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
April 2, 2011
Thilo Deckersbach, Britta K. Hölzel, Lori Eisner et al.
130 citations
A mindfulness-based cognitive therapy (MBCT) program tailored for bipolar disorder was tested in 12 individuals. After 12 group sessions and at a 3-month follow-up, participants showed increased mindfulness, reduced residual depressive mood symptoms, fewer attentional difficulties, and improvements in emotion regulation, psychological well-being, positive affect, and psychosocial functioning. The findings suggest MBCT may help manage residual mood symptoms and improve overall functioning in people with bipolar disorder.
CNS Neuroscience & Therapeutics
April 12, 2013
Giacomo Salvadore, Jaskaran Singh
80 citations
A single intravenous subanesthetic dose of ketamine, an NMDA receptor antagonist, rapidly reduces depressive symptoms and suicidal thoughts in patients with treatment-resistant mood disorders. Emerging evidence suggests that ketamine's antidepressant effects depend on increasing AMPA signaling and rapidly inducing synaptogenesis. However, critical questions remain about safe and effective use, including optimal dose, administration method, and biomarkers of response. This review summarizes clinical evidence, preclinical and human studies on ketamine's mechanisms and predictors of antidepressant response, and identifies knowledge gaps to guide future research toward developing more effective, fast-acting antidepressants.
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.
CNS Neuroscience & Therapeutics
December 1, 2024
Xiaoyu Niu, Yuanyuan Zheng, Wang Wang et al.
7 citations
Esketamine, a drug that blocks NMDA receptors, improved neurological function and promoted nerve repair in mice with intracerebral hemorrhage. RNA sequencing and network pharmacology identified neurotrophin-3 and the PI3K/AKT signaling pathway as key targets. Experiments confirmed that esketamine increased NTF3 protein levels, and blocking the PI3K/AKT pathway with a specific inhibitor reduced the drug's therapeutic effects. The findings suggest esketamine activates the NTF3/PI3K/AKT pathway to aid recovery after brain hemorrhage.
CNS Neuroscience & Therapeutics
March 1, 2025
Zerui You, Xiaofeng Lan, Chengyu Wang et al.
1 citation
Ketamine improves depressive symptoms in major depressive disorder by altering energy metabolism, including changes in adenosine triphosphate, adenosine diphosphate (ADP), and pyruvate. The shift in ADP levels strongly correlated with reductions in depression severity scores. Lower baseline levels of free triiodothyronine (FT3) predicted a better response to ketamine, suggesting FT3 may serve as a biological marker for treatment efficacy. These findings come from a study of 40 patients in a discovery cohort and 24 in a validation cohort, using metabolomic analysis of serum samples.
CNS Neuroscience & Therapeutics
April 1, 2024
Liang Zhou, Jingjing Duan
Ketamine, a dissociative anesthetic and PCP analog, produces rapid loss of consciousness at anesthetic doses and rapid, lasting antidepressant effects at subanesthetic doses. This review describes ketamine's metabolism and recent advances in understanding how NMDAR inhibition mediates both effects. The roles of NMDARs in anesthesia are well studied, but their involvement in antidepressant actions is complex and debated. The authors also explore possible functions of NMDAR subunits and discuss future directions for ketamine-based drugs.