Ketamine is a noncompetitive antagonist of N-methyl-d-asparate (NMDA) receptor and has been long used as an anesthetic agent in humans and veterinary medicine. The present article reviews the epidemiology, pharmacology, neurochemistry, and treatment of ketamine abuse. Ketamine has a unique mood controlling property and a number of studies have demonstrated a significant and rapid antidepressant effect of ketamine. However, the therapeutic value of ketamine to treat psychiatric disorders faces a major challenge that ketamine also owns significant reinforcing and toxic effects. Its abuse has posted severe harms on individuals and society. Disrupted learning and memory processing has long been related with ketamine use. It is hypothesized that ketamine blocks NMDA receptors on gamma-aminobutyric acid (GABA) neurons inside the thalamic reticular nucleus, which leads to disinhibition of dopaminergic neurons and increased release of dopamine. Currently, there is no specific treatment for treating every ketamine patient presenting peripheral toxicity. Interestingly, ketamine psychotherapy has been suggested to be a promising approach to treat addiction of other drugs. Future research can continue to develop creative ways to investigate potential mechanism and treatments related to ketamine abuse that have posted severe individual and social harms.

Ketamine users with at least a 2-year habit of 3 or more hits per week have altered bladder function that can be recognized and that causes bother. These early functional changes have the potential to normalize after 1 year of ketamine abstinence. This study provides a basis for the development of health promotion material that can be used in the community by welfare workers seeking to encourage drug cessation.

The molecular mechanism and treatment of methamphetamine (METH) use disorder remain unclear. The current study aimed to investigate the role of central angiotensin II receptor (ATR) in drug taking and seeking behavior associated with METH use disorder. The effect of an ATR type 1 (AT1R) antagonist, candesartan cilexetil, on the reinforcing and motivational effects of METH was first assessed using the animal model of METH self-administration (SA) and reinstatement. The levels of dopamine D2 receptor (D2R) and AT1R were subsequently examined. Furthermore, the present study determined the expression of microRNAs (miRNAs) by comparing METH SA, METH-yoked, and Saline-yoked groups. The target miRNAs were further overexpressed in the nucleus accumbens (NAc) via a lentivirus vector to investigate the effects of target miRNAs on METH SA maintained under a fixed ratio 1, progressive ratio, and cue/drug reinstatement of METH SA. The potential role of the AT1R-PLCb-CREB signaling pathway was finally investigated. The results suggest that AT1R blockade effectively reduced METH SA and reinstatement, in conjunction with the counter-regulation of D2R and AT1R. A total of 17 miRNAs targeting Ang II in NAc were found to be associated with the voluntary intake of METH. Furthermore, overexpression of specific miR-219a-5p targeting AT1R-regulated METH SA and reinstatement. The AT1R-PLCb-CREB signaling pathway was found to be associated with the effect of AT1R on the drug-taking and drug-seeking behavior involving METH use disorder.Both yoked-METH SA (yoked-METH) and yoked-Saline groups were tested simultaneously with the METH SA group in different conditions. Either a yoked-METH or a yoked-Saline rat was paired with one METH SA rat. Yoked-METH rats received the intravenous infusions of METH at the same dose, number, and rate as the METH SA group. The yoked-Saline group received the intravenous infusions of saline at the same number and rate as the METH SA group. The nose-pokes by the yoked rats were recorded but had no programmed consequences. Cue-and Drug-Induced Reinstatement of METH SAAfter METH SA, the animals were subjected to extinction for 7 days. During the extinction phase, the animals were placed in chambers, AT1R Blockade of Methamphetamine Self-Administration in Rats