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SCRAs and other NPS may not be detected by point-of-care DOA tests.
During test sessions, both levers were active, such that ten consecutive responses on either lever led to reinforcement.
Eight in-vivo metabolites tentatively identified were mainly products of ester hydrolysis with or without additional dehydrogenation, N-dealkylation, monohydroxylation and oxidative defluorination with further oxidation to butanoic acid.
5F-MDMB-PINACA (also known as 5F-ADB, 5F-ADB-PINACA), MDMB-CHIMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA (also known as FUB-AMB, MMB-FUBINACA) were tested for in vivo cannabinoid-like effects to assess their abuse liability.
LC-QTOF-MS represents a significant advancement in the field of drug detection, offering higher sensitivity, specificity, and a broader spectrum of detectable substances.
Synthetic cannabinoids (SCBs) are agonists at cannabinoid receptor type 1 (CB1) and type 2 (CB2), where they elicit their main effects.
The locomotor activity of the mice was measured 30 min and 2 hrs after the last substance administration.
5F-MDMB-PINACA (also known as 5F-ADB, 5F-ADB-PINACA), MDMB-CHIMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA (also known as FUB-AMB, MMB-FUBINACA) were tested for in vivo cannabinoid-like effects to assess their abuse liability.
Assessment of abuse liability is based on several factors, including chemical structure, pharmacological mechanism of action, and finally, subjective and reinforcing behavioral effects (FDA, 2010; Swedberg, 2013).
Twenty-four male Sprague-Dawley rats were obtained from Envigo (Houston, TX).
Manufactured under strict quality control protocols, is processed to meet high laboratory standards.
Since there is currently no robust measure of the reinforcing/rewarding effects of cannabinoids, drug discrimination is currently the best model for assessing abuse liability of cannabinoids.
It is not known whether the increased toxicity is due only to activation of CB1 cannabinoid receptors more strongly than Δ9-THC or whether these “super-strength” cannabinoids produce effects at other receptors.
A two-way analysis of variance, with dose as a between groups factor and time as a within subject factor, was conducted on horizontal activity counts/10 min interval.
Average potency of the discriminative stimulus effects of early compounds was 0.81±0.17 mg/kg (Gatch et al., 2014), whereas the potency of a recent set was 0.09±0.03 mg/kg (Gatch et al., 2018), and the potency of the current set is 0.05±0.01 mg/kg.
There are two case-reports published describing severe toxicological effects of vaping SCRA in humans, indicating that the EC50 of the SCRA may provide an estimate of the severity of intoxication.
SCRAs belong, together with synthetic opioids, cathinones, amphetamines and hallucinogens to the new psychoactive substances (NPS) that are currently developed at high speed.
The product ion detected at m/z 235, indicating loss of sulfate, confirmed the identity of the sulfation metabolite.
Concentrations of SCRAs in postmortem cases cover a wide range ; however, some reports of survival have also been published—even at relatively high blood SCRA concentrations [19, 20].
Percent drug-appropriate responding was shown only if at least three rats completed the first fixed ratio, whereas all rats are shown for the response rate data.
A 30-min period, beginning when maximal depression of locomotor activity first appeared as a function of dose, was used for analysis of dose-response data and calculation of ED50 values.
Results of the DOA test (including testing for amphetamines, methamphetamines, barbiturates, benzodiazepines, cocaine, methadone, opioids, cannabis, tricyclic antidepressants) were available within 30 minutes and were all negative.
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