The Chemistry and Pharmacology of Synthetic Cannabinoid Receptor Agonists as New Psychoactive Substances: Origins

2018 ◽  
pp. 165-190 ◽  
Author(s):  
Samuel D. Banister ◽  
Mark Connor
Keyword(s):  
Cannabinoid Receptor ◽  
Synthetic Cannabinoid ◽  
New Psychoactive Substances ◽  
Psychoactive Substances ◽  
Receptor Agonists ◽  
Synthetic Cannabinoid Receptor Agonists

An index of fatal toxicity for new psychoactive substances

2018 ◽  
Vol 32 (7) ◽  
pp. 793-801 ◽  
Author(s):  
Leslie A King ◽  
John M Corkery
Keyword(s):  
Cannabinoid Receptor ◽  
Synthetic Cannabinoid ◽  
New Psychoactive Substances ◽  
Death Certificates ◽  
Psychoactive Substances ◽  
Receptor Agonists ◽  
A Value ◽  
Other Substances ◽  
Synthetic Cannabinoid Receptor Agonists ◽  
Original Reference

An index of fatal toxicity for new psychoactive substances has been developed based solely on information provided on death certificates. An updated index of fatal toxicity (Tf), as first described in 2010, was calculated based on the ratio of deaths to prevalence and seizures for the original five substances (amphetamine, cannabis, cocaine/crack, heroin and 3,4-methylenedioxymethylamphetamine)*. These correlated well with the 2010 index. Deaths were then examined for cases both where the substance was and was not found in association with other substances. This ratio (sole to all mentions; S/A) was then calculated for deaths in the period 1993 to 2016. This new measure of fatal toxicity, expressed by S/A, was well-correlated with the index Ln (Tf) of the original reference compounds. The calculation of S/A was then extended to a group of new psychoactive substances where insufficient prevalence or seizure data were available to directly determine a value of Tf by interpolation of a graph of Tf versus S/A. Benzodiazepine analogues had particularly low values of S/A and hence Tf. By contrast, γ-hydroxybutyrate/γ-butyrolactone, α-methyltryptamine, synthetic cannabinoid receptor agonists and benzofurans had a higher fatal toxicity.

Structure-activity relationships of valine-, tert-leucine-, and phenylalanine amino acid-derived synthetic cannabinoid receptor agonists related to ADB-BUTINACA, APP-BUTINACA, and ADB-P7AICA

2021 ◽  
Author(s):  
Eric Sparkes ◽  
Elizabeth Cairns ◽  
Richard Kevin ◽  
Felcia Lai ◽  
Katharina Grafinger ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cannabinoid Receptor ◽  
Synthetic Cannabinoid ◽  
New Psychoactive Substances ◽  
Psychoactive Substances ◽  
Structure Activity Relationships ◽  
Receptor Agonists ◽  
Structure Activity ◽  
Synthetic Cannabinoid Receptor Agonists

Synthetic cannabinoid receptor agonists (SCRAs) remain one the most prevalent classes of new psychoactive substances (NPS) worldwide, and examples are generally poorly characterised at the time of first detection. We...

scholarly journals Differential activation of G-protein-mediated signalling by synthetic cannabinoid receptor agonists

2019 ◽  
Author(s):  
Shivani Sachdev ◽  
Samuel D. Banister ◽  
Marina Santiago ◽  
Chris Bladen ◽  
Michael Kassiou ◽  
...  
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
Cannabinoid Receptor ◽  
Rank Order ◽  
Synthetic Cannabinoid ◽  
New Psychoactive Substances ◽  
Differential Activation ◽  
Receptor Agonists ◽  
Synthetic Cannabinoid Receptor Agonists ◽  
Camp Levels

AbstractSynthetic cannabinoid receptor agonists (SCRAs) are new psychoactive substances associated with acute intoxication and even death. However, the molecular mechanisms through which SCRAs may exert their toxic effects remain unclear - including the potential differential activation of G protein subtypes by CB1, a major target of SCRA. We measured CB1-mediated activation of Gαs and Gαi/o proteins by SCRAs by examining stimulation (PTX-treated) as well as inhibition (non-PTX treated) of forskolin-induced cAMP accumulation in HEK cells stably expressing CB1. Real-time measurements of stimulation and inhibition of cAMP levels were made using a BRET biosensor. We found that the maximum concentration of SCRAs tested (10 μM), increased cAMP levels 12 to 45% above that produced by forskolin alone, while the phytocannabinoid THC did not significantly alter cAMP levels in PTX-treated HEK-CB1 cells. All SCRAs had greater potency to inhibit of forskolin-induced cAMP levels than to stimulate cAMP levels. The rank order of potencies for SCRA stimulation of cAMP (Gαs) was PB-22 > 5F-MDMB-PICA > JWH-018 > AB-FUBINACA > XLR-11. By contrast, the potency of SCRAs for inhibition of cAMP (Gαi/o) was 5F-MDMB-PICA > AB-FUBINACA > PB-22 > JWH-018 > XLR-11. The different rank order of potency of the SCRAs to stimulate Gαs-like signalling compared to Gαi/o signalling suggests differences in G protein preference between SCRAs. Understanding the apparent differences among these drugs may contribute to unravelling their complex effects in humans.

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

Molecules ◽  
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.

scholarly journals Modulation of human T-type calcium channels by synthetic cannabinoid receptor agonists in vitro

2021 ◽  
Vol 187 ◽  
pp. 108478
Author(s):  
Chris Bladen ◽  
Somayeh Mirlohi ◽  
Marina Santiago ◽  
Mitchell Longworth ◽  
Michael Kassiou ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Cannabinoid Receptor ◽  
Synthetic Cannabinoid ◽  
Receptor Agonists ◽  
Synthetic Cannabinoid Receptor Agonists

scholarly journals Human Toxicity Caused by Indole and Indazole Carboxylate Synthetic Cannabinoid Receptor Agonists: From Horizon Scanning to Notification

2018 ◽  
Vol 64 (2) ◽  
pp. 346-354 ◽  
Author(s):  
Simon L Hill ◽  
Michael Dunn ◽  
Céline Cano ◽  
Suzannah J Harnor ◽  
Ian R Hardcastle ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Synthetic Cannabinoid ◽  
Severe Toxicity ◽  
Accurate Identification ◽  
Receptor Agonists ◽  
Horizon Scanning ◽  
Other Substances ◽  
Using Data ◽  
Synthetic Cannabinoid Receptor Agonists ◽  
The Uk

Abstract BACKGROUND The emergence of novel psychoactive substances (NPS), particularly synthetic cannabinoid receptor agonists (SCRA), has involved hundreds of potentially harmful chemicals in a highly dynamic international market challenging users', clinicians', and regulators' understanding of what circulating substances are causing harm. We describe a toxicovigilance system for NPS that predicted the UK emergence and identified the clinical toxicity caused by novel indole and indazole carboxylate SCRA. METHODS To assist early accurate identification, we synthesized 5 examples of commercially unavailable indole and indazole carboxylate SCRA (FUB-NPB-22, 5F-NPB-22, 5F-SDB-005, FUB-PB-22, NM-2201). We analyzed plasma and urine samples from 160 patients presenting to emergency departments with severe toxicity after suspected NPS use during 2015 to 2016 for these and other NPS using data-independent LC-MS/MS. RESULTS We successfully synthesized 5 carboxylate SCRAs using established synthetic and analytical chemistry methodologies. We identified at least 1 SCRA in samples from 49 patients, including an indole or indazole carboxylate SCRA in 17 (35%), specifically 5F-PB-22 (14%), FUB PB-22 (6%), BB-22 (2%), 5F NPB-22 (20%), FUB NPB-22 (2%), and 5F-SDB-005 (4%). In these 17 patients, there was analytical evidence of other substances in 16. Clinical features included agitation and aggression (82%), reduced consciousness (76%), acidosis (47%), hallucinations and paranoid features (41%), tachycardia (35%), hypertension (29%), raised creatine kinase (24%), and seizures (12%). CONCLUSIONS This toxicovigilance system predicted the emergence of misuse of indole and indazole carboxylate SCRA, documented associated clinical harms, and notified relevant agencies. Toxicity appears consistent with other SCRA, including mental state disturbances and reduced consciousness.

Sign in / Sign up

Export Citation Format

Share Document