Kaixi Li, Deli Xu, Yanling Qiao, Lixin Kuai, Xuwen Luo, Bin Di, Peng Xu
{"title":"评估 5F-EDMB-PICA、CUMYL-PEGACLONE 和 NM-2201 对小鼠的药理作用和滥用潜力。","authors":"Kaixi Li, Deli Xu, Yanling Qiao, Lixin Kuai, Xuwen Luo, Bin Di, Peng Xu","doi":"10.1007/s00213-024-06703-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>The newly emerging synthetic cannabinoids (SCs) 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 have been observed to produce effects by activating cannabinoid type 1 (CB1) receptors. Nevertheless, the pharmacological effects and potential for abuse of these three substances remain to be studied. These substances have yet to be regulated in many countries.</p><p><strong>Objectives: </strong>We investigated the safety, pharmacological effects, rewarding effects, and cannabinoid withdrawal of 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201.</p><p><strong>Methods: </strong>This study evaluated the drug safety and the cannabinoid-specific pharmacological effects of the three substances through acute toxicity experiments (in which the LD<sub>50</sub> of each substance was obtained) and tetrad experiments (comprising assessments of hypothermia, analgesia, locomotion inhibition, and catalepsy). Furthermore, the conditioned place preference (CPP) experiments and withdrawal experiments were conducted to evaluate the rewarding effect and cannabinoid withdrawal potential of the substances in question.</p><p><strong>Results: </strong>The results demonstrated that all three drugs exhibited certain acute toxic effects and could potentially induce tetrad effects. The data were analyzed using non-linear regression, and the corresponding ED<sub>50</sub> values and 95% confidence intervals (CI) were obtained. The rank order of potency was determined to be CUMYL-PEGACLONE > 5F-EDMB-PICA > NM-2201. In the CPP experiments, it was demonstrated that 5F-EDMB-PICA significantly induced an increase in CPP score at a dose of 0.3 mg/kg, while NM-2201 caused an increase in CPP score and a significant aversion effect at a dose of 2 and 3 mg/kg, respectively. It is noteworthy that all three types of SCs were observed to produce a significant biphasic effect, indicating that CPP scores were biphasic for all compounds. Following the administration of the CB1 receptor antagonist rimonabant, a notable increase in head twitches and paw tremors was observed, indicating that these three SCs induce cannabinoid withdrawal through the mediation of CB1 receptors.</p><p><strong>Conclusions: </strong>The results of this study indicated that these SCs possess cannabinoid-specific pharmacological effects and abuse potential, which provides substantial experimental data to support the future regulation of these substances.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Assessment of pharmacological effects and abuse potential of 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 in mice.\",\"authors\":\"Kaixi Li, Deli Xu, Yanling Qiao, Lixin Kuai, Xuwen Luo, Bin Di, Peng Xu\",\"doi\":\"10.1007/s00213-024-06703-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale: </strong>The newly emerging synthetic cannabinoids (SCs) 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 have been observed to produce effects by activating cannabinoid type 1 (CB1) receptors. Nevertheless, the pharmacological effects and potential for abuse of these three substances remain to be studied. These substances have yet to be regulated in many countries.</p><p><strong>Objectives: </strong>We investigated the safety, pharmacological effects, rewarding effects, and cannabinoid withdrawal of 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201.</p><p><strong>Methods: </strong>This study evaluated the drug safety and the cannabinoid-specific pharmacological effects of the three substances through acute toxicity experiments (in which the LD<sub>50</sub> of each substance was obtained) and tetrad experiments (comprising assessments of hypothermia, analgesia, locomotion inhibition, and catalepsy). Furthermore, the conditioned place preference (CPP) experiments and withdrawal experiments were conducted to evaluate the rewarding effect and cannabinoid withdrawal potential of the substances in question.</p><p><strong>Results: </strong>The results demonstrated that all three drugs exhibited certain acute toxic effects and could potentially induce tetrad effects. The data were analyzed using non-linear regression, and the corresponding ED<sub>50</sub> values and 95% confidence intervals (CI) were obtained. The rank order of potency was determined to be CUMYL-PEGACLONE > 5F-EDMB-PICA > NM-2201. In the CPP experiments, it was demonstrated that 5F-EDMB-PICA significantly induced an increase in CPP score at a dose of 0.3 mg/kg, while NM-2201 caused an increase in CPP score and a significant aversion effect at a dose of 2 and 3 mg/kg, respectively. It is noteworthy that all three types of SCs were observed to produce a significant biphasic effect, indicating that CPP scores were biphasic for all compounds. Following the administration of the CB1 receptor antagonist rimonabant, a notable increase in head twitches and paw tremors was observed, indicating that these three SCs induce cannabinoid withdrawal through the mediation of CB1 receptors.</p><p><strong>Conclusions: </strong>The results of this study indicated that these SCs possess cannabinoid-specific pharmacological effects and abuse potential, which provides substantial experimental data to support the future regulation of these substances.</p>\",\"PeriodicalId\":20783,\"journal\":{\"name\":\"Psychopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-10-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Psychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00213-024-06703-9\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-024-06703-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Assessment of pharmacological effects and abuse potential of 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 in mice.
Rationale: The newly emerging synthetic cannabinoids (SCs) 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 have been observed to produce effects by activating cannabinoid type 1 (CB1) receptors. Nevertheless, the pharmacological effects and potential for abuse of these three substances remain to be studied. These substances have yet to be regulated in many countries.
Objectives: We investigated the safety, pharmacological effects, rewarding effects, and cannabinoid withdrawal of 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201.
Methods: This study evaluated the drug safety and the cannabinoid-specific pharmacological effects of the three substances through acute toxicity experiments (in which the LD50 of each substance was obtained) and tetrad experiments (comprising assessments of hypothermia, analgesia, locomotion inhibition, and catalepsy). Furthermore, the conditioned place preference (CPP) experiments and withdrawal experiments were conducted to evaluate the rewarding effect and cannabinoid withdrawal potential of the substances in question.
Results: The results demonstrated that all three drugs exhibited certain acute toxic effects and could potentially induce tetrad effects. The data were analyzed using non-linear regression, and the corresponding ED50 values and 95% confidence intervals (CI) were obtained. The rank order of potency was determined to be CUMYL-PEGACLONE > 5F-EDMB-PICA > NM-2201. In the CPP experiments, it was demonstrated that 5F-EDMB-PICA significantly induced an increase in CPP score at a dose of 0.3 mg/kg, while NM-2201 caused an increase in CPP score and a significant aversion effect at a dose of 2 and 3 mg/kg, respectively. It is noteworthy that all three types of SCs were observed to produce a significant biphasic effect, indicating that CPP scores were biphasic for all compounds. Following the administration of the CB1 receptor antagonist rimonabant, a notable increase in head twitches and paw tremors was observed, indicating that these three SCs induce cannabinoid withdrawal through the mediation of CB1 receptors.
Conclusions: The results of this study indicated that these SCs possess cannabinoid-specific pharmacological effects and abuse potential, which provides substantial experimental data to support the future regulation of these substances.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
