Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder. A Randomized Clinical Trial Alan K. Davis, PhD; Frederick S. Barrett, PhD; Darrick G. May, MD; Mary P. Cosimano, MSW; Nathan D. Sepeda, BS; Matthew W. Johnson, PhD; Patrick H. Finan, PhD; Roland R. Griffiths, PhD JAMA Psychiatry, 2020, E1-E9. doi : 10.1001/jamapsychiatry.2020.3285 IMPORTANCE : Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression. OBJECTIVE : To investigate the effect of psilocybin [...]
Lire la suiteAntidepressant mechanisms of ketamine: Focus on GABAergic inhibition Bernhard Luscher, Mengyang Fenga, Sarah J. Jefferson Advances in Pharmacology, 2020 doi : 10.1016/bs.apha.2020.03.002 Contents 1. Introduction 3 2. Molecular targets of subanesthetic ketamine and its metabolites 6 3. Insights from ketamine indicate a key role for reduced GABAergic inhibition in the pathophysiology of major depression 7 3.1 Antidepressant efficacy of ketamine is controlled by imbalances between neural excitation and inhibition 7 3.2 Chronic imbalances of neural excitation and inhibition lead to homeostatic downregulation of glutamatergic synapses that compromises normal neuronal communication 9 3.3 Chronic imbalances between neural excitation and inhibition lead to defects in GABAergic inhibition that delimit spontaneous recovery from [...]
Lire la suiteSingle Shot of Ketamine May Herald 'Last Call' for Problem Drinking Deborah Brauser Medscape, December 11, 2019 Medscape Medical News © 2019 https://www.medscape.com/viewarticle/922460?src=wnl_tp10n_200116_mscpedit&uac=292598PZ&impID=2238619&faf=1 An experimental treatment that includes a single infusion of ketamine may lead to long-term improvement in problem drinking, new research suggests. In an study of 90 heavy drinkers, those who received a single dose of intravenous (IV) ketamine plus cognitive behavioral therapy (CBT) that focused on reactivating drinking-related "maladaptive reward memories" (MRMs) significantly curbed the urge to drink and reduced alcohol intake compared with those who received the ketamine alone or a placebo infusion. In addition, the combination group reduced their average weekly alcohol consumption by [...]
Lire la suiteMolecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites Chun Yang, Jianjun Yang, Ailin Luo and Kenji Hashimoto Translational Psychiatry, 2019, 9, 280 doi : 10.1038/s41398-019-0624-1 Abstract Although the robust antidepressant effects of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine in patients with treatment-resistant depression are beyond doubt, the precise molecular and cellular mechanisms underlying its antidepressant effects remain unknown. NMDAR inhibition and the subsequent α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid receptor (AMPAR) activation are suggested to play a role in the antidepressant effects of ketamine. Although (R)-ketamine is a less potent NMDAR antagonist than (S)-ketamine, (R)-ketamine has shown more marked and longer-lasting antidepressant-like [...]
Lire la suiteSome distorted thoughts about ketamine as a psychedelic and a novel hypothesis based on NMDA receptor-mediated synaptic plasticity Rachael Ingram, Heather Kang, Stafford Lightman, David E. Jane, Zuner A. Bortolotto, Graham L. Collingridge, David Lodge, Arturas Volianskis Neuropharmacology, 2018, 142, 30e40 https://doi.org/10.1016/j.neuropharm.2018.06.008 Abstract Ketamine, a channel blocking NMDA receptor antagonist, is used off-label for its psychedelic effects, which may arise from a combination of several inter-related actions. Firstly, reductions of the contribution of NMDA receptors to afferent information from external and internal sensory inputs may distort sensations and their processing in higher brain centres. Secondly, reductions of NMDA receptormediated excitation of GABAergic interneurons can result in [...]
Lire la suite