Psychopharmacology
May 1, 2018
Mendel Kaelen, Bruna Giribaldi, Jordan Raine et al.
9 citations
correction
Music plays a central role in psychedelic therapy by helping to guide and support the therapeutic process. The article synthesizes evidence that music can influence emotional states, facilitate psychological insights, and enhance the overall therapeutic outcome when combined with psychedelic substances. The authors argue that music acts as a "hidden therapist" by directing the trajectory of the psychedelic experience, promoting emotional release, and supporting the integration of the experience afterward. This suggests that careful selection and use of music is crucial for optimizing the therapeutic benefits of psychedelic therapy.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
May 1, 2025
Paolo Cardone, Pablo Núñez, Naji L N Alnagger et al.
7 citations
A patient in a minimally conscious state plus received psilocybin, a classic psychedelic, for the first time. No increase in overt behavioral repertoire was observed on validated scales, but new spontaneous behavior not previously seen emerged, and brain complexity, measured by the Lempel-Ziv complexity index, increased with changes in underlying periodic rhythms. This case report contributes to future investigations of psychedelics for disorders of consciousness and the link between brain complexity and consciousness.
George Deane, Jonas Mago, Aikaterini Fotopoulou et al.
7 citations
preprint
A computational theory called adaptive narrative control explains how subpersonal processes shape conscious experience to enable adaptive behavior. Systems with an attention schema can anticipate the epistemic and pragmatic consequences of attentional states, using mental action—endogenous control of attention—to regulate affective states. This capacity also produces avoidant mental action or motivated inattention, which is argued to be a core mechanism underlying psychopathology, leading to rigid belief formation, reduced emotional recognition (alexithymia), and decreased subjective well-being under certain environmental conditions. The account partially echoes Freudian defense mechanisms and introduces a computational unconscious. It refines the REBUS model of psychedelic therapy and explains improvements in well-being from meditation.
Communications biology
March 11, 2025
Juan Ignacio Piccinini, Yonatan Sanz Perl, Carla Pallavicini et al.
6 citations
The transition into a psychedelic brain state is often overlooked in favor of static descriptions of acute effects. Using a time-dependent whole-brain model and fMRI data from 15 volunteers given intravenous DMT, the work shows that a transient of heightened reactivity in fronto-parietal regions and visual cortices correlates with serotonin 5HT2a receptor density. Simulated perturbations suggest that minimal disturbances can achieve maximal effects during this brief period, and the temporal evolution of these features aligns with pharmacokinetics. These findings indicate a mechanism for how short psychedelic episodes may exert a lasting influence over time.
Research square
March 8, 2024
Hannes Kettner, Leor Roseman, Adam Gazzaley et al.
5 citations
Older adults (age 60+) who participated in a guided psychedelic group retreat showed significant improvements in well-being, with larger gains among those with a prior psychiatric diagnosis. Compared to younger adults, older adults experienced weaker acute psychedelic effects, and these effects did not predict well-being changes. Instead, a sense of communitas—the relational or social connection during the group session—predicted well-being improvements in older adults, suggesting that the social context of psychedelic therapy may be especially important for this age group.
Andrea I. Luppi, Pedro Mediano, Fernando Rosas et al.
5 citations
preprint
Consciousness can be understood not as a single unified thing but as composed of distinct information-theoretic elements. A new approach called Integrated Information Decomposition (ΦID) shifts from measuring how much integrated information a system has to analyzing its composition. This provides a formal way to determine whether consciousness is an emergent phenomenon based on that composition. Two organisms can have the same amount of integrated information yet differ in its composition. A new measure, ΦR, and the ΦR-ing rate quantify how efficiently an entity uses information for conscious processing. This decomposition identifies qualitatively different 'modes of consciousness,' enabling mapping between phenomenology and information-theoretic structure, starting with selfhood.
Human brain mapping
April 1, 2025
Clayton R Coleman, Kenneth Shinozuka, Robert Tromm et al.
4 citations
LSD alters consciousness by changing connectivity between the dorsolateral prefrontal cortex (DLPFC), thalamus, and visual areas. In healthy participants, stronger functional connectivity between the left and right DLPFC, thalamus, and fusiform face area correlated with greater ego dissolution. Emotional arousal was linked to increased connectivity between the right DLPFC, intraparietal sulcus, and salience network. A confirmatory reverse analysis supported these findings. Magnetoencephalography data showed that LSD increased theta-band information flow from the thalamus to the DLPFC, supporting the idea that disrupted thalamic gating underlies ego dissolution. The results clarify the DLPFC's role in LSD-induced altered states.
Annals of the New York Academy of Sciences
July 21, 2025
Marcel Socoró-garrigosa, Yonatan Sanz Perl, Morten L Kringelbach et al.
3 citations
The scale at which the brain represents information remains a key question in neuroscience. Evidence shows that information is encoded not just in localized areas but across distributed, hierarchical networks. The hierarchy of causal influences shaping brain activity patterns is a signature of different brain states, relevant to neuropsychiatric disorders. Using whole-brain models guided by the thermodynamics of mind framework, researchers estimated brain hierarchy and studied in-silico transitions in static functional connectivity. Applying this to major depressive disorder, they built resting-state whole-brain models of depressed patients before and after treatment with psilocybin or escitalopram.
Journal of affective disorders
August 1, 2026
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
2 citations
In people with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support, the therapeutic alliance before dosing had only weak correlations with improvement in depression scores at three weeks. Stronger correlations were seen with the intensity of the psychedelic experience itself, particularly emotional breakthrough and visual restructuring. Path analysis suggested that therapeutic alliance helped facilitate the psychedelic experience, but it was the psychedelic experience—not the alliance—that had stronger direct effects on clinical outcomes. The alliance's direct effect on antidepressant response was limited or absent.
Cureus
January 29, 2025
Sorcha O'Connor, Kate Godfrey, Sara Reed et al.
2 citations
The study aims to uncover the neural mechanisms by which psilocybin-assisted therapy affects obsessive-compulsive disorder (OCD) and whether those brain changes align with improvements in cognitive symptoms. A secondary goal is to test whether a low, tolerable dose is both practical and effective as a clinical treatment. The results will provide essential data for designing a future randomized controlled trial.
The Oxford Handbook of Psychedelic, Religious, Spiritual, and Mystical Experiences
December 18, 2024
Aaron D. Cherniak, Robin Carhart-Harris, Joel Gruneau Brulin et al.
2 citations
A theoretical synthesis of attachment theory and the REBUS neuroscientific model offers an organizing framework for psychedelic science. Attachment theory holds that people develop internal working models (IWMs) of relational experiences that function as predictive models shaping social and emotional worlds. Effective psychedelic interventions may induce a hyper-plastic neural state that, supported by corrective relational experiences, facilitates rapid learning and revision of IWMs toward greater security. Three proposals guide future research: individual differences in attachment security predict psychedelic phenomenology and integration; increasing attachment security may be a clinical outcome; and clinical utility involves attachment-related dynamics such as connectedness and alleviation of worries.
JMIR formative research
March 4, 2024
Grant Jones, Felipe Herrmann, Adam Bear et al.
2 citations
In a group of people who recently used psychedelics, increases in mindfulness were followed by improvements in well-being. The findings suggest that mindfulness may be a mechanism through which psychedelic experiences lead to positive mental health outcomes.
October 19, 2022
Stefan Baumann, Robin Carhart-Harris, David Nutt et al.
2 citations
preprint
In a placebo-controlled citizen science trial with 240 participants, microdosing tolerance was assessed by tracking whether correct guesses of receiving a microdose decreased with more doses taken. Correct guess probability declined overall, indicating tolerance developed. This tolerance was specific to LSD and LSD-analogue microdoses, not psilocybin microdoses. The findings suggest that microdosers may need to periodically suspend their routine to avoid tolerance and that psilocybin may be better suited for long-term protocols.
bioRxiv (Cold Spring Harbor Laboratory)
January 29, 2026
Venkatesh Subramani, Timothy Nest, Annalisa Pascarella et al.
1 citation
LSD alters brain activity by increasing alpha and beta brain-wave frequencies while genuinely reducing oscillatory power, with these effects showing distinct cortical patterns. The drug also flattens the aperiodic 1/f spectral slope and increases neural signal fractality and complexity, particularly in sensory, language, emotion, and imagery-related networks, while sparing motor cortex. Machine learning identified peak-frequency shifts, aperiodic parameters, and complexity measures as key discriminators of the psychedelic state. Music did not amplify these neural signatures and showed a trend toward attenuation. These findings provide a comprehensive account of how LSD reorganizes large-scale human brain dynamics.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
June 23, 2025
Jessica Henry, Bruna Giribaldi, David J Nutt et al.
1 citation
In patients with major depressive disorder, two high-dose psilocybin therapy sessions produced large increases in optimism and improvements in all three domains of dysfunctional attitudes (achievement, dependency, self-control) at six weeks, while a six-week daily course of escitalopram improved only the achievement domain and did not change optimism. Psilocybin also made patients more optimistic about desirable life events, whereas escitalopram reduced pessimism about negative life events. The findings suggest psilocybin therapy is superior to escitalopram for remediating negative cognitive biases in 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.
CPT: pharmacometrics & systems pharmacology
October 1, 2023
Emma Eckernäs, Jeroen Koomen, Christopher Timmermann et al.
1 citation
A modeling study designed an infusion protocol for the psychedelic compound DMT, aiming to maintain a specific level of psychedelic intensity. Using computer simulations based on pharmacokinetic/pharmacodynamic models, optimal doses to achieve intensity ratings between 7 and 9 on a 0-10 scale were a bolus of 14-16 mg DMT fumarate followed by an infusion rate of 1.2-1.4 mg/min. However, the proportion of simulated individuals achieving the target intensity was low (below 53%), indicating that individual dose adjustments would be necessary. Differences between the models were observed, particularly at scale boundaries, with bounded integer models predicting more cases exceeding the target than the continuous variable model.
Research Square
June 19, 2026
Aline Frick, Grace Blest‐hopley, Manesh Grin et al.
In a reanalysis of a six-week randomized controlled trial comparing psilocybin with escitalopram for moderate-to-severe major depressive disorder, sex-related patterns emerged for anxiety and anhedonia. Women receiving psilocybin showed greater reductions in anxiety than men, while women receiving escitalopram showed greater reductions in anhedonia than men. For other depressive symptoms, thought suppression, and well-being, sex differences were small and uncertain. Sexual dysfunction severity was lower overall in the psilocybin group than in the escitalopram group and lower in women than in men, though the treatment-by-sex interaction was not significant. These preliminary findings suggest that responses to these serotonergic treatments may differ between women and men, supporting the need for adequately powered, sex-balanced trials.
arXiv (Cornell University)
May 15, 2026
Jonas Mago, Edmundo Lopez-Sola, Jakub Vohryzek et al.
States of consciousness with minimal phenomenal content, such as those induced by certain meditation practices, show increased brain entropy similar to high-content psychedelic states, challenging the Entropic Brain Hypothesis that links entropy to phenomenal richness. The Complex Brain Hypothesis resolves this by proposing that brain complexity, not entropy, better indexes the richness of experience. Complexity is modulated by the grain of inference the brain uses to resolve uncertainty: fine-grained inference loosens constraints and proliferates content, as in psychedelic states; coarse-grained inference simplifies experience into contentless awareness, as in minimal phenomenal experiences. Both regimes can elevate entropy but differ in phenomenology and perturbational signatures, refining the Entropic Brain Hypothesis and highlighting minimal phenomenal experiences as a test case for computational theories of consciousness.
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Otto Simonsson, Taylor Lyons, Joseph Marks et al.
Across three studies—a naturalistic observation, a single-arm psilocybin trial with healthy volunteers, and a randomized controlled trial comparing psilocybin to escitalopram in depressed patients—psychedelic use did not produce significant changes in authoritarian attitudes. Contrary to earlier suggestions, the evidence does not reliably show that psychedelics decrease authoritarian attitudes. Future work should use larger, more diverse samples and examine other political outcomes.
Discover Mental Health
March 7, 2026
Nicholas Fabiano, Brendon Stubbs, David W. Lawrence et al.
More than half of people with major depressive disorder do not respond to standard treatments, prompting interest in alternatives such as exercise and psychedelics. This commentary examines how these two approaches might work together. Biologically, psychedelics briefly boost brain-derived neurotrophic factor (BDNF) signaling, while exercise provides sustained BDNF elevation; psychedelics enhance neuroplasticity mainly in the cortex, whereas exercise promotes hippocampal neurogenesis; both increase serotonin release. Psychologically, psychedelics may help people adopt exercise habits, and exercise may improve emotional resilience, potentially deepening the psychedelic experience. The authors suggest that these complementary mechanisms warrant future research on their combined efficacy, tolerability, safety, and neurobiology.
bioRxiv (Cold Spring Harbor Laboratory)
March 5, 2026
Venkatesh Subramani, Annalisa Pascarella, Jérémy Brunel et al.
Lysergic acid diethylamide (LSD) loosens the brain's usual alignment between anatomical structure and neural activity in a frequency-dependent way. Low-frequency brain waves (theta, alpha, beta) become less constrained by the structural connectome, indicating a global relaxation of large-scale dynamics. High-frequency gamma activity shows selective reorganization rather than uniform disruption. Greater gamma-band decoupling within core default-mode network regions predicts the intensity of ego dissolution across individuals. LSD does not cause indiscriminate disintegration but drives system-specific rebalancing: visual and attentional systems decouple while auditory networks strengthen coupling. These findings suggest psychedelic states emerge from frequency-dependent relaxation of structural constraints, with default-mode reorganization as a neural correlate of ego dissolution.
Behavioral Sciences
February 23, 2026
Joshua Lipson, Hannes Kettner, Robin Carhart-Harris et al.
Mood before taking a psychedelic substance and factors like social connectedness, mindfulness, and spirituality influence how the experience unfolds. People with higher baseline depression and anxiety tend to have more challenging experiences but not more mystical ones, while those with greater wellbeing report more mystical and fewer challenging experiences. Mindfulness and spirituality are linked to more mystical experiences, and social connectedness and mindfulness are linked to fewer challenging ones. Mystical and challenging experiences were weakly but positively correlated overall.
medRxiv
February 19, 2026
Amanda Gow, Emily Shih, Ryan Reid et al.
Under Oregon's regulated psilocybin program, adults who consumed an average of 27.8 mg of psilocybin showed significant improvements in depression, anxiety, and well-being 30 days after a session, including those concurrently using psychiatric medication. Of 88 participants (median age 43, 52% male, 64.8% with prior psychedelic experience), two reported symptoms of hallucinogen persisting perception disorder one day after the session, but none at 30 days. The findings suggest that legal psilocybin services can produce clinically meaningful mental health benefits.
Neuroscience of consciousness
January 1, 2026
Jonas Mago, George Deane, Lars Sandved-Smith et al.
People under the influence of psychedelics often report encountering autonomous entities such as spirits, elves, or ancestors. A neurocomputational model, grounded in the active inference framework, explains these experiences by proposing that psychedelics reduce the predictability of sensory perceptions, leading the brain to interpret both internal and external perceptions as coming from non-self agents. The model synthesizes earlier theories including the entropic brain model, computational accounts of felt presence, and sensory attenuation theories of self-other discrimination. It aims to account for how the brain supports entity encounters and for the diversity and similarity of these experiences across cultural contexts.