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Objective Synthetic cannabinoids(SCs)will be widely metabolized to phase I metabolites and glucuronide metabolites after entering human body.It is usually difficult to detect the parent drug of SCs in urine.Therefore,it is necessary to undergo de-glucuronidation in the preparation of urine samples.We aimed to optimize the enzymatic hydrolysis methods for SCs detection in urine.Methods We studied enzymatic hydrolysis for the determination of 11-demethyl-9-carboxyl-THC(Δ9-THC-COOH)in THC positive urine samples by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and compared it with the alkaline digestion method.Meanwhile,we studied enzymatic hydrolysis for the determination of the related metabolites in MDMB-4en-PINACA and ADB-BUTINACA positive urine samples.Results The Δ9-THC-COOH glucuronic acid conjugate could be hydrolyzed by adding 3μL β-d-glucuronidase solution(＞100 000 units/mL)for 30 min at 55℃.The MDMB-4en-PINACA M and ADB-BUTINACA M glucuronide conjugates were hydrolyzed by adding 3μL β-d-glucuronidase solution(＞100 000 units/mL)for 30 min at 75℃.Conclusion This study can provide reference for the establishment of rapid,accurate and reliable enzymatic hydrolysis methods when detecting SCs in urine.
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Major depression disorder (MDD) is a common but serious affective disorder in modern society. Suicide idea and suicide behaviour induced by MDD during its later stage put a heavy burden on society and family. Anti-depression drugs lack efficiency in treating a portion of MDD patients. This is referred to as treatment resistant depression (TRD). A study reported the rapid onset and long lasting anti-depression effect of ketamine, which also come into effect in TRD patients. Δ9-Tetrahydrocannabinol is the active substance of marijuana, which also exerts rapid anti-depression effect via targeting at brain cannabinoid receptors. The two central nerve system stimulants belonging to the tightly controlled psychoactive substances have obvious adverse effects. This article summarizes the action of ketamine and endocannabinoid system in rapid anti-depression therapy in recent researches.
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Objective To explore the role of cyclooxgense-2 (COX-2) in tetrahydrocannabinol (THC)-induced inhibition of long-term depression (LTD) in CA1 area in vitro. Methods The hippocampal slices were prepared at 24 h after intraperitoneal injection of Δ~9-THC (10 mg/kg) or COX-2 inhibitor NS398 (10 mg/kg). Field excitatory post-synaptic potentials (fEPSP) were recorded in the stratum radiatum of the CA1 area in vitro to observe the effect of NS398, a selective inhibitor of COX-2, on the THC-induced inhibition of LTD and THC's effect on membrane excitability in pyramidal neurons by using the whole-cell patch clamp technique. Results ① Low-frequency stimulation (1 Hz, 15 min) induced-LTD in CA1 area was significantly attenuated by Δ9-THC. ② Δ~9-THC did not affect the basal synaptic transmission and membrane excitability (including membrane resting potentials, input resistance and firing property). ③ THC-induced inhibition of LTD was reversed by NS398. ④ THC-induced inhibition of LTD was robustly impaired in COX-2 knockout mice. Conclusion THC-induced inhibition of LTD in CA1 area was mediated via COX-2.