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Molecular and Behavioral Pharmacological Characterization of Abused Synthetic Cannabinoids MMB- and MDMB-FUBINACA, MN-18, NNEI, CUMYL-PICA, and 5-Fluoro-CUMYL-PICA.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2018 May; Vol. 365 (2), pp. 437-446. Date of Electronic Publication: 2018 Mar 16. - Publication Year :
- 2018
-
Abstract
- Synthetic cannabinoids are a class of novel psychoactive substances that exhibit high affinity at the cannabinoid type-1 (CB <subscript>1</subscript> ) receptor and produce effects similar to those of Δ-9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis. Illicit drug manufacturers are continually circumventing laws banning the sale of synthetic cannabinoids by synthesizing novel structures and doing so with little regard for the potential impact on pharmacological and toxicological effects. Synthetic cannabinoids produce a wide range of effects that include cardiotoxicity, seizure activity, and kidney damage, and they can cause death. Six synthetic cannabinoids, recently detected in illicit preparations, MMB-FUBINACA, MDMB-FUBINACA, CUMYL-PICA, 5F-CUMYL-PICA, NNEI, and MN-18 were assessed for: 1) receptor binding affinity at the human CB <subscript>1</subscript> and human CB <subscript>2</subscript> receptors, 2) function in [ <superscript>35</superscript> S]GTP γ S and cAMP signaling, and 3) THC-like effects in a mouse drug discrimination assay. All six synthetic cannabinoids exhibited high affinity for human cannabinoid receptors type-1 and type-2 and produced greater maximal effects than THC in [ <superscript>35</superscript> S]GTP γ S and cAMP signaling. Additionally, all six synthetic cannabinoids substituted for THC in drug discrimination, suggesting they probably possess subjective effects similar to those of cannabis. Notably, MDMB-FUBINACA, a methylated analog of MMB-FUBINACA, had higher affinity for CB <subscript>1</subscript> than the parent, showing that minor structural modifications being introduced can have a large impact on the pharmacological properties of these drugs. This study demonstrates that novel structures being sold and used illicitly as substitutes for cannabis are retaining high affinity at the CB <subscript>1</subscript> receptor, exhibiting greater efficacy than THC, and producing THC-like effects in models relevant to subjective effects in humans.<br /> (Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.)
- Subjects :
- 1-Naphthylamine pharmacology
Animals
CHO Cells
Cricetulus
Cyclic AMP metabolism
HEK293 Cells
Humans
Illicit Drugs pharmacology
Male
Mice
Mice, Inbred C57BL
Receptor, Cannabinoid, CB1 metabolism
Receptor, Cannabinoid, CB2 metabolism
Signal Transduction drug effects
Valine analogs & derivatives
Valine pharmacology
1-Naphthylamine analogs & derivatives
Cannabinoids pharmacology
Indazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0103
- Volume :
- 365
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 29549157
- Full Text :
- https://doi.org/10.1124/jpet.117.246983