British Journal of Pharmacology
December 19, 2024
David J Nutt, Peter Hunt, Anne Katrin Schlag et al.
21 citations
In 2023, the Australian Therapeutic Goods Administration (TGA) approved psilocybin for treatment-resistant depression and MDMA for PTSD, effective from 1 July 2023. The approval followed a campaign led by Mind Medicine Australia, Professor David Nutt, Drug Science, and Monash University professors, supported by clinical, academic, and patient groups. Prescribing rights are limited to psychiatrists authorized under the TGA's Authorised Prescriber Scheme. This paper reviews the background of the decision, its implications for approvals in other jurisdictions, and development pathways for other psychedelic drugs.
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.
J Psychopharmacol
December 13, 2021
Ben Sessa, Jacob S Aday, Steve O’Brien et al.
18 citations
An open-label study of 14 participants found that mood remained positive during the week after receiving MDMA in a clinical setting, contrary to the 'Blue Monday' crash reported by recreational users. Self-reported sleep quality improved at 3- and 6-month follow-ups compared to baseline. No participants used or desired to use illicit MDMA, and anecdotal reports were favorable. The findings suggest that negative after-effects previously associated with MDMA may stem from confounds such as illicit drug sourcing and recreational settings, rather than the drug itself.
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
November 14, 2022
Meg J Spriggs, Bruna Giribaldi, Taylor Lyons et al.
15 citations
A fixed 25 mg dose of psilocybin produces similar acute psychedelic effects and improvements in well-being regardless of body mass index (BMI). Pooling data from three therapeutic studies, results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes, or emotional breakthroughs. There was weak evidence that lower BMI participants reported greater 'dread of ego dissolution,' but BMI did not meaningfully add to predictions beyond age, sex, and study. Mystical-type experiences and emotional breakthroughs strongly predicted well-being improvements, but BMI did not. These findings suggest body weight-adjusted dosing may be unnecessary, supporting fixed dosing to reduce practical and financial burdens on psychedelic therapy scalability.
National science review
May 1, 2024
Jakub Vohryzek, Joana Cabral, Christopher Timmermann et al.
13 citations
The human brain's activity constantly reorganizes across space and time, and decomposing whole-brain recordings into harmonic modes reveals gradient-like patterns linked to different functions. Using the HADES framework, researchers analyzed brain activity in healthy participants after taking the serotonergic psychedelic DMT. They found significant decreases in contributions across most low-frequency harmonic modes during the DMT state. Specifically, the second functional harmonic, which represents the uni- to transmodal functional hierarchy, decreased, supporting the hypothesis that psychedelics alter this hierarchy. Dynamic measures of fractional occupancy, lifetime, and latent space precisely described the changes in the brain's spacetime hierarchical organization during the psychedelic state.
bioRxiv
August 21, 2023
Jakub Vohryzek, Joana Cabral, Christopher Timmermann et al.
7 citations
preprint
The brain's activity constantly reorganizes across space and time. A new framework called Harmonic Decomposition of Spacetime (HADES) was developed to track how spatial activity patterns (harmonic modes) change over time. As a proof-of-principle, HADES was applied to brain recordings from healthy participants under the psychedelic DMT and in a normal state. DMT significantly decreased contributions from most low-frequency harmonic modes. After normalizing by condition, a specific decrease appeared in the second functional harmonic, which represents the brain's hierarchy from unimodal to transmodal regions, supporting the hypothesis that psychedelics alter this functional hierarchy. Dynamic measures of fractional occupancy, lifetime, and latent space precisely described changes in the spacetime hierarchical organization of brain activity during the psychedelic state.
Elife
November 9, 2020
Andrea Alamia, Christopher Timmermann, David J Nutt et al.
7 citations
correction
No Summary
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.
Alcohol and alcoholism (Oxford, Oxfordshire)
May 14, 2025
Hannah Thurgur, Ben Sessa, Laurie Higbed et al.
3 citations
In an open-label feasibility study, 14 adults with alcohol use disorder who had recently completed detoxification underwent an eight-week course of ten psychotherapy sessions, including two sessions with MDMA. Bayesian analysis estimated a 55%–63% probability of a two-level reduction in World Health Organization drinking risk three months after treatment. Preliminary findings also indicated reductions in alcohol craving and improvements in sleep and aspects of psychosocial functioning at the three-month follow-up compared to baseline. The results provide initial insights into MDMA-assisted psychotherapy's potential to improve quality of life and well-being beyond reducing drinking.
Neurosci Insights
October 8, 2024
Matthew B Wall, Rebecca Harding, Natalie Ertl et al.
3 citations
Psychedelic therapies are new psychiatric treatments that may need to be combined with existing medications, but little is known about their interactions with common psychiatric drugs. This commentary reviews key findings on such drug-drug interactions and proposes that multimodal neuroimaging, combining PET and fMRI with other measures, offers the most thorough way to study these interactions across molecular, functional, and clinical levels.
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
February 8, 2025
Natalie Ertl, Imran Ashraf, Lisa Azizi et al.
1 citation
preprint
LSD and MDMA, two psychoactive drugs being explored for psychiatric use, alter how the striatum—a brain region central to reward and motivation—communicates with other areas. In a resting-state fMRI study, neither drug changed connectivity within the striatum's own networks. However, MDMA reduced connectivity between the limbic striatum and the amygdala, while LSD increased connectivity between the associative striatum and frontal, sensorimotor, and visual cortices. These changes occurred mostly outside standard striatal networks, suggesting the drugs reduce the brain's usual network segregation, which may help explain their therapeutic potential for conditions like addiction, mood disorders, and PTSD.
Lancet Psychiatry
September 1, 2016
Robin L Carhart-Harris, David J Nutt
1 citation
No Summary
British journal of clinical pharmacology
May 8, 2026
Ioanna Artemis Vamvakopoulou, Dasha Nicholls, David J Nutt et al.
Rates of mental illness among young people are rising, but few new treatments have emerged. Psychedelic-assisted therapy with psilocybin and MDMA has shown promise for adults with depression, anxiety, and PTSD, and interest is growing in its use for adolescents. A comprehensive review of all research on children and young people—from 1950s experiments to recent observational and retrospective studies of traditional and non-medical use—finds that psychedelics appear safe overall and may improve mental wellbeing in this age group. However, young people may face greater risks of anxiety, challenging experiences, and ego dissolution, warranting more thorough clinical research. The authors recommend a rigorous ethical framework with family involvement and consideration of lower doses to reduce potential harms.
May 4, 2026
Victoria Burmester, Laura Aggett, David J Nutt et al.
preprint
MDMA reliably enhances subjective social feelings such as sociability, emotional openness, closeness, and emotional empathy, but these changes do not consistently translate into observable prosocial behaviors like cooperation or trust, which remain highly context dependent. The most robust social effect is a reduction in the processing of social threat, including diminished sensitivity to negative social cues and impaired recognition of fear and anger. This divergence between felt and enacted social effects helps explain variability in laboratory findings and underscores the importance of context and measurement. These mechanisms may inform MDMA's therapeutic use for conditions involving heightened social threat and avoidance.
BMJ
February 3, 2026
Adam Winstock, David J Nutt, Caroline Copeland
Reclassifying ketamine without accompanying public health measures would be a symbolic action rather than an effective strategy for reducing harm, according to the authors. They argue that regulatory changes alone are insufficient and must be paired with broader public health interventions to meaningfully address risks associated with ketamine use.