Abuse of amphetamine-type stimulants (ATS), including amphetamine, methamphetamine (METH), and 3,4-methylenedioxymethamphetamine (MDMA; ecstasy), has become a major public health problem worldwide. Use of these stimulants has significant psychiatric and medical consequences, including psychosis, dependence, overdose, and death. METH abuse in particular is an extremely serious and growing problem in many countries. The development of treatments for METH-related problems is particularly critical for users who experience persistent psychosis, pregnant women and women with children, gay and bisexual men, and users involved in the criminal justice system. However, there are currently no pharmacological treatments for the wide range of symptoms associated with METH-related problems. One of the reasons for this problem is that our knowledge of the cellular and molecular mechanisms underlying the development of METH-induced psychosis and dependence is limited. In this article, we review recent reports on potential pharmacotherapies (naltrexone, minocycline, antioxidants, immunotherapy, and dopaminergic, serotonergic, cholinergic, and GABAergic agents) for the treatment of ATS abusers.

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Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.