Neuropsychologia
April 5, 2016
Devin B. Terhune, David P. Luke, Mendel Kaelen et al.
45 citations
Lysergic acid diethylamide (LSD) induces synaesthesia-like experiences in non-synaesthetes, but these experiences do not meet two key criteria for genuine synaesthesia: consistency of stimulus-colour associations over time and inducer specificity. In a placebo-controlled pilot study, participants reported more spontaneous synaesthesia-like experiences under LSD compared to placebo, yet their colour responses to standardized graphemes and sounds did not differ across conditions in consistency or specificity. Individual differences in absorption propensity were linked to some effects. The findings suggest that LSD-induced synaesthesia-like experiences are not equivalent to genuine synaesthesia.
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.
Psychopharmacology (Berl)
November 4, 2021
Joanna Kuć, Hannes Kettner, Fernando Rosas et al.
37 citations
People who use cannabis at the same time as a classic psychedelic report more intense subjective effects, with higher cannabis doses linked to stronger mystical, visual, and ego-dissolution experiences. The relationship between cannabis dose and challenging experiences followed a U-shaped pattern, while emotional breakthrough showed no connection to cannabis dose. The findings suggest an interaction between cannabis and psychedelics, but the study's design cannot establish cause or clinical implications.
J Psychopharmacol
June 15, 2020
Anna Borissova, Bart Ferguson, Matthew B Wall et al.
37 citations
MDMA did not increase prosocial behavior in a controlled laboratory setting, despite raising blood levels of the drug and self-reported feelings of closeness and euphoria. In a double-blind, placebo-controlled experiment with 20 healthy volunteers, MDMA (100 mg) failed to significantly change task-based measures of empathy, trust, or cooperative behavior compared to placebo. Bayesian analyses supported the conclusion that MDMA and placebo had equivalent effects on empathy and cooperation. The drug also did not alter mood three days after administration. These findings suggest that the acute prosocial effects of MDMA observed in naturalistic or therapeutic contexts may not replicate under controlled experimental conditions.
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.
Conscious Cogn
December 8, 2020
Camila Sanz, Carla Pallavicini, Facundo Carrillo et al.
34 citations
Language produced under the influence of LSD shows increased entropy and reduced semantic coherence, consistent with a state of heightened neural entropy. Non-semantic analysis of speech organization revealed increased verbosity and a reduced lexicon, changes more similar to manic psychoses than to schizophrenia, as confirmed by direct comparison with reference samples. Features related to language organization allowed machine learning classifiers to identify speech under LSD with accuracy comparable to that obtained by examining semantic content. These results provide a quantitative characterization of disorganized natural speech as a landmark feature of the psychedelic state.
Sci Rep
July 26, 2023
Balázs Szigeti, David Nutt, Robin Carhart-Harris et al.
33 citations
Blinding in medical trials aims to evenly distribute expectancy effects between treatment groups, but it often fails. Using computational modeling, this work shows that weak blinding combined with positive treatment expectancy creates an 'activated expectancy bias' (AEB), which can inflate treatment effect estimates and produce false positive results. The authors introduce the Correct Guess Rate Curve (CGRC) to estimate outcomes of a perfectly blinded trial from imperfectly blinded data. Re-analyzing a self-blinding psychedelic microdose trial dataset, they find that observed placebo-microdose differences are susceptible to AEB and may be false positives, suggesting microdosing acts as an active placebo. The findings highlight the distinction between trials with a placebo control group and genuinely placebo-controlled trials.
J Affect Disord
February 27, 2024
Debora Copa, David Erritzøe, Bruna Giribaldi et al.
31 citations
Brain connectivity patterns measured before psilocybin treatment can predict how much depression symptoms will improve. In people with treatment-resistant depression given two doses of psilocybin (25 mg each, one week apart), baseline resting-state functional MRI scans showed that connectivity within visual, default mode, and executive networks predicted early symptom improvement, while salience network connectivity predicted who would respond up to 24 weeks later, with about 90% accuracy. Similar patterns appeared in a separate trial comparing psilocybin to escitalopram. Fronto-occipital and fronto-temporal connections predicted early and late symptom reduction, respectively. Small sample sizes and differences between datasets limit generalizability, and the lack of a placebo arm limits specificity.
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.
Psychological Medicine
April 28, 2020
Claire Mokrysz, Natacha D. C. Shaban, Tom P. Freeman et al.
24 citations
Inhaling cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may raise the incidence of speech illusion—hearing words in meaningless white noise. Cannabidiol (CBD) did not blunt these effects. In one study, adults had stronger psychotic-like symptom responses than adolescents, suggesting adolescents may be less vulnerable to the acute psychotic-like effects of cannabis. The odds of experiencing speech illusion were 3.1 times higher after inhaling cannabis with THC and negligible CBD compared to placebo.
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.
Naunyn Schmiedebergs Arch Pharmacol
September 20, 2016
Jakob A. Shimshoni, Ilan Winkler, Ezekiel Golan et al.
23 citations
Four MDMA analogues—three benzofuran compounds (5-APB, 6-MAPB, 5-MAPB) and one indole compound (5-IT)—were screened as potential second-generation drugs for PTSD. All analogues showed high binding affinities for serotonin 5-HT2a,b,c and norepinephrine α2 receptors, and significantly inhibited serotonin, dopamine, and norepinephrine uptake. 5-APB acted as an agonist at all three 5-HT2 receptor subtypes, while 6-MAPB, 5-MAPB, and 5-IT were agonists at the 5-HT2c receptor. The analogues also emerged as potent and selective inhibitors of monoamine oxidase A. 6-MAPB, with a favorable pharmacological profile, was further tested for its potency at monoamine transporters. Overall, the analogues displayed higher binding affinities and greater agonist activity at 5-HT2a,c receptors compared to MDMA.
Journal of Psychopharmacology
May 20, 2022
Matthew B. Wall, Tom P. Freeman, Chandni Hindocha et al.
21 citations
THC strongly disrupts connectivity between the striatum and cortex, but co-administering CBD mitigates this effect in the limbic striatum network. In one study, inhaled cannabis with 8 mg THC or 8 mg THC plus 10 mg CBD disrupted associative and sensorimotor networks, while THC alone also disrupted the limbic striatum network. In a second study, oral 600 mg CBD increased connectivity in the associative network and caused minor disruptions in limbic and sensorimotor networks. The insula emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with implications for understanding cannabis-related disorders and developing cannabinoid therapeutics.
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.
J Psychopharmacol
December 1, 2016
David Nutt
19 citations
Psilocybin therapy shows promise for alleviating anxiety and depression in cancer patients, drawing on lessons from past research to guide future applications. The text reviews historical studies and outlines prospects for integrating psilocybin-assisted psychotherapy into cancer care, suggesting it may provide significant mental health relief. It emphasizes the need for careful clinical implementation and further investigation to confirm efficacy and safety.
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.
Psychopharmacology (Berl)
February 1, 2018
H. Valerie Curran, David Nutt, Harriet de Wit
17 citations
Psychedelics and related drugs show therapeutic possibilities for mental health conditions, with research exploring their mechanisms, including brain modulation and neuroplasticity. The work discusses how these compounds may alter brain pathways and states of consciousness to produce therapeutic benefits. It also addresses the regulatory landscape for these substances in medical research and mental healthcare. The authors suggest that understanding the neurobiology and therapeutic mechanisms is crucial for advancing treatment research and medical innovation.
Psychedelic Medicine
October 28, 2022
Bruna Giribaldi, Sandeep M. Nayak, Bilal A. Bari et al.
15 citations
A Bayesian reanalysis of a trial comparing psilocybin (25 mg) to escitalopram (20 mg) over 6 weeks in 59 patients with major depressive disorder found that psilocybin outperformed escitalopram on three of four depression scales, though evidence was not uniformly clinically meaningful. Using skeptical priors that bias results toward zero, the analysis showed strong to extremely strong evidence favoring psilocybin on the BDI-1A, MADRS, and HAMD-17, while evidence on the primary outcome (QIDS SR-16) was indeterminate. For clinically meaningful superiority, evidence was moderate against it for the QIDS SR-16 but moderate to strong for the MADRS and HAMD-17. Psilocybin showed extremely strong evidence of noninferiority to escitalopram across all scales. The findings support further research on psilocybin's relative efficacy.