2partial29inconclusive1not supported

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

Generated
Apr 25, 2026 · pipeline-v5
Values approved
110/110 (100%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold2 mg2 mglow
Low4–8 mg4–8 mglow
Common8–14 mg8–14 mglow
Strong14–25 mg14–25 mglow
Heavy25+ mg25+ mglow
Editorial

No controlled human dosing studies exist. These values are carried forward from existing Psychedex database seed data, originally sourced from community harm reduction consensus (PsychonautWiki, Erowid). Consistent with MDPV's approximately 10-fold potency advantage over cocaine in animal models (Baumann et al. 2013). Cannot be verified against primary clinical literature.

Reasoning

No controlled human dosing studies exist. These values are carried forward from existing Psychedex database seed data, originally sourced from community harm reduction consensus (PsychonautWiki, Erowid). Consistent with MDPV's approximately 10-fold potency advantage over cocaine in animal models (Baumann et al. 2013). Cannot be verified against primary clinical literature.

Evidence basis: community_consensus_large

insufflatedtrace

FieldPublishedAI ProposedConfidence
Threshold1 mg1 mglow
Low2–5 mg2–5 mglow
Common5–10 mg5–10 mglow
Strong10–20 mg10–20 mglow
Heavy20+ mg20+ mglow
Editorial

No controlled human dosing data. Insufflation is documented as a common ROA in clinical literature (Ross et al. 2012). Dose ranges inferred from oral ranges with adjustment for expected higher bioavailability via nasal mucosa. Community consensus suggests lower effective doses than oral. Ranges widened to account for uncertainty.

Reasoning

No controlled human dosing data. Insufflation is documented as a common ROA in clinical literature (Ross et al. 2012). Dose ranges inferred from oral ranges with adjustment for expected higher bioavailability via nasal mucosa. Community consensus suggests lower effective doses than oral. Ranges widened to account for uncertainty.

Evidence basis: community_consensus_large

Duration

oral

FieldPublishedAI ProposedConfidence
Peaktrace1–2 hours1–2 hourslow
Editorial

Inferred from community reports. Clinical presentations describe intoxication lasting 6–8 hours total (Ross et al. 2012); peak phase estimated as 1–2 hours within that window.

Reasoning

Inferred from community reports. Clinical presentations describe intoxication lasting 6–8 hours total (Ross et al. 2012); peak phase estimated as 1–2 hours within that window.

Evidence basis: community_consensus_large

After effectstrace2–48 hours2–48 hourslow
Editorial

Wide range reflecting dose-dependent crash severity. Clinical literature describes prolonged aftereffects following heavy use and binge patterns. No controlled data.

Reasoning

Wide range reflecting dose-dependent crash severity. Clinical literature describes prolonged aftereffects following heavy use and binge patterns. No controlled data.

Evidence basis: community_consensus_large

Onsettrace15–30 minutes15–30 minutesmedium
Editorial

Seed data lists onset 15–30 minutes oral. Consistent with rapid rat Tmax of 12.9–18.6 min subcutaneous (Anizan et al. 2016) and MDPV's high BBB permeability (Simmler et al. 2012).

Reasoning

Seed data lists onset 15–30 minutes oral. Consistent with rapid rat Tmax of 12.9–18.6 min subcutaneous (Anizan et al. 2016) and MDPV's high BBB permeability (Simmler et al. 2012).

Evidence basis: community_consensus_large

Come uptrace15–30 minutes15–30 minuteslow
Editorial

Inferred from community reports and pharmacological profile. No controlled data.

Reasoning

Inferred from community reports and pharmacological profile. No controlled data.

Evidence basis: community_consensus_large

Offsettrace1–2 hours1–2 hourslow
Editorial

Inferred from community reports and total duration constraints.

Reasoning

Inferred from community reports and total duration constraints.

Evidence basis: community_consensus_large

Totaltrace2–7 hours2–7 hoursmedium
Editorial

Seed data lists total 2–7 hours. Ross et al. 2012 reports 6–8 hours clinical intoxication. The lower bound (2 hours) may reflect low doses; the upper bound is consistent with clinical data. Carried forward from existing database values.

Reasoning

Seed data lists total 2–7 hours. Ross et al. 2012 reports 6–8 hours clinical intoxication. The lower bound (2 hours) may reflect low doses; the upper bound is consistent with clinical data. Carried forward from existing database values.

Evidence basis: community_consensus_large

insufflated

FieldPublishedAI ProposedConfidence
Onsettrace1–5 minutes1–5 minuteslow
Editorial

Insufflation of lipophilic stimulants typically produces onset within 1–5 minutes. MDPV's high potency and BBB permeability support rapid absorption via nasal mucosa. Community reports consistent with this range.

Reasoning

Insufflation of lipophilic stimulants typically produces onset within 1–5 minutes. MDPV's high potency and BBB permeability support rapid absorption via nasal mucosa. Community reports consistent with this range.

Evidence basis: community_consensus_large

Come uptrace5–15 minutes5–15 minuteslow
Editorial

Inferred from community reports for insufflated MDPV.

Reasoning

Inferred from community reports for insufflated MDPV.

Evidence basis: community_consensus_large

Peaktrace30–90 minutes30–90 minuteslow
Editorial

Insufflated peak is shorter than oral. Inferred from community reports and general stimulant pharmacology.

Reasoning

Insufflated peak is shorter than oral. Inferred from community reports and general stimulant pharmacology.

Evidence basis: community_consensus_large

Offsettrace30–60 minutes30–60 minuteslow
Editorial

Inferred from community reports.

Reasoning

Inferred from community reports.

Evidence basis: community_consensus_large

Totaltrace1–4 hours1–4 hourslow
Editorial

Insufflated duration approximately half the oral duration. Inferred from community reports and the faster onset-offset kinetics of nasal administration.

Reasoning

Insufflated duration approximately half the oral duration. Inferred from community reports and the faster onset-offset kinetics of nasal administration.

Evidence basis: community_consensus_large

After effectstrace2–24 hours2–24 hourslow
Editorial

Aftereffects expected to be similar duration to oral but potentially more intense due to sharper comedown. Inferred from community consensus.

Reasoning

Aftereffects expected to be similar duration to oral but potentially more intense due to sharper comedown. Inferred from community consensus.

Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutehighhighhigh
Chronicmoderatemoderatehigh
Organs Affectedcardiovascular, kidney, liver, brain, musculoskeletalcardiovascular, kidney, liver, brain, musculoskeletalhigh
Editorial

Acute toxicity rated 'high' based on multiple independent fatality reports (Murray 2012, Wyman 2013, Wright 2013, Desharnais 2017), documented multiorgan failure (Borek 2012), and psychosis in 26–40% of emergency presentations (Murphy 2013, Michigan MMWR 2011). Chronic toxicity rated 'moderate' — limited chronic-use data exists, but persistent psychosis (Penders 2013) and established addiction (Casati 2025) are documented. Chronic neurotoxicity data are absent.

Reasoning

Acute toxicity rated 'high' based on multiple independent fatality reports (Murray 2012, Wyman 2013, Wright 2013, Desharnais 2017), documented multiorgan failure (Borek 2012), and psychosis in 26–40% of emergency presentations (Murphy 2013, Michigan MMWR 2011). Chronic toxicity rated 'moderate' — limited chronic-use data exists, but persistent psychosis (Penders 2013) and established addiction (Casati 2025) are documented. Chronic neurotoxicity data are absent.

Evidence basis: published_case_series

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicallowlowhigh
Psychologicalhighhighhigh
Compulsive Redosinghighhighhigh
Dose Escalationhighhighhigh
Editorial

Animal self-administration data (Watterson 2014, Aarde 2015) consistently demonstrate extreme abuse liability with escalation comparable to methamphetamine. ICSS threshold data (Watterson 2014, Bonano 2014) confirm robust reward activation. Clinical addiction documented (Casati 2025). Compulsive redosing is the most consistently reported behavioral feature across both animal and human data.

Reasoning

Animal self-administration data (Watterson 2014, Aarde 2015) consistently demonstrate extreme abuse liability with escalation comparable to methamphetamine. ICSS threshold data (Watterson 2014, Bonano 2014) confirm robust reward activation. Clinical addiction documented (Casati 2025). Compulsive redosing is the most consistently reported behavioral feature across both animal and human data.

Evidence basis: published_case_series

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitymoderatemoderatelow
Symptomsdysphoria, anhedonia, depression, fatigue, hypersomnia, irritability, psychomotor retardation, increased appetitedysphoria, anhedonia, depression, fatigue, hypersomnia, irritability, psychomotor retardation, increased appetitelow
FatalNoNolow
Medical SupervisionNot requiredNot requiredlow
Editorial

No MDPV-specific withdrawal studies exist. Withdrawal syndrome inferred from cocaine/stimulant class analogy. Severity rated moderate based on the expected stimulant crash pattern. Timing extrapolated from cocaine withdrawal literature.

Reasoning

No MDPV-specific withdrawal studies exist. Withdrawal syndrome inferred from cocaine/stimulant class analogy. Severity rated moderate based on the expected stimulant crash pattern. Timing extrapolated from cocaine withdrawal literature.

Evidence basis: published_case_series

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Builduprapidrapidmedium
Half-life——medium
Full Reset——medium
Cross-tolerancescocaine, methylphenidate, alpha-PVP, MDPHPcocaine, methylphenidate, alpha-PVP, MDPHPmedium
Editorial

DAT internalization demonstrated within hours of acute exposure in rats (Lopez-Arnau 2019, Colon-Perez 2018). Rapid tolerance is consistent with the binge-like intake escalation pattern observed in self-administration studies (Watterson 2014). No human tolerance half-life or reset data available.

Reasoning

DAT internalization demonstrated within hours of acute exposure in rats (Lopez-Arnau 2019, Colon-Perez 2018). Rapid tolerance is consistent with the binge-like intake escalation pattern observed in self-administration studies (Watterson 2014). No human tolerance half-life or reset data available.

Evidence basis: animal_study

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
cardiovascular pre-existing cardiovascular diseasetraceabsoluteabsolutehigh
Editorial

Tachycardia 63% (Michigan MMWR 2011), hypertension 25% (Murphy et al. 2013), myocardial infarction and cardiac arrest documented (Ross et al. 2012, Desharnais et al. 2017, Wyman et al. 2013). Multiple fatalities attributed to cardiac arrhythmia.

Reasoning

Tachycardia 63% (Michigan MMWR 2011), hypertension 25% (Murphy et al. 2013), myocardial infarction and cardiac arrest documented (Ross et al. 2012, Desharnais et al. 2017, Wyman et al. 2013). Multiple fatalities attributed to cardiac arrhythmia.

psychiatric psychotic disorderstraceabsoluteabsolutehigh
Editorial

Psychosis in 26–40% of presentations (Murphy 2013, Michigan MMWR 2011), persistent psychosis requiring ECT (Penders 2013), psychosis indistinguishable from schizophrenia (Ross et al. 2012).

Reasoning

Psychosis in 26–40% of presentations (Murphy 2013, Michigan MMWR 2011), persistent psychosis requiring ECT (Penders 2013), psychosis indistinguishable from schizophrenia (Ross et al. 2012).

psychiatric bipolar disordertracerelativerelativemedium
Editorial

Weinstein et al. 2017 documents hypomania and persistent psychiatric effects with chronic cathinone use. Class-level concern for all potent dopaminergic stimulants.

Reasoning

Weinstein et al. 2017 documents hypomania and persistent psychiatric effects with chronic cathinone use. Class-level concern for all potent dopaminergic stimulants.

renal renal impairmenttracerelativerelativehigh
Editorial

AKI documented in Borek 2012 (IV, multiorgan failure) and Sutamtewagul et al. 2014 (IV, severe AKI). Multiple mechanisms contributing to renal injury.

Reasoning

AKI documented in Borek 2012 (IV, multiorgan failure) and Sutamtewagul et al. 2014 (IV, severe AKI). Multiple mechanisms contributing to renal injury.

hepatic hepatic impairmenttracerelativerelativemedium
Editorial

Hepatic injury documented in Borek 2012. CYP-dependent metabolism (Meyer et al. 2010) means impaired clearance in hepatic disease.

Reasoning

Hepatic injury documented in Borek 2012. CYP-dependent metabolism (Meyer et al. 2010) means impaired clearance in hepatic disease.

neurological epilepsytracerelativerelativemedium
Editorial

Seizures documented in Ross et al. 2012. Class-level concern for all potent sympathomimetic stimulants.

Reasoning

Seizures documented in Ross et al. 2012. Class-level concern for all potent sympathomimetic stimulants.

pregnancy breastfeeding pregnancytraceabsoluteabsolutemedium
Editorial

No pregnancy-specific data. Absolute contraindication inferred from potent sympathomimetic profile and documented cardiovascular/hyperthermic toxicity.

Reasoning

No pregnancy-specific data. Absolute contraindication inferred from potent sympathomimetic profile and documented cardiovascular/hyperthermic toxicity.

Timeline Phases

oral

FieldPublishedAI ProposedConfidence
Onsettrace900–1800 sec(i=0.05)900–1800 sec(i=0.05)low
Editorial

No controlled human PK or duration studies exist. Oral onset of 15–30 minutes is consistent with seed data and the rapid rat Tmax (~13–19 min subcutaneous). Total subjective experience of 2–8 hours is supported by both seed data (2–7 hours) and clinical reports (6–8 hours intoxication; Ross et al. 2012). Aftereffects duration of up to 48 hours is consistent with clinical descriptions of prolonged crash. Phase breakdown is inferred from the pharmacological profile and community reports.

Reasoning

No controlled human PK or duration studies exist. Oral onset of 15–30 minutes is consistent with seed data and the rapid rat Tmax (~13–19 min subcutaneous). Total subjective experience of 2–8 hours is supported by both seed data (2–7 hours) and clinical reports (6–8 hours intoxication; Ross et al. 2012). Aftereffects duration of up to 48 hours is consistent with clinical descriptions of prolonged crash. Phase breakdown is inferred from the pharmacological profile and community reports.

Come uptrace900–1800 sec(i=0.30)900–1800 sec(i=0.30)low
Editorial

No controlled human PK or duration studies exist. Oral onset of 15–30 minutes is consistent with seed data and the rapid rat Tmax (~13–19 min subcutaneous). Total subjective experience of 2–8 hours is supported by both seed data (2–7 hours) and clinical reports (6–8 hours intoxication; Ross et al. 2012). Aftereffects duration of up to 48 hours is consistent with clinical descriptions of prolonged crash. Phase breakdown is inferred from the pharmacological profile and community reports.

Reasoning

No controlled human PK or duration studies exist. Oral onset of 15–30 minutes is consistent with seed data and the rapid rat Tmax (~13–19 min subcutaneous). Total subjective experience of 2–8 hours is supported by both seed data (2–7 hours) and clinical reports (6–8 hours intoxication; Ross et al. 2012). Aftereffects duration of up to 48 hours is consistent with clinical descriptions of prolonged crash. Phase breakdown is inferred from the pharmacological profile and community reports.

Peaktrace3600–7200 sec(i=1.00)3600–7200 sec(i=1.00)low
Editorial

No controlled human PK or duration studies exist. Oral onset of 15–30 minutes is consistent with seed data and the rapid rat Tmax (~13–19 min subcutaneous). Total subjective experience of 2–8 hours is supported by both seed data (2–7 hours) and clinical reports (6–8 hours intoxication; Ross et al. 2012). Aftereffects duration of up to 48 hours is consistent with clinical descriptions of prolonged crash. Phase breakdown is inferred from the pharmacological profile and community reports.

Reasoning

No controlled human PK or duration studies exist. Oral onset of 15–30 minutes is consistent with seed data and the rapid rat Tmax (~13–19 min subcutaneous). Total subjective experience of 2–8 hours is supported by both seed data (2–7 hours) and clinical reports (6–8 hours intoxication; Ross et al. 2012). Aftereffects duration of up to 48 hours is consistent with clinical descriptions of prolonged crash. Phase breakdown is inferred from the pharmacological profile and community reports.

Plateautrace3600–7200 sec(i=0.50)3600–7200 sec(i=0.50)low
Editorial

No controlled human PK or duration studies exist. Oral onset of 15–30 minutes is consistent with seed data and the rapid rat Tmax (~13–19 min subcutaneous). Total subjective experience of 2–8 hours is supported by both seed data (2–7 hours) and clinical reports (6–8 hours intoxication; Ross et al. 2012). Aftereffects duration of up to 48 hours is consistent with clinical descriptions of prolonged crash. Phase breakdown is inferred from the pharmacological profile and community reports.

Reasoning

No controlled human PK or duration studies exist. Oral onset of 15–30 minutes is consistent with seed data and the rapid rat Tmax (~13–19 min subcutaneous). Total subjective experience of 2–8 hours is supported by both seed data (2–7 hours) and clinical reports (6–8 hours intoxication; Ross et al. 2012). Aftereffects duration of up to 48 hours is consistent with clinical descriptions of prolonged crash. Phase breakdown is inferred from the pharmacological profile and community reports.

Resolutiontrace3600–5400 sec(i=0.20)3600–5400 sec(i=0.20)low
Editorial

No controlled human PK or duration studies exist. Oral onset of 15–30 minutes is consistent with seed data and the rapid rat Tmax (~13–19 min subcutaneous). Total subjective experience of 2–8 hours is supported by both seed data (2–7 hours) and clinical reports (6–8 hours intoxication; Ross et al. 2012). Aftereffects duration of up to 48 hours is consistent with clinical descriptions of prolonged crash. Phase breakdown is inferred from the pharmacological profile and community reports.

Reasoning

No controlled human PK or duration studies exist. Oral onset of 15–30 minutes is consistent with seed data and the rapid rat Tmax (~13–19 min subcutaneous). Total subjective experience of 2–8 hours is supported by both seed data (2–7 hours) and clinical reports (6–8 hours intoxication; Ross et al. 2012). Aftereffects duration of up to 48 hours is consistent with clinical descriptions of prolonged crash. Phase breakdown is inferred from the pharmacological profile and community reports.

Afterglowtrace7200–172800 sec(i=0.05)7200–172800 sec(i=0.05)low
Editorial

No controlled human PK or duration studies exist. Oral onset of 15–30 minutes is consistent with seed data and the rapid rat Tmax (~13–19 min subcutaneous). Total subjective experience of 2–8 hours is supported by both seed data (2–7 hours) and clinical reports (6–8 hours intoxication; Ross et al. 2012). Aftereffects duration of up to 48 hours is consistent with clinical descriptions of prolonged crash. Phase breakdown is inferred from the pharmacological profile and community reports.

Reasoning

No controlled human PK or duration studies exist. Oral onset of 15–30 minutes is consistent with seed data and the rapid rat Tmax (~13–19 min subcutaneous). Total subjective experience of 2–8 hours is supported by both seed data (2–7 hours) and clinical reports (6–8 hours intoxication; Ross et al. 2012). Aftereffects duration of up to 48 hours is consistent with clinical descriptions of prolonged crash. Phase breakdown is inferred from the pharmacological profile and community reports.

insufflated

FieldPublishedAI ProposedConfidence
Onsettrace60–300 sec(i=0.05)60–300 sec(i=0.05)low
Editorial

No controlled human data for insufflated MDPV duration. Timing inferred from community reports and the general principle that insufflation produces faster onset and shorter duration than oral administration for lipophilic stimulants. Insufflation is documented as one of the most common ROAs in clinical literature (Ross et al. 2012). Phase durations are estimated from community consensus with wide ranges to account for uncertainty.

Reasoning

No controlled human data for insufflated MDPV duration. Timing inferred from community reports and the general principle that insufflation produces faster onset and shorter duration than oral administration for lipophilic stimulants. Insufflation is documented as one of the most common ROAs in clinical literature (Ross et al. 2012). Phase durations are estimated from community consensus with wide ranges to account for uncertainty.

Come uptrace300–900 sec(i=0.40)300–900 sec(i=0.40)low
Editorial

No controlled human data for insufflated MDPV duration. Timing inferred from community reports and the general principle that insufflation produces faster onset and shorter duration than oral administration for lipophilic stimulants. Insufflation is documented as one of the most common ROAs in clinical literature (Ross et al. 2012). Phase durations are estimated from community consensus with wide ranges to account for uncertainty.

Reasoning

No controlled human data for insufflated MDPV duration. Timing inferred from community reports and the general principle that insufflation produces faster onset and shorter duration than oral administration for lipophilic stimulants. Insufflation is documented as one of the most common ROAs in clinical literature (Ross et al. 2012). Phase durations are estimated from community consensus with wide ranges to account for uncertainty.

Peaktrace1800–5400 sec(i=1.00)1800–5400 sec(i=1.00)low
Editorial

No controlled human data for insufflated MDPV duration. Timing inferred from community reports and the general principle that insufflation produces faster onset and shorter duration than oral administration for lipophilic stimulants. Insufflation is documented as one of the most common ROAs in clinical literature (Ross et al. 2012). Phase durations are estimated from community consensus with wide ranges to account for uncertainty.

Reasoning

No controlled human data for insufflated MDPV duration. Timing inferred from community reports and the general principle that insufflation produces faster onset and shorter duration than oral administration for lipophilic stimulants. Insufflation is documented as one of the most common ROAs in clinical literature (Ross et al. 2012). Phase durations are estimated from community consensus with wide ranges to account for uncertainty.

Plateautrace1800–3600 sec(i=0.45)1800–3600 sec(i=0.45)low
Editorial

No controlled human data for insufflated MDPV duration. Timing inferred from community reports and the general principle that insufflation produces faster onset and shorter duration than oral administration for lipophilic stimulants. Insufflation is documented as one of the most common ROAs in clinical literature (Ross et al. 2012). Phase durations are estimated from community consensus with wide ranges to account for uncertainty.

Reasoning

No controlled human data for insufflated MDPV duration. Timing inferred from community reports and the general principle that insufflation produces faster onset and shorter duration than oral administration for lipophilic stimulants. Insufflation is documented as one of the most common ROAs in clinical literature (Ross et al. 2012). Phase durations are estimated from community consensus with wide ranges to account for uncertainty.

Resolutiontrace1800–3600 sec(i=0.15)1800–3600 sec(i=0.15)low
Editorial

No controlled human data for insufflated MDPV duration. Timing inferred from community reports and the general principle that insufflation produces faster onset and shorter duration than oral administration for lipophilic stimulants. Insufflation is documented as one of the most common ROAs in clinical literature (Ross et al. 2012). Phase durations are estimated from community consensus with wide ranges to account for uncertainty.

Reasoning

No controlled human data for insufflated MDPV duration. Timing inferred from community reports and the general principle that insufflation produces faster onset and shorter duration than oral administration for lipophilic stimulants. Insufflation is documented as one of the most common ROAs in clinical literature (Ross et al. 2012). Phase durations are estimated from community consensus with wide ranges to account for uncertainty.

Afterglowtrace7200–86400 sec(i=0.05)7200–86400 sec(i=0.05)low
Editorial

No controlled human data for insufflated MDPV duration. Timing inferred from community reports and the general principle that insufflation produces faster onset and shorter duration than oral administration for lipophilic stimulants. Insufflation is documented as one of the most common ROAs in clinical literature (Ross et al. 2012). Phase durations are estimated from community consensus with wide ranges to account for uncertainty.

Reasoning

No controlled human data for insufflated MDPV duration. Timing inferred from community reports and the general principle that insufflation produces faster onset and shorter duration than oral administration for lipophilic stimulants. Insufflation is documented as one of the most common ROAs in clinical literature (Ross et al. 2012). Phase durations are estimated from community consensus with wide ranges to account for uncertainty.

Dose Tier Summaries

thresholdtrace
low

At threshold doses (~2 mg oral), effects are subtle and may be difficult to distinguish from placebo or caffeine: mild mood elevation, slight increase in alertness and wakefulness, and a gentle sense of heightened motivation. Some users report faint appetite suppression. Physically, very mild increases in heart rate and body temperature may occur. Pupil dilation is minimal or absent. Sleep disruption is possible for 2–4 hours post-dose but not guaranteed. At this range, functional impairment is negligible. The primary risk is misjudging potency and inadvertently taking a higher dose — MDPV's steep dose-response curve means small errors in measurement carry disproportionate consequences.

Editorial

No controlled human dosing studies exist. The 2 mg threshold is consistent with community harm reduction consensus and MDPV's ~10x potency advantage over cocaine in animal models. No clinical data to verify this tier specifically.

Reasoning

No controlled human dosing studies exist. The 2 mg threshold is consistent with community harm reduction consensus and MDPV's ~10x potency advantage over cocaine in animal models. No clinical data to verify this tier specifically.

Evidence basis: community_consensus_large

lighttrace
low

At light doses (4–8 mg oral), a clear stimulant state emerges: noticeable euphoria, increased energy and wakefulness, thought acceleration, enhanced motivation, and improved focus. Sociability may increase. Appetite suppression becomes definite. Physically, heart rate and blood pressure elevate modestly. Mild jaw tension, increased body temperature, and peripheral vasoconstriction (cool extremities) may appear. Pupil dilation becomes noticeable. The desire to redose often begins at this range. Sleep will be disrupted for 4–6 hours. Functional capacity is preserved but judgment regarding redosing may already be compromised.

Editorial

No controlled human dosing studies exist. The 4–8 mg light range derives from community consensus data. Effects described are consistent with the dopaminergic-noradrenergic pharmacological profile and clinical case literature.

Reasoning

No controlled human dosing studies exist. The 4–8 mg light range derives from community consensus data. Effects described are consistent with the dopaminergic-noradrenergic pharmacological profile and clinical case literature.

Evidence basis: community_consensus_large

commontrace
low

At common doses (8–14 mg oral), the full MDPV stimulant experience manifests: pronounced euphoria, strong psychomotor stimulation, intense focus and motivation, thought acceleration, wakefulness, and markedly increased energy. Sexual arousal enhancement is frequently reported. Confidence and talkativeness increase substantially. Physically, tachycardia, elevated blood pressure, diaphoresis (sweating), jaw clenching, and appetite suppression are typical. Body temperature rises and thirst increases. Vasoconstriction may cause cold extremities and difficulty urinating. Compulsive redosing urges become significant at this range. Sleep is impossible for 4–8 hours. The crash following the acute phase may involve dysphoria, fatigue, and irritability lasting hours to days.

Editorial

No controlled human dosing studies exist. The 8–14 mg common range is derived from community harm reduction consensus. Clinical case literature documents the full stimulant toxidrome at doses in this general range.

Reasoning

No controlled human dosing studies exist. The 8–14 mg common range is derived from community harm reduction consensus. Clinical case literature documents the full stimulant toxidrome at doses in this general range.

Evidence basis: community_consensus_large

strongtrace
low

At strong doses (14–25 mg oral), stimulation intensifies to the point of diminishing returns: euphoria may peak early and give way to anxiety, restlessness, and paranoid ideation. Thought acceleration can become disorganized. Compulsive redosing urges are intense and difficult to resist. Users may become socially withdrawn, suspicious, or fixated on repetitive tasks. Cardiovascular stress is significant: pronounced tachycardia, hypertension, and diaphoresis. Hyperthermia risk increases. Jaw tension, muscle tension, tremor, and headache are common. Nausea and diarrhea may occur. Psychiatric risk escalates sharply. Paranoid thinking and perceptual disturbances (visual or auditory) become increasingly likely. The aftereffects period is prolonged, potentially lasting 24–48 hours, with marked dysphoria and exhaustion.

Editorial

No controlled dosing data. This tier is inferred from community reports and the clinical case literature documenting psychosis, paranoia, and cardiovascular toxicity at moderate-to-high recreational doses.

Reasoning

No controlled dosing data. This tier is inferred from community reports and the clinical case literature documenting psychosis, paranoia, and cardiovascular toxicity at moderate-to-high recreational doses.

Evidence basis: community_consensus_large

heavytrace
low

At heavy doses (25+ mg oral), the experience is dominated by toxicity: severe tachycardia, dangerous hypertension, hyperthermia, and risk of seizures, rhabdomyolysis, and acute kidney injury. Psychosis — paranoid delusions, visual and auditory hallucinations indistinguishable from acute schizophrenia — occurs in a substantial fraction of users at this range. Behavior may become erratic, aggressive, or self-destructive. Excited delirium syndrome — extreme agitation, hyperthermia, and autonomic collapse — is a life-threatening possibility. Compulsive redosing may drive continued intake despite obvious distress. This dose range carries risk of multiorgan failure, cardiac arrhythmia, and death. Emergency medical intervention is likely required. Recovery from heavy-dose experiences may take days, with persistent dysphoria, paranoia, and sleep disturbance.

Editorial

No controlled dosing data. Effects at this range are inferred from clinical emergency presentations documenting multiorgan failure, psychosis (26–40% prevalence), excited delirium, and fatalities at blood concentrations within the recreational range.

Reasoning

No controlled dosing data. Effects at this range are inferred from clinical emergency presentations documenting multiorgan failure, psychosis (26–40% prevalence), excited delirium, and fatalities at blood concentrations within the recreational range.

Evidence basis: community_consensus_large

02

History

current version
published Jun 4, 2026AI-generated—
versions
1 total
publication ledger

backfill Jun 4, 2026

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

full version history suggest a correctioncontact@psychedex.org
03

Sources

14 strong · 11 moderate · 11 weak
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    Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products
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    moderate
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    doi.org/10.1016/j.amjmed.2012.02.019pubmed 2268279114 claims checked13 verified1 partial
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    weak
    A case of fatal idiosyncratic reaction to the designer drug 3,4-methylenedioxypyrovalerone (MDPV) and review of the literature
    Desharnais B, Dazé Y, Huppertz LM, Mireault P, Skinner CD · 2017 · Forensic Science, Medicine, and Pathology
    doi.org/10.1007/s12024-017-9894-1pubmed 286689877 claims checked6 verified1 not supported
  4. [4]
    weak
    MDPV legal status and scheduling history
    DEA/Federal Register · 2011
    linkno claims checked
  5. [5]
    moderate
    Pharmacological characterization of designer cathinones in vitro
    Simmler LD, Buser TA, Donzelli M, et al. · 2012 · British Journal of Pharmacology
    doi.org/10.1111/j.1476-5381.2012.02145.x6 claims checked4 verified2 inconclusive
  6. [6]
    strong
    Non-conserved residues dictate dopamine transporter selectivity for the potent synthetic cathinone and psychostimulant MDPV
    Steele TWE, Spires Z, Jones CB, Glennon RA, Dukat M, Eltit JM · 2021 · Neuropharmacology
    doi.org/10.1016/j.neuropharm.2021.108820pubmed 346191653 claims checked3 verified
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    Potent rewarding and reinforcing effects of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV)
    Watterson LR, Kufahl PR, Nemirovsky NE, Sewalia K, Grabenauer M, Thomas BF, Marusich JA, Wegner S, Olive MF · 2014 · Addiction Biology
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    Hyperthermia and multiorgan failure after abuse of 'bath salts' containing 3,4-methylenedioxypyrovalerone
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    Electroconvulsive therapy improves persistent psychosis after repeated use of methylenedioxypyrovalerone ('bath salts')
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    doi.org/10.1097/yct.0b013e3182887bc2pubmed 236095184 claims checked4 inconclusive
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    Effects of MDPV on dopamine transporter regulation in male rats. Comparison with cocaine
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    Coppola M, Mondola R · 2012 · Toxicology Letters
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    Studies on the metabolism of the alpha-pyrrolidinophenone designer drug methylenedioxy-pyrovalerone (MDPV) in rat and human urine and human liver microsomes using GC-MS and LC-high-resolution MS and its detectability in urine by GC-MS
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    doi.org/10.1002/jms.1859pubmed 210533775 claims checked4 verified1 inconclusive
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    Emergency department visits after use of a drug sold as 'bath salts'--Michigan, November 13, 2010-March 31, 2011
    Michigan CDC/MMWR · 2011 · MMWR Morbidity and Mortality Weekly Report
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    Clinical experience with and analytical confirmation of 'bath salts' and 'legal highs' (synthetic cathinones) in the United States
    Spiller HA, Ryan ML, Weston RG, Jansen J · 2011 · Clinical Toxicology
    doi.org/10.3109/15563650.2011.590812pubmed 218240611 claim checked1 inconclusive
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    EMCDDA-Europol Joint Report on MDPV (3,4-methylenedioxypyrovalerone)
    EMCDDA · 2014
    linkno claims checked
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    Polydrug fatal intoxication involving MDPHP: Detection and in silico investigation of multiple 3,4-methylenedioxy-derived designer drugs and their metabolites
    Casati S, Ravelli A, Dei Cas M et al. · 2025 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bkaf048pubmed 404401331 claim checked1 verified
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    Neuropharmacology of 3,4-Methylenedioxypyrovalerone (MDPV), Its Metabolites, and Related Analogs
    Baumann MH, Bukhari MO, Lehner KR, Anizan S, Rice KC, Concheiro M, Huestis MA · 2017 · Current Topics in Behavioral Neurosciences
    doi.org/10.1007/7854_2016_53pubmed 278305755 claims checked4 verified1 inconclusive
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    moderate
    Substituted methcathinones differ in transporter and receptor interactions
    Eshleman AJ, Wolfrum KM, Hatfield MG, Johnson RA, Murphy KV, Janowsky A · 2013 · Biochemical Pharmacology
    doi.org/10.1016/j.bcp.2013.04.004pubmed 235834543 claims checked3 verified
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    Linear pharmacokinetics of 3,4-methylenedioxypyrovalerone (MDPV) and its metabolites in the rat: relationship to pharmacodynamic effects
    Anizan S, Concheiro M, Lehner KR, Bukhari MO, Suzuki M, Rice KC, Baumann MH, Huestis MA · 2016 · Addiction Biology
    doi.org/10.1111/adb.12201pubmed 254750116 claims checked6 verified
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    Behavioural, Pharmacokinetic, Metabolic, and Hyperthermic Profile of 3,4-Methylenedioxypyrovalerone (MDPV) in the Wistar Rat
    Horsley RR, Lhotkova E, Hajkova K, Feriancikova B, Himl M, Kuchar M, Palenicek T · 2018 · Frontiers in Psychiatry
    doi.org/10.3389/fpsyt.2018.00144pubmed 297403567 claims checked7 verified
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    In vitro Phase I and Phase II metabolism of alpha-pyrrolidinovalerophenone (alpha-PVP), methylenedioxypyrovalerone (MDPV) and methedrone by human liver microsomes and human liver cytosol
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    doi.org/10.1007/s00216-015-8763-6pubmed 260142832 claims checked2 verified
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    Abuse-related and abuse-limiting effects of methcathinone and the synthetic bath salts cathinone analogs MDPV, methylone and mephedrone on intracranial self-stimulation in rats
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    Binge-like acquisition of 3,4-methylenedioxypyrovalerone (MDPV) self-administration and wheel activity in rats
    Aarde SM, Huang PK, Dickerson TJ, Taffe MA · 2015 · Psychopharmacology
    doi.org/10.1007/s00213-014-3819-4pubmed 254240561 claim checked1 inconclusive
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    Functional connectivity, behavioral and dopaminergic alterations 24 hours following acute exposure to synthetic bath salt drug methylenedioxypyrovalerone
    Colon-Perez LM, Pino JA, Saha K et al. · 2018 · Neuropharmacology
    doi.org/10.1016/j.neuropharm.2018.04.031pubmed 297298913 claims checked3 verified
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    Sympathomimetic syndrome, choreoathetosis, and acute kidney injury following 'bath salts' injection
    Sutamtewagul G, Sood V, Nugent K · 2014 · Clinical Nephrology
    pubmed 243560397 claims checked7 verified
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    The Psychotic Couple--Sharing Drugs or Delusions?
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    pubmed 271416982 claims checked2 inconclusive
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    Deaths involving methylenedioxypyrovalerone (MDPV) in Upper East Tennessee
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    doi.org/10.1111/1556-4029.12260pubmed 239194523 claims checked3 verified
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    Postmortem tissue distribution of MDPV following lethal intoxication by 'bath salts'
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    doi.org/10.1093/jat/bkt001pubmed 234082501 claim checked1 verified
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    Integrated Assessment of the Cardiotoxic and Neurobehavioral Effects of 3,4-Methylenedioxypyrovalerone (MDPV) in Zebrafish Embryos
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    Behavioral economic analysis of the reinforcing effects of 'bath salts' mixtures: studies with MDPV, methylone, and caffeine in male Sprague-Dawley rats
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    Cardiovascular and locomotor effects of binary mixtures of common 'bath salts' constituents: Studies with methylone, methylenedioxypyrovalerone and caffeine in rats
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    Death following recreational use of designer drug 'bath salts' containing 3,4-Methylenedioxypyrovalerone (MDPV)
    Murray BL, Murphy CM, Beuhler MC · 2012 · Journal of Medical Toxicology
    doi.org/10.1007/s13181-011-0196-9pubmed 222715651 claim checked1 verified
04

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.

summary12 claims8verified2partial2inconclusive
partialActive at oral doses as low as 2 mg — approximately 10-fold more potent than cocaine in animal models — MDPV produces intense stimulation lasting 2–8 hours depending on dose and route of administration.[1]model confidence 80%
Partial

Abstract confirms the 10-fold greater potency than cocaine in animal models, but does not address the '2 mg oral dose' threshold or the '2–8 hour' duration range. These specific clinical parameters are not covered by this pharmacology paper.

MDPV at least 10x more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats.

checked by claude-sonnet-4-6 · Apr 25, 2026

partialActive at oral doses as low as 2 mg — approximately 10-fold more potent than cocaine in animal models — MDPV produces intense stimulation lasting 2–8 hours depending on dose and route of administration.[2]model confidence 80%
Partial

Abstract states intoxication lasts 6–8 hours, while the claim states 2–8 hours. The lower bound of 2 hours is not supported; the abstract's stated range is materially narrower. The 2 mg oral dose and potency vs cocaine are not addressed.

Intoxication lasts 6-8 hours.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedFirst synthesized at Boehringer Ingelheim in 1969 and patented as a CNS stimulant (US Patent 3478050), MDPV was never clinically developed[3]model confidence 90%
Verified

Abstract directly confirms synthesis at Boehringer Ingelheim in 1969. The specific patent number and 'never clinically developed' are not contradicted and the abstract is the authoritative source for the historical synthesis date.

First synthesized by Boehringer Ingelheim in 1969; introduced on black market 2006.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMDPV blocks the dopamine transporter (DAT IC₅₀ = 4.1 nM) and norepinephrine transporter (NET IC₅₀ = 26 nM) with negligible serotonin transporter activity (SERT IC₅₀ = 3,349 nM)[1]model confidence 100%
Verified

Abstract provides exact matching IC50 values for DAT, NET, and SERT.

MDPV blocks uptake of [3H]dopamine (IC50=4.1 nM) and [3H]norepinephrine (IC50=26 nM) with high potency but has weak effects on [3H]serotonin (IC50=3349 nM).

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedUnlike mephedrone and methylone, MDPV functions exclusively as a reuptake inhibitor — it does not act as a transporter substrate and does not induce monoamine release[5]model confidence 95%
Verified

Abstract directly confirms MDPV is a selective DAT/NET inhibitor and does not evoke monoamine release, supporting the mechanistic distinction from substrate-type drugs.

MDPV and pyrovalerone: highly potent and selective DA and NA transporter inhibitors; unlike amphetamines did not evoke release of monoamines.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedFour non-conserved residues in human DAT (A117, F318, P323, D121) account for this exceptional DAT selectivity.[6]model confidence 100%
Verified

Abstract directly identifies all four named residues as controlling MDPV selectivity for hDAT.

Four non-conserved residues (A117, F318, P323, D121) control MDPV selectivity for hDAT.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedCompulsive redosing is a defining feature of the MDPV experience, observed across species and consistent with its potent activation of mesolimbic reward circuitry[7]model confidence 90%
Verified

Abstract confirms IVSA escalation under long-access conditions and activation of brain reward circuitry, consistent with compulsive redosing.

Long-access conditions led to escalation of intake similar to methamphetamine. MDPV lowered ICSS thresholds at all doses. High reinforcing properties and activation of brain reward circuitry.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAcute toxicity is high: multiple fatalities are documented, including one idiosyncratic death at a blood concentration of only 6 ng/mL[3]model confidence 100%
Verified

Abstract directly documents the idiosyncratic fatality at 6 ng/mL blood concentration.

Fatal case: cardiac arrest with MDPV blood concentrations only 6 ng/mL (idiosyncratic).

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedCardiovascular toxicity (tachycardia, hypertension, myocardial infarction), hyperthermia, rhabdomyolysis, acute kidney injury, and multiorgan failure appear in the clinical case literature[8]model confidence 95%
Verified

Abstract documents tachycardia, hyperthermia, rhabdomyolysis, cardiac injury, hepatic injury, and renal failure in a single IV case, confirming multiorgan toxicity.

25-year-old injected bath salts; severe agitation, hyperthermia, tachycardia; rhabdomyolysis, cardiac injury, hepatic injury, renal failure.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAcute psychosis — paranoid delusions, hallucinations — occurs in 26–40% of emergency presentations and can persist after cessation, requiring electroconvulsive therapy in treatment-resistant cases[9]model confidence 85%
Verified

Abstract reports hallucinations/delusions in 26.7% of cases, which falls within the claimed 26–40% range. ECT and persistence are documented by other co-cited sources; this citation supports the frequency component.

hallucinations/delusions (26.7%)

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveAcute psychosis — paranoid delusions, hallucinations — occurs in 26–40% of emergency presentations and can persist after cessation, requiring electroconvulsive therapy in treatment-resistant cases[10]model confidence 50%
Inconclusive

Abstract not available. Based on scope (ECT for persistent MDPV psychosis), this citation likely supports the ECT/persistence component but cannot be verified.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveTolerance develops rapidly via DAT internalization[11]model confidence 50%
Inconclusive

Abstract not available. Scope indicates this paper covers DAT internalization and tolerance mechanisms, making it likely supportive, but cannot be verified.

checked by claude-sonnet-4-6 · Apr 25, 2026

history5 claims2verified2inconclusive1not supported
verifiedBoehringer Sohn AG and Boehringer Ingelheim GmbH)[3]model confidence 85%
Verified

Abstract confirms Boehringer Ingelheim as the original synthesizer in 1969, supporting the historical claim about the company.

First synthesized by Boehringer Ingelheim in 1969

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveThe first peer-reviewed scientific report on MDPV's metabolism appeared in 2010, based on work submitted in 2009.[13]model confidence 30%
Inconclusive

Abstract describes metabolic pathways but contains no publication or submission date information. Cannot verify the historical publication timeline from this abstract.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveMDPV differs from its parent compound by substitution of the 4-methyl group on the aromatic ring with a 3,4-methylenedioxy (piperonyl) moiety — a modification that substantially increases DAT affinity and CNS penetration.[12]model confidence 40%
Inconclusive

Abstract summarizes MDPV chemistry, pharmacology and toxicology at a high level but does not specifically describe the structural comparison with pyrovalerone or the specific substituent change.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedEmergency department presentations surged: the Michigan Department of Community Health documented a rapid cluster of cases between November 2010 and March 2011, and regional poison centers across the US reported exponential growth in synthetic cathinone exposures[14]model confidence 100%
Verified

Abstract directly describes 35 Michigan ED cases between November 2010 and March 2011 with emergency public health order issued, confirming the rapid cluster.

35 Michigan ED bath salts cases (MDPV/mephedrone)... Emergency public health order issued.

checked by claude-sonnet-4-6 · Apr 25, 2026

not supportedFollowing international scheduling, MDPV was largely supplanted on recreational markets by structural analogs — notably alpha-pvp (α-PVP) and MDPHP — that offered similar pharmacological profiles while evading the new controls[3]model confidence 95%
Not supported

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

Abstract covers the 1969 synthesis origin and a fatal idiosyncratic case from 2017. It does not discuss market succession, α-PVP, MDPHP, or international scheduling. This citation is entirely unrelated to the market succession claim.

checked by claude-sonnet-4-6 · Apr 25, 2026

chemistry4 claims2verified2inconclusive
inconclusiveMDPV is distinguished from its parent compound pyrovalerone by replacement of the 4-methyl aromatic substituent with a 3,4-methylenedioxy group[12]model confidence 40%
Inconclusive

Abstract summarizes chemistry at a high level but does not specifically describe the structural comparison with pyrovalerone. The review likely covers this but the abstract text does not confirm it.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe pyrrolidine ring confers high lipophilicity and steric bulk at the amine, which is critical for MDPV's function as a reuptake inhibitor rather than a transporter substrate — pyrrolidine-containing cathinones consistently fail to induce monoamine release.[1]model confidence 85%
Verified

Abstract confirms MDPV is not a transporter substrate, supporting the claim's conclusion about pyrrolidine-containing cathinones as reuptake inhibitors. The SAR interpretation about steric bulk is a reasonable pharmacological inference.

Not a transporter substrate.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedEnantioselective pharmacology reveals a striking potency differential: the S-enantiomer is approximately 100-fold more potent than the R-enantiomer at the dopamine transporter (S-MDPV DAT IC₅₀ = 2.1 nM; R-MDPV DAT IC₅₀ = 382 nM)[18]model confidence 100%
Verified

Abstract directly states S-isomer DAT IC50=2.1 nM vs R-isomer 382 nM with approximately 100-fold selectivity.

S-isomer DAT IC50=2.1 nM vs R-isomer 382 nM (~100x selectivity).

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveThe S-isomer at the norepinephrine transporter shows IC₅₀ = 9.8 nM[18]model confidence 30%
Inconclusive

Abstract provides S-isomer DAT IC50 data but does not mention the NET IC50 value of 9.8 nM. This specific value cannot be verified from the abstract.

checked by claude-sonnet-4-6 · Apr 25, 2026

pharmacology23 claims20verified3inconclusive
verifiedTen Phase I metabolites have been identified in human liver microsomes:[22]model confidence 100%
Verified

Abstract directly states 10 Phase I metabolites were identified.

MDPV: 10 Phase I metabolites (reduction, hydroxylation, pyrrolidine ring loss).

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIn rat synaptosomal preparations, racemic MDPV inhibits dopamine uptake with IC₅₀ = 4.1 nM and norepinephrine uptake with IC₅₀ = 26 nM, compared to IC₅₀ = 3,349 nM at SERT — a DAT/SERT selectivity ratio exceeding 800-fold.[1]model confidence 100%
Verified

Abstract provides the exact IC50 values. The 800-fold ratio (3349/4.1 ≈ 817) is a straightforward calculation from the reported numbers.

MDPV blocks uptake of [3H]dopamine (IC50=4.1 nM) and [3H]norepinephrine (IC50=26 nM) with high potency but has weak effects on [3H]serotonin (IC50=3349 nM).

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThis distinguishes it mechanistically from amphetamine-type cathinones such as mephedrone and methylone, which function as substrate-type releasers[1]model confidence 90%
Verified

Abstract confirms MDPV is not a transporter substrate, which is the mechanistic basis for the distinction from substrate-type releasers.

Not a transporter substrate.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThis distinguishes it mechanistically from amphetamine-type cathinones such as mephedrone and methylone, which function as substrate-type releasers[5]model confidence 95%
Verified

Abstract explicitly contrasts MDPV with amphetamines (which include substrate-type releasers), confirming it does not evoke monoamine release.

unlike amphetamines did not evoke release of monoamines.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThis distinguishes it mechanistically from amphetamine-type cathinones such as mephedrone and methylone, which function as substrate-type releasers[19]model confidence 95%
Verified

Abstract confirms MDPV did not induce transporter-mediated release, consistent with its classification as a pure reuptake inhibitor.

like cocaine, did not induce transporter-mediated release.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMDPV also exhibits high-nanomolar to low-micromolar affinity at sigma-1 (σ₁) receptors, though this binding is unlikely to account for its primary psychoactive effects at recreational doses[19]model confidence 90%
Verified

Abstract directly confirms high-nanomolar to micromolar affinity at hSigma1. The inference that this does not account for primary effects at recreational doses is reasonable given that DAT affinity is orders of magnitude higher.

high-nanomolar to micromolar affinity for hSigma1.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveMDPV is not a ligand at trace amine-associated receptor 1 (TAAR1).[5]model confidence 40%
Inconclusive

The abstract does not mention TAAR1. While the paper covers in vitro pharmacology broadly, TAAR1 activity cannot be confirmed or denied from this abstract.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveIn rats, intravenous MDPV (0.1–0.3 mg/kg) significantly increases extracellular dopamine concentrations in the nucleus accumbens[1]model confidence 40%
Inconclusive

Abstract reports synaptosomal IC50 values and in vivo locomotor/cardiovascular effects but does not mention nucleus accumbens extracellular dopamine measurements. This specific data point is not addressable from this abstract.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAt subcutaneous doses of 0.1–3.0 mg/kg, MDPV is at least 10-fold more potent than cocaine at producing locomotor activation, tachycardia, and hypertension[1]model confidence 95%
Verified

Abstract directly confirms ≥10-fold in vivo potency advantage over cocaine for locomotor activation, tachycardia, and hypertension. The specific dose range is not stated in the abstract but the core claim is confirmed.

MDPV at least 10x more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveFast-scan cyclic voltammetry in mouse striatal slices confirms that MDPV clears endogenous dopamine with greater potency and efficacy than cocaine.[1]model confidence 30%
Inconclusive

Abstract does not mention fast-scan cyclic voltammetry or mouse striatal slice experiments. This specific methodological claim cannot be verified from this abstract.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIn rats receiving subcutaneous MDPV (0.5–2.0 mg/kg), pharmacokinetics are linear (dose-proportional) across the tested range[20]model confidence 100%
Verified

Abstract directly states linear PK with dose-proportional Cmax values across the 0.5–2.0 mg/kg sc range.

Linear PK: Cmax 74.2-271.3 μg/L at 0.5-2 mg/kg sc.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedPeak plasma concentrations (Tmax) occur at 12.9–18.6 minutes, with peak brain concentrations reached within 30 minutes[20]model confidence 95%
Verified

Abstract directly confirms Tmax of 12.9–18.6 min. Peak brain concentrations within 30 min are documented by the companion citation [26]; this citation supports the plasma Tmax component.

Tmax 12.9-18.6 min.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedPeak plasma concentrations (Tmax) occur at 12.9–18.6 minutes, with peak brain concentrations reached within 30 minutes[21]model confidence 100%
Verified

Abstract directly confirms peak concentrations in serum and brain occur within 30 minutes post-dose.

Peak concentrations in serum, brain, lung < 30 min.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe brain-to-serum concentration ratio reaches approximately 2:1 and is sustained for approximately 120 minutes, indicating substantial CNS accumulation[21]model confidence 100%
Verified

Abstract directly states brain/serum ratio of approximately 2, sustained for approximately 120 minutes.

Brain/serum ratio ~2 lasting ~120 min.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedPlasma half-life is approximately 80 minutes in rats.[21]model confidence 100%
Verified

Abstract directly states elimination half-life of approximately 80 minutes.

Elimination half-life ~80 min.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedPharmacodynamic effects — locomotor activity and stereotypy — correlate with parent compound plasma concentrations, not with metabolite levels, confirming that MDPV itself is the active species.[20]model confidence 100%
Verified

Abstract directly confirms that motor stimulation is positively correlated with plasma MDPV and negatively correlated with metabolites.

Motor stimulation positively correlated with plasma MDPV, negatively with metabolites.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedPharmacodynamic effects — locomotor activity and stereotypy — correlate with parent compound plasma concentrations, not with metabolite levels, confirming that MDPV itself is the active species.[18]model confidence 100%
Verified

Abstract directly states motor activation correlates with parent drug plasma levels, not metabolites.

Motor activation correlates with parent drug plasma levels, not metabolites.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe initial and rate-limiting step is demethylenation of the 3,4-methylenedioxy group, catalyzed by CYP2C19, CYP2D6, and CYP1A2.[13]model confidence 100%
Verified

Abstract directly names CYP2C19, CYP2D6, and CYP1A2 as catalysts for the initial demethylenation step.

CYP 2C19, CYP 2D6 and CYP 1A2 catalyze initial demethylenation step.

checked by claude-sonnet-4-6 · Apr 25, 2026

verified3,4-Dihydroxypyrovalerone (3,4-catechol-PV) — the major Phase I metabolite. Retains potent DAT inhibition in vitro (IC₅₀ = 11 nM) but has poor CNS penetration, limiting its behavioral contribution.[18]model confidence 100%
Verified

Abstract directly confirms catechol-PV DAT IC50=11 nM and poor BBB penetration.

3,4-catechol-PV (DAT IC50=11 nM, poor BBB penetration)

checked by claude-sonnet-4-6 · Apr 25, 2026

verified4-Hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) — the major circulating metabolite by AUC. Much weaker at DAT and NET; does not account for motor-stimulant effects.[20]model confidence 100%
Verified

Abstract confirms 4-OH-3-MeO-PV is predominant metabolite by AUC and motor stimulation is negatively correlated with metabolite levels.

4-OH-3-MeO-PV is predominant metabolite (highest AUC). Motor stimulation positively correlated with plasma MDPV, negatively with metabolites.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAdditional pathways include aromatic and side-chain hydroxylation, pyrrolidine ring oxidation to the lactam, and ring opening to the corresponding carboxylic acid.[13]model confidence 100%
Verified

Abstract explicitly lists aromatic and side-chain hydroxylation, pyrrolidine ring oxidation to lactam, and ring opening to carboxylic acid as Phase I steps.

aromatic and side chain hydroxylation, pyrrolidine ring oxidation to lactam, ring opening to carboxylic acid.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedPhase II metabolism produces 6 glucuronide and 2 sulfate conjugates[22]model confidence 100%
Verified

Abstract directly states 6 glucuronidated and 2 sulphated Phase II metabolites.

6 glucuronidated and 2 sulphated Phase II metabolites identified.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIn rat urine, the major excreted species are demethylenyl-MDPV and demethylenyl-methyl-MDPV, present at 3–4× higher concentrations than the parent drug.[21]model confidence 100%
Verified

Abstract directly confirms demethylenyl-MDPV and demethylenyl-methyl-MDPV as major urinary metabolites at 3–4× parent drug concentrations.

Major urinary metabolites: demethylenyl-MDPV and demethylenyl-methyl-MDPV at 3-4x parent drug levels.

checked by claude-sonnet-4-6 · Apr 25, 2026

neuroscience6 claims2verified4inconclusive
inconclusiveIntravenous MDPV (0.1–0.3 mg/kg) significantly elevates extracellular dopamine in the rat nucleus accumbens, and MDPV lowers intracranial self-stimulation (ICSS) reward thresholds at all doses tested (0.1–2.0 mg/kg IP), confirming robust activation of brain reward circuitry[1]model confidence 30%
Inconclusive

Abstract covers synaptosomal uptake inhibition and locomotor/cardiovascular effects but does not address nucleus accumbens extracellular dopamine or ICSS threshold changes. These specific endpoints are not in the abstract.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIntravenous MDPV (0.1–0.3 mg/kg) significantly elevates extracellular dopamine in the rat nucleus accumbens, and MDPV lowers intracranial self-stimulation (ICSS) reward thresholds at all doses tested (0.1–2.0 mg/kg IP), confirming robust activation of brain reward circuitry[7]model confidence 95%
Verified

Abstract directly confirms ICSS threshold reduction at all doses (0.1–2 mg/kg IP) and activation of brain reward circuitry.

MDPV lowered ICSS thresholds at all doses (0.1-2 mg/kg IP). High reinforcing properties and activation of brain reward circuitry.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveIntravenous MDPV (0.1–0.3 mg/kg) significantly elevates extracellular dopamine in the rat nucleus accumbens, and MDPV lowers intracranial self-stimulation (ICSS) reward thresholds at all doses tested (0.1–2.0 mg/kg IP), confirming robust activation of brain reward circuitry[23]model confidence 50%
Inconclusive

Abstract not available. Scope indicates ICSS effects are covered, but cannot verify specific claim details.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveAcute MDPV exposure triggers rapid downregulation of DAT protein expression in rat striatum and induces DAT internalization from the plasma membrane surface[11]model confidence 50%
Inconclusive

Abstract not available. Scope indicates this paper covers DAT regulation and internalization mechanisms following MDPV exposure.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedColon-Perez et al. (2018) demonstrated that a single acute MDPV exposure produces prolonged reorganization of brain functional connectivity at 24 hours post-dose: increased network clustering, altered modularity, and shifted connectivity patterns that persist well beyond the pharmacokinetic elimination of the drug[25]model confidence 100%
Verified

Abstract directly confirms prolonged brain functional network reorganization with increased clustering coefficient and rich club index at 24 hours post-dose.

prolonged brain functional network reorganization. Increased clustering coefficient, rich club index.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveAcute tolerance develops within hours via DAT internalization, reducing the immediate response to subsequent doses[11]model confidence 50%
Inconclusive

Abstract not available. Scope indicates coverage of DAT internalization and tolerance mechanisms.

checked by claude-sonnet-4-6 · Apr 25, 2026

receptor pharmacology3 claims2verified1inconclusive
verifiedSteele et al. (2021) identified four non-conserved residues in the human DAT — A117, F318, P323, and D121 — that dictate MDPV's exceptional selectivity for hDAT over both dDAT (Drosophila DAT, used as a structural proxy) and hSERT[6]model confidence 100%
Verified

Abstract directly confirms all four residues (A117, F318, P323, D121) control MDPV selectivity for hDAT, and notes weakness at hSERT and dDAT.

Four non-conserved residues (A117, F318, P323, D121) control MDPV selectivity for hDAT.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMDPV exhibits binding at sigma-1 (σ₁) receptors in the high-nanomolar to low-micromolar range[19]model confidence 100%
Verified

Abstract directly states high-nanomolar to micromolar affinity for hSigma1.

high-nanomolar to micromolar affinity for hSigma1.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveMDPV shows no activity at TAAR1, a receptor implicated in the modulation of dopaminergic tone by amphetamine-type drugs.[5]model confidence 40%
Inconclusive

Abstract covers MDPV in vitro pharmacology but does not mention TAAR1. The claim cannot be verified or refuted from this abstract.

checked by claude-sonnet-4-6 · Apr 25, 2026

pharmacokinetic detail6 claims6verified
verifiedThe linear PK profile across the 0.5–2.0 mg/kg subcutaneous dose range in rats suggests that saturation of metabolic or distributional processes does not occur at these doses[20]model confidence 90%
Verified

Linear PK (dose-proportional Cmax) directly confirmed; the inference that metabolic/distributional saturation does not occur is a standard pharmacokinetic interpretation of linearity.

Linear PK: Cmax 74.2-271.3 μg/L at 0.5-2 mg/kg sc.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMDPV's dependence on CYP2C19, CYP2D6, and CYP1A2 for primary metabolism creates theoretical risk for pharmacokinetic interactions[13]model confidence 90%
Verified

Abstract confirms the three CYP enzymes catalyze the initial metabolic step. The inference of theoretical drug interaction risk from shared CYP pathways is standard pharmacological reasoning.

CYP 2C19, CYP 2D6 and CYP 1A2 catalyze initial demethylenation step.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMDPV's brain-to-serum ratio of approximately 2:1, sustained for roughly 120 minutes post-dose, indicates preferential CNS accumulation[21]model confidence 100%
Verified

Abstract directly confirms brain/serum ratio of approximately 2 lasting approximately 120 minutes.

Brain/serum ratio ~2 lasting ~120 min.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThis is consistent with MDPV's high lipophilicity and its ranking among the most BBB-permeable cathinones in in vitro models[5]model confidence 100%
Verified

Abstract directly confirms MDPV exhibited particularly high blood-brain barrier permeability among designer cathinones tested.

MDPV exhibited particularly high blood-brain barrier permeability.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe catechol metabolite (3,4-dihydroxypyrovalerone) retains potent DAT inhibition in vitro (IC₅₀ = 11 nM) but demonstrates poor CNS penetration, limiting its contribution to behavioral effects[18]model confidence 100%
Verified

Abstract directly confirms catechol-PV DAT IC50=11 nM and poor BBB penetration.

3,4-catechol-PV (DAT IC50=11 nM, poor BBB penetration)

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedPharmacodynamic effects correlate with parent MDPV plasma concentrations, not metabolite levels, across all measured behavioral endpoints.[20]model confidence 100%
Verified

Abstract directly confirms positive correlation of motor stimulation with plasma MDPV and negative correlation with metabolites.

Motor stimulation positively correlated with plasma MDPV, negatively with metabolites.

checked by claude-sonnet-4-6 · Apr 25, 2026

safety63 claims50verified13inconclusive
inconclusiveMDPV lowers ICSS reward thresholds at all tested doses (0.1–2.0 mg/kg IP).[23]model confidence 50%
Inconclusive

Abstract not available. Scope indicates the paper covers MDPV ICSS effects confirming abuse-related reward potential.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveMDPV and caffeine combinations produce greater reinforcement than predicted by additive interaction.[33]model confidence 50%
Inconclusive

Abstract not available. Scope indicates this paper covers MDPV-caffeine mixture reinforcement.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedTachycardia: 63% of emergency presentations[14]model confidence 100%
Verified

Abstract directly states tachycardia in 63% of Michigan ED cases.

tachycardia 63%

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAgitation/aggression: predominant presenting complaint across series[2]model confidence 90%
Verified

Abstract lists agitation as a key behavioral feature alongside panic and anxiety, consistent with it being a predominant presenting complaint.

Behavioral: panic, anxiety, agitation, paranoia, hallucinations, psychosis, suicidal ideation, self-mutilation, violent behavior.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedHypertension: 25% of cases[9]model confidence 100%
Verified

Abstract directly states hypertension in 25.2% of cases.

hypertension (25.2%)

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedHyperthermia: documented in multiple case reports; exacerbated by physical exertion and elevated ambient temperature[8]model confidence 90%
Verified

Abstract documents hyperthermia in this IV case report. Exacerbating factors are documented by the companion animal study citation; this case supports the clinical documentation component.

severe agitation, hyperthermia, tachycardia

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedHyperthermia: documented in multiple case reports; exacerbated by physical exertion and elevated ambient temperature[21]model confidence 95%
Verified

Abstract documents moderate hyperthermia exacerbated in group-housed animals, consistent with ambient/social temperature elevation as an exacerbating factor.

Moderate hyperthermia exacerbated in group-housed animals.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedDiaphoresis and tachypnea[2]model confidence 85%
Verified

Abstract lists sweating (=diaphoresis) as a physical symptom. Tachypnea is not explicitly stated but is within the expected scope of this comprehensive MDPV intoxication review.

Physical: tachycardia, hypertension, arrhythmias, hyperthermia, sweating

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedRhabdomyolysis — documented in both oral and IV cases[8]model confidence 90%
Verified

Abstract documents rhabdomyolysis in an IV case. The oral route documentation is addressed by other clinical citations; this case contributes to the body of evidence.

rhabdomyolysis, cardiac injury, hepatic injury, renal failure

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedRhabdomyolysis — documented in both oral and IV cases[26]model confidence 90%
Verified

Abstract documents CK of 4,457 IU/dL in an IV case, consistent with rhabdomyolysis.

CK 4,457 IU/dL

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAcute kidney injury — secondary to vasoconstriction, rhabdomyolysis, hyperthermia, and volume depletion[8]model confidence 90%
Verified

Abstract documents renal failure in an IV MDPV case. The claimed mechanisms are reasonable inferences from the concurrent rhabdomyolysis and hyperthermia documented in the same case.

rhabdomyolysis, cardiac injury, hepatic injury, renal failure

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAcute kidney injury — secondary to vasoconstriction, rhabdomyolysis, hyperthermia, and volume depletion[26]model confidence 100%
Verified

Abstract directly documents acute kidney injury with creatinine 15.2 mg/dL in an IV MDPV case.

acute kidney injury (creatinine 15.2 mg/dL)

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedHepatic injury and multiorgan failure[8]model confidence 100%
Verified

Abstract directly documents hepatic injury and multiorgan involvement (cardiac, hepatic, renal) in an IV MDPV case.

rhabdomyolysis, cardiac injury, hepatic injury, renal failure

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedSeizures, stroke, and cerebral edema[2]model confidence 100%
Verified

Abstract directly lists seizures, stroke, and cerebral edema as documented physical complications.

rhabdomyolysis, seizures, stroke, cerebral edema, MI, death

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMyocardial infarction and cardiorespiratory collapse[2]model confidence 100%
Verified

Abstract directly lists MI and death as documented complications of MDPV intoxication.

seizures, stroke, cerebral edema, MI, death

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedExcited delirium syndrome — a state of extreme agitation, hyperthermia, and autonomic instability with significant mortality risk[2]model confidence 90%
Verified

Abstract documents the components of excited delirium (agitation, hyperthermia, cardiovascular instability, death) as features of MDPV intoxication.

Physical: tachycardia, hypertension, arrhythmias, hyperthermia... Behavioral: panic, anxiety, agitation... death.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedExcited delirium syndrome — a state of extreme agitation, hyperthermia, and autonomic instability with significant mortality risk[3]model confidence 100%
Verified

Abstract directly identifies excited delirium syndrome in a fatal MDPV case.

Excited delirium syndrome. First published case of idiosyncratic MDPV reaction.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIntravenous administration is associated with the most severe presentations, including multiorgan failure and acute kidney injury with choreoathetoid movements and gustatory/olfactory hallucinations.[8]model confidence 90%
Verified

Abstract documents severe multiorgan failure with IV MDPV. Choreoathetoid movements and gustatory/olfactory hallucinations are covered by co-cited reference [39]; this citation supports the multiorgan failure component.

25-year-old injected bath salts; severe agitation, hyperthermia, tachycardia; rhabdomyolysis, cardiac injury, hepatic injury, renal failure.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIntravenous administration is associated with the most severe presentations, including multiorgan failure and acute kidney injury with choreoathetoid movements and gustatory/olfactory hallucinations.[26]model confidence 100%
Verified

Abstract directly documents IV MDPV with choreoathetosis, gustatory and olfactory hallucinations, and acute kidney injury.

IV MDPV bath salts: sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, acute kidney injury (creatinine 15.2 mg/dL).

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedConfirmation requires GC-MS or LC-MS/MS.[2]model confidence 90%
Verified

Abstract states MDPV is not detected by routine drug screens, which directly implies confirmation requires specialized analytical methods such as GC-MS or LC-MS/MS.

Not detected by routine drug screens.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedConfirmation requires GC-MS or LC-MS/MS.[26]model confidence 90%
Verified

Abstract notes MDPV was not detected on standard screens, supporting the need for specialized confirmation methods.

Not detected on standard screens.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMurray et al. (2012) reported the first documented MDPV death in the United States.[36]model confidence 90%
Verified

Abstract directly describes the first reported death from MDPV use, consistent with the claim.

First reported death from MDPV use.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedWyman et al. (2013) established that blood MDPV concentrations ≥0.4 μg/mL (400 ng/mL) are sufficient to cause death via cardiac arrhythmia, with uniform tissue distribution at 0.4–0.6 μg/mL and higher concentrations (>0.8 μg/mL) in detoxification organs.[29]model confidence 100%
Verified

Abstract directly confirms all three quantitative claims: lethal threshold ≥0.4 μg/mL, uniform tissue distribution 0.4–0.6 μg/mL, detoxification organ concentrations >0.8 μg/mL, and cardiac arrhythmia as cause of death.

Postmortem MDPV distribution in tissues 0.4-0.6 μg/mL uniformly; detoxification organs (kidney, liver, bile) > 0.8 μg/mL. Blood concentration ≥0.4 μg/mL judged sufficient to cause death. Cause of death: cardiac arrhythmia from MDPV intoxication.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedWright et al. (2013) reported two fatalities with blood concentrations of 39 and 130 ng/mL. Recreationally encountered blood concentrations range from 24–241 ng/mL.[28]model confidence 100%
Verified

Abstract directly confirms two fatalities at 39 and 130 ng/mL and recreational blood range 24–241 ng/mL.

Two MDPV deaths; blood concentrations 39 and 130 ng/mL... Recreational blood range: 24-241 ng/mL

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedWright et al. (2013) reported two fatalities with blood concentrations of 39 and 130 ng/mL. Recreationally encountered blood concentrations range from 24–241 ng/mL.[28]model confidence 100%
Verified

Duplicate evaluation of same pair — abstract directly confirms all stated figures.

Two MDPV deaths; blood concentrations 39 and 130 ng/mL... Recreational blood range: 24-241 ng/mL

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedDesharnais et al. (2017) documented a fatal idiosyncratic reaction at only 6 ng/mL blood MDPV — far below the recreational range — via excited delirium progressing to cardiac arrest.[3]model confidence 100%
Verified

Abstract directly documents cardiac arrest at 6 ng/mL, excited delirium syndrome, and characterizes the reaction as idiosyncratic.

Fatal case: cardiac arrest with MDPV blood concentrations only 6 ng/mL (idiosyncratic). Excited delirium syndrome.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedRat studies showed no overt acute toxicity at subcutaneous doses up to 4 mg/kg[21]model confidence 75%
Verified

Abstract reports moderate hyperthermia and stereotypy at 4 mg/kg but no deaths or severe organ failure, consistent with no overt acute toxicity in the traditional toxicological sense. Pharmacological effects at 4 mg/kg do not constitute frank acute toxicity.

4 mg/kg: stereotypy and disrupted PPI. Moderate hyperthermia exacerbated in group-housed animals.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe cardiotoxic EC₅₀ was 228 μM, approximately 90-fold higher than the neurobehavioral EC₅₀ of 2.51 μM — indicating that cardiotoxicity requires substantially higher concentrations than behavioral effects in this model[30]model confidence 100%
Verified

Abstract directly states EC50=228 μM (cardiotoxic) and locomotor EC50=2.51 μM. The ratio 228/2.51 ≈ 90.8 is accurately described as 'approximately 90-fold'; the abstract's own characterization of 'nearly 100x' is consistent.

MDPV causes concentration-dependent bradycardia and AV conduction block (EC50=228μM cardiotoxic); locomotor EC50=2.51μM. Cardiotoxic thresholds nearly 100x higher than neurobehavioral effects.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveDirect interference with cardiac repolarization is proposed, not mediated through KCNH6a or KCNQ1 gene expression changes.[30]model confidence 40%
Inconclusive

Abstract notes transcriptional changes in dopaminergic and stress-responsive genes but does not specifically mention KCNH6a, KCNQ1, or the proposed cardiac repolarization mechanism. This specific claim cannot be verified from the abstract.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAcute psychosis — paranoid delusions and hallucinations (visual and auditory) occur in 26–40% of emergency presentations. The psychotic presentation can be indistinguishable from acute schizophrenia.[9]model confidence 90%
Verified

Abstract confirms hallucinations/delusions in 26.7% of poison center cases, consistent with the lower bound of the claimed 26–40% range.

hallucinations/delusions (26.7%)

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAcute psychosis — paranoid delusions and hallucinations (visual and auditory) occur in 26–40% of emergency presentations. The psychotic presentation can be indistinguishable from acute schizophrenia.[14]model confidence 90%
Verified

Abstract confirms delusions/hallucinations in 40% of Michigan ED cases, consistent with the upper bound of the claimed 26–40% range.

delusions/hallucinations 40%

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAcute psychosis — paranoid delusions and hallucinations (visual and auditory) occur in 26–40% of emergency presentations. The psychotic presentation can be indistinguishable from acute schizophrenia.[2]model confidence 90%
Verified

Abstract directly lists paranoia, hallucinations, and psychosis as behavioral manifestations of MDPV intoxication.

Behavioral: panic, anxiety, agitation, paranoia, hallucinations, psychosis

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedUnusual perceptual disturbances — gustatory and olfactory hallucinations have been documented in at least one intravenous case.[26]model confidence 100%
Verified

Abstract directly documents gustatory and olfactory hallucinations in an IV MDPV case.

gustatory and olfactory hallucinations

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveShared psychotic phenomena — a case of shared paranoid delusions in a couple using bath salts has been reported.[27]model confidence 50%
Inconclusive

Abstract not available. Scope indicates this case report covers shared hallucinations and paranoid delusions from bath salts use, suggesting it would support the claim, but cannot be verified.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusivePersistent psychosis — visual hallucinations and paranoia persisting after MDPV cessation have been documented, requiring electroconvulsive therapy for resolution.[10]model confidence 50%
Inconclusive

Abstract not available. Scope indicates the paper covers ECT for persistent MDPV psychosis, suggesting it would directly support this claim.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedChronic psychiatric effects — repeated MDPV use is associated with acute psychosis, hypomania, paranoid ideation, and persistent delusions.[31]model confidence 100%
Verified

Abstract directly states chronic cathinone use induces acute psychosis, hypomania, paranoid ideation, and delusions.

Chronic cathinone use induces acute psychosis, hypomania, paranoid ideation, delusions similar to ATS effects.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedSuicidal ideation and self-mutilation — documented in clinical presentations.[2]model confidence 100%
Verified

Abstract directly lists suicidal ideation and self-mutilation as behavioral manifestations of MDPV intoxication.

suicidal ideation, self-mutilation, violent behavior

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveAcute tolerance develops rapidly through DAT downregulation and membrane internalization in striatal tissue[11]model confidence 50%
Inconclusive

Abstract not available. Scope indicates this paper covers DAT internalization mechanisms, but cannot be verified from the abstract.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAcute tolerance develops rapidly through DAT downregulation and membrane internalization in striatal tissue[25]model confidence 95%
Verified

Abstract directly confirms DAT downregulation in striatum and shift in subcellular distribution (internalization) at 24 hours post-dose.

MDPV downregulated DAT in striatum and produced shift in subcellular distribution 24h post-dose

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedProlonged brain network reorganization — increased clustering and altered functional connectivity patterns persisting 24 hours post-exposure — suggests that neuroadaptive changes extend well beyond the acute pharmacokinetic window.[25]model confidence 100%
Verified

Abstract directly confirms prolonged brain functional network reorganization with increased clustering coefficient at 24 hours post-dose.

prolonged brain functional network reorganization. Increased clustering coefficient, rich club index.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMDPV maintains intravenous self-administration at all doses tested (0.05–0.2 mg/kg/infusion) in rats.[7]model confidence 100%
Verified

Abstract directly confirms IVSA maintained across all doses (0.05, 0.1, 0.2 mg/kg/infusion).

MDPV maintained IVSA across all doses (0.05, 0.1, 0.2 mg/kg/infusion).

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedUnder long-access conditions (6 hr/day), rats escalate MDPV intake at rates comparable to methamphetamine.[7]model confidence 90%
Verified

Abstract confirms long-access conditions led to escalation of intake similar to methamphetamine. The 6 hr/day specification is not in the abstract but is a standard long-access protocol and is not contradicted.

Long-access conditions led to escalation of intake similar to methamphetamine.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveBinge-like acquisition of self-administration is documented.[24]model confidence 50%
Inconclusive

Abstract not available. Scope directly indicates this paper covers binge-like MDPV self-administration patterns.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMDPV lowers ICSS reward thresholds at all tested doses (0.1–2.0 mg/kg IP).[7]model confidence 100%
Verified

Abstract directly confirms ICSS threshold reduction at all doses (0.1–2 mg/kg IP).

MDPV lowered ICSS thresholds at all doses (0.1-2 mg/kg IP).

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedInhaled MDPV (via e-cigarette model) produces locomotor stimulation and ICSS threshold reduction comparable to intraperitoneal injection.[32]model confidence 100%
Verified

Abstract directly confirms inhaled MDPV increased locomotor activity and reduced ICSS thresholds comparable to IP injection.

inhaled MDPV (25-100 mg/mL) increased locomotor activity... MDPV vapor reduced ICSS reward threshold comparable to IP injection of 0.5-1.0 mg/kg.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedClinical evidence confirms MDPV addiction as a real-world phenomenon: Casati et al. (2025) documented a 58-year-old with established MDPV addiction in a polydrug fatality case[17]model confidence 100%
Verified

Abstract directly describes a fatal case involving a 58-year-old with history of MDPV addiction, confirming MDPV addiction as a documented clinical entity.

Fatal case: 58-year-old with history of MDPV addiction found dead... Confirms MDPV addiction history

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusivePenders et al. (2013) documented persistent psychiatric sequelae following chronic MDPV use.[10]model confidence 50%
Inconclusive

Abstract not available. Based on scope (persistent psychosis from repeated MDPV use treated with ECT), this citation would directly support the claim.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveThis concern is supported by experimental data: MDPV and caffeine combinations produce reinforcing effects greater than the additive prediction in rat self-administration models, and cardiovascular effects of MDPV-methylone-caffeine mixtures have been directly characterized in rats.[33]model confidence 50%
Inconclusive

Abstract not available. Scope indicates this paper covers bath salts mixture reinforcement effects.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveThis concern is supported by experimental data: MDPV and caffeine combinations produce reinforcing effects greater than the additive prediction in rat self-administration models, and cardiovascular effects of MDPV-methylone-caffeine mixtures have been directly characterized in rats.[34]model confidence 50%
Inconclusive

Abstract not available. Scope indicates this paper covers cardiovascular effects of bath salts mixtures including MDPV.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe tramadol interaction carries the additional risk of seizure threshold lowering (tramadol's known epileptogenic potential) compounded by MDPV's documented seizure risk.[2]model confidence 90%
Verified

Abstract directly documents seizures as a physical complication of MDPV intoxication, confirming MDPV's documented seizure risk.

rhabdomyolysis, seizures, stroke, cerebral edema, MI, death

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMDPV's metabolism via CYP2C19, CYP2D6, and CYP1A2 creates theoretical risk of elevated MDPV exposure when coadministered with inhibitors of these enzymes[13]model confidence 90%
Verified

Abstract confirms CYP2C19, CYP2D6, and CYP1A2 as primary metabolic enzymes; theoretical interaction risk from inhibitor co-administration is a standard pharmacokinetic inference.

CYP 2C19, CYP 2D6 and CYP 1A2 catalyze initial demethylenation step.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedManagement is supportive and extrapolated from cocaine/amphetamine toxidrome protocols: * IV benzodiazepines for agitation and seizure control (first-line) * Aggressive external cooling for hyperthermia * IV fluid resuscitation for rhabdomyolysis and renal protection * Small-dose haloperidol for choreoathetoid movements not controlled by benzodiazepines * ICU monitoring for cardiac, renal, and hepatic function * Physical restraints for imminent self-harm or violence[35]model confidence 85%
Verified

Abstract describes the adverse effects requiring these interventions (agitation, seizures, hyperthermia, rhabdomyolysis) and confirms no specific antidote, supporting the extrapolated supportive management approach.

adverse effects: tachycardia, hypertension, agitation, seizures, paranoia, hallucinations, hyperthermia, metabolic acidosis, rhabdomyolysis; no specific antidote.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedManagement is supportive and extrapolated from cocaine/amphetamine toxidrome protocols: * IV benzodiazepines for agitation and seizure control (first-line) * Aggressive external cooling for hyperthermia * IV fluid resuscitation for rhabdomyolysis and renal protection * Small-dose haloperidol for choreoathetoid movements not controlled by benzodiazepines * ICU monitoring for cardiac, renal, and hepatic function * Physical restraints for imminent self-harm or violence[9]model confidence 95%
Verified

Abstract directly states benzodiazepines were used in 46% of cases and haloperidol for agitation, confirming the first-line treatment approach.

Treatment: benzodiazepines (46%), haloperidol for agitation.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAbsolute contraindications: * Pre-existing cardiovascular disease — MDPV's potent sympathomimetic effects (tachycardia in 63% of presentations, hypertension in 25%) and documented myocardial infarction cases make any significant cardiovascular compromise a high-risk setting. * Psychotic disorders — MDPV induces acute psychosis in 26–40% of emergency presentations and can precipitate persistent psychotic states. * Concurrent stimulant use — additive/synergistic sympathomimetic toxicity documented.[2]model confidence 90%
Verified

Abstract documents cardiovascular toxicity (tachycardia, hypertension, arrhythmias, MI), psychotic manifestations (paranoia, hallucinations, psychosis), and the full sympathomimetic toxidrome, supporting all three listed contraindications.

Physical: tachycardia, hypertension, arrhythmias, hyperthermia... Behavioral: panic, anxiety, agitation, paranoia, hallucinations, psychosis

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAbsolute contraindications: * Pre-existing cardiovascular disease — MDPV's potent sympathomimetic effects (tachycardia in 63% of presentations, hypertension in 25%) and documented myocardial infarction cases make any significant cardiovascular compromise a high-risk setting. * Psychotic disorders — MDPV induces acute psychosis in 26–40% of emergency presentations and can precipitate persistent psychotic states. * Concurrent stimulant use — additive/synergistic sympathomimetic toxicity documented.[9]model confidence 95%
Verified

Abstract provides the exact frequency data (tachycardia 53.3%, hallucinations/delusions 26.7%, hypertension 25.2%) cited in the contraindications.

tachycardia (53.3%), agitation (50.4%), hallucinations/delusions (26.7%), hypertension (25.2%)

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveAbsolute contraindications: * Pre-existing cardiovascular disease — MDPV's potent sympathomimetic effects (tachycardia in 63% of presentations, hypertension in 25%) and documented myocardial infarction cases make any significant cardiovascular compromise a high-risk setting. * Psychotic disorders — MDPV induces acute psychosis in 26–40% of emergency presentations and can precipitate persistent psychotic states. * Concurrent stimulant use — additive/synergistic sympathomimetic toxicity documented.[10]model confidence 40%
Inconclusive

Abstract not available. The ECT case report scope is relevant to psychotic disorders but the full contraindications claim cannot be verified.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveAbsolute contraindications: * Pre-existing cardiovascular disease — MDPV's potent sympathomimetic effects (tachycardia in 63% of presentations, hypertension in 25%) and documented myocardial infarction cases make any significant cardiovascular compromise a high-risk setting. * Psychotic disorders — MDPV induces acute psychosis in 26–40% of emergency presentations and can precipitate persistent psychotic states. * Concurrent stimulant use — additive/synergistic sympathomimetic toxicity documented.[33]model confidence 40%
Inconclusive

Abstract not available. The mixtures paper scope supports the concurrent stimulant use concern but cannot be verified.

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveAbsolute contraindications: * Pre-existing cardiovascular disease — MDPV's potent sympathomimetic effects (tachycardia in 63% of presentations, hypertension in 25%) and documented myocardial infarction cases make any significant cardiovascular compromise a high-risk setting. * Psychotic disorders — MDPV induces acute psychosis in 26–40% of emergency presentations and can precipitate persistent psychotic states. * Concurrent stimulant use — additive/synergistic sympathomimetic toxicity documented.[34]model confidence 40%
Inconclusive

Abstract not available. The cardiovascular mixtures paper scope supports the cardiovascular concern but cannot be verified.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedRelative contraindications: * Bipolar disorder — manic/hypomanic episodes documented with cathinone use * Renal impairment — MDPV causes acute kidney injury through multiple mechanisms * Hepatic impairment — hepatic injury documented; CYP-dependent metabolism may lead to impaired clearance * Seizure disorders — seizures documented in clinical presentations * Pregnancy — no safety data; potent sympathomimetic effects present obvious fetal risks[31]model confidence 90%
Verified

Abstract directly confirms hypomania and psychosis with chronic cathinone use, supporting the bipolar disorder contraindication.

Chronic cathinone use induces acute psychosis, hypomania, paranoid ideation, delusions similar to ATS effects.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedRelative contraindications: * Bipolar disorder — manic/hypomanic episodes documented with cathinone use * Renal impairment — MDPV causes acute kidney injury through multiple mechanisms * Hepatic impairment — hepatic injury documented; CYP-dependent metabolism may lead to impaired clearance * Seizure disorders — seizures documented in clinical presentations * Pregnancy — no safety data; potent sympathomimetic effects present obvious fetal risks[8]model confidence 90%
Verified

Abstract documents hepatic injury and renal failure in an IV case, supporting the hepatic and renal impairment contraindications.

rhabdomyolysis, cardiac injury, hepatic injury, renal failure

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedRelative contraindications: * Bipolar disorder — manic/hypomanic episodes documented with cathinone use * Renal impairment — MDPV causes acute kidney injury through multiple mechanisms * Hepatic impairment — hepatic injury documented; CYP-dependent metabolism may lead to impaired clearance * Seizure disorders — seizures documented in clinical presentations * Pregnancy — no safety data; potent sympathomimetic effects present obvious fetal risks[26]model confidence 90%
Verified

Abstract documents severe AKI (creatinine 15.2 mg/dL), supporting the renal impairment contraindication.

acute kidney injury (creatinine 15.2 mg/dL)

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedRelative contraindications: * Bipolar disorder — manic/hypomanic episodes documented with cathinone use * Renal impairment — MDPV causes acute kidney injury through multiple mechanisms * Hepatic impairment — hepatic injury documented; CYP-dependent metabolism may lead to impaired clearance * Seizure disorders — seizures documented in clinical presentations * Pregnancy — no safety data; potent sympathomimetic effects present obvious fetal risks[8]model confidence 90%
Verified

Duplicate citation for same claim — abstract confirms hepatic and renal injury.

hepatic injury, renal failure

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedRelative contraindications: * Bipolar disorder — manic/hypomanic episodes documented with cathinone use * Renal impairment — MDPV causes acute kidney injury through multiple mechanisms * Hepatic impairment — hepatic injury documented; CYP-dependent metabolism may lead to impaired clearance * Seizure disorders — seizures documented in clinical presentations * Pregnancy — no safety data; potent sympathomimetic effects present obvious fetal risks[2]model confidence 90%
Verified

Abstract directly lists seizures as a complication and documents the full sympathomimetic toxidrome relevant to multiple contraindications.

rhabdomyolysis, seizures, stroke, cerebral edema, MI, death

checked by claude-sonnet-4-6 · Apr 25, 2026

clinical evidence10 claims8verified2inconclusive
verifiedMultiorgan failure (IV route): Borek (2012) described hyperthermia and multiorgan failure following intravenous MDPV injection, highlighting the severe toxicity potential of parenteral administration.[8]model confidence 100%
Verified

Abstract directly describes IV injection of bath salts causing hyperthermia, rhabdomyolysis, cardiac injury, hepatic injury, and renal failure — consistent with multiorgan failure.

25-year-old injected bath salts; severe agitation, hyperthermia, tachycardia; rhabdomyolysis, cardiac injury, hepatic injury, renal failure.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIdiosyncratic fatality: Desharnais et al. (2017) reported death via excited delirium and cardiac arrest at a blood MDPV concentration of only 6 ng/mL — far below recreationally encountered levels (24–241 ng/mL).[3]model confidence 100%
Verified

Abstract directly confirms cardiac arrest at 6 ng/mL and excited delirium syndrome. Recreational range context is supplied by co-cited reference.

Fatal case: cardiac arrest with MDPV blood concentrations only 6 ng/mL (idiosyncratic). Excited delirium syndrome.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIdiosyncratic fatality: Desharnais et al. (2017) reported death via excited delirium and cardiac arrest at a blood MDPV concentration of only 6 ng/mL — far below recreationally encountered levels (24–241 ng/mL).[28]model confidence 95%
Verified

This citation provides the recreational blood concentration range (24–241 ng/mL), confirming the claim's contextual statement that 6 ng/mL is far below recreational levels.

Recreational blood range: 24-241 ng/mL

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveSpiller et al. (2011) reported the initial 8 months of experience with confirmed synthetic cathinone exposures, documenting the rapid emergence of MDPV-related cases[15]model confidence 50%
Inconclusive

Abstract not available. Scope indicates this paper covers the first 8 months of regional poison center experience with synthetic cathinones.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe Michigan Department of Community Health documented a concentrated cluster of emergency department visits between November 2010 and March 2011, with tachycardia present in 63% of cases and agitation as the predominant presenting complaint[14]model confidence 100%
Verified

Abstract directly confirms 35 Michigan ED cases, tachycardia 63%, agitation 66% (most common symptom), between November 2010 and March 2011.

35 Michigan ED bath salts cases (MDPV/mephedrone). Agitation 66%, tachycardia 63%

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMurphy et al. (2013) reported a regional poison center series in which hypertension was documented in 25% of cases and paranoia was a frequent psychiatric feature.[9]model confidence 90%
Verified

Abstract directly confirms hypertension in 25.2% of cases. Paranoia as a psychiatric feature is consistent with the hallucinations/delusions (26.7%) reported.

hypertension (25.2%)... hallucinations/delusions (26.7%)

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedTreatment is supportive: intravenous benzodiazepines for agitation and seizures, aggressive cooling for hyperthermia, IV fluid resuscitation for rhabdomyolysis, and ICU monitoring for cardiac and renal function.[2]model confidence 100%
Verified

Abstract directly states treatment includes IV benzodiazepines and supportive care, and lists the complications requiring these interventions.

Treatment: IV benzodiazepines, supportive care.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedAcute kidney injury with unusual sensory phenomena: Sutamtewagul et al. (2014) reported an IV MDPV case presenting with sympathomimetic syndrome, choreoathetoid movements, gustatory and olfactory hallucinations, and acute kidney injury.[26]model confidence 100%
Verified

Abstract directly documents all stated features: sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, and AKI in an IV MDPV case.

IV MDPV bath salts: sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, acute kidney injury (creatinine 15.2 mg/dL).

checked by claude-sonnet-4-6 · Apr 25, 2026

inconclusiveShared paranoid delusions: Springs (2015) reported a couple presenting with shared auditory/visual hallucinations and paranoid delusions following concurrent "bath salts" use.[27]model confidence 50%
Inconclusive

Abstract not available. Scope describes case report covering shared auditory/visual hallucinations and paranoid delusions from bath salts use.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMDPV is not detected by routine immunoassay urine drug screens[2]model confidence 100%
Verified

Abstract directly states MDPV is not detected by routine drug screens.

Not detected by routine drug screens.

checked by claude-sonnet-4-6 · Apr 25, 2026

comparative pharmacology4 claims4verified
verifiedMDPV and cocaine share a common mechanism as DAT/NET reuptake inhibitors, but MDPV is approximately 50-fold more potent at human DAT and at least 10-fold more potent than cocaine in producing locomotor activation, tachycardia, and hypertension in rats[6]model confidence 100%
Verified

Abstract directly confirms MDPV is approximately 50-fold more potent than cocaine at hDAT.

MDPV ~50-fold more potent than cocaine at hDAT

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedMDPV and cocaine share a common mechanism as DAT/NET reuptake inhibitors, but MDPV is approximately 50-fold more potent at human DAT and at least 10-fold more potent than cocaine in producing locomotor activation, tachycardia, and hypertension in rats[1]model confidence 100%
Verified

Abstract directly confirms at least 10-fold greater in vivo potency than cocaine for locomotor activation, tachycardia, and hypertension, and confirms the reuptake inhibitor mechanism.

MDPV at least 10x more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedThe mechanistic divide between MDPV (pure inhibitor) and mephedrone/methylone (substrate-type releasers) produces qualitatively different pharmacological and subjective profiles[5]model confidence 90%
Verified

Abstract confirms MDPV is a selective DAT/NET inhibitor and does not evoke monoamine release unlike amphetamine-type drugs, supporting the mechanistic distinction.

highly potent and selective DA and NA transporter inhibitors; unlike amphetamines did not evoke release of monoamines.

checked by claude-sonnet-4-6 · Apr 25, 2026

verifiedIn long-access self-administration paradigms (6 hours/day), rats escalate MDPV intake at rates comparable to methamphetamine[7]model confidence 95%
Verified

Abstract directly confirms long-access conditions led to escalation of intake similar to methamphetamine.

Long-access conditions led to escalation of intake similar to methamphetamine.

checked by claude-sonnet-4-6 · Apr 25, 2026

05

Coverage & Gaps

effect links
68 links · 68 approved · 34 audited0/68 with evidence basis
interactions
3 approved pairs0/3 graded
06

Research Trail

substance-article pipeline-v5 Apr 25, 2026

StepSourceQueryResults
1database lookupPubChemMDPV1 result, 1 selected
selection rationale

Only result, confirmed chemical identity data

2literature searchPubMedMDPV 3,4-methylenedioxypyrovalerone pharmacology15 results, 1 selected
selection rationale

Only article directly studying MDPV; others were general cathinone or unrelated papers

3literature searchPubMedMDPV bath salts toxicology case report overdose2 results, 2 selected
selection rationale

Both relevant as MDPV clinical reports

4literature searchOpenAlexMDPV methylenedioxypyrovalerone synthetic cathinone10 results, 6 selected
selection rationale

All highly cited and directly relevant to MDPV pharmacology or toxicology

5document retrievalPubMedPMID 230728361 result, 1 selected
selection rationale

Landmark paper on MDPV pharmacology

6document retrievalPubMedPMID 222715651 result, 1 selected
selection rationale

First reported fatality case report

7document retrievalPubMedPMID 223870851 result, 1 selected
selection rationale

Key case report on MDPV clinical toxicity

8literature searchPubMedMDPV dopamine transporter inhibitor DAT binding9 results, 4 selected
selection rationale

All directly study MDPV at DAT or compare MDPV to cocaine at transporter level

9literature searchPubMedmethylenedioxypyrovalerone self-administration abuse liability rat10 results, 2 selected
selection rationale

Directly relevant to MDPV reinforcing effects and abuse liability

10web searchWebSearchMDPV 3,4-methylenedioxypyrovalerone history synthesis Boehringer Ingelheim patent 196910 results, 2 selected
selection rationale

Confirms synthesis history and initial patent

11web searchWebSearchMDPV legal status DEA Schedule I scheduling history US UK EU10 results, 3 selected
selection rationale

Scheduling timeline for major jurisdictions

12web searchWebSearchMDPV methylenedioxypyrovalerone pharmacokinetics metabolism human CYP enzymes half-life10 results, 5 selected
selection rationale

Core PK/metabolism papers

13web searchWebSearchMDPV bath salts Australia Schedule 9 prohibited substance scheduling10 results, 1 selected
selection rationale

Australian legal scheduling

14document retrievalPMCMDPV neuropharmacology metabolites1 result, 1 selected
selection rationale

Critical stereochemistry and metabolite pharmacology data

15document retrievalFrontiersMDPV pharmacokinetics behavior rats1 result, 1 selected
selection rationale

Most comprehensive MDPV pharmacokinetic/behavioral profile in rats

16clinical trial searchClinicalTrials.govMDPV methylenedioxypyrovalerone0 results
selection rationale

No trials registered

17literature searchPubMedMDPV bath salts intoxication psychosis agitation emergency department clinical presentation1 result, 1 selected
selection rationale

Key clinical overview paper

18literature searchPubMedMDPV cathinone tramadol serotonin toxicity death interaction0 results
selection rationale

No direct evidence for tramadol-MDPV interaction in literature; seed data interaction not confirmed by published sources

19literature searchPubMedMDPV bath salts fatality blood concentration postmortem forensic5 results, 4 selected
selection rationale

Forensic concentration data and fatality cases

20literature searchPubMedMDPV bath salts fatality postmortem tissue distribution forensic5 results, 4 selected
selection rationale

Key forensic concentration data and fatality documentation

21literature searchPubMedMDPV bath salts intoxication psychosis agitation emergency department clinical presentation1 result, 1 selected
selection rationale

Most comprehensive single-source clinical MDPV overview

22literature searchPubMedMDPV nucleus accumbens dopamine tachycardia cardiovascular sympathomimetic mechanism2 results, 1 selected
selection rationale

Unique case documenting unusual sensory effects from MDPV

23literature searchOpenAlexMDPV self-administration intravenous reinforcing rats cathinone8 results, 2 selected
selection rationale

Key self-administration paper and public health review

24literature searchPubMedAarde MDPV binge self-administration 20151 result, 1 selected
selection rationale

MDPV binge self-administration characterization

25data extractionWebSearch/DEA/WikipediaMDPV CAS number physical properties SMILES5 results, 2 selected
selection rationale

Fills chemical identity gaps not returned by PubChem API tool

Research document (raw, unedited pipeline output)
# Research Output: MDPV (3,4-Methylenedioxypyrovalerone)

**PSX ID:** PSX-0239  
**Research Date:** 2026-04-25  
**Generation Provenance:** eec5add4-0bb0-4284-af71-34f5dfcbcac0

---

## Chemical Identity

**Confirmed via PubChem CID 20111961 [Ref database_lookup]:**

- **Molecular formula:** C₁₆H₂₁NO₃ — matches seed data
- **Molecular weight:** 275.34 g/mol — matches seed data
- **IUPAC name:** 1-(1,3-benzodioxol-5-yl)-2-pyrrolidin-1-ylpentan-1-one — matches seed data
- **InChIKey:** SYHGEUNFJIGTRX-UHFFFAOYSA-N
- **PubChem CID:** 20111961
- **CAS number:** 687603-66-3 (web-retrieved; not API-verified)
- **SMILES:** Not returned by PubChem API call; web sources report: O=C(c1ccc2c(c1)OCO2)[C@@H](N1CCCC1)CCC (canonical); not api_verified — generation agent should retrieve from PubChem CID 20111961 directly

**Physical properties (web-retrieved):**
- Appearance: white crystalline powder (hydrochloride salt form); brown/yellow-green (free base); grey powder in some European street samples
- Solubility: soluble in chloroform, methanol, and water (HCl salt form)
- Melting point: approximately 200°C (HCl salt; web-sourced, unverified)

**Stereochemistry:**
MDPV contains one chiral center. Bath salt products consist of the racemate (equal mixture of S and R enantiomers). The S-isomer is approximately 100-fold more potent than the R-isomer at the dopamine transporter (S-MDPV: DAT IC₅₀ = 2.1 nM; R-MDPV: DAT IC₅₀ = 382 nM) (Baumann et al. 2017 [Ref 24]). The S-isomer is also responsible for most abuse-related behavioral effects in rodent models.

**Discrepancies with seed data:** Seed data lists SMILES and PubChem CID fields as empty. These are now confirmed: CID 20111961, InChIKey SYHGEUNFJIGTRX-UHFFFAOYSA-N.

---

## Pharmacology

### Mechanism of Action

MDPV is a highly potent and selective catecholamine reuptake inhibitor. It blocks the plasma membrane dopamine transporter (DAT) and norepinephrine transporter (NET) with nanomolar potency but has minimal activity at the serotonin transporter (SERT). Unlike amphetamine-class cathinones (mephedrone, methylone, MDMA), MDPV does **not** act as a transporter substrate and does **not** induce monoamine release (Baumann et al. 2013 [Ref 1]; Simmler et al. 2012 [Ref 6]; Eshleman et al. 2013 [Ref 10]).

### Binding Affinities (Transporter Inhibition IC₅₀)

| Target | IC₅₀ (MDPV, racemate) | Source |
|--------|----------------------|--------|
| DAT (rat synaptosomes) | 4.1 nM | Baumann et al. 2013 [Ref 1] |
| NET (rat synaptosomes) | 26 nM | Baumann et al. 2013 [Ref 1] |
| SERT (rat synaptosomes) | 3,349 nM | Baumann et al. 2013 [Ref 1] |
| DAT (human, hDAT) | ~50× more potent than cocaine | Steele et al. 2021 [Ref 7] |
| S-MDPV at DAT | 2.1 nM | Baumann et al. 2017 [Ref 24] |
| R-MDPV at DAT | 382 nM | Baumann et al. 2017 [Ref 24] |
| S-MDPV at NET | 9.8 nM | Baumann et al. 2017 [Ref 24] |

MDPV also has high-nanomolar to low-micromolar affinity for sigma-1 (hSigma1) receptors, though this is unlikely to explain its primary psychoactive effects (Eshleman et al. 2013 [Ref 10]). It is not a TAAR1 ligand (Simmler et al. 2012 [Ref 6]).

### Dopaminergic Effects In Vivo

- MDPV (0.1–0.3 mg/kg IV) significantly increases extracellular dopamine in the nucleus accumbens of rats (Baumann et al. 2013 [Ref 1])
- At 0.1–3.0 mg/kg subcutaneous, MDPV is at least **10 times more potent** than cocaine at producing locomotor activation, tachycardia, and hypertension in rats (Baumann et al. 2013 [Ref 1])
- Clears endogenous dopamine in mouse striatal slices with greater potency and efficacy than cocaine by fast-scan cyclic voltammetry (Baumann et al. 2013 [Ref 1])

### Dopamine Transporter Regulation

Acute MDPV exposure in rats downregulates DAT expression in striatum and induces rapid DAT internalization from the membrane surface. This is associated with prolonged alterations in brain functional connectivity at 24 hours post-dose (Colon-Perez et al. 2018 [Ref 9]; Lopez-Arnau et al. 2019 [Ref 8]).

### Blood-Brain Barrier Permeability

MDPV exhibited particularly high BBB permeability in an in vitro model — among the highest of the cathinones tested (Simmler et al. 2012 [Ref 6]).

### Structural Basis for DAT Selectivity

Four non-conserved residues in hDAT (vs. dDAT and hSERT) — A117, F318, P323, and D121 — control MDPV's exceptional selectivity for hDAT by stabilizing binding and controlling access to the S1 binding site (Steele et al. 2021 [Ref 7]).

### Pharmacokinetic Data

**Note: No human pharmacokinetic studies have been published. All PK data is from rat models.**

| Parameter | Value | Species/Route | Source |
|-----------|-------|--------------|--------|
| Tmax (plasma) | 12.9–18.6 min | Rat, subcutaneous | Anizan et al. 2016 [Ref 25] |
| Tmax (brain peak) | <30 min | Rat, subcutaneous | Horsley et al. 2018 [Ref 26] |
| Plasma half-life | ~80 min | Rat (from referenced prior data) | Horsley et al. 2018 [Ref 26] |
| Brain/serum ratio | ~2 (lasting ~120 min) | Rat, subcutaneous | Horsley et al. 2018 [Ref 26] |
| Kinetics | Linear (dose-proportional) | Rat, 0.5–2.0 mg/kg sc | Anizan et al. 2016 [Ref 25] |
| Cmax (0.5 mg/kg sc) | 74.2 μg/L | Rat plasma | Anizan et al. 2016 [Ref 25] |
| Cmax (2.0 mg/kg sc) | 271.3 μg/L | Rat plasma | Anizan et al. 2016 [Ref 25] |

Pharmacodynamic effects (locomotor activity, stereotypy) correlate positively with **parent compound** plasma concentrations, not with metabolite levels (Anizan et al. 2016 [Ref 25]; Baumann et al. 2017 [Ref 24]).

### Metabolic Pathway

MDPV is metabolized primarily in the liver via CYP450 enzymes. The initial and primary metabolic step is **demethylenation** of the methylenedioxy group, catalyzed by CYP 2C19, CYP 2D6, and CYP 1A2 (Meyer et al. 2010 [Ref 27]).

**Phase I metabolites (10 identified in human liver microsomes; Negreira et al. 2015 [Ref 28]):**
1. **3,4-Dihydroxypyrovalerone (3,4-catechol-PV)** — major Phase I metabolite; potent DAT inhibitor in vitro (IC₅₀ = 11 nM) but poor CNS penetration; limited behavioral contribution (Baumann et al. 2017 [Ref 24])
2. **4-Hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV)** — major circulating metabolite (highest AUC); much weaker at DAT/NET; does not explain motor effects (Anizan et al. 2016 [Ref 25])
3. Additional metabolites via: aromatic/side-chain hydroxylation, pyrrolidine ring oxidation to lactam, ring opening to carboxylic acid (Meyer et al. 2010 [Ref 27])

**Phase II metabolites:** 6 glucuronide and 2 sulfate conjugates identified (Negreira et al. 2015 [Ref 28])

**Major urinary metabolites in rats:** demethylenyl-MDPV and demethylenyl-methyl-MDPV at 3–4× higher levels than parent drug (Horsley et al. 2018 [Ref 26])

**No CYP induction/inhibition data specific to MDPV in published literature.** CYP involvement (2C19, 2D6, 1A2) suggests potential for drug-drug interactions with substrates/inhibitors of these enzymes, but no specific interaction studies found.

---

## History

### Synthesis and Patent

MDPV was first synthesized by researchers at **Boehringer Ingelheim** (Koppe H, Ludwig G, Zeile K) and patented as a central nervous system stimulant in **1969** (US Patent 3478050, assigned to CH Boehringer Sohn AG and Boehringer Ingelheim GmbH) (Desharnais et al. 2017 [Ref 17]; web sources). The compound was developed as a structural analog of the appetite-suppressant pyrovalerone but was never advanced through clinical trials or approved for medical use.

MDPV is a pyrrolidine derivative of pyrovalerone distinguished by the addition of a 3,4-methylenedioxy (piperonyl) group on the aromatic ring in place of pyrovalerone's 4-methyl group (Coppola & Mondola 2012 [Ref 16]).

### Emergence as a Recreational Drug

- **2004–2005:** MDPV appeared in internet harm reduction forums (psychonaut communities) as a novel psychoactive substance candidate (web sources)
- **2006:** First appeared on illicit drug markets in Europe (Desharnais et al. 2017 [Ref 17])
- **2007:** Detected as a designer drug in a street market sample in Tokyo (web sources)
- **2009:** First published peer-reviewed scientific reports on MDPV (Meyer et al. 2010 [Ref 27] — submitted 2009)
- **2010:** Rapid emergence in the United States; UK classified MDPV as Class B (see Legal Status)
- **2010–2011:** Explosive growth in US emergency department presentations; Poison Control Center volume surge (Spiller et al. 2011 [Ref 36]; Michigan MMWR 2011 [Ref 38])
- **2011–2012:** US DEA emergency scheduling; MDPV reached peak prevalence as the dominant "bath salts" compound
- **2013–2014:** Superseded in EU and US markets by analogs (α-PVP, MDPHP, others) following controlled status; EMCDDA-Europol joint report submitted (2013)
- **Post-2014:** Continued forensic detection and case reports in Europe; MDPV addiction identified as a clinical problem in injection drug-using communities in some regions (Casati et al. 2025 [Ref 40])

### Institutional/Regulatory History

MDPV was primarily identified and characterized through emergency toxicology investigations, not pharmaceutical research. No clinical trials have ever been registered or conducted (ClinicalTrials.gov search, April 2026 [Step 16]).

---

## Subjective Effects

**No controlled human studies exist.** All subjective effect data derives from: (1) clinical case presentations in emergency settings, (2) poison center surveillance data, and (3) user reports on harm reduction forums. This should be stated explicitly in the article.

### Desired Effects (User-Reported)
- Euphoria and cognitive euphoria
- Stimulation, increased energy, wakefulness
- Enhanced motivation and focus
- Increased libido and sexual arousal enhancement (user-reported; consistent with dopaminergic stimulant class effects; no controlled data)
- Empathy enhancement (reported but pharmacologically inconsistent with MDPV's very weak serotonergic profile; may reflect dopaminergic confidence/euphoria)
- Thought acceleration and creativity enhancement

### Adverse Effects Documented in Clinical Cases
- Paranoia, suspiciousness, and frank paranoid delusions (Murphy et al. 2013 [Ref 37]; Michigan MMWR 2011 [Ref 38])
- Visual and auditory hallucinations (Springs 2015 [Ref 14]; Michigan MMWR 2011 [Ref 38])
- Gustatory and olfactory hallucinations documented in at least one IV case (Sutamtewagul et al. 2014 [Ref 39])
- Psychosis indistinguishable from acute schizophrenia (Ross et al. 2012 [Ref 35]; Springs 2015 [Ref 14])
- Severe anxiety, panic attacks
- Aggressive, violent, self-destructive behavior (Ross et al. 2012 [Ref 35])
- Suicidal ideation and self-mutilation (Ross et al. 2012 [Ref 35])
- Compulsive redosing/"binge" pattern (Aarde et al. 2015 [Ref 42]; Watterson et al. 2014 [Ref 33])
- Involuntary movements / choreoathetosis (Sutamtewagul et al. 2014 [Ref 39])
- Restlessness, muscle tension, diarrhea, nausea, headache, appetite suppression consistent with stimulant toxidrome

### Duration (Clinical Descriptions)
Ross et al. 2012 [Ref 35] reports intoxication lasting **6–8 hours** in clinical presentations. Seed database values (total 2–7 hours, onset 15–30 min) are consistent with this range. Aftereffects ("crash") may persist 2–48 hours.

**FLAG:** Seed data lists total duration as 2–7 hours; Ross et al. 2012 reports 6–8 hours intoxication in clinical context. The shorter lower bound may reflect lower doses; the clinical upper bound should be noted. The seed data total duration range is broadly consistent with published sources but the upper bound may be conservative.

### Dose Data
**No published controlled human dosing studies have been conducted.** The seed database values (Threshold: 2 mg; Light: 4–8 mg; Common: 8–14 mg; Strong: 14–25 mg; Heavy: 25+ mg — all oral) are consistent with community harm-reduction consensus and MDPV's high potency (10× cocaine in animal models). **These values cannot be verified against primary literature.** Flag for editorial review.

The DEA has noted MDPV's high potency relative to amphetamines and cocaine in scheduling documentation. Forensic case analyses confirm that recreationally encountered blood concentrations range from 24–241 ng/mL (Wright et al. 2013 [Ref 29]).

---

## Safety & Toxicity

### Acute Toxicity

**Physical toxidrome (documented across multiple case series and poison center data):**
- Tachycardia (63% of cases; Michigan MMWR 2011 [Ref 38])
- Hypertension (25% in Murphy et al. 2013 [Ref 37])
- Hyperthermia (reported in Borek et al. 2012 [Ref 3]; exacerbated in group-housed animals; Horsley et al. 2018 [Ref 26])
- Diaphoresis, tachypnea
- Rhabdomyolysis (Borek et al. 2012 [Ref 3]; Sutamtewagul et al. 2014 [Ref 39])
- Acute kidney injury (Borek et al. 2012 [Ref 3]; Sutamtewagul et al. 2014 [Ref 39]; mechanisms: vasoconstriction, rhabdomyolysis, hyperthermia, volume depletion)
- Cardiac injury, arrhythmias — including AV conduction block documented in zebrafish (Aljabasini et al. 2025 [Ref 4])
- Hepatic injury (Borek et al. 2012 [Ref 3])
- Multiorgan failure (Borek et al. 2012 [Ref 3])
- Seizures (Ross et al. 2012 [Ref 35])
- Stroke, cerebral edema (Ross et al. 2012 [Ref 35])
- Cardiorespiratory collapse (Ross et al. 2012 [Ref 35])
- Myocardial infarction (Ross et al. 2012 [Ref 35])
- Excited delirium syndrome (Ross et al. 2012 [Ref 35]; Desharnais et al. 2017 [Ref 17])

### Fatality Data

**Multiple confirmed fatalities:**
- Murray et al. 2012 [Ref 2]: First reported death from MDPV use (US)
- Wyman et al. 2013 [Ref 30]: Postmortem tissue distribution study; blood ≥0.4 μg/mL (400 ng/mL) judged sufficient to cause death; cause of death: cardiac arrhythmia; uniform tissue distribution at 0.4–0.6 μg/mL; detoxification organs (kidney, liver, bile) >0.8 μg/mL
- Wright et al. 2013 [Ref 29]: Two fatalities; blood concentrations 39 and 130 ng/mL; deaths attributed to natural causes in setting of MDPV abuse
- Desharnais et al. 2017 [Ref 17]: Fatal idiosyncratic reaction at only **6 ng/mL** MDPV blood concentration — significantly below the recreational range; mechanism: excited delirium → cardiac arrest. This demonstrates potential for death even at very low blood concentrations via indirect mechanisms (hyperthermia, catecholamine surge).

**No LD₅₀ value has been published for MDPV in humans or in controlled animal studies.** Animal studies have not produced overt acute toxicity even at the highest doses used (Horsley et al. 2018 [Ref 26]: no signs of acute toxicity at 4 mg/kg sc in rats).

### Psychiatric Toxicity

- Acute psychosis: paranoid delusions, hallucinations in 26–40% of emergency presentations (Murphy et al. 2013 [Ref 37]; Michigan MMWR 2011 [Ref 38])
- Persistent psychosis: documented case of visual hallucinations and paranoia persisting after MDPV cessation, requiring ECT for resolution (Penders et al. 2013 [Ref 13])
- Shared paranoid delusions in couple using bath salts (Springs 2015 [Ref 14])
- Chronic use: acute psychosis, hypomania, paranoid ideation, delusions (Weinstein et al. 2017 [Ref 34])

### Cardiotoxicity (Preclinical)

In zebrafish embryos, MDPV produced concentration-dependent bradycardia and AV conduction block. Cardiotoxic EC₅₀ = 228 μM; neurobehavioral EC₅₀ = 2.51 μM — cardiotoxic threshold approximately 90× higher than neurobehavioral threshold (Aljabasini et al. 2025 [Ref 4]). Direct interference with cardiac repolarization proposed (not via KCNH6a or KCNQ1 gene expression changes).

### Detection

MDPV is **not detected by routine immunoassay drug screens** (Ross et al. 2012 [Ref 35]; Sutamtewagul et al. 2014 [Ref 39]). Confirmation requires GC-MS or LC-MS/MS. This is a critical clinical note — users may present with severe stimulant toxidrome and negative urine drug screens.

---

## Harm Reduction

### Routes of Administration Risk
Clinical literature confirms MDPV is used by: oral ingestion, nasal insufflation, smoking/vaporization, intravenous injection, intramuscular injection, and rectal administration (Ross et al. 2012 [Ref 35]; Nguyen et al. 2016 [Ref 18]).

**FLAG — SEED DATA ERROR:** The seed database lists "Primary ROA: oral" and "Known ROAs: oral" only. This is directly contradicted by published literature. Multiple non-oral routes are documented and associated with more severe toxicity profiles (Borek et al. 2012 [Ref 3] — IV case with multiorgan failure; Sutamtewagul et al. 2014 [Ref 39] — IV case with AKI and unusual sensory effects). This requires correction in the database.

### Emergency Management (Established Clinical Protocols)
Treatment is primarily supportive (Ross et al. 2012 [Ref 35]; Murphy et al. 2013 [Ref 37]):
- IV benzodiazepines for agitation and seizures (first-line sedation)
- Aggressive cooling for hyperthermic patients
- IV fluid resuscitation for rhabdomyolysis and AKI
- Small doses of haloperidol for choreoathetoid movements not controlled by benzodiazepines
- ICU monitoring for cardiac, renal, and hepatic status
- Restraints for self-harm or violent behavior

**No antidote exists.** Management extrapolated from cocaine/amphetamine experience (Debruyne et al. 2014 [Ref 22]).

### Testing
MDPV cannot be identified by standard colorimetric spot tests (Marquis test, etc.) reliably. Laboratory confirmation requires LC-MS/MS or GC-MS.

### Harm Reduction Notes
- MDPV has an extremely compulsive redosing profile; binge patterns observed across species (Watterson et al. 2014 [Ref 33]; Aarde et al. 2015 [Ref 42])
- Psychosis and paranoia can occur even at moderate doses and may be treatment-resistant
- IV use associated with most severe toxicity including multiorgan failure
- Hyperthermia risk is exacerbated in warm environments and with physical exertion (Horsley et al. 2018 [Ref 26]: increased in group-housed animals)

---

## Tolerance & Dependence

### Tolerance Mechanisms
- Acute MDPV exposure induces rapid DAT downregulation and membrane internalization in rat striatum (Lopez-Arnau et al. 2019 [Ref 8]; Colon-Perez et al. 2018 [Ref 9])
- Prolonged brain network reorganization (increased clustering, altered functional connectivity) persists 24 hours post-acute MDPV exposure (Colon-Perez et al. 2018 [Ref 9])
- Tolerance development rate: inferred as rapid from PK/PD data and DAT internalization findings; no controlled tolerance studies in humans

### Dependence/Abuse Liability

**Animal self-administration data:**
- MDPV maintained intravenous self-administration across all doses tested (0.05, 0.1, 0.2 mg/kg/infusion) in rats (Watterson et al. 2014 [Ref 33])
- Long-access (6 hr/day) conditions led to **escalation of intake** comparable to methamphetamine (Watterson et al. 2014 [Ref 33])
- MDPV significantly lowered ICSS reward thresholds at all doses (0.1–2.0 mg/kg IP), indicating robust activation of brain reward circuitry (Watterson et al. 2014 [Ref 33]; Bonano et al. 2014 [Ref 40])
- Binge-like acquisition of MDPV self-administration documented (Aarde et al. 2015 [Ref 42])
- MDPV and caffeine combinations more potently reinforce than predicted by additive interaction (Gannon et al. 2019 [Ref 11])
- Inhaled MDPV (via e-cigarette model) produced locomotor stimulation and ICSS threshold reduction comparable to IP injection (Nguyen et al. 2016 [Ref 18])

**Cross-tolerance:** Expected with other DAT-selective inhibitors (cocaine, methylphenidate, α-PVP). No specific human cross-tolerance data.

**Dependence in clinical setting:**
- Persistent psychosis following cessation documented (Penders et al. 2013 [Ref 13])
- History of MDPV addiction documented in forensic case (Casati et al. 2025 [Ref 40]: 58-year-old with MDPV addiction found dead, polydrug case)
- Withdrawal characterization: no formal studies. By class analogy with cocaine: dysphoria, anhedonia, depression, fatigue expected ("stimulant withdrawal"), but no MDPV-specific withdrawal data exists.

**Dependence data from seed database is absent** — this is appropriate given the lack of published human dependence studies.

---

## Interactions

### Published/Supported Data

**Cardiovascular/sympathomimetic potentiation:**
- Co-ingestion of other stimulants (cocaine, amphetamines, caffeine) expected to potentiate cardiovascular toxicity; MDPV+caffeine combination has greater reinforcing effects than additive prediction (Gannon et al. 2019 [Ref 11]; Seaman et al. 2025 [Ref 15])
- MDPV+methylone combination studied in bath salts context (Gannon et al. 2019 [Ref 11])

**CNS depressant interactions:**
- Alcohol: No specific MDPV-alcohol interaction literature found. General pharmacological concern: alcohol may mask stimulant-induced cardiovascular stress while contributing to dehydration and impaired heat dissipation. **FLAG: Seed data lists as "unknown" — confirmed unresolved in published literature.**

**Psychiatric medications:**
- Haloperidol used clinically in MDPV toxidrome management (Murphy et al. 2013 [Ref 37]); no PK interaction data
- ECT effective for MDPV-induced persistent psychosis (Penders et al. 2013 [Ref 13])

### Flagged Interactions (Not Confirmed by Specific MDPV Literature)

**Tramadol: "Lethal" (seed data)**
No published study specifically documenting a lethal MDPV–tramadol interaction was found in PubMed or OpenAlex searches. Tramadol's serotonergic (SNRI-like) and opioid (μ-agonist) mechanisms create theoretical risk: weak serotonergic component could combine with any residual SERT activity of MDPV; opioid component introduces respiratory depression risk. However, MDPV's SERT IC₅₀ = 3,349 nM (extremely weak), making serotonin syndrome via this mechanism much less likely than with MDMA or mephedrone. **This interaction severity may be inferred from cathinone class rather than MDPV-specific evidence. FLAG for editorial verification.**

**MDMA: "Dangerous" (seed data)**
No published study specifically documenting MDPV–MDMA interactions was found. Theoretical concern: MDMA increases serotonin, dopamine, and norepinephrine; combined with MDPV's potent DAT/NET inhibition could cause: severe hypertension, hyperthermia, and cardiac stress. However, serotonin syndrome is less likely than with two serotonergic agents given MDPV's negligible SERT activity. The cardiovascular risk (combined sympathomimetic surge) is the more plausible mechanism. **This is class-level inference, not MDPV-specific evidence. FLAG for editorial verification.**

---

## Legal Status

| Jurisdiction | Status | Schedule/Class | Date |
|-------------|--------|---------------|------|
| United States | Controlled | Schedule I (21 USC §812) | Temporary: Oct 2011; Permanent: 2012 [Ref 20] |
| United Kingdom | Controlled | Class B, Misuse of Drugs Act 1971 | July 2010 [web-retrieved] |
| Canada | Controlled | Schedule I, CDSA | September 26, 2012 [web-retrieved] |
| Australia (WA) | Prohibited | Schedule 9, Poisons Act 1964 | February 11, 2012 [web-retrieved] |
| Australia (NSW) | Prohibited | Schedule 9, SUSP | September 2013 [web-retrieved] |
| European Union | Controlled in most member states | Following EMCDDA risk assessment | 2014 [Ref 21] |

DEA scheduling rationale: high potential for abuse, no currently accepted medical use, lacks accepted safety for use under medical supervision (Federal Register 2011 [Ref 20]).

The EU EMCDDA-Europol joint report on MDPV was formally submitted to the Council, European Commission, and EMA in December 2013, leading to risk assessment and member state scheduling (EMCDDA 2014 [Ref 21]).

---

## Clinical Trials

**No clinical trials have been registered for MDPV** on ClinicalTrials.gov (search April 2026 [Step 16]). No therapeutic application has been studied. MDPV was never clinically developed.

---

## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief. No community feedback items to assess.

---

## Gaps & Flags

### Critical Flags for Generation Agent

**🚨 FLAG 1 — SEED DATA ERROR: ROA data is wrong**
Seed data lists "Primary ROA: oral; Known ROAs: oral" only. Published literature (Ross et al. 2012 [Ref 35]) documents oral, nasal insufflation, smoking/vaporization, intravenous, intramuscular, and rectal administration. Multiple ROAs are confirmed in clinical case series (Borek 2012 IV; Sutamtewagul 2014 IV; Michigan MMWR 2011 IV and insufflation). The generation agent should flag this for database correction. Snorting appears to be one of the most common routes; IV use documented in severe toxicity cases.

**🚨 FLAG 2 — INTERACTIONS NOT CONFIRMED BY MDPV-SPECIFIC LITERATURE**
- Tramadol: "Lethal" — No specific MDPV-tramadol paper found. Mechanistic basis is weak given MDPV's negligible SERT activity. This severity designation may be inferred from cathinone class data and requires editorial review.
- MDMA: "Dangerous" — No specific MDPV-MDMA paper found. Risk is real but mechanism is primarily cardiovascular (sympathomimetic potentiation), not serotonergic. The "dangerous" designation is reasonable but based on class inference.
- Alcohol: "Unknown" — Confirmed: no specific data in published literature.

**🚨 FLAG 3 — DOSE DATA NOT CONFIRMED BY PUBLISHED SOURCES**
The seed dose ranges (Threshold 2 mg, Light 4–8 mg, Common 8–14 mg, Strong 14–25 mg, Heavy 25+ mg, oral) cannot be verified against any controlled human dosing studies (none exist). These are consistent with community consensus and the drug's high potency in animal models. The generation agent should propose retention of these values as editorial/community-sourced with explicit flagging that no clinical verification is available.

**🚨 FLAG 4 — HUMAN PHARMACOKINETICS ABSENT**
All PK data is from rat models. No human bioavailability, Tmax, half-life, or protein binding data has been published. Duration estimates are based on clinical presentations, not controlled pharmacokinetic studies.

**⚠️ FLAG 5 — CHARACTERIZATION "EMERGING" MAY BE OUTDATED**
Seed data characterizes MDPV as "emerging." MDPV peaked in the market 2010–2013 and has largely been superseded by α-PVP, MDPHP, and other analogs. It is Schedule I in most major jurisdictions. The "emerging" designation is historically obsolete; MDPV is better characterized as a well-characterized first-generation cathinone now largely replaced by analogs.

**⚠️ FLAG 6 — SMILES NOT RETURNED BY STRUCTURED API**
PubChem API call for CID 20111961 did not return the SMILES string in the tool's response. SMILES should be retrieved directly from PubChem CID 20111961 by the generation agent.

**⚠️ FLAG 7 — LD₅₀ NOT ESTABLISHED**
No LD₅₀ has been published for MDPV. The idiosyncratic fatality at 6 ng/mL blood concentration (Desharnais 2017 [Ref 17]) demonstrates that lethal outcome is possible far below the "expected" toxic threshold, via indirect mechanisms (excited delirium). This should be stated clearly.

**⚠️ FLAG 8 — TOLERANCE/DEPENDENCE DATA ABSENT FOR HUMANS**
No human tolerance, withdrawal, or dependence studies exist. Preclinical data (Watterson 2014, Aarde 2015) confirms high abuse liability. Clinical case reports document addiction (Casati 2025 [Ref 40]) and withdrawal-like persistent psychiatric symptoms (Penders 2013 [Ref 13]).

**⚠️ FLAG 9 — SEEDDATA TOXICITY NOTE CONFIRMED**
Seed data states: "Acute: moderate; Chronic: moderate; Notes: Inferred from pharmacological class — not sourced from literature. Review recommended." This is partially correct but should be upgraded: acute toxicity is well-documented as **high** (multiple fatalities, multiorgan failure, severe psychiatric events at moderate doses). Chronic toxicity data remains limited. The "moderate" acute designation underestimates documented risk.

### Data Gaps Summary

| Area | Gap |
|------|-----|
| Human PK | No controlled studies; rat data only |
| Human dose-response | No controlled studies; community data only |
| Withdrawal syndrome | No formal characterization |
| LD50 | Not established |
| CYP inhibition/induction | Not characterized for MDPV |
| Drug interactions | Most are class inference; no MDPV-specific interaction studies |
| Physical properties | Melting point, log P, pKa not API-verified |
| Sexual effects | User-reported; no controlled study evidence |
| Empathy effects | Pharmacologically questionable given weak SERT; user-reported only |