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The Chemistry and Pharmacology of Synthetic Cannabinoid Receptor Agonists as New Psychoactive Substances: Origins

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New Psychoactive Substances

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 252))

Abstract

Synthetic cannabinoid receptor agonists (SCRAs) have proliferated as new psychoactive substances (NPS) over the past decade. Relative to other classes of NPS, SCRAs are structurally heterogeneous; however, most SCRAs act as potent, high-efficacy agonists of cannabinoid type 1 and type 2 receptors (CB1 and CB2, respectively). Characterization of the pharmacology and toxicology of these substances is hindered by the dynamic nature of the SCRA marketplace. Beyond basic pharmacological profiling at CB1 and CB2 receptors, very little is known about the acute or chronic effects of SCRAs. Many of the effects of SCRAs are qualitatively similar to those of the Δ9-tetrahydrocannabinol (Δ9-THC) found in cannabis. However, unlike Δ9-THC, SCRAs are frequently associated with serious adverse effects, including cardiotoxicity, nephrotoxicity, and death. This chapter will provide an overview of the structure and function of the primary target for SCRAs, the CB1 receptor, and survey the structure-activity relationships of the historical SCRAs that served as templates for the earliest generations of NPS.

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Abbreviations

5F-AB-001:

(Adamantan-1-yl)[1-(5-fluoropentyl)-1H-indol-3-yl]methanone

A-796,260:

[1-(2-Morpholin-4-ylethyl)-1H-indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone

AB-001:

(Adamantan-1-yl)(1-pentyl-1H-indol-3-yl)methanone

AB-005:

{1-[(1-Methylpiperidin-2-yl)methyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone

AB-FUBINACA:

(S)-N-(1-Amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide

2-AG:

2-Arachidonoylglycerol

AEA:

Arachidonylethanolamide

AM-679:

(2-Iodophenyl)(1-pentyl-1H-indol-3-yl)methanone

AM-1241:

(2-Iodo-5-nitrophenyl){1-[(1-methylpiperidin-2-yl)methyl]-1H-indol-3-yl}methanone

AM-1248:

[1-(1-Methylpiperidin-2-yl)-1H-indol-3-yl](adamant-1-yl)methanone

AM-2201:

[1-(5-Fluoropentyl)-1H-indol-3-yl](naphthalen-1-yl)methanone

AM-2232:

[1-(4-Cyanobutyl)-1H-indol-3-yl](naphthalen-1-yl)methanone

AM-2233:

(2-Iodophenyl){1-[(1-methyl-2-piperidinyl)methyl]-1H-indol-3-yl}methanone

BB-22:

8-Quinolinyl-1-(cyclohexylmethyl)-1H-indole-3-carboxylate

CBD:

Cannabidiol

CBN:

Cannabinol

CBND:

Cannabinodiol

CCH:

Cannabicyclohexanol

CP 47,497:

2-[(1R,3S)-3-Hydroxycyclohexyl]-5-(2-methyloctan-2-yl)phenol

CP 47,497-C8:

2-[(1R,3S)-3-Hydroxycyclohexyl]-5-(2-methylnonan-2-yl)phenol

CP 55,940:

2-[(1R,2R,5R)-5-Hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol

CPE:

Cannabipiperidiethanone

DMHP:

Dimethylheptylpyran

EAM-2201:

(4-Ethylnaphthalen-1-yl)[1-(5-fluoropentyl)indol-3-yl]methanone

HHC:

9-nor-9β-Hydroxyhexahydrocannabinol

HU-210:

(6aR,10aR)-9-(Hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol

JWH-018:

Naphthalen-1-yl(1-pentyl-1H-indol-3-yl)methanone

JWH-019:

(1-Hexyl-1H-indol-3-yl)(naphthalen-1-yl)methanone

JWH-020:

(1-Heptyl-1H-indol-3-yl)(naphthalen-1-yl)methanone

JWH-030:

(1-Hexylpyrrol-3-yl)-naphthalen-1-ylmethanone

JWH-073:

(1-Butyl-1H-indol-3-yl)(naphthalen-1-yl)methanone

JWH-081:

(4-Methoxynaphthalen-1-yl)(1-pentyl-1H-indol-3-yl)methanone

JWH-122:

(4-Methylnaphthalen-1-yl)(1-pentyl-1H-indol-3-yl)methanone

JWH-145:

Naphthalen-1-yl(1-pentyl-5-phenyl-1H-pyrrol-3-yl)methanone

JWH-147:

(1-Hexyl-5-phenyl-1H-pyrrol-3-yl)-naphthalen-1-ylmethanone

JWH-182:

(1-Pentyl-1H-indol-3-yl)(4-propylnaphthalen-1-yl)methanone

JWH-203:

2-(2-Chlorophenyl)-1-(2-methyl-1-pentyl-1H-indol-3-yl)ethanone

JWH-210:

(4-Ethyl-1-naphthalenyl)(1-pentyl-1H-indol-3-yl)-methanone

JWH-250:

2-(2-Methoxyphenyl)-1-(1-pentyl-1H-indol-3-yl)ethanone

JWH-251:

2-(3-Methylphenyl)-1-(1-pentyl-1H-indol-3-yl)ethanone

JWH-307:

[5-(2-Fluorophenyl)-1-pentyl-1H-pyrrol-3-yl](naphthalene-1-yl)methanone

JWH-398:

(4-Chloronaphthalen-1-yl)(1-pentyl-1H-indole-3-yl)methanone

JWH-412:

(4-Fluoronaphthalen-1-yl)(1-pentyl-1H-indol-3-yl)methanone

MAM-2201:

[1-(5-Fluoropentyl)-1H-indol-3-yl](4-methylnaphthalen-1-yl)methanone

RCS-2:

(2-Methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone

RCS-4:

(4-Methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone

RCS-8:

1-[1-(2-Cyclohexylethyl)-1H-indol-3-yl]-2-(2-methoxyphenyl)ethanone

Δ8-THC:

(−)-trans-Δ8-Tetrahydrocannabinol

Δ9-THC:

(−)-trans-Δ9-Tetrahydrocannabinol

UR-144:

(1-Pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone

WIN 55,212-2:

(R)-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone

XLR-11:

[1-(5-Fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone

XLR-12:

(2,2,3,3-Tetramethylcyclopropyl)[1-(4,4,4-trifluorobutyl)-1H-indol-3-yl]methanone

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Authors and Affiliations

  1. Department of Pathology, Stanford University, Stanford, CA, USA

    Samuel D. Banister

  2. Brain and Mind Centre, The University of Sydney, Camperdown, NSW, Australia

    Samuel D. Banister

  3. Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia

    Mark Connor

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  1. Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Homburg (Saar), Germany

    Hans H. Maurer

  2. School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK

    Simon D. Brandt

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Banister, S.D., Connor, M. (2018). The Chemistry and Pharmacology of Synthetic Cannabinoid Receptor Agonists as New Psychoactive Substances: Origins. In: Maurer, H., Brandt, S. (eds) New Psychoactive Substances . Handbook of Experimental Pharmacology, vol 252. Springer, Cham. https://doi.org/10.1007/164_2018_143

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