MDMB-CHMICA

MDMB-CHMICA

Legal status
Legal status	CA: Schedule II DE: Anlage II (Prohibited) Illegal in Austria, China, Croatia, Denmark, Estonia, Finland, Greece, Hungary, Latvia, Lithuania, Louisiana, Luxembourg, Norway, Poland, Turkey, Sweden & Switzerland[1]
Identifiers
IUPAC name Methyl (2S)-2-{[1-(cyclohexylmethyl)-1H-indol-3-yl]formamido}-3,3-dimethylbutanoate
CAS Number	1863065-84-2
ChemSpider	34450863
Chemical and physical data
Formula	C23H32N2O3
Molar mass	384.52 g·mol^−1
3D model (Jmol)	Interactive image
SMILES COC(=O)[C@@H](NC(=O)c1cn(CC2CCCCC2)c3ccccc13)C(C)(C)C
InChI 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-CHMICA (also incorrectly known as MMB-CHMINACA) is an indole-based synthetic cannabinoid that is a potent agonist of the CB₁ receptor and has been sold online as a designer drug.^[1][2][3][4] 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.^[5]

Seizures

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),^[1] including a 40 kg seizure in Luxembourg in December 2014.^[6]

Chemistry

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.^[7] 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

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).^[1][8]

Metabolism

MDMB-CHMICAs main metabolic reactions comprise mono-hydroxylations and hydrolysis of the carboxylic ester function. In total, 31 metabolites could be identified in vivo.^[9][10][11]

Side Effects

71 serious adverse events, including 42 acute intoxications and 29 deaths (Germany (5), Hungary (3), Poland (1), Sweden (9), United Kingdom (10), Norway (1)) which occurred in 9 European countries between 2014 and 2016 have been associated with MDMB-CHMICA.^{[1][12][13][14][15]}

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.^{[1][16][17][18][19][20]}

Legal status

MDMB-CHMICA is illegal in Austria, Canada, China,^[21] Croatia, Denmark, Estonia, Finland, Germany, Greece, Hungary, Latvia, Lithuania, Louisiana,^[22] Luxembourg, Norway, Poland, Turkey, Sweden & Switzerland.^[1]

In August 2016 the European Commission proposed a ban on MDMB-CHMICA across the European Union.^[23]

See also

• AB-CHMINACA
• ADB-CHMINACA
• AMB-CHMINACA
• MDMB-CHMINACA
• MDMB-FUBINACA
• PX-3

References

1. "EMCDDA–Europol Joint Report on MDMB-CHMICA" (PDF). European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). July 2016. doi:10.2810/08132. ISBN 978-92-9168-925-5.
2. "MDMB-CHMICA". Cayman Chemical. Retrieved 29 June 2015.
3. "MDMB-CHMICA". Southern Association of Forensic Scientists. Retrieved 29 June 2015.
4. Banister, Samuel D.; Longworth, Mitchell; Kevin, Richard; Sachdev, Shivani; Santiago, Marina; Stuart, Jordyn; Mack, James B. C.; Glass, Michelle; McGregor, Iain S.; Connor, Mark; Kassiou, Michael (27 July 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. doi:10.1021/acschemneuro.6b00137. PMID 27421060.
5. Shevyrin, Vadim; Melkozerov, Vladimir; Nevero, Alexander; Eltsov, Oleg; Shafran, Yuri; Morzherin, Yuri; Lebedev, Albert T. (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): 6301–6315. doi:10.1007/s00216-015-8612-7. PMID 25893797.
6. "Global SMART update" (PDF). United Nations Office on Drugs and Crime. 13 March 2015. Retrieved 29 June 2015.
7. Andernach, Lars; Pusch, Stefan; Weber, Carina; Schollmeyer, Dieter; Münster-Müller, Sascha; Pütz, Michael; Opatz, Till (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.
8. Langer, Nico; Lindigkeit, Rainer; Schiebel, Hans-Martin; Papke, Uli; Ernst, Ludger; Beuerle, Till (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.
9. Florian Franz; Nadja Schwörer; Verena Angerer; Bjoern Moosmann; Volker Auwärter (2015). "Metabolism and urine analysis of the new synthetic cannabinoid MDMB-CHMICA" (PDF). Toxichem Krimtech. 82: 192.
10. Grigoryev, Andrej; Kavanagh, Pierce; Pechnikov, Alexandr (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.
11. Franz, Florian; Angerer, Verena; Moosmann, Bjoern; Auwärter, Volker (August 2016). "Phase I metabolism of the highly potent synthetic cannabinoid MDMB-CHMICA and detection in human urine samples". Drug Testing and Analysis. doi:10.1002/dta.2049. ISSN 1942-7611.
12. "Derby legal high confusion prompts police warning". BBC. 29 April 2015. Retrieved 29 June 2015.
13. "Drug Alert: Dangerous Synthetic Cannabinoid MMB-CHMINACA Causing Hospitalizations, Deaths in Europe". TalkingDrugs. 2 July 2015. Retrieved 2 July 2015.
14. Andreas Austgulen Westin; Joachim Frost; Wenche Rødseth Brede; Per Ole M. Gundersen; Steinar Einvik; Harald Aarset; Lars Slørdal (February 2016). "Sudden Cardiac Death Following Use of the Synthetic Cannabinoid MDMB-CHMICA". Journal of Analytical Toxicology. 40 (1): 86–87. doi:10.1093/jat/bkv110. PMID 26353925.
15. Piotr Adamowicz (April 2016). "Fatal intoxication with synthetic cannabinoid MDMB-CHMICA". Forensic Science International. 261: e5–e10. doi:10.1016/j.forsciint.2016.02.024. PMID 26934903.
16. Seywright, Alice; Torrance, Hazel J.; Wylie, Fiona M.; McKeown, Denise A.; Lowe, David J.; Stevenson, Richard (13 September 2016). "Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA". Clinical Toxicology. 54 (8): 632–637. doi:10.1080/15563650.2016.1186805. ISSN 1556-3650. PMID 27213960.
17. Hill, Simon L.; Najafi, Javad; Dunn, Michael; Acheampong, Paul; Kamour, Ashraf; Grundlingh, Johann; Blain, Peter G.; Thomas, Simon H. L. (13 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): 638–643. doi:10.1080/15563650.2016.1190980. ISSN 1556-3650. PMID 27251903.
18. Tait, Robert J.; Caldicott, David; Mountain, David; Hill, Simon L.; Lenton, Simon (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. PMID 26567470.
19. Meyyappan, Chitra; Ford, Loretta; Vale, Allister (2016). "Poisoning due to MDMB-CHMICA, a synthetic cannabinoid receptor agonist". Clinical Toxicology: 1–2. doi:10.1080/15563650.2016.1227832. ISSN 1556-3650. PMID 27635694.
20. Bäckberg, Matilda; Tworek, Luiza; Beck, Olof; Helander, Anders (2016). "Analytically Confirmed Intoxications Involving MDMB-CHMICA from the STRIDA Project". Journal of Medical Toxicology. doi:10.1007/s13181-016-0584-2. ISSN 1937-6995. PMID 27638057.
21. "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.
22. "Gov. Jindal and State Officials Ban New Synthetic Marijuana Compound". Retrieved 29 June 2015.
23. "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.