Background and aims: Despite promising findings indicating the therapeutic potential of psychedelic experience across a variety of domains, the mechanisms and factors affecting its efficacy remain unclear. The present paper explores this by focusing on two psychedelic states which have been suggested as therapeutically significant in past literature: ego-dissolution and connectedness. The aim of the study is to investigate the impact of ego-dissolution and connectedness on the therapeutic effects of the psychedelic experience. Methods: The investigation was carried out as a mixed methods systematic review, with the data from four databases analysed thematically and results presented through narrative synthesis. Results: The analysis and synthesis of findings from 15 unique studies (n 5 2,182) indicated that both ego-dissolution and connectedness are associated with a higher chance of improvement following a psychedelic experience. However, there seem to be differences in the way the two experiences affect individuals psychologically. Ego-dissolution appears to trigger psychological change but does not typically exceed the psychedelic experience in its duration, while connectedness can be more sustained and is associated with several positive, potentially therapeutic feelings. Conclusions: Moreover, the findings of this review have implications for further theory-building about the mechanisms which enable therapeutic effects in psychedelic experience. This in turn might lead to improved models for psychedelic therapy practice. Emphasis on ego-dissolution during the preparation phase and on connectedness during integration is one suggestion presented here, alongside overarching implications for the mental health debate and general practice.