Cannabinoid-like effects of five novel carboxamide synthetic cannabinoids

Gatch, Michael B.; Forster, Michael J.

doi:10.1016/j.neuro.2018.11.004

Cited by 39 publications

(33 citation statements)

References 38 publications

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“…Therefore, AMB‐FUBINACA is not only more potent, it also generates a stronger response at CB1 than the reference compound JWH‐018 at high concentrations. Although it is difficult to compare EC 50 values from different assays (due to different experimental setups), our low nanomolar values are in line with those found in other reports investigating the in vitro and in vivo activity of AMB‐FUBINACA . More particularly, Banister et al and Gamage et al estimated the EC 50 and the E max values for AMB‐FUBINACA via the FLIPR ® assay and via the [ 35 S]GTP binding assay and via the inhibition of forskolin‐stimulated cAMP production, respectively.…”

Section: Resultssupporting

confidence: 89%

Comprehensive investigation on synthetic cannabinoids: Metabolic behavior and potency testing, using 5F‐APP‐PICA and AMB‐FUBINACA as model compounds

Fabregat‐Safont

Mardal

Noble

et al. 2019

Drug Testing and Analysis

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Synthetic cannabinoids (SCs) represented 45% of new psychoactive substances seizures in Europe (data from 2016). The consumption of SCs is an issue of concern due to their still unknown toxicity and effects on human health, the great variety of compounds synthetized, and the continuous modifications being made to their chemical structure to avoid regulatory issues. These compounds are extensively metabolized in the organism and often cannot be detected as the intact molecule in human urine. The monitoring of SCs in forensic samples must be performed by the analysis of their metabolites. In this work, a workflow for the comprehensive study of SC consumption is proposed and applied to 5F‐APP‐PICA (also known as PX 1 or SRF‐30) and AMB‐FUBINACA (also known as FUB‐AMB or MMB‐FUBINACA), based not only on the elucidation of their metabolites but also including functional data using the NanoLuc approach, previously published. Both cannabinoids were completely metabolized by human hepatocytes (12 and 8 metabolites were elucidated by high resolution mass spectrometry for 5F‐APP‐PICA and AMB‐FUBINACA, respectively) and therefore suitable consumption markers are proposed. The bioassays revealed that 5F‐APP‐PICA presented lower activity than AMB‐FUBINACA at CB1 and CB2 receptors, based on the half maximal effective concentration (EC50) and the maximum response (Emax). These results are in agreement with the different intoxication cases found in the literature for AMB‐FUBINACA.

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Section: Resultssupporting

confidence: 89%

Comprehensive investigation on synthetic cannabinoids: Metabolic behavior and potency testing, using 5F‐APP‐PICA and AMB‐FUBINACA as model compounds

Fabregat‐Safont

Mardal

Noble

et al. 2019

Drug Testing and Analysis

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“…Acute intoxication by JWH-018, also led participants to score higher on drug compulsivity and drug liking. Compulsive craving is a typical feature of drug dependence (Heishman et al 2001); hence, these effects demonstrate the abuse liability of JWH-018, similar to that shown previously for SCs in rodents (Gatch and Forster 2019;Zanda and Fattore 2018;Fantegrossi et al 2014). From natural cannabis, it is known that it can cause psychotomimetic symptoms in healthy volunteers and induce psychosis in vulnerable people (Johns 2001;Henquet et al 2005).…”

Section: Discussionsupporting

confidence: 75%

Psychotomimetic symptoms after a moderate dose of a synthetic cannabinoid (JWH-018): implications for psychosis

et al. 2021

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Background Synthetic cannabinoids (SCs) are the largest class of novel psychoactive substances (NPS) and are associated with an increased risk of overdosing and adverse events such as psychosis. JWH-018 is one of the earliest SCs and still widely available in large parts of the world. Controlled studies to assess the safety and behavioural profiles of SCs are extremely scarce. Aim The current study was designed to assess the psychotomimetic effects of a moderate dose of JWH-018. Methods Twenty-four healthy participants (10 males, 14 females) entered a placebo-controlled, double blind, within-subjects trial and inhaled vapour of placebo or 75μg/kg bodyweight JWH-018. To ascertain a minimum level of intoxication, a booster dose of JWH-018 was administered on an as-needed basis. The average dose of JWH-018 administered was 5.52 mg. Subjective high, dissociative states (CADSS), psychedelic symptoms (Bowdle), mood (POMS) and cannabis reinforcement (SCRQ) were assessed within a 4.5-h time window after drug administration. Results JWH-018 caused psychedelic effects, such as altered internal and external perception, and dissociative effects, such as amnesia, derealisation and depersonalisation and induced feelings of confusion. Conclusion Overall, these findings suggest that a moderate dose of JWH-018 induces pronounced psychotomimetic symptoms in healthy participants with no history of mental illness, which confirms that SCs pose a serious risk for public health.

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“…Adverse effects may be cardiovascular (e.g., sympathomimetic effects such as tachycardia, palpitations, hypertension, myocardial infarction, and arrhythmias), neurological (e.g., seizures, tremors, stroke, fear, aggressive behavior, changing moods, and confusion [ 9 ]), gastrointestinal (e.g., nausea and vomiting), psychological (e.g., agitation, confusion, drowsiness, lethargy, hallucination, irritability, and paranoia), pulmonary (e.g., respiratory depression), metabolic, or muscular [ 10 , 11 ]. However, unlike cannabis, SCs have significant potential to cause severe and life-threatening toxicity.…”

Section: Discussionmentioning

confidence: 99%

Accidental Ingestion of a Novel Psychoactive Substance: A Case Report

Kant¹,

Mong²,

Tan³

2020

Cureus

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Novel psychoactive substances (NPSs) are a new generation of designer drugs that are quickly replacing the traditionally abused street drugs. Since their development, the number of molecules in NPSs and their variants have expanded exponentially. Little is known locally about the toxic effects of the exposure of these NPSs. We report two cases of accidental ingestion of methyl (2S)-2-{[1-(5-fluoropentyl)-1H-indole-3arbonyl]amino}-3,3-dimethylbutanoate (5-fluoro-MDMB-PICA), a recent NPS. They were drinking the liquid in a winter melon tea bottle, and one patient had a seizure episode directly after ingestion. Both patients were managed supportively and discharged after a brief hospitalization period. Presentation to the emergency departments (EDs) following exposure to NPSs may become more common. Knowledge about the impact of NPS exposure and their clinical effects is lacking amongst emergency physicians in Singapore, and this case report serves as a potential resource for physicians.

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Cannabinoid-like effects of five novel carboxamide synthetic cannabinoids

Cited by 39 publications

References 38 publications

Comprehensive investigation on synthetic cannabinoids: Metabolic behavior and potency testing, using 5F‐APP‐PICA and AMB‐FUBINACA as model compounds

Comprehensive investigation on synthetic cannabinoids: Metabolic behavior and potency testing, using 5F‐APP‐PICA and AMB‐FUBINACA as model compounds

Psychotomimetic symptoms after a moderate dose of a synthetic cannabinoid (JWH-018): implications for psychosis

Accidental Ingestion of a Novel Psychoactive Substance: A Case Report

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