CNS Neuroscience & Therapeutics
April 10, 2013
G. Mion, Thierry Villevieille
690 citations
For over 50 years, ketamine has been a safe anesthetic with potent pain-relieving properties. Its active form is S(+)-ketamine, and it is mainly metabolized into norketamine, an active metabolite. During dissociative anesthesia, sensory inputs reach the brain but are not perceived in some association areas. Ketamine also enhances the descending serotonin pathway for pain relief and has antidepressant effects. Pain relief persists at plasma concentrations ten times lower than those needed for hypnosis. By blocking the NMDA receptor, ketamine reduces the wind-up phenomenon and hyperalgesia, including opioid-induced hyperalgesia.
CNS Neuroscience & Therapeutics
November 11, 2008
Torsten Passie, John H. Halpern, Dirk O. Stichtenoth et al.
459 citations
Lysergic acid diethylamide (LSD) was synthesized in 1938 and its psychoactive effects discovered in 1943. It was used in psychiatric research during the 1950s and 1960s to produce experimental psychosis and in psycholytic and psychedelic therapy. After becoming an illegal drug of abuse from the mid-1960s, scientific interest has resumed with new methods and oversight. This review covers all aspects of LSD's pharmacology and psychopharmacology, based on nearly 10,000 scientific papers. LSD is physiologically well tolerated and psychological reactions can be controlled in a medical setting, but uncontrolled use risks complications. New interest focuses on LSD as a tool for studying consciousness and potential treatments for cluster headache and terminally ill patients.
CNS Neuroscience & Therapeutics
June 1, 2013
O. Corazza, S. Assi, F. Schifano
147 citations
Ketamine, discovered in 1962, is used recreationally for its rapid, short-lived dissociative effects, including the 'K-hole' experience of confusion, dissociation, and depersonalization. Its abuse is linked to physical and psychological side effects, notably bladder toxicity. A newer derivative, methoxetamine, emerged as a legal and purportedly 'bladder-friendly' alternative, offering similar dissociation but with slower onset and longer duration. However, methoxetamine appears associated with worse side effects than ketamine, including mood disturbances, suicidal attempts, and acute cerebellar toxicity. After 50 years, ketamine has spawned methoxetamine, but this derivative does not seem a safer alternative.
CNS Neuroscience & Therapeutics
January 10, 2023
Jing Wang, Min Liang, Qing Shang et al.
23 citations
Psilocin, the active metabolite of psilocybin, counteracts methamphetamine (METH)-induced hyperactivity and blocks the formation of conditioned place preference (CPP) in mice, indicating it may reduce the rewarding effects of METH. In an acute model, 1 mg/kg psilocin reduced the elevated activity caused by 2 mg/kg METH. In the CPP model, the same dose of psilocin prevented the development of place preference during acquisition but did not affect extinction or relapse. Molecular analysis revealed that psilocin's effects involve altered expression of dopamine 2 receptor (D2R) and phosphorylated ERK in the prefrontal cortex, nucleus accumbens, and ventral tegmental area. Inhibitors of D2R and ERK phosphorylation also blocked METH-induced hyperactivity and CPP acquisition, suggesting psilocin acts through D2R-mediated regulation of ERK phosphorylation.