Delving into the Latest Updates on JWH-018 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

AM-678, NA-PIMO

Target

CB1R x CB2

Action

agonists

Mechanism

CB1 agonists(Cannabinoid CB1 receptor agonists), CB2 agonists(Cannabinoid CB2 receptor agonists)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication

Anxiety DisordersPain

Inactive Indication-

Originator Organization

Clemson University

Active Organization

Clemson University

Hebei Medical UniversityShandong Medical University

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC24H23NO

InChIKeyJDNLPKCAXICMBW-UHFFFAOYSA-N

CAS Registry209414-07-3

The goal of this placebo-controlled study is to learn about the neural mechanisms underlying the acute effects of the synthetical cannabinoid JWH-018 in healthy, occasional cannabis users. It aims to assess neural underpinnings of neurocognitive impairments and psychotomimetic symptoms expected during the intoxication. Neuronal changes similar to those seen in cannabis intoxication are expected, such as altered neurotransmission and loss of functional connectivity within the mesocorticolimbic circuit. MRS, fMRI and blood parameters will be used for assessment. Participants will be asked to complete cognitive tasks and subjective questionnaires related to the subjective experience of the drug.

Start Date01 Oct 2023

Sponsor / Collaborator

Maastricht University

NL-OMON29562

/ CompletedNot ApplicableIIT

Safety profile and pharmacokinetics of a synthetic cannabinoid (JWH-018)

Start Date01 Mar 2015

Sponsor / Collaborator

Maastricht University

100 Clinical Results associated with JWH-018

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100 Translational Medicine associated with JWH-018

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100 Patents (Medical) associated with JWH-018

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562

Literatures (Medical) associated with JWH-018

01 Jul 2025·EUROPEAN JOURNAL OF PHARMACOLOGY

Repeated treatment with JWH-018 progressively increases motor activity and aggressiveness in male mice: involvement of CB1 cannabinoid and D1/D2 dopaminergic receptors

Article

Author: Corli, Giorgia ; Rossi, Paola ; Bassi, Marta ; Roda, Elisa ; Marti, Matteo ; De Luca, Fabrizio ; Bilel, Sabrine ; Locatelli, Carlo Alessandro ; Fattore, Liana

RATIONALE:

To date, the exposure to Synthetic Cannabinoids (SCs) has been linked to unanticipated psychiatric symptoms such as agitation, psychosis, and aggressive behavior. In line with this, preclinical studies have shown that acute and long-term exposure to these compounds can result in psychostimulant effects that may be related to CB₁-mediated and dopamine-dependent mechanisms.

OBJECTIVES:

This study focuses on the progressive effects induced by repeated injection of 1-pentyl-3-(1-naphthoyl)indole JWH-018 (6 mg/kg, i.p.) on the locomotor activity and aggressive behavior in adult male ICR-CD1® mice. Thus, the interaction with the cannabinoid CB₁ receptor-preferring antagonist/inverse agonist AM-251 (6 mg/kg, i.p.), the dopamine D_1/5 receptor antagonist SCH23390 (0.1 mg/kg, i.p.), and the dopamine D_2/3 receptor antagonist haloperidol (0.05 mg/kg, i.p.) have been evaluated. Expression and distribution of D₁ and D₂ receptors and tyrosine hydroxylase (TH) have been also investigated by immunohistochemistry on brain and cerebellar samples to explore potential neuroplastic events.

RESULTS:

The repeated treatment with JWH-018 lead to the exacerbation of unanticipated psychomotor agitation, progressively increasing spontaneous locomotion and aggressiveness. Pre-treatment with AM-251 prevents the effects induced by the SC first, third and seventh injection. SCH23390 and haloperidol significantly attenuate and fully prevent the effects induced by JWH-018 seventh injection when pre-administered, respectively, alone and in combination. Behavioral changes observed in JWH-018-treated mice are accompanied by alterations in cortical, hippocampal, striatal and cerebellar D₁, D₂ and TH gene expression levels.

CONCLUSION:

The present results demonstrated that repeated treatment with high dosage of JWH-018 induces psycho-stimulants effects via both CB₁ receptor-mediated and dopamine-dependent mechanisms.

01 Jul 2025·Forensic Toxicology

Acute and subacute cardiovascular effects of synthetic cannabinoid JWH-018 in rat

Article

Author: Koparir, Pelin ; Soylu, Ozcan ; Ermis, Necip ; Acet, Ahmet ; Celbis, Osman ; Oruc, Mucahit ; Samdanci, Emine ; Petekkaya, Semih ; Parlakpinar, Hakan ; Ozhan, Onural

Abstract:

Purpose:

This study investigates the cardiovascular effects of the synthetic cannabinoid naphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-018) in rats. The research aims to evaluate the pharmacologic, cardiologic, biochemical, and histopathological effects of acute and subacute administration at low and high doses. The primary research question is how JWH-018 impacts heart function, blood pressure, ECG patterns, and cardiac tissue integrity.

Methods:

Wistar albino rats were divided into five groups: control, acute low-dose (ALD, 0.5 mg/kg), acute high-dose (AHD, 5 mg/kg), subacute low-dose (SALD, 0.5 mg/kg for 14 days), and subacute high-dose (SAHD, 5 mg/kg for 14 days). Cardiovascular effects were assessed using echocardiography, hemodynamic and ECG analysis, histopathology, biochemical markers, and LC–MS/MS quantification of JWH-018 and its metabolites in heart tissue.

Results:

Acute high-dose JWH-018 caused bradycardia and hypotension, while subacute high-dose increased heart rate but continued to lower blood pressure. JWH-018 induced cardiac arrhythmias, conduction blocks, and ischemic ECG changes, with prolonged QT intervals in subacute high-dose rats. Histopathological findings revealed myocardial infarction-like features, including contraction bands and ischemic damage, particularly in subacute groups. Elevated pro-BNP and triglycerides indicated cardiac stress and metabolic effects. JWH-018 and its metabolites were detected in heart tissue, primarily in high-dose groups.

Conclusions:

JWH-018 has significant cardiovascular risks, causing heart rate dysregulation, hypotension, arrhythmias, and ischemic damage. These effects depend on dose and duration. The study highlights the potential dangers of synthetic cannabinoids, emphasizing that they should not be considered safe alternatives to natural cannabis.

01 Jun 2025·EUROPEAN JOURNAL OF PHARMACOLOGY

Pharmaco-toxicological effects of the synthetic cannabinoids 4F-ABUTINACA, SDB-005, and JWH-018 in mice. In vitro and in vivo studies

Article

Author: Luo, Xuwen ; Yan, Fang ; Xu, Peng ; Kuai, Lixin ; Qiao, Yanling ; Di, Bin ; Li, Kaixi ; Shi, Xuesong ; Xu, Deli

BACKGROUND:

Synthetic cannabinoids (SCs) are currently one of the most severely abused new psychoactive substances in the world. However, there remains a notable lack of pharmacological data on the newly emerged synthetic cannabinoids. In the present study, the in vitro and in vivo pharmacological effects of the fourth-generation synthetic cannabinoids 4F-ABUTINACA and SDB-005 are determined and compared to those of the first-generation synthetic cannabinoid JWH-018.

METHODS:

In this study, the affinities of three SCs for CB1 receptors were evaluated using surface plasmon resonance (SPR) experiments. The acute toxicity of these three SCs was assessed through the up-and-down procedure, while their cannabinoid-specific pharmacological effects were determined through tetrad assays, which examined parameters such as temperature regulation, analgesia, locomotor activity, and catalepsy. Additionally, conditioned place preference (CPP) experiments and a precipitated withdrawal tests were conducted to assess the psychoactive effects and physical dependence of the SCs.

RESULTS:

SPR experiments and acute toxicity tests demonstrated that in vitro KD values were positively correlated with in vivo ED₅₀ potency estimates. All SCs were found to induce the classical "tetrad effects" in a dose-dependent manner. Notably, all SCs displayed significant biphasic effects in CPP experiments. Following the administration of the CB1 receptor antagonist rimonabant, a significant increase in head twitches and paw tremors was observed, indicating that the physical dependence manifested after the ingestion of SCs is mediated by the CB1 receptor.

CONCLUSIONS:

These findings suggest that these SCs have cannabinoid-specific pharmacological effects and abuse potential, providing robust experimental data to support future regulatory efforts.

100 Deals associated with JWH-018

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Anxiety Disorders	Preclinical	China	Hebei Medical University	01 Jan 2025
Anxiety Disorders	Preclinical	China	Shandong Medical University	01 Jan 2025
Pain	Discovery	-	Clemson University	-