The short-acting synthetic cannabinoid AB-FUBINACA induces physical dependence in mice

Abstract

Background: Recent years have seen a rise in the diversity and use of synthetic cannabinoids. The present study evaluated the behavioral effects of the third-generation indazole-3-carboxamide-type synthetic cannabinoid, AB-FUBINACA. Methods: Adult male and female C57BL/6J mice were treated with AB-FUBINACA (0–3 mg/kg, i.p.) and tested repeatedly in the tetrad battery measuring catalepsy, antinociception, hypothermia, and locomotor activity. Mice treated with AB-FUBINACA (≥2 mg/kg, i.p.) displayed classic cannabinoid effects in the tetrad that were blocked by the CB 1 receptor selective antagonist rimonabant. To address tolerance and withdrawal effects, a second group of mice was injected with AB-FUBINACA (3 mg/kg, s.c.) or vehicle consisting of 5% ethanol, 5% Kolliphor EL, and 90 % saline every 12 h and tested daily in modified tetrad over the course of 5 days. On the 6th day, withdrawal was precipitated using rimonabant (3 mg/kg, s.c.), and somatic signs of withdrawal (i.e., head twitches and paw tremors) were quantified. Results: Although mice did not develop tolerance to AB-FUBINACA or cross-tolerance to Δ 9 -tetrahydrocannabinol (THC; 50 mg/kg, i.p.), somatic precipitated withdrawal signs were observed. Repeated tetrad testing up to 48 h post injection indicated that AB-FUBINACA effects are relatively short-lived, as compared with THC. Brain levels of AB-FUBINACA, as quantified by UHPLC-MS/MS, were undetectable 4 h post injection. Conclusions: These data indicate that the cannabinoid effects of AB-FUBINACA are relatively short-lived, yet sufficient to induce dependence in mice.

Intraperitoneal injection of MDMB-4en-PINACA mixed with clozapine: Biochemical, Behavioral and Histopathological assessment

“…Our results revealed that intraperitoneal injection of MDMB-PINACA mixed with clozapine induced tetrad effect in mice by showing hypolocomotion and cataleptic effect at high doses, besides hypothermia and antinoception with both high and low doses which supported by [11] who reported that use of synthetic cannabinoids AB-FUBINACA induced classic cannabinoid effects in tetrad tests. The reduced locomotor activity at high doses and increased locomotor activity at low doses which run in parallel with previous studies that reported a dose-dependent locomotor effects with AB-FUBINACA, AB-PINACA, PB-22 and THC cannabinoids [23] & [24] & [25].…”

“…(B) Body temperature Body temperature was measured by taking rectal temperature using digital thermometer to assess incidence of hypothermia. Basal rectal temperature was recorded 5minutes before drug administration and 50 minutes after [10] & [11].…”

“…Anti-nociception was measured by using tail immersion test where the distal tip of the tail was immersed into a 52-56 °C water bath and latency to remove the tail from the water was recorded, with a maximum cutoff of 10-12 seconds [13] & [11].…”

Benzydamine—An Affordable Over-the-Counter Drug with Psychoactive Properties—From Chemical Structure to Possible Pharmacological Properties

“…Due to adverse reactions of these compounds observed in rodent studies (catalepsy, hypothermia, dose-dependent and inconsistent effect on locomotor activity, agitation, anxiety), as well as those reported in humans (agitation, anxiety, hallucinations), these substances have never been recorded in therapy. However, the previously mentioned compounds are found as "impurities" in various trafficked preparations, especially on the black market, or used as street drugs [65]. CB1R are located in presynaptic neurons in various regions of the CNS, such as the cerebral cortex, hippocampus, hypothalamus, cerebellum, globus pallidus, and mesencephalic periaqueductal gray matter.…”

Experimental Study on Sub-acute Testicular Toxicity of AMB-FUBINACA in Adult Male Albino Rats

“…The doses of AMB-FUBINACA treated groups were selected as Group III received the lowest dose 2.5mg/kg which was confirmed to occupy all cannabinoid receptors with no or little clinical effect according to (Wilson et al, 2019;Trexler et al, 2020), Group V received the highest dose 10 mg/kg which cause confirmed toxicity and tolerated by animals according to ( Mousa et al,2021;Wilson et al, 2019) and Group IV received dose 5mk/kg midway between the lowest and the highest dose according to (Hsin-Hung Chen et al, 2016) .…”