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MDMB-CHMICA

MDMB-CHMICA
Legal status
Legal status
Identifiers
  • Methyl (2S)-2-{[1-(cyclohexylmethyl)-1H-indol-3-yl]formamido}-3,3-dimethylbutanoate
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC23H32N2O3
Molar mass384.520 g·mol−1
3D model (JSmol)
  • COC(=O)[C@@H](NC(=O)c1cn(CC2CCCCC2)c3ccccc13)C(C)(C)C
  • InChI=1S/C23H32N2O3/c1-23(2,3)20(22(27)28-4)24-21(26)18-15-25(14-16-10-6-5-7-11-16)19-13-9-8-12-17(18)19/h8-9,12-13,15-16,20H,5-7,10-11,14H2,1-4H3,(H,24,26)/t20-/m1/s1
  • Key:SRJKCVHWIDFUBO-HXUWFJFHSA-N

'MDMB-CHMICAa'[3] is an indole-based synthetic cannabinoid that is a potent agonist of the CB1 receptor and has been sold online as a designer drug.[2][4][5][6] While MDMB-CHMICA was initially sold under the name "MMB-CHMINACA", the compound corresponding to this code name (i.e. the isopropyl instead of t-butyl analogue of MDMB-CHMINACA) has been identified on the designer drug market in 2015 as AMB-CHMINACA.[7]

Chemistry

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Several commercial samples of MDMB-CHMICA were found to exclusively contain the (S)-enantiomer based on vibrational and electronic circular dichroism spectroscopy and X-ray crystallography.[8] An (S)-configuration for the tert-leucinate group is unsurprising since MDMB-CHMICA is likely synthesized from the abundant and inexpensive "L" form of the appropriate tert-leucinate reactant.

Pharmacology

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MDMB-CHMICA acts as a highly potent full agonist of the CB1 receptor with an efficacy of 94% and an EC50 value of 0.14 nM, which is approximately 8 times lower than the EC50 of JWH-018 (1.13 nM) and twofold lower than AB-CHMINACA (0.27 nM).[2][9][10]

Metabolism

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MDMB-CHMICA's main metabolic reactions comprise mono-hydroxylations and hydrolysis of the carboxylic ester function. In total, 31 metabolites could be identified in vivo.[11][12][13]

Side effects

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Seventy-one serious adverse events, including 42 acute intoxications and 29 deaths (Germany (5), Hungary (3), Poland (1), Sweden (9), United Kingdom (10), Norway (1)) that occurred in nine European countries between 2014 and 2016 have been associated with MDMB-CHMICA.[2][14][15][16][17]

Side effects such as unconsciousness or coma, hyperemesis, nausea, seizures, convulsions, tachycardia, bradycardia, mydriasis, syncope, spontaneous urinating and defecating, shortness of breath, somnolence, respiratory acidosis, metabolic acidosis, collapse, lower limbs paralysis, chest pain, aggression and severe disturbance of behaviour were reported.[2][18][19][20][21][22]

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In the United States, MDMB-CHMICA is a Schedule I controlled substance.[23]

MDMB-CHMICA is illegal in Austria, Canada, China,[24] Croatia, Denmark, Estonia, Finland, Germany, Greece, Hungary, Latvia, Lithuania, Louisiana,[25] Luxembourg, Norway, Portugal, Turkey, the UK, Sweden and Switzerland.[2]

In August 2016 the European Commission proposed a ban on MDMB-CHMICA across the European Union. [26] In 27 February 2017 the Commission adopted an implementing act in banning MDMB-CHMICA, and Member States shall take the necessary measures to subject it to control measures and criminal penalties no later than by 4 March 2018. [27]

Seizures

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Over 3600 MDMB-CHMICA seizures between 2014 and 2016 in 19 member states of the European Union have been reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA),[2] including a 40 kg seizure [sic] in Luxembourg in December 2014.[28]

See also

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References

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  1. ^ "Substance Details MDMB-CHMICA". Retrieved 2024-01-22.
  2. ^ a b c d e f g European Monitoring Centre for Drugs Drug Addiction, European Police Office (July 2016). EMCDDA–Europol Joint Report on MDMB-CHMICA (PDF). European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). doi:10.2810/08132. ISBN 978-92-9168-925-5.
  3. ^ Pulver B, Fischmann S, Gallegos A, Christie R (March 2023). "EMCDDA framework and practical guidance for naming synthetic cannabinoids". Drug Testing and Analysis. 15 (3): 255–276. doi:10.1002/dta.3403. PMID 36346325.
  4. ^ "MDMB-CHMICA". Cayman Chemical. Retrieved 29 June 2015.
  5. ^ "MDMB-CHMICA". Southern Association of Forensic Scientists. Retrieved 29 June 2015.
  6. ^ Banister SD, Longworth M, Kevin R, Sachdev S, Santiago M, Stuart J, et al. (September 2016). "Pharmacology of Valinate and tert-Leucinate Synthetic Cannabinoids 5F-AMBICA, 5F-AMB, 5F-ADB, AMB-FUBINACA, MDMB-FUBINACA, MDMB-CHMICA, and Their Analogues". ACS Chemical Neuroscience. 7 (9): 1241–54. doi:10.1021/acschemneuro.6b00137. PMID 27421060.
  7. ^ Shevyrin V, Melkozerov V, Nevero A, Eltsov O, Shafran Y, Morzherin Y, et al. (August 2015). "Identification and analytical characteristics of synthetic cannabinoids with an indazole-3-carboxamide structure bearing a N-1-methoxycarbonylalkyl group". Analytical and Bioanalytical Chemistry. 407 (21): 6301–15. doi:10.1007/s00216-015-8612-7. PMID 25893797. S2CID 31838655.
  8. ^ Andernach L, Pusch S, Weber C, Schollmeyer D, Münster-Müller S, Pütz M, et al. (1 June 2016). "Absolute configuration of the synthetic cannabinoid MDMB-CHMICA with its chemical characteristics in illegal products". Forensic Toxicology. 34 (2): 344–352. doi:10.1007/s11419-016-0321-1. S2CID 20075407.
  9. ^ Langer N, Lindigkeit R, Schiebel HM, Papke U, Ernst L, Beuerle T (January 2016). "Identification and quantification of synthetic cannabinoids in "spice-like" herbal mixtures: update of the German situation for the spring of 2015". Forensic Toxicology. 34 (1): 94–107. doi:10.1007/s11419-015-0292-7. S2CID 24851329.
  10. ^ Maeda H, Nagashima E, Hayashi YK, Kikura-Hanajiri R, Yoshida KI (2018). "MDMB-CHMICA induces thrashing behavior, bradycardia, and slow pressor response in a CB1- and CB2-receptor-dependent manner in conscious rats". Forensic Toxicology. 36 (2): 313–319. doi:10.1007/s11419-018-0405-1. ISSN 1860-8965. S2CID 46869442.
  11. ^ Franz F, Schwörer N, Angerer V, Moosmann B, Auwärter V (2015). "Metabolism and urine analysis of the new synthetic cannabinoid MDMB-CHMICA" (PDF). Toxichem Krimtech. 82: 192.
  12. ^ Grigoryev A, Kavanagh P, Pechnikov A (July 2016). "Human urinary metabolite pattern of a new synthetic cannabimimetic, methyl 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate". Forensic Toxicology. 34 (2): 316–328. doi:10.1007/s11419-016-0319-8. S2CID 20993024.
  13. ^ Franz F, Angerer V, Moosmann B, Auwärter V (May 2017). "Phase I metabolism of the highly potent synthetic cannabinoid MDMB-CHMICA and detection in human urine samples". Drug Testing and Analysis. 9 (5): 744–753. doi:10.1002/dta.2049. PMID 27504870.
  14. ^ "Derby legal high confusion prompts police warning". BBC. 29 April 2015. Retrieved 29 June 2015.
  15. ^ "Drug Alert: Dangerous Synthetic Cannabinoid MMB-CHMINACA Causing Hospitalizations, Deaths in Europe". TalkingDrugs. 2 July 2015. Retrieved 2 July 2015.
  16. ^ Westin AA, Frost J, Brede WR, Gundersen PO, Einvik S, Aarset H, et al. (February 2016). "Sudden Cardiac Death Following Use of the Synthetic Cannabinoid MDMB-CHMICA". Journal of Analytical Toxicology. 40 (1): 86–7. doi:10.1093/jat/bkv110. PMID 26353925.
  17. ^ Adamowicz P (April 2016). "Fatal intoxication with synthetic cannabinoid MDMB-CHMICA". Forensic Science International. 261: e5-10. doi:10.1016/j.forsciint.2016.02.024. PMID 26934903.
  18. ^ Seywright A, Torrance HJ, Wylie FM, McKeown DA, Lowe DJ, Stevenson R (September 2016). "Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA" (PDF). Clinical Toxicology. 54 (8): 632–7. doi:10.1080/15563650.2016.1186805. PMID 27213960. S2CID 25866502.
  19. ^ Hill SL, Najafi J, Dunn M, Acheampong P, Kamour A, Grundlingh J, et al. (September 2016). "Clinical toxicity following analytically confirmed use of the synthetic cannabinoid receptor agonist MDMB-CHMICA. A report from the Identification Of Novel psychoActive substances (IONA) study". Clinical Toxicology. 54 (8): 638–43. doi:10.1080/15563650.2016.1190980. PMID 27251903. S2CID 11915432.
  20. ^ Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S (2 January 2016). "A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment". Clinical Toxicology. 54 (1): 1–13. doi:10.3109/15563650.2015.1110590. hdl:20.500.11937/44051. PMID 26567470. S2CID 4120093.
  21. ^ Meyyappan C, Ford L, Vale A (February 2017). "Poisoning due to MDMB-CHMICA, a synthetic cannabinoid receptor agonist". Clinical Toxicology. 55 (2): 151–152. doi:10.1080/15563650.2016.1227832. PMID 27635694. S2CID 34048973.
  22. ^ Bäckberg M, Tworek L, Beck O, Helander A (March 2017). "Analytically Confirmed Intoxications Involving MDMB-CHMICA from the STRIDA Project". Journal of Medical Toxicology. 13 (1): 52–60. doi:10.1007/s13181-016-0584-2. PMC 5330960. PMID 27638057.
  23. ^ "Schedules of Controlled Substances: Temporary Placement of Six Synthetic Cannabinoids (5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-CHMICA and MDMB-FUBINACA) Into Schedule I". Drug Enforcement Administration.
  24. ^ "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Retrieved 1 October 2015.
  25. ^ "Gov. Jindal and State Officials Ban New Synthetic Marijuana Compound". Retrieved 29 June 2015.
  26. ^ "New psychoactive substances: Commission proposes new ban and strengthens the EU's Early Warning System and risk assessment". Lisbon: European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). 31 August 2016.
  27. ^ "COUNCIL IMPLEMENTING DECISION (EU) 2017/369". Brussels: European Commission. 27 February 2017.
  28. ^ "Global SMART update" (PDF). United Nations Office on Drugs and Crime. 13 March 2015. Retrieved 29 June 2015.