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.
Psychological Medicine
February 5, 2016
Robin Carhart‐Harris, Mendel Kaelen, Mark Bolstridge et al.
301 citations
A single intravenous dose of LSD (75 µg) in 20 healthy volunteers produced robust acute psychological effects, including heightened mood and elevated scores on a measure of psychosis-like symptoms. Two weeks later, participants showed increased optimism and trait openness compared to after placebo, with no changes in delusional thinking. The findings suggest that psychedelics can acutely induce psychosis-like symptoms yet improve psychological wellbeing in the mid to long term. The authors propose that acute mood changes stem from a more fundamental modulation of cognition, and that increased cognitive flexibility from serotonin 2A receptor stimulation promotes emotional lability during intoxication and leaves a lasting loosened cognition conducive to improved wellbeing.
Psychopharmacology
February 1, 2018
Mendel Kaelen, Bruna Giribaldi, Jordan Raine et al.
274 citations
Music plays a central therapeutic role in psychedelic therapy with psilocybin for treatment-resistant depression. In interviews with 19 patients, music had both welcome influences—evoking meaningful emotion, mental imagery, guidance, openness, calm, and safety—and unwelcome influences, such as unpleasant emotion, imagery, and resistance. Patients' experience of the music correlated with mystical experiences and insightfulness. Critically, the nature of the music experience significantly predicted reductions in depression one week after psilocybin, whereas general drug intensity did not.
Acta Psychiatrica Scandinavica
June 19, 2018
David Erritzøe, Leor Roseman, Matthew M. Nour et al.
268 citations
In patients with treatment-resistant depression, psilocybin therapy was associated with a decrease in neuroticism and increases in extraversion and openness three months later. These personality shifts moved toward normative population averages and were predicted by the degree of insight experienced during the psilocybin session. Conscientiousness showed trend-level increases, while agreeableness did not change. The pattern partly resembles changes seen with conventional antidepressants, but the pronounced rises in extraversion and openness may be more specific to psychedelic therapy.
Psychopharmacology
August 8, 2022
Rosalind Watts, Hannes Kettner, Dana Geerts et al.
159 citations
A new scale, the Watts Connectedness Scale (WCS), measures a three-dimensional sense of connectedness to self, others, and the wider world. Analysis of data from 1,226 participants in online surveys and a randomized controlled trial of 52 people with major depressive disorder showed the scale has good internal consistency and construct validity. After psychedelic use, total connectedness scores increased significantly, and acute experiences of mystical experience, emotional breakthrough, and communitas correlated with these changes. In the trial, psilocybin-assisted therapy produced greater increases in WCS scores than daily escitalopram. The WCS may sensitively capture therapeutically relevant psychological changes.
Journal of Psychopharmacology
January 1, 2016
Jana Speth, Clemens Speth, Mendel Kaelen et al.
119 citations
A single dose of LSD (75 μg) reduced how often people spontaneously thought about the past, while thoughts about the present or future remained unchanged. In a placebo-controlled crossover study with 20 healthy volunteers, fewer references to past mental spaces appeared in reports collected about 2.5 hours after intravenous administration. This reduction correlated with the drug's subjective intensity and with decreased resting-state functional connectivity within the default-mode network, a brain system involved in autobiographical memory and rumination. The findings suggest LSD may reduce past-focused thinking, which could be relevant for treating conditions like depression where excessive reflection on the past is common.
The International Journal of Neuropsychopharmacology
December 17, 2013
Robin Carhart‐Harris, Matthew B. Wall, David Erritzøe et al.
110 citations
MDMA (ecstasy) makes recalling favorite autobiographical memories feel more vivid, emotionally intense, and positive, while making recall of worst memories feel less negative. In a double-blind, placebo-controlled fMRI study with 19 participants who had prior MDMA experience, 100 mg of MDMA altered brain activity during memory recall: it increased activation in the fusiform gyrus and somatosensory cortex for favorite memories and decreased activation in the left anterior temporal cortex for worst memories. These neural changes suggest MDMA creates a positive emotional bias, which may explain why it helps patients revisit traumatic memories during psychotherapy for PTSD.
Frontiers in Psychiatry
June 29, 2021
Keri Mans, Hannes Kettner, David Erritzøe et al.
65 citations
Psychedelic substances like LSD and psilocybin have regained legitimacy in clinical research. In this naturalistic observational study of volunteers intending to take a psychedelic, well-being was assessed using fourteen measures at four time points: 1 week before and 2 weeks, 4 weeks, and 2 years after the experience (sample sizes 654, 315, 212, and 64, respectively). Changes clustered into three factors: 'Being well,' 'Staying well,' and 'Spirituality.' Repeated measures analysis showed improvements in Being Well and Staying Well in the weeks following the experience, and mixed model analyses indicated these improvements remained statistically significant up to 2 years, despite high attrition. Spirituality did not show significant change.
ACS chemical neuroscience
February 7, 2024
Pedro A M Mediano, Fernando E Rosas, Christopher Timmermann et al.
60 citations
LSD increases brain entropy (neural signal diversity) across all conditions, but the effect is strongest when eyes are closed. Brain entropy changes correlate with subjective psychedelic experience ratings, except when viewing a video, possibly because external stimuli compete with LSD-induced imagery. This shows context modulates neural dynamics during psychedelic experiences, highlighting the importance of environment in psychedelic psychotherapy.
Language Cognition and Neuroscience
August 11, 2016
Neiloufar Family, David Vinson, Gabriella Vigliocco et al.
53 citations
LSD alters cognition by expanding the breadth of semantic activation. In a picture-naming task with ten participants, LSD reduced accuracy and altered error correction patterns compared to placebo, consistent with an increased spread of semantic activation. These effects align with a generalized entropic effect on the mind. The authors recommend future studies include direct neuroimaging and more naturalistic measures of semantic processing.
bioRxiv (Cold Spring Harbor Laboratory)
November 2, 2020
Pedro A. M. Mediano, Fernando E. Rosas, Christopher Timmermann et al.
39 citations
preprint
Psychedelics reliably increase brain entropy (neural signal diversity), an effect linked to psychological changes and opposite to the decrease seen during loss of consciousness. This study investigated how context—specifically stimulus manipulation—modulates that entropy increase. Participants under LSD or placebo experienced eyes-closed versus eyes-open conditions, or no stimulus, music, or video. Brain entropy rose with LSD across all conditions but was largest with eyes closed. Entropy changes consistently matched subjective ratings of the psychedelic experience, except during video viewing, suggesting competition between external stimuli and internal LSD-induced imagery. The findings provide quantitative evidence that context shapes neural dynamics during psychedelic experiences, supporting the practice of eyes-closed psychedelic psychotherapy, and challenge simplistic views of brain entropy as a direct measure of conscious level.
Journal of Psychopharmacology
November 26, 2022
Melissa Shukuroglou, Leor Roseman, David Nutt et al.
38 citations
Listening to music after psilocybin therapy for treatment-resistant depression increases the pleasure people feel from music, and this increase correlates with a reduction in anhedonia (loss of pleasure). Nineteen patients received a low dose (10 mg) and then a high dose (25 mg) of psilocybin one week apart. Functional MRI scans before and after treatment showed that during music listening, functional connectivity between the nucleus accumbens (a brain reward region) and areas resembling the default mode network decreased after treatment. The findings suggest psilocybin therapy enhances music-evoked pleasure and point to a possible brain mechanism involving reduced connectivity in the default mode network.
JAMA Network Open
December 5, 2024
Anthony L Back, Timara K Freeman-Young, Ladybird Morgan et al.
37 citations
A double-blind randomized trial tested psilocybin therapy against niacin in 30 US clinicians (physicians, advanced practice practitioners, and nurses) who developed depression, burnout, or PTSD from frontline COVID-19 pandemic work. Participants had no prepandemic mental health diagnoses but had moderate or severe depression at enrollment. After one medication session, depression symptoms (measured by the Montgomery-Asberg Depression Rating Scale) improved significantly more with psilocybin (mean decrease of 21.33 points) than with niacin (mean decrease of 9.33 points), a difference of 12.00 points. Burnout and PTSD symptoms showed numerically larger improvements with psilocybin, but these differences were not statistically significant. The findings suggest psilocybin therapy can reduce depression in this postpandemic condition.
Journal of affective disorders
July 15, 2023
Matthew B Wall, Cynthia Lam, Natalie Ertl et al.
36 citations
Psilocybin-assisted therapy for depression alters the brain's response to music, suggesting an elevated responsiveness to music after treatment that is related to subjective drug effects during dosing. Nineteen patients with treatment-resistant depression underwent two psilocybin dosing sessions. Brain scans before and after treatment showed increased activity in the superior temporal cortex when listening to music, and decreased activity in the medial frontal lobes during rest. These changes in music-related brain activity correlated with the intensity of subjective effects felt during the psilocybin sessions. The findings imply that psychedelic therapy may enhance emotional responsiveness to music, which could be relevant for treating depression.
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.
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.
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.
Spiral (Imperial College London)
April 1, 2017
Mendel Kaelen
10 citations
Psychedelics intensify music-evoked emotions, including wonder and transcendence, and alter brain activity. Under LSD, increased activation in the inferior frontal gyrus and precuneus correlates with heightened wonder. LSD and music together enhance information flow from the parahippocampus to the visual cortex, linked to complex mental imagery and autobiographical memories. In patients with depression, music quality during psilocybin therapy predicts peak experiences, insight, and subsequent reductions in depression. These findings support the therapeutic significance of intensified music-experience under psychedelics, though further research is needed to understand underlying brain mechanisms and optimize music use in therapy.
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.
The British Journal of Psychiatry
June 18, 2025
Kyle T Greenway, Nicolas Garel, Lê-Anh L Dinh-Williams et al.
8 citations
In a clinical trial of ketamine combined with psychotherapy for severe treatment-resistant depression, 32 participants received six ketamine infusions with psychological support, either with or without music. Both groups showed large and sustained reductions in depression, anxiety, and suicidality at four weeks, fully maintained at eight-week follow-up. The ketamine experiences were highly emotional and mystical, comparable to those seen with psilocybin. Converging analyses suggested that mystical-like experiences contributed to the immediate and lasting antidepressant effects. Music did not enhance outcomes or psychedelic experiences.
bioRxiv (Cold Spring Harbor Laboratory)
February 15, 2022
Matthew B. Wall, Cynthia Lam, Natalie Ertl et al.
8 citations
preprint
Psychedelic-assisted psychotherapy with psilocybin, which often incorporates music, may enhance the brain's response to emotional stimuli. In nineteen patients with treatment-resistant depression, functional MRI scans taken before and after two psilocybin dosing sessions showed that music listening, compared to resting-state, triggered greater brain activity in the bilateral superior temporal cortex after treatment. The right ventral occipital lobe showed increased activity during the resting-state scan post-treatment. Activity in music-related brain regions correlated with the intensity of subjective effects experienced during dosing. These results suggest psilocybin therapy specifically elevates responsiveness to music, linked to the drug's subjective effects.
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.
Journal of Vision
September 1, 2016
Leor Roseman, Martin I. Sereno, Robert Leech et al.
4 citations
Under LSD, the visual cortex's resting-state functional connectivity (RSFC) becomes more dependent on its intrinsic retinotopic organization, as if the brain were processing actual visual input despite closed eyes. In 10 healthy subjects, RSFC between non-adjacent patches of V1 and V3 that represent congruent parts of the visual field (both horizontal or both vertical meridians) was significantly stronger than connectivity between incongruent patches (horizontal-vertical), compared to placebo. The difference between congruent and incongruent connectivity was greater under LSD (Cohen's d=1.6), suggesting that psychedelic imagery involves transient local retinotopic activation similar to that from visual stimulation.
Sebastian Hübner, Eline Haijen, Mendel Kaelen et al.
2 citations
Younger age, lower educational levels, lower conscientiousness, and higher extraversion predict dropout in web-based prospective studies of psychedelic use. Baseline attitudes toward psychedelics and the intensity of acute challenging experiences do not predict attrition. These demographic and personality predictors align with those found in longitudinal research in other fields, suggesting that concerns about bias from psychedelic advocacy or negative drug experiences may be less problematic than previously thought.
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.