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.
Neuropharmacology
December 27, 2022
Robin Carhart‐Harris, Shamil Chandaria, David Erritzøe et al.
106 citations
A theoretical model proposes that psychopathology arises from a defensive process called canalization, which narrows an individual's range of thoughts, feelings, and behaviors by increasing precision or reducing variance in neural responses. This contrasts with an early form of plasticity, TEMP (Temperature or Entropy Mediated Plasticity), which increases variance and learning rate. Canalization entrenches pathology as the agent develops expertise in their disorder, while TEMP, combined with gentle psychological support, may counter this entrenchment. The model distinguishes adaptive from maladaptive canalization and suggests concrete experiments to test its hypotheses.
Neuropharmacology
October 14, 2022
Ian Campbell, Ioanna A. Vamvakopoulou, Kelly A.d. Narine et al.
97 citations
Mescaline's pharmacological mechanisms resemble those of other classical psychedelics such as psilocybin and LSD. Consumption appears safe, with most intoxications being mild and easily treatable. The substance may offer clinical benefits, including improvements in mental well-being and potential to help overcome alcoholism. This article is part of a special issue on psilocybin research.
Frontiers in Psychiatry
June 12, 2023
Rayyan Zafar, Maxim Siegel, Rebecca Harding et al.
95 citations
Psychedelic therapy is regaining scientific and medical interest, with growing evidence for its safety and efficacy in treating psychiatric disorders, including addiction. This review charts research on these interventions for addiction, starting with the socioeconomic impact of addiction and current treatment options. It examines historical studies from the mid-late 1900s, real-world evidence from naturalistic and survey-based studies, and modern clinical trials from first-in-human to phase II. The review also covers translational neuropsychopharmacology techniques like fMRI and PET that help explain therapeutic mechanisms. A better understanding of these treatment effects can optimize psychedelic therapy development and improve patient outcomes.
Frontiers in Psychiatry
October 20, 2021
Meg J. Spriggs, Hannah Douglass, Rebecca J. Park et al.
78 citations
Anorexia nervosa is a severe psychiatric condition with few approved treatments. This paper describes how individuals with lived experience of anorexia nervosa helped shape a pilot study of psilocybin-assisted therapy through two online focus groups involving eleven people, and presents the protocol for that study at Imperial College London. Twenty female participants aged 21–65 with a body mass index of 15 kg/m² or above will receive three oral doses of psilocybin (up to 25 mg) over six weeks, supported by psychological preparation and integration, with a 12-month remote follow-up.
Psychological medicine
June 1, 2024
Balázs Szigeti, Brandon Weiss, Fernando E Rosas et al.
74 citations
In a double-blind trial comparing escitalopram and COMP360 psilocybin for major depressive disorder, patients held higher expectations for psilocybin than for escitalopram. Higher pre-trial expectancy for escitalopram predicted better outcomes with escitalopram, but expectancy for psilocybin did not predict response to psilocybin. Pre-treatment trait suggestibility was linked to therapeutic response in the psilocybin arm but not the escitalopram arm. These findings suggest that psychedelic therapy may be less influenced by expectancy biases than previously thought, and that highly suggestible individuals may be especially responsive to psilocybin treatment.
Acta Neuropsychiatrica
May 20, 2019
Oskar Hougaard Jefsen, Kristoffer Højgaard, Sofie Laage Christiansen et al.
66 citations
Psilocybin, a serotonin receptor agonist being studied for treatment-resistant depression, showed no antidepressant-like effect in a rat model of depression. In Flinders Sensitive Line rats, which model depression, neither psilocybin nor its active form psilocin reduced immobility time in the forced swim test, a standard measure of antidepressant activity. The drugs also did not alter locomotor activity in an open field test, ruling out stimulant effects. The rats bred to be depression-prone did show more immobility than their control counterparts, confirming the model's validity. The findings suggest that different animal models and behavioral tests may better translate the positive effects of psilocybin observed in humans.
PLoS Biology
January 27, 2015
David Nutt
66 citations
The United Nations drug control conventions from 1960 and 1971, along with later additions, have inadvertently created major restrictions on medical and life sciences research. These conventions need revision to allow neuroscience to advance without hindrance and to support innovation in treatments for brain disorders. In the interim, local changes like the United Kingdom reclassifying cannabis from Schedule 1 to Schedule 2 should be implemented to enable appropriate medical research development.
BJPsych Open
September 1, 2022
Tommaso Barba, Sarah Buehler, Hannes Kettner et al.
57 citations
Psilocybin, but not the antidepressant escitalopram, reduced rumination and thought suppression in people with major depressive disorder six weeks after treatment. In a randomized trial of 59 participants, only those given psilocybin showed significant decreases in both maladaptive coping strategies. Among treatment responders, thought suppression decreased exclusively in psilocybin responders, while rumination decreased in both psilocybin and escitalopram responders. Reductions in rumination and thought suppression correlated with ego dissolution and psychological insight during psilocybin sessions, suggesting distinct therapeutic mechanisms for the two treatments.
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.
Journal of Psychopharmacology
April 15, 2010
Ben Sessa, Amanda Feilding, Robin Carhart‐Harris et al.
53 citations
Up to 2 mg of psilocybin administered as a slow intravenous injection to healthy, hallucinogen-experienced volunteers in a mock-MRI environment produces short-lived but typical drug effects that are psychologically and physiologically well tolerated. The pilot work supports the viability of using functional magnetic resonance imaging to investigate psilocybin's effects on cerebral blood flow and activity.
EClinicalMedicine
September 23, 2024
David Erritzoe, Tommaso Barba, Kyle T Greenway et al.
46 citations
In a clinical trial, psilocybin therapy showed comparable effectiveness to a common SSRI antidepressant for treating depression, with both treatments leading to significant reductions in depressive symptoms over a follow-up period. The findings suggest psilocybin may offer a viable alternative to standard antidepressant medication, though the study's design and sample size limit the strength of conclusions.
Frontiers in Psychology
April 4, 2014
Robin Carhart-Harris, David Nutt
42 citations
A commentary argues that dreaming is not a unique state of consciousness but rather a form of imaginative experience that shares core features with waking imagination. The author contends that dreams and waking fantasies are both products of the same cognitive processes, specifically the default mode network and memory consolidation mechanisms. The piece suggests that the vividness and narrative structure of dreams arise from the same neural dynamics that generate daydreams and creative thought, challenging the traditional view of dreaming as a separate or altered state of consciousness.
Current Opinion in Behavioral Sciences
November 15, 2016
Celia J. A. Morgan, Amy Mcandrew, Tobias Stevens et al.
41 citations
No Summary
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 1, 2007
Ben Sessa, David Nutt
39 citations
MDMA, originally used as a clinical tool in couples therapy on the West Coast of America after LSD was banned, leaked into recreational use and was prohibited in the mid-1980s. Despite its growing recreational use in rave and party scenes, medical research on MDMA stopped, and the drug became demonized by politicians. Doctors and pharmacologists debated its short-, medium-, and long-term dangers, while its therapeutic potential was forgotten. The paper argues that political restrictions, such as MDMA's classification as a class A schedule 1 drug in the UK, severely limit human research and threaten scientific objectivity and evidence-based clinical excellence. It calls for exploring MDMA's potential medical and research uses without political influence.
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.
The British journal of psychiatry : the journal of mental science
January 1, 2015
Ben Sessa, David Nutt
36 citations
MDMA has been recognized for its therapeutic potential since its first use, but research halted when it became a recreational drug. Over the past decade, studies have slowly resumed, and there is now enough evidence to reclassify MDMA from Schedule 1 ('no medical use') to Schedule 2, alongside other misused but medically useful drugs like heroin and amphetamine. This regulatory change would allow its use as a medicine for patients with severe mental illnesses, such as treatment-resistant post-traumatic stress disorder.
Network Neuroscience
January 1, 2022
Josephine Cruzat, Yonatan Sanz Perl, Anira Escrichs et al.
28 citations
Psychedelic drugs like LSD and psilocybin may treat neuropsychiatric disorders by dose-dependently altering the brain's functional hierarchy—the organization of neural activity across regions. Using a turbulence framework that measures local synchronization (vorticity) in both space and time, researchers found that both drugs produce consistent and distinct effects, particularly compressing the default mode network, a higher-level network. These findings support the hypothesis that psychedelics modulate the functional hierarchy and provide a quantitative comparison of how LSD and psilocybin change brain dynamics, with implications for therapeutic use.
Journal of Psychopharmacology
March 22, 2024
Tommaso Barba, David Erritzøe, Meg J. Spriggs et al.
26 citations
In a clinical trial comparing psilocybin plus psychological support to escitalopram plus psychological support for major depressive disorder, patients who discontinued their SSRI or SNRI medication before receiving psilocybin showed a reduced treatment effect on all depression severity and well-being measures compared with those who were unmedicated at trial entry. Discontinuation did not affect the intensity of the acute psychedelic experience. The findings are exploratory and hypothesis-generating, not confirmatory, and the study did not test SSRI/SNRI continuation. A controlled trial comparing discontinuation versus continuation before psilocybin is needed.
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.
Neuroethics
November 6, 2023
Edward Jacobs, Ashleigh Murphy-Beiner, Ian Rouiller et al.
23 citations
In psychedelic clinical trials, the case for providing patients with continued access to the investigational drug after the trial ends is especially strong due to the drugs' broader legal status, the unique therapist-participant relationship, and the extended therapeutic process. Because the therapy's effectiveness relies heavily on non-drug factors and the cultural setting, the authors argue for expanding post-trial care beyond just drug access. They outline potential provisions and contend that viewing post-trial care as an integral part of research—and a proper use of funding—will help build the infrastructure needed for a future psychedelic medicine system after legalization.
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.
The British Journal of Psychiatry
May 20, 2024
David Nutt, Ilana Crome, Allan H Young
18 citations
Australia has reclassified psilocybin and MDMA from prohibited substances to prescription medicines for treatment-resistant depression and post-traumatic stress disorder, respectively. The feature examines the rationale behind these regulatory changes, the potential benefits and difficulties they present to psychiatric practice, and how mental health professionals and healthcare systems can adapt to integrate these treatments.
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.