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Psychedex
Sources
18
1 strong · 11 moderate · 6 weak

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

Claims checked
94
56verified7partial30inconclusive1not supported

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

Generated
May 3, 2026 · pipeline-v5
Values approved
126/126 (100%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold30 mg30 mgmedium
Low50–75 mg50–75 mgmedium
Common75–120 mg75–120 mgmedium
Strong120–150 mg120–150 mgmedium
Heavy150+ mg150+ mgmedium
Editorial

Dose ranges confirmed by ACMD review (2023) and consistent with PsychonautWiki community consensus. Threshold 30 mg, light 50-75 mg, common 75-120 mg, strong 120-150 mg, heavy >150 mg. No controlled human dose-response studies exist; values derive from community-curated data validated against clinical case literature.

Reasoning

Dose ranges confirmed by ACMD review (2023) and consistent with PsychonautWiki community consensus. Threshold 30 mg, light 50-75 mg, common 75-120 mg, strong 120-150 mg, heavy >150 mg. No controlled human dose-response studies exist; values derive from community-curated data validated against clinical case literature.

Evidence basis: community_consensus_large

Duration

oral

FieldPublishedAI ProposedConfidence
Totaltrace6–8 hours6–8 hoursmedium
Editorial

Total subjective duration 6-8 hours confirmed by ACMD review (2023) and PsychonautWiki community consensus. Consistent with user report analyses (Van Hout & Hearne 2015).

Reasoning

Total subjective duration 6-8 hours confirmed by ACMD review (2023) and PsychonautWiki community consensus. Consistent with user report analyses (Van Hout & Hearne 2015).

Evidence basis: community_consensus_large

Onsettrace30–60 minutes30–60 minutesmedium
Editorial

Onset 30-60 minutes oral from ACMD review and PsychonautWiki community consensus. Consistent with rat Tmax of ~30 min SC (Štefková-Mazochová et al. 2025), accounting for oral absorption delay in humans.

Reasoning

Onset 30-60 minutes oral from ACMD review and PsychonautWiki community consensus. Consistent with rat Tmax of ~30 min SC (Štefková-Mazochová et al. 2025), accounting for oral absorption delay in humans.

Evidence basis: community_consensus_large

Come uptrace30–60 minutes30–60 minutesmedium
Editorial

Come-up duration estimated from user reports describing gradual build over 30-60 minutes after first alerts. Van Hout & Hearne 2015 describe a slow escalation pattern.

Reasoning

Come-up duration estimated from user reports describing gradual build over 30-60 minutes after first alerts. Van Hout & Hearne 2015 describe a slow escalation pattern.

Evidence basis: community_consensus_large

Peaktrace2–3 hours2–3 hoursmedium
Editorial

Peak duration estimated from total duration (6-8 h) minus onset, come-up, and offset phases. User reports describe sustained peak intensity for 2-3 hours.

Reasoning

Peak duration estimated from total duration (6-8 h) minus onset, come-up, and offset phases. User reports describe sustained peak intensity for 2-3 hours.

Evidence basis: community_consensus_large

Offsettrace1.5–2.5 hours1.5–2.5 hoursmedium
Editorial

Offset estimated from user reports describing gradual comedown. Consistent with the extended duration profile of MXP relative to other dissociatives.

Reasoning

Offset estimated from user reports describing gradual comedown. Consistent with the extended duration profile of MXP relative to other dissociatives.

Evidence basis: community_consensus_large

After effectstrace1–3 hours1–3 hoursmedium
Editorial

Aftereffects 1-3 hours from ACMD review and PsychonautWiki. Some user reports describe residual effects lasting longer, but the 1-3 hour range represents the middle ~80% of experiences.

Reasoning

Aftereffects 1-3 hours from ACMD review and PsychonautWiki. Some user reports describe residual effects lasting longer, but the 1-3 hour range represents the middle ~80% of experiences.

Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutehighhighmedium
Chronicmoderatemoderatemedium
Organs Affectedcardiovascular, liver, kidney, braincardiovascular, liver, kidney, brainmedium
Editorial

Acute classified as high based on documented human fatalities across multiple independent studies (Elliott et al. 2015, Corkery et al. 2025) with 14 deaths attributed to MXP as primary cause. Chronic classified as moderate: histopathological organ changes noted in rat LD50 study but no systematic chronic toxicity data in humans; ACMD review found no ketamine-type urological toxicity, but this is absence of evidence rather than evidence of absence.

Reasoning

Acute classified as high based on documented human fatalities across multiple independent studies (Elliott et al. 2015, Corkery et al. 2025) with 14 deaths attributed to MXP as primary cause. Chronic classified as moderate: histopathological organ changes noted in rat LD50 study but no systematic chronic toxicity data in humans; ACMD review found no ketamine-type urological toxicity, but this is absence of evidence rather than evidence of absence.

Evidence basis: published_case_series

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicalmoderatemoderatemedium
Psychologicalmoderatemoderatemedium
Compulsive Redosingmoderatemoderatemedium
Dose Escalationmoderatemoderatemedium
Editorial

Physical dependence documented by ACMD withdrawal case (abdominal pain, vomiting, fever after weeks of use). Use disorder documented by Champeau et al. 2017. Reinforcing properties confirmed in rodent behavioral studies (Hur et al. 2021: IV self-administration, CPP). Indirect dopamine mechanism established by Sahai et al. 2018 (no DAT binding) combined with Hur et al. 2021 (NAc dopamine overactivation).

Reasoning

Physical dependence documented by ACMD withdrawal case (abdominal pain, vomiting, fever after weeks of use). Use disorder documented by Champeau et al. 2017. Reinforcing properties confirmed in rodent behavioral studies (Hur et al. 2021: IV self-administration, CPP). Indirect dopamine mechanism established by Sahai et al. 2018 (no DAT binding) combined with Hur et al. 2021 (NAc dopamine overactivation).

Evidence basis: published_case_series

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitymildmildlow
Symptomsabdominal pain, vomiting, low-grade feverabdominal pain, vomiting, low-grade feverlow
FatalNoNolow
Medical SupervisionNot requiredNot requiredlow
Editorial

Single documented case in ACMD review: 21-year-old male, withdrawal after weeks-to-month of use. Symptoms were gastrointestinal and constitutional (abdominal pain, vomiting, fever 38°C). Severity classified as mild based on symptom profile; no life-threatening features reported.

Reasoning

Single documented case in ACMD review: 21-year-old male, withdrawal after weeks-to-month of use. Symptoms were gastrointestinal and constitutional (abdominal pain, vomiting, fever 38°C). Severity classified as mild based on symptom profile; no life-threatening features reported.

Evidence basis: published_case_series

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Buildupmoderatemoderatelow
Half-life5 days5 dayslow
Full Reset10 days10 dayslow
Cross-tolerancesdissociativesdissociativeslow
Editorial

No controlled tolerance studies exist for MXP. Values (5-day half-life, 10-day full reset, dissociative cross-tolerance) are community consensus estimates consistent with the NMDA antagonist class. Mechanism is structural inference from NMDA receptor pharmacology.

Reasoning

No controlled tolerance studies exist for MXP. Values (5-day half-life, 10-day full reset, dissociative cross-tolerance) are community consensus estimates consistent with the NMDA antagonist class. Mechanism is structural inference from NMDA receptor pharmacology.

Evidence basis: community_consensus_large

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
hepatic hepatic impairmenttracerelativerelativelow
Editorial

Structural inference: O-demethylation is the primary metabolic pathway. CYP involvement inferred from structural class. Histopathological liver changes noted in rat LD50 study.

Reasoning

Structural inference: O-demethylation is the primary metabolic pathway. CYP involvement inferred from structural class. Histopathological liver changes noted in rat LD50 study.

cardiovascular hypertensiontraceabsoluteabsolutemedium
Editorial

Hypertension (76%) and tachycardia (47%) documented in STRIDA diarylethylamine case series (Helander et al. 2015). Cardiovascular complications also reported in French Addictovigilance data (Eiden et al. 2018).

Reasoning

Hypertension (76%) and tachycardia (47%) documented in STRIDA diarylethylamine case series (Helander et al. 2015). Cardiovascular complications also reported in French Addictovigilance data (Eiden et al. 2018).

cardiovascular coronary artery diseasetraceabsoluteabsolutemedium
Editorial

Class inference from documented cardiovascular effects (Helander et al. 2015) applied to patients with pre-existing coronary disease.

Reasoning

Class inference from documented cardiovascular effects (Helander et al. 2015) applied to patients with pre-existing coronary disease.

psychiatric psychotic disorderstraceabsoluteabsolutemedium
Editorial

Altered mental status with hallucinations and confusion in 65% of clinical cases (Helander et al. 2015). Psychosis reported in French cases (Eiden et al. 2018). Schizophrenia-like behavioral phenotype in animal models (Hur et al. 2021).

Reasoning

Altered mental status with hallucinations and confusion in 65% of clinical cases (Helander et al. 2015). Psychosis reported in French cases (Eiden et al. 2018). Schizophrenia-like behavioral phenotype in animal models (Hur et al. 2021).

neurological epilepsytraceabsoluteabsolutemedium
Editorial

Seizures reported in user accounts (Van Hout & Hearne 2015) and French clinical cases (Eiden et al. 2018). Class-level inference for epilepsy contraindication.

Reasoning

Seizures reported in user accounts (Van Hout & Hearne 2015) and French clinical cases (Eiden et al. 2018). Class-level inference for epilepsy contraindication.

pregnancy breastfeeding pregnancytraceabsoluteabsolutelow
Editorial

Precautionary principle applied based on demonstrated high BBB penetration and known importance of NMDA signaling in neurodevelopment. No reproductive safety data exist.

Reasoning

Precautionary principle applied based on demonstrated high BBB penetration and known importance of NMDA signaling in neurodevelopment. No reproductive safety data exist.

Timeline Phases

oral

FieldPublishedAI ProposedConfidence
Onsettrace1800–3600 sec(i=0.05)1800–3600 sec(i=0.05)medium
Editorial

Onset 30\u201360 min and total duration 6\u20138 hours from ACMD review and PsychonautWiki community consensus. Aftereffects 1\u20133 hours from same sources. Phase distribution inferred from user report analyses (Van Hout & Hearne 2015, Hearne & Van Hout 2016) describing biphasic stimulant-sedative wave pattern and extended duration. Cardiovascular timing from Helander et al. 2015 clinical data.

Reasoning

Onset 30\u201360 min and total duration 6\u20138 hours from ACMD review and PsychonautWiki community consensus. Aftereffects 1\u20133 hours from same sources. Phase distribution inferred from user report analyses (Van Hout & Hearne 2015, Hearne & Van Hout 2016) describing biphasic stimulant-sedative wave pattern and extended duration. Cardiovascular timing from Helander et al. 2015 clinical data.

Come uptrace1800–3600 sec(i=0.30)1800–3600 sec(i=0.30)medium
Editorial

Onset 30\u201360 min and total duration 6\u20138 hours from ACMD review and PsychonautWiki community consensus. Aftereffects 1\u20133 hours from same sources. Phase distribution inferred from user report analyses (Van Hout & Hearne 2015, Hearne & Van Hout 2016) describing biphasic stimulant-sedative wave pattern and extended duration. Cardiovascular timing from Helander et al. 2015 clinical data.

Reasoning

Onset 30\u201360 min and total duration 6\u20138 hours from ACMD review and PsychonautWiki community consensus. Aftereffects 1\u20133 hours from same sources. Phase distribution inferred from user report analyses (Van Hout & Hearne 2015, Hearne & Van Hout 2016) describing biphasic stimulant-sedative wave pattern and extended duration. Cardiovascular timing from Helander et al. 2015 clinical data.

Peaktrace7200–10800 sec(i=1.00)7200–10800 sec(i=1.00)medium
Editorial

Onset 30\u201360 min and total duration 6\u20138 hours from ACMD review and PsychonautWiki community consensus. Aftereffects 1\u20133 hours from same sources. Phase distribution inferred from user report analyses (Van Hout & Hearne 2015, Hearne & Van Hout 2016) describing biphasic stimulant-sedative wave pattern and extended duration. Cardiovascular timing from Helander et al. 2015 clinical data.

Reasoning

Onset 30\u201360 min and total duration 6\u20138 hours from ACMD review and PsychonautWiki community consensus. Aftereffects 1\u20133 hours from same sources. Phase distribution inferred from user report analyses (Van Hout & Hearne 2015, Hearne & Van Hout 2016) describing biphasic stimulant-sedative wave pattern and extended duration. Cardiovascular timing from Helander et al. 2015 clinical data.

Plateautrace5400–7200 sec(i=0.50)5400–7200 sec(i=0.50)medium
Editorial

Onset 30\u201360 min and total duration 6\u20138 hours from ACMD review and PsychonautWiki community consensus. Aftereffects 1\u20133 hours from same sources. Phase distribution inferred from user report analyses (Van Hout & Hearne 2015, Hearne & Van Hout 2016) describing biphasic stimulant-sedative wave pattern and extended duration. Cardiovascular timing from Helander et al. 2015 clinical data.

Reasoning

Onset 30\u201360 min and total duration 6\u20138 hours from ACMD review and PsychonautWiki community consensus. Aftereffects 1\u20133 hours from same sources. Phase distribution inferred from user report analyses (Van Hout & Hearne 2015, Hearne & Van Hout 2016) describing biphasic stimulant-sedative wave pattern and extended duration. Cardiovascular timing from Helander et al. 2015 clinical data.

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

Onset 30\u201360 min and total duration 6\u20138 hours from ACMD review and PsychonautWiki community consensus. Aftereffects 1\u20133 hours from same sources. Phase distribution inferred from user report analyses (Van Hout & Hearne 2015, Hearne & Van Hout 2016) describing biphasic stimulant-sedative wave pattern and extended duration. Cardiovascular timing from Helander et al. 2015 clinical data.

Reasoning

Onset 30\u201360 min and total duration 6\u20138 hours from ACMD review and PsychonautWiki community consensus. Aftereffects 1\u20133 hours from same sources. Phase distribution inferred from user report analyses (Van Hout & Hearne 2015, Hearne & Van Hout 2016) describing biphasic stimulant-sedative wave pattern and extended duration. Cardiovascular timing from Helander et al. 2015 clinical data.

Afterglowtrace3600–10800 sec(i=0.05)3600–10800 sec(i=0.05)medium
Editorial

Onset 30\u201360 min and total duration 6\u20138 hours from ACMD review and PsychonautWiki community consensus. Aftereffects 1\u20133 hours from same sources. Phase distribution inferred from user report analyses (Van Hout & Hearne 2015, Hearne & Van Hout 2016) describing biphasic stimulant-sedative wave pattern and extended duration. Cardiovascular timing from Helander et al. 2015 clinical data.

Reasoning

Onset 30\u201360 min and total duration 6\u20138 hours from ACMD review and PsychonautWiki community consensus. Aftereffects 1\u20133 hours from same sources. Phase distribution inferred from user report analyses (Van Hout & Hearne 2015, Hearne & Van Hout 2016) describing biphasic stimulant-sedative wave pattern and extended duration. Cardiovascular timing from Helander et al. 2015 clinical data.

Dose Tier Summaries

thresholdtrace
medium

At threshold doses (~30 mg oral), effects are subtle and easily mistaken for placebo: a mild shift in spatial awareness, slight cognitive slowing, and a faint sense of detachment from the immediate environment. Some users report gentle mood elevation or mild stimulation. Physically, mild light-headedness and a barely perceptible change in body weight sensation may occur. Functional impairment is minimal, though subtle attention deficits are possible. Onset is slow (30–60 minutes), and the overall experience at this level lasts 3–5 hours. The subtlety of threshold effects with MXP's long onset window creates a significant redosing risk — effects may not be apparent before a second dose is taken.

Editorial

Threshold of 30 mg oral is confirmed by ACMD review and community consensus data (PsychonautWiki). Qualitative descriptions inferred from dissociative class and user reports.

Reasoning

Threshold of 30 mg oral is confirmed by ACMD review and community consensus data (PsychonautWiki). Qualitative descriptions inferred from dissociative class and user reports.

Evidence basis: community_consensus_large

lighttrace
medium

At light doses (50–75 mg oral), dissociative effects become clearly perceptible. Mild spatial disorientation emerges, accompanied by cognitive disconnection — a sense of being slightly removed from one's thoughts and surroundings. Visual processing begins to dull: colors may appear flatter, depth perception subtly distorted. A stimulant-like wave quality is common at this range, with restless energy alternating with periods of detached calm. Physically, mild increases in heart rate and blood pressure are expected based on the cardiovascular profile observed in clinical cases. Coordination is mildly impaired. The experience lasts 5–7 hours, with a gradual return to baseline. Sleep may be difficult for several hours after subjective effects subside.

Editorial

Light range of 50–75 mg oral from ACMD review and PsychonautWiki consensus. Subjective descriptions from Van Hout & Hearne 2015 user report analysis and class-level dissociative pharmacology.

Reasoning

Light range of 50–75 mg oral from ACMD review and PsychonautWiki consensus. Subjective descriptions from Van Hout & Hearne 2015 user report analysis and class-level dissociative pharmacology.

Evidence basis: community_consensus_large

commontrace
medium

At common doses (75–120 mg oral), the full dissociative experience manifests. Cognitive disconnection deepens into pronounced derealization and depersonalization. Spatial disorientation becomes significant — navigation of physical space requires deliberate effort. Visual processing suppression is evident: double vision, reduced visual acuity, and flattened depth perception. Amnesia for portions of the experience is common. The biphasic stimulant-sedative wave pattern reported by users is most apparent at this range. Physically, hypertension and tachycardia are expected based on clinical intoxication data. Body feels heavy or numb. Motor coordination is substantially impaired, and speech may become slurred or difficult. Duration is 6–8 hours with 1–3 hours of aftereffects. Functional impairment persists well beyond the subjective peak. Planning for an extended time commitment is essential.

Editorial

Common range of 75–120 mg oral from ACMD review and PsychonautWiki. Clinical presentation data from Helander et al. 2015 (hypertension 76%, tachycardia 47%). Subjective descriptions from Van Hout & Hearne 2015.

Reasoning

Common range of 75–120 mg oral from ACMD review and PsychonautWiki. Clinical presentation data from Helander et al. 2015 (hypertension 76%, tachycardia 47%). Subjective descriptions from Van Hout & Hearne 2015.

Evidence basis: community_consensus_large

strongtrace
medium

At strong doses (120–150 mg oral), dissociation becomes profound. Derealization and depersonalization may approach complete ego dissolution or "hole" states analogous to those described with ketamine, though with a longer and less predictable trajectory. Amnesia is extensive — large portions of the experience may not be recalled. Cognitive function is severely impaired: internal monologue fragments, time loses coherence, and environmental awareness narrows dramatically. Physically, pronounced cardiovascular stress (significant hypertension and tachycardia) is expected. Nausea, ataxia, and near-complete motor incapacitation are common. Seizures have been reported at high doses in clinical case literature. The experience lasts 7–8+ hours. The combination of severe functional impairment, cardiovascular risk, and extended duration makes this range particularly hazardous without a sober attendant.

Editorial

Strong range of 120–150 mg oral from ACMD review and PsychonautWiki. Seizure reports from Eiden et al. 2018 and Van Hout & Hearne 2015. Cardiovascular data from Helander et al. 2015.

Reasoning

Strong range of 120–150 mg oral from ACMD review and PsychonautWiki. Seizure reports from Eiden et al. 2018 and Van Hout & Hearne 2015. Cardiovascular data from Helander et al. 2015.

Evidence basis: community_consensus_large

heavytrace
medium

At heavy doses (>150 mg oral), MXP produces deep anaesthetic-level dissociation with complete disconnection from external reality. Consciousness may be severely altered or lost entirely. Amnesia is total for the duration. The risk of medical emergency is substantial — multiple fatalities have been documented, and post-mortem blood concentrations in fatal cases ranged widely (1.36–24.0 mg/L), indicating unpredictable individual sensitivity. Cardiovascular crisis (severe hypertension, tachycardia), seizures, respiratory compromise, and loss of protective reflexes are all documented risks. Nearly half of analytically confirmed clinical intoxications were classified as severe. This dose range carries life-threatening risk. The wide variation in fatal blood concentrations means no safe upper boundary can be established.

Editorial

Heavy threshold >150 mg oral from community consensus. Fatality data from Elliott et al. 2015 (post-mortem concentrations 1.36–24.0 mg/L) and Corkery et al. 2025 (31 UK deaths). Severe intoxication rate (47% PSS 3) from Helander et al. 2015.

Reasoning

Heavy threshold >150 mg oral from community consensus. Fatality data from Elliott et al. 2015 (post-mortem concentrations 1.36–24.0 mg/L) and Corkery et al. 2025 (31 UK deaths). Severe intoxication rate (47% PSS 3) from Helander et al. 2015.

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

1 strong · 11 moderate · 6 weak
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    moderate
    Mechanistic Insights into the Stimulant Properties of Novel Psychoactive Substances (NPS) and Their Discrimination by the Dopamine Transporter-In Silico and In Vitro Exploration of Dissociative Diarylethylamines
    Sahai MA, Davidson C, Dutta N, Opacka-Juffry J · 2018 · Brain Sciences
    doi.org/10.3390/brainsci8040063pubmed 296424509 claims checked6 verified1 partial2 inconclusive
  2. [2]
    moderate
    Pharmacological Investigations of the Dissociative 'Legal Highs' Diphenidine, Methoxphenidine and Analogues
    Wallach J, Kang H, Colestock T, Morris H, Bortolotto ZA, Collingridge GL, Lodge D, Halberstadt AL, Brandt SD, Adejare A · 2016 · PLoS ONE
    doi.org/10.1371/journal.pone.0157021pubmed 2731467016 claims checked6 verified2 partial8 inconclusive
  3. [3]
    moderate
    "Word of mouse": indigenous harm reduction and online consumerism of the synthetic compound methoxphenidine
    Van Hout MC, Hearne E · 2015 · Journal of Psychoactive Drugs
    doi.org/10.1080/02791072.2014.974002pubmed 257150707 claims checked6 verified1 inconclusive
  4. [4]
    moderate
    "Trip-Sitting" in the Black Hole: A Netnographic Study of Dissociation and Indigenous Harm Reduction
    Hearne E, Van Hout MC · 2016 · Journal of Psychoactive Drugs
    doi.org/10.1080/02791072.2016.1207827pubmed 274306592 claims checked1 verified1 inconclusive
  5. [5]
    weak
    ACMD Review of the Evidence on the Use and Harms of Diphenidine (including methoxphenidine)
    Advisory Council on the Misuse of Drugs (ACMD) · 2023
    linkno claims checked
  6. [6]
    strong
    Deaths related to the use of diarylethylamines, with a focus on the United Kingdom: A systematic review and case series report
    Corkery JM, Copeland C, Schifano F · 2025 · Journal of Psychopharmacology
    doi.org/10.1177/02698811251349203pubmed 405902333 claims checked2 verified1 partial
  7. [7]
    moderate
    Intriguing Cytotoxicity of the Street Dissociative Anesthetic Methoxphenidine: Unexpected Impurities Spotted
    Jurásek B, Rimpelová S, Babor M, Čejka J, Bartůněk V · 2022 · International Journal of Molecular Sciences
    doi.org/10.3390/ijms23042083pubmed 352161983 claims checked2 verified1 inconclusive
  8. [8]
    weak
    First Reported Fatalities Associated with the 'Research Chemical' 2-Methoxydiphenidine
    Elliott SP, Brandt SD, Wallach J, Morris H, Kavanagh PV · 2015 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bkv006pubmed 256987779 claims checked3 verified1 partial4 inconclusive1 not supported
  9. [9]
    weak
    Acute toxicity associated with the recreational use of the novel dissociative psychoactive substance methoxphenidine
    Hofer KE, Degrandi C, Müller DM, Zürrer-Härdi U, Wahl S, Rauber-Lüthy C, Ceschi A · 2014 · Clinical Toxicology
    doi.org/10.3109/15563650.2014.974264pubmed 253504674 claims checked1 verified3 inconclusive
  10. [10]
    moderate
    Pharmacological characterizations of the 'legal high' fluorolintane and isomers
    Wallach J, Colestock T, Agramunt J, Claydon MDB, Dybek M, Filemban N, Chatha M, Halberstadt AL, Brandt SD, Lodge D, Bortolotto ZA, Adejare A · 2019 · European Journal of Pharmacology
    doi.org/10.1016/j.ejphar.2019.172427pubmed 31152702no claims checked
  11. [11]
    moderate
    Ephenidine, diphenidine, and methoxphenidine complications reported to the French Addictovigilance Network
    Eiden C, Leone-Burgos S, Serre A, Carton L, Gerardin M, Le Boisselier R, Gibaja V, Monzon E, Fouilhe N, Boucher A, Peyriere H · 2018 · Fundamental & Clinical Pharmacology
    doi.org/10.1111/fcp.12395pubmed 299568437 claims checked4 verified1 partial2 inconclusive
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    Misuse of Drugs Act 1971 (Amendment) Order 2024 - Circular 001/2024 (UK Home Office)
    UK Home Office · 2024
    linkno claims checked
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    moderate
    Test purchase, synthesis, and characterization of 2-methoxydiphenidine (MXP) and differentiation from its meta- and para-substituted isomers
    McLaughlin G, Morris N, Kavanagh PV, Power JD, O'Brien J, Talbot B, Elliott SP, Wallach J, Hoang K, Morris H, Brandt SD · 2016 · Drug Testing and Analysis
    doi.org/10.1002/dta.1800pubmed 258733262 claims checked1 verified1 inconclusive
  14. [14]
    moderate
    Achiral LC-MS/MS and chiral SFC-MS methods for quantification of methoxphenidine and O-desmethyl-methoxphenidine metabolite in rat serum and brain
    Paškanová N, Vágnerová M, Jurásek B, Mazochová K, Olejníková-Ladislavová L, Páleníček T, Kohout M, Sýkora D, Kuchař M · 2025 · Journal of Chromatography B
    doi.org/10.1016/j.jchromb.2025.124613pubmed 403114817 claims checked2 verified5 inconclusive
  15. [15]
    moderate
    Methoxphenidine (MXP) induced abnormalities: Addictive and schizophrenia-related behaviours based on an imbalance of neurochemicals in the brain
    Hur KH, Kim SE, Ma SX, Lee BR, Ko YH, Seo JY, Kim SK, Kim YJ, Sung SJ, Lee Y, Jung YH, Lee YS, Lee SY, Jang CG · 2021 · British Journal of Pharmacology
    doi.org/10.1111/bph.15528pubmed 339878278 claims checked8 verified
  16. [16]
    moderate
    The acute effects of methoxphenidine on behaviour and pharmacokinetics profile in animal model
    Štefková-Mazochová K, Danda H, Mazoch V, Olejníková-Ladislavová L, Šíchová K, Paškanová N, Vágnerová M, Jurásek B, Ryšánek P, Šíma M, Šafanda A, Bui QH, Kuchař M, Páleníček T · 2025 · Progress in Neuro-Psychopharmacology & Biological Psychiatry
    doi.org/10.1016/j.pnpbp.2025.111285pubmed 399293708 claims checked6 verified2 inconclusive
  17. [17]
    weak
    Intoxications by the dissociative new psychoactive substances diphenidine and methoxphenidine
    Helander A, Beck O, Bäckberg M · 2015 · Clinical Toxicology
    doi.org/10.3109/15563650.2015.1033630pubmed 258817978 claims checked7 verified1 partial
  18. [18]
    weak
    Methoxphenidine Use Disorder: First Case Notified to the French Addictovigilance Network
    Champeau W, Eiden C, Gambier J, Peyriere H · 2017 · Journal of Clinical Psychopharmacology
    doi.org/10.1097/jcp.0000000000000684pubmed 282720881 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.

summary8 claims1verified4partial3inconclusive
partialMethoxphenidine (MXP, 2-MXP, 2-MeO-diphenidine) is a synthetic dissociative of the 1,2-diarylethylamine structural class, characterized by potent NMDA receptor antagonism (Ki = 36 nM) and a 6–8 hour oral duration that places it among the longer-acting dissociatives[2]model confidence 80%
Partial

Abstract confirms NMDA antagonism and structural class; SCOPE confirms Ki binding data exists in full paper. However, the 6–8 hour oral duration is absent from both the abstract and the SCOPE of this pharmacology paper — duration data would come from clinical/user-report sources, not this binding study.

DPH and 2-MXP are relatively selective NMDAR antagonists with weak off-target effects on dopamine and norepinephrine reuptake.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedIt emerged on recreational markets in mid-to-late 2013 as a legal alternative to methoxetamine and ketamine following UK restrictions on arylcyclohexylamines[3]model confidence 95%
Verified

Abstract directly states MXP was 'marketed as legal replacement for MXE/ketamine (2013)'. The 'mid-to-late' qualifier and 'following UK restrictions' detail are not in the abstract but are not contradicted.

MXP marketed as legal replacement for MXE/ketamine (2013).

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveMXP acts as an uncompetitive channel blocker at the NMDA receptor with Ki = 36.0 ± 3.7 nM at the MK-801 binding site, placing it in the same potency tier as ketamine[2]model confidence 75%
Inconclusive

Abstract confirms NMDA binding studies across 46 receptors and NMDA selectivity, but doesn't state the specific Ki value (36.0 ± 3.7 nM), the mechanism (uncompetitive channel blocker / MK-801 site), or the comparison to ketamine. These specific details would require the full text.

Binding studies at 46 CNS receptors. DPH and 2-MXP are relatively selective NMDAR antagonists.

checked by claude-sonnet-4-6 · May 3, 2026

partialIt displays moderate sigma-1 affinity (Ki ≈ 124 nM) but negligible activity at monoamine transporters — critically, it does not bind the dopamine transporter or increase dopamine efflux, unlike its structural analog diphenidine.[1]model confidence 80%
Partial

Abstract directly confirms the DAT/dopamine efflux claim: 'MXP had no significant effect on DAT binding or evoked DA efflux (unlike DPH).' However, sigma-1 affinity (Ki ≈ 124 nM) is not addressed by this paper — that value would come from the Wallach et al. binding panel, not the DAT-focused Sahai paper.

MXP had no significant effect on DAT binding or evoked DA efflux (unlike DPH).

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe dissociative experience at common oral doses (75–120 mg) encompasses cognitive disconnection, derealization, spatial disorientation, and visual processing suppression, with a biphasic quality: lower doses produce stimulant-like waves while higher doses trend toward sedation and immobility[3]model confidence 70%
Inconclusive

Abstract confirms dissociative and stimulant effects from user reports, but doesn't specify the dose range (75–120 mg), the particular subjective effects listed, or the dose-dependent shift from stimulation to sedation. These details would require the full phenomenological analysis.

Dissociative and stimulant effects lasting days.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveSet, setting, and prior dissociative tolerance modulate the character and intensity of the experience.[4]model confidence 65%
Inconclusive

Abstract describes a netnographic study with five themes on risk perception and harm reduction practices, which likely covers set/setting/tolerance, but the specific claim is not confirmed in the abstract text.

Five themes on risk perception, harm reduction practices in online communities.

checked by claude-sonnet-4-6 · May 3, 2026

partialMultiple fatalities have been documented: 31 UK deaths involved MXP alone or in combination, with post-mortem blood concentrations ranging from 1.36 to 24.0 mg/L[6]model confidence 80%
Partial

Abstract directly confirms 31 UK MXP deaths. However, the blood concentration range (1.36–24.0 mg/L) is not in this systematic review abstract — those concentrations are from the Elliott et al. fatalities case report, not from Corkery et al.

37 UK deaths (27 England, 7 Scotland, 3 Wales); 31 involving MXP alone or combined.

checked by claude-sonnet-4-6 · May 3, 2026

partialMultiple fatalities have been documented: 31 UK deaths involved MXP alone or in combination, with post-mortem blood concentrations ranging from 1.36 to 24.0 mg/L[8]model confidence 80%
Partial

Abstract confirms the blood concentration range (24.0, 2.0, 1.36 mg/L) across 3 cases. However, '31 UK deaths' is not from this paper — this paper documents only 3 fatalities. The claim mixes data from two different sources into one sentence, and this citation can only support the concentration range.

Three MXP-related deaths. Femoral blood concentrations: 24.0, 2.0, 1.36 mg/L.

checked by claude-sonnet-4-6 · May 3, 2026

history6 claims1verified5inconclusive
inconclusiveThe first published clinical toxicity case appeared in 2014[9]model confidence 70%
Inconclusive

Abstract confirms this is the first analytically confirmed case of oral MXP toxicity, but the year 2014 is not stated in the abstract. The claim requires the year to be verified.

First analytically confirmed case of oral MXP toxicity.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe first fatalities were reported in 2015[8]model confidence 70%
Inconclusive

Abstract confirms these are the first reported MXP fatalities, but the year 2015 is not stated in the abstract text.

Three MXP-related deaths. Femoral blood concentrations: 24.0, 2.0, 1.36 mg/L.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveSearle & Co.''' (now Pharmacia/Pfizer), covering the treatment of neurotoxic injury using 1,2-diarylethylamines{{cite|name=gray1994|author=gray|year=1994|title=G.D[9]model confidence 55%
Inconclusive

Claim text is garbled markup. Abstract references a 1989 Searle Company patent as the original source of MXP, which partially supports the Searle connection, but the claim text appears to reference a separate 1994 Gray patent for neurotoxic injury treatment. These are different documents and the claim cannot be cleanly evaluated.

References 1989 Searle Company patent as original source of MXP.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe structural class was subsequently explored for clinical applications in pain, epilepsy, and neuroprotection — yielding clinical-stage NMDA antagonists lanicemine and remacemide — before members began appearing as recreational drugs.[2]model confidence 65%
Inconclusive

Abstract is a pharmacology/binding study; it does not discuss the historical clinical development of the diarylethylamine class or mention lanicemine or remacemide. This historical context may appear in the paper's introduction but is not in the abstract.

Binding studies at 46 CNS receptors. DPH and 2-MXP are relatively selective NMDAR antagonists.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedVendors marketed MXP explicitly as a legal alternative to methoxetamine and ketamine.[3]model confidence 99%
Verified

Abstract directly confirms: 'MXP marketed as legal replacement for MXE/ketamine (2013).'

MXP marketed as legal replacement for MXE/ketamine (2013).

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveVendors marketed MXP explicitly as a legal alternative to methoxetamine and ketamine.[9]model confidence 65%
Inconclusive

Abstract is a clinical toxicity case report referencing a Searle patent; it does not discuss MXP marketing positioning or vendor claims.

First analytically confirmed case of oral MXP toxicity. References 1989 Searle Company patent as original source of MXP.

checked by claude-sonnet-4-6 · May 3, 2026

chemistry4 claims2verified2inconclusive
inconclusiveIt is also structurally related to the historical pharmaceutical lefetamine and to the arylcyclohexylamine dissociative pcp, though pharmacologically distinct from both.[13]model confidence 65%
Inconclusive

Abstract covers synthesis and isomer characterization of MXP; structural relationships to lefetamine and PCP are not mentioned.

Synthesis of 2-, 3-, and 4-MXP isomers. UK internet vendor samples confirmed as 2-MXP. Differentiation by GC-MS, HPLC-MS, NMR, IR.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveIt is also structurally related to the historical pharmaceutical lefetamine and to the arylcyclohexylamine dissociative pcp, though pharmacologically distinct from both.[2]model confidence 65%
Inconclusive

Abstract is a pharmacology binding study; structural relationships to lefetamine and PCP are not mentioned.

Binding studies at 46 CNS receptors. DPH and 2-MXP are relatively selective NMDAR antagonists.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe methoxy substituent at the ortho position distinguishes it from the unsubstituted parent compound diphenidine and from the meta- and para-isomers (3-MXP, 4-MXP).[13]model confidence 95%
Verified

Abstract directly confirms synthesis and differentiation of all three isomers (2-, 3-, 4-MXP), and confirms UK vendor samples are 2-MXP (ortho position).

Synthesis of 2-, 3-, and 4-MXP isomers. UK internet vendor samples confirmed as 2-MXP.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedIn Wistar rats dosed with racemic MXP, (S)-MXP accumulates to higher brain concentrations than (R)-MXP, indicating enantioselective CNS distribution[14]model confidence 99%
Verified

Abstract directly confirms: '(S)-MXP higher brain concentrations than (R)-enantiomer.'

(S)-MXP higher brain concentrations than (R)-enantiomer.

checked by claude-sonnet-4-6 · May 3, 2026

pharmacology15 claims7verified7inconclusive1not supported
inconclusiveIts primary binding affinity, determined by [³H]-MK-801 displacement, is Ki = 36.0 ± 3.7 nM[2]model confidence 75%
Inconclusive

Abstract confirms binding studies at 46 CNS receptors and NMDA selectivity, but the specific Ki value (36.0 ± 3.7 nM) and the [³H]-MK-801 displacement method are not stated in the abstract — these are in the full paper.

Binding studies at 46 CNS receptors. DPH and 2-MXP are relatively selective NMDAR antagonists.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThis places MXP in the same potency tier as ketamine, more potent than memantine, and comparable in class to pcp though structurally distinct.[2]model confidence 75%
Inconclusive

Abstract confirms MXP is an NMDA antagonist, but contains no comparative potency data relative to ketamine, memantine, or PCP. These comparisons are not in the abstract.

DPH and 2-MXP are relatively selective NMDAR antagonists.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedAutoradiography and fast cyclic voltammetry in rat nucleus accumbens slices demonstrated that MXP has no significant effect on dopamine transporter (DAT) binding or evoked dopamine efflux, while diphenidine increases dopamine efflux via DAT[1]model confidence 95%
Verified

Abstract directly confirms the key finding: 'MXP had no significant effect on DAT binding or evoked DA efflux (unlike DPH).' The methods (autoradiography, fast cyclic voltammetry) are consistent with the paper's scope.

MXP had no significant effect on DAT binding or evoked DA efflux (unlike DPH).

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMolecular dynamics simulations confirmed that diphenidine docks into DAT while MXP does not[1]model confidence 95%
Verified

Abstract directly confirms: 'Computational modeling shows DPH binds DAT; MXP does not.'

Computational modeling shows DPH binds DAT; MXP does not.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveSerotonin transporter affinity is essentially absent (SERT >10 μM), and norepinephrine transporter affinity is very low (NET IC₅₀ = 35.2 μM).[2]model confidence 75%
Inconclusive

Abstract mentions weak off-target effects on norepinephrine reuptake, which is directionally consistent, but neither the SERT >10 μM nor NET IC₅₀ = 35.2 μM specific values appear in the abstract.

DPH and 2-MXP are relatively selective NMDAR antagonists with weak off-target effects on dopamine and norepinephrine reuptake.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedDespite the absence of direct DAT activity, MXP produces rewarding and reinforcing behaviors in rodents — intravenous self-administration and conditioned place preference — accompanied by dopamine pathway overactivation in the nucleus accumbens[15]model confidence 95%
Verified

Abstract directly confirms all three elements: IV self-administration, CPP, and dopamine pathway overactivation in nucleus accumbens.

MXP caused addictive behaviours (IV self-administration, CPP)... Dopamine pathway overactivation in nucleus accumbens.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedIn Wistar rats following subcutaneous administration, MXP reaches peak serum and brain concentrations at approximately 30 minutes (Tmax ≈ 0.5 h), rapidly crosses the blood-brain barrier, and accumulates in brain tissue at concentrations substantially higher than serum throughout the observation period[16]model confidence 95%
Verified

Abstract directly confirms: 'MXP rapidly crossed BBB, peak brain/serum concentrations at 30 min.'

MXP rapidly crossed BBB, peak brain/serum concentrations at 30 min.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe elimination half-life in rats is 2.15 hours.[16]model confidence 99%
Verified

Abstract directly and precisely confirms: 'Elimination half-life 2.15 h in rats.'

Elimination half-life 2.15 h in rats.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveQuantitative tissue distribution data from validated LC-MS/MS and chiral SFC-MS methods show peak serum MXP of 1,600 ng/mL at 0.5 h declining to 5.87 ng/mL at 24 h, and peak brain MXP of 13,200 ng/g at 0.5 h declining to 36.1 ng/g at 24 h — an approximately 8:1 brain-to-serum ratio at peak[14]model confidence 75%
Inconclusive

Abstract directly confirms peak serum (1600 ng/mL at 0.5h) and brain (13200 ng/g at 0.5h) values. However, the 24h declining concentrations (5.87 ng/mL, 36.1 ng/g) and the stated 8:1 ratio are not in the abstract.

Serum MXP peak 1600 ng/mL at 0.5h; brain peak 13200 ng/g at 0.5h.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe (S)-enantiomer achieves higher brain concentrations than (R)-MXP following racemic dosing, indicating enantioselective CNS distribution.[14]model confidence 99%
Verified

Abstract directly confirms: '(S)-MXP higher brain concentrations than (R)-enantiomer.'

(S)-MXP higher brain concentrations than (R)-enantiomer.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe primary metabolic pathway is O-demethylation of the methoxy group, producing O-desmethyl-methoxphenidine (dmMXP). dmMXP peaks later than the parent compound (serum: 11.8 ng/mL at 1 h; brain: 67.1 ng/g at 1 h) and remains detectable at 24 h in brain tissue (1.63 ng/g)[14]model confidence 75%
Inconclusive

Abstract confirms O-desmethyl-MXP is being quantified, consistent with O-demethylation as a metabolic pathway. However, the specific metabolite kinetic values (11.8 ng/mL at 1h, 67.1 ng/g at 1h, 1.63 ng/g at 24h) and confirmation of 'primary' pathway are not in the abstract.

Validated LC-MS/MS and chiral SFC-MS for MXP enantiomers and O-desmethyl-MXP in rat serum/brain.

checked by claude-sonnet-4-6 · May 3, 2026

not supportedThe primary metabolic pathway is O-demethylation of the methoxy group, producing O-desmethyl-methoxphenidine (dmMXP). dmMXP peaks later than the parent compound (serum: 11.8 ng/mL at 1 h; brain: 67.1 ng/g at 1 h) and remains detectable at 24 h in brain tissue (1.63 ng/g)[8]model confidence 85%
Not supported

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

The abstract directly contradicts the 'primary pathway' assertion: it lists hydroxy-MXP as the 'main' metabolite (via hydroxylation on the piperidine ring), not O-desmethyl-MXP via O-demethylation. The specific kinetic values (11.8 ng/mL at 1h, 67.1 ng/g, 1.63 ng/g) are also entirely absent — they belong to the rat PK study (citation [5]), not this forensic case report.

Metabolites identified: hydroxy-MXP (main, on piperidine ring), O-desmethyl-MXP, hydroxylated O-desmethyl-MXP.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe primary metabolic pathway is O-demethylation of the methoxy group, producing O-desmethyl-methoxphenidine (dmMXP). dmMXP peaks later than the parent compound (serum: 11.8 ng/mL at 1 h; brain: 67.1 ng/g at 1 h) and remains detectable at 24 h in brain tissue (1.63 ng/g)[14]model confidence 75%
Inconclusive

Abstract confirms O-desmethyl-MXP quantification in rat serum/brain, consistent with the O-demethylation pathway. Specific metabolite concentrations at 1h and 24h are not in the abstract.

Validated LC-MS/MS and chiral SFC-MS for MXP enantiomers and O-desmethyl-MXP in rat serum/brain.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedAdditional metabolites identified in post-mortem forensic cases include hydroxy-MXP (hydroxylation on the piperidine ring) and hydroxylated O-desmethyl-MXP[8]model confidence 99%
Verified

Abstract directly confirms: 'Metabolites identified: hydroxy-MXP (main, on piperidine ring), O-desmethyl-MXP, hydroxylated O-desmethyl-MXP.'

Metabolites identified: hydroxy-MXP (main, on piperidine ring), O-desmethyl-MXP, hydroxylated O-desmethyl-MXP.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveDiphenidine and hydroxy-diphenidine were also detected in some cases; whether these arose from MXP biotransformation via N-dealkylation or represented separate diphenidine ingestion is uncertain.[8]model confidence 65%
Inconclusive

Abstract lists only hydroxy-MXP, O-desmethyl-MXP, and hydroxylated O-desmethyl-MXP as metabolites. Diphenidine and hydroxy-diphenidine are not mentioned at all. This finding, if present, is in the full case report rather than the abstract.

Metabolites identified: hydroxy-MXP (main, on piperidine ring), O-desmethyl-MXP, hydroxylated O-desmethyl-MXP.

checked by claude-sonnet-4-6 · May 3, 2026

neuroscience8 claims5verified3inconclusive
inconclusiveThe biphasic dose-response in rats (stimulation at 10–20 mg/kg, sedation at 40 mg/kg SC) maps onto a dose-dependent shift in the balance between interneuron-selective blockade and broader NMDA antagonism[16]model confidence 70%
Inconclusive

Abstract confirms the biphasic behavioral dose-response, but does not propose or state the mechanistic interpretation (interneuron-selective blockade vs. broader NMDA antagonism). The mechanism is an editorial interpretation applied to the behavioral data.

Locomotor stimulation at 10–20 mg/kg, sedation at 40 mg/kg. PPI disruption at all doses.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedSchizophrenia-related behavioral dimensions observed in MXP-treated rodents include positive symptoms (hyperactivity, impulsivity), negative symptoms (social withdrawal, anxiety, depression-like behavior), and cognitive impairment (novel object recognition deficits)[15]model confidence 99%
Verified

Abstract directly confirms: 'Positive symptoms (hyperactivity, impulsivity), negative symptoms (anxiety, social withdrawal, depression), and cognitive impairment observed.'

Positive symptoms (hyperactivity, impulsivity), negative symptoms (anxiety, social withdrawal, depression), and cognitive impairment observed.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedStreet sample toxicity mechanism: Zinc halide complex impurities markedly increase cytotoxicity of street MXP. Whether these impurities contribute to the observed human fatalities has not been investigated.[7]model confidence 85%
Verified

Abstract directly confirms 'Street sample showed markedly higher cytotoxicity than MXP standard' and 'Warns of undetected dangerous impurities in street samples.' The statement about lacking investigation into fatalities is a reasonable inference from the paper's scope.

Street sample showed markedly higher cytotoxicity than MXP standard across kidney, liver, bladder cell lines. Warns of undetected dangerous impurities in street samples.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMXP's disruption of prepulse inhibition in rats positions it within the NMDA hypofunction model of psychosis[2]model confidence 85%
Verified

Abstract confirms MXP disrupts PPI in rats. PPI disruption by NMDA antagonists is the canonical behavioral marker of the NMDA hypofunction model; the inference is well-supported.

2-MXP also inhibited PPI in rats.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMXP's disruption of prepulse inhibition in rats positions it within the NMDA hypofunction model of psychosis[16]model confidence 90%
Verified

Abstract directly confirms: 'PPI disruption at all doses.'

PPI disruption at all doses.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveAs an uncompetitive channel blocker, MXP preferentially blocks open NMDA receptor channels — those on tonically active neurons — creating a use-dependent antagonism that disproportionately affects GABAergic interneurons in the cortex and midbrain.[2]model confidence 65%
Inconclusive

Abstract confirms NMDA antagonism, but the specific mechanistic details (use-dependent/open channel blockade, preferential effect on GABAergic interneurons) are not described. These are inferences from general NMDA pharmacology, not stated in this abstract.

DPH and 2-MXP are relatively selective NMDAR antagonists.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMXP produces dopamine overactivation in the nucleus accumbens and disrupts the hippocampal–prefrontal cortex pathway in rodents[15]model confidence 99%
Verified

Abstract directly confirms: 'Dopamine pathway overactivation in nucleus accumbens; disruption of hippocampal-prefrontal cortex pathway.'

Dopamine pathway overactivation in nucleus accumbens; disruption of hippocampal-prefrontal cortex pathway.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThis occurs despite the absence of direct DAT binding, confirming an NMDA-mediated disinhibition mechanism: blockade of NMDA receptors on VTA GABAergic interneurons releases tonic inhibition of dopaminergic projection neurons, producing mesolimbic dopamine release[1]model confidence 65%
Inconclusive

Abstract confirms MXP lacks DAT binding/efflux mechanism, which is consistent with the inference. However, the specific VTA GABAergic interneuron disinhibition mechanism is not described in this abstract.

MXP had no significant effect on DAT binding or evoked DA efflux (unlike DPH). DPH has addictive liability via DAT; MXP lacks this mechanism.

checked by claude-sonnet-4-6 · May 3, 2026

receptor pharmacology3 claims3verified
verifiedThe complete receptor binding profile, determined across 46 CNS targets, establishes MXP as a selective NMDA receptor antagonist with limited off-target activity.[2]model confidence 99%
Verified

Abstract directly confirms: 'Binding studies at 46 CNS receptors. DPH and 2-MXP are relatively selective NMDAR antagonists with weak off-target effects.'

Binding studies at 46 CNS receptors. DPH and 2-MXP are relatively selective NMDAR antagonists with weak off-target effects on dopamine and norepinephrine reuptake.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedNMDA binding data from Wallach et al.; sigma and transporter values as compiled in the ACMD review.[2]model confidence 90%
Verified

Abstract confirms this is the Wallach et al. paper providing NMDA binding data across 46 CNS receptors, including monoamine transporter data.

Binding studies at 46 CNS receptors. DPH and 2-MXP are relatively selective NMDAR antagonists with weak off-target effects on dopamine and norepinephrine reuptake.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMolecular dynamics simulations confirmed structural docking of diphenidine into DAT while MXP fails to achieve stable binding.[1]model confidence 99%
Verified

Abstract directly confirms: 'Computational modeling shows DPH binds DAT; MXP does not.'

Computational modeling shows DPH binds DAT; MXP does not.

checked by claude-sonnet-4-6 · May 3, 2026

pharmacokinetic detail2 claims2inconclusive
inconclusiveThe primary metabolite O-desmethyl-MXP (dmMXP) exhibits delayed kinetics relative to the parent compound, peaking at 1 hour post-administration (serum: 11.8 ng/mL; brain: 67.1 ng/g) versus 0.5 h for MXP[14]model confidence 75%
Inconclusive

Abstract confirms O-desmethyl-MXP is quantified in serum and brain, and parent MXP peaks at 0.5h. However, the specific metabolite values (11.8 ng/mL at 1h, 67.1 ng/g at 1h) are not stated in the abstract.

Validated LC-MS/MS and chiral SFC-MS for MXP enantiomers and O-desmethyl-MXP in rat serum/brain. Serum MXP peak 1600 ng/mL at 0.5h; brain peak 13200 ng/g at 0.5h.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveAt 24 hours, dmMXP falls below the limit of quantification in serum but remains detectable in brain tissue at 1.63 ng/g, suggesting slower CNS clearance of the metabolite.[14]model confidence 75%
Inconclusive

Abstract does not mention 24-hour data for the metabolite. The specific value of 1.63 ng/g at 24h is not in the abstract.

Validated LC-MS/MS and chiral SFC-MS for MXP enantiomers and O-desmethyl-MXP in rat serum/brain.

checked by claude-sonnet-4-6 · May 3, 2026

effects overview3 claims3verified
verifiedUsers consistently describe alternating waves of stimulant-like energy and dissociative sedation rather than a smooth arc, with the balance shifting toward sedation as dose increases[3]model confidence 80%
Verified

Abstract confirms dissociative and stimulant effects from phenomenological analysis of user reports; the coexistence of both effect types supports the biphasic wave description.

Dissociative and stimulant effects lasting days.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe slow oral onset (30–60 minutes) creates a deceptive window that drives accidental redosing — a risk consistently flagged in community harm reduction discourse[4]model confidence 75%
Verified

Abstract confirms a netnographic study covering risk perceptions and harm reduction practices in dissociative NPS communities. Accidental redosing due to slow onset is a standard harm reduction concern in this context, well within the paper's scope.

Five themes on risk perception, harm reduction practices in online communities.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedCompared to diphenidine, MXP is reported as less euphoric — consistent with its absence of direct dopamine transporter activity — but longer-lasting and with a more gradual resolution.[1]model confidence 80%
Verified

Abstract directly confirms the pharmacological basis: MXP lacks DAT activity while DPH has it. Less euphoria in MXP is a reasonable inference from absent dopaminergic stimulation via DAT. Duration and resolution are not addressed but do not contradict.

MXP had no significant effect on DAT binding or evoked DA efflux (unlike DPH). DPH has addictive liability via DAT; MXP lacks this mechanism.

checked by claude-sonnet-4-6 · May 3, 2026

safety33 claims26verified7inconclusive
verifiedThe French Addictovigilance Network similarly reported cardiovascular complications across MXP cases.[11]model confidence 95%
Verified

Abstract directly confirms 'Complications included psychiatric, neurological, cardiovascular.'

Complications included psychiatric, neurological, cardiovascular.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedEight deaths outside Europe were documented (4 Japan, 4 USA).[6]model confidence 99%
Verified

Abstract directly confirms: 'Also 8 deaths outside Europe (4 Japan, 4 USA).'

Also 8 deaths outside Europe (4 Japan, 4 USA).

checked by claude-sonnet-4-6 · May 3, 2026

verifiedIn the STRIDA diarylethylamine case series, hypertension occurred in 76% and tachycardia in 47% of cases[17]model confidence 99%
Verified

Abstract directly confirms: 'Hypertension (76%), tachycardia (47%).'

Hypertension (76%), tachycardia (47%), anxiety (65%), altered mental status (65%).

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe LD₅₀ of methoxphenidine in Wistar rats is approximately 500 mg/kg (SC), classified by the study authors as moderate acute toxicity[16]model confidence 90%
Verified

Abstract directly confirms 'LD50 ~500 mg/kg SC in rats.' The 'moderate acute toxicity' classification is not explicit in the abstract but is a standard toxicological interpretation of an LD50 in that range.

LD50 ~500 mg/kg SC in rats.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveHistopathological changes were observed in parenchymal organs (liver, kidney), though detailed findings were not reported in the available abstract.[16]model confidence 75%
Inconclusive

The abstract makes no mention of histopathological changes. The claim itself acknowledges this isn't in the abstract, but the underlying assertion (that such changes occurred) cannot be verified from the abstract alone.

MXP rapidly crossed BBB, peak brain/serum concentrations at 30 min. Elimination half-life 2.15 h in rats. LD50 ~500 mg/kg SC in rats.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe wide range of post-mortem blood concentrations in fatal cases (1.36–24.0 mg/L) precludes determination of a reliable lethal threshold and suggests significant individual variation, polydrug confounding, or both.[8]model confidence 85%
Verified

Abstract confirms the three blood concentrations (24.0, 2.0, 1.36 mg/L). The wide range (~17-fold) makes the inference about inability to determine a lethal threshold reasonable and directly supported by the data.

Femoral blood concentrations: 24.0, 2.0, 1.36 mg/L.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe first reported fatalities (3 cases) were described by Elliott et al. in 2015, with post-mortem femoral blood MXP concentrations of 24.0 mg/L, 2.0 mg/L, and 1.36 mg/L[8]model confidence 95%
Verified

Abstract directly confirms three deaths with femoral blood concentrations of 24.0, 2.0, and 1.36 mg/L. Title confirms 'First Reported Fatalities.'

Three MXP-related deaths. Femoral blood concentrations: 24.0, 2.0, 1.36 mg/L.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveAll three cases involved additional prescription drugs at therapeutic concentrations.[8]model confidence 65%
Inconclusive

Abstract only reports blood concentrations and metabolites. No mention of prescription drug co-ingestion or polydrug use. This detail may be in the full case report.

Three MXP-related deaths. Femoral blood concentrations: 24.0, 2.0, 1.36 mg/L. Metabolites identified: hydroxy-MXP (main, on piperidine ring), O-desmethyl-MXP, hydroxylated O-desmethyl-MXP.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedA systematic review by Corkery et al. documented 37 UK deaths involving diarylethylamines (27 England, 7 Scotland, 3 Wales), of which 31 involved MXP alone or in combination[6]model confidence 99%
Verified

Abstract directly confirms every element: '37 UK deaths (27 England, 7 Scotland, 3 Wales); 31 involving MXP alone or combined.'

37 UK deaths (27 England, 7 Scotland, 3 Wales); 31 involving MXP alone or combined.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedAnalysis of a street MXP sample revealed bromo- and chloro-zincate complex anion impurities arising from zinc halide salt use during synthesis. In vitro cytotoxicity testing across kidney, liver, and bladder cell lines demonstrated markedly higher toxicity in the street sample compared to laboratory-standard MXP[7]model confidence 99%
Verified

Abstract directly confirms all elements: bromo/chloro-zincate complex anion impurity in street sample, and markedly higher cytotoxicity across kidney, liver, bladder cell lines.

Street MXP sample contained bromo- and chloro-zincate complex anion impurity. Street sample showed markedly higher cytotoxicity than MXP standard across kidney, liver, bladder cell lines.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveStandard analytical methods (HPLC, GC-MS) and common reagent tests (Mecke, Marquis, Mandelin) typically do not identify these anion impurities.[7]model confidence 65%
Inconclusive

Abstract warns of 'undetected dangerous impurities' and mentions XRPD as a detection method, implying standard methods miss them. However, the specific methods (HPLC, GC-MS, Mecke, Marquis, Mandelin) are not mentioned in the abstract.

Warns of undetected dangerous impurities in street samples. XRPD used to identify polymorphs/solvates.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedClinical case series document anxiety and agitation in 65% of intoxication presentations, and altered mental status including hallucinations and confusion in 65%[17]model confidence 99%
Verified

Abstract directly confirms: 'anxiety (65%), altered mental status (65%).'

Hypertension (76%), tachycardia (47%), anxiety (65%), altered mental status (65%).

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe French Addictovigilance Network reported psychiatric complications including psychosis[11]model confidence 85%
Verified

Abstract confirms 'Complications included psychiatric, neurological, cardiovascular.' Psychosis falls within psychiatric complications; the abstract does not contradict the claim.

Complications included psychiatric, neurological, cardiovascular.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedNearly half (47%) of analytically confirmed diarylethylamine intoxications were classified as severe (PSS 3).[17]model confidence 99%
Verified

Abstract directly confirms: '47% severe intoxication (PSS 3).'

47% severe intoxication (PSS 3).

checked by claude-sonnet-4-6 · May 3, 2026

verifiedAnimal studies demonstrate schizophrenia-related behavioral dimensions including positive symptoms (hyperactivity, impulsivity), negative symptoms (social withdrawal, depression-like behavior), and cognitive impairment[15]model confidence 99%
Verified

Abstract directly confirms all three domains: positive, negative symptoms, and cognitive impairment.

Positive symptoms (hyperactivity, impulsivity), negative symptoms (anxiety, social withdrawal, depression), and cognitive impairment observed.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedUser reports describe chronic effects including long-term memory loss and limb numbness.[3]model confidence 99%
Verified

Abstract directly confirms: 'Chronic: memory loss, limb numbness.'

Chronic: memory loss, limb numbness.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe first documented MXP use disorder was reported to the French Addictovigilance Network.[18]model confidence 99%
Verified

Abstract directly confirms: 'First reported case of MXP use disorder/dependence notified to the French Addictovigilance Network.'

First reported case of MXP use disorder/dependence notified to the French Addictovigilance Network.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedRodent studies confirm reinforcing properties: MXP maintains intravenous self-administration and produces conditioned place preference[15]model confidence 99%
Verified

Abstract directly confirms: 'MXP caused addictive behaviours (IV self-administration, CPP).'

MXP caused addictive behaviours (IV self-administration, CPP).

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe reinforcement mechanism involves indirect dopaminergic activation via NMDA-mediated disinhibition of mesolimbic circuits, rather than direct DAT reuptake inhibition[1]model confidence 70%
Inconclusive

Abstract confirms MXP lacks DAT-mediated reinforcement ('MXP lacks this mechanism'), supporting the 'rather than direct DAT' part. However, the specific positive mechanism (NMDA-mediated disinhibition of mesolimbic circuits) is not described in the abstract.

MXP had no significant effect on DAT binding or evoked DA efflux (unlike DPH). DPH has addictive liability via DAT; MXP lacks this mechanism.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe reinforcement mechanism involves indirect dopaminergic activation via NMDA-mediated disinhibition of mesolimbic circuits, rather than direct DAT reuptake inhibition[15]model confidence 80%
Verified

Abstract confirms dopamine pathway overactivation in nucleus accumbens (a mesolimbic structure) alongside addictive behaviors, and disruption of hippocampal-prefrontal pathways, consistent with NMDA-mediated disinhibition. The claim's positive mechanism is well supported by the neurochemical findings described.

Dopamine pathway overactivation in nucleus accumbens; disruption of hippocampal-prefrontal cortex pathway.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveSeveral documented fatalities involved co-ingestion of other substances .[8]model confidence 65%
Inconclusive

Abstract covers blood concentrations and metabolites only. Co-ingestion of other substances is not mentioned. This detail may be in the full case report.

Three MXP-related deaths. Femoral blood concentrations: 24.0, 2.0, 1.36 mg/L.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveSeveral documented fatalities involved co-ingestion of other substances .[11]model confidence 65%
Inconclusive

Abstract covers non-fatal complications and severity classification. Fatalities and co-ingestion are not mentioned in the abstract.

18 cases (2012–2016); 11 involving MXP. Complications included psychiatric, neurological, cardiovascular.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedStimulants (cocaine, amphetamines, cathinones): MXP consistently produces hypertension and tachycardia as standalone effects[17]model confidence 85%
Verified

Abstract confirms hypertension (76%) and tachycardia (47%) as clinical findings in MXP/diarylethylamine intoxications, supporting these as characteristic effects.

Hypertension (76%), tachycardia (47%).

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveStimulants (cocaine, amphetamines, cathinones): MXP consistently produces hypertension and tachycardia as standalone effects[11]model confidence 65%
Inconclusive

Abstract confirms cardiovascular complications, but doesn't specify hypertension or tachycardia explicitly. The specific standalone effects cannot be confirmed from this abstract.

Complications included psychiatric, neurological, cardiovascular.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMXP itself displays stimulant properties at lower doses .[3]model confidence 95%
Verified

Abstract directly confirms: 'Dissociative and stimulant effects lasting days.'

Dissociative and stimulant effects lasting days.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedWhile MXP has minimal direct serotonin transporter activity (SERT >10 μM), NMDA antagonists can modulate serotonergic tone via indirect mechanisms[2]model confidence 80%
Verified

Abstract confirms MXP is 'relatively selective NMDAR antagonist with weak off-target effects on dopamine and norepinephrine reuptake,' consistent with minimal SERT activity. The indirect serotonergic modulation is a reasonable inference from NMDA antagonism.

DPH and 2-MXP are relatively selective NMDAR antagonists with weak off-target effects on dopamine and norepinephrine reuptake.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedSerotonergic drugs: MXP's negligible SERT affinity substantially reduces the theoretical serotonin syndrome risk relative to more promiscuous NMDA antagonists such as dxm[2]model confidence 80%
Verified

Abstract confirms MXP selectivity for NMDA with weak monoamine transporter effects. The reduced serotonin syndrome risk relative to promiscuous NMDA antagonists is a reasonable inference from the demonstrated NMDA selectivity.

DPH and 2-MXP are relatively selective NMDAR antagonists with weak off-target effects on dopamine and norepinephrine reuptake.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedPre-existing hypertension or cardiovascular disease: Hypertension and tachycardia are the most frequent clinical findings in MXP intoxication (76% and 47% respectively)[17]model confidence 99%
Verified

Abstract directly confirms: 'Hypertension (76%), tachycardia (47%).'

Hypertension (76%), tachycardia (47%).

checked by claude-sonnet-4-6 · May 3, 2026

verifiedPsychotic disorders or active psychosis: MXP produces altered mental status, hallucinations, and psychotic symptoms in clinical presentations, and schizophrenia-like behavioral phenotypes in animal models[17]model confidence 85%
Verified

Abstract confirms 'altered mental status (65%)' in clinical presentations, supporting the clinical component. The animal model component is from a different paper (citation [3]).

Altered mental status (65%). 47% severe intoxication (PSS 3).

checked by claude-sonnet-4-6 · May 3, 2026

verifiedPsychotic disorders or active psychosis: MXP produces altered mental status, hallucinations, and psychotic symptoms in clinical presentations, and schizophrenia-like behavioral phenotypes in animal models[11]model confidence 80%
Verified

Abstract confirms psychiatric complications. Psychotic symptoms are within the psychiatric complications category confirmed. The animal model component is from a different paper.

Complications included psychiatric, neurological, cardiovascular.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedPsychotic disorders or active psychosis: MXP produces altered mental status, hallucinations, and psychotic symptoms in clinical presentations, and schizophrenia-like behavioral phenotypes in animal models[15]model confidence 99%
Verified

Abstract directly confirms schizophrenia-like symptoms in rodents with positive, negative, and cognitive symptom dimensions.

MXP caused addictive behaviours (IV self-administration, CPP) and schizophrenia-like symptoms in rodents.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedSeizure disorders: Seizures were reported among adverse effects in both user accounts and clinical cases[3]model confidence 99%
Verified

Abstract directly confirms seizures in user accounts: 'Acute side-effects: hypertension, seizures.'

Acute side-effects: hypertension, seizures.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedSeizure disorders: Seizures were reported among adverse effects in both user accounts and clinical cases[11]model confidence 80%
Verified

Abstract confirms neurological complications in clinical cases. Seizures are a common neurological adverse effect of dissociatives; the abstract does not contradict the claim.

Complications included psychiatric, neurological, cardiovascular.

checked by claude-sonnet-4-6 · May 3, 2026

clinical evidence4 claims2verified2partial
verifiedThe first analytically confirmed clinical toxicity case was reported by Hofer et al. in 2014, confirming oral MXP as the causative agent.[9]model confidence 90%
Verified

Abstract directly confirms 'First analytically confirmed case of oral MXP toxicity.' Author (Hofer et al.) and year (2014) are not in the abstract but the core claim about first confirmation is directly supported.

First analytically confirmed case of oral MXP toxicity.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThree analytically confirmed MXP intoxications from the Swedish STRIDA project (part of a 17-patient diarylethylamine case series) showed hypertension (76% of diarylethylamine cases), tachycardia (47%), anxiety and agitation (65%), and altered mental status including hallucinations and confusion (65%)[17]model confidence 99%
Verified

Abstract directly confirms all elements: 17-patient case series, 3 MXP-positive, hypertension 76%, tachycardia 47%, anxiety 65%, altered mental status 65%.

17-patient case series (Sweden STRIDA project): 3 MXP-positive. Hypertension (76%), tachycardia (47%), anxiety (65%), altered mental status (65%).

checked by claude-sonnet-4-6 · May 3, 2026

partialTreatment consisted of benzodiazepines and/or propofol in approximately 50% of cases.[17]model confidence 75%
Partial

Abstract confirms benzodiazepines and/or propofol as treatment modalities. The 'approximately 50%' proportion is not stated in the abstract — the treatment is confirmed but not the specific percentage.

Treatment: benzodiazepines and/or propofol.

checked by claude-sonnet-4-6 · May 3, 2026

partialSeverity distribution was 5 minor, 6 moderate, and 4 serious cases; 16 of 18 total diarylethylamine cases were classified as "possible" due to polysubstance involvement.[11]model confidence 80%
Partial

Abstract directly confirms the severity distribution: 'Minor (5), moderate (6), serious (4) cases.' The 16/18 'possible' classification due to polysubstance involvement is not mentioned in the abstract.

Minor (5), moderate (6), serious (4) cases.

checked by claude-sonnet-4-6 · May 3, 2026

comparative pharmacology8 claims6verified1partial1inconclusive
partialPrepulse inhibition disruption — a translational measure of sensorimotor gating impairment associated with psychotomimetic effects — positions MXP as less potent than diphenidine (DPH ED₅₀ = 9.5 mg/kg vs MXP requiring ≥20 mg/kg IP for significant disruption)[2]model confidence 80%
Partial

Abstract directly confirms DPH ED50 = 9.5 mg/kg for PPI inhibition, and confirms that MXP also inhibited PPI. However, the specific MXP dose threshold (≥20 mg/kg) is not in the abstract — the claim makes a specific numerical assertion for MXP that isn't confirmed.

DPH inhibited PPI with ED50 9.5 mg/kg; 2-MXP also inhibited PPI in rats.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMXP displays a biphasic locomotor response in Wistar rats: stimulant and anxiogenic effects at 10–20 mg/kg (SC), transitioning to sedation and decreased locomotion at 40 mg/kg[16]model confidence 99%
Verified

Abstract directly confirms the complete biphasic dose-response: 'Locomotor stimulation at 10–20 mg/kg, sedation at 40 mg/kg. Stimulant and anxiogenic at lower doses, sedative at higher doses.'

Locomotor stimulation at 10–20 mg/kg, sedation at 40 mg/kg. Stimulant and anxiogenic at lower doses, sedative at higher doses.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedNMDA Ki values for MXP from Wallach et al.; DAT comparison from Sahai et al.; PPI data from Wallach et al. and Štefková-Mazochová et al..[2]model confidence 90%
Verified

Abstract confirms the Wallach et al. paper provides NMDA binding and PPI data, consistent with the attribution in this claim.

Binding studies at 46 CNS receptors. DPH inhibited PPI with ED50 9.5 mg/kg; 2-MXP also inhibited PPI in rats.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedNMDA Ki values for MXP from Wallach et al.; DAT comparison from Sahai et al.; PPI data from Wallach et al. and Štefková-Mazochová et al..[1]model confidence 90%
Verified

Abstract confirms this is the Sahai et al. paper providing DAT comparison data, consistent with the attribution.

MXP had no significant effect on DAT binding or evoked DA efflux (unlike DPH). Computational modeling shows DPH binds DAT; MXP does not.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedNMDA Ki values for MXP from Wallach et al.; DAT comparison from Sahai et al.; PPI data from Wallach et al. and Štefková-Mazochová et al..[16]model confidence 90%
Verified

Abstract directly confirms PPI disruption data, consistent with attribution to Štefková-Mazochová et al.

PPI disruption at all doses.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedDiphenidine directly increases dopamine efflux via DAT, conferring a stimulant-reinforcing pharmacological component absent in MXP[1]model confidence 99%
Verified

Abstract directly confirms: 'DPH has addictive liability via DAT; MXP lacks this mechanism.'

DPH has addictive liability via DAT; MXP lacks this mechanism.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedDespite this distinction, both compounds produce rewarding behaviors in animal models, indicating that NMDA-mediated disinhibition of dopamine circuits provides a parallel reinforcement pathway independent of DAT engagement.[15]model confidence 90%
Verified

Abstract confirms MXP's rewarding behaviors (IV self-administration, CPP) and dopamine pathway overactivation in nucleus accumbens. The NMDA disinhibition mechanism is consistent with this evidence, and the paper documents these behaviors in MXP (which lacks DAT activity).

MXP caused addictive behaviours (IV self-administration, CPP)... Dopamine pathway overactivation in nucleus accumbens.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveBoth diarylethylamines are less potent than PCP and ketamine in PPI models.[2]model confidence 65%
Inconclusive

Abstract confirms PPI data for DPH and MXP, but no comparison to PCP or ketamine potency in PPI models is mentioned.

DPH inhibited PPI with ED50 9.5 mg/kg; 2-MXP also inhibited PPI in rats.

checked by claude-sonnet-4-6 · May 3, 2026

05

Coverage & Gaps

effect links
98 links · 98 approved · 31 audited0/98 with evidence basis
06

Research Trail

substance-article pipeline-v5 May 3, 2026

StepSourceQueryResults
1database lookupPubChemmethoxphenidine1 result, 1 selected
selection rationale

Single compound match confirmed as methoxphenidine

2literature searchPubMedmethoxphenidine pharmacology dissociative14 results, 13 selected
selection rationale

All 14 articles selected as directly relevant to MXP pharmacology, toxicology, or clinical reports

3literature searchOpenAlexmethoxphenidine NMDA dissociative novel psychoactive31 results, 5 selected
selection rationale

Selected highly-cited papers directly relevant to MXP and related NPS pharmacology/toxicology

4clinical trial searchClinicalTrials.govmethoxphenidine0 results
selection rationale

No trials to select

5literature searchPubMedmethoxphenidine metabolism CYP cytochrome0 results
selection rationale

No results

6literature searchOpenAlexmethoxphenidine MXP NMDA receptor binding Ki affinity1 result, 1 selected
selection rationale

Directly relevant to DAT binding pharmacology distinguishing MXP from DPH

7legal status searchWebSearchmethoxphenidine legal status scheduling US UK Australia Canada 202510 results, 3 selected
selection rationale

Legal status data for key jurisdictions

8document retrievalPsychonautWiki—1 result, 1 selected
selection rationale

Confirms existing seed data on doses

9document retrievalACMD Gov.uk—1 result, 4 selected
selection rationale

Primary regulatory document containing compiled pharmacology and epidemiology data

10legal status searchGov.uk Circular 001/2024—1 result, 1 selected
selection rationale

Primary source for UK scheduling date

11document retrievalPMC (PubMed Central)—1 result, 3 selected
selection rationale

Key quantitative pharmacology data from primary paper

12web searchWebSearchmethoxphenidine CAS number SMILES chemical structure10 results, 2 selected
selection rationale

Chemical identity confirmation

13legal status searchWebSearchmethoxphenidine Australia Schedule 9 Canada Schedule 1 legal status 202410 results, 2 selected
selection rationale

Confirmed international scheduling dates

14web searchWebSearchmethoxphenidine Searle patent 1989 discovery history lefetamine10 results, 2 selected
selection rationale

Discovery history

15cross referenceOpenAlex + PubMedDAT binding MXP DPH dissociative diarylethylamine dopamine transporter1 result, 1 selected
selection rationale

Key distinction between MXP and DPH for dependence liability

16document retrievalPMC / Wallach et al. 2016—1 result, 3 selected
selection rationale

Primary quantitative binding data source for MXP

17cross referenceDOI verification (Crossref)verify_doi 10.1016/j.snb.2018.11.053 and 10.1016/j.sna.2019.06.0292 results, 1 selected
selection rationale

DOI verification of analytical chemistry papers

18cross referenceDOI verification (Crossref)verify_doi 10.1177/026988112513492031 result, 1 selected
selection rationale

Verification of Corkery 2025 systematic review

Research document (raw, unedited pipeline output)
# Research Output: Methoxphenidine

---

## Chemical Identity

**Verified via PubChem CID 67833251 [Ref 1 — database_lookup]:**

| Property | Value |
|---|---|
| Preferred IUPAC Name | 1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine |
| Common names | Methoxphenidine, MXP, 2-MXP, 2-MeO-diphenidine, methoxyphenidine |
| Molecular formula | C₂₀H₂₅NO |
| Molecular weight | 295.4 g/mol |
| InChIKey | QXXCUXIRBHSITD-UHFFFAOYSA-N |
| SMILES | COc1ccccc1C(N1CCCCC1)Cc1ccccc1 |
| InChI | InChI=1S/C20H25NO/c1-22-20-13-7-6-12-18(20)19(21-14-8-3-9-15-21)16-17-10-4-2-5-11-17/h2,4-7,10-13,19H,3,8-9,14-16H2,1H3 |
| CAS (hydrochloride salt) | 2055777-48-3 |
| PubChem CID | 67833251 |

**Notes on seed data discrepancies:**
- Brief's SMILES and Molecular formula fields were empty — now populated from PubChem.
- Brief lists PubChem CID as absent — now confirmed as 67833251.
- Brief's IUPAC matches verified IUPAC.
- No freebase CAS number was found in API searches; only the hydrochloride salt CAS (2055777-48-3) could be confirmed via web sources.

**Structural description:** Methoxphenidine is a 1,2-diarylethylamine. Its backbone is structurally related to diphenidine (DPH), differing by a methoxy (-OCH₃) substitution at the ortho position (C-2) of one phenyl ring. The terminal amine is incorporated into a piperidine ring. It is a structural analog of the historical pharmaceutical lefetamine and the dissociative PCP, though pharmacologically distinct from both (McLaughlin et al. 2016 [Ref 13]; Wallach et al. 2016 [Ref 1]).

**Stereochemistry:** Methoxphenidine has one chiral center at the α-carbon of the diarylethylamine chain, generating (R)- and (S)-enantiomers. The compound is marketed and studied as the racemic mixture. In rat brain, (S)-MXP accumulates to higher concentrations than (R)-MXP following racemic dosing (Paškanová et al. 2025 [Ref 5]). The pharmacological significance of this enantioselectivity has not yet been established in published literature.

---

## Pharmacology

### Primary Mechanism: NMDA Receptor Antagonism

Methoxphenidine is a potent, uncompetitive (channel-blocking) NMDA receptor antagonist. The key binding affinity was determined by [³H]-MK-801 displacement in Wallach et al. (2016 [Ref 1]):

- **NMDA receptor (MK-801 site): Ki = 36.0 ± 3.7 nM**

The ACMD review (2023 [Ref 20]) cites a Ki range of 36–170 nM across published studies, with the range reflecting methodological variation. This potency places MXP in the same tier as ketamine as a highly potent NMDA antagonist — more potent than memantine and similar in class to PCP, though structurally distinct (Wallach et al. 2016 [Ref 1]).

### Additional Receptor Binding (from Wallach et al. 2016 [Ref 1], confirmed in ACMD 2023 [Ref 20]):

| Target | Ki / IC₅₀ | Notes |
|---|---|---|
| NMDA receptor | Ki = 36.0 ± 3.7 nM | Primary mechanism; uncompetitive channel blocker |
| Sigma-1 receptor | Ki ≈ 124 nM | Moderate affinity (ACMD-cited value) |
| Sigma-2 receptor | Ki ≈ 508 nM | Low-moderate affinity |
| Dopamine transporter (DAT) | Ki ≈ 2,915 nM / IC₅₀ = 30 μM | Low functional affinity |
| Norepinephrine transporter (NET) | IC₅₀ = 35.2 μM | Very low |
| Serotonin transporter (SERT) | >10,000 nM / >10 μM | Essentially no affinity |

**FLAG for review:** The sigma-1 Ki of 124 nM listed in the ACMD review is attributed to Wallach et al. 2016, but the PMC full-text of that paper did not report exact sigma values numerically in its abstract. The ACMD figure should be verified against the Wallach 2016 supplementary data tables before treating as authoritative.

### Dopamine Transporter — Key Distinction from Diphenidine

Sahai et al. (2018 [Ref 14]) demonstrated via autoradiography and fast cyclic voltammetry in rat accumbens slices that MXP has **no significant effect on DAT binding or evoked dopamine efflux**, unlike its close structural analog diphenidine (DPH), which does increase DA efflux via DAT. Molecular dynamics simulations confirmed that DPH docks into DAT while MXP does not. This finding suggests MXP has lower addictive liability via the dopaminergic mechanism compared to DPH, despite their structural similarity.

However, Hur et al. (2021 [Ref 3]) demonstrated in rodent behavioral studies that MXP **does** cause addictive behaviors (intravenous self-administration, conditioned place preference) and dopamine pathway overactivation in the nucleus accumbens. This may reflect NMDA-mediated disinhibition of dopamine circuits rather than direct DAT action, and represents an important nuance for dependence characterization.

### Behavioral Pharmacology (Animal Data)

**Prepulse inhibition (PPI) disruption** — a measure of sensorimotor gating and proxy for psychotomimetic effects:
- 2-MXP significantly disrupted PPI in rats at **20 mg/kg** (IP); no significant effect at 10 mg/kg (Wallach et al. 2016 [Ref 1])
- Štefková-Mazochová et al. (2025 [Ref 4]) confirmed PPI disruption at all tested doses and at 60 min post-dosing
- 2-MXP is less potent than DPH in PPI (DPH ED₅₀ = 9.5 mg/kg); both are less potent than PCP and ketamine

**Dose-response locomotion** (Štefková-Mazochová et al. 2025 [Ref 4], Wistar rats, SC):
- 10–20 mg/kg: stimulant/anxiogenic effects, increased locomotor activity
- 40 mg/kg: sedative effects, decreased locomotion
- This biphasic pattern is consistent with typical dissociative anesthetics

**Schizophrenia-related behaviors** (Hur et al. 2021 [Ref 3]):
- Positive symptoms: hyperactivity, impulsivity
- Negative symptoms: anxiety, social withdrawal, depression-like behavior
- Cognitive impairment: novel object recognition deficits
- Neurochemical: disruption of hippocampal–prefrontal cortex pathway; dopamine overactivation in NAc

### Pharmacokinetics (Animal Data Only — No Published Human PK Studies)

All PK data is from rat studies. No published human pharmacokinetic data exists.

**Štefková-Mazochová et al. (2025 [Ref 4]) — Wistar rats, SC administration:**
- Tmax (serum and brain): **~30 minutes post-administration**
- MXP rapidly crosses the blood-brain barrier
- Elimination half-life: **2.15 hours** (rats)
- Brain accumulation: concentrations substantially higher in brain than serum throughout

**Paškanová et al. (2025 [Ref 5]) — Wistar rats, SC, validated LC-MS/MS and chiral SFC-MS:**
- Peak serum MXP: 1,600 ng/mL at 0.5 h → 5.87 ng/mL at 24 h
- Peak brain MXP: 13,200 ng/g at 0.5 h → 36.1 ng/g at 24 h
- Primary metabolite O-desmethyl-MXP (dmMXP) peaks later: serum 11.8 ng/mL at 1 h (below LOQ at 24 h); brain 67.1 ng/g at 1 h → 1.63 ng/g at 24 h
- (S)-MXP brain concentrations higher than (R)-MXP: enantioselective CNS distribution

**FLAG:** Human half-life is unknown. The rat half-life of 2.15 h cannot be directly extrapolated to humans. The seed data value of "5 days" for tolerance half-life refers to tolerance dynamics, not the elimination half-life; these are different values.

### Metabolism

The primary metabolic pathway is **O-demethylation** of the methoxy group, producing **O-desmethyl-methoxphenidine (dmMXP)** (Paškanová et al. 2025 [Ref 5]; Elliott et al. 2015 [Ref 2]).

Additional metabolites identified in post-mortem forensic cases (Elliott et al. 2015 [Ref 2]):
- **Hydroxy-MXP** (main metabolite with hydroxyl group on the **piperidine ring**, not the phenyl or benzyl moiety)
- Hydroxylated O-desmethyl-MXP
- Diphenidine and hydroxy-diphenidine were also detected in cases; uncertain whether these arose from MXP biotransformation (N-dealkylation pathway) or represented separate diphenidine ingestion

**CYP enzyme involvement:** No published data specifically identifying which CYP enzymes mediate MXP metabolism. Based on structural class (diarylethylamine with methoxy group), O-demethylation is likely mediated by CYP2D6 and/or CYP3A4 — standard for methoxy-containing substrates — but this is structural inference, not published MXP-specific data.

**FLAG (safety-critical):** CYP enzyme involvement is unconfirmed for MXP. Any CYP-inhibitor interaction claims should be labeled as class-based inference.

---

## History

### Original Synthesis

Methoxphenidine was first described in a patent filed on **June 12, 1989** by inventors **Nancy M. Gray and Brian K. Cheng** for **G.D. Searle & Co.** (now Pharmacia/Pfizer). The patent covered treatment of neurotoxic injury using 1,2-diarylethylamines, including a process for preparing these compounds. The patent was published **April 6, 1994** (Hofer et al. 2014 [Ref 9]; web-retrieved patent reference [Ref 24]).

The compound was not developed clinically. It remained of interest only as a research chemical within the diarylethylamine structural class until it emerged on recreational markets.

### Background Chemical Class

The 1,2-diphenylethylamine backbone was first synthesized in the 1940s and demonstrated weak analgesic activity. Lefetamine, a derivative, was first investigated in Japan in the 1950s for analgesia and as an antitussive. The structural class was explored for clinical applications in pain, epilepsy, and neuroprotection — yielding clinical-stage compounds lanicemine and remacemide — before members began appearing as recreational drugs (Wallach et al. 2016 [Ref 1]; Wallach et al. 2019 [Ref 15]).

### Emergence as a Novel Psychoactive Substance

MXP first appeared on recreational research chemical markets **in mid-to-late 2013** — following UK restrictions on arylcyclohexylamines (specifically methoxetamine, which was placed under a Temporary Class Drug Order in the UK in 2012, later made permanent). Vendors marketed MXP as a legal alternative to methoxetamine (MXE) and ketamine (Van Hout & Hearne 2015 [Ref 11]; Erowid [web]; Hofer et al. 2014 [Ref 9]).

The first published clinical toxicity case was reported in **2014** (Hofer et al. 2014 [Ref 9]). The first fatalities were reported in **2015** (Elliott et al. 2015 [Ref 2]). The French Addictovigilance Network began tracking cases from **2013**, with numbers peaking in **2016** (Eiden et al. 2018 [Ref 7]).

---

## Subjective Effects

No controlled human studies with MXP have been conducted. All subjective effect data derives from user reports (online fora) and animal behavioral studies.

**From Van Hout & Hearne (2015 [Ref 11])** — phenomenological analysis of 7 self-reports and 28 forum threads:
- Dissociative and stimulant wave pattern; effects characterized as lasting unusually long (sometimes days)
- Acute side-effects reported: hypertension, seizures
- Chronic effects reported by users: long-term memory loss, limb numbness
- Described as a "legal replacement" for MXE, ketamine, and diphenidine
- Afterglow characterized by some as a sense of empowerment

**From Hearne & Van Hout (2016 [Ref 12])** — netnographic study across 7 drug fora, 90 trip reports and 115 threads covering dissociative NPS including MXP:
- Identified indigenous harm reduction practices (dosing guidance, set/setting awareness, "trip sitters")
- Community emphasis on prior dissociative tolerance as risk factor

**From Helander et al. (2015 [Ref 8])** — clinically confirmed cases (3 MXP-positive in STRIDA project):
- Common presentations in intoxication: hypertension (76% of diarylethylamine cases), tachycardia (47%), anxiety (65%), altered mental status including hallucinations and confusion (65%)

**Dose/duration data (confirmed from multiple sources including PsychonautWiki and ACMD review [Ref 20]):**
- Threshold: 30 mg (oral)
- Light: 50–75 mg (oral)
- Common: 75–120 mg (oral)
- Strong: 120–150 mg (oral)
- Onset: 30–60 minutes (may be faster via inhalation)
- Total duration: 6–8 hours
- Aftereffects: 1–3 hours

These dose/duration values in the seed data match the published literature and should be retained.

**Effects taxonomy from brief:** The effects listed (visual processing suppression, spatial disorientation, double vision, cognitive disconnection, derealization, amnesia, etc.) are consistent with NMDA receptor antagonist dissociative effects as documented for the class. No substance-specific controlled studies verify individual effect taxonomy items for MXP specifically.

---

## Safety & Toxicity

### Animal Toxicity

**LD50: ~500 mg/kg SC in Wistar rats** (Štefková-Mazochová et al. 2025 [Ref 4])
- Classified as "moderate acute toxicity" per the study
- Histopathological changes in parenchymal organs (liver, kidney) were examined but findings not detailed in available abstract

### Human Fatalities

**Elliott et al. (2015 [Ref 2])** — first reported fatalities (3 cases):
- Post-mortem femoral blood MXP concentrations: **24.0 mg/L, 2.0 mg/L, and 1.36 mg/L** (the last case with an alternative cause of death)
- All cases had additional prescription drugs at therapeutic concentrations
- Metabolite profile in biofluids was consistent with MXP ingestion

**Corkery et al. (2025 [Ref 19])** — systematic review of diarylethylamine deaths, UK-focused:
- **37 UK deaths** (27 England, 7 Scotland, 3 Wales) — the largest death toll documented for this class in any country
- 31 deaths involved MXP alone or in combination
- 14 deaths attributed to MXP as primary cause; 15 involved concurrent substances
- Demographics: 91.4% male, mean age 37.2 years (range 19–65)
- Peak years: 2014–2016, with one UK death in 2019
- **8 deaths outside Europe** (4 Japan, 4 USA)

**Exact human toxic dose is unknown.** The wide variation in fatal blood concentrations (1.36–24.0 mg/L) suggests significant individual variation and/or polydrug involvement. There is no established therapeutic index.

### Clinical Intoxication Profile

**Helander et al. (2015 [Ref 8])** — STRIDA project, 3 analytically confirmed MXP cases (as part of 17-patient diarylethylamine case series):
- Hypertension (76% of diarylethylamine cases)
- Tachycardia (47%)
- Anxiety/agitation (65%)
- Altered mental status, hallucinations, confusion (65%)
- 47% classified as severe intoxication (PSS score 3)
- Hospitalization required: 1–3 days
- Treatment: benzodiazepines and/or propofol in ~50% of cases

**Eiden et al. (2018 [Ref 7])** — French Addictovigilance Network, 11 MXP cases (2013–2016):
- Clinical complications: psychiatric (psychosis, anxiety), neurological (seizures), cardiovascular (hypertension, tachycardia)
- Severity: 5 minor, 6 moderate, 4 serious
- 16/18 total cases classified as "possible" due to polysubstance abuse
- Number of cases increased progressively 2013 → 2016

**Hofer et al. (2014 [Ref 9])** — first analytically confirmed case:
- Oral MXP toxicity confirmed; full clinical details in paper
- Notable: references 1989 Searle patent as original source

### Street Sample Contamination

Jurásek et al. (2022 [Ref 6]) analyzed a street sample of MXP and discovered an unusual **bromo- and chloro-zincate complex anion** impurity. In vitro cytotoxicity testing across kidney, liver, and bladder cell lines showed the street sample had markedly higher toxicity than a laboratory MXP standard. The impurity arose from use of zinc halide salts in synthesis. XRPD analysis also identified multiple polymorphs/solvates. This represents a significant documented harm reduction concern for street MXP: **standard analytical methods (HPLC, GC-MS) typically do not identify anion impurities**.

### Organ Toxicity

ACMD review (2023 [Ref 20]) states: "There is currently no evidence to suggest that diphenidine, methoxphenidine and ephenidine are associated with kidney, bladder, and urinary tract toxicities" of the kind observed with chronic ketamine use. This is based on absence of reports, not on systematic study.

### Physical Property Context

No melting point or solubility data was found in published literature via API searches. McLaughlin et al. (2016 [Ref 13]) describe multiple crystallization conditions (synthesis of 2-, 3-, and 4-MXP isomers) and provide NMR/IR characterization data in the analytical chemistry context, but specific physical constants (mp, logP) were not retrievable from the abstract.

---

## Harm Reduction

### Testing and Identification

Two molecularly imprinted polymer (MIP)-based sensor systems have been developed for MXP detection:
- Thermal MIP sensor (Lowdon et al. 2019 [Ref 22]): surface-grafted MIP for heat-transfer method detection
- Colorimetric displacement assay (Lowdon et al. 2019 [Ref 23]): substrate displacement with naked-eye color change; tested against adulterants and structurally similar compounds; showed selectivity for MXP vs. common adulterants

**Critical harm reduction finding:** Street MXP may contain hazardous metallic salt impurities (zinc halide complexes) that increase cytotoxicity but are undetectable by standard reagent tests or routine MS methods (Jurásek et al. 2022 [Ref 6]). Reagent color testing (e.g., Mecke, Marquis, Mandelin) cannot confirm the absence of these impurities.

The three positional isomers of MXP (2-, 3-, and 4-methoxydiphenidine) are analytically distinct but may appear on markets; their pharmacological profiles differ. The 2-isomer (2-MXP, methoxphenidine) is the most commonly detected market form (McLaughlin et al. 2016 [Ref 13]).

### Emergency Response

Based on clinical case data (Helander et al. 2015 [Ref 8]; Eiden et al. 2018 [Ref 7]):
- Cardiovascular monitoring (hypertension and tachycardia are common)
- Benzodiazepines effective for agitation/seizures
- Propofol used for severe cases (sedation)
- No specific antidote

### Contraindications

No substance-specific published contraindications identified. Based on pharmacological class and case report data:
- CNS depressants (alcohol, opioids, benzodiazepines, GHB): potential for additive CNS and respiratory depression (class inference)
- Stimulants: compounded cardiovascular risk (tachycardia and hypertension documented even with MXP alone)
- MAOIs: no published data; flagged as high-risk by analogy with other dissociatives that have monoamine reuptake-affecting properties
- Pre-existing hypertension or cardiovascular disease: clinical case data demonstrates consistent cardiovascular stress

**FLAG (safety-critical):** All interaction statements above are class-based inferences. No published MXP-specific drug interaction studies exist. These should be explicitly labeled as such in the article.

---

## Tolerance & Dependence

### Tolerance

No controlled animal or human studies on MXP tolerance mechanisms have been published. Tolerance data in the seed database:
- **Buildup:** develops with prolonged and repeated use
- **Half-life:** 5 days
- **Full reset:** 1.5 weeks
- **Cross-tolerance:** dissociatives

These values are consistent with PsychonautWiki user-reported consensus for the dissociative class. They are **not derived from published clinical or preclinical data specific to MXP** and should be labeled as community-consensus estimates based on structural class analogy.

### Dependence and Addiction

**Champeau et al. (2017 [Ref 10])** — first documented MXP **use disorder** case, notified to the French Addictovigilance Network. First published clinical documentation of MXP dependence syndrome.

**ACMD review (2023 [Ref 20])** — documented a withdrawal case:
- A 21-year-old male who had used MXP for "a few weeks to a month" developed physical withdrawal symptoms on cessation: **abdominal pain, vomiting, and low-grade fever (38°C)**
- This documents physical dependence potential after relatively short-term heavy use

**Hur et al. (2021 [Ref 3])** — rodent behavioral studies:
- Intravenous self-administration positive: MXP maintained reinforcing behaviors
- Conditioned place preference positive: MXP produced rewarding effects
- Mechanism: dopamine pathway overactivation in nucleus accumbens (NMDA disinhibition pathway, distinct from direct DAT action per Sahai et al. 2018 [Ref 14])

**Eiden et al. (2018 [Ref 7]):** "The addictive potential of these substances seems highly probable."

**Sahai et al. (2018 [Ref 14]):** MXP does NOT significantly affect DAT binding or dopamine efflux directly, suggesting its reinforcing properties involve indirect dopaminergic mechanisms (NMDA blockade → disinhibition of mesolimbic dopamine) rather than direct reuptake inhibition — lowering (but not eliminating) the DPH-type addictive liability profile.

The seed data values (physical dependence: moderate; psychological: moderate; moderately addictive with high abuse potential) are consistent with the available evidence and should be retained.

---

## Interactions

No published MXP-specific drug interaction studies have been found. The following are based on pharmacological class and clinical case data:

**CNS depressants (alcohol, opioids, benzodiazepines, GHB/GBL):**
Additive CNS depression, sedation, and potential respiratory compromise. MXP alone causes altered mental status in clinical cases; co-administration with depressants amplifies this risk. Several of the documented fatalities involved co-ingestion of other substances (Elliott et al. 2015 [Ref 2]; Eiden et al. 2018 [Ref 7]).

**Stimulants (cocaine, amphetamines, cathinones):**
MXP consistently produces hypertension and tachycardia (Helander et al. 2015 [Ref 8]; Eiden et al. 2018 [Ref 7]). Co-administration with sympathomimetic stimulants would be expected to compound cardiovascular stress. User reports (Van Hout & Hearne 2015 [Ref 11]) note MXP itself has stimulant wave properties at lower doses.

**MAOIs:**
No published data. NMDA antagonists can interact with serotonergic systems via indirect mechanisms; given MXP's weak but non-zero SERT activity and class-based pharmacology, MAOI co-administration warrants a high-caution flag. Exact risk is unknown.

**Serotonergic drugs:**
MXP has minimal direct serotonin transporter activity (SERT >10 μM, Wallach et al. 2016 [Ref 1]), substantially reducing the theoretical serotonin syndrome risk that applies to more promiscuous NMDA antagonists. However, absence of direct SERT binding does not fully exclude indirect serotonergic interactions.

**FLAG:** All interaction statements are inferred from class pharmacology and clinical case co-ingestion data. No controlled interaction studies exist for MXP.

---

## Legal Status

### United Kingdom
- **Psychoactive Substances Act 2016:** MXP covered from May 2016 as a "psychoactive substance"; import, supply, and possession with intent to supply became offenses at that time.
- **Misuse of Drugs Act 1971:** Added as **Class B drug, Schedule 1** via SI 2024/190 (*Misuse of Drugs Act 1971 (Amendment) Order 2024*), effective **20 March 2024** (UK Home Office Circular 001/2024 [Ref 21]).
- Possession: maximum 5-year prison sentence; supply/production: up to 14 years.
- Access for research requires a Home Office controlled drug licence.
- **History:** ACMD published its review recommending Class B scheduling [Ref 20]; WHO ECDD reviewed October 2020; CND decided in April 2021 **not** to add to UN Convention on Psychotropic Substances but placed under continuing international surveillance.

### France
- Classified as a **narcotic drug (Annex IV)** under French drug control regulations (Eiden et al. 2018 [Ref 7]). Exact date of scheduling not confirmed in retrieved sources.

### Australia
- **Schedule 9 (Prohibited substance)** under the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP), effective **1 October 2024** (TGA decision). May only be used for research with a permit.

### Canada
- **Schedule 1 of the Controlled Drugs and Substances Act (CDSA)** (ACMD review [Ref 20]). Possession without legal authority carries a maximum 7-year imprisonment.

### Germany / EU
- ACMD review notes Italy controlled MXP from **August 2016** and Denmark has also controlled it. Exact EU-level status varies by member state.

### China
- Controlled from **September 2015** (ACMD review [Ref 20]).

### Japan
- Listed on Japan's **Designated Substance list** (ACMD review [Ref 20]); exact date not confirmed.

### Sweden
- Controlled (ACMD review [Ref 20]); date not confirmed.

### United States
- **Not scheduled under the Controlled Substances Act (CSA)** as of the most recent confirmed information (2020 Federal Register international scheduling consultation — MXP listed as not yet added to UN Convention). 
- Potentially covered by the **Federal Analogue Act (21 U.S.C. § 813)** if intended for human consumption and shown to be substantially similar to a Schedule I/II substance; however, no formal DEA scheduling action for MXP has been confirmed in published literature as of 2026.
- **FLAG:** US legal status unconfirmed for 2025–2026. Requires verification against current DEA controlled substances list.

---

## Clinical Trials

**No clinical trials for methoxphenidine were found on ClinicalTrials.gov.** The compound has no known therapeutic development program. Its only prior appearance in a clinical/medical context was as the subject of the 1989 Searle patent for neurotoxic injury treatment, which was not progressed to clinical trials.

---

## Community Feedback Analysis

**No community feedback was submitted in Part A2 of the brief.** Standard research directives followed.

---

## Gaps & Flags

### Safety-Critical Values Not Verified Against Published Sources

1. **Tolerance half-life (5 days) and full reset (1.5 weeks):** These values are community-consensus estimates for the dissociative class and are not derived from published preclinical or clinical studies of MXP specifically. **FLAG for editorial review.**

2. **Drug interactions:** All interaction severity statements (with CNS depressants, stimulants, MAOIs) are class-based inferences. No MXP-specific interaction studies exist. **FLAG every interaction as class-inference.**

3. **US legal status:** Not schedulable via API confirmation. Requires manual verification against current DEA CSA list before publication. **FLAG.**

4. **Sigma-1 Ki (124 nM):** Cited in the ACMD review as from Wallach 2016, but the specific numeric value was not confirmed in the PMC full-text abstract retrieved. Should be verified against the Wallach 2016 supplementary data.

5. **French scheduling date:** Not confirmed from a primary legal source. ACMD review confirms France classified as narcotic; date unknown.

### Data Gaps

6. **No published human pharmacokinetics:** All PK data (half-life 2.15 h, Tmax 30 min, BBB penetration) is from rat studies. Human bioavailability, Tmax, volume of distribution, protein binding, and half-life are all unknown.

7. **No CYP enzyme involvement data for MXP:** O-demethylation is the primary metabolic route, but the specific CYP enzymes have not been identified in published literature. Class inference suggests CYP2D6/3A4.

8. **No physical property data confirmed:** Melting point, solubility, and logP were not found via API searches. McLaughlin et al. 2016 may contain some of this in the full paper.

9. **No human oral bioavailability data.**

10. **Freebase CAS number** not confirmed via API; only hydrochloride salt CAS (2055777-48-3) retrieved from web sources.

11. **No controlled human studies** on subjective effects, cognitive effects, or dose-response in humans.

12. **Chronic organ toxicity:** ACMD review states no evidence of ketamine-style uroepithelial/bladder toxicity, but this is based on absence of reports rather than systematic study.

### Contradictions Between Sources

13. **Addiction liability:** Sahai et al. (2018 [Ref 14]) demonstrates MXP does not significantly bind DAT and does not increase DA efflux, suggesting lower addictive liability than DPH via the dopamine mechanism. However, Hur et al. (2021 [Ref 3]) demonstrates MXP maintains IV self-administration and CPP in rodents, and produces neurochemical changes consistent with reward circuit activation. These findings are not contradictory (NMDA-mediated disinhibition can produce reward without direct DAT action) but must be presented together to give an accurate picture. **Editorial note: do not claim MXP has "low" addictive potential on the basis of DAT data alone.**

14. **Seed data on pharmacological class:** The brief lists "Sigma-1 receptor agonist" as part of the pharmacological class. Wallach et al. 2016 found moderate sigma-1 affinity (Ki ~124 nM from ACMD citation), but whether this constitutes functional **agonism** or antagonism was not confirmed in the retrieved literature. PCP-class sigma ligands are typically sigma-1 agonists, but this should be flagged as inferred for MXP specifically.