Open Access

Nicolas Singewald, Simone Sartori, Andreas Reif, Andrew Holmes

• Highlights • Up-to-date overview on developing new medications including candidates with novel bioloigical targets for the treatment of anxiety disorders and PTSD. • Targeting glutamatergic, cholinergic and neurosteroid mechanisms can produce acute anxiolytic effects. • Drugs, including psychedelics, are hypothesized to produce neuroplasticity to cause enduring clinical effects. • Combining medication with psychological approaches may augment therapeutic efficacy. • Advances in circuit neuroscience can be leveraged to inform the design of rationale drug targets. Abstract Psychiatric disorders associated with psychological trauma, stress and anxiety are a highly prevalent and increasing cause of morbidity worldwide. Current therapeutic approaches, including medication, are effective in alleviating symptoms of anxiety disorders and posttraumatic stress disorder (PTSD), at least in some individuals, but have unwanted side-effects and do not resolve underlying pathophysiology. After a period of stagnation, there is renewed enthusiasm from public, academic and commercial parties in designing and developing drug treatments for these disorders. Here, we aim to provide a snapshot of the current state of this field that is written for neuropharmacologists, but also practicing clinicians and the interested lay-reader. After introducing currently available drug treatments, we summarize recent/ongoing clinical assessment of novel medicines for anxiety and PTSD, grouped according to primary neurochemical targets and their potential to produce acute and/or enduring therapeutic effects. The evaluation of putative treatments targeting monoamine (including psychedelics), GABA, glutamate, cannabinoid, cholinergic and neuropeptide systems, amongst others, are discussed. We emphasize the importance of designing and clinically assessing new medications based on a firm understanding of the underlying neurobiology stemming from the rapid advances being made in neuroscience. This includes harnessing neuroplasticity to bring about lasting beneficial changes in the brain rather than – as many current medications do – produce a transient attenuation of symptoms, as exemplified by combining psychotropic/cognitive enhancing drugs with psychotherapeutic approaches. We conclude by noting some of the other emerging trends in this promising new phase of drug development.