bioRxiv (Cold Spring Harbor Laboratory)
May 17, 2021
S. Parker Singleton, Andrea I. Luppi, Robin L. Carhart-Harris et al.
30 citations
preprint
LSD and psilocybin reduce the amount of energy the brain needs to transition between different activity states, as measured by functional MRI. This flattening of the brain's control energy landscape allows for more frequent state transitions and more diverse (entropic) brain activity. The effects are linked to the spatial distribution of serotonin 2a receptors, the main target of these psychedelics. The findings suggest that these compounds make brain state transitions more facile and temporally diverse, offering a mechanistic explanation for the altered subjective experience induced by psychedelics.
International Journal of Mental Health and Addiction
March 7, 2024
Brandon Weiss, Leor Roseman, Bruna Giribaldi et al.
26 citations
Acute psychological experiences, particularly mystical experience and ego dissolution, partially account for how psilocybin therapy improves depression compared to escitalopram. In a phase 2 trial of patients with moderate-to-severe major depressive disorder, mystical experience and ego dissolution uniquely mediated the effect of treatment on depressive response. Higher levels of mystical experience, emotional breakthrough, and intense music-listening responses were also linked to greater antidepressant improvement. These findings suggest that acute psychological experiences play a causal mechanistic role in psilocybin therapy for depression.
The Biochemist
March 25, 2024
David J. Nutt
3 citations
Natural psychedelics like magic mushrooms have been used for at least 7000 years, with a resurgence in the 1950s and 1960s after LSD was synthesized and used therapeutically. Non-medical use led to a global ban in the early 1970s. Over the past 20 years, research has revived, showing that psychedelics act as agonists of the serotonin 5-HT2A receptor, altering neuro-circuitry to produce more integrated and flexible brain activity. These changes, observed in healthy volunteers, predicted benefits for mental illnesses like depression and addiction, confirmed by subsequent trials. A single psychedelic experience can yield very long-lasting improvements across several mental illnesses. Given these consistent positive outcomes, psychedelic therapy will likely soon be widely approved in Western medicine, as it already is in Australia for treatment-resistant depression.
bioRxiv Preprint Server
December 9, 2024
Clayton R. Coleman, Kenneth Shinozuka, Robert Tromm et al.
1 citation
preprint
Lysergic acid diethylamide (LSD) alters consciousness by affecting brain connectivity, particularly in the dorsolateral prefrontal cortex (DLPFC). Using fMRI and MEG data from healthy participants, the study found that ego dissolution—a hallmark of the psychedelic experience—was positively correlated with increased functional connectivity between the left and right DLPFC, thalamus, and fusiform face area. Emotional arousal was linked to stronger connectivity between the right DLPFC, intraparietal sulcus, and salience network. A confirmatory analysis supported these findings. MEG data showed that LSD increased directed information flow from the thalamus to the DLPFC in the theta band, suggesting disrupted thalamic gating contributes to ego dissolution. These results indicate a key role for the DLPFC in LSD-induced states of consciousness.
PLoS ONE
June 18, 2026
Elisa Liberati, Hv Curran, Peter Fonagy et al.
MDMA-assisted psychotherapy shows promise for treating PTSD, but the psychological mechanisms behind its effects are not well understood. This qualitative study will have approximately 25 experienced psychodynamic psychotherapists receive two doses of MDMA (80-120 mg, oral) in an open-label design. Participants will complete interviews before, during, and after MDMA sessions, plus daily journals. Researchers will use phenomenological and thematic analysis, along with grounded theory, to develop a model of MDMA's psychological mechanisms of action. The study treats therapists as expert observers of their own psychological processes, aiming to generate insights that can inform future treatment models and offer a framework for qualitative mechanistic research on psychedelics.