Major depression disorder (MDD) is a common but serious affective disorder in modern society. Suicide idea and suicide behaviour inducedMDD 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. [Key words]ketamine; endocannabinoid system; major depression disorder; Δ9-tetrahydrocannabinol (Δ9-THC); brain derived neurontrophic factor (BDNF); mammalian target of rapamycin (mTOR) pathway; N-methyl-D-aspartate (NMDA) receptor