This work presents seven investigations conducted with the aim to determine the effects of DMT (a compound which is able to cause remarkable effects in consciousness) and associated psychedelic drugs on the human brain and mind. Including a variety of neuroimaging (EEG, MEG and fMRI), phenomenological, psychometric and naturalistic research methods, these are the first controlled investigations of the impact of DMT in the human resting brain. Results revealed that DMT disrupted several brain mechanisms associated with top-down control (alpha power, integrity of high-level networks, modularity), increased measures related to entropy, or disorder (Lempel-Ziv complexity, novel pairwise connectivity) and immersive states of consciousness (delta/theta power), with some of these effects following the experiential trajectories of the DMT state. We also observed a significant temporal correlation between some of these effects (alpha power and default-mode network integrity fluctuations), which were supported by LSD effects of reduced feedback connectivity and neural adaption mechanisms. suggesting that the psychedelic brain state is one of reduced modularity, increased integration and functional plasticity. These findings were complemented by psychological studies showing that the DMT state is one of immersive visual imagery, intense somatic experiences and partial disconnection from the environment, which we found shared significant overlap with near- death experiences. DMT administration also resulted in positive mental health outcomes in healthy volunteers providing evidence for the first time that DMT may provide a useful alternative to currently- investigated psychedelic treatments. Finally, results from our last study performed in naturalistic environments revealed that psychedelics are able to have a transformative potential on core beliefs concerning the fundamental nature of reality and consciousness for up to 6 months, with important social and bioethical implications. Collectively these results attest to the strong impact that psychedelics have on varied human domains, which range experience, brain activity, mental health, intersubjectivity and beliefs.