What it is
Neuroscience asks what happens in the brain when a psychedelic acts, and what, if anything, stays changed afterwards. The acute state lasts hours, the post-acute period runs from the next day to a few weeks, and anything beyond that would be a durable change, the hardest thing to show.
A few tools do most of the work. Receptor pharmacology asks which molecular doorways a compound uses, chiefly the serotonin 2A receptor (5-HT2A). Functional magnetic resonance imaging (fMRI) tracks blood-oxygen signals, and "functional connectivity" is how closely signals from two regions rise and fall together. Electroencephalography (EEG) records scalp electrical activity. Plasticity, the growth or strengthening of neuron connections, is watched under a microscope in animals and cells and inferred in people from blood proteins, brain stimulation, or positron emission tomography (PET).
The compounds differ, and so do the results. Psilocybin and DMT are natural products and LSD is semi-synthetic. Each is named where it appears, because a result for one does not carry over to another.
Metanoia's interest is narrow. It studies natural psychedelics for personal growth in healthy adults, so the useful brain question is whether anything measurable differs afterwards in someone who was well to begin with, and whether that tracks a change the person cares about. Almost all of the literature below was built to answer other questions.
What is known
The short version. The first step is well established: classic psychedelics need the 5-HT2A receptor to produce their effects. Across the whole brain, the best-supported signature is more communication between networks that usually stay apart. Evidence for lasting change in healthy adults is thin. One small precision-imaging study in six people found a single connection that stayed altered for about three weeks, but that region was picked in an exploratory screen and the result was not corrected for multiple comparisons. One randomized trial found modest differences the next day and a week later that its own authors treat with caution. Plasticity is well supported in cells and animals and weakly in people, and blood BDNF has not shown a consistent change.
Where the effect starts: the receptor
A 2016 review sets out the consensus. Classic psychedelics act as agonists or partial agonists at 5-HT2A, meaning they switch the receptor on fully or in part, and many of these molecules also bind other receptors, so 5-HT2A being necessary does not make it the whole story [1].
The human evidence comes from blocking experiments. Ketanserin, a drug that blocks 5-HT2A, reduced psilocybin's psychological effects in healthy volunteers in 1998 [2], and in a randomized crossover study of 24 healthy participants it fully blocked the felt effects and the connectivity changes produced by LSD, and the spatial pattern matched where the receptor gene is expressed in the cortex [3]. That result depends on an analysis step that removes the brain-wide average signal. Without it the pattern was different and the match was weak, and the authors call the result very sensitive to this choice. Ketanserin also blocked psilocybin's effects on visual-cortex electrical signals in 15 analysed healthy volunteers [4] and the sense of personal meaning that LSD attaches to ordinary stimuli [5]. These are acute effects only.
The acute state: hours
Early imaging suggested a quieting brain. In 2012, fifteen healthy volunteers had blood flow measured and a separate fifteen had blood-oxygen signals measured after intravenous psilocybin. Only decreases appeared, and the blood-flow drop in medial prefrontal cortex tracked how intense the experience was [6]. All had earlier psychedelic experience, and in the blood-flow group placebo always came first. A 2016 single-blind LSD study, analysing 15 volunteers with earlier experience, linked weaker connectivity between two memory-related regions to ego dissolution, a temporary loosening of the sense of self, but found no link between reduced separation of networks and ego dissolution, although its authors had predicted one [7]. Another paper from the same scans found wider global connectivity in cortical areas overlapping the map of 5-HT2A receptors, keeping 15 of 20 volunteers after strict motion screening [8]. A later study noted that this analysis did not account for the brain-wide average signal [3]. The two papers share one small dataset, so they are not independent confirmations.
That early work fed a popular claim that psychedelics switch off the default mode network (DMN), a set of regions active when attention turns inward, and inspired two theory papers that integrate limited data. The entropic brain hypothesis proposes that psychedelic states raise the diversity of brain activity patterns [9]. REBUS, relaxed beliefs under psychedelics, proposes that 5-HT2A activation loosens the high-level expectations through which the brain interprets the world [10]. The entropic paper rests mainly on one set of intravenous psilocybin scans, 15 people per group, and calls its claims untested hypotheses, and the REBUS authors name a test that would count against the entropic idea, if stimulants raised brain entropy to a similar degree. Neither theory has been shown to be causal.
A 2023 systematic review concluded that DMN connectivity is consistently disrupted in the acute state and that connectivity between networks rises, while saying it was unclear how central the DMN is to any lasting effect. It was not preregistered, most samples were small, many volunteers had taken psychedelics before, only 2 of the 28 papers had 60 or more participants, and several reanalysed the same two small datasets, so the findings are less independent than they look. It found no studies of DMT or mescaline, and one small open-label study, with 10 people, found no significant DMN change a week or three months after psilocybin [11]. A 2026 mega-analysis pooled 11 resting-state fMRI datasets from five countries, about 270 healthy adults who had taken psilocybin, LSD, mescaline, DMT or ayahuasca [12]. The clearest shared pattern was stronger coupling between association networks, including the default and frontoparietal ones, and sensory networks (and, in some analyses, dorsal attention). The thalamus, which earlier reports described as more connected, did not hold up, and reductions inside networks were weak to moderate and often overlapped zero. Ayahuasca contributed 9 people in a study with no placebo and a fixed order, which did not show the shared pattern, and the paper's own counts range from 267 to 281 [12]. A separate 2026 analysis of eight datasets found a mirror image, with psychedelic states raising integration and lowering separation between networks while sleep and propofol sedation did the reverse. But its "psychedelic" group included ketamine and nitrous oxide, its psilocybin dataset had seven people, its authors stress that the result is specific to the measures they chose and that other frameworks find partly shared signatures, and counting weaker connectivity inside networks as part of the pattern is in tension with the mega-analysis [13] [12].
The most detailed single study took the opposite approach to pooling. Seven healthy adults, six analysed, all with at least one earlier psychedelic experience, were scanned about 18 times each, before, during and after a single psilocybin session and a separate session with methylphenidate, a stimulant that matches the physical arousal. Psilocybin changed connectivity more than three times as much as the stimulant. The largest change sat in DMN-linked regions and tracked the intensity of the mystical-type experience across 16 sessions (r² = 0.81, about 81 percent of the variation, from very few people and calculated on the sessions of both drugs pooled together). Doing a simple task partly reduced it. The authors describe the change as desynchronization [14].
The two accounts fit together. In DMN-linked regions the change looked like looser coordination with the rest of the brain, and nothing in these data shows the network going quiet.
After the experience: days to weeks
In the precision study, whole-brain connectivity was close to baseline within one to 21 days. One exception stood out. Connectivity between the anterior hippocampus and the DMN fell slightly for about three weeks after psilocybin and not after the stimulant. This region emerged from an exploratory screen, not a prior choice, and the reported p-value (0.0033) was not corrected for multiple comparisons, as the authors state. The result comes from six people, all with earlier psychedelic experience, and the authors offer a link to plasticity as a hypothesis, not a finding. It had returned to baseline in the four participants retested six to twelve months later, too few to detect a small change [14].
Other post-acute studies are weaker in design. Twelve healthy volunteers in an open-label pilot with no control group, a homogeneous sample with little earlier psychedelic experience, showed less negative affect and a smaller amygdala response to faces one week after psilocybin. At one month negative affect was back at baseline and positive affect was still higher, connectivity counts rose without a distinct network pattern, and an emotion-discrimination task showed no amygdala or anterior cingulate change. With no placebo, expectation cannot be separated from drug [15]. A naturalistic study of 105 people compared a compassion-imagery preparation with attention to breathing before psilocybin. The groups were not randomized, since participants chose among available ceremony dates, which the authors list as a limitation, and 100 of the 105 were scanned afterwards and 93 completed follow-up. Absorption rose in the higher-dose group as a whole, driven by the compassion subgroup, as the breathing group alone showed no change, and decentering rose in both dose groups with no significant difference between the preparations. The lower-dose groups showed only a trend that did not survive correction, and computer models told the preparations apart only in the higher-dose group, modestly. The study was not preregistered, blinding was not checked, the mushroom material was not chemically analysed, and the brain-behaviour correlations were exploratory and uncorrected for multiple comparisons [16]. Its authors call it a hypothesis for confirmation.
One further result comes from patients, so it carries over only cautiously. In two depression trials, the antidepressant response after psilocybin tracked a drop in network modularity. The escitalopram comparison arm showed no such change, but the difference between arms was not significant (p = 0.107), the link in the randomized trial (22 people) used a one-tailed test, which is easier to pass, and the open-label trial's network-specific findings were not reproduced in the randomized one [17].
Plasticity: cells and animals first
Plasticity means structural growth of new spines and branches on neurons or functional strengthening of existing connections. The strongest evidence is structural, and it comes from animals. In cultured neurons and in live animals, not in people, serotonergic psychedelics increased neurite growth, spine formation and synapse function through signalling involving TrkB (the receptor for BDNF), mTOR and 5-HT2A, though BDNF protein itself did not rise significantly in cultured neurons [18]. In mice, a single psilocybin exposure raised the density of dendritic spines by about 7 percent after one day and about 12 percent after a week, an effect clearer in females in one analysis. The "one month" finding is narrower, since about a third of the new spines formed on day 1 were still present on day 34, in a subset of four mice. In a learned-helplessness test, escape failures fell within animals, but the main between-group effect of treatment was not significant (p = 0.09) [19]. A later mouse study tied psilocybin's lasting effect on stress-related behaviour to one class of frontal-cortex pyramidal cell and to 5-HT2A, with a floor effect in one test [20]. A 2021 systematic review that searched only PubMed, up to October 2020, found 20 studies, 16 of them preclinical, and 15 of those reported some change in plasticity measures, while the four clinical studies measured only blood BDNF, with mixed results. The reviewers write that subacute and long-term effects of a single exposure had not been studied, so lasting change rests on few studies, mainly animal and cell work [21]. A companion narrative review, not a systematic one, lists what remains unknown [22].
For human cells, a 2026 study found that DMT made neural stem cells derived from human induced pluripotent stem cells divide up to about 24 percent more in a dish, using two or three of five cell lines per test, and the larger neurospheres seen at day 3 (about 22 percent) were not significant at days 5 and 10 after correction [23].
The mechanism is contested. One group reported that LSD and psilocin bind directly to TrkB, the BDNF receptor, and that plasticity and antidepressant-like behaviour depended on that binding independently of 5-HT2A, which conflicts with earlier work in which ketanserin blocked LSD's growth effects [18], a conflict the authors attribute to non-specific actions of ketanserin [24]. Another found that ketanserin did not block psilocybin's antidepressant-like and synaptic effects in stressed mice, but it used male mice only, looked 24 to 48 hours after a single exposure, used groups of roughly 6 to 13, found no psilocybin effect in a forced-swim test in unstressed mice, and cannot rule out a role for 5-HT2A at later times [25]. A third reported that plasticity depends on 5-HT2A receptors inside the cell [26], and the 2025 mouse study above found 5-HT2A necessary [20]. A limited search on 1 October 2026 found no independent replication of the TrkB binding result, which does not prove none exists.
Blood BDNF: a marker that has not worked
BDNF is a growth-related protein tied to plasticity in animals that can be measured with a blood draw. A 2025 meta-analysis of 29 studies, 17 of them on ketamine and the rest on classic psychedelics and related compounds, with a search that ended in June 2023, found no change in peripheral BDNF (p = 0.64), whatever the drug, blood fraction, age or diagnosis, and better-controlled studies reported smaller effects. The authors suggest that blood BDNF may not measure fast brain change, or that the animal effects may be weaker or absent in people [27]. A small placebo-controlled study in healthy recreational users had found increases at some time points after low LSD exposures, but only 5 of 23 volunteers had complete data, so each analysis rested on 8 to 10 people, and the authors called it preliminary [28]. In the 43 healthy adults analysed in the 2026 LSD trial, neither plasma nor serum BDNF changed at eight hours, one day or one week, and since the meta-analysis shares a first author with that trial, the two are not independent confirmations [29].
Synaptic density in living people
PET with a tracer for SV2A, a protein found in synaptic vesicles, offers a more direct window. In a 2026 study, 15 healthy participants were scanned before and one week after psilocybin, in a single group with no placebo arm. The trial, designed to detect a rise in SV2A density in two regions, was stopped early for futility at an interim analysis of 12 people. Across all 15 there was no statistically significant overall increase, so the main result was null. In an exploratory comparison, five people who took psilocybin inside the scanner were compared with ten who took it in a room set up like a therapy session. Allocation was not random, the SV2A difference between settings was significant in the frontal cortex (p = 0.03) and not in the hippocampus (p = 0.09), and within the room group the confidence intervals for the increase included zero in both regions. The authors call the setting findings preliminary and hypothesis-generating. The version read is an unedited "Article in Press" manuscript that may change before final publication [30].
Does any of it show up in what people can do?
The 2026 trial of LSD in healthy adults is the most direct controlled test found for this page. Forty-five volunteers took part in a randomized, double-blind crossover design, 43 analysed. The day after LSD, volunteers improved more than after placebo on one part of a finger-typing task (analysed in 42 people), speed gains after a rest, with the LSD condition 32.8 percent better, while accuracy and learning during practice did not differ. A week later perceived stress was lower and the Alternatives subscale of a cognitive-flexibility inventory was higher, while its Control subscale did not change. All participants correctly identified the LSD session, so expectation may explain part of the self-reported changes, and the authors could not tell whether the motor result reflects plasticity or lingering differences in motivation, arousal and fatigue. The brain-stimulation and EEG tests meant to show plasticity-like potentiation showed none, and a one-week change in one EEG wave, the P2, did not survive correction and is called exploratory. One possibly treatment-related serious adverse event occurred and resolved within the study period [29].
Other evidence points the same cautious way. In 24 healthy volunteers, LSD at the acute peak raised novelty and symbolic thinking and lowered convergent thinking, a change during the experience and not a lasting one [31]. A 2026 systematic review of 67 studies found psilocybin had the most consistent evidence for improved cognitive flexibility and attention, with gains more often in psychiatric populations than in healthy people, while LSD and DMT showed no consistent change after the acute period [32]. For very small repeated exposures, a 2026 meta-analysis covered 24 studies, but only six entered the pooled analyses and the randomized pool held just two trials with 117 participants, and it found no clear benefit on depression, anxiety or stress and minimal effects on cognition or creativity in randomized trials [33]. These counts come from the abstract, since the full text was not accessible. A double-blind trial of 34 people starting very small amounts of psilocybin mushrooms found subjective effects and altered EEG rhythms, no support for better creativity or cognition, and stronger effects only in people who guessed their condition correctly, and the active week was identified correctly in 75 percent of weeks. Small shifts toward worse attention-test performance were not corrected for multiple comparisons [34].
Safety signals in healthy adults
A 2024 meta-analysis of 214 studies of classic psychedelics could analyse adverse events for 3,504 participants, 1,726 of them healthy. It found no serious adverse events among healthy participants and about 4 percent among participants with pre-existing neuropsychiatric disorders. In outpatients the late serious event rates were 3.9 percent for psilocybin and 5.2 percent for LSD, and some of those events were not linked to the drug by the authors, for example a death from worsening cancer. Healthy participants did report a small number of non-serious events that needed medical or psychiatric attention. The review also found no reported persistent psychotic disorders or persisting perception disorders in contemporary research settings. But 47 percent of the studies reported no adverse event data at all, and only 16 of 68 studies published since 2005 described a systematic approach to recording them, so low counts partly reflect how little was looked for. The studies covered exposures large enough to produce a full psychedelic experience and not very small repeated ones, and modern trials screened volunteers carefully and ran in supervised settings. The authors caution that the findings cannot be meaningfully generalized to unsupervised use outside a clinical setting [35]. One animal result bears on the adults-only boundary. Repeated adolescent exposure to the synthetic compound 25C-NBOMe produced lasting avoidance behaviour and disrupted hippocampal-orbitofrontal synchrony in male rats, and the same exposure in adulthood did not [36]. It does not transfer to people, but is consistent with studying adults only.
Null results, failures to replicate and weak methods
Several problems recur across this literature, and they bear on every result above.
Brain maps disagree between laboratories. The mega-analysis begins by noting that a direct comparison of three datasets found no single between-network increase common to all, and that two groups analysing global connectivity reported topographically opposite patterns [12].
Imaging samples are small, and small samples mislead. A study of tens of thousands of brain scans found that associations between brain measures and behaviour are tiny and that reliable results need thousands of people, not the 25 typical of imaging studies, though designs with bigger effects, such as within-person comparisons, can work in smaller samples. It is not a psychedelic study, but the warning applies to any claim that a particular brain change predicts who will grow [37].
Blinding often fails. In the 2026 LSD trial every participant identified the LSD session [29], and in the microdosing trial effects appeared only in those who guessed right [34]. In a meta-analysis of depression trials, psilocybin effects were larger with self-report scales and with prior psychedelic users, though the authors label those subgroup analyses exploratory and note that no trial recorded expectations before treatment. That population is clinical, and the same pattern has not been tested in healthy volunteers in the studies read here [38].
Usona Institute supplied the psilocybin in the precision study [14] and appears among the funders of the 2018 LSD receptor study [3]. Authors of the DMT stem-cell study are affiliated with Promega, Scirama Psychedelic Science and Usona Institute [23], authors of the TrkB paper are named on a related patent [24], the senior author of the ketanserin mouse study on a provisional patent [25], the senior author of the intracellular receptor study co-founded Delix Therapeutics [26], and many authors of the mega-analysis report consulting roles or shareholdings in psychedelic companies [12].
What is not known
Does anything measurable still differ in a healthy adult's brain months after an experience? The longest healthy-adult brain follow-up found here lasted weeks, ended with a return to baseline in a handful of people, and would not have detected a small change [14]. Does a brain change translate into a change in capacity? The only controlled healthy-adult trial of post-acute learning found a narrow next-day gain that its authors cannot separate from arousal, motivation and expectation [29].
Which molecular route carries plasticity? In cell and animal work, at least three accounts compete [18] [24] [25] [26]. Is there a marker of a plasticity window that works in living people? Blood BDNF has not shown a consistent change [27], the first PET attempt was null overall [30], and the stimulation tests did not respond [29]. How much depends on setting and preparation? Task engagement reduced the acute brain effect in one study [14], and setting and priming appear in two small studies with non-random grouping [30] [16], so none is strong enough to settle the point.
A further gap concerns what Metanoia calls natural psychedelics. Most imaging used purified or manufactured compounds. Whole natural preparations are rare here: ayahuasca supplied 9 participants to the mega-analysis [12], and the one naturalistic study using dried mushroom material did not measure its chemistry [16]. Whether natural preparations and purified compounds act alike on the brain is unstudied in healthy adults.
What Metanoia asks
The first question is whether anything measurable in the brain still differs months after an experience in a healthy adult, and whether it tracks what the person set out to change. The second is whether a marker of a plasticity window exists that works in living people, given that blood BDNF has not. The third is how much of any lasting brain change depends on preparation and setting as well as on the substance. The fourth is whether natural preparations and purified compounds behave alike.
Metanoia's long-term goal is a research center. It is planned and not built, and its location is not yet decided. For neuroscience the plan starts with an EEG and physiology laboratory, with brain imaging through a partnership with an established medical institution. Every study with human participants would pass an ethics review board, and any protocol involving a controlled substance would run only under the federal registrations and approvals it requires. Any future human work would start from four record-keeping standards (what the material was, what exposure occurred, the surrounding context, and the outcome) and an outcome measure, still in development, addressed to the twelve dimensions of human potential.
Neuroscience cannot say whether a person grew. It can say whether a claimed change leaves a trace in the body, so it can support an outcome measure and cannot replace one. Learning & Memory, Perception, Mindfulness, Self-Awareness, Creativity and Problem-Solving are the dimensions closest to the brain questions above. No study read for this page linked the network changes described here to lasting gains on any of them in healthy adults.
History in brief
Human brain imaging of psychedelics is recent. In 2016 the authors of a global-connectivity study wrote that no modern imaging of LSD's acute effects had existed before [8]. Traditional and ethnographic use is graded 4 and is not described here, because no ethnographic source was read for this page. Tradition validates neither a safety claim nor a benefit claim.
Sources
Reliability levels: 1 is a primary source or any peer-reviewed publication, including reviews, meta-analyses and theory papers. 2 is a reliable secondary source that is not peer-reviewed. 3 is a grey or community source, including company statements and preprints. 4 is a traditional or ethnographic source. Every source below is a peer-reviewed journal publication, so every entry is level 1. Identifiers were checked on PubMed and Europe PMC on 1 October 2026, and the full-text reading was done on 4 October 2026. "Read in full" means the whole main text was read in an open full-text version, from the introduction to the limitations, and supplementary material was not read for any source. Where an entry says methods partly scanned, some of the methods section was only skimmed or sits in a supplement. "Read in part" names the sections that were read. "Abstract only" means the published abstract was read. For six sources (numbers 2, 5, 31, 32, 33 and 36) the full text was not accessible, so the page relies on their abstracts alone.
- Nichols DE. Psychedelics. Pharmacol Rev 2016, 68(2):264-355. DOI 10.1124/pr.115.011478 Grade 1. Review. Read in part: abstract, the section on 5-HT2A agonist evidence, the section on 5-HT2A expression in cortex, and the conclusions. Most of the review was not read. Note: the receptors on the long branches of layer V pyramidal neurons, large neurons in a deep layer of the cortex, seem especially important.
- Vollenweider FX et al. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport 1998, 9(17):3897-3902. DOI 10.1097/00001756-199812010-00024 Grade 1. Controlled study in healthy volunteers. Abstract only. Full text not accessible.
- Preller KH et al. Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor. eLife 2018, 7:e35082. DOI 10.7554/eLife.35082 Grade 1. Randomized double-blind crossover, 24 healthy participants. Read in full, methods partly scanned. Supplement not read.
- Kometer M et al. Activation of serotonin 2A receptors underlies the psilocybin-induced effects on alpha oscillations, N170 visual-evoked potentials, and visual hallucinations. J Neurosci 2013, 33(25):10544-10551. DOI 10.1523/JNEUROSCI.3007-12.2013 Grade 1. Randomized double-blind placebo-controlled study in healthy volunteers, 15 analysed. Read in full.
- Preller KH et al. The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation. Curr Biol 2017, 27(3):451-457. DOI 10.1016/j.cub.2016.12.030 Grade 1. Randomized double-blind crossover in healthy volunteers. Abstract only. Full text not accessible.
- Carhart-Harris RL et al. Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci USA 2012, 109(6):2138-2143. DOI 10.1073/pnas.1119598109 Grade 1. Placebo-controlled imaging study, 15 plus 15 healthy volunteers. Read in full. Supplement not read. Note: the largest decreases were in hub regions such as the thalamus and the cingulate cortex.
- Carhart-Harris RL et al. Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proc Natl Acad Sci USA 2016, 113(17):4853-4858. DOI 10.1073/pnas.1518377113 Grade 1. Single-blind placebo-controlled imaging study, 15 healthy volunteers analysed. Read in full, methods partly scanned. Supplement not read.
- Tagliazucchi E et al. Increased global functional connectivity correlates with LSD-induced ego dissolution. Curr Biol 2016, 26(8):1043-1050. DOI 10.1016/j.cub.2016.02.010 Grade 1. Placebo-controlled imaging study, 15 of 20 healthy volunteers analysed, same dataset as source 7. Read in full from the author version, but the methods section sits in the supplement and was not read.
- Carhart-Harris RL et al. The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Front Hum Neurosci 2014, 8:20. DOI 10.3389/fnhum.2014.00020 Grade 1. Theory paper. Read in full.
- Carhart-Harris RL, Friston KJ. REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics. Pharmacol Rev 2019, 71(3):316-344. DOI 10.1124/pr.118.017160 Grade 1. Theory and review paper whose predictions the authors describe as untested. Read in full. Note: in REBUS the loosened expectations let lower-level information get through. The test that would count against the entropic idea is whether stimulants, which raise arousal without changing the content of experience, raise brain entropy to a similar degree.
- Gattuso JJ et al. Default mode network modulation by psychedelics: a systematic review. Int J Neuropsychopharmacol 2023, 26(3):155-188. DOI 10.1093/ijnp/pyac074 Grade 1. Systematic review, not preregistered. Read in full.
- Girn M et al. An international mega-analysis of psychedelic drug effects on brain circuit function. Nat Med 2026, 32(4):1543-1554. DOI 10.1038/s41591-026-04287-9 Grade 1. Pooled analysis of 11 resting-state fMRI datasets of healthy adults, acute effects only. Read in full. Supplement not read. Note: the clearer coupling also involved sensory networks for vision and movement, and all datasets went through one processing pipeline. The thalamus result rests on a Bayesian analysis that gave only weak support. Psilocybin and LSD supplied most of the data and DMT about 16 people. The authors suggest earlier single-site reports may have overstated the reductions inside networks, while noting that earlier work used a different analysis method. There was also stronger coupling between sensory cortex and the striatum.
- Dai R et al. Opposite network patterns of integration-segregation in psychedelic and sedated states of consciousness. Cell Rep 2026, 45(8):117830. DOI 10.1016/j.celrep.2026.117830 Grade 1. Eight human fMRI datasets, psychedelic, sleep and sedated states. Read in full. Supplementary tables not read. Note: the effects of ketamine and nitrous oxide in the "psychedelic" group were weaker and more variable than those of LSD and psilocybin.
- Siegel JS et al. Psilocybin desynchronizes the human brain. Nature 2024, 632:131-138 (PMID 39020167). DOI 10.1038/s41586-024-07624-5 Grade 1. Precision imaging, 7 enrolled and 6 analysed healthy adults with earlier psychedelic experience. Read in full. Extended data and supplement not read. Note: psilocybin changed connectivity about as much as brains differ between two people, and the same signature was found in an existing LSD dataset. The mystical-type experience correlation used 16 sessions, 10 with psilocybin and 6 with methylphenidate. The anterior hippocampus is a memory region, and its connectivity with the DMN fell from 0.180 to 0.163 on the authors' scale. Usona Institute is a US nonprofit that makes psilocybin for trials. One author was a participant in the study.
- Barrett FS et al. Emotions and brain function are altered up to one month after a single high dose of psilocybin. Sci Rep 2020, 10:2214. DOI 10.1038/s41598-020-59282-y Grade 1. Open-label pilot with no control group, 12 healthy volunteers. Read in full. Supplement not read. Note: the sample was all white and mostly college graduates. The count of significant resting-state connections was higher at both follow-ups.
- Pallavicini C et al. Longitudinal neural and psychological changes following psilocybin under compassion imagery priming. Front Hum Neurosci 2026, 20:1874178. DOI 10.3389/fnhum.2026.1874178 Grade 1. Naturalistic study, 105 participants, not preregistered, groups not randomized. Read in full. Supplementary figures not read. Note: absorption is the tendency to be fully caught up in an experience, and decentering is a step back from one's own thoughts. Self-compassion also rose in the higher-dose group. The models' accuracy index was about 0.70, where 0.5 is chance, and performed at chance in the lower-dose group. Not preregistered means the plan was not filed publicly before data collection.
- Daws RE et al. Increased global integration in the brain after psilocybin therapy for depression. Nat Med 2022, 28(4):844-851. DOI 10.1038/s41591-022-01744-z Grade 1. Two clinical trials in people with depression (clinical population). Read in full from the accepted author manuscript, methods partly scanned. Supplement not read. Note: the authors say psychological factors cannot be ruled out.
- Ly C et al. Psychedelics promote structural and functional neural plasticity. Cell Rep 2018, 23(11):3170-3182. DOI 10.1016/j.celrep.2018.05.022 Grade 1. Cell culture and animal study. Read in full, detailed methods and supplement not read.
- Shao LX et al. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron 2021, 109(16):2535-2544. DOI 10.1016/j.neuron.2021.06.008 Grade 1. Mouse study with chronic two-photon imaging. Read in full from the author version. Supplementary table of sample sizes not read. Note: spine heads widened by about 11 percent after one day. Spines are the small protrusions where a neuron receives signals, imaged repeatedly under a two-photon microscope. In the same study ketanserin abolished a behaviour that depends on 5-HT2A but not the structural change, although the authors note the dose may block only about 30 percent of the receptors.
- Shao LX et al. Psilocybin's lasting action requires pyramidal cell types and 5-HT2A receptors. Nature 2025, 642(8067):411-420. DOI 10.1038/s41586-025-08813-6 Grade 1. Mouse study. Read in full, methods partly scanned. Supplementary table and extended data not read.
- de Vos CMH, Mason NL, Kuypers KPC. Psychedelics and neuroplasticity: a systematic review unraveling the biological underpinnings of psychedelics. Front Psychiatry 2021, 12:724606. DOI 10.3389/fpsyt.2021.724606 Grade 1. Systematic review (PubMed search only, to October 2020), 16 preclinical and 4 clinical studies. Read in full.
- Calder AE, Hasler G. Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023, 48(1):104-112. DOI 10.1038/s41386-022-01389-z Grade 1. Narrative review. Read in full.
- Salerno JA et al. Proliferative effects of the psychedelic N,N-dimethyltryptamine (DMT) in human neural stem cells. ACS Chem Neurosci 2026, 17(15):2901-2909. DOI 10.1021/acschemneuro.6c00209 Grade 1. Human stem-cell culture study, five cell lines in all, two or three per test. Read in full, main text and methods. Supporting information not read. Note: proliferation rose in proportion to concentration, with a half-maximal effect near 60 nanomolar. It was measured in three lines across five independent experiments. Intracellular BDNF protein rose about fivefold in two lines across three independent experiments. No single receptor blocker prevented the proliferation. At days 5 and 10 the neurosphere difference was about 12 percent and not significant after correction, and early neuronal markers at day 10 matched controls.
- Moliner R et al. Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nat Neurosci 2023, 26(6):1032-1041. DOI 10.1038/s41593-023-01316-5 Grade 1. Cell and mouse study. Read in full, laboratory methods partly scanned. Supplementary table and extended data not read.
- Hesselgrave N et al. Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice. Proc Natl Acad Sci USA 2021, 118(17):e2022489118. DOI 10.1073/pnas.2022489118 Grade 1. Mouse study, males only. Read in full. Supplementary appendix not read.
- Vargas MV et al. Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors. Science 2023, 379(6633):700-706. DOI 10.1126/science.adf0435 Grade 1. Cell and mouse study. Read in full from the author version, except the methods and supplement, which were not read. Note: the work was in cultured cells and rodents, and the receptors inside the cell are not engaged by serotonin unless it is carried into the cell.
- Calder AE, Hase A, Hasler G. Effects of psychoplastogens on blood levels of brain-derived neurotrophic factor (BDNF) in humans: a systematic review and meta-analysis. Mol Psychiatry 2025, 30(2):763-776. DOI 10.1038/s41380-024-02830-z Grade 1. Pre-registered meta-analysis, 29 studies (17 on ketamine), healthy and clinical samples, search to June 2023. Read in full. Supplement not read. Note: the standardized mean difference was 0.024, where 0 means no change. Samples were healthy and clinical.
- Hutten NRPW et al. Low doses of LSD acutely increase BDNF blood plasma levels in healthy volunteers. ACS Pharmacol Transl Sci 2021, 4(2):461-466. DOI 10.1021/acsptsci.0c00099 Grade 1. Placebo-controlled within-subject study in healthy volunteers who were recreational psychedelic users. Read in full. Note: the measurements stopped at 6 hours.
- Calder AE et al. Acute and post-acute neurobehavioral responses to lysergic acid diethylamide in healthy subjects: a randomized controlled study. Neuropsychopharmacology 2026, 51(9):1577-1587. DOI 10.1038/s41386-026-02454-7 Grade 1. Randomized double-blind crossover, 45 enrolled and 43 analysed healthy adults. Read in full, main text. Supplement not read. Note: most blood BDNF does not come from the brain. The typing-task speed gains were measured in the second test block 80 minutes after practice. Baseline scores on the flexibility inventory were near the best possible, leaving little room to improve, and responder rates in the stimulation and EEG tests hover near 50 percent.
- Johansen A et al. Psilocybin's effect on human brain synaptic plasticity. Transl Psychiatry 2026. DOI 10.1038/s41398-026-04285-y Grade 1. Single-arm open-label PET study, 15 healthy participants, no placebo arm, stopped early for futility. Unedited Article in Press version that may change before final publication. Read in full, supplement not read. Note: the first five participants were the scanner group, who had tasks to do while on psilocybin, and the room group had stronger mystical-type experiences and larger changes in some measures. With no placebo arm the true effect may have been underestimated, since other SV2A studies saw small decreases on a second scan. This is the only study of its kind found for this page, and it is null on its main question.
- Wiessner I et al. LSD and creativity: increased novelty and symbolic thinking, decreased utility and convergent thinking. J Psychopharmacol 2022, 36(3):348-359. DOI 10.1177/02698811211069113 Grade 1. Randomized double-blind placebo-controlled crossover, 24 healthy volunteers. Abstract only. Full text not accessible. Note: the design was a randomized crossover study.
- Kelly C et al. Subacute and long-term changes in cognitive functioning after administration of classic psychedelics, MDMA and ketamine: a systematic review of clinical and preclinical evidence. Neurosci Biobehav Rev 2026, 190:106911. DOI 10.1016/j.neubiorev.2026.106911 Grade 1. Systematic review, 47 clinical and 20 preclinical studies. Abstract only. Full text not accessible. Note: 47 of the 67 studies were clinical and 20 preclinical. The review also found selective outcome reporting and thin methodological detail.
- Meshkat S et al. Efficacy and safety of psychedelic microdosing on psychological outcomes in healthy adults: a systematic review and meta-analysis. CNS Drugs 2026, 40(10):1369-1393. DOI 10.1007/s40263-026-01325-5 Grade 1. Systematic review and meta-analysis of healthy adults. Abstract only. Full text not accessible. Note: the meta-analysis covered 3,681 people.
- Cavanna F et al. Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study. Transl Psychiatry 2022, 12(1):307. DOI 10.1038/s41398-022-02039-0 Grade 1. Double-blind placebo-controlled trial, 34 healthy participants. Read in full. Supplement not read.
- Hinkle JT et al. Adverse events in studies of classic psychedelics: a systematic review and meta-analysis. JAMA Psychiatry 2024, 81(12):1225-1235. DOI 10.1001/jamapsychiatry.2024.2546 Grade 1. Systematic review and meta-analysis, 214 studies, clinical and healthy samples. Read in full. Supplement not read.
- Yu ZP et al. Adolescent exposure to the psychedelic 25C-NBOMe in rats induces lasting competitive avoidance through disrupted hippocampal-prefrontal synchrony. Nat Neurosci 2026, 29(9):2249-2260. DOI 10.1038/s41593-026-02369-y Grade 1. Rat study of a synthetic compound. Abstract only. Full text not accessible. Note: the compound is of a different chemical class from psilocybin or LSD. The effect was competitive avoidance, and the disrupted synchrony was between the ventral hippocampus and the orbitofrontal cortex.
- Marek S et al. Reproducible brain-wide association studies require thousands of individuals. Nature 2022, 603(7902):654-660. DOI 10.1038/s41586-022-04492-9 Grade 1. Analysis of three large imaging datasets (not psychedelic). Read in full, imaging-processing methods only partly scanned. Supplement and extended data not read. Note: the median correlation was about 0.01 in the largest sample and the strongest replicated about 0.16. The finding concerns links between brain and behaviour across people. Within-person drug effects are larger, which is why dense repeated scanning of a few individuals can work. The paper does not measure drug effects.
- Metaxa AM, Clarke M. Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis. BMJ 2024, 385:e078084. DOI 10.1136/bmj-2023-078084 Grade 1. Meta-analysis in clinical depression (clinical population). Read in full. Appendices not read.
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