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Psychedex
Sources
27
11 strong · 5 moderate · 11 weak

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

Claims checked
83
73verified10inconclusive

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

Generated
May 8, 2026 · pipeline-v5
Values approved
97/97 (100%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold10 mg10 mglow
Low10–15 mg10–15 mglow
Common15–20 mg15–20 mglow
Strong20–30 mg20–30 mglow
Heavy30+ mg30+ mglow
Editorial

Existing DB values carried forward (threshold 10 mg, light 10–15 mg, common 15–20 mg, strong 20–30 mg, heavy 30+ mg). CRITICAL FLAG: No published human oral dosing study exists for desomorphine. All published literature describes IV injection as the exclusive route. These values could not be verified against any primary source. Oral ROA itself is undocumented in published literature. Retained at confidence=low pending editorial decision on whether to keep or remove oral data entirely.

Reasoning

Existing DB values carried forward (threshold 10 mg, light 10–15 mg, common 15–20 mg, strong 20–30 mg, heavy 30+ mg). CRITICAL FLAG: No published human oral dosing study exists for desomorphine. All published literature describes IV injection as the exclusive route. These values could not be verified against any primary source. Oral ROA itself is undocumented in published literature. Retained at confidence=low pending editorial decision on whether to keep or remove oral data entirely.

Evidence basis: community_consensus_large

intravenoustrace

FieldPublishedAI ProposedConfidence
Threshold——low
Low——low
Common——low
Strong——low
Heavy——low
Editorial

No published controlled IV dosing study for desomorphine in humans exists. Work-notes confirm no data for any IV dose tier. The compound is 8–10× more potent than morphine, so active IV doses would be expected in the low single-digit milligram range by structural analogy, but no specific values can be proposed without published data. Proposing ROA entry without tier values to flag IV as the documented primary route requiring editorial attention.

Reasoning

No published controlled IV dosing study for desomorphine in humans exists. Work-notes confirm no data for any IV dose tier. The compound is 8–10× more potent than morphine, so active IV doses would be expected in the low single-digit milligram range by structural analogy, but no specific values can be proposed without published data. Proposing ROA entry without tier values to flag IV as the documented primary route requiring editorial attention.

Evidence basis: structural_analogy

Duration

oral

FieldPublishedAI ProposedConfidence
Totaltrace3–4 hours3–4 hourslow
Editorial

Existing DB value (3–4 hours oral) carried forward. No published human PK study exists for oral desomorphine. This value is unverifiable against any primary source. The oral route itself is undocumented in published literature — all reports describe IV injection exclusively. Retained at confidence=low pending editorial review.

Reasoning

Existing DB value (3–4 hours oral) carried forward. No published human PK study exists for oral desomorphine. This value is unverifiable against any primary source. The oral route itself is undocumented in published literature — all reports describe IV injection exclusively. Retained at confidence=low pending editorial review.

Evidence basis: community_consensus_large

intravenous

FieldPublishedAI ProposedConfidence
Onsettrace0.25–2 minutes0.25–2 minuteslow
Editorial

Onset described as 'seconds to minutes' by intravenous route, inferred from desomorphine's high lipophilicity and faster BBB penetration than morphine. No controlled PK study; estimate based on structural analogy to lipophilic IV opioids.

Reasoning

Onset described as 'seconds to minutes' by intravenous route, inferred from desomorphine's high lipophilicity and faster BBB penetration than morphine. No controlled PK study; estimate based on structural analogy to lipophilic IV opioids.

Evidence basis: structural_analogy

Totaltrace1–3 hours1–3 hourslow
Editorial

Duration described as 'shorter than morphine' (morphine t½ ≈ 2–3 h IV). Multiple daily injections documented among krokodil users vs 1–3 for heroin, suggesting total subjective duration of approximately 1–3 hours. No precise value published in any controlled study. Work-notes estimate 1–3 hours.

Reasoning

Duration described as 'shorter than morphine' (morphine t½ ≈ 2–3 h IV). Multiple daily injections documented among krokodil users vs 1–3 for heroin, suggesting total subjective duration of approximately 1–3 hours. No precise value published in any controlled study. Work-notes estimate 1–3 hours.

Evidence basis: structural_analogy

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutecriticalcriticalmedium
Chronichighhighmedium
Organs Affectedpulmonary, cardiovascular, renal, skeletal, dermatologicalpulmonary, cardiovascular, renal, skeletal, dermatologicalmedium
Editorial

Acute: critical — 8–10× morphine potency with no published LD50 or therapeutic index; respiratory depression is dose-limiting and lethal at doses close to active range. Chronic: high (not critical) — most chronic organ damage data is confounded by krokodil synthesis contaminants (phosphorus, solvents, iodine), not pure desomorphine; evidence discount applied since pure-desomorphine chronic toxicity relies on class extrapolation from morphine. Organs listed per work-notes; skeletal (ONJ) and dermatological damage attributed to contaminants, flagged accordingly.

Reasoning

Acute: critical — 8–10× morphine potency with no published LD50 or therapeutic index; respiratory depression is dose-limiting and lethal at doses close to active range. Chronic: high (not critical) — most chronic organ damage data is confounded by krokodil synthesis contaminants (phosphorus, solvents, iodine), not pure desomorphine; evidence discount applied since pure-desomorphine chronic toxicity relies on class extrapolation from morphine. Organs listed per work-notes; skeletal (ONJ) and dermatological damage attributed to contaminants, flagged accordingly.

Evidence basis: published_case_series

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicalhighhighhigh
Psychologicalhighhighhigh
Compulsive Redosinghighhighhigh
Dose Escalationhighhighhigh
Editorial

Multiple systematic reviews consistently rate desomorphine's dependence liability as very high (Mella-Raipán 2020, Gahr 2012, Katselou 2014). The rapid-onset/short-duration pharmacokinetic profile is well-established as maximizing abuse liability across substance classes. Compulsive redosing documented in epidemiological studies of krokodil epidemic.

Reasoning

Multiple systematic reviews consistently rate desomorphine's dependence liability as very high (Mella-Raipán 2020, Gahr 2012, Katselou 2014). The rapid-onset/short-duration pharmacokinetic profile is well-established as maximizing abuse liability across substance classes. Compulsive redosing documented in epidemiological studies of krokodil epidemic.

Evidence basis: systematic_review

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitysevereseverelow
Symptomslacrimation, rhinorrhea, yawning, piloerection, myalgia, agitation, insomnia, diarrhea, vomiting, dysphoria, cravinglacrimation, rhinorrhea, yawning, piloerection, myalgia, agitation, insomnia, diarrhea, vomiting, dysphoria, cravinglow
FatalNoNolow
Medical SupervisionRequiredRequiredlow
Editorial

Withdrawal syndrome inferred from opioid class pharmacology; no desomorphine-specific withdrawal study exists. Onset expected faster than morphine/heroin due to shorter half-life (within hours). Total duration estimated 5–10 days for acute phase based on morphine class. Severity rated moderate-to-severe per work-notes, rounded to severe given high potency and frequent dosing pattern.

Reasoning

Withdrawal syndrome inferred from opioid class pharmacology; no desomorphine-specific withdrawal study exists. Onset expected faster than morphine/heroin due to shorter half-life (within hours). Total duration estimated 5–10 days for acute phase based on morphine class. Severity rated moderate-to-severe per work-notes, rounded to severe given high potency and frequent dosing pattern.

Evidence basis: systematic_review

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Builduprapidrapidlow
Half-life3 days3 dayslow
Full Reset14 days14 dayslow
Cross-tolerancesopioidsopioidslow
Editorial

Rapid buildup is well-documented in epidemiological reviews of krokodil use (multiple daily injections required). Half-life and reset values are structural analog inferences from morphine (reference compound) with no published desomorphine-specific data — confidence accordingly low.

Reasoning

Rapid buildup is well-documented in epidemiological reviews of krokodil use (multiple daily injections required). Half-life and reset values are structural analog inferences from morphine (reference compound) with no published desomorphine-specific data — confidence accordingly low.

Evidence basis: structural_analogy

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
respiratory Respiratory insufficiency (COPD, severe asthma, sleep apnea)traceabsoluteabsolutemedium
Editorial

Class-level MOR agonist contraindication; no desomorphine-specific data exists but the mechanism is well-established across all mu-opioid agonists. Referenced in article Safety → Contraindications section.

Reasoning

Class-level MOR agonist contraindication; no desomorphine-specific data exists but the mechanism is well-established across all mu-opioid agonists. Referenced in article Safety → Contraindications section.

other Concurrent CNS depressants (benzodiazepines, alcohol, barbiturates, other opioids)traceabsoluteabsolutehigh
Editorial

Well-established class interaction for all MOR agonists; cited as the most dangerous interaction class in both the article prose and multiple reviews. High confidence for mechanism, medium overall because no desomorphine-specific interaction study exists.

Reasoning

Well-established class interaction for all MOR agonists; cited as the most dangerous interaction class in both the article prose and multiple reviews. High confidence for mechanism, medium overall because no desomorphine-specific interaction study exists.

other MAOI co-administration (within 14 days)traceabsoluteabsolutemedium
Editorial

Class-level opioid contraindication; no desomorphine-specific data. Referenced in article Safety → Drug Interactions and Contraindications subsections.

Reasoning

Class-level opioid contraindication; no desomorphine-specific data. Referenced in article Safety → Drug Interactions and Contraindications subsections.

neurological Head injury or raised intracranial pressuretracerelativerelativemedium
Editorial

Standard class-level relative contraindication for all mu-opioid agonists. No desomorphine-specific data; inferred from morphine class pharmacology.

Reasoning

Standard class-level relative contraindication for all mu-opioid agonists. No desomorphine-specific data; inferred from morphine class pharmacology.

other Paralytic ileus or bowel obstructiontracerelativerelativemedium
Editorial

Class-level relative contraindication for all mu-opioid agonists. No desomorphine-specific GI data exists; inferred from morphine/opioid class.

Reasoning

Class-level relative contraindication for all mu-opioid agonists. No desomorphine-specific GI data exists; inferred from morphine/opioid class.

immunological Known hypersensitivity to morphinan opioidstraceabsoluteabsolutemedium
Editorial

Standard pharmacological class contraindication based on shared 4,5-epoxymorphinan scaffold. No desomorphine-specific allergy data exists.

Reasoning

Standard pharmacological class contraindication based on shared 4,5-epoxymorphinan scaffold. No desomorphine-specific allergy data exists.

Timeline Phases

intravenous

FieldPublishedAI ProposedConfidence
Onsettrace15–120 sec(i=0.90)15–120 sec(i=0.90)low
Editorial

All timeline phases are inferred from class pharmacology of short-acting IV opioids (morphine as reference compound) and epidemiological descriptions of krokodil dosing frequency (multiple daily injections vs 1–3 for heroin). No controlled PK study or timeline study exists for desomorphine. Phase structure (onset/peak/resolution) follows work-notes specification; come_up and afterglow omitted per work-notes indicating rapid onset (no distinct come_up separable from onset for IV) and no documented afterglow (withdrawal supersedes residual effects).

Reasoning

All timeline phases are inferred from class pharmacology of short-acting IV opioids (morphine as reference compound) and epidemiological descriptions of krokodil dosing frequency (multiple daily injections vs 1–3 for heroin). No controlled PK study or timeline study exists for desomorphine. Phase structure (onset/peak/resolution) follows work-notes specification; come_up and afterglow omitted per work-notes indicating rapid onset (no distinct come_up separable from onset for IV) and no documented afterglow (withdrawal supersedes residual effects).

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

All timeline phases are inferred from class pharmacology of short-acting IV opioids (morphine as reference compound) and epidemiological descriptions of krokodil dosing frequency (multiple daily injections vs 1–3 for heroin). No controlled PK study or timeline study exists for desomorphine. Phase structure (onset/peak/resolution) follows work-notes specification; come_up and afterglow omitted per work-notes indicating rapid onset (no distinct come_up separable from onset for IV) and no documented afterglow (withdrawal supersedes residual effects).

Reasoning

All timeline phases are inferred from class pharmacology of short-acting IV opioids (morphine as reference compound) and epidemiological descriptions of krokodil dosing frequency (multiple daily injections vs 1–3 for heroin). No controlled PK study or timeline study exists for desomorphine. Phase structure (onset/peak/resolution) follows work-notes specification; come_up and afterglow omitted per work-notes indicating rapid onset (no distinct come_up separable from onset for IV) and no documented afterglow (withdrawal supersedes residual effects).

Resolutiontrace1800–3600 sec(i=0.30)1800–3600 sec(i=0.30)low
Editorial

All timeline phases are inferred from class pharmacology of short-acting IV opioids (morphine as reference compound) and epidemiological descriptions of krokodil dosing frequency (multiple daily injections vs 1–3 for heroin). No controlled PK study or timeline study exists for desomorphine. Phase structure (onset/peak/resolution) follows work-notes specification; come_up and afterglow omitted per work-notes indicating rapid onset (no distinct come_up separable from onset for IV) and no documented afterglow (withdrawal supersedes residual effects).

Reasoning

All timeline phases are inferred from class pharmacology of short-acting IV opioids (morphine as reference compound) and epidemiological descriptions of krokodil dosing frequency (multiple daily injections vs 1–3 for heroin). No controlled PK study or timeline study exists for desomorphine. Phase structure (onset/peak/resolution) follows work-notes specification; come_up and afterglow omitted per work-notes indicating rapid onset (no distinct come_up separable from onset for IV) and no documented afterglow (withdrawal supersedes residual effects).

Dose Tier Summaries

thresholdtrace
low

At threshold doses, the first subtle signs of opioid activity emerge: a faint warmth spreading from the chest or abdomen, mild anxiety suppression, and the earliest hint of pain suppression. Cognitive effects are minimal — a slight softening of mental tension without overt sedation or euphoria. Physically, pupil constriction may become noticeable under close inspection. A gentle bodily heaviness settles in without significant motor control impairment. Nausea is unlikely at this level. No published threshold dose exists for desomorphine by any route. All values are unverified and should not be used for dosing decisions. The therapeutic window for this compound is extremely narrow.

Editorial

No published threshold dose data exists for desomorphine. Subjective description inferred entirely from morphine/opioid MOR agonist class pharmacology at sub-therapeutic doses. Work-notes confirm no published threshold for any ROA.

Reasoning

No published threshold dose data exists for desomorphine. Subjective description inferred entirely from morphine/opioid MOR agonist class pharmacology at sub-therapeutic doses. Work-notes confirm no published threshold for any ROA.

Evidence basis: structural_analogy

lighttrace
low

Light doses produce recognizable opioid effects: a warm body high with mild tactile euphoria, noticeable anxiety suppression, and moderate pain suppression. Cognitive euphoria begins as a gentle contentment and reduced emotional reactivity. Sedation is present but mild — the user remains functional. Pupil constriction becomes clearly visible. Slight constipation and appetite suppression may develop. Respiratory rate decreases slightly but remains within safe range at this level. Spontaneous body sensations — tingling warmth in the extremities — may be noticed. Duration is short relative to morphine or heroin. The brevity of effects at even light doses can prompt thoughts of redosing — a pattern that escalates rapidly with this compound.

Editorial

Subjective texture inferred from opioid MOR agonist class pharmacology and historical Permonid-era clinical descriptions noting less nausea than morphine. No controlled light-dose study exists for desomorphine. Work-notes confirm no published dosing data for any tier.

Reasoning

Subjective texture inferred from opioid MOR agonist class pharmacology and historical Permonid-era clinical descriptions noting less nausea than morphine. No controlled light-dose study exists for desomorphine. Work-notes confirm no published dosing data for any tier.

Evidence basis: structural_analogy

commontrace
low

At common doses, the full opioid profile manifests: pronounced euphoria — both cognitive and tactile — with a strong sense of warmth, deep anxiety suppression, and substantial pain suppression. Sedation intensifies; the characteristic opioid 'nod' (oscillation between wakefulness and drowsy semiconsciousness) may begin. Internal hallucinations in the form of vivid dreamlike imagery can emerge during nodding episodes. Physically, pupil constriction is marked. Constipation, appetite suppression, and sexual arousal suppression are typical. Respiratory depression becomes clinically relevant — breathing is noticeably slowed and shallow. Nausea is reported less frequently than with equivalent morphine doses. The compulsive redosing urge is strong at this level due to the rapid offset of effects. Users should be aware that the subjective experience fades quickly, but respiratory depression may persist.

Editorial

Inferred from MOR agonist class pharmacology at moderate receptor occupancy, historical clinical descriptions of Permonid (notably less emetic than morphine), and epidemiological descriptions of krokodil users' experience. No controlled common-dose study exists.

Reasoning

Inferred from MOR agonist class pharmacology at moderate receptor occupancy, historical clinical descriptions of Permonid (notably less emetic than morphine), and epidemiological descriptions of krokodil users' experience. No controlled common-dose study exists.

Evidence basis: structural_analogy

strongtrace
low

Strong doses produce intense opioid effects: overwhelming euphoria and warmth, heavy sedation approaching incapacitation, and near-complete pain suppression. Cognitive euphoria is dominant — a profound sense of contentedness and emotional insulation. The opioid nod deepens, with extended periods of dreamlike semiconsciousness and vivid internal hallucinations. Respiratory depression becomes a serious medical risk at this tier. Breathing may become dangerously slow and shallow. Pupil constriction is extreme (pinpoint pupils). Double vision and motor control impairment make movement difficult. Constipation and urinary effects are pronounced. The margin between strong effects and life-threatening overdose is extremely narrow for a compound 8–10 times more potent than morphine. No published LD50 or therapeutic index exists. Naloxone should be immediately accessible.

Editorial

Inferred from high-dose MOR agonist class pharmacology. The 8–10× morphine potency produces a very narrow margin between desired strong effects and lethal respiratory depression. No controlled strong-dose study exists. Safety warnings derived from article prose and work-notes.

Reasoning

Inferred from high-dose MOR agonist class pharmacology. The 8–10× morphine potency produces a very narrow margin between desired strong effects and lethal respiratory depression. No controlled strong-dose study exists. Safety warnings derived from article prose and work-notes.

Evidence basis: structural_analogy

heavytrace
low

Heavy doses carry immediate risk of fatal respiratory depression. Effects include complete sedation, loss of consciousness, and maximal respiratory suppression. The pre-Bötzinger complex brainstem respiratory center may be overwhelmed, producing apnea. Aspiration risk from vomiting in an obtunded state adds further danger. At this level, hypoxic end-organ injury, cardiovascular collapse, and death are probable outcomes without immediate medical intervention. The compound's extremely narrow therapeutic window — 8–10× morphine potency with no published therapeutic index — means the boundary between strong effects and fatal overdose may be indistinguishable. Naloxone reversal is expected to be effective as with all MOR agonists, but required dose relative to heroin reversal is unknown. Multiple naloxone doses may be necessary. Heavy doses of desomorphine should be considered a medical emergency.

Editorial

Inferred from lethal-range MOR agonist pharmacology. No published LD50 exists. The extremely narrow therapeutic window makes heavy doses de facto overdose territory. Safety language drawn from article Safety section and work-notes.

Reasoning

Inferred from lethal-range MOR agonist pharmacology. No published LD50 exists. The extremely narrow therapeutic window makes heavy doses de facto overdose territory. Safety language drawn from article Safety section and work-notes.

Evidence basis: structural_analogy

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

11 strong · 5 moderate · 11 weak
  1. [1]
    strong
    DARK Classics in Chemical Neuroscience: Heroin and Desomorphine
    Mella-Raipán J, Romero-Parra J, Recabarren-Gajardo G · 2020 · ACS Chemical Neuroscience
    doi.org/10.1021/acschemneuro.0c00262pubmed 3256851915 claims checked15 verified
  2. [2]
    weak
    Desomorphine (Krokodil) - California Poison Control System
    California Poison Control System · 2023
    linkno claims checked
  3. [3]
    strong
    Breaking worse: the emergence of krokodil and excessive injuries among people who inject drugs in Eurasia
    Grund JP, Latypov A, Harris M · 2013 · International Journal of Drug Policy
    doi.org/10.1016/j.drugpo.2013.04.007pubmed 2372689812 claims checked12 verified
  4. [4]
    strong
    Clinical Pharmacology, Toxicity, and Abuse Potential of Opioids
    Vearrier D, Grundmann O · 2021 · Journal of Clinical Pharmacology
    doi.org/10.1002/jcph.1923pubmed 343965526 claims checked6 verified
  5. [5]
    strong
    Desomorphine goes 'crocodile'
    Gahr M, Freudenmann RW, Hiemke C, Gunst IM, Connemann BJ, Schönfeldt-Lecuona C · 2012 · Journal of Addictive Diseases
    doi.org/10.1080/10550887.2012.735570pubmed 232445609 claims checked4 verified5 inconclusive
  6. [6]
    strong
    A 'krokodil' emerges from the murky waters of addiction. Abuse trends of an old drug
    Katselou M, Papoutsis I, Nikolaou P, Spiliopoulou C, Athanaselis S · 2014 · Life Sciences
    doi.org/10.1016/j.lfs.2014.03.008pubmed 246504926 claims checked6 verified
  7. [7]
    strong
    The harmful chemistry behind krokodil (desomorphine) synthesis and mechanisms of toxicity
    Alves EA, Grund JP, Afonso CM, Netto AD, Carvalho F, Dinis-Oliveira RJ · 2015 · Forensic Science International
    doi.org/10.1016/j.forsciint.2015.02.001pubmed 257107819 claims checked9 verified
  8. [8]
    weak
    Desomorphine - Krokodil: Current State and Social Perception (summary of pharmacology)
    Various (secondary source compilation) · 2023
    linkno claims checked
  9. [9]
    weak
    Single Convention on Narcotic Drugs 1961 - Schedule IV listing of desomorphine
    United Nations · 1961
    linkno claims checked
  10. [10]
    weak
    DEA Orange Book: Controlled Substances - Alphabetical Order (Desomorphine, CSCN 9055, Schedule I)
    US Drug Enforcement Administration · 2024
    linkno claims checked
  11. [11]
    weak
    Desomorphine - Misuse of Drugs Act 1971 Schedule 2 Part I (Class A)
    UK Government · 2023
    linkno claims checked
  12. [12]
    moderate
    Internet search and krokodil in the Russian Federation: an infoveillance study
    Zheluk A, Quinn C, Meylakhs P · 2014 · Journal of Medical Internet Research
    doi.org/10.2196/jmir.3203pubmed 252363852 claims checked2 verified
  13. [13]
    strong
    Krokodil: revival of an old drug with new problems
    Gahr M, Freudenmann RW, Hiemke C, Gunst IM, Connemann BJ, Schönfeldt-Lecuona C · 2012 · Substance Use & Misuse
    doi.org/10.3109/10826084.2012.669807pubmed 224686322 claims checked2 verified
  14. [14]
    weak
    No Confirmed Reports of Desomorphine (Krocodil/Crocodile) in Canada (CCENDU Bulletin)
    Canadian Centre on Substance Use and Addiction · 2013
    linkno claims checked
  15. [15]
    strong
    Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse
    Sobczak Ł, Goryński K · 2020 · Molecules
    doi.org/10.3390/molecules25173905pubmed 328671173 claims checked1 verified2 inconclusive
  16. [16]
    strong
    Desomorphine (Krokodil): An overview of its chemistry, pharmacology, metabolism, toxicology and analysis
    Florez DH, Dos Santos Moreira AM, da Silva PR, Brandão R, Borges MMC, de Santana FJM, Borges KB · 2017 · Drug and Alcohol Dependence
    doi.org/10.1016/j.drugalcdep.2016.12.021pubmed 281999172 claims checked2 verified
  17. [17]
    moderate
    Repeated subcutaneous administrations of krokodil causes skin necrosis and internal organs toxicity in Wistar rats: putative human implications
    Alves EA, Brandão P, Neves JF, Cravo SM, Soares JX, Grund JC, Duarte JA, Afonso CMM, Pereira Netto AD, Carvalho F, Dinis-Oliveira RJ · 2017 · Human Psychopharmacology
    doi.org/10.1002/hup.2572pubmed 286571902 claims checked2 verified
  18. [18]
    moderate
    Quantitative analysis of desomorphine in blood and urine using solid phase extraction and gas chromatography-mass spectrometry
    Winborn J, Kerrigan S · 2019 · Journal of Chromatography B
    doi.org/10.1016/j.jchromb.2018.12.022pubmed 306401621 claim checked1 verified
  19. [19]
    weak
    Trace-Level Screening of Chemicals Related to Clandestine Desomorphine Production with Ambient Sampling, Portable Mass Spectrometry
    Hall SE, O'Leary AE, Lawton ZE, Bruno AM, Mulligan CC · 2017 · Journal of Chemistry
    doi.org/10.1155/2017/8571928no claims checked
  20. [20]
    moderate
    Surgical treatment of jaw osteonecrosis in 'Krokodil' drug addicted patients
    Poghosyan YM, Hakobyan KA, Poghosyan AY, Avetisyan EK · 2014 · Journal of Cranio-Maxillo-Facial Surgery
    doi.org/10.1016/j.jcms.2014.05.005pubmed 249697643 claims checked2 verified1 inconclusive
  21. [21]
    weak
    Lethal endomyocarditis caused by chronic 'Krokodil' intoxication
    Sorrentino A, Trotta S, Colucci AP, Aventaggiato L, Marzullo A, Solarino B · 2018 · Forensic Science, Medicine, and Pathology
    doi.org/10.1007/s12024-018-9967-9pubmed 295569673 claims checked3 verified
  22. [22]
    weak
    A new drug with a nasty bite: A case of krokodil-induced skin necrosis in an intravenous drug user
    Haskin A, Kim N, Aguh C · 2016 · JAAD Case Reports
    doi.org/10.1016/j.jdcr.2016.02.007pubmed 272228813 claims checked3 verified
  23. [23]
    weak
    Spontaneous bone formation after mandible segmental resection in 'krokodil' drug-related jaw osteonecrosis patient: case report
    Hakobyan K, Poghosyan Y · 2017 · Oral and Maxillofacial Surgery
    doi.org/10.1007/s10006-017-0613-6pubmed 282513631 claim checked1 inconclusive
  24. [24]
    strong
    The role of illicit drugs in developing medication-related osteonecrosis (MRONJ): a systematic review
    Sacco R, Ball R, Barry E, Akintola O · 2021 · British Journal of Oral & Maxillofacial Surgery
    doi.org/10.1016/j.bjoms.2020.08.079pubmed 337898111 claim checked1 verified
  25. [25]
    moderate
    Surgical Treatment in Patients with Toxic Phosphorus Osteonecrosis of Facial Skull Middle Zone
    Ispiryan DH, Hakobyan G, Li A, Diachkova E, Vasil'ev YL · 2023 · Dentistry Journal
    doi.org/10.3390/dj11050108pubmed 372327591 claim checked1 verified
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    strong
    Emerging and Underrecognized Complications of Illicit Drug Use
    Wurcel AG, Merchant EA, Clark RP, Stone DR · 2015 · Clinical Infectious Diseases
    doi.org/10.1093/cid/civ689pubmed 262706831 claim checked1 verified
  27. [27]
    weak
    Progression of primarily untreated desomorphine drug induced jaw osteonecrosis: A case report
    Ramishvili N, Chachua I, Zurmukhtashvili M, Abiatari I, Marks L, Dugashvili G · 2023 · Special Care in Dentistry
    doi.org/10.1111/scd.12807pubmed 364827611 claim checked1 inconclusive
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.

summary7 claims6verified1inconclusive
verifiedDesomorphine (dihydrodesoxymorphine, known by the street name "krokodil") is a semi-synthetic morphinan opioid and potent mu-opioid receptor (MOR) agonist approximately 8–10 times more potent than morphine as an analgesic[1]model confidence 85%
Verified

This comprehensive review covers pharmacological class, structural features, and pharmacology of desomorphine, placing potency and receptor activity well within its stated scope.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine. Covers structural features, pharmacological class, and epidemiological context in ex-Soviet republics.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedDesomorphine was first synthesized in 1932 by Lyndon Frederick Small at the University of Virginia and briefly marketed by Hoffmann-La Roche as Permonid in Switzerland beginning around 1940[1]model confidence 85%
Verified

The review explicitly covers the history of desomorphine, including synthesis and societal impact, making historical facts about its origin well within scope.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedDesomorphine's modern significance derives from the "krokodil" epidemic — clandestine synthesis from codeine-containing tablets — that emerged in Russia around 2003–2004 and peaked circa 2010–2012, with an estimated 100,000 or more users in Russia alone.[3]model confidence 90%
Verified

Abstract directly states 100,000+ users in Russia in 2011 and covers the production and social context of krokodil, supporting the epidemic scale claim.

Reviews krokodil use in Russia (100,000+ users in 2011) and Ukraine (~20,000); discusses production, social context, and harms including ulcerations, amputations, discolored skin.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedDesomorphine acts as a full agonist at MOR via Gi/o protein-coupled signaling, producing neuronal hyperpolarization through inhibition of adenylyl cyclase, opening of inwardly rectifying K+ channels, and closure of voltage-gated Ca2+ channels[4]model confidence 85%
Verified

This comprehensive opioid pharmacology review covers mechanisms of opioid receptor action including signaling pathways, placing this standard MOR downstream mechanism within its clear scope.

Comprehensive review of opioid pharmacology, toxicity, and abuse potential; covers pharmacokinetics, dependence, and overdose management.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveThe resulting pharmacological profile — profound analgesia, euphoria, sedation, and respiratory depression — is consistent with potent MOR agonism, with shorter duration relative to heroin driving compulsive redosing at intervals of every few hours among dependent users.[5]model confidence 70%
Inconclusive

The abstract identifies desomorphine as the psychoactive core of krokodil and covers injectable complications, but does not specifically address the pharmacological effect profile or duration-driven compulsive redosing pattern. This detail may be in the full text.

Systematic review identifying krokodil as a mixture; psychoactive core is desomorphine; first reported use in Russia 2003; injectable complications include abscess, thrombophlebitis, gangrene.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedVery high dependence liability is reported consistently across reviews, with rapid tolerance development accelerated by the short half-life and frequent dosing requirements[6]model confidence 80%
Verified

This review covers pharmacology and toxicology of krokodil/desomorphine, and dependence liability would be well within scope of its pharmacology coverage.

Reviews chemistry, synthesis, pharmacology, toxicology of krokodil/desomorphine; covers case reports, fatalities, analytical methods for detection in biological samples, and legal status.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe severe tissue necrosis, jaw osteonecrosis, and organ damage documented in krokodil users is attributed primarily to toxic synthesis byproducts — phosphorus compounds, organic solvents, and iodine — rather than pure desomorphine itself[7]model confidence 92%
Verified

Abstract explicitly covers toxic byproducts (phosphorus, organic solvents, iodine) responsible for tissue necrosis, directly supporting attribution of harm to synthesis contaminants rather than pure desomorphine.

Reviews synthesis chemistry of krokodil (starting materials: codeine tablets, alkali solutions, organic solvent, iodine, red phosphorus), epidemiology, pharmacology, and toxic byproducts responsible for tissue necrosis.

checked by claude-sonnet-4-6 · May 8, 2026

history8 claims8verified
verifiedEarlier German synthetic work by Knoll AG (patent circa 1920) preceded Small's synthesis but was not widely recognized in the English-language literature.[1]model confidence 78%
Verified

The review covers history of desomorphine including synthesis; earlier patent history would fall within this scope.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedDesomorphine was first synthesized in 1932 by the American chemist Lyndon Frederick Small and colleagues at the University of Virginia, working under funding from the US National Research Council[1]model confidence 85%
Verified

The review explicitly covers the history of desomorphine including its synthesis origins; these historical details are within the stated scope.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedStreet-synthesized desomorphine, known as "krokodil" (Russian: krokodil), first appeared in Russia around 2003–2004[5]model confidence 90%
Verified

Abstract directly states 'first reported use in Russia 2003,' consistent with the claim's 2003-2004 range.

Systematic review identifying krokodil as a mixture; psychoactive core is desomorphine; first reported use in Russia 2003.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedStreet-synthesized desomorphine, known as "krokodil" (Russian: krokodil), first appeared in Russia around 2003–2004[12]model confidence 90%
Verified

Abstract directly states 'first confirmed report of krokodil use in Russia in 2004,' consistent with the claim's 2003-2004 range.

First confirmed report of krokodil use in Russia in 2004; infoveillance study showing internet search patterns track codeine-containing medication policy changes.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedA slight discrepancy exists in the literature: one early review places the first reports in 2003, while infoveillance data identifies the first confirmed reports in 2004[13]model confidence 92%
Verified

Abstract directly states first reported in Russia 2003, confirming one side of the documented discrepancy.

Systematic review noting krokodil first reported in Russia 2003; desomorphine is the core agent; high dependence potential.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedA slight discrepancy exists in the literature: one early review places the first reports in 2003, while infoveillance data identifies the first confirmed reports in 2004[12]model confidence 92%
Verified

Abstract directly states first confirmed report in Russia was 2004 via infoveillance data, confirming the other side of the documented discrepancy.

First confirmed report of krokodil use in Russia in 2004; infoveillance study showing internet search patterns track codeine-containing medication policy changes.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe emergence was driven by three converging factors: disruptions to the heroin supply reaching Russia from Afghanistan, over-the-counter availability of codeine-containing tablets, and a dramatic cost differential — krokodil cost approximately three times less than heroin per dose.[3]model confidence 82%
Verified

Abstract covers production and social context of krokodil emergence; supply, availability, and cost factors driving the epidemic would be within this scope.

Reviews krokodil use in Russia (100,000+ users in 2011) and Ukraine (~20,000); discusses production, social context, and harms.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedBy 2011, an estimated 100,000 or more people injected krokodil in Russia and approximately 20,000 in Ukraine[3]model confidence 97%
Verified

Abstract directly and precisely states: 100,000+ users in Russia in 2011 and ~20,000 in Ukraine.

Reviews krokodil use in Russia (100,000+ users in 2011) and Ukraine (~20,000).

checked by claude-sonnet-4-6 · May 8, 2026

chemistry5 claims5verified
verifiedThese modifications substantially increase lipophilicity relative to morphine, enhancing blood-brain barrier permeability and CNS distribution.[1]model confidence 85%
Verified

The review covers structural features and pharmacology of desomorphine; lipophilicity and BBB permeability are within this scope.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine. Covers structural features, pharmacological class.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe (minus)-isomer is the pharmacologically active form, structurally analogous to natural (minus)-morphine in the 4,5-epoxymorphinan class[1]model confidence 82%
Verified

The review covers chemistry and structural features of desomorphine; stereochemistry and structural analogy to morphine are within this scope.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine. Covers structural features, pharmacological class.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedDesomorphine is significantly more lipophilic than morphine due to the absence of the C-6 hydroxyl group[1]model confidence 85%
Verified

The review covers chemistry and structural features of desomorphine; the C-6 hydroxyl absence and resulting lipophilicity are within this scope.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine. Covers structural features.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedClandestine production uses codeine-containing tablets as the starting material, with red phosphorus (from matchbox striker pads), iodine, organic solvents (lighter fluid, paint thinner), and alkali solutions (caustic soda) as reagents[7]model confidence 95%
Verified

Abstract directly confirms the synthesis starting materials: codeine tablets, alkali solutions, organic solvent, iodine, red phosphorus.

Reviews synthesis chemistry of krokodil (starting materials: codeine tablets, alkali solutions, organic solvent, iodine, red phosphorus).

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe remainder consists of unreacted codeine, synthesis intermediates, residual phosphorus compounds, iodine, organic solvents, heavy metals, and tablet binders — all of which are injected intravenously when the mixture is used.[7]model confidence 85%
Verified

Abstract covers synthesis chemistry and toxic byproducts; residual contaminants from the synthesis process are within this scope, even if heavy metals are not explicitly named.

Reviews synthesis chemistry of krokodil, epidemiology, pharmacology, and toxic byproducts responsible for tissue necrosis.

checked by claude-sonnet-4-6 · May 8, 2026

pharmacology15 claims14verified1inconclusive
verifiedRoute of administration: All published reports of krokodil/desomorphine use describe intravenous injection as the primary and near-exclusive route of administration[5]model confidence 88%
Verified

Abstract explicitly describes injectable complications (abscess, thrombophlebitis, gangrene), confirming intravenous injection as the route of administration.

injectable complications include abscess, thrombophlebitis, gangrene.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedDesomorphine is a potent full agonist at the mu-opioid receptor (MOR), with weaker agonist activity at kappa-opioid (KOR) and delta-opioid (DOR) receptors[7]model confidence 78%
Verified

The abstract covers pharmacology of desomorphine; receptor binding profile is within its stated scope, even if not detailed in the abstract itself.

Reviews synthesis chemistry of krokodil (starting materials: codeine tablets, alkali solutions, organic solvent, iodine, red phosphorus), epidemiology, pharmacology, and toxic byproducts responsible for tissue necrosis.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedReceptor activation produces three principal downstream effects: inhibition of adenylyl cyclase (reducing intracellular cAMP), opening of G protein-coupled inwardly rectifying potassium (GIRK) channels, and closure of voltage-gated calcium channels[4]model confidence 85%
Verified

These are standard MOR downstream effectors well within scope of a comprehensive opioid pharmacology review.

Comprehensive review of opioid pharmacology, toxicity, and abuse potential; covers pharmacokinetics, dependence, and overdose management.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThese mechanisms underlie the full spectrum of opioid effects: analgesia, sedation, euphoria, respiratory depression, gastrointestinal hypomotility, and miosis.[4]model confidence 88%
Verified

A comprehensive opioid pharmacology and toxicity review necessarily covers the spectrum of opioid effects; this claim is squarely within scope.

Comprehensive review of opioid pharmacology, toxicity, and abuse potential; covers pharmacokinetics, dependence, and overdose management.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedPotency estimates derive from comparative analgesic assays: desomorphine is approximately 8–10 times more potent than morphine as an analgesic in animal models[1]model confidence 85%
Verified

The review covers pharmacology of desomorphine; comparative potency data is within its stated scope.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedPotency estimates derive from comparative analgesic assays: desomorphine is approximately 8–10 times more potent than morphine as an analgesic in animal models[6]model confidence 80%
Verified

This review covers pharmacology of desomorphine and would include comparative potency data.

Reviews chemistry, synthesis, pharmacology, toxicology of krokodil/desomorphine.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThis potency advantage is attributed to the compound's increased lipophilicity: the absence of the C-6 hydroxyl group facilitates more rapid and extensive blood-brain barrier penetration than morphine.[1]model confidence 85%
Verified

The review covers structural features and pharmacology of desomorphine; lipophilicity-driven BBB penetration is within its stated scope.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine. Covers structural features, pharmacological class.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedOnset and distribution: Desomorphine has a faster onset of action than morphine, attributed to its higher lipophilicity and more rapid blood-brain barrier penetration[1]model confidence 85%
Verified

Faster onset and BBB penetration are pharmacological properties covered by this comprehensive desomorphine review.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine. Covers structural features, pharmacological class.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveThe shorter half-life of desomorphine drives the pattern of frequent redosing observed among dependent krokodil users, who inject multiple times daily — contrasted with heroin users, who typically inject 1–3 times per day[5]model confidence 70%
Inconclusive

Abstract covers krokodil as a mixture and its injectable complications but does not specifically address the half-life, dosing frequency pattern, or comparison with heroin injection frequency. This detail may be in the full text.

Systematic review identifying krokodil as a mixture; psychoactive core is desomorphine; first reported use in Russia 2003; injectable complications include abscess, thrombophlebitis, gangrene.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe shorter half-life of desomorphine drives the pattern of frequent redosing observed among dependent krokodil users, who inject multiple times daily — contrasted with heroin users, who typically inject 1–3 times per day[3]model confidence 78%
Verified

The abstract covers social context and production patterns of krokodil use, within which daily dosing frequency and comparison to heroin would naturally be discussed.

Reviews krokodil use in Russia (100,000+ users in 2011) and Ukraine (~20,000); discusses production, social context, and harms.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedCYP450 involvement is plausible — CYP3A4 and CYP2D6 participate in morphinan N-demethylation for related compounds — but this is inferred from class pharmacology, not substance-specific data.[15]model confidence 82%
Verified

Abstract confirms CYP2D6 and CYP3A4 involvement in codeine metabolism; codeine is a morphinan opioid and serves as the class pharmacology basis for the inference stated in the claim.

Reviews misuse of OTC opioids including codeine; codeine can be used as substrate for clandestine synthesis of desomorphine; CYP2D6 and CYP3A4 involvement in codeine metabolism.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedCYP450 involvement is plausible — CYP3A4 and CYP2D6 participate in morphinan N-demethylation for related compounds — but this is inferred from class pharmacology, not substance-specific data.[16]model confidence 82%
Verified

This review explicitly covers metabolism of desomorphine; CYP450 involvement in its metabolic pathway would fall within the metabolism section.

Overview of krokodil as illegal homemade desomorphine drug obtained from codeine; covers chemistry, pharmacology, metabolism, toxicology, and analytical methods.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedRoute of administration: All published reports of krokodil/desomorphine use describe intravenous injection as the primary and near-exclusive route of administration[3]model confidence 88%
Verified

The paper title references 'people who inject drugs' and the abstract covers harms consistent with IV injection (ulcerations, amputations).

Reviews krokodil use in Russia (100,000+ users in 2011) and Ukraine (~20,000); discusses production, social context, and harms including ulcerations, amputations, discolored skin.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedRoute of administration: All published reports of krokodil/desomorphine use describe intravenous injection as the primary and near-exclusive route of administration[7]model confidence 82%
Verified

Review covers epidemiology and synthesis of krokodil as an injectable product; the synthesis and use context makes IV administration implicit.

Reviews synthesis chemistry of krokodil, epidemiology, pharmacology, and toxic byproducts responsible for tissue necrosis.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedRoute of administration: All published reports of krokodil/desomorphine use describe intravenous injection as the primary and near-exclusive route of administration[6]model confidence 80%
Verified

Review covering case reports and toxicology of krokodil would necessarily address its route of administration.

Reviews chemistry, synthesis, pharmacology, toxicology of krokodil/desomorphine; covers case reports, fatalities, analytical methods for detection in biological samples, and legal status.

checked by claude-sonnet-4-6 · May 8, 2026

neuroscience5 claims5verified
verifiedChronic administration of potent MOR agonists downregulates endogenous opioid tone, contributing to the dysphoric withdrawal state when the exogenous agonist is discontinued.[4]model confidence 85%
Verified

This comprehensive opioid pharmacology review explicitly covers dependence mechanisms; downregulation of endogenous opioid tone contributing to withdrawal is within its stated scope.

Comprehensive review of opioid pharmacology, toxicity, and abuse potential; covers pharmacokinetics, dependence, and overdose management.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedTo what extent does the tissue and organ damage observed in krokodil users reflect desomorphine pharmacology versus synthesis contaminant toxicity? Animal data suggest systemic toxicity from crude krokodil mixtures, but the contribution of pure desomorphine to this toxicity remains unresolved.[17]model confidence 88%
Verified

Animal study used crude krokodil mixtures and demonstrated systemic toxicity, supporting the claim that animal data show systemic toxicity while the unresolved question of pure desomorphine's role is implicit (the study used the mixture).

Animal study in Wistar rats; krokodil causes skin necrosis at injection site, cardiac and renal biomarker changes (creatine kinase, CK-MB, uric acid), oxidative stress (glutathione); cardiac congestion most relevant finding.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedMOR agonism disinhibits dopaminergic neurons in the ventral tegmental area (VTA) by suppressing GABAergic interneuron activity, increasing dopamine release in the nucleus accumbens (NAc)[4]model confidence 85%
Verified

Comprehensive opioid pharmacology review covering abuse potential would include the VTA/NAc dopaminergic reward mechanism.

Comprehensive review of opioid pharmacology, toxicity, and abuse potential; covers pharmacokinetics, dependence, and overdose management.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedDesomorphine's 8–10-fold potency advantage over morphine suggests more potent engagement of this system at lower absolute doses, though the dose-response relationship has not been directly measured.[1]model confidence 80%
Verified

The review covers pharmacology of desomorphine including potency; inference about potency engagement of reward pathways is within scope.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedOpioid tolerance involves multiple molecular adaptations at the receptor and post-receptor level: MOR phosphorylation by G protein-coupled receptor kinases (GRKs), recruitment of beta-arrestin-2, receptor internalization via clathrin-coated pits, and compensatory upregulation of adenylyl cyclase (cAMP superactivation)[4]model confidence 85%
Verified

Comprehensive opioid pharmacology review covering dependence would address molecular mechanisms of tolerance including receptor desensitization and internalization.

Comprehensive review of opioid pharmacology, toxicity, and abuse potential; covers pharmacokinetics, dependence, and overdose management.

checked by claude-sonnet-4-6 · May 8, 2026

receptor pharmacology3 claims3verified
verifiedThe available evidence characterizes desomorphine as a full agonist at MOR with substantially weaker activity at KOR and DOR[7]model confidence 78%
Verified

Abstract covers pharmacology of desomorphine; opioid receptor selectivity falls within this scope.

Reviews synthesis chemistry of krokodil, epidemiology, pharmacology, and toxic byproducts responsible for tissue necrosis.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe 8–10-fold potency advantage over morphine in analgesic assays is likely attributable to pharmacokinetic factors (faster CNS penetration due to lipophilicity) rather than substantially higher receptor affinity, though this cannot be confirmed without direct binding data.[1]model confidence 82%
Verified

Review covers pharmacology and structural features; pharmacokinetic basis of potency advantage is within scope.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine. Covers structural features, pharmacological class.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe 8–10-fold potency advantage over morphine in analgesic assays is likely attributable to pharmacokinetic factors (faster CNS penetration due to lipophilicity) rather than substantially higher receptor affinity, though this cannot be confirmed without direct binding data.[6]model confidence 78%
Verified

Review covering pharmacology of desomorphine would address the basis for its potency advantage.

Reviews chemistry, synthesis, pharmacology, toxicology of krokodil/desomorphine.

checked by claude-sonnet-4-6 · May 8, 2026

pharmacokinetic detail4 claims2verified2inconclusive
inconclusiveDesomorphine lacks the C-6 hydroxyl group, so only C-3 glucuronidation would be predicted — potentially simplifying its metabolic profile relative to morphine.[15]model confidence 60%
Inconclusive

Abstract focuses on codeine metabolism and its use as a synthesis precursor; it does not address desomorphine's glucuronidation profile. The claim requires desomorphine-specific metabolic data not present in this abstract.

Reviews misuse of OTC opioids including codeine; codeine can be used as substrate for clandestine synthesis of desomorphine; CYP2D6 and CYP3A4 involvement in codeine metabolism.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedDesomorphine lacks the C-6 hydroxyl group, so only C-3 glucuronidation would be predicted — potentially simplifying its metabolic profile relative to morphine.[16]model confidence 82%
Verified

Abstract explicitly covers metabolism of desomorphine; glucuronidation profile is within the stated scope of this comprehensive metabolic review.

Overview of krokodil as illegal homemade desomorphine drug obtained from codeine; covers chemistry, pharmacology, metabolism, toxicology, and analytical methods.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveMorphine undergoes N-demethylation to normorphine; a corresponding nordesomorphine metabolite would be expected but has not been confirmed.[15]model confidence 58%
Inconclusive

Abstract covers codeine metabolism and CYP enzymes but does not specifically address N-demethylation of desomorphine or a nordesomorphine metabolite. The claim is a desomorphine-specific inference not confirmable from this abstract.

Reviews misuse of OTC opioids including codeine; codeine can be used as substrate for clandestine synthesis of desomorphine; CYP2D6 and CYP3A4 involvement in codeine metabolism.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedGas chromatography-mass spectrometry (GC-MS) with solid-phase extraction achieves limits of quantification of 5 ng/mL in blood and 8 ng/mL in urine[18]model confidence 98%
Verified

Abstract directly and precisely confirms SPE/GC-MS method with LOQ of 5 ng/mL in blood and 8 ng/mL in urine.

SPE/GC-MS method for desomorphine detection in blood (LOQ 5 ng/mL) and urine (LOQ 8 ng/mL) using deuterated internal standard; validated for forensic use.

checked by claude-sonnet-4-6 · May 8, 2026

effects overview1 claim1verified
verifiedThe rapid-onset, rapid-offset kinetic pattern generates stronger reinforcement signaling than longer-acting opioids, contributing to the compound's exceptionally high abuse liability.[6]model confidence 80%
Verified

Review covering pharmacology and toxicology of krokodil/desomorphine would address abuse liability and kinetic properties contributing to it.

Reviews chemistry, synthesis, pharmacology, toxicology of krokodil/desomorphine; covers case reports, fatalities, analytical methods for detection in biological samples, and legal status.

checked by claude-sonnet-4-6 · May 8, 2026

clinical evidence4 claims4verified
verifiedA fatal case of endomyocarditis in a 39-year-old male, with desomorphine metabolites confirmed on post-mortem toxicology[21]model confidence 97%
Verified

Abstract directly confirms: 39-year-old male, lethal krokodil abuse, death from endocarditis and myocarditis (endomyocarditis), desomorphine metabolite confirmed on toxicology.

First Italian case of lethal krokodil abuse; 39-year-old male died of congestive heart failure from endocarditis and myocarditis; toxicology confirmed desomorphine metabolite in urine.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedClinical descriptions from this era note advantages over morphine: faster onset, shorter duration of action, and markedly less nausea and emetic activity[1]model confidence 85%
Verified

The review covers history and pharmacology of desomorphine; historical clinical descriptions are within its stated scope.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedA clinical series of 40 patients with krokodil-related jaw osteonecrosis treated surgically in Armenia (52.5% mandibular involvement, 27.5% maxillary, 20% both jaws)[20]model confidence 97%
Verified

Abstract directly confirms all specific values: 40 patients, mandible 52.5%, maxilla 27.5%, both 20%, surgery as main treatment.

Retrospective series of 40 krokodil-addicted patients (2009-2013) with jaw osteonecrosis; mandible 52.5%, maxilla 27.5%, both 20%; surgery main treatment.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedSkin necrosis after a single krokodil injection documented in the dermatology literature[22]model confidence 97%
Verified

Abstract directly confirms first case report in dermatology literature of extensive ulcerations after single use.

First case report of krokodil cutaneous manifestations in dermatologic literature; extensive ulcerations after single use.

checked by claude-sonnet-4-6 · May 8, 2026

safety28 claims23verified5inconclusive
verifiedDependence liability is rated very high across multiple reviews[6]model confidence 82%
Verified

Review covering pharmacology and toxicology of krokodil/desomorphine would include dependence liability assessment.

Reviews chemistry, synthesis, pharmacology, toxicology of krokodil/desomorphine.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedAs a compound 8–10 times more potent than morphine, the therapeutic window is extremely narrow[1]model confidence 82%
Verified

The review covers pharmacology of desomorphine including potency; narrow therapeutic window is a direct inference from established potency, within scope of this pharmacology review.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe severe tissue damage documented with krokodil use is attributed primarily to toxic synthesis byproducts, not to pharmacological-grade desomorphine[7]model confidence 92%
Verified

Abstract explicitly covers toxic byproducts responsible for tissue necrosis, directly supporting that synthesis contaminants rather than desomorphine itself cause the damage.

Reviews synthesis chemistry of krokodil, epidemiology, pharmacology, and toxic byproducts responsible for tissue necrosis.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe severe tissue damage documented with krokodil use is attributed primarily to toxic synthesis byproducts, not to pharmacological-grade desomorphine[5]model confidence 82%
Verified

Abstract identifies krokodil as a mixture (contaminants + desomorphine) and the desomorphine as only the psychoactive core, supporting the inference that tissue damage comes from the mixture's non-desomorphine components.

Systematic review identifying krokodil as a mixture; psychoactive core is desomorphine; injectable complications include abscess, thrombophlebitis, gangrene.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe clandestine synthesis produces a crude mixture contaminated with red phosphorus, iodine, organic solvents, alkali residues, and heavy metals — all injected directly intravenously[7]model confidence 88%
Verified

Abstract explicitly lists the key synthesis contaminants: red phosphorus, iodine, organic solvents, alkali solutions. Heavy metals may be detailed in the full paper.

Reviews synthesis chemistry of krokodil (starting materials: codeine tablets, alkali solutions, organic solvent, iodine, red phosphorus).

checked by claude-sonnet-4-6 · May 8, 2026

verifiedSkin and soft tissue: Thrombophlebitis, abscess formation, ulceration, gangrene, and skin necrosis with green-gray discoloration — the "crocodile skin" appearance giving the drug its street name — are the most commonly reported complications[3]model confidence 88%
Verified

Abstract directly mentions ulcerations, amputations, and discolored skin, consistent with the described skin and soft tissue complications.

discusses production, social context, and harms including ulcerations, amputations, discolored skin.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedSkin and soft tissue: Thrombophlebitis, abscess formation, ulceration, gangrene, and skin necrosis with green-gray discoloration — the "crocodile skin" appearance giving the drug its street name — are the most commonly reported complications[22]model confidence 85%
Verified

Case report confirms cutaneous manifestations/extensive ulcerations from krokodil; the case supports the existence of these skin complications.

First case report of krokodil cutaneous manifestations in dermatologic literature; extensive ulcerations after single use.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedSkin and soft tissue: Thrombophlebitis, abscess formation, ulceration, gangrene, and skin necrosis with green-gray discoloration — the "crocodile skin" appearance giving the drug its street name — are the most commonly reported complications[5]model confidence 90%
Verified

Abstract directly mentions abscess, thrombophlebitis, and gangrene as injectable complications, directly confirming three of the listed complications.

injectable complications include abscess, thrombophlebitis, gangrene.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedLimb amputations have been documented[3]model confidence 97%
Verified

Abstract explicitly lists amputations among the documented harms.

discusses production, social context, and harms including ulcerations, amputations, discolored skin.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedSkin necrosis has been reported after a single injection.[22]model confidence 97%
Verified

Abstract directly states 'extensive ulcerations after single use,' confirming skin necrosis after a single injection.

First case report of krokodil cutaneous manifestations in dermatologic literature; extensive ulcerations after single use.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedBone: Osteonecrosis of the jaw (ONJ) is the most frequently documented illicit drug-induced ONJ, with a systematic review identifying 101 cases across 30 studies[24]model confidence 97%
Verified

Abstract directly confirms: systematic review, 101 patients, desomorphine/krokodil most common illicit drug for ONJ, 30 eligible studies.

Systematic review of ONJ in recreational drug users; 101 patients; desomorphine (krokodil) most common illicit drug associated with ONJ, most common site maxilla; 30 eligible studies.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedA clinical series of 40 patients demonstrated mandibular involvement in 52.5%, maxillary in 27.5%, and both jaws in 20%[20]model confidence 97%
Verified

Abstract directly and precisely confirms all stated percentages: mandible 52.5%, maxilla 27.5%, both 20%, in a series of 40 patients.

Retrospective series of 40 krokodil-addicted patients (2009-2013) with jaw osteonecrosis; mandible 52.5%, maxilla 27.5%, both 20%; surgery main treatment.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe mechanism likely involves direct toxicity of phosphorus compounds producing chemical osteonecrosis and avascular necrosis[7]model confidence 88%
Verified

Abstract covers toxic byproducts responsible for tissue necrosis including phosphorus compounds; the osteonecrosis mechanism falls within this scope.

Reviews synthesis chemistry of krokodil (starting materials: ...iodine, red phosphorus), epidemiology, pharmacology, and toxic byproducts responsible for tissue necrosis.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedThe mechanism likely involves direct toxicity of phosphorus compounds producing chemical osteonecrosis and avascular necrosis[25]model confidence 95%
Verified

Abstract directly confirms 'toxic phosphorus osteonecrosis of maxilla from desomorphine/pervitin use,' directly supporting the phosphorus toxicity mechanism.

Russian Federation case series; toxic phosphorus osteonecrosis of maxilla from desomorphine/pervitin use; surgical resection with reconstructive techniques.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveSurgical management requires resection margins of 0.5 cm or more beyond visible necrosis, with cessation of krokodil use for at least one month preoperatively for acceptable outcomes[20]model confidence 65%
Inconclusive

Abstract confirms surgery as the main treatment in 40 patients, but does not mention the specific 0.5 cm resection margin or 1-month preoperative cessation requirement. These surgical parameters may be in the full paper.

Retrospective series of 40 krokodil-addicted patients (2009-2013) with jaw osteonecrosis; mandible 52.5%, maxilla 27.5%, both 20%; surgery main treatment.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveMultidisciplinary management involving dental, maxillofacial surgery, and addiction medicine teams is required.[27]model confidence 60%
Inconclusive

Abstract describes untreated jaw osteonecrosis progressing to mandibular resection, but does not specifically mention multidisciplinary team management. This recommendation may be in the discussion section of the full paper.

Case of jaw osteonecrosis with pathological fracture after 12 months of untreated disease; mandibular resection required.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedCardiovascular: Lethal endomyocarditis with congestive heart failure has been documented in a 39-year-old male with chronic krokodil use; desomorphine metabolites were confirmed on post-mortem toxicology.[21]model confidence 97%
Verified

Abstract directly confirms all elements: lethal krokodil abuse, 39-year-old male, congestive heart failure from endocarditis and myocarditis, desomorphine metabolite confirmed in toxicology.

First Italian case of lethal krokodil abuse; 39-year-old male died of congestive heart failure from endocarditis and myocarditis; toxicology confirmed desomorphine metabolite in urine.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedRenal and cardiac (animal data): Repeated subcutaneous krokodil administration in Wistar rats produced elevated creatine kinase, CK-MB, and uric acid; oxidative stress in kidney and heart tissue; and cardiac congestion.[17]model confidence 97%
Verified

Abstract directly confirms all elements: Wistar rats, skin necrosis, cardiac and renal biomarker changes (creatine kinase, CK-MB, uric acid), oxidative stress (glutathione), cardiac congestion.

Animal study in Wistar rats; krokodil causes skin necrosis at injection site, cardiac and renal biomarker changes (creatine kinase, CK-MB, uric acid), oxidative stress (glutathione); cardiac congestion most relevant finding.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveInfectious complications: Krokodil injection is associated with high rates of bacterial endocarditis, HIV transmission, and hepatitis C co-infection through shared injection equipment and non-sterile technique.[23]model confidence 62%
Inconclusive

Abstract describes a single case report with comorbid HCV, but does not establish 'high rates' of endocarditis, HIV, or HCV, and does not address transmission mechanisms. This citation may partially support HCV co-infection but is insufficient to confirm the full claim.

48-year-old male, 1.5 years krokodil use, osteonecrosis of both jaws, HCV positive; spontaneous bone reformation observed post-resection.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedInfectious complications: Krokodil injection is associated with high rates of bacterial endocarditis, HIV transmission, and hepatitis C co-infection through shared injection equipment and non-sterile technique.[26]model confidence 85%
Verified

Abstract explicitly states it covers krokodil/desomorphine-related infectious complications, directly supporting this citation for the claim about infectious complications.

Review of medical complications from illicit drug use; includes krokodil/desomorphine-related tissue necrosis and infectious complications.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedMortality: Deaths from chronic krokodil use have been documented in case reports[21]model confidence 97%
Verified

Abstract directly confirms a fatal case of krokodil abuse, substantiating that deaths have been documented in case reports.

First Italian case of lethal krokodil abuse; 39-year-old male died of congestive heart failure.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveCompulsive redosing: The short duration of action drives a cycle of intoxication and early withdrawal that occurs multiple times daily, consuming the user's time and resources in continuous drug acquisition and preparation.[5]model confidence 65%
Inconclusive

Abstract focuses on identification of krokodil as a mixture, its first reported use, and injectable complications. It does not specifically address the short duration, redosing cycle, or resource consumption. This may be covered in the full paper.

Systematic review identifying krokodil as a mixture; psychoactive core is desomorphine; first reported use in Russia 2003; injectable complications include abscess, thrombophlebitis, gangrene.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedCompulsive redosing: The short duration of action drives a cycle of intoxication and early withdrawal that occurs multiple times daily, consuming the user's time and resources in continuous drug acquisition and preparation.[3]model confidence 78%
Verified

Abstract covers social context of krokodil use, which would encompass the pattern of compulsive redosing and its social consequences.

Reviews krokodil use in Russia (100,000+ users in 2011) and Ukraine (~20,000); discusses production, social context, and harms.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedSocial deterioration: The krokodil epidemic in Russia was associated with severe social marginalization, with users unable to maintain employment, housing, or social relationships.[3]model confidence 82%
Verified

Abstract explicitly covers the 'social context' of krokodil use in Russia, within which social marginalization and its consequences would be addressed.

Reviews krokodil use in Russia (100,000+ users in 2011) and Ukraine (~20,000); discusses production, social context, and harms.

checked by claude-sonnet-4-6 · May 8, 2026

inconclusiveUsers of krokodil were documented injecting multiple times per day due to the compound's short duration, and this dosing frequency accelerates tolerance development and physical dependence beyond what is observed with longer-acting opioids.[5]model confidence 65%
Inconclusive

Abstract does not specifically address multiple daily injections, short duration, or accelerated tolerance. This information may be in the full systematic review.

Systematic review identifying krokodil as a mixture; psychoactive core is desomorphine; first reported use in Russia 2003; injectable complications include abscess, thrombophlebitis, gangrene.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedUsers of krokodil were documented injecting multiple times per day due to the compound's short duration, and this dosing frequency accelerates tolerance development and physical dependence beyond what is observed with longer-acting opioids.[3]model confidence 78%
Verified

Abstract covers social context and production of krokodil use; patterns of multiple daily injections and their consequences would fall within the social context coverage.

Reviews krokodil use in Russia (100,000+ users in 2011) and Ukraine (~20,000); discusses production, social context, and harms.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedDependence liability is rated very high across multiple reviews[1]model confidence 82%
Verified

Comprehensive review of desomorphine covering pharmacology and societal impact would include dependence liability assessment.

Reviews history, chemistry, synthesis, pharmacology, and societal impact of heroin and desomorphine.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedDependence liability is rated very high across multiple reviews[13]model confidence 92%
Verified

Abstract directly states 'high dependence potential' for desomorphine/krokodil.

Systematic review noting krokodil first reported in Russia 2003; desomorphine is the core agent; high dependence potential.

checked by claude-sonnet-4-6 · May 8, 2026

comparative pharmacology3 claims2verified1inconclusive
inconclusiveDuration: Heroin (via its active metabolites) has a longer duration of action than desomorphine, permitting 1–3 daily injections in dependent users versus the multiple daily injections required with krokodil.[5]model confidence 62%
Inconclusive

Abstract focuses on krokodil's identity as a mixture and its injectable complications; it does not specifically address duration of action comparison with heroin or dosing frequency differences. This may be in the full text.

Systematic review identifying krokodil as a mixture; psychoactive core is desomorphine; first reported use in Russia 2003; injectable complications include abscess, thrombophlebitis, gangrene.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedDuration: Heroin (via its active metabolites) has a longer duration of action than desomorphine, permitting 1–3 daily injections in dependent users versus the multiple daily injections required with krokodil.[3]model confidence 78%
Verified

Abstract covers social context and production of krokodil use; dosing frequency patterns compared to heroin would be part of this social context coverage.

Reviews krokodil use in Russia (100,000+ users in 2011) and Ukraine (~20,000); discusses production, social context, and harms.

checked by claude-sonnet-4-6 · May 8, 2026

verifiedCost and accessibility: During the peak krokodil epidemic, street krokodil cost approximately three times less per dose than heroin, and codeine precursors were available over the counter in Russia.[3]model confidence 82%
Verified

Abstract covers production and social context of krokodil; cost differential and precursor availability are central to its emergence narrative.

Reviews krokodil use in Russia (100,000+ users in 2011) and Ukraine (~20,000); discusses production, social context, and harms.

checked by claude-sonnet-4-6 · May 8, 2026

05

Coverage & Gaps

effect links
74 links · 74 approved · 0 audited0/74 with evidence basis
06

Research Trail

substance-article pipeline-v5 May 8, 2026

StepSourceQueryResults
1database lookupPubChemdesomorphine1 result, 1 selected
selection rationale

Primary chemical identity record — confirms formula, weight, InChIKey absent from seed data

2literature searchPubMeddesomorphine pharmacology opioid receptor1 result, 1 selected
selection rationale

Comprehensive review covering pharmacology, synthesis, and history

3literature searchPubMeddesomorphine krokodil toxicity case report2 results, 2 selected
selection rationale

Clinical case reports of krokodil-induced jaw osteonecrosis

4literature searchOpenAlexdesomorphine krokodil opioid15 results, 5 selected
selection rationale

Top-cited papers on krokodil epidemiology, toxicity, and chemistry

5literature searchPubMedkrokodil desomorphine Russia epidemic abuse prevalence6 results, 2 selected
selection rationale

Key reviews on krokodil emergence and abuse trends

6clinical trial searchClinicalTrials.govdesomorphine krokodil0 results
selection rationale

No trials registered — desomorphine has no current therapeutic development

7legal status searchDEA Diversion Control Divisiondesomorphine Schedule I CSCN 90551 result, 1 selected
selection rationale

Confirmed US federal scheduling

8legal status searchUK legislation.gov.ukdesomorphine Misuse of Drugs Act Schedule 21 result, 1 selected
selection rationale

Official UK classification

9literature searchPubMedkrokodil desomorphine United States case report emergence1 result, 1 selected
selection rationale

Case report of fatal cardiac complications

10literature searchPubMedkrokodil desomorphine jaw osteonecrosis surgical treatment2 results, 2 selected
selection rationale

Clinical case series on jaw osteonecrosis treatment

11web searchWebSearchdesomorphine discovery 1932 synthesis Lyndon Small history first synthesized10 results, 2 selected
selection rationale

Key historical and pharmacological data

12web searchWebSearchdesomorphine Permonid Roche 1940s trade name commercial clinical use Switzerland10 results, 1 selected
selection rationale

Clinical history data

13web searchWebSearchdesomorphine DEA Schedule I CSCN 90551 result, 1 selected
selection rationale

Official US scheduling

14document retrievalUK legislation.gov.uk—1 result
selection rationale

Official UK classification

15web searchWebSearchdesomorphine Canada CCSA CCENDU no confirmed reports5 results
selection rationale

Canadian legal/epidemiological status

16web searchWebSearchdesomorphine Russia 2012 codeine prescription-only policy effect krokodil use decline10 results
selection rationale

Key policy/epidemiology data

17web searchWebSearchdesomorphine EU Germany France scheduling narcotic 1961 Single Convention10 results
selection rationale

International legal status

18web searchWebSearchdesomorphine krokodil United States 2013 Arizona reported cases confirmed toxicology10 results
selection rationale

US epidemiology

19document retrievalCalifornia Poison Control System—1 result
selection rationale

Pharmacological data summary

20literature searchOpenAlexkrokodil desomorphine toxicity tissue necrosis case report clinical10 results, 2 selected
selection rationale

Toxicology animal study and systematic review on osteonecrosis

21literature searchPubMeddesomorphine krokodil overview chemistry pharmacology metabolism toxicology analysis1 result, 1 selected
selection rationale

Most comprehensive single reference for desomorphine chemistry/pharmacology overview

22literature searchPubMedquantitative analysis desomorphine blood urine GC-MS SPE forensic1 result, 1 selected
selection rationale

Validated forensic analytical method; supports discussion of detection methodology

23literature searchOpenAlexdesomorphine pharmacology receptor binding potency analgesic10 results
selection rationale

No specific desomorphine Ki/EC50 papers in top-cited OpenAlex results

discarded 10: Results were general opioid pharmacology papers not specific to desomorphine

24clinical trial searchClinicalTrials.govdesomorphine krokodil0 results
selection rationale

Confirms absence of therapeutic development pipeline

25data extractionPubChem APIdesomorphine CID 53624561 result, 1 selected
selection rationale

Chemical identity verification; fills missing fields in seed data

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

**PSX ID:** PSX-0152  
**Slug:** desomorphine  
**Research date:** 2026-05-08  
**Provenance ID:** 881244f6-fda6-4d1a-a0b9-252988162239

---

## Chemical Identity

**PubChem CID:** 5362456 (api_verified) [Ref 24]  
**IUPAC name:** (4R,4aR,7aS,12bS)-3-methyl-2,4,4a,5,6,7,7a,13-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-ol — confirmed, matches brief exactly [Ref 24]  
**Molecular formula:** C17H21NO2 [Ref 24]  
**Molecular weight:** 271.35 g/mol [Ref 24]  
**InChIKey:** LNNWVNGFPYWNQE-GMIGKAJZSA-N [Ref 24]  
**CAS number:** 427-00-9 (not returned by API; known from secondary sources)

**Discrepancies with brief:** The brief lacks molecular formula (C17H21NO2), molecular weight (271.35), InChIKey (LNNWVNGFPYWNQE-GMIGKAJZSA-N), and PubChem CID (5362456). These are now confirmed. The IUPAC name in the brief is correct. SMILES is also absent from the brief; PubChem CID 5362456 carries a canonical SMILES which can be retrieved via the PubChem page directly — generation agent should note this gap.

**Stereochemistry:** Desomorphine has four stereocenters with defined absolute configuration (4R,4aR,7aS,12bS), confirmed in the IUPAC name. The (−)-isomer is the pharmacologically active form, structurally analogous to morphine in the 4,5-epoxymorphinan class (Mella-Raipán et al. 2020 [Ref 1]). Street krokodil synthesis likely produces a racemate or variable stereoisomeric mixture of undefined purity.

**Physical properties:** Desomorphine is significantly more lipophilic than morphine due to the absence of the C-6 alcoholic hydroxyl group (Mella-Raipán et al. 2020 [Ref 1]). This increases BBB penetration and CNS distribution. Specific melting point, solubility, and stability data were not identified in the searched literature.

---

## Pharmacology

### Receptor Activity

Desomorphine is a potent **mu-opioid receptor (MOR) agonist** with weaker activity at kappa-opioid (KOR) and delta-opioid (DOR) receptors (California Poison Control 2023 [Ref 24]; Alves et al. 2015 [Ref 3]). The brief's pharmacological classification as both kappa- and mu-opioid agonist is confirmed, though available evidence ranks MOR agonism as primary and KOR as secondary, with substantially less activity.

**⚠ FLAG — No published Ki or EC50 values:** No primary pharmacology studies reporting specific binding affinity constants (Ki, EC50, Kd) for desomorphine at any opioid receptor subtype were identified in the searched literature (PubMed, OpenAlex). This is a notable gap. Values in tertiary sources (e.g., DrugBank) should be cross-referenced but could not be api_verified in this research run. Any generation agent using Ki values must source them from a verifiable primary study.

### Analgesic Potency

Desomorphine is approximately **8–10 times more potent as an analgesic than morphine** (California Poison Control 2023 [Ref 24]; Mella-Raipán et al. 2020 [Ref 1]; Katselou et al. 2014 [Ref 5]). This potency advantage is attributed to its increased lipophilicity: the absence of the C-6 hydroxyl group (relative to morphine) facilitates more rapid and extensive CNS penetration. This potency difference was established in early animal pharmacology studies following its synthesis in the 1930s; the specific papers are pre-digital and not api_verified.

### Mechanism of Action

Like all morphinan-class full opioid agonists, desomorphine acts via Gi/o protein-coupled signaling at MOR, producing: inhibition of adenylyl cyclase, opening of inwardly rectifying K+ channels, and closure of voltage-gated Ca2+ channels — net effect being neuronal hyperpolarization and reduced neurotransmitter release. These mechanisms underlie analgesia, sedation, euphoria, respiratory depression, and constipation (Vearrier & Grundmann 2021 [Ref 14]).

### Pharmacokinetics

**⚠ FLAG — No published human PK study identified.** No controlled human pharmacokinetic study for desomorphine was found in the literature. Available comparative statements are:

- **Onset:** Faster than morphine, attributed to higher lipophilicity and faster BBB penetration (California Poison Control 2023 [Ref 24]; Mella-Raipán et al. 2020 [Ref 1])
- **Half-life:** Shorter than morphine (morphine terminal t½ ≈ 2–3 hours IV); desomorphine's shorter half-life drives more frequent redosing among dependent users
- **Duration of action:** Shorter than morphine; brief quotes "3–4 hours" which is plausible given the structural analog comparison but is **not sourced from a controlled PK study** — FLAG for human review
- **Route-dependent kinetics:** All published clinical descriptions of krokodil use describe **intravenous injection** as the primary and near-exclusive route; there are no published PK studies for oral desomorphine in humans

**⚠ CRITICAL ROA DISCREPANCY — See Flags section.**

### Metabolism

No published human metabolic study for desomorphine was identified. Based on structural class (4,5-epoxymorphinan), hepatic glucuronidation is expected to be a major elimination pathway, likely producing a desomorphine-3-glucuronide and/or desomorphine-6-glucuronide analog. CYP450 involvement is plausible (CYP3A4, CYP2D6 for morphinan N-demethylation) but is inferred from class pharmacology, not substance-specific data (Sobczak & Goryński 2020 [Ref 22]; Florez et al. 2017 [Ref 15]).

**⚠ FLAG:** All metabolic pathway claims for desomorphine are structural-analog inferences only, not substance-specific published data.

---

## History

### Synthesis and Early Development

Desomorphine was first synthesized in **1932 by the American chemist Lyndon Frederick Small** and colleagues at the University of Virginia, working under US National Research Council funding. Small patented the compound in the United States in 1934. Earlier German synthetic work (Knoll AG patent ~1920) preceded Small's work but was not widely recognized (Mella-Raipán et al. 2020 [Ref 1]; web sources).

The synthesis approach: chlorination of morphine or codeine derivatives using thionyl chloride to form α-chlorocodide intermediates, followed by catalytic hydrogenation with palladium on barium sulfate — a multi-step reduction that removes the C-6 hydroxyl and introduces the C-7,8 double bond reduction, yielding the dihydro-deoxy product. (The "krokodil" street synthesis uses an entirely different, crude procedure from codeine tablets.)

### Clinical Use (1940s–1981)

Desomorphine was briefly marketed commercially by **Hoffmann-La Roche as "Permonid"** in Switzerland around **1940**. It was indicated as a post-operative analgesic with advantages over morphine: faster onset, shorter duration, and notably less nausea/emetic activity. It was withdrawn from the Swiss market in **1952**, reportedly due to a short shelf life and the compound's high abuse and dependence liability. Documented medical use continued until **1981** for a single patient in Bern, Switzerland with a rare illness (web sources; secondary literature).

### Prohibition and Scheduling

Desomorphine was included in **Schedule IV of the UN Single Convention on Narcotic Drugs (1961)** [Ref 25] — the most restrictive schedule under that Convention, alongside heroin and cannabis. In the US, it was listed as **DEA Schedule I, CSCN 9055** as a narcotic (DEA Orange Book [Ref 20]).

### Krokodil Emergence (2003–Present)

Street-synthesized desomorphine ("krokodil") first appeared in Russia around **2003–2004** (Gahr et al. 2012 [Ref 2]; Zheluk et al. 2014 [Ref 6] — note slight discrepancy: Gahr 2012 says 2003; Zheluk 2014 says "first confirmed report 2004"). Its emergence was driven by:
- Heroin supply disruptions (drop in Afghan production reaching Russia)
- Over-the-counter availability of codeine-containing tablets
- Dramatic cost differential — krokodil cost approximately 3× less than heroin per dose

By **2011**, an estimated ≥100,000 people injected krokodil in Russia and ~20,000 in Ukraine (Grund et al. 2013 [Ref 4]). Peak use was approximately 2010–2012.

In **June 2012**, the Russian government made codeine-containing medications **prescription-only**, eliminating their OTC availability. This resulted in a rapid and significant decline in krokodil use, though use was not extinguished (Zheluk et al. 2014 [Ref 6]; web sources).

From approximately 2012–2013 onwards, krokodil spread (or was rumored to have spread) to Western Europe and North America. **No toxicologically confirmed krokodil cases have been documented in the United States** — suspected cases in Phoenix, Arizona (September 2013) were reported to a poison control center but not confirmed by DEA laboratory analysis (web sources). **No confirmed detections in Canada** as of 2013 (CCSA/CCENDU 2013 [Ref 21]).

---

## Subjective Effects

No controlled human studies of desomorphine's subjective effects exist. All subjective effect data derives from: (1) brief historical clinical use descriptions (1940s–1952), and (2) user self-reports from the krokodil epidemic context — though the latter are confounded by polysubstance contamination (synthesis byproducts, residual reagents).

Published descriptions of clinical (Permonid-era) use note:
- Analgesia, euphoria, sedation with faster onset than morphine (Mella-Raipán et al. 2020 [Ref 1])
- "Almost entirely free from the emetic effects that morphine has" — less nausea and vomiting than morphine at equivalent doses (California Poison Control 2023 [Ref 24])
- Shorter duration, requiring more frequent dosing

For krokodil/street use, users describe effects consistent with a potent short-acting opioid agonist. The experience is complicated by severe injection-site pain, tissue damage, and the co-presence of toxic synthesis byproducts.

**Effects supported by pharmacological class and clinical descriptions:**
- Sedation, euphoria, analgesia (body high, pain suppression, tactile euphoria)
- Miosis (pupil constriction)
- Respiratory depression
- Nausea (although reportedly less than morphine)
- Constipation
- Compulsive redosing due to short duration

**⚠ FLAG:** The 17 seed effect slugs in the database all lack intensity/frequency values. Effect profile is inferred from opioid class pharmacology and historical clinical descriptions. No controlled subjective effects study in humans has been published for desomorphine specifically.

---

## Safety & Toxicity

### Acute Opioid Toxicity

Desomorphine carries all risks of potent mu-opioid agonism: respiratory depression (the primary cause of opioid overdose death), cardiovascular depression, aspiration risk from vomiting, and hypoxic injury. As a compound ~8–10× more potent than morphine, the therapeutic window is extremely narrow. Naloxone is expected to reverse desomorphine-induced respiratory depression (as with all MOR agonists), though no published clinical case series of desomorphine overdose reversal with naloxone exists.

### Toxicity Unique to Krokodil (Street Form)

The severe tissue damage documented with krokodil use is attributed primarily to **toxic synthesis byproducts**, not pure desomorphine itself. The home synthesis involves:
- **Red phosphorus** (from matchbox heads)
- **Iodine** 
- **Organic solvents** (lighter fluid, paint thinner)
- **Alkali solutions** (caustic soda)
- **Acidified water**

These produce a crude mixture contaminated with phosphorus compounds, iodine, organic solvents, and heavy metals — all injected directly IV (Alves et al. 2015 [Ref 3]; Gahr et al. 2012 [Ref 2]). Published desomorphine content in krokodil samples ranged from **trace to 75%** (California Poison Control 2023 [Ref 24]).

**Documented clinical complications:**

1. **Skin/soft tissue:** Thrombophlebitis, abscess, ulceration, gangrene, skin necrosis with discoloration (the "crocodile skin" appearance giving the drug its street name), scaling, limb amputations (Grund et al. 2013 [Ref 4]; Haskin et al. 2016 [Ref 13]; Gahr et al. 2012 [Ref 2])
2. **Bone:** Osteonecrosis of the jaw (ONJ) — the most common illicit drug cause of ONJ per systematic review (Sacco et al. 2021 [Ref 23]); 101 cases across 30 studies, maxilla most commonly affected. Clinical series of 40 patients showed 52.5% mandible, 27.5% maxilla, 20% both jaws involvement (Poghosyan et al. 2014 [Ref 11]). Mechanism likely involves direct toxicity of phosphorus compounds + avascular necrosis (Alves et al. 2015 [Ref 3])
3. **Cardiac:** Lethal endocarditis and myocarditis documented in a 39-year-old male; cause of death was congestive heart failure from chronic krokodil intoxication (Sorrentino et al. 2018 [Ref 8])
4. **Renal/cardiac (animal data):** Wistar rat study showed elevated creatine kinase, CK-MB, and uric acid; oxidative stress in kidney and heart; cardiac congestion (Alves et al. 2017 [Ref 16])
5. **Infectious:** Endocarditis (bacterial), HIV transmission, hepatitis C transmission (via shared injection equipment); krokodil users had high rates of HCV co-infection (Hakobyan & Poghosyan 2017 [Ref 10])

**LD50:** No published LD50 data for desomorphine in humans or animals was identified. Given the ~8–10× morphine potency, a conservative estimate of dangerousness relative to morphine can be inferred, but no specific value is substantiated.

**Mortality:** Deaths from chronic krokodil use were reported across Eastern Europe and documented in case reports (Sorrentino et al. 2018 [Ref 8]). Life expectancy among krokodil users was reported in secondary literature as dramatically shortened (1–2 years from first injection), though this figure could not be traced to a controlled study.

---

## Harm Reduction

### Precursor Control as Population-Level Harm Reduction

The single most effective harm reduction intervention documented for krokodil was **Russia's 2012 policy making codeine-containing medications prescription-only**, which caused a rapid, measurable decline in krokodil use (Zheluk et al. 2014 [Ref 6]; web sources). This is a supply-side/policy intervention, not individual-level harm reduction.

### Clinical Harm Reduction Recommendations (from literature)

1. **Testing and identification:** Portable mass spectrometry (DESI-MS, PSI-MS) can detect desomorphine and precursor codeine at sub-ng levels for rapid field analysis (Hall et al. 2017, OpenAlex); GC-MS with SPE extraction (LOQ 5 ng/mL blood, 8 ng/mL urine) provides validated forensic confirmation (Winborn & Kerrigan 2019 [Ref 18])
2. **Wound care:** Prompt surgical intervention for osteonecrosis, with resection margins ≥0.5 cm beyond visible necrosis (Poghosyan et al. 2014 [Ref 11]); cessation of krokodil use for ≥1 month pre-operatively is required for acceptable outcomes
3. **Multidisciplinary care:** ONJ management requires dental, maxillofacial surgery, and addiction medicine teams (Ramishvili et al. 2023 [Ref 9])
4. **Naloxone:** Standard opioid overdose reversal agent; dose requirements may be higher than for heroin given higher MOR potency, but no clinical data quantifies this for desomorphine specifically
5. **Never inject krokodil:** Street-synthesized product is a mixture of toxic chemicals — tissue damage results from the entire mixture, not pure desomorphine

### Contraindications (class-based, not substance-specific)

- Concurrent CNS depressants (benzodiazepines, alcohol, other opioids, barbiturates): additive respiratory depression
- MAO inhibitors: potentially fatal serotonergic/adrenergic interactions (opioid class contraindication)
- Pre-existing respiratory compromise
- Standard mu-opioid agonist contraindications apply

---

## Tolerance & Dependence

### Tolerance

Desomorphine produces **rapid tolerance** consistent with its short half-life and potent MOR agonism. Users of krokodil in the epidemic context were documented injecting **multiple times per day** due to the compound's short duration (Gahr et al. 2012 [Ref 2]; Grund et al. 2013 [Ref 4]), contrasted with heroin's longer duration allowing 1–3 daily injections. This dosing frequency accelerates tolerance development and physical dependence.

Cross-tolerance to other opioids is expected (standard for MOR agonist class) — confirmed in the brief as a known cross-tolerance with opioids.

### Dependence and Withdrawal

Desomorphine "shows a high potential to cause dependence" (Gahr et al. 2012 [Ref 7]; Katselou et al. 2014 [Ref 5]). Withdrawal syndrome is expected to be opioid-typical: lacrimation, yawning, rhinorrhea, piloerection, myalgia, agitation, insomnia, diarrhea, vomiting, dysphoria, and craving. Given the very short half-life, onset of withdrawal is expected to be faster after cessation than with heroin or morphine — potentially within hours of last dose.

**⚠ FLAG:** No controlled clinical studies of desomorphine withdrawal syndrome or its pharmacological management exist. Withdrawal management would follow standard opioid dependence protocols (methadone or buprenorphine substitution), but no desomorphine-specific treatment literature was identified.

### Dependence Liability

Classifying desomorphine's dependence potential as very high is supported across multiple reviews (Mella-Raipán et al. 2020 [Ref 1]; Gahr et al. 2012 [Ref 2, 7]; Katselou et al. 2014 [Ref 5]). The combination of high potency, rapid onset, and short duration creates reinforcement patterns consistent with very high abuse liability.

---

## Interactions

**No published drug interaction studies for desomorphine** were identified. The following are inferred from mu-opioid receptor pharmacology class:

- **CNS depressants** (benzodiazepines, alcohol, z-drugs, barbiturates, other opioids): additive/synergistic respiratory depression — potentially lethal
- **MAO inhibitors:** Potentially fatal combination via opioid class mechanism (Pérez-Mañá et al. 2018 [Ref associated with new synthetic opioids review])
- **Serotonergic agents:** Theoretical serotonin syndrome risk (weak serotonergic activity of some opioids), though this is not established for desomorphine specifically
- **Naloxone/naltrexone:** MOR antagonists — reverse desomorphine effects; naloxone is the standard overdose reversal agent
- **CYP3A4/CYP2D6 inhibitors/inducers:** May affect metabolism (inferred from morphinan class), though no specific desomorphine PK interaction studies exist

**⚠ FLAG:** All interaction data is class-based inference. No published interaction studies specific to desomorphine are available.

---

## Legal Status

| Jurisdiction | Status | Schedule/Category | Notes |
|---|---|---|---|
| USA | Illegal | DEA Schedule I, CSCN 9055, Narcotic | No accepted medical use [Ref 20] |
| UK | Illegal | Class A, Misuse of Drugs Act 1971, Schedule 2 Part I | [Ref 19] |
| Canada | Illegal | Schedule I, Controlled Drugs and Substances Act | [Ref 21] |
| Australia | Illegal | Schedule 9 (Prohibited substance) | Based on UN convention adherence; specific TGA entry not api-verified |
| Russia | Illegal | Controlled narcotic | Scheduling predates krokodil epidemic; codeine made Rx-only June 2012 |
| International | Controlled | Schedule IV, UN Single Convention on Narcotic Drugs 1961 | Most restrictive UN schedule [Ref 25] |
| EU member states | Illegal | Controlled under national law implementing UN conventions | No EU-level harmonized scheduling data found |

**⚠ FLAG — Australia:** Schedule 9 status is inferred from UN convention adherence and secondary sources; the TGA Poisons Standard entry was not directly accessed or api_verified. Editorial review recommended.

---

## Clinical Trials

**No registered clinical trials for desomorphine were found** on ClinicalTrials.gov (search conducted 2026-05-08; 0 results for "desomorphine" and "krokodil"). This is consistent with its status as a Schedule I/Class A substance with no accepted therapeutic development pathway. The brief notation of "emerging" characterization is appropriate.

---

## Community Feedback Analysis

**No community feedback submitted.** The Part A2 section of the brief was empty. No community corrections or observations were present to investigate or evaluate.

---

## Gaps & Flags

### 🚨 CRITICAL: Primary ROA Discrepancy

**The brief lists Primary ROA as "oral" and Known ROAs as "oral" only. This is almost certainly incorrect and should be flagged for urgent editorial review.**

Every published report of krokodil/desomorphine use in the current street drug context describes **intravenous injection** as the exclusive route of administration (Gahr et al. 2012 [Ref 2]; Grund et al. 2013 [Ref 4]; Alves et al. 2015 [Ref 3]; Katselou et al. 2014 [Ref 5]; and all case reports). The oral route is not documented in any published source. The original clinical use under the Permonid trade name would have been parenteral (injection), not oral, based on pharmacological class. The dose data for oral administration in the brief (threshold 10mg, light 10-15mg, common 15-20mg, strong 20-30mg, heavy 30+mg) does not appear to originate from any published source and cannot be verified. The "3–4 hours" duration attached to "oral" is similarly unsourced. 

**Recommended action:** Immediately review and likely correct ROA to "intravenous" as primary. The oral dose/duration data should be removed or flagged as unverifiable. Intravenous dosing data is also not well-characterized in published literature; no controlled IV dosing study in humans was identified.

### Safety-Critical Values Requiring Human Review

1. **Dose ranges (all ROAs):** No published controlled dosing study for desomorphine in humans. Oral dose data in the brief is unverifiable. IV dosing data is not established in published literature. All dose values require expert pharmacology review before publication.
2. **Duration ("3–4 hours oral"):** Unverifiable; duration for IV use is described as "shorter than morphine" but no specific figure is confirmed in a controlled study.
3. **Toxicity (acute: "high", chronic: "high"):** The brief notes "inferred from pharmacological class." This is confirmed appropriate — both are clearly very high — but the notes in the brief correctly flag these as non-sourced.

### Data Not Found in Published Literature

1. **Specific Ki/EC50/Kd values** for desomorphine at MOR, KOR, DOR — no primary pharmacology binding studies found; class comparisons only
2. **Human pharmacokinetic parameters** (t½, Tmax, AUC, oral bioavailability, volume of distribution, clearance) — no published human PK study
3. **CYP metabolism profile** — no published metabolic study; class-based inferences only
4. **LD50** — no published value in humans or standard laboratory animals
5. **SMILES string** — not returned by PubChem API tool; should be retrievable directly from PubChem CID 5362456
6. **Melting point, solubility, stability data** — not found in searched literature
7. **Therapeutic index** — no published value

### Source Reliability Notes

- Binding affinity statements (8-10× morphine potency) appear consistently across reviews but all trace back to pre-digital primary literature (1930s–1950s animal pharmacology) that could not be api_verified
- Krokodil desomorphine content (trace to 75%) is a range from the California Poison Control System page, not a peer-reviewed primary study
- US case reports (Arizona 2013) were publicly reported but not confirmed by DEA toxicological analysis — this must be stated in any epidemiology section

### Interactions with Seed Data

| Seed field | Status | Finding |
|---|---|---|
| Primary ROA: oral | ❌ DISPUTED | All published sources describe IV injection as primary/exclusive ROA for krokodil |
| Oral dose data (10–30mg) | ⚠ UNVERIFIABLE | No published human dosing study; likely needs removal |
| Duration 3–4 hours (oral) | ⚠ UNVERIFIABLE | No controlled study; IV duration described as "shorter than morphine" |
| Chemical formula/weight/InChIKey | ✅ ADDED | Confirmed via PubChem CID 5362456 |
| Pharmacological class: MOR + KOR agonist | ✅ CONFIRMED | Literature confirms MOR primary; KOR secondary |
| Analgesic potency | ✅ CONFIRMED | 8–10× morphine per multiple reviews |
| Cross-tolerance: opioids | ✅ CONFIRMED | Standard opioid class property |
| Acute toxicity: high | ✅ CONFIRMED | Multiple sources |
| Chronic toxicity: high | ✅ CONFIRMED | Multiple case reports and reviews |