Dataset Information

The clinical challenges of synthetic cathinones.

ABSTRACT:

Aims

Within the new psychoactive substances (NPS) scenario, several hundred different molecules, mostly including synthetic cannabinoids and cathinones, have been identified so far. The aims of the paper were to: (i) identify the number of synthetic cathinones mentioned in a range of psychonaut, NPS-related, online sources; and (ii) describe the associated acute/long term clinical scenario and the related treatment/management plan.

Methods

After about 18 months of operation and exclusion of false positives/duplicates, some 4204 unique NPS molecules were included in the NPSfinder® crawling/navigating software database. Most popular NPS included: 1265 psychedelic phenethylamines (30.1%; confidence interval [CI] 95%: 28.7-31.5%); 1253 synthetic cannabinoids (29.8%; CI 95%: 28.4-31.2%); 429 synthetic opioids (10.2%; CI 95%: 9.3-10.2%); and 171 synthetic cathinones (4.1%; CI 95% 3.5-4.7%). Conversely, the United Nations Office on Drugs and Crime and the European Monitoring Centre for Drugs and Drug Addiction databases respectively included 169 and 140 cathinones. Overall, the 3 databases reported some 222 synthetic cathinones, and 41 were uniquely identified by the NPSfinder®.

Results

In terms of clinical scenarios, synthetic cathinone ingestion is initially associated with stimulant effects; however, psychopathological disturbances, violence, suicidal behaviour, hyperthermia, coma and death have also been described.

Conclusion

The proportion of cathinones commented on by psychonaut fora appeared to be relatively small, and similar to those reported by both the United Nations Office on Drugs and Crime and European Monitoring Centre for Drugs and Drug Addiction. This may be associated with a recent significant decline in both cathinone-related consumption and acute medical presentation. Due to their complex behavioural and medical toxicity issues, healthcare professionals should be, however, be educated to recognise the signs and symptoms of NPS, including synthetic cathinone, ingestion.

SUBMITTER: Schifano F

PROVIDER: S-EPMC7080616 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

The clinical challenges of synthetic cathinones.

Schifano Fabrizio F Napoletano Flavia F Arillotta Davide D Zangani Caroline C Gilgar Liam L Guirguis Amira A Corkery John Martin JM Vento Alessandro A

British journal of clinical pharmacology 20200203 3

<h4>Aims</h4>Within the new psychoactive substances (NPS) scenario, several hundred different molecules, mostly including synthetic cannabinoids and cathinones, have been identified so far. The aims of the paper were to: (i) identify the number of synthetic cathinones mentioned in a range of psychonaut, NPS-related, online sources; and (ii) describe the associated acute/long term clinical scenario and the related treatment/management plan.<h4>Methods</h4>After about 18 months of operation and ex ...[more]

PMID: 31674690

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Project description:PurposeThe emergence of novel psychoactive substances (NPS) has been being a continuous and evolving problem for more than a decade. Every year, dozens of new, previously unknown drugs appear on the illegal market, posing a significant threat to the health and lives of their users. Synthetic cathinones are one of the most numerous and widespread groups among NPS. The purpose of this work was to identify and summarize available data on newly emerging cathinones in very recent years.MethodsVarious online databases such as PubMed, Google Scholar, but also databases of government agencies including those involved in early warning systems, were used in search of reports on the identification of newly emerging synthetic cathinones. In addition, threads on various forums created by users of these drugs were searched for reports on the effects of these new substances.ResultsWe have identified 29 synthetic cathinones that have been detected for the first time from early 2019 to mid-2022. We described their structures, known intoxication symptoms, detected concentrations in biological material in poisoning cases, as well as the countries and dates of their first appearance. Due to the lack of studies on the properties of the novel compounds, we compared data on the pharmacological profiles of the better-known synthetic cathinones with available information on the newly emerged ones. Some of these new agents already posed a threat, as the first cases of poisonings, including fatal ones, have been reported.ConclusionsMost of the newly developed synthetic cathinones can be seen as analogs and replacements for once-popular compounds that have been declining in popularity as a result of legislative efforts. Although it appears that some of the newly emerging cathinones are not widely used, they may become more popular in the future and could become a significant threat to health and life. Therefore, it is important to continue developing early warning systems and identifying new compounds so that their widespread can be prevented.

Project description:Synthetic cathinones are the second largest class of new psychoactive substances (NPS) on the drug market. Despite the large number of different cathinones and their abundant use, hazard characterization is mainly limited to their potential to inhibit monoamine transporters. To expand the current hazard characterization, we first investigated the acute effects of several synthetic cathinones [4-methylethcathinone (4-MEC), 3-methylmethcathinone (3-MMC), 4-MMC, methylone, pentedrone, ?-pyrrolidinovalerophenone (?-PVP), and 3,4-methylenedioxypyrovalerone (MDPV)] on human dopamine, norepinephrine, and serotonin reuptake transporters (hDAT, hNET, and hSERT), which were stably transfected in human embryonic kidney (HEK) 293 cells. Next, we examined effects on spontaneous neuronal activity in rat primary cortical cultures grown on microelectrode arrays (MEAs) as an integrated endpoint for neurotoxicity. Changes in neuronal activity were assessed after acute (30 min) and prolonged (4.5 h) exposure. Moreover, we investigated whether neuronal activity recovered after washout of the exposure (24 h after the start of the 5 h exposure). Low micromolar concentrations of synthetic cathinones inhibited monoamine uptake via hDAT and hNET, while higher cathinone concentrations were needed to inhibit uptake via hSERT. Comparable high concentrations were needed to inhibit spontaneous neuronal activity during acute (30 min) and prolonged (4.5 h) exposure. Notably, while the inhibition of neuronal activity was reversible at low concentrations, only partial recovery was seen following high, but non-cytotoxic, concentrations of synthetic cathinones. Synthetic cathinones with either a pyrrolidine moiety or long alkyl-tail carbon chain more potently inhibit monoamine uptake via hDAT and neuronal activity. Monoamine uptake via hNET was most potently inhibited by synthetic cathinones with a pyrrolidine moiety. The combination of integrated measurements (MEA recordings of neuronal activity) with single target assays (monoamine reuptake transporter inhibition) indicates inhibition of hDAT and hNET as the primary mode of action of these synthetic cathinones. Changes in neuronal activity, indicative for additional mechanisms, were observed at higher concentrations.

Project description:The list of pharmacological agents that can modify the gut microbiome or be modified by it continues to grow at a high rate. The greatest amount of attention on drug-gut microbiome interactions has been directed primarily at pharmaceuticals used to treat infection, diabetes, cardiovascular conditions and cancer. By comparison, drugs of abuse and addiction, which can powerfully and chronically worsen human health, have received relatively little attention in this regard. Therefore, the main objective of this study was to characterize how selected synthetic psychoactive cathinones (aka "Bath Salts") and amphetamine stimulants modify the gut microbiome. Mice were treated with mephedrone (40 mg/kg), methcathinone (80 mg/kg), methamphetamine (5 mg/kg) or 4-methyl-methamphetamine (40 mg/kg), following a binge regimen consisting of 4 injections at 2h intervals. These drugs were selected for study because they are structural analogs that contain a β-keto substituent (methcathinone), a 4-methyl group (4-methyl-methamphetamine), both substituents (mephedrone) or neither (methamphetamine). Mice were sacrificed 1, 2 or 7 days after treatment and DNA from caecum contents was subjected to 16S rRNA sequencing. We found that all drugs caused significant time- and structure-dependent alterations in the diversity and taxonomic structure of the gut microbiome. The two phyla most changed by drug treatments were Firmicutes (methcathinone, 4-methyl-methamphetamine) and Bacteriodetes (methcathinone, 4-methyl-methamphetamine, methamphetamine, mephedrone). Across time, broad microbiome changes from the phylum to genus levels were characteristic of all drugs. The present results signify that these selected psychoactive drugs, which are thought to exert their primary effects within the CNS, can have profound effects on the gut microbiome. They also suggest new avenues of investigation into the possibility that gut-derived signals could modulate drug abuse and addiction via altered communication along the gut-brain axis.

Dataset Information

The clinical challenges of synthetic cathinones.

Aims

Methods

Results

Conclusion

Publications

The clinical challenges of synthetic cathinones.

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