MDMB-CHMICA

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MDMB-CHMICA
MDMB-CHMICA.svg
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
Formula C23H32N2O3
Molar mass 384.520 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-CHMICA 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] [3] [4] [5] 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. [6]

Contents

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). [2] [8] [9]

Metabolism

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. [10] [11] [12]

Side effects

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] [13] [14] [15] [16]

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] [17] [18] [19] [20] [21]

In the United States, MDMB-CHMICA is a Schedule I controlled substance. [22]

MDMB-CHMICA is illegal in Austria, Canada, China, [23] Croatia, Denmark, Estonia, Finland, Germany, Greece, Hungary, Latvia, Lithuania, Louisiana, [24] 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. [25] 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. [26]

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), [2] including a 40 kg seizure [sic] in Luxembourg in December 2014. [27]

See also

Related Research Articles

<span class="mw-page-title-main">APICA (synthetic cannabinoid drug)</span> Chemical compound

APICA is an indole based drug that acts as a potent agonist for the cannabinoid receptors.

<span class="mw-page-title-main">ADBICA</span> Group of stereoisomers

ADBICA (also known as ADB-PICA) is a designer drug identified in synthetic cannabis blends in Japan in 2013. ADBICA had not previously been reported in the scientific literature prior to its sale as a component of synthetic cannabis blends. ADBICA features a carboxamide group at the 3-indole position, like SDB-001 and STS-135. The stereochemistry of the tert-butyl side-chain in the product is unresolved, though in a large series of indazole derivatives structurally similar to ADBICA that are disclosed in Pfizer patent WO 2009/106980, activity resides exclusively in the (S) enantiomers. ADBICA is a potent agonist of the CB1 receptor and CB2 receptor with an EC50 value of 0.69 nM and 1.8 nM respectively.

<span class="mw-page-title-main">ADB-FUBINACA</span> Chemical compound

ADB-FUBINACA is a designer drug identified in synthetic cannabis blends in Japan in 2013. In 2018, it was the third-most common synthetic cannabinoid identified in drugs seized by the Drug Enforcement Administration.

<span class="mw-page-title-main">AB-CHMINACA</span> Chemical compound

AB-CHMINACA is an indazole-based synthetic cannabinoid. It is a potent agonist of the CB1 receptor (Ki = 0.78 nM) and CB2 receptor (Ki = 0.45 nM) and fully substitutes for Δ9-THC in rat discrimination studies, while being 16x more potent. Continuing the trend seen in other cannabinoids of this generation, such as AB-FUBINACA and AB-PINACA, it contains a valine amino acid amide residue as part of its structure, where older cannabinoids contained a naphthyl or adamantane residue.

<span class="mw-page-title-main">5F-ADB</span> Chemical compound

5F-ADB (also known as 5F-MDMB-PINACA) is an indazole-based synthetic cannabinoid from the indazole-3-carboxamide family, which has been used as an active ingredient in synthetic cannabis products and has been sold online as a designer drug. 5F-ADB is a potent agonist of the CB1 receptor, though it is unclear whether it is selective for this target. 5F-ADB was first identified in November 2014 from post-mortem samples taken from an individual who had died after using a product containing this substance. Subsequent testing identified 5F-ADB to have been present in a total of ten people who had died from unexplained drug overdoses in Japan between September 2014 and December 2014. 5F-ADB is believed to be extremely potent based on the very low levels detected in tissue samples, and appears to be significantly more toxic than earlier synthetic cannabinoid drugs that had previously been sold.

<span class="mw-page-title-main">ADB-CHMINACA</span> Chemical compound

ADB-CHMINACA (also known as MAB-CHMINACA) is an indazole-based synthetic cannabinoid. It is a potent agonist of the CB1 receptor with a binding affinity of Ki = 0.289 nM and was originally developed by Pfizer in 2009 as an analgesic medication. It was identified in cannabinoid blends in Japan in early 2015.

<span class="mw-page-title-main">5F-AMB</span> Chemical compound

5F-AMB (also known as 5F-MMB-PINACA and 5F-AMB-PINACA) is an indazole-based synthetic cannabinoid from the indazole-3-carboxamide family, which has been used as an active ingredient in synthetic cannabis products. It was first identified in Japan in early 2014. Although only very little pharmacological information about 5F-AMB itself exists, its 4-cyanobutyl analogue (instead of 5-fluoropentyl) has been reported to be a potent agonist for the CB1 receptor (KI = 0.7 nM).

<span class="mw-page-title-main">5F-AB-PINACA</span> Chemical compound

5F-AB-PINACA is an indazole-based synthetic cannabinoid that is derived from a series of compounds originally developed by Pfizer in 2009 as an analgesic medication, and has been sold online as a designer drug.

<span class="mw-page-title-main">5F-APINACA</span> Chemical compound

5F-APINACA is an indazole-based synthetic cannabinoid that has been sold online as a designer drug. Structurally it closely resembles cannabinoid compounds from patent WO 2003/035005 but with a 5-fluoropentyl chain on the indazole 1-position, and 5F-APINACA falls within the claims of this patent, as despite not being disclosed as an example, it is very similar to the corresponding pentanenitrile and 4-chlorobutyl compounds which are claimed as examples 3 and 4.

<span class="mw-page-title-main">MDMB-FUBINACA</span> Chemical compound

MDMB-FUBINACA (also known as MDMB(N)-Bz-F and FUB-MDMB) is an indazole-based synthetic cannabinoid that is a potent agonist for the cannabinoid receptors, with Ki values of 1.14 nM at CB1 and 0.1228 nM at CB2 and EC50 values of 0.2668 nM at CB1 and 0.1411 nM at CB2, and has been sold online as a designer drug. Its benzyl analogue (instead of 4-fluorobenzyl) has been reported to be a potent agonist for the CB1 receptor (Ki = 0.14 nM, EC50 = 2.42 nM). The structure of MDMB-FUBINACA contains the amino acid, 3-methylvaline or tert-leucine methyl ester.

<span class="mw-page-title-main">MDMB-CHMINACA</span> Chemical compound

MDMB-CHMINACA (also known as MDMB(N)-CHM) is an indazole-based synthetic cannabinoid that acts as a potent agonist of the CB1 receptor, and has been sold online as a designer drug. It was invented by Pfizer in 2008, and is one of the most potent cannabinoid agonists known, with a binding affinity of 0.0944 nM at CB1, and an EC50 of 0.330 nM. It is closely related to MDMB-FUBINACA, which caused at least 1000 hospitalizations and 40 deaths in Russia as consequence of intoxication.

<span class="mw-page-title-main">PX-1</span> Chemical compound

PX-1 is an indole-based synthetic cannabinoid that has been sold online as a designer drug.

<span class="mw-page-title-main">PX-2</span> Chemical compound

PX-2 is an indazole-based synthetic cannabinoid that has been sold online as a designer drug. It contains a phenylalanine amino acid amide as part of its structure.

<span class="mw-page-title-main">5F-ADB-PINACA</span> Chemical compound

5F-ADB-PINACA is a cannabinoid designer drug that is an ingredient in some synthetic cannabis products. It is a potent agonist of the CB1 receptor and CB2 receptor with EC50 values of 0.24 nM and 2.1 nM respectively.

<span class="mw-page-title-main">AMB-FUBINACA</span> Chemical compound

AMB-FUBINACA (also known as FUB-AMB and MMB-FUBINACA) is an indazole-based synthetic cannabinoid that is a potent agonist for the cannabinoid receptors, with Ki values of 10.04 nM at CB1 and 0.786 nM at CB2 and EC50 values of 0.5433 nM at CB1 and 0.1278 nM at CB2, and has been sold online as a designer drug. It was originally developed by Pfizer which described the compound in a patent in 2009, but was later abandoned and never tested on humans. AMB-FUBINACA was the most common synthetic cannabinoid identified in drug seizures by the Drug Enforcement Administration in 2017 and the first half of 2018.

<span class="mw-page-title-main">AMB-CHMINACA</span> Chemical compound

AMB-CHMINACA or MMB-CHMINACA (also known as MA-CHMINACA) is an indazole-based synthetic cannabinoid that is a potent agonist of the CB1 receptor and has been sold online as a designer drug.

<span class="mw-page-title-main">FUB-APINACA</span> Chemical compound

FUB-APINACA (also known as A-FUBINACA according to the EMCCDA framework for naming synthetic cannabinoids and FUB-AKB48) is an indazole-based synthetic cannabinoid that is presumed to be a potent agonist of the CB1 receptor and has been sold online as a designer drug. It is an analog of APINACA and 5F-APINACA where the pentyl chain has been replaced with fluorobenzyl.

<span class="mw-page-title-main">MDMB-FUBICA</span> Chemical compound

MDMB-FUBICA is an indole-based synthetic cannabinoid that is presumed to be a potent agonist of the CB1 receptor and has been sold online as a designer drug.

<span class="mw-page-title-main">ADB-BINACA</span> Chemical compound

ADB-BINACA is a cannabinoid designer drug that has been found as an ingredient in some synthetic cannabis products. It was originally developed by Pfizer as a potential analgesic, and is a potent agonist of the CB1 receptor with a binding affinity (Ki) of 0.33 nM and an EC50 of 14.7 nM.

References

  1. ↑ "Substance Details MDMB-CHMICA" . Retrieved 2024-01-22.
  2. 1 2 3 4 5 6 7 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. ↑ "MDMB-CHMICA". Cayman Chemical. Retrieved 29 June 2015.
  4. ↑ "MDMB-CHMICA". Southern Association of Forensic Scientists. Retrieved 29 June 2015.
  5. ↑ 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.
  6. ↑ Shevyrin V, Melkozerov V, Nevero A, Eltsov O, Shafran Y, Morzherin Y, Lebedev AT (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.
  7. ↑ Andernach L, Pusch S, Weber C, Schollmeyer D, Münster-Müller S, Pütz M, Opatz T (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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ "Derby legal high confusion prompts police warning". BBC. 29 April 2015. Retrieved 29 June 2015.
  14. ↑ "Drug Alert: Dangerous Synthetic Cannabinoid MMB-CHMINACA Causing Hospitalizations, Deaths in Europe". TalkingDrugs. 2 July 2015. Retrieved 2 July 2015.
  15. ↑ Westin AA, Frost J, Brede WR, Gundersen PO, Einvik S, Aarset H, Slørdal L (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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ "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.
  23. ↑ "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.
  24. ↑ "Gov. Jindal and State Officials Ban New Synthetic Marijuana Compound" . Retrieved 29 June 2015.
  25. ↑ "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.
  26. ↑ "COUNCIL IMPLEMENTING DECISION (EU) 2017/369". Brussels: European Commission. 27 February 2017.
  27. ↑ "Global SMART update" (PDF). United Nations Office on Drugs and Crime. 13 March 2015. Retrieved 29 June 2015.
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