Network Neuroscience
November 1, 2023
Juan Carlos Farah, Pablo Mallaroni, Enrico Amico et al.
21 citations
Functional connectomes become more idiosyncratic under psilocybin, with greater dissimilarity between individuals than under placebo. While idiosyncratic features in placebo subjects appear mainly in the frontoparietal network, under psilocybin they concentrate in the default mode network (DMN). A DMN-focused pattern predicts subjective psilocybin experience, marked by reduced within-DMN and DMN-limbic connectivity and increased connectivity between the DMN and attentional systems. These findings link psilocybin's brain effects to subjective experience and demonstrate the value of brain-fingerprinting in pharmacological neuroimaging.
Frontiers in Pharmacology
July 6, 2018
Elizabeth B. de Sousa Fernandes Perna, Eef L. Theunissen, Patrick C. Dolder et al.
18 citations
A single 100 mg dose of 4-fluoroamphetamine (4-FA), a phenethylamine novel psychoactive substance, produced strong elevation in blood pressure for 4-5 hours followed by sustained increased heart rate in healthy volunteers. Effects on mood and neurocognitive function peaked at 1 hour, including significant elevations of vigor, friendliness, elation, arousal, and positive mood, along with improvements in attention and motor performance. Negative affect also increased during the acute and subacute phases. The 150 mg dose was canceled after an interim safety review. The findings confirm clinical observations of acute toxicity and warrant warnings about health risks.
Neuroscience & Biobehavioral Reviews
February 3, 2024
Ivana Solaja, Kate Haldane, Natasha L. Mason et al.
17 citations
A systematic review and meta-analysis of ten controlled studies involving 304 participants found no lasting changes in cognition, creativity, emotional processing, or personality from serotonergic psychedelics for most measures. However, faster reaction times were observed for recognizing disgust and sadness in active treatment groups. The authors call for larger samples and standardized methods to confirm these preliminary findings.
Journal of Psychedelic Studies
August 26, 2021
Kim van Oorsouw, Malin V. Uthaug, Natasha L. Mason et al.
16 citations
A single ayahuasca ceremony reduced self-reported stress, anxiety, and somatization, and increased non-judging awareness four weeks later in 73 ceremony attendants. Satisfaction with life and awareness improved the day after the ceremony but returned to baseline after four weeks. No reduction in depression was found, contrary to earlier work. The intensity of ego dissolution during the ceremony predicted sub-acute mental health improvements. Effects were similar for first-time and experienced users. The authors call for placebo-controlled trials to confirm ayahuasca's therapeutic potential.
European Neuropsychopharmacology
February 25, 2021
Natasha L. Mason, Kim P. C. Kuypers, Johannes T. Reckweg et al.
16 citations
No Summary
Journal of Psychedelic Studies
December 15, 2021
Malin V. Uthaug, Natasha L. Mason, Martha N. Havenith et al.
15 citations
A naturalistic observational study of 58 Czech-speaking adults found that a single session of Holotropic Breathwork (a breathing technique intended to produce altered states of consciousness) was associated with lasting improvements in non-judgment, satisfaction with life, and reductions in stress-related symptoms. Although participants reported only low levels of psychedelic-like experience (averaging 0–34% on a 100% scale), the increase in non-judgment appeared sub-acutely and persisted for four weeks. Satisfaction with life increased and stress symptoms decreased at the four-week follow-up.
Drug Science Policy and Law
January 1, 2020
Natasha L. Mason, Patrick C. Dolder, Kim P. C. Kuypers
15 citations
Psychedelics like LSD and psilocybin are most often used at home, while MDMA is more common at parties or festivals. Most people take these substances when already in a positive mood, and their mood stays positive or shifts to positive afterward. Individuals with low psychological well-being are more likely to experience a positive mood change after using LSD, psilocybin, or MDMA compared to those with normal well-being. Higher neuroticism scores are linked to both a greater likelihood of positive mood change and a greater likelihood of negative side effects. The findings suggest that psychedelic use can yield positive outcomes even in people with lower well-being and higher neuroticism.
Biomedicine & Pharmacotherapy
March 24, 2022
Francisco Madrid-Gambin, Àlex Gomez‐gómez, Arnau Busquets-García et al.
14 citations
Consumption of ayahuasca increases N-acyl-ethanolamine endocannabinoids, decreases 2-acyl-glycerol endocannabinoids, and alters several large-neutral amino acids (LNAAs) in human plasma. Most LNAAs were inversely associated with nine of eleven subscales of the 5-Dimension Altered States of Consciousness Rating Scale, except tryptophan, which was positively associated. Several endocannabinoids and hexosylceramides were directly associated with ayahuasca alkaloids. Enrichment analysis confirmed dysregulation in pathways involved in serotonin and dopamine synthesis. A crosstalk between circulating LNAAs and subjective effects is suggested, independent of alkaloid concentrations, providing insights into the metabolic fingerprint and mechanism of action underlying ayahuasca experiences.
June 10, 2021
Drummond E-Wen Mcculloch, Gitte M. Knudsen, Frederick S. Barrett et al.
14 citations
preprint
Research into psychedelic drugs like psilocybin, LSD, and DMT is growing, with clinical trials showing promise for psychiatric conditions. Resting-state fMRI is a common method to study brain mechanisms in these contexts. A review of 42 articles from 17 datasets found high heterogeneity in methods and analyses; two datasets underlie over half the publications, and terms like "entropy" are used inconsistently. The authors suggest that the field needs greater methodological consistency and replicability to identify stable neural markers of psychedelic effects, and encourage development of new models and quantification methods.
Psychopharmacology
May 31, 2018
Kim P. C. Kuypers, E. B. de Sousa Fernandes Perna, Patrick C. Dolder et al.
14 citations
A single 100 mg dose of the new psychoactive substance 4-fluoroamphetamine (4-FA) increased self-reported drug liking, wanting, and good drug effect one hour after administration in 12 healthy poly-drug users, but these effects were absent 11 hours later. Impulsive behavior was not affected by 4-FA. The increase in liking and wanting suggests a potential for abuse, but the lack of effect on impulsivity and the small sample size limit the conclusions.
International Journal of Environmental Research and Public Health
July 21, 2023
Guido Huisman, Maximilian Menke, Oliver Grundmann et al.
13 citations
Kratom, a Southeast Asian plant containing alkaloids that affect humans, is sold online in strains marketed as having distinct effects. A survey of 644 current kratom users compared self-reported effects of red, green, and white strains. Respondents reported distinct subjective experiences matching marketing claims, but independent laboratory analysis of the products found no significant differences in alkaloid content across strains. This suggests marketing narratives and anecdotal reports may disproportionately influence perceived effects. Future work should include more diverse populations and vendors, and blinded experiments could determine whether reported differences stem from placebo or other factors like minor alkaloids or terpenes.
Journal of Psychoactive Drugs
January 24, 2019
Kim P. C. Kuypers, E. B. de Sousa Fernandes Perna, Eef L. Theunissen et al.
13 citations
4-Fluoroamphetamine (4-FA), a novel psychoactive substance with a chemical structure similar to amphetamine and MDMA, induces a mild psychedelic state. In a placebo-controlled crossover study of 12 healthy poly-drug users, the psychedelic state peaked one hour after administration, coinciding with highest serum concentrations, and declined over time as concentrations fell. No change in creative (flexible) thinking occurred. The intensity of the 4-FA-induced psychedelic state falls between that produced by amphetamine and MDMA, consistent with user reports. More research is needed to determine whether 4-FA can alter creative thinking.
Nature Medicine
April 1, 2026
Manesh Girn, Manoj K. Doss, Leor Roseman et al.
8 citations
Psychedelic drugs are being studied again for their therapeutic potential, but how they change brain function is not well understood. By combining 11 brain-scanning datasets from five different psychedelics (psilocybin, LSD, mescaline, DMT, and ayahuasca) across three continents, researchers found a common pattern: increased communication between brain networks that handle high-level thinking (default, frontoparietal, and limbic) and those that handle sensory input (visual and somatomotor). Key deep-brain regions (thalamus, caudate, putamen) and the cerebellum also changed how they connect with sensorimotor networks. Contrary to some earlier studies, reductions in within-network connectivity were weak to moderate and varied by drug. These findings help resolve previous inconsistencies and provide a comprehensive map of how psychedelics alter large-scale brain organization.
Frontiers in Neuroscience
October 5, 2023
Pablo Mallaroni, Lilian Kloft, Natasha L. Mason et al.
8 citations
Repeated ayahuasca use is associated with a spatially distributed pattern of brain structural changes: sensorimotor areas become more distinct from surrounding regions while transmodal areas become less distinct. These changes correlate with the expression of genes for 5-HT2A receptors and other targets of ayahuasca, as well as with genes for transcription factors and immediate early genes previously linked to psychedelic-induced neuroplasticity in animal studies. The findings suggest that molecular mechanisms of psychedelic action may scale up to large-scale brain organization in living humans, potentially helping to explain behavioral differences in experienced users.
bioRxiv (Cold Spring Harbor Laboratory)
September 18, 2023
Sepehr Mortaheb, Larry D. Fort, Natasha L. Mason et al.
7 citations
preprint
Psilocybin increases functional connectivity across the brain and induces a recurrent hyperconnected pattern with low BOLD signal amplitude, suggesting heightened cortical arousal. These brain dynamics are linked to feelings of oceanic boundlessness and visionary restructuralization, as measured by the 5-Dimensional Altered States of Consciousness Rating Scale. The brain's tendency to enter this hyperconnected-hyperarousal pattern under psilocybin may enable variant mental associations. For the first time, these findings connect brain dynamics with phenomenological alterations, offering new insights into the neurophenomenology and neurophysiology of the psychedelic state.
Frontiers in Psychiatry
May 19, 2022
Eef L. Theunissen, Kim P. C. Kuypers, Natasha L. Mason et al.
7 citations
At equal levels of subjective intoxication, natural cannabis (THC) and the synthetic cannabinoid JWH-018 both impair psychomotor function, divided attention, and impulse control to a similar degree. Both drugs also produce psychotomimetic effects, but JWH-018 causes considerably more pronounced dissociative effects than THC. The study matched participants from two placebo-controlled experiments by their subjective high to compare the drugs' neurocognitive and psychotomimetic profiles, concluding that psychotropic dose equivalence offers a uniform method for comparing CB1 receptor agonists.
medRxiv
November 1, 2022
Natasha L. Mason, Attila Szabo, Kim P. C. Kuypers et al.
6 citations
preprint
Psilocybin immediately reduced concentrations of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), while other inflammatory markers (interleukin-1α, IL-1β, IL-6, and C-reactive protein) remained unchanged. Seven days later, TNF-α returned to baseline, but IL-6 and CRP were persistently reduced in the psilocybin group. Changes in immune profile were linked to acute neurometabolic activity: reductions in TNF-α were associated with lower hippocampal glutamate concentrations. Greater reductions in IL-6 and CRP at seven days correlated with persisting positive mood and social effects. Psilocybin also blunted the cortisol response to a psychosocial stressor compared to placebo.
Frontiers in Psychiatry
April 14, 2022
Johannes G. Ramaekers, Eef L. Theunissen, Peter van Ruitenbeek et al.
6 citations
Comparing brain function between chronic cannabis users and non-users may be confounded by factors like polydrug use, alcohol, withdrawal, or lifestyle. A proposed methodology uses acute Δ9-tetrahydrocannabinol (THC) dosing studies to directly assess neuroadaptations in chronic users. This approach quantifies neurochemical, receptor, and functional brain network changes in response to an acute cannabis challenge and stratifies users from occasional to dependent. It enables evaluation of THC-induced neuroadaptive and neurocognitive changes across cannabis use history, informing neurobiological models of reward-driven, compulsive cannabis use.
Human Psychopharmacology Clinical and Experimental
October 25, 2018
Patrick C. Dolder, Elizabeth B. de Sousa Fernandes Perna, Natasha L. Mason et al.
6 citations
4-Fluoroamphetamine (4-FA), a novel psychoactive substance with effects between MDMA and amphetamine, reduced cognitive empathy while leaving emotional empathy unaffected in healthy poly-drug users. Plasma oxytocin levels increased one hour after a 100 mg dose compared with placebo, but this hormonal change was unrelated to the behavioral effects on empathy. The findings indicate that 4-FA affects empathy differently from MDMA and amphetamine, and confirm that drug-induced changes in peripheral oxytocin are not associated with empathy.
Psychopharmacology
April 30, 2025
Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason et al.
4 citations
Low to moderate doses of 3-methylmethcathinone (3-MMC) produce prolonged, dose-related analgesic effects in healthy volunteers. In a cross-over, placebo-controlled study with 14 participants, doses of 25, 50, and 100 mg elevated pressure pain threshold and reduced subjective painfulness and unpleasantness in both pressure pain threshold and cold pressor test paradigms. The analgesic effects were most prominent after 50 and 100 mg and persisted for up to 5 hours after dosing. 3-MMC also produced dose-related mood improvements at 1 hour but not at 5 hours. The findings suggest that doses low enough to avoid challenging subjective experiences and associated with a benign side effect profile may be sufficient for analgesia.
bioRxiv (Cold Spring Harbor Laboratory)
October 11, 2022
Pablo Mallaroni, Natasha L. Mason, Lilian Kloft et al.
4 citations
preprint
Brain functional connectomes are unique and reliable identifiers of individuals, but it was unknown whether these 'fingerprints' persist during altered states of consciousness. Ayahuasca, a serotonergic psychedelic, disrupts functional connectivity. In a within-subject study using 7T fMRI, 21 members of the Santo Daime church were scanned after collective ayahuasca intake. Connectome fingerprinting revealed a shared functional space and a spatiotemporal reallocation of key edges. Differences in higher-order functional connectivity motifs predicted perceptual drug effects, showing that individualized connectivity markers can trace a subject's functional connectome across altered states.
bioRxiv (Cold Spring Harbor Laboratory)
July 19, 2019
Natasha L. Mason, Eef L. Theunissen, Nadia R. P. W. Hutten et al.
4 citations
preprint
Regular cannabis users develop tolerance to the drug's impairing and rewarding effects, but the underlying brain changes are unclear. In a double-blind, randomized, placebo-controlled crossover study, 12 occasional and 12 chronic cannabis users received acute doses of cannabis (300 μg/kg THC) and placebo, then underwent ultra-high field fMRI and magnetic resonance spectroscopy. In occasional users, cannabis caused decreased functional connectivity and increased striatal glutamate concentrations in reward circuitry, linked to greater subjective high and worse sustained attention. These changes were absent in chronic users, suggesting reduced responsiveness of reward circuitry to cannabis intoxication and a pharmacodynamic mechanism for tolerance development.
bioRxiv (Cold Spring Harbor Laboratory)
August 19, 2024
Naji Alnagger, Paolo Cardone, Charlotte Martial et al.
3 citations
preprint
Disorders of consciousness, such as unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have few treatments. Using whole-brain computational models built from individual patients' fMRI and diffusion-weighted imaging data, this virtual clinical trial simulated the effects of LSD and psilocybin. The psychedelics shifted the brains of patients with disorders of consciousness closer to a critical dynamical state, with a larger effect in MCS patients. In UWS patients, the treatment response depended on structural connectivity, whereas in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for considering psychedelics in treating disorders of consciousness and highlight the role of computational modeling in drug discovery and personalized medicine.
January 1, 2021
Natasha L. Mason, Kim P. C. Kuypers
3 citations
Psychedelics like psilocybin and ayahuasca show promise in enhancing empathy and reducing anxiety. In a sample of 200 participants, 70% reported improved mood after sessions with these substances. Additionally, cognitive assessments indicated a 30% increase in emotional recognition skills. These findings highlight the potential of psychedelics in clinical psychology, particularly for psychotherapists seeking innovative approaches to treatment. The biochemical influence on neurotransmitter receptors suggests a pathway for understanding how these substances can positively affect behavior and mental health outcomes.
Advanced Science
November 20, 2025
Paolo Cardone, Charlotte Martial, Yonatan Sanz Perl et al.
2 citations
Simulated administration of LSD and psilocybin in computational models of patients with disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), shifted brain activity closer to criticality—the phase transition between order and chaos. The effect was greater in MCS patients. In UWS patients, the treatment response correlated with structural connectivity, while in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for using psychedelics in DoC treatment and highlight the potential role of computational modeling in drug discovery and personalized medicine.