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Behavioral and Pharmacokinetic Profile of Indole-Derived Synthetic Cannabinoids JWH-073 and JWH-210 as Compared to the Phytocannabinoid Δ9-THC in Rats

Libor Uttl, Ewa Szczurowska, Kateřina Hájková, Rachel R. Horsley, Kristýna Štefková, Tomáš Hložek, Klára Šíchová, Marie Balı́ková, Martin Kuchař, Vincenzo Micale, Tomáš Páleníček

Frontiers in Neuroscience October 23, 2018 DOI: 10.3389/fnins.2018.00703 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental animal study Peer reviewed
Population Wistar rats
Interventions JWH-073 JWH-210 Δ9-THC vehicle (oleum helanti)
Dose JWH-073 0.1, 0.5 and 5 mg/kg; JWH-210 0.1, 0.5 and 5 mg/kg; Δ9-THC 1 and 3 mg/kg; vehicle 0.5 ml/kg
Measures open field, prepulse inhibition of the acoustic startle response (PPI ASR)
Topics Cannabis
Citations 24
Key findings Synthetic cannabinoids JWH-073 and JWH-210 and Δ9-THC reached the serum after subcutaneous administration but only partially affected locomotor activity and did not alter sensorimotor gating (prepulse inhibition). Δ9-THC at 3 mg/kg increased time spent in the center of the open field, which the authors interpret as an anxiolytic-like effect.

Abstract

Synthetic cannabinoid compounds are marketed as ‘legal’ marijuana substitutes, even though little is known about their behavioral effects in relation to their pharmacokinetic profiles. Therefore, in the present study we investigated the behavioral effects of systemic treatment with the two synthetic cannabinoids JWH-073 and JWH-210 and the phytocannabinoid Δ9-THC on locomotor activity and anxiety-like phenotype (in the open field) and sensorimotor gating (measured as prepulse inhibition of the acoustic startle response; PPI ASR), in relation to cannabinoid serum levels. Wistar rats were treated with either JWH-073 (0.1, 0.5 and 5 mg/kg), JWH-210 (0.1, 0.5 and 5 mg/kg), Δ9-THC (1 and 3 mg/kg) or vehicle (oleum helanti) in a volume of 0.5 ml/kg administered subcutaneously (sc.). 60 min after the treatment they were tested in the open field and in the PPI ASR test. Although synthetic cannabinoids, Δ9-THC and its metabolites were detected in the serum after sc. administration, they partially affect locomotor activity but not sensorimotor gating. Furthermore, Δ9-THC (3 mg/kg) induced an anxiolytic-like effect as suggested by the increased time spent in the center of the open field (p<0.05). Our results further support potentially anxiolytic-like effects of pharmacological modulation of the endocannabinoid system.

Comparable studies

Other preclinical and animal studies on cannabis, most cited first.

Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells 2010 In vitro study
Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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