Frontiers in Pharmacology
November 2, 2018
Adam D. G. Hampshire, Christopher Timmermann, Christopher Timmermann et al.
422 citations
Psychological well-being increased two weeks after a psychedelic experience and remained elevated at four weeks. Higher ratings of a 'mystical-type experience' positively influenced this change in well-being, while 'challenging experience' and 'visual effects' did not. Having 'clear intentions' for the experience fostered mystical-type experiences. A positive 'set' and recreational intentions reduced the likelihood of a challenging experience. The trait 'absorption' and higher drug doses amplified all aspects of the acute experience. Baseline traits had the strongest effect on well-being change, underscoring the importance of extra-pharmacological factors in shaping responses to psychedelics.
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.
Pedro A.M. Mediano, Fernando E. Rosas, Andrea I. Luppi et al.
10 citations
A new method called Complexity via State-space Entropy Rate (CSER) estimates neural signal complexity with better temporal resolution and spectral decomposition than the standard Lempel-Ziv complexity (LZ) approach. CSER matches LZ in distinguishing conscious states but offers two key advantages: it can break complexity down by frequency bands, and it provides temporal resolution about 100 times finer. Using MEG, EEG, and ECoG data from humans and monkeys, CSER revealed that gamma-band activity primarily drives complexity changes across states of consciousness. In an auditory mismatch negativity experiment, CSER detected early entropy increases roughly 20 milliseconds before the standard event-related potential. This method enables finer-grained study of how signal complexity relates to cognitive processes and conscious states.
American Journal of Geriatric Psychiatry
January 1, 2026
Jacob S. Aday, Robin L. Carhart-Harris, Kevin F. Boehnke
2 citations
Psilocybin, a hallucinogen found in certain mushrooms, demonstrated significant therapeutic potential in a study involving 200 participants with treatment-resistant depression. After just three doses, 60% reported substantial symptom relief lasting up to six months. In comparison, traditional antidepressants typically show around 30% effectiveness. The findings suggest that psychedelics like psilocybin could revolutionize psychiatry by addressing the underlying pathogenesis of mental health disorders. This breakthrough highlights the need for more exploration into psychedelics and their implications for clinical psychology and medicine.
Imaging Neuroscience
April 16, 2025
Lorenzo Pasquini, Alexander J. Simon, Courtney L. Gallen et al.
1 citation
DMT rapidly induces a short-lasting altered state of consciousness marked by physical transcendence, vivid auditory distortions, and visual imagery. Using simultaneous fMRI and EKG data from 14 healthy volunteers before, during, and after intravenous DMT or placebo, a brain substate emerged immediately after DMT injection, characterized by deactivations in the hippocampus and medial parietal cortex and increased activity in the superior temporal lobe. Hippocampal and medial parietal deactivations correlated with altered sense of time, space, and self-referential processes, reflecting a deconstruction of ordinary consciousness. Superior temporal lobe activations correlated with audio/visual hallucinations and the experience of "entities.
bioRxiv (Cold Spring Harbor Laboratory)
Hanna M. Tolle, Andrea I Luppi, Timothy Lawn et al.
1 citation
preprint
A geometric deep learning model called graphTRIP predicts post-treatment depression severity from pretreatment clinical and brain imaging data. Trained on a clinical trial comparing psilocybin and escitalopram, it achieves strong predictive accuracy (r = 0.75) and generalizes to an independent dataset. The model links better outcomes to reduced functional coupling within serotonin systems and broader serotonergic integration with sensory-motor networks. Causal analysis shows a group-level advantage of psilocybin over escitalopram but identifies individuals with specific stress-related neuromodulatory profiles who may benefit more from escitalopram, advancing precision medicine and biomarker discovery in depression.
Frontiers in Pharmacology
June 3, 2026
Burton J. Tabaac, Robin L. Carhart-Harris, Teresa Yung
Three individuals with persistent symptoms after traumatic brain injury or hypoxic-ischemic brain injury completed a six-week protocol combining a participant-directed iboga-containing microdosing regimen (using whole root bark biomass with about 3.845% ibogaine content, yielding an estimated 3.8–38.5 mg/day ibogaine equivalent) with weekly Accelerated Experiential Dynamic Psychotherapy and supportive nutraceuticals. All three showed progressive neurological recovery; two reported complete symptom remission at long-term follow-up. Participants discontinued all prescription medications and reported resolution of headaches, brain fog, fatigue, irritability, and mood swings, with a return to regular activities and renewed enthusiasm. The authors note that the findings do not establish causality or iboga-specific efficacy due to the multimodal intervention and methodological limitations.
Nature Mental Health
April 1, 2026
Saif S. Ali, Robin L. Carhart-Harris, Karl G. Sieg
LSD and psilocybin may help treat obsessive-compulsive disorder (OCD) by disrupting maladaptive brain circuits and enhancing neuroplasticity. OCD involves dysfunction in the cortico-striatal-thalamo-cortical circuit, default mode network, and salience network. Psychedelics acutely dysregulate the default mode network and increase connectivity between normally segregated networks, potentially breaking cycles of rumination and self-referential thought. They also modulate the cortico-striatal-thalamo-cortical circuit and rapidly promote dendritic spine formation via 5-HT2A receptors in rodents. These dual mechanisms could reset pathological patterns and support long-term restructuring of maladaptive circuits, but clinical trials with neuroimaging endpoints are needed to validate this framework.