The last few decades have been characterised by a resurgence in research and clinical interest in classic serotonergic psychedelics including N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD) and psilocybin, with a growing body of literature pointing to their treatment potential. Ayahuasca is a psychedelic brew commonly composed of plants carrying the psychoactive compound DMT, and...
The clinical use of psychedelic substances and Psychedelic-Assisted Therapy (PAT) is an area of growing interest that also raises significant social concerns and controversy. Despite existing legal restrictions, empirical research on substances such as psilocybin, mescaline, MDMA, LSD, DMT, and ibogaine has been developing, particularly in the treatment of conditions such as treatment-resistant...
Importance Psilocybin simultaneously holds contradictory legal classifications across seven overlapping governance systems—Schedule I under U.S. federal law, FDA Breakthrough Therapy designation, authorized therapeutic use in Oregon and Colorado, operational state-level medical access in New Mexico, national medical rescheduling in Australia, and an active petition for DEA rescheduling. As...
Background: Serotonergic psychedelics induce their psychoactive effects by stimulating the brain’s serotonin 2A receptor (5-HT2AR). In humans, a cerebral 5-HT2AR occupancy of ≥60% is required to elicit a profound psychedelic experience with psilocybin [1] and for pigs, a dose corresponding to ∼65% 5-HT2AR occupancy elicits headshakes [2]. We posit that in order to assess biochemical and...
Treatment-resistant depression (TRD) affects about 30% of patients with major depressive disorder and remains a major clinical challenge.The limited effectiveness of classical antidepressants suggests that the pathophysiology of TRD is complex and extends beyond the traditional monoamine hypothesis.The aim of this paper was to present current concepts of the neurobiological background of TRD...
Despite divergent behavioral and phenomenological profiles, both psychedelic states and reduced states of consciousness have been associated with a flattening of the brain's functional hierarchy. To address this apparent paradox, we developed a more specific definition of hierarchy based on the proximity of the brain to thermodynamic equilibrium and then applied it to investigate the changes to...
Microdosing psychedelics has attracted growing attention from public commentators, scientists, investors and user communities across the globe. Microdosing is the use of small doses of psychedelic substances such as psilocybin mushrooms and LSD. Its proponents speak of microdosing as a use modality that improves various human abilities and life areas, including cognitive function, mood,...
Classical psychedelics such as N,N-dimethyltryptamine (DMT) modulate consciousness via serotonergic receptor agonism, and are increasingly investigated for their psychotherapeutic potential. When combined with the monoamine oxidase A (MAO-A) inhibitor harmine—mimicking the pharmacological profile of ayahuasca—oral DMT induces a psychedelic experience lasting 4–5 h. While some neuroimaging...
Mystical dynamics-the notion that mystical oneness may unfold involving ego disintegration, renewal, and luminous light-has been discussed anecdotally by psychedelic researchers and therapists but has not yet been empirically examined in controlled settings. This study investigated the occurrence and dose-dependency of mystical dynamics in healthy participants after administration of...
Network Neuroscience2026Hiba Sheheitli, Robert Hermosillo, Gracie Grimsrud et al.
Metastability of BOLD fMRI signals is a commonly used proxy of brain dynamics in behavioral and clinical studies. To date, little has been done to assess the confidence with which we can use estimates of metastability as reliable biomarkers of individual brain state. We analyze whole-brain and network-specific metastability for a highly sampled individual brain (84 sessions taken over 18...