The semi-synthetic cannabinoid hexahydrocannabinol (HHC) has become a highly discussed topic in forensic toxicology since 2022 due to its legal availability at this time and its psychoactive effects. This study aimed to investigate the pharmacokinetics, effects, and immunological detectability of HHC after oral (25 mg HHC fruit gum) and inhalative (three puffs from HHC vape) consumption with three participants per group. Serum (up to 48 h), urine (up to five days), and saliva (up to 48 h) samples were collected at different relevant time points and analyzed by HPLC-MS/MS for (9R)/(9S)-HHC, 11-hydroxy-HHC, and (9R)/(9S)-HHC carboxylic acid with a fully validated method. Additionally, immunological detectability was investigated with three different commercially available tests. To address the psychoactive effects, the subjective "high" feeling (scale 0-10) was monitored and different psychophysical tests (e.g. modified Romberg test, walk and turn) were conducted. Overall, the pharmacokinetics and effects of HHC were comparable to tetrahydrocannabinol (THC). However, the route of administration as well as inter-individual factors played a crucial role regarding maximum concentrations, pharmacokinetic profiles, and psychoactive effects.

• MeSH
• agonisté kanabinoidních receptorů farmakokinetika   farmakologie   MeSH
• aplikace inhalační * MeSH
• aplikace orální * MeSH
• dospělí MeSH
• emoce účinky léků   MeSH
• farmakokinetika * MeSH
• imunologické testy MeSH
• kanabinoidy * analýza   krev   farmakokinetika   farmakologie   moč   MeSH
• kapalinová chromatografie-hmotnostní spektrometrie MeSH
• lidé MeSH
• psychofyziologie * MeSH
• psychotropní léky * analýza   krev   farmakokinetika   farmakologie   moč   MeSH
• sliny chemie   MeSH
• tetrahydrokanabinol farmakokinetika   farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Hlavním cílem tohoto textu je představit nové psychoaktivní látky zahrnující širokou a různorodou skupinu látek, většinou syntetického původu, zejména se stimulačními, sedativními a halucinogenními účinky. Tyto látky byly vyvinuty nebo znovu uvedeny na trh, aby na jedné straně nahradily tradiční návykové látky, jejichž výroba a zejména distribuce často cílí na obcházení legislativy. Na druhé straně se jedná o velký obchodní potenciál pro výrobce a distributory těchto látek. V textu jsou představeny různé podskupiny těchto látek, jako jsou syntetické kanabinoidy a opioidy, a jejich závažná zdravotní rizika, včetně neurotoxických a kardiovaskulárních komplikací. Dále se zaměřuje na specifické skupiny uživatelů, které tyto látky preferují, na jejich důvody pro užívání, včetně snahy vyhnout se detekci drog nebo zlepšit sexuální prožitek. Zvláštní pozornost je věnována i novým psychedelickým látkám a kratomu, včetně jejich farmakologických vlastností a zdravotních rizik. Článek zdůrazňuje složitost fenoménu nových psychoaktivních látek a nutnost zvýšené pozornosti zdravotnických pracovníků při identifikaci a léčbě intoxikací těmito látkami.

The main objective of this text is to introduce new psychoactive substances, which encompass a broad and diverse group of substances, mostly of synthetic origin, with primarily stimulating, sedative, and hallucinogenic effects. These substances were developed or reintroduced to the market to replace traditional addictive substances, and their production often aims to circumvent legislation. The text discusses various subgroups of these substances, such as synthetic cannabinoids and opioids, and their serious health risks, including neurotoxic and cardiovascular complications. It also focuses on specific user groups who prefer these substances and their reasons for use, including attempts to avoid drug detection or enhance sexual experiences. Special attention is also given to new psychedelic substances and kratom, including their pharmacological properties and health risks. The article emphasizes the complexity of the phenomenon of new psychoactive substances and the need for increased attention from healthcare professionals in identifying and treating intoxications with these substances.

• MeSH
• dimethoxyfenylethylamin aplikace a dávkování   farmakologie   MeSH
• kanabinoidy farmakologie   škodlivé účinky   MeSH
• ketamin aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• lidé MeSH
• Mitragyna chemie   škodlivé účinky   MeSH
• opioidní analgetika škodlivé účinky   MeSH
• psychotropní léky * farmakologie   klasifikace   škodlivé účinky   MeSH
• stimulancia farmakologie   škodlivé účinky   MeSH
• uživatelé drog MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

INTRODUCTION: Cannabis is the most common recreational drug worldwide and synthetic cannabinoid receptor agonists are currently the largest group of new psychoactive substances. The aim of this study was to compare the clinical features and outcomes of lone acute cannabis toxicity with lone acute synthetic cannabinoid receptor agonist toxicity in a large series of presentations to European emergency departments between 2013-2020. METHODS: Self-reported drug exposure, clinical, and outcome data were extracted from the European Drug Emergencies Network Plus which is a surveillance network that records data on drug-related emergency department presentations to 36 centres in 24 European countries. Cannabis exposure was considered the control in all analyses. To compare the lone cannabis and lone synthetic cannabinoid receptor agonist groups, univariate analysis using chi squared testing was used for categorical variables and non-parametric Mann-Whitney U- testing for continuous variables. Statistical significance was defined as a P value of <0.05. RESULTS: Between 2013-2020 there were 54,314 drug related presentations of which 2,657 were lone cannabis exposures and 503 lone synthetic cannabinoid receptor agonist exposures. Synthetic cannabinoid receptor agonist presentations had statistically significantly higher rates of drowsiness, coma, agitation, seizures and bradycardia at the time of presentation. Cannabis presentations were significantly more likely to have palpitations, chest pain, hypertension, tachycardia, anxiety, vomiting and headache. DISCUSSION: Emergency department presentations involving lone synthetic cannabinoid receptor agonist exposures were more likely to have neuropsychiatric features and be admitted to a psychiatric ward, and lone cannabis exposures were more likely to have cardiovascular features. Previous studies have shown variability in the acute toxicity of synthetic cannabinoid receptor agonists compared with cannabis but there is little comparative data available on lone exposures. There is limited direct comparison in the current literature between lone synthetic cannabinoid receptor agonist and lone cannabis exposure, with only two previous poison centre series and two clinical series. Whilst this study is limited by self-report being used to identify the drug(s) involved in the presentations, previous studies have demonstrated that self-report is reliable in emergency department presentations with acute drug toxicity. CONCLUSION: This study directly compares presentations with acute drug toxicity related to the lone use of cannabis or synthetic cannabinoid receptor agonists. It supports previous findings of increased neuropsychiatric toxicity from synthetic cannabinoid receptor agonists compared to cannabis and provides further data on cardiovascular toxicity in lone cannabis use.

• MeSH
• agonisté kanabinoidních receptorů * toxicita   MeSH
• Cannabis toxicita   MeSH
• dospělí MeSH
• kanabinoidy toxicita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• retrospektivní studie MeSH
• urgentní služby nemocnice * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

A novel group of 5,6-dihydropyrido [2',1':2,3]imidazo [4,5-c]quinolines was prepared via a microwave assisted one-pot telescopic approach. The synthetic sequence involves the formation of an amine precursor of imidazo [1,2-a]pyridine via condensation and reduction under microwave irradiation. Subsequently, the Pictet-Spengler cyclisation reaction occurs with ketones (cyclic or acyclic) to obtain substituted 5,6-dihydropyrido [2',1':2,3]imidazo [4,5-c]quinolines in excellent yields. The compounds were tested as neuroprotective agents. Observed protection of neuron-like cells, SH-SY5Y differentiated with ATRA, in Parkinson's and Huntington's disease models inspired further mechanistic studies of protective activity against damage induced by 1-methyl-4-phenylpyridinium (MPP+), a compound causing Parkinson's disease. The novel compounds exhibit similar or higher potency than ebselen, an established drug with antioxidant activity, in the cells against MPP + -induced total cellular superoxide production and cell death. However, they exhibit a significantly higher capacity to reduce mitochondrial superoxide and preserve mitochondrial membrane potential. We also observed marked differences between a selected derivative and ebselen in terms of normalizing MPP + -induced phosphorylation of Akt and ERK1/2. The cytoprotective activity was abrogated when signaling through cannabinoid receptor CB2 was blocked. The compounds also inhibit both acetylcholine and butyrylcholine esterases. Overall the data show that novel 5,6-dihydropyrido [2',1':2,3]imidazo [4,5-c]quinoline have a broad cytoprotective activity which is mediated by several mechanisms including mitoprotection.

• MeSH
• chinoliny * farmakologie   chemie   chemická syntéza   MeSH
• cholinesterasové inhibitory * farmakologie   chemie   chemická syntéza   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• neuroprotektivní látky * farmakologie   chemie   chemická syntéza   MeSH
• receptor kanabinoidní CB2 * metabolismus   antagonisté a inhibitory   MeSH
• signální transdukce * účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Syntetické kanabinoidy jsou heterogenní skupinou látek ovlivňujících endogenní kanabinoidní systém. HHC je polosyntetický kanabinoid chemicky podobný delta-9-tetrahydrokanabinolu (delta-9-THC), hlavní psychoaktivní látce v konopí, a má do značné míry podobné účinky. Příspěvek přináší přehled účinků a zdravotních rizik spojených s užíváním syntetických kanabinoidů a doporučení pro práci s jejich uživateli. Data byla získána rešerší odborných vědeckých databází a zpracována obsahovou a tematickou analýzou do tří částí: akutní intoxikace, zdravotní rizika a doporučení pro léčbu akutních stavů po užití SK a další terapeutické postupy. Syntetické kanabinoidy mají podobné účinky jako přírodní THC, ale vyvolávají závažnější nežádoucí účinky, např. dýchací obtíže, hypertenzi, tachykardii, bolest na hrudi, svalové záškuby, akutní selhání ledvin, úzkost, agitovanost, psychózy, sebevražedné myšlenky. Dlouhodobé užívání může vést ke kognitivním poruchám, kardiovaskulárním komplikacím, respiračním problémům a poruchám duševního zdraví. Výzkum v oblasti účinků a zdravotních rizik polosyntetických kanabinoidů a HHC je poměrně omezený a neexistuje dostatečné množství informací. Zkoumáním rizik a zavedením účinných léčebných a preventivních strategií dochází k minimalizaci škod spojených s užíváním syntetických kanabinoidů.

Synthetic cannabinoids comprise a heterogeneous group of substances that affect the endogenous cannabinoid system. HHC is a semi-synthetic cannabinoid chemically similar to delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive substance in cannabis, and appears to have broadly similar effects. This paper provides an overview of the effects and health risks associated with the use of synthetic cannabinoids and recommendations for working with their users. Data was obtained by searching professional scientific databases and organised by content and thematic analysis into three sections: effects, acute intoxication, and treatment/therapeutic intervention. Synthetic cannabinoids replicate the effects of natural cannabis but induce more severe adverse effects, including respiratory difficulties, hypertension, tachycardia, chest pain, muscle twitches, acute renal failure, anxiety, agitation, psychosis, and suicidal thoughts. Long-term use can lead to cognitive impairment, cardiovascular complications, respiratory problems, and mental health disorders. Research into the effects and health risks of semi-synthetic cannabinoids and HHCs is relatively limited and there is insufficient information. The harms associated with the use of synthetic cannabinoids can be reduced by understanding these risks and implementing effective treatment and prevention strategies.

Kanabinoidy, aktivní složky rostliny Cannabis, ovlivňují širokou škálu fyziologických procesů prostřednictvím endokanabinoidního systému, který zahrnuje receptory CB1 a CB2, endogenní ligandy a regulační enzymy. Tento přehledový článek shrnuje mechanismy působení fytokanabinoidů, syntetických kanabinoidů a endokanabi noidů, včetně jejich farmakologických vlastností, terapeutického potenciálu a rizik spojených s jejich použitím. Diskutována je také toxicita syntetických kanabinoidů, jejichž rekreační užívání představuje významnou hrozbu pro veřejné zdraví. Závěrem jsou uvedeny současné aplikace kanabinoidů v klinické praxi, zejména při léčbě bolesti, nevolnosti a neurologických onemocnění.

Cannabinoids, active compounds of the Cannabis plant, influence a wide range of physiological processes through the endocannabinoid system, comprising CB1 a CB2 receptors, endogenous ligands, and regulatory enzymes. This review summarizes the mechanisms of action of phytocannabinoids, synthetic cannabinoids, and endo­cannabinoids, including their pharmacological properties, therapeutic potential, and associated risks. The article also discusses the toxicity of synthetic cannabinoids, highlighting the public health threat posed by their recreational use. Finally, it explores current clinical applications of cannabinoids, particularly in the treatment of pain, nausea, and neurological disorders.

• Klíčová slova
• syntetické kanabinoidy,
• MeSH
• endokanabinoidy farmakologie   terapeutické užití   MeSH
• kanabinoidy farmakologie   terapeutické užití   MeSH
• lidé MeSH
• marihuana pro léčebné účely * farmakologie   terapeutické užití   MeSH
• receptor kanabinoidní CB1 MeSH
• receptor kanabinoidní CB2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

CONTEXT: Acute toxicity caused by illicit substance use is a common reason for emergency department (ED) presentation. Knowledge of the substances involved is helpful for predicting and managing potential toxicity, but limited information is available about the accuracy of patient-reported substance exposure. This study assessed the accuracy of the history of exposure in those reporting use of a single substance by comparison with those identified by detailed toxicological analysis, focusing on synthetic cannabinoid receptor agonists (SCRA). METHODS: Adults (≥16 years) presenting between March 2015 and July 2021 to participating UK hospitals with toxicity after reporting use of a single illicit substance were included. Exposure details were documented from medical records and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry (HRAM LCMS). Sensitivity, specificity, and positive and negative predictive values of the exposure history were calculated by comparison with biological sample analysis ("gold standard"). RESULTS: Single substance exposure was reported for 474 (median age 33 years, IQR: 18 range 16-75, 80% males) patients. Analysis commonly identified multiple substances (Median 3, IQR 2-5). A history of exposure was documented for 121 of 151 patients where a SCRA or metabolite was detected on analysis (sensitivity 80.1%, 95% CI 72.9, 86.2%). Corresponding proportions were lower for 3,4-methylenedioxymethamphetamine (MDMA, 44/70, 62.9%., 95% CI 50.5%, 74.1%), heroin 41/108 (38.0% 95% CI 28.8-47.8%) and cocaine (22/56, 31.3%, 95% CI 20.9, 43.6%). CONCLUSIONS: Multiple undeclared substances were detected analytically in most patients reporting single substance use. Clinicians should be alert to the potential presence and toxicity of unreported substances when managing patients presenting after substance misuse.

• MeSH
• agonisté kanabinoidních receptorů MeSH
• dospělí MeSH
• hmotnostní spektrometrie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• odhalování abúzu drog metody   MeSH
• poruchy spojené s užíváním psychoaktivních látek * diagnóza   epidemiologie   MeSH
• senioři MeSH
• urgentní služby nemocnice MeSH
• zakázané drogy * toxicita   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Autaptic hippocampal neurons are an architecturally simple model of neurotransmission that express several forms of cannabinoid signaling. Over the past twenty years this model has proven valuable for studies ranging from enzymatic control of endocannabinoid production and breakdown, to CB1 receptor structure/function, to CB2 signaling, understanding 'spice' (synthetic cannabinoid) pharmacology, and more. However, while studying cannabinoid signaling in these neurons, we have occasionally encountered what one might call 'interesting negatives', valid and informative findings in the context of our experimental design that, given the nature of scientific publishing, may not otherwise find their way into the scientific literature. In autaptic hippocampal neurons we have found that: (1) The fatty acid binding protein (FABP) blocker SBFI-26 does not alter CB1-mediated neuroplasticity. (2) 1-AG signals poorly relative to 2-AG in autaptic neurons. (3) Indomethacin is not a CB1 PAM in autaptic neurons. (4) The CB1-associated protein SGIP1a is not necessary for CB1 desensitization. We are presenting these negative or perplexing findings in the hope that they will prove beneficial to other laboratories and elicit fruitful discussions regarding their relevance and significance.

• MeSH
• endokanabinoidy MeSH
• hipokampus MeSH
• kanabinoidy * farmakologie   MeSH
• nervový přenos MeSH
• neurony MeSH
• Publikační typ
• časopisecké články MeSH

Cannabidiol (CBD) and cannabigerol (CBG) are the two main non-psychotropic phytocannabinoids with high application potential in drug development. Both substances are redox-active and are intensively investigated for their cytoprotective and antioxidant action in vitro. In this study, we focused on an in vivo safety evaluation and the effect of CBD and CBG on the redox status in rats in a 90-d experiment. The substances were administered orogastrically in a dose of 0.66 mg synthetic CBD or 0.66 mg/1.33 mg CBG/kg/day. CBD produced no changes in the red or white blood count or biochemical blood parameters in comparison to the control. No deviations in the morphology or histology of the gastrointestinal tract and liver were observed. After 90 d of CBD exposure, a significant improvement in redox status was found in the blood plasma and liver. The concentration of malondialdehyde and carbonylated proteins was reduced compared to the control. In contrast to CBD, total oxidative stress was significantly increased and this was accompanied by an elevated level of malondialdehyde and carbonylated proteins in CBG-treated animals. Hepatotoxic (regressive changes) manifestations, disruption in white cell count, and alterations in the ALT activity, level of creatinine and ionized calcium were also found in CBG-treated animals. Based on liquid chromatography-mass spectrometry analysis, CBD/CBG accumulated in rat tissues (in the liver, brain, muscle, heart, kidney and skin) at a low ng level per gram. Both CBD and CBG molecular structures include a resorcinol moiety. In CBG, there is an extra dimethyloctadienyl structural pattern, which is most likely responsible for the disruption to the redox status and hepatic environment. The results are valuable to further investigation of the effects of CBD on redox status and should contribute towards opening up critical discussion on the applicability of other non-psychotropic cannabinoids.

• MeSH
• kanabidiol * toxicita   MeSH
• kanabinoidy * toxicita   MeSH
• krysa rodu rattus MeSH
• oxidace-redukce MeSH
• vápník MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Organic molecules that interact with the cannabinoid receptors are called cannabinoids, which can be endogenous, natural or synthetic compounds. They possess similar pharmacological properties as produced by the plant, Cannabis sativa L. Before cannabinoids can be analysed, they need to be extracted from the matrices. OBJECTIVE: To review literature on the methods and protocols for the extraction of naturally occurring cannabinoids. METHODOLOGY: An extensive literature search was performed incorporating several databases, notably, Web of Knowledge, PubMed and Google Scholar, and other relevant published materials. The keywords used in the search, in various combinations, with cannabinoids and extraction being present in all combinations, were Cannabis, hemp, cannabinoids, Cannabis sativa, marijuana, and extraction. RESULTS: In addition to classical maceration with organic solvents, e.g. ethanol, pressurised solvent extraction, solvent heat reflux, Soxhlet extraction, supercritical fluid extraction, ultrasound-assisted extraction and microwave-assisted extraction, are routinely used nowadays for the extraction of cannabinoids from plant materials and cannabis consumer products. For the extraction of cannabinoids from biological samples, e.g. human blood, and also from food and beverages, and wastewater, solid-phase extraction and its variants, as well as liquid-liquid extraction are commonly used. Parameters for extraction can be optimised by response surface methodology or other mathematical modelling tools. There are at least six US patents on extraction of cannabinoids available to date. CONCLUSIONS: Irrespective of the extraction method, extraction temperature, extraction time and extraction pressure play a vital role in overall yield of extraction. Solvent polarity can also be an important factor in some extraction methods.

• MeSH
• Cannabis * MeSH
• extrakce kapalina-kapalina MeSH
• kanabinoidy * analýza   MeSH
• rostlinné extrakty MeSH
• rozpouštědla MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH