Pharmacology Of Noval Cannabinoids

Cannabis is a plant rich in various compounds that have a variety of impacts on the physiology of humans and the effects of these metabolites have a significant role in managing a variety of clinical diseases. A substantial increase in the use of SC (synthetic cannabinoids) had seen in the last few years especially infrequent cannabis users. The SCs will generate psychoactive effects that were similar to cannabis. However, the composition and pharmacological characteristics of these drugs make them possibly hazardous. Like all drugs, cannabis’ pharmacokinetics depends on the route of administration. Several studies showed that the bioavailability is less in oral administration when compared to inhalation. The main reason for this decrease in oral bioavailability is that cannabinoids undergo the first-pass metabolism before entering into the systemic circulation whereas in inhalation, it enters the circulation directly through the lungs. Cannabis sativa is a psychoactive plant that contains more than 500 components of which 104 cannabinoids had been identified. Of these, 2 components such as Δ9-THC (Δ9-tetrahydrocannabinol) and CBD (cannabidol) were under the scientific investigation. Δ9-THC is the primary cannabinoid which was responsible for the consequences of psychotrophy. The potency of cannabis is assessed based on the THC concentration of a sample that is the main psychoactive cannabinoid in cannabis. The adverse effects are in direct relation to the concentration of THC in the product after regular cannabis use. It can be assumed that several cannabinoids will find their way into the pharmacies from preclinical research within a century.

Action of ketamine and endocannabinoid system in rapid anti-depression therapy / 上海交通大学学报（医学版）

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.

COX-2 modulates Δ~9-THC-induced inhibition of LTD in CA1 area / 西安交通大学学报(医学版)

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.