bioRxiv (Cold Spring Harbor Laboratory)
July 14, 2017
Selen Atasoy, Leor Roseman, Mendel Kaelen et al.
25 citations
preprint
Lysergic acid diethylamide (LSD) alters the energy and power of individual harmonic brain states in a frequency-selective manner, expanding the repertoire of active brain states. This non-random increase in co-activation across frequencies suggests a general re-organization of brain dynamics. The frequency distribution of active brain states under LSD follows power-laws, indicating dynamics at the edge of criticality. These methods offer insights into complex brain dynamics in health and disease.
Scientific Reports
February 7, 2024
Tommaso Barba, Hannes Kettner, Caterina Radu et al.
24 citations
Psychedelics may improve sexual functioning and satisfaction days or weeks after use, according to two studies. In a large naturalistic study, people who used psychedelics reported greater pleasure, communication during sex, and satisfaction with their partner and appearance. A controlled clinical trial comparing psilocybin therapy with the SSRI escitalopram for depression found that those given psilocybin reported positive changes in sexual functioning after treatment, while those given escitalopram did not. This is the first quantitative investigation of psychedelics' post-acute effects on sexual functioning, suggesting a potential benefit and a need for further research.
Psychiatry Research
July 23, 2023
Otto Simonsson, Per Carlbring, Robin Carhart-Harris et al.
24 citations
In a meta-analysis of three psilocybin trials for depression involving 102 participants, clinically significant symptom worsening occurred for a minority of those receiving psilocybin or escitalopram (about 10%) and for a majority of those in the waitlist condition (63.6%). The psilocybin arm showed a lower likelihood of symptom worsening compared to waitlist and no difference compared to escitalopram. The authors note the limitation of a relatively small sample size.
Journal of Psychopharmacology
April 25, 2023
Brandon Weiss, David Erritzøe, Bruna Giribaldi et al.
24 citations
A reanalysis of data from a trial comparing psilocybin therapy (PT) to escitalopram (ET) for major depressive disorder found that 14 of 16 outcome measures favored PT, but the QIDS-SR-16 did not. The QIDS-SR-16 showed higher variance, imprecision from compound items and sum-scoring, vague response options, and lack of focus on a core depression factor. When the trial data were examined at item, facet, and factor levels, results suggested PT was superior in reducing depressed mood, anhedonia, a core depression factor, and specific symptoms like sexual dysfunction. This raises concerns about relying on individual scales that miss depression's multidimensional structure.
Psychopharmacology
December 11, 2023
Haley Maria Dourron, Charles D. Nichols, Otto Simonsson et al.
23 citations
5-MeO-DMT, a tryptamine being developed as an antidepressant, may work through a mechanism distinct from typical psychedelics. This review compares the acute and post-acute effects of 5-MeO-DMT to epileptiform activity, particularly in temporal lobe epileptogenic zones. The authors note that 5-MeO-DMT has notable 5-HT1A receptor agonist properties and that aberrant 5-HT1A receptor functioning occurs in epilepsy. They suggest that 5-MeO-DMT's therapeutic mechanism might be partly mediated by evoking temporary epileptiform activity, similar to electroconvulsive therapy. The phenomenon of 'reactivations'—sudden re-experiencing of drug effects common after 5-MeO-DMT but not typical psychedelics—may indicate recurrent epileptiform activity. The review concludes that further evaluation of 5-MeO-DMT's unique mechanisms is warranted.
Neuroimage
November 1, 2022
Hardik Rajpal, Pedro A. M. Mediano, Fernando E. Rosas et al.
23 citations
Schizophrenia and drug-induced states from LSD and ketamine both increase neural signal diversity, but they differ in brain connectivity: schizophrenia shows increased information flow from front to back of the brain, while the drugs reduce it. These differences can be modeled by altering Bayesian inference in a predictive processing framework: drug effects correspond to reduced precision of prior beliefs, whereas schizophrenia involves increased precision of sensory information. The findings clarify similarities and differences between these altered states, with implications for understanding consciousness and developing mental health treatments.
Journal of Medical Internet Research
May 4, 2021
Sebastian Hübner, Eline Haijen, Mendel Kaelen et al.
23 citations
In web-based studies that track people before and after they use psychedelics, many participants stop responding, which can bias the results. Analyzing data from 654 initial participants, younger age, lower education, higher extraversion, and lower conscientiousness predicted dropping out before the four-week endpoint. Neither positive attitudes toward psychedelics nor intense challenging experiences during the drug session predicted dropout. These attrition patterns match those seen in other long-term studies, suggesting they are not unique to psychedelic research. The absence of dropout linked to psychedelic advocacy or negative drug experiences reduces concerns about certain biases in this type of data.
Clinical and Translational Science
September 11, 2022
Emma Eckernäs, Christopher Timmermann, Daniel Röshammar et al.
22 citations
The psychedelic compound DMT is cleared from the body at a very high rate—26 L/min—indicating its elimination is independent of blood flow. Plasma concentrations follow a two-compartment model, with DMT metabolized to indole 3-acetic acid. The intensity of the psychedelic experience is linked to DMT concentration at an effect site, with half-maximal effect at 95 nM. Simulated median intensity ratings after doses of 1, 4, 7, 14, and 20 mg were zero, 2, 4, 8, and 9 on a 0–10 scale. The model can help predict suitable doses for clinical studies based on desired subjective experience intensity.
Scientific Reports
July 17, 2024
Sara de la Salle, Hannes Kettner, Julien Thibault Lévesque et al.
21 citations
A prospective longitudinal survey of eight Canadians with cancer who received legal psilocybin-assisted psychotherapy under Section 56 exemptions found significant improvements in anxiety, depression, pain, fear of COVID-19, quality of life, and spiritual well-being two weeks after the session. Attitudes toward death, medical assistance in dying, and desire for hastened death remained unchanged. Most participants found the sessions highly meaningful, though one reported a substantial decrease in well-being. These preliminary data suggest that real-world psilocybin-assisted psychotherapy can produce psychiatric benefits similar to those in clinical trials, but limited enrollment and negative experiences indicate a need for formal real-world evaluation programs.
Psychopharmacology
August 22, 2023
Robert F. Dougherty, Patrick Clarke, Merve Atli et al.
21 citations
A machine learning model that analyzes language from therapy sessions can predict which patients with treatment-resistant depression will respond to psilocybin therapy. Researchers used a zero-shot classifier based on the BART large language model to measure sentiment (valence and arousal) in transcripts of therapist-patient conversations one day after COMP360 psilocybin administration. These sentiment scores, combined with the Emotional Breakthrough Index and treatment arm, were fed into multinomial logistic regression models. The models predicted responder status at week 3 and through week 12 with 85% and 88% accuracy, respectively, and AUC values of 88% and 85%. This approach could enable early identification of patients needing alternative treatments.
Frontiers in Psychiatry
September 30, 2021
James B. Close, Julia Bornemann, Maria Piggin et al.
21 citations
A co-designed guide for patient and public involvement (PPI) in psychedelic research addresses the lack of field-specific frameworks. Core values—trust, learning, purpose, and inclusivity—emerged from a workshop with public collaborators. The guidance aims to help researchers plan, evaluate, and improve PPI so that research is done with and by the public rather than on them, strengthening accountability and relevance as the field grows.
bioRxiv (Cold Spring Harbor Laboratory)
June 25, 2017
Mendel Kaelen, Romy Lorenz, Frederick S. Barrett et al.
20 citations
preprint
Lysergic acid diethylamide (LSD) alters how the brain processes music, particularly by enhancing activity and connectivity in networks linked to music perception and emotion. Sixteen healthy volunteers listened to a 7-minute music piece during fMRI after taking either 75 mcg of LSD or a placebo. The acoustic feature of timbral complexity—the richness of the music's spectral distribution—drove the most pronounced changes in brain activity and connectivity under LSD. These changes correlated with increased feelings of wonder evoked by the music. The results suggest a neurobiological basis for why music is useful in psychedelic therapy.
Neuroscience of Consciousness
January 1, 2025
Christopher Timmermann, James W. Sanders, David Reydellet et al.
19 citations
The psychedelic 5-MeO-DMT can, in its most extreme cases, produce a complete absence of self-experience and other perceptual content while preserving a quality of aroused, waking awareness. In an exploratory observational study in naturalistic ceremonial settings, micro-phenomenological interviews, questionnaires, and EEG recordings revealed a dynamic progression of effects, including variable disruptions of bodily and narrative self, reduced phenomenal distinctions, and visual imagery. EEG showed global alpha and posterior beta power reductions, suggesting inhibition of top-down brain models. The findings indicate 5-MeO-DMT's potential as a pharmacological model for deconstructed consciousness, though retrospective questionnaires have limitations.
Psychiatr Res Clin Pract
February 11, 2025
Jules Evans, Marc Aixalà, Brian T Anderson et al.
18 citations
Thirty psychedelic researchers identified critical gaps in knowledge about harms from psychedelic use, including how to define those harms, predict them, and treat them effectively. They recommend better online information, peer support groups, affordable therapy, and psychiatric consultation for people experiencing post-psychedelic difficulties. The researchers also call for improved funding for a psychedelic safety net, suggesting that psychedelic philanthropists, investors, and companies commit 1% of their investment to support safety measures such as research and support services. The article outlines practical steps to make the field of psychedelic medicine safer.
Am J Geriatr Psychiatry
May 19, 2024
Hannes Kettner, Leor Roseman, Adam Gazzaley et al.
18 citations
Guided psychedelic group sessions improve well-being in older adults (age 60+) similarly to younger adults, but through different mechanisms. Acute psychedelic effects are less intense in older adults and do not predict later well-being changes, whereas relational experiences before and after the sessions do predict improvements. Among older adults, having a lifetime psychiatric diagnosis was linked to greater well-being increases at the four-week follow-up. These findings suggest that the social and relational aspects of psychedelic group therapy may be especially important for older adults, warranting further research into psychedelic interventions for this population.
Biological psychiatry. Cognitive neuroscience and neuroimaging
July 1, 2023
Stefano Delli Pizzi, Piero Chiacchiaretta, Carlo Sestieri et al.
18 citations
LSD alters brain functional connectivity and local signal amplitude in opposite directions depending on the type of serotonin receptor involved. In healthy volunteers, LSD increased activity and connectivity in cortical regions of the default mode and attention networks, which have high densities of 5-HT2A receptors; these changes correlated with visual hallucinations. Conversely, LSD decreased activity and connectivity in limbic areas rich in 5-HT1A receptors. The spatial patterns of these functional changes overlapped with the distribution of the two serotonin receptor subtypes, suggesting distinct receptor-mediated mechanisms underlie LSD's reorganization of brain networks.
Journal of Psychopharmacology
January 1, 2023
Matthias Forstmann, Christina Sagioglou, Alexander Irvine et al.
18 citations
Among people who have used psychedelics, only past use of psilocybin—not LSD, mescaline, Salvia divinorum, ketamine, ibogaine, or DMT—reliably predicted a stronger sense of connection to nature (nature relatedness). The finding held even when people who had never used psychedelics were included in the analysis. For those who had used only psilocybin, more frequent use was linked to higher nature relatedness. This suggests that psilocybin may have a unique association with nature relatedness, possibly due to its pharmacology or the contexts in which it is used.
J Pharm Biomed Anal
February 3, 2022
Emma Eckernäs, Adam Bendrioua, Chiara Cancellerini et al.
18 citations
A highly sensitive LC-MS/MS method was developed and applied to simultaneously quantify N,N-dimethyltryptamine (DMT) and two of its metabolites in human plasma. This new method accurately and precisely measures DMT and its breakdown products, providing a robust tool for studying how DMT behaves in the body, its metabolism, and its effects.
Comprehensive Psychiatry
July 1, 2025
Luca Pellegrini, Naomi A Fineberg, Sorcha O'Connor et al.
17 citations
A 10 mg dose of psilocybin produced a rapid, moderate-to-large reduction in compulsive symptoms in people with obsessive-compulsive disorder (OCD), lasting up to one week after dosing. In a blinded pharmacological challenge study, 18 adults with at least moderate OCD received a 1 mg and then a 10 mg dose of oral psilocybin, separated by four weeks. One week after the 10 mg dose, scores on the compulsion subscale of the Yale-Brown Obsessive Compulsive Scale showed a significant improvement compared to the 1 mg dose (Cohen's d = 0.74). No effect on depression was detected. The drug was well tolerated with no serious adverse events.
Translational Psychiatry
December 4, 2024
Kenneth Shinozuka, Katarina Jerotic, Pedro A. M. Mediano et al.
17 citations
Serotonergic psychedelics such as LSD, psilocybin, and DMT alter consciousness and may help treat depression and addiction, but their mechanisms remain unclear. A systematic review and meta-analysis across three levels—subjective experience, neuroimaging, and molecular pharmacology—reveals that medium and high doses of LSD produce stronger visionary restructuring than psilocybin. Neuroimaging shows psychedelics generally strengthen connectivity between brain networks while weakening connectivity within networks. Pharmacologically, LSD triggers more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, but no significant differences exist in receptor selectivity among the drugs. The analysis finds high heterogeneity and risk of bias, calling for standardized methods and more research.
bioRxiv (Cold Spring Harbor Laboratory)
May 12, 2023
Christopher Timmermann, Emma Eckernäs, Leor Roseman et al.
17 citations
preprint
The serotonergic psychedelic DMT rapidly induces a profoundly immersive altered state lasting less than 20 minutes, allowing the entire drug experience to be captured during a single fMRI scan. Using network control theory, which quantifies the input needed to drive transitions between brain states, brain structure and function were integrated to map energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. Global control energy was reduced following DMT compared to placebo. Longitudinal trajectories of global control energy correlated with EEG signal diversity and subjective drug intensity ratings. Regional effects correlated with serotonin 2a receptor density. Receptor distribution and pharmacokinetic information successfully recapitulated DMT's effects on global control energy trajectories.
bioRxiv (Cold Spring Harbor Laboratory)
August 20, 2020
Carla Pallavicini, Federico Cavanna, Federico Zamberlán et al.
17 citations
preprint
Inhaled DMT, a short-acting psychedelic found in plants and animals, was studied in 35 experienced participants in natural settings using wireless EEG and questionnaires. DMT reduced alpha brain waves (8-12 Hz) across the scalp while increasing delta (1-4 Hz) and gamma (30-40 Hz) waves. Increases in gamma power correlated with reports of mystical-type experiences. DMT also altered global synchrony and metastability in gamma and alpha bands and increased signal complexity. These findings align with prior psychedelic research and suggest EEG markers for mystical experiences in natural contexts, underscoring the value of studying these compounds in real-world settings.
American Journal of Psychiatry
May 7, 2025
Matthew B. Wall, Lysia Demetriou, Bruna Giribaldi et al.
16 citations
Psilocybin therapy greatly improved depressive symptoms but had only a small effect on how the brain responds to emotional stimuli. This contrasts with SSRIs, which often reduce emotional responsiveness alongside their antidepressant action. The findings suggest that psychedelic therapy may work through different neural mechanisms than conventional antidepressants.
Journal of psychopharmacology (Oxford, England)
October 1, 2024
Valerie Bonnelle, Amanda Feilding, Fernando E. Rosas et al.
16 citations
The joint influence of the sympathetic and parasympathetic nervous systems over cardiac activity, known as sympathovagal coactivation, is positively related to ratings of spiritual experience and insightfulness during the DMT-induced peak experience, and also to improved well-being two weeks later. The balance between the two autonomic branches before DMT injection predicted insightfulness scores and subsequent coactivation. These findings demonstrate the autonomic nervous system's involvement in psychedelic-induced peak experiences.
Journal of Psychopharmacology
April 12, 2024
Joseph Peill, Miriam Marguilho, David Erritzøe et al.
16 citations
In a double-blind randomized controlled trial, 59 patients with depression received either a high (25 mg) or placebo (1 mg) dose of psilocybin. Those given the high dose reported stronger perceived 'inner healing' effects, and within that group, higher inner healer scores predicted greater improvement in depressive symptoms two weeks later. The findings suggest that the concept of an intrinsic healing mechanism activated by psychedelics merits further scientific investigation, though the idea remains scientifically nascent.