Synthetic cannabinoids

Drug-induced cardiotoxicity has become one of the most common and detrimental health concerns, which causes significant loss to public health and drug resources. Cannabinoid receptors (CBRs) have recently achieved great attention for their vital roles in the regulation of heart health and disease, with mounting evidence linking CBRs with the pathogenesis and progression of drug-induced cardiotoxicity. This review aims to summarize fundamental characteristics of two well-documented CBRs (CB1R and CB2R) from aspects of molecular structure, signaling and their functions in cardiovascular physiology and pathophysiology...

Prenatal exposure to alcohol or cannabinoids can produce enduring neurobiological, cognitive, and behavioral changes in the offspring. Furthermore, prenatal co-exposure to alcohol and cannabinoids induces malformations in brain regions associated with reward and stress-related circuitry. This study examined the effects of co-exposure to alcohol and the synthetic cannabinoid (SCB) CP55,940 throughout gastrulation and neurulation in rats on basal corticosterone levels and a battery of behavioral tests during adolescence and alcohol self-administration in adulthood...

5F-MDMB-PICA, an indole-type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F-MDMB-PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F-MDMB-PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16...

PURPOSE: To guide clinicians, adults with cancer, caregivers, researchers, and oncology institutions on the medical use of cannabis and cannabinoids, including synthetic cannabinoids and herbal cannabis derivatives; single, purified cannabinoids; combinations of cannabis ingredients; and full-spectrum cannabis. METHODS: A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and cohort studies on the efficacy and safety of cannabis and cannabinoids when used by adults with cancer...

BACKGROUND: Natural and synthetic cannabinoids are being used worldwide to treat various symptoms in cancer patients. This study aims to map the therapeutic benefits and adverse effects associated with the use of cannabis-based drugs in these outcomes. METHODS: Following Joanna Briggs Institute guidelines a scoping review was conducted. The study protocol was available in the Open Science Framework public repository. An extensive search strategy involving databases like Cochrane Library, Embase, CINAHL, Medline/PubMed, Lilacs, Google Scholar, and Open Gray for gray literature analysis was executed by a skilled librarian...

This study aimed to compare the concentration of various xenobiotics in both cerebrospinal fluid (CSF) and blood. We examined 175 autopsy cases covering a wide range of ages, causes of death, and drug ingestion histories, with cerebrospinal fluid and blood samples available for toxicological testing. Analytes studied included opioids, benzodiazepines, antidepressants, antipsychotics, and illicit substances such as cannabinoids, stimulants and new psychoactive substances, including synthetic cathinones and synthetic cannabinoids...

Aim: Validate a method to quantify 1-(5-fluoropentyl)-N-(2-phenylpropan-2-yl)-1H-indole-3-carboxamide (5F-CUMYL-PICA) and methyl 2-[[1-(5-fluoropentyl) indole-3-carbonyl] amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA) in blood samples using GC-MS/MS. Materials & methods: A solid-phase extraction (SPE) method has been developed to quantify 5F-MDMB-PICA and 5F-CUMYL-PICA in authentic human blood samples. Results & conclusion: The limit of detection (LOD) was 0.1 and 0.11 ng/ml for 5F-CUMYL-PICA and 5F-MDMB-PICA, respectively, while the limit of quantification (LOQ) was 0...

To test the hypothesis that genetic and pharmacological modulation of the classical cannabinoid type 1 (CB1 ) and 2 (CB2 ) receptors attenuate cancer-induced bone pain, we searched Medline, Web of Science and Scopus for relevant skeletal and non-skeletal cancer studies from inception to July 28, 2022. We identified 29 animal and 35 human studies. In mice, a meta-analysis of pooled studies showed that treatment of osteolysis-bearing males with the endocannabinoids AEA and 2-AG (mean difference [MD] - 24...

Production of phytocannabinoids remains an area of active scientific interest due to the growing use of cannabis by the public and the underexplored therapeutic potential of the over 100 minor cannabinoids. While phytocannabinoids are biosynthesized by Cannabis sativa and other select plants and fungi, structural analogs and stereoisomers can only be accessed synthetically or through heterologous expression. To date, the bioproduction of cannabinoids has required eukaryotic hosts like yeast since key, native oxidative cyclization enzymes do not express well in bacterial hosts...

Over the last years, Synthetic Cannabinoids (SCs) have been among the largest and most frequently seized groups of Novel Psychoactive Substances (NPS). These substances have been frequently detected in biological samples from patients involved in several intoxication and death cases. Their serious adverse effects have been related to their action as potent agonist of cannabinoid CB1 receptors. However, evidence concerning the potential interaction between SCs and serotoninergic mechanisms has emerged. Therefore, this study aims to evaluate the involvement of 5-HT2A receptors in the effects induced by acute systemic administration of 1-pentyl-3-(1-naphthoyl)indole (JWH-018; 1 mg/kg) and quinolin-8-yl 1-pentyfluoro-1H-indole-3-8-carboxylate (5F-PB22; 1 mg/kg)...

RATIONALE: ADB-FUBIATA is one of the most recently identified new psychoactive substance (NPS) of synthetic cannabinoids. The co-use of in vitro (human liver microsomes) and in vivo (zebrafish) models offers abundant metabolites and may give a deep insight into the metabolism of NPS. METHODS: In vivo and in vitro metabolic studies of new synthetic cannabinoid ADB-FUBIATA were carried out using zebrafish and pooled human liver microsome models. Metabilites were structurally characterized by liquid chromatography-high-resolution mass spectrometry...

In 2019, Italian National Institute of Health established an external quality assessment program (EQA) to evaluate the performance of oral fluid testing for classical and new psychoactive substances by laboratories participating in the National Early Warning System collaborative centres. This report presents the results of four rounds between 2019 and 2023. Eleven oral fluid specimens, including 3 blank samples, were prepared by adding different classes of and new psychoactive drugs at known concentrations to pre-screened drug-free oral fluid...

Synthetic cannabinoids (SCs), a class of new psychoactive substances (NPS) commonly known as "spice," has rapidly gained popularity and become the most ubiquitous NPS on the illegitimate drug market. SCs, unlike natural cannabis (NC), are not controlled by international drug conventions, posing a significant risk to public health. These substances are easily accessible, relatively inexpensive, and challenging to detect in routine drug screenings. The existing literature provides strong evidence of an association between NC use and psychosis, but there is significantly less data on SC psychosis...

Dementia, with loss of memory, cognitive abilities, and independent daily functioning, is increasing worldwide, related to an aging population. Currently, there is no curative treatment for dementia. Treatment of the frequently occurring behavioral and psychological symptoms of dementia (BPSD) is partially effective and associated with significant side effects. Cannabinoids are lipophilic molecules acting on the CB1 end CB2 receptors, essential for main biological processes such as sleep, appetite, memory, and pain...

The recent change from the popular carboxamide to an acetamide (ATA) linker scaffold in synthetic cannabinoid receptor agonists (SCRAs) can be interpreted as an attempt to circumvent legal regulations, setting new analytical challenges. Metabolites of N-cyclohexyl-2-(1-pentyl-1H-indol-3-yl)acetamide: CH-PIATA, the second ATA type SCRA detected in the EU, were investigated in urine and serum samples by LC-HRMS-MS and LC-MS-MS. Two different in vitro models: a pHLM assay and HepG2-cells as well as an in silico prediction by GLORYx freeware assisted in metabolite formation/identification...

Toll-like receptors (TLRs) have become a focus in biomedicine and biomedical research given the roles of this unique family of innate immune proteins in immune activation, infection, and autoimmunity. It is evident that TLR dysregulation, and subsequent alterations in TLR-mediated inflammatory signalling, can contribute to disease pathogenesis, and TLR targeted therapies are in development. This review highlights evidence that cannabinoids are key regulators of TLR signalling. Cannabinoids include component of the plant Cannabis sativa L...

We present the case of a 32-year-old woman who developed life-threatening catatonia in the setting of synthetic cannabis use. She was treated with high doses of lorazepam (up to 26 mg) and eventually transferred to receive electroconvulsive therapy (ECT). Synthetic cannabis poses a unique risk as it is widely available, difficult to regulate, and with adverse effects that are not well understood due to the presence of ever-changing chemical compounds. In this case report, we present one of the first cases of catatonia induced by first-time synthetic cannabinoids with no previous history of cannabis use disorder...

The use of synthetic cannabinoid receptor agonists (SCRAs) poses major psychiatric risks. We previously showed that repeated exposure to the prototypical SCRA JWH-018 induces alterations in dopamine (DA) transmission, abnormalities in the emotional state, and glial cell activation in the mesocorticolimbic DA circuits of rats. Despite growing evidence suggesting the relationship between substance use disorders (SUD) and neuroinflammation, little is known about the impact of SCRAs on the neuroimmune system. Here, we investigated whether repeated JWH-018 exposure altered neuroimmune signaling, which could be linked with previously reported central effects...

Wastewater-based epidemiology (WBE) can provide objective and timely information on the use of new psychoactive substances (NPS), originally designed as legal alternatives of internationally controlled drugs. NPS have rapidly emerged on the global drug market, posing a challenge to drug policy and constituting a risk to public health. In this study, a WBE approach was applied to monitor the use of more than 300 NPS, together with fentanyl and its main metabolite norfentanyl, in influent wastewater collected from 12 European cities during March-June 2021...

Cannabidiol (CBD), a prominent phytocannabinoid found in various Cannabis chemotypes, is under extensive investigation for its therapeutic potential. Moreover, because it is nonpsychoactive, it can also be utilized as a functional ingredient in foods and supplements in certain countries, depending on its legal status. From a chemical reactivity point of view, CBD can undergo conversion into different structurally related compounds both during storage and after the consumption of CBD-based products. The analytical determination of these compounds is of paramount concern due to potential toxicity and the risk of losing the active ingredient (CBD) title...