Structure–activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB1 and CB2 receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB2 receptor agonists

Huffman, John W.; Zengin, Gülay; Wu, Ming‐Jung; Lu, Jianzhong; Hynd, George W.; Bushell, Kristen; Thompson, Alicia L. S.; Bushell, Simon M.; Tartal, Cindy L.; Hurst, Dow P.; Reggio, Patricia H.; Selley, Dana E.; Cassidy, Michael P.; Wiley, Jenny L.; Martin, Billy R.

doi:10.1016/j.bmc.2004.09.050

Cited by 244 publications

(211 citation statements)

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“…A series of cannabinoids originally synthesized by Huffman et al, (2005), labeled as JWH, have entered the recreational market. Highly purified JWH compounds, which are more readily synthesized than plant-derived cannabinoids, are available from online vendors in gram quantities with no age verification.…”

Section: Introductionmentioning

confidence: 99%

“…⌬ 9 -THC and its actions at CB 1 receptors are responsible primarily for the behavioral effects of cannabis (Wiley, 1999). Both JWH-018 and JWH-073 are reported to be CB 1 receptor agonists in vitro, similar to ⌬ 9 -THC, although JWH-018 seems to have higher CB 1 agonist efficacy than JWH-073 or ⌬ 9 -THC (Wiley et al, 1998;Huffman et al, 2005;Brents et al, 2011). For example, in one recent study, the maximal effect of ⌬ 9 -THC was less than 25% of that of JWH-018 (Brents et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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JWH-018 and JWH-073: Δ⁹-Tetrahydrocannabinol-Like Discriminative Stimulus Effects in Monkeys

Ginsburg

Schulze

Hrubá

et al. 2011

J Pharmacol Exp Ther

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Products containing naphthalen-1-yl-(1-pentylindol-3-yl) methanone (JWH-018) and naphthalen-1-yl-(1-butylindol-3-yl) methanone (JWH-073) are emerging drugs of abuse. Here, the behavioral effects of JWH-018 and JWH-073 were examined in one behavioral assay selective for cannabinoid agonism, rhesus monkeys (n ϭ 4) discriminating ⌬ 9 -tetrahydrocannabinol (⌬ 9 -THC; 0.1 mg/kg i.v.), and another assay sensitive to cannabinoid withdrawal, i.e., monkeys (n ϭ 3) discriminating the cannabinoid antagonist rimonabant (1 mg/kg i.v.) during chronic ⌬ 9 -THC (1 mg/kg s.c. 12 h) treatment. ⌬ 9 -THC, JWH-018, and JWH-073 increased drug-lever responding in monkeys discriminating ⌬ 9 -THC; the ED 50 values were 0.044, 0.013, and 0.058 mg/kg, respectively and the duration of action was 4, 2, and 1 h, respectively. Rimonabant (0.32-3.2 mg/kg) produced surmountable antagonism of ⌬ 9 -THC, JWH-018, and JWH-073. Schild analyses and single-dose apparent affinity estimates yielded apparent pA 2 /pK B values of 6.65, 6.68, and 6.79 in the presence of ⌬ 9 -THC, JWH-018, and JWH-073, respectively. In ⌬ 9 -THC-treated monkeys discriminating rimonabant, the training drug increased responding on the rimonabant lever; the ED 50 value of rimonabant was 0.20 mg/kg. ⌬ 9 -THC (1-10 mg/kg), JWH-018 (0.32-3.2 mg/kg), and JWH-073 (3.2-32 mg/kg) dose-dependently attenuated the rimonabantdiscriminative stimulus (i.e., withdrawal). These results suggest that ⌬ 9 -THC, JWH-018, and JWH-073 act through the same receptors to produce ⌬ 9 -THC-like subjective effects and attenuate ⌬ 9 -THC withdrawal. The relatively short duration of action of JWH-018 and JWH-073 might lead to more frequent use, which could strengthen habitual use by increasing the frequency of stimulusoutcome pairings. This coupled with the possible greater efficacy of JWH-018 at cannabinoid 1 receptors could be associated with greater dependence liability than ⌬ 9 -THC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

JWH-018 and JWH-073: Δ⁹-Tetrahydrocannabinol-Like Discriminative Stimulus Effects in Monkeys

Ginsburg

Schulze

Hrubá

et al. 2011

J Pharmacol Exp Ther

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“…The main aim of these studies was to synthesize compounds with high specificity for the second cannabinoid receptor (CB2), transmitting antiinflammatory effects and pain release [35][36][37] . However, these efforts resulted in a large number of structurally different drug candidates that exhibited undesirable psychoactive effects [38][39][40] due to their binding affinity to the first cannabinoid receptor (CB1). These substances, which often were rejected as drug candidates, have instead appeared on the drug market as unregulated and illicit drugs.…”

Section: The Evolution Of Synthetic Cannabinoidsmentioning

confidence: 99%

Synthesis and spectroscopic characterization of emerging synthetic cannabinoids and cathinones

Carlsson¹

2016

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The application of different analytical techniques is fundamental in forensic drug analysis. In the wake of the occurrence of large numbers of new psychoactive substances possessing similar chemical structures as already known ones, focus has been placed on applied criteria for their univocal identification. These criteria vary, obviously, depending on the applied technique and analytical approach. However, when two or more substances are proven to have similar analytical properties, these criteria no longer apply, which imply that complementary techniques have to be used in their differentiation.This work describes the synthesis of some structural analogues to synthetic cannabinoids and cathinones based on the evolving patterns in the illicit drug market. Six synthetic cannabinoids and six synthetic cathinones were synthesized, that, at the time for this study, were not as yet found in drug seizures. Further, a selection of their spectroscopic data is compared to those of already existing analogues; mainly isomers and homologues. The applied techniques were mass spectrometry (MS), Fourier transformed infrared (FTIR, gas phase) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. In total, 59 different compounds were analyzed with the selected techniques.

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“…Effects of SC use can include acute agitation, paranoia, depression, hallucinations and other perceptual disturbances and a number of medical manifestations including nausea, vomiting, tachycardia, seizures, kidney failure and death. 5 Cardiovascular and CNS toxicity are reported to be related to the long term abuse-related effects of dependence and withdrawal. 6 A case report noted how SC use initially caused a pressor-like effect, followed by vasodilation, subsequent reflex tachycardia and ischemia.…”

Section: Adverse Effectsmentioning

confidence: 99%

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2016

MOJAMT

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Structure–activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB1 and CB2 receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB2 receptor agonists

Cited by 244 publications

References 43 publications

JWH-018 and JWH-073: Δ⁹-Tetrahydrocannabinol-Like Discriminative Stimulus Effects in Monkeys

JWH-018 and JWH-073: Δ⁹-Tetrahydrocannabinol-Like Discriminative Stimulus Effects in Monkeys

Synthesis and spectroscopic characterization of emerging synthetic cannabinoids and cathinones

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Structure–activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB1 and CB2 receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB2 receptor agonists

Cited by 244 publications

References 43 publications

JWH-018 and JWH-073: Δ9-Tetrahydrocannabinol-Like Discriminative Stimulus Effects in Monkeys

JWH-018 and JWH-073: Δ9-Tetrahydrocannabinol-Like Discriminative Stimulus Effects in Monkeys

Synthesis and spectroscopic characterization of emerging synthetic cannabinoids and cathinones

Untitled

Contact Info

Product

Resources

About

JWH-018 and JWH-073: Δ⁹-Tetrahydrocannabinol-Like Discriminative Stimulus Effects in Monkeys

JWH-018 and JWH-073: Δ⁹-Tetrahydrocannabinol-Like Discriminative Stimulus Effects in Monkeys