The history of psychedelic drug use in psychotherapy spans over half of a century. Presently, psychedelic drugs are being studied as psychotherapy adjuncts. There are promising findings (Evans et al. 2018; Watts et al. 2017; Gasser et al. 2014) on the usage of such drugs as lysergic acid diethylamide, psilocybin, ketamine, and ayahuasca in the treatment of mood disorders. This may be an alternative way to solve the problem of treatment-resistant mood disorders. Novel findings suggest that psychedelic drugs are capable of changing the neural mechanisms underlying mental dysfunction and producing long-lasting improvements in functioning of clinical populations. The alterations produced by these drugs are clustered in a set of regions - the default-mode network (DMN) - which are engaged in various intrinsic processes, e.g. forming internal experience and building self-narrative. Research shows that changes in the DMN are characteristic for mood disorders (Mulders et al. 2015; Kaiser et al. 2015), and for this reason the DMN can become a trigger for response to therapy. Alterations in the DMN may be a marker of psychedelic-assisted psychotherapy efficacy, as the state produced by psychedelics is characterised by a pattern of DMN functioning in an opposite way to that seen in mood disorders. In this narrative review we will take a closer look at how some psychedelics effect DMN activity and functional connectivity, sum up the proposed interpretations of such changes, compare those results to findings in the field of mood disorders (mainly depression), and propose future directions for research on psychedelic-assisted psychotherapy.