Overview of Synthetic Cannabinoids ADB-FUBINACA and AMB-FUBINACA: Clinical, Analytical, and Forensic Implications

ADB-FUBINACA and AMB-FUBINACA are two synthetic indazole-derived cannabinoid receptor agonists, up to 140- and 85-fold more potent, respectively, than trans-∆9-tetrahydrocannabinol (∆9-THC), the main psychoactive compound of cannabis. Synthesised in 2009 as a pharmaceutical drug candidate, the recreational use of ADB-FUBINACA was first reported in 2013 in Japan, with fatal cases being described in 2015. ADB-FUBINACA is one of the most apprehended and consumed synthetic cannabinoid (SC), following AMB-FUBINACA, which emerged in 2014 as a drug of abuse and has since been responsible for several intoxication and death outbreaks. Here, we critically review the physicochemical properties, detection methods, prevalence, biological effects, pharmacodynamics and pharmacokinetics of both drugs. When smoked, these SCs produce almost immediate effects (about 10 to 15 s after use) that last up to 60 min. They are rapidly and extensively metabolised, being the O-demethylated metabolite of AMB-FUBINACA, 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamide)-3-methylbutanoic acid, the main excreted in urine, while for ADB-FUBINACA the main biomarkers are the hydroxdimethylpropyl ADB-FUBINACA, hydroxydehydrodimethylpropyl ADB-FUBINACA and hydroxylindazole ADB-FUBINACA. ADB-FUBINACA and AMB-FUBINACA display full agonism of the CB1 receptor, this being responsible for their cardiovascular and neurological effects (e.g., altered perception, agitation, anxiety, paranoia, hallucinations, loss of consciousness and memory, chest pain, hypertension, tachycardia, seizures). This review highlights the urgent requirement for additional studies on the toxicokinetic properties of AMB-FUBINACA and ADB-FUBINACA, as this is imperative to improve the methods for detecting and quantifying these drugs and to determine the best exposure markers in the various biological matrices. Furthermore, it stresses the need for clinicians and pathologists involved in the management of these intoxications to describe their findings in the scientific literature, thus assisting in the risk assessment and treatment of the harmful effects of these drugs in future medical and forensic investigations.

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Can Physical Activity Support the Endocannabinoid System in the Preventive and Therapeutic Approach to Neurological Disorders?

International Journal of Molecular Sciences ◽

10.3390/ijms21124221 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4221

Author(s):

Tomasz Charytoniuk ◽

Hubert Zywno ◽

Karolina Konstantynowicz-Nowicka ◽

Klaudia Berk ◽

Wiktor Bzdega ◽

...

Keyword(s):

Physical Activity ◽

Neurodegenerative Disorders ◽

Therapeutic Approach ◽

Cannabinoid Receptor ◽

Synthetic Cannabinoids ◽

Endocannabinoid System ◽

Antidepressant Effect ◽

Brain Physiology ◽

Current State ◽

Neurological Effects

The worldwide prevalence of neurological and neurodegenerative disorders, such as depression or Alzheimer’s disease, has spread extensively throughout the last decades, becoming an enormous health issue. Numerous data indicate a distinct correlation between the altered endocannabinoid signaling and different aspects of brain physiology, such as memory or neurogenesis. Moreover, the endocannabinoid system is widely regarded as a crucial factor in the development of neuropathologies. Thus, targeting those disorders via synthetic cannabinoids, as well as phytocannabinoids, becomes a widespread research issue. Over the last decade, the endocannabinoid system has been extensively studied for its correlation with physical activity. Recent data showed that physical activity correlates with elevated endocannabinoid serum concentrations and increased cannabinoid receptor type 1 (CB1R) expression in the brain, which results in positive neurological effects including antidepressant effect, ameliorated memory, neuroplasticity development, and reduced neuroinflammation. However, none of the prior reviews presented a comprehensive correlation between physical activity, the endocannabinoid system, and neuropathologies. Thus, our review provides a current state of knowledge of the endocannabinoid system, its action in physical activity, as well as neuropathologies and a possible correlation between all those fields. We believe that this might contribute to finding a new preventive and therapeutic approach to both neurological and neurodegenerative disorders.

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Identification and Analytical Characterization of a Novel Synthetic Cannabinoid-Type Substance in Herbal Material in Europe

Molecules ◽

10.3390/molecules26040793 ◽

2021 ◽

Vol 26 (4) ◽

pp. 793

Author(s):

Emmanouil D. Tsochatzis ◽

Joao Alberto Lopes ◽

Margaret V. Holland ◽

Fabiano Reniero ◽

Giovanni Palmieri ◽

...

Keyword(s):

Mass Spectrometry ◽

Cannabinoid Receptor ◽

Analytical Data ◽

Synthetic Cannabinoids ◽

Synthetic Cannabinoid ◽

Gas Chromatography Mass Spectrometry ◽

New Psychoactive Substances ◽

Synthetic Cannabinoid Receptor Agonists ◽

Analytical Laboratories

The rapid diffusion of new psychoactive substances (NPS) presents unprecedented challenges to both customs authorities and analytical laboratories involved in their detection and characterization. In this study an analytical approach to the identification and structural elucidation of a novel synthetic cannabimimetic, quinolin-8-yl-3-[(4,4-difluoropiperidin-1-yl) sulfonyl]-4-methylbenzoate (2F-QMPSB), detected in seized herbal material, is detailed. An acid precursor 4-methyl-3-(4,4-difluoro-1-piperidinylsulfonyl) benzoic acid (2F-MPSBA), has also been identified in the same seized material. After extraction from the herbal material the synthetic cannabimimetic, also referred to as synthetic cannabinoid receptor agonists or “synthetic cannabinoids”, was characterized using gas chromatography-mass spectrometry (GC-MS), 1H, 13C, 19F and 15N nuclear magnetic resonance (NMR) and high-resolution tandem mass spectrometry (HR-MS/MS) combined with chromatographic separation. A cheminformatics platform was used to manage and interpret the analytical data from these techniques.

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Comprehensive review of the detection methods for synthetic cannabinoids and cathinones

Forensic Toxicology ◽

10.1007/s11419-015-0270-0 ◽

2015 ◽

Vol 33 (2) ◽

pp. 175-194 ◽

Cited By ~ 107

Author(s):

Akira Namera ◽

Maho Kawamura ◽

Akihiro Nakamoto ◽

Takeshi Saito ◽

Masataka Nagao

Keyword(s):

Synthetic Cannabinoids ◽

Detection Methods ◽

Comprehensive Review

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Biological Effects of Atmospheric Fields and Radiation

International Journal of Innovative Technology and Exploring Engineering - Special Issue ◽

10.35940/ijitee.j1011.08810s219 ◽

2020 ◽

Vol 8 (10S2) ◽

pp. 38-40

Keyword(s):

Electromagnetic Fields ◽

Video Game ◽

Biological Effects ◽

Base Station ◽

Microwave Oven ◽

Line Radiation ◽

Electrical Systems ◽

Geomagnetic Fields ◽

Mobile Phone Radiation ◽

Harmful Effects

Our atmosphere is full of electromagnetic fields emitted from wireless communication transmitters. At the same time the bio-systems (including humans, animals & birds and vegetation as well) are complex electrical systems. Naturally therefore, they are likely to have interaction and to be affected in some way or the other. Research into this field started with the knowledge about pleasing presence of negative charges and unpleasant presence of positive charges around us, concentrating effects of static or pulsating fields. Also came the explanation (and experimental verification) of Hindu mythological effects of geomagnetic fields coupled with solar activity. The effects of power line radiation and radiation from video game TV sets, microwave oven and other domestic instruments like electric blankets also figured in the research. At last the fastest emerging mobile telephony overpowered all others. Though the results of researches into possible harmful effects of mobile phone radiation and those of radiation from base station towers remain inconclusive partly because of influencing pressure from manufacturing and service providing companies, some of the researchers conclusively assert the harmfulness of the radiation at some level of field intensity present near the tower or the handset relating it to the specific absorption ratio (SAR) value. Recent increased observation of infertility among young couples is also attributed by some researchers to the effect of radiation from mobile kept in pantaloons pockets which becomes near their genitals affecting sperm or ovum. This review explains all these researches into bio-effects of electromagnetic fields and concludes that there is certainly some possible harmfulness of radiation above some level of intensity of fields.

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Multivariate Classification of Drugs using Parametric and Nonparametric Machine Learning Models

International Journal of Innovative Technology and Exploring Engineering - Special Issue ◽

10.35940/ijitee.c8740.019320 ◽

2020 ◽

Vol 9 (3) ◽

pp. 2021-2027

Keyword(s):

Machine Learning ◽

Drug Discovery ◽

Biological Activities ◽

Biological Effects ◽

Recursive Feature Elimination ◽

Drug Candidate ◽

Learning Models ◽

Machine Learning Models ◽

Non Parametric

In pharmaceutical research, traditional drug discovery process is time consuming and expensive, where several compounds are experimentally tested for their biological activities. Series of lab experiments are conducted to analyze newly synthesized drug’s pharmaceutical activities and its biological effects on human. With every new drug discovery, the required clinical properties can be determined using machine learning models and this greatly reduces the experimental cost. This paper explores parametric and non-parametric machine learning models to classify administration properties of drugs and its toxicity. The multinomial classification of drugs was based on their physicochemical and ADMET properties. Balanced data samples were drawn from chEMBL and was pre-processed. Features were reduced using Recursive Feature Elimination and the attributes were ranked based on their importance to reduce highly correlated attributes. The performance of parametric and non-parametric machine learning models was analyzed on cheminformatic data that includes physiochemical, biological and pharmaceutical properties of the drug molecules. Selecting the potent drug candidate along with its administration properties greatly reduces wet lab experimental time and cost. Multiclass classification can be determined efficiently using non-parametric machine learning model. Optimal feature engineering, tuning hyperparameters and adopting hybrid algorithms would result in more accurate predictions in future for cheminformatics data.

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Activity-Based Detection of Cannabinoids in Serum and Plasma Samples

Clinical Chemistry ◽

10.1373/clinchem.2017.285361 ◽

2018 ◽

Vol 64 (6) ◽

pp. 918-926 ◽

Cited By ~ 18

Author(s):

Annelies Cannaert ◽

Jolien Storme ◽

Cornelius Hess ◽

Volker Auwärter ◽

Sarah M R Wille ◽

...

Keyword(s):

Cannabinoid Receptors ◽

Cannabinoid Receptor ◽

Synthetic Cannabinoids ◽

Receptor Activation ◽

Synthetic Cannabinoid ◽

New Psychoactive Substances ◽

Simple Liquid ◽

Analytical Sensitivity ◽

Monitoring Centre ◽

Screening Strategies

Abstract BACKGROUND Synthetic cannabinoids are the largest group of new psychoactive substances monitored by the European Monitoring Centre of Drugs and Drug Addiction. The rapid proliferation of novel analogs makes the detection of these new derivatives challenging and has initiated considerable interest in the development of so-called “untargeted” screening strategies to detect these compounds. METHODS We developed new, stable bioassays in which cannabinoid receptor activation by cannabinoids led to recruitment of truncated β-arrestin 2 (βarr2) to the cannabinoid receptors, resulting in functional complementation of a split luciferase, allowing readout via bioluminescence. Aliquots (500 μL) of authentic serum (n = 45) and plasma (n = 73) samples were used for simple liquid–liquid extraction with hexane:ethyl acetate (99:1 v/v). Following evaporation and reconstitution in 100 μL of Opti-MEM® I/methanol (50/50 v/v), 10 μL of these extracts was analyzed in the bioassays. RESULTS Truncation of βarr2 significantly (for both cannabinoid receptors; P = 0.0034 and 0.0427) improved the analytical sensitivity over the previously published bioassays applied on urine samples. The new bioassays detected cannabinoid receptor activation by authentic serum or plasma extracts, in which synthetic cannabinoids were present at low- or sub-nanogram per milliliter concentration or in which Δ9-tetrahydrocannabinol was present at concentrations >12 ng/mL. For synthetic cannabinoid detection, analytical sensitivity was 82%, with an analytical specificity of 100%. CONCLUSIONS The bioassays have the potential to serve as a first-line screening tool for (synthetic) cannabinoid activity in serum or plasma and may complement conventional analytical assays and/or precede analytical (mass spectrometry based) confirmation.

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The Molecular targets of Cannabinoids in the treatment of Cancer and Inflammation

Current Pharmaceutical Design ◽

10.2174/1381612827666210426092847 ◽

2021 ◽

Vol 27 ◽

Author(s):

Alenabi Aylar ◽

Malekinejad Hassan

Keyword(s):

Cannabinoid Receptors ◽

Inflammatory Diseases ◽

Biological Effects ◽

Synthetic Cannabinoids ◽

Endocannabinoid System ◽

Anticancer Effects ◽

Anti Cancer ◽

Culture Models ◽

Cancer And Inflammation ◽

G Protein Coupled

Objective: In this review we discuss the emerging evidence for the effectiveness of cannabinoids in the treatment of cancer and inflammation. The remarkable effects complete the traditional evidence for their successful application in the treatment of pain and cancer-related side effects. Methods: we searched Pub Med (132 articles) and Google scholar (9 articles) databases and gathered the clinical (4 articles), preclinical (28 articles) studies, reports on cell culture models (30 articles) and other original and review articles (78 articles) related to inflammation, cancer and cannabinoids. Results: Cannabinoids are described in three different forms, comprising endo- phyto- and synthetic compounds that exert biological effects. The molecular and cellular pathways of endogenous cannabinoids in the maintenance of homeostasis are well documented. In addition to classical cannabinoid receptors type 1 and 2, Vanilloid receptors and G protein-coupled receptor 55 were identified as common receptors. Subsequently, the effectiveness of phyto- and synthetic cannabinoids mediated by cannabinoid receptors has been demonstrated in the treatment of inflammatory diseases including neurodegenerative diseases as well as gastrointestinal and respiratory inflammations. Another accepted property of cannabinoids is their anti-cancer effects. Cannabinoids were found to be effective in the treatment of lung, colorectal, prostate, breast, pancreas and hepatic cancers. The anticancer effects of cannabinoids were characterized by their anti-proliferative property, inhibition of cancer cells migration, suppression of vascularization and induction of apoptosis. Conclusion: The current review provides and overview the role of endocannabinoid system in the mediation of physiological functions, the type and expression of cannabinoids receptors under physiological and pathological conditions. In additions, the molecular pathways involved in the effects of cannabinoids and the effectiveness of cannabinoids in the treatment of inflammations and cancers are highlighted.

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Medicinal Cannabis and Synthetic Cannabinoid Use

Medicina ◽

10.3390/medicina56090453 ◽

2020 ◽

Vol 56 (9) ◽

pp. 453

Author(s):

Simona Pichini ◽

Alfredo Fabrizio Lo Faro ◽

Francesco Paolo Busardò ◽

Raffaele Giorgetti

Keyword(s):

Adverse Effects ◽

Therapeutic Potential ◽

Neurological Diseases ◽

Synthetic Cannabinoids ◽

Current Data ◽

Special Issue ◽

Biological Matrices ◽

Wide Range ◽

Medicinal Cannabis ◽

Harmful Effects

Cannabis products have been used for centuries by humans for recreational and medical purposes. Resent research, proposed the promising therapeutic potential of cannabis and related cannabinoids for a wide range of medical conditions, including psychiatric and neurological diseases. This Special Issue presents the latest updates on medicinal cannabis and synthetic cannabinoids pharmacology, toxicology and new analytical methods to identify and quantify these compounds in conventional and non-conventional biological matrices. Moreover, it provides current data regarding their adverse effects, safety, application for medical purposes and their harmful effects.

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Toxicological profiles of selected synthetic cannabinoids showing high binding affinities to the cannabinoid receptor subtype CB1

Archives of Toxicology ◽

10.1007/s00204-013-1029-1 ◽

2013 ◽

Vol 87 (7) ◽

pp. 1287-1297 ◽

Cited By ~ 33

Author(s):

Verena J. Koller ◽

Gerhard J. Zlabinger ◽

Volker Auwärter ◽

Sabine Fuchs ◽

Siegfried Knasmueller

Keyword(s):

Cannabinoid Receptor ◽

Synthetic Cannabinoids ◽

Receptor Subtype ◽

Binding Affinities ◽

High Binding

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Cannabinoids: A New Group of Agonists of PPARs

PPAR Research ◽

10.1155/2007/23513 ◽

2007 ◽

Vol 2007 ◽

pp. 1-7 ◽

Cited By ~ 48

Author(s):

Yan Sun ◽

Andy Bennett

Keyword(s):

Cannabinoid Receptor ◽

Peroxisome Proliferator ◽

Cannabinoid Receptor 1 ◽

Nuclear Receptor Superfamily ◽

Psychotropic Effects ◽

Inflammatory Drugs ◽

Peroxisome Proliferator Activated Receptors ◽

New Compounds ◽

G Protein Coupled ◽

Recreational Use

Cannabinoids have been used medicinally and recreationally for thousands of years and their effects were proposed to occur mainly via activation of the G-protein-coupled receptorCB1/CB2(cannabinoid receptor 1/2). Discovery of potent synthetic analogs of the natural cannabinoids as clinically useful drugs is the sustained aim of cannabinoid research. This demands that these new compounds be free of the psychotropic effects that connected with the recreational use of cannabinoids. In preclinical studies cannabinoids displayed many of the characteristics of nonsteroidal anti-inflammatory drugs (NSAIDs) and it seems to be free of unwanted side effects. An increasing number of therapeutic actions of cannabinoid are being reported that do not appear to be mediated by eitherCB1orCB2, and recently nuclear receptor superfamily PPARs (peroxisome-proliferator-activated receptors) have been suggested as the target of certain cannabinoids. This review summarizes the evidence for cannabinoid activation on PPARs and possible associated remedial potentials.

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