This popular commentary article (2020) describes the current resurrection of research into psychedelics (both neuroscience and therapeutic applications). It describes the evidence for the serotonin receptor (5-HT2a) agonism (psychedelics binding to that receptor) and the possible mechanisms through which long-lasting therapeutic effects can be found.
After a legally mandated, decades-long global arrest of research on psychedelic drugs, investigation of psychedelics in the context of psychiatric disorders is yielding exciting results. Outcomes of neuroscience and clinical research into 5-Hydroxytryptamine 2A (5-HT2A) receptor agonists, such as psilocybin, show promise for addressing a range of serious disorders, including depression and addiction.
Research on psychedelic drugs was effectively halted for decades by legal and political restrictions, despite early mid-20th century clinical interest and some promising therapeutic signals. Nutt and colleagues frame this hiatus as having stifled progress in psychiatric pharmacology at a time when few genuinely novel drug classes have emerged; psychedelics such as LSD, psilocybin, ayahuasca, mescaline and newer 5-MeO-DMT analogues are now being revisited as potential treatments for a broad set of internalising disorders including depression and addiction. This paper surveys recent clinical and neuroscientific developments around serotonergic psychedelics, especially psilocybin, and discusses mechanistic hypotheses, clinical evidence to date (including trials for depression and end-of-life distress), practical aspects of psychedelic therapy (dose, duration, and the role of psychotherapy), and broader barriers to research such as scheduling and funding. The authors set out to synthesise current knowledge, highlight outstanding questions, and argue for coordinated multidisciplinary research to translate early findings into reliable clinical applications.
Papers cited by this study that are also in Blossom
Barrett, F. S., Doss, M. K., Sepeda, N. D. et al. · Scientific Reports (2020)
Carhart-Harris, R. L., Friston, K. J. · Pharmacological Reviews (2019)
Carhart-Harris, R. L., Nutt, D. J. · Journal of Psychopharmacology (2017)
Carhart-Harris, R. L., Roseman, L., Bolstridge, M. et al. · Scientific Reports (2017)
Clinical studies and early trials reviewed by the authors report substantial and sometimes enduring therapeutic effects of psilocybin across several indications. Small trials and case series showed rapid improvements in depressive symptoms that in some participants persisted for weeks to years; three placebo-controlled trials have investigated psilocybin for anxiety and depression in people with life‑threatening illness. Results have also suggested efficacy signals in alcohol and tobacco dependence, and trials for anorexia, obsessive‑compulsive disorder, chronic pain and opioid use disorder are in development. Industry activity is growing: at least two companies (COMPASS Pathways and Usona) are producing psilocybin at scale and sponsoring multi‑centre dose‑finding and efficacy studies, and a double‑blind trial comparing psilocybin with the SSRI escitalopram is under way. On mechanism, the defining pharmacology of classic psychedelics is 5‑HT2A receptor agonism. Neuroimaging evidence cited includes PET work in which the degree of 5‑HT2A receptor occupancy predicted the subjective psychedelic effects of psilocybin, and pharmacological blockade with a 5‑HT2A antagonist (ketanserin) abolishes psychedelic effects. Anatomically, 5‑HT2A receptors are highly expressed in cortex—especially visual and association areas and layer V pyramidal neurons—with lesser expression on GABAergic interneurons. Activation of these receptors increases pyramidal excitability and produces cortical desynchronisation (reduced alpha oscillations) and increased entropy in ongoing activity, phenomena the authors link to a relaxation of precision weighting of predictive models (priors) and to altered hierarchical intrinsic network organisation. Alternative mechanistic models are noted: an earlier thalamic gating hypothesis proposes altered sensory gating as central, but the authors suggest thalamic effects may be secondary to cortical disruption given low thalamic 5‑HT2A density. Differences among psychedelic compounds are discussed in practical terms: LSD and mescaline act for about 8–14 h, psilocybin for about 4–5 h after oral dosing, DMT and 5‑MeO‑DMT produce much shorter effects when smoked or injected (<30 min) while DMT in ayahuasca lasts ~2–3 h. The oral route is preferred clinically for allowing longer therapeutic engagement, though the potential of short‑acting compounds to induce a rapid ‘‘reset’’ is flagged as an area for future testing. Several questions about the necessity and nature of the subjective experience are reviewed. Microdosing (regular sub‑perceptual dosing) has not been trialled for psychiatric disorders, and the authors note that larger psychedelic (‘‘macrodose’’) trials suggest that stronger subjective or mystical/peak experiences predict better outcomes. COMPASS Pathways’ dose‑ranging study randomising participants to 1 mg (microdose), 10 mg, or 25 mg is cited as a test of the dose–response and the importance of subjective effects. The persistence of therapeutic gains is discussed from psychological and neurobiological angles. Psychologically, psychedelics may relax rigid, self‑critical beliefs and promote insight and emotional release, which can lead to lasting behavioural and outlook changes; in the authors’ depression trial, measures of insight and emotional breakthrough predicted longer‑term benefit. Preclinical data are invoked to suggest psychedelics promote neural plasticity in circuits relevant to neuropsychiatric disorders, although human mechanistic links remain to be clarified. Notably, relapse is common: about half of patients treated for depression relapsed within 6 months in the cited work, implying that some presentations may need repeated or adjunctive interventions. Practical aspects of current psychedelic therapy models are outlined: treatment is delivered in structured psychotherapeutic settings with preparatory sessions, one or two therapists present during long (up to ~6 h) drug sessions, and post‑session integration, all of which entail substantial therapist time and cost. The authors raise the open question of whether the psychotherapeutic context is necessary for durable benefit, suggesting experimental approaches (e.g., microdosing, administration under anaesthesia) that could, in principle, probe the relative contributions of subjective experience versus purely pharmacological/neuroplastic effects, though they acknowledge ethical and blinding challenges. With respect to circuit‑level biomarkers, the amygdala and prefrontal regulation receive attention: depression is associated with elevated amygdala responses to threat, and various antidepressant interventions suppress this hyperresponsivity. Psilocybin reduced threat‑related amygdala responsivity in healthy volunteers one week after dosing, whereas treatment‑resistant depressed patients showed an opposite effect one day after therapy, illustrating complex, time‑dependent and possibly non‑linear changes. The authors also report decreased resting‑state blood flow in temporal cortex after psilocybin that predicted positive outcomes in their TRD sample. Barriers to research are emphasised. The Schedule 1 classification of many psychedelics raised regulatory burdens, costs and stigma that largely halted academic and industry work for decades; prior to recent changes, manufacturing-grade compounds were difficult to obtain and major funders withdrew support. The authors note evolving legal and commercial landscapes—manufacturing by COMPASS and Usona, changing legality of plant‑based psychedelics in some jurisdictions, and decriminalisation trends in parts of the USA and Netherlands—which create both research opportunities and public‑health challenges. They argue for rescheduling of psychedelics with proven therapeutic utility (notably psilocybin) to facilitate research and clinical translation.
Nutt and colleagues interpret the revival of psychedelic research as a major and timely scientific opportunity that could yield novel treatments distinct from standard daily pharmacotherapies. They characterise classic serotonergic psychedelics as agents that open a transient window of increased brain plasticity and altered predictive processing, which—when combined with psychotherapeutic support—can permit insight, emotional release and revision of maladaptive beliefs underlying internalising disorders. The authors position these developments relative to prior literature by noting that psychedelics act via 5‑HT2A receptor agonism and produce robust changes in cortical dynamics and network organisation; this mechanistic framing both differentiates psychedelics from conventional antidepressants and provides a parsimonious account for effects across apparently disparate disorders (depression, addiction, OCD, anorexia). They also acknowledge competing models (for example, thalamic gating) and suggest these ideas may be reconcilable insofar as cortical disruption could drive downstream thalamic effects. Key limitations and uncertainties are emphasised. Clinical evidence is promising but still limited in scale and duration: relapse is common and about half of treated patients may relapse within 6 months. Critical mechanistic questions remain unresolved, including whether 5‑HT2A activation is necessary for therapeutic benefit in humans (a definitive antagonist‑challenge trial has not been done), whether the subjective psychedelic experience is essential for long‑term change, and how neuroplastic effects observed preclinically translate to durable clinical outcomes. Practical constraints—Schedule 1 regulation, limited mainstream funding, and historical stigma—have impeded wider study and slowed clinical translation. Finally, the authors call for coordinated action: larger, multidisciplinary programmes of research combining neurobiology, clinical trials, and implementation science are needed to define optimal dosing regimens, therapeutic context, biomarkers of response, and strategies to sustain benefits. They recommend regulatory reform (rescheduling of compounds with established utility) and continued systematic investigation to ensure safe and effective clinical adoption while monitoring public‑health implications of expanding recreational use.
The authors conclude that the renewed scientific study of psychedelics represents one of the most significant advances in psychiatry and brain science in recent decades, correcting a long period of research paralysis caused by drug policy. Early clinical and neuroimaging studies have delivered novel insights into brain function and suggested a promising new therapeutic approach for a range of psychiatric disorders. To capitalise on these findings, Nutt and colleagues urge a coordinated, multi‑level, multidisciplinary research programme to clarify mechanisms, optimise clinical protocols, address safety and relapse, and advocate regulatory changes that will allow rigorous investigation and responsible therapeutic implementation.
Research leading to the discovery of new pharmacological treatments for psychiatric disorders has been painfully slow. With a few exceptions, including the use of orexin antagonists for insomnia, current medicines are derivatives of drugs discovered in the 1950s through serendipity and refined through pharmacological modifications. For these reasons, most major pharmaceutical companies have retreated from researching brain targets, threatening to halt a progression in research knowledge and possibly inducing the same sort of dark age that antibiotic research has found itself in. One way out is to revisit drugs that were once used but fell out of use because of political machinations, especially the war on drugs. Cannabis was the first to be resurrected and the glutamate receptor antagonist anesthetic ketamine has recently been shown to have antidepressant properties, leading to the enantiomer esketamine becoming licensed in the USA and Europe. Now, serotonergic psychedelics, particularly psilocybin (the active compound in ''magic mushrooms'') are being resurrected as potential treatments for a range of different psychiatric disorders. These drugs include LSD, ayahuasca (a drink that contains dimethyltryptamineand a monoamine oxidase inhibitor that prevents its breakdown in the gut), as well as 5-MeO-DMT (from the Sonora toad) and mescaline (from the peyote cactus). In the 1950s and 1960s, LSD was widely researched and was considered to achieve major breakthrough treatments by many psychiatrists. At the same time, psilocybin was an experimental medicine supplied by Sandoz as ''Indocybin''. However, once LSD became used recreationally by young people, it was banned and most other psychedelics were sucked into the legislation; research on their potential therapeutic efficacy ground to a halt. In the past decade, research on these compounds has been re-established by a few groups around the world, culminating in new centers for psychedelic research at Imperial College London and Johns Hopkins University. Because psilocybin is a Schedule 1 controlled drug, meaning that it has been defined as having high potential for abuse with limited therapeutic utility, it took several years of battling with regulators and ethics committees to gain permission to do clinical research with it, but the struggle was worth it. Its effects on patients suffering from depression were remarkable-e.g., two experiences with psilocybin improved depression scores for weeks, and in some people, years, positioning it as one of the most powerful therapeutics for treatment-resistant depression. There have also been three placebo-controlled trials of psilocybin for anxiety and depression related to end-of-life diagnoses (reviewed in. Based on this body of positive findings, at least two companies have been set up to take psilocybin to the clinic, funding multi-center dose-finding studies of psilocybin in depression (U.S. National Library of. In parallel, we will soon be completing a double-blind trial of psilocybin versus the selective serotonin reuptake inhibitor (SSRI) escitalopram in depression (U.S. National Library of Medicine, 2020c). There have also been studies showing efficacy in alcoholism and tobacco dependence, and similar studies in anorexia, obsessive-compulsive disorder (OCD), chronic pain, and opioid use disorder are being developed. This might seem a strange and disparate set of disorders for a single medicine to work in, and this speaks to the innovative nature of psychedelic therapy. In most studies, the psychedelic is given just once (though in a few studies, twice or three times over a period of weeks) as part of an ongoing psychotherapy course, in complete contrast to currently available medications, which are given at least daily, often with little therapeutic support. We suggest one way of looking at the difference between them is that current medicines suppress symptoms in a similar way that insulin suppresses hyperglycemia in diabetes. Standard antidepressants protect against the stressors that lead to and perpetuate depression, but don't directly access and remedy underlying biopsychosocial causes. In contrast, psychedelic therapy harnesses a therapeutic window opened up by the brain via the effects of the drugs to facilitate insight and emotional release and, with psychotherapeutic support, a subsequent healthy revision of outlook and lifestyle. Arguably all of the conditions in which psychedelics have been shown to work share the common feature of being internalizing disorders. In depression, patients continually ruminate about their failings, reiterate thoughts of guilt, and engage in self-critical inner narratives. In addictions, the object of addiction takes on the role of negative thinking in depression, driving behavior that is specific, narrow, and rigid; addicts ruminate on relief afforded by the object, how to get it, how to pay for it, etc. The rationale for using psychedelics in OCD and anorexia is consistent given that there is rumination on intrusive thoughts, e.g., about contamination or calorie mismanagement. Psychedelics likely work by dysregulating activity in systems and circuits that encode these habits of thought and behavior, allowing them to recalibrate as the acute effects of the drugs subside. Despite this potential for efficacy across a range of disorders and the initial promising results, many questions remain.
The defining action of classic serotonergic psychedelics is mediated primarily through agonism of the 5-Hydroxytryptamine 2A (5-HT2A) receptor (Figure). This is exemplified by recent positron emission tomog-raphy research, showing that the psychedelic effects of psilocybin in humans are predicted by the degree of occupancy of the 5-HT2A receptor revealed by displacement of the agonist tracer [11C]Cimbi-36. Moreover, 5-HT2A receptor antagonists such as ketanserin block psychedelic effects. The 5-HT2A receptor is maximally expressed in the cerebral cortex, and because humans have considerably more cortex than other species, they logically have the highest expression. These receptors show some regional heterogeneity in the cortex, being relatively sparse in the sensorimotor cortex, and especially dense in visual and association cortices-with high expression also noted in the claustrum in vitro. 5-HT2A receptors are localized on the cell bodies and apical dendrites of large pyramidal neurons concentrated in layer V of the cortex. There are also found, albeit to a lesser degree, on GABAergic interneurons that regulate pyramidal cell firing. Activation of 5-HT2A receptors appears to increase the excitability of the host neuron, causing a spike to wave decoherence and associated dysregulation of spontaneous activity in cortical populations. This dysregulation reliably manifests as increased entropy in on-going activity recorded via local field or scalp potentials, as well as related changes in the power spectrum, e.g., marked decreases in alpha oscillations. A number of aspects of cortical functioning associated with predictive processing appear to be dysregulated under psychedelics, including the following: functioning of layer V pyramidal neurons; the strength of alpha oscillations; the strength of backward traveling waves; and the integrity, segregation, and hierarchical organization of intrinsic networks. This is consistent with our current hypothesis that the main functional effect of psychedelics is to relax the precision weighting of the predictive models encoded in the brain (Carhart-Harris and Friston, Psilocybin, along with other serotoninergic psychedelics, acts to stimulate 5-HT2A receptors in the cortex, particularly layer 5 pyramidal cells. This leads to massive depolarization and thence rapid repeated firing of these neurons (lower inset). Because these neurons are responsible for organizing cross-cortical integration, this activity results in a profound alteration of cortical signaling. Both magnetoencephalography and electroencephalography measures reveal a major loss of typical rhythmical activity, resulting in a state of extreme desynchronization or enhanced entropy (middle inset). Also, these layer 5 neurons mediate the ''top down'' perceptual and cognitive predictions (so called ''priors''), which form the basis of normal brain processing. Thus, under psychedelics the brain ''escapes'' from its usual tightly constrained and predictable ways of working; this leads to a global increase in connectivity (top inset) that allows new insights into past behavior, memories, actions, feelings, and beliefs. These in turn can lead to therapeutic changes in conditions such as depression and addiction, which are driven by dysfunctional brain processing. Average density map for 5-HT2A receptor adapted from.
). An earlier model takes a different view: that psychedelics disrupt the normal gating of sensory inputs via the thalamus, and this leads to altered perceptions. However, given a low density of 5-HT2A receptors in the thalamus, it might be that thalamic effects are driven by psychedelics disrupting cortical activity that projects to the thalamus, so the two theories might not be so different. The therapeutic benefit we theorize is also mediated via this receptor, but as yet, this has not been established in humans-because to do this would require a trial in which a 5-HT2A receptor antagonist is given before the psychedelic to see whether this blocks its therapeutic effects. Would Shorter-Acting Psychedelic Drugs Work? Different psychedelics have very different durations of action. LSD and mescaline are two of the longer lasting (8-14 h), whereas the effects of DMT and 5-MeO-DMT are much shorter, with effects lasting less than 30 min from either a smoked or injected dose, although DMT consumed in ayahuasca will work for about 2-3 h. Psilocybin acts for about 4-5 h after oral ingestion. The oral route is generally considered the most appealing for therapeutic work because the resulting ''trip'' allows the patient to enter into the psychedelic state with plenty of time for them to explore personal material and potentially experience therapeutic breakthrough. It is theoretically possible, however, that a short trip, such as with i.v. DMT, might ''shake-up'' and ''reset'' abnormal patterns of brain activity and so could have some therapeutic benefit. It seems likely that this idea will soon be tested, and if it works, it could significantly reduce the costs of psychedelic therapy by saving on therapist time.
The extensive use of microdosing psychedelics to putatively improve wellbeing and creativityraises the question of whether a full psychedelic experience is needed. Microdosing involves taking-usually on a regular basis, e.g., 3 times a week-a low dose of a psychedelic that is devoid of subjective psy-choactive effects. As yet there have been no trials of microdosing for any psychiatric disorder, and it seems improbable that a single microdose of psilocybin would have as big an effect in depression as the 25 mg psilocybin ''macrodose'' usually used. Growing evidence suggests the best outcomes from psilocybin are in patients experiencing the most powerful psychedelic effects, variously called breakthrough, peak, or mystical experiences. Additional insight on this question might come from the COMPASS Pathways study (U.S. National Library of Medicine, 2020a), where patients are randomized to either a 1 mg (i.e., a microdose) or to a 10 mg or 25 mg dose (which do have psychedelic effects). The prediction is that the 25 mg dose will be more effective than the 10 mg dose and the 1 mg (microdose) will be ineffective, but the outcomes remain to be seen.
Both the depression and tobacco smoking trials have shown that, in some people, psilocybin can produce clinical remission, in some cases persisting for years. Similar findings are described in the older psychedelic literature, where enduring positive psychological changes were commonly reported. So how does this happen? For now, this question is easier to address from the perspective of psychology, where the key might be how psychedelics relax limiting beliefs and, in parallel, promote insight and an emotional release that can motivate the revision of these beliefs. Indeed, in our depression trial, insight and emotional breakthrough were significant predictors of the longer-term changes. More work is needed to address how insight and emotional release registers in terms of altered brain functioning and anatomy, but several pre-clinical studies have shown that psychedelics promote neural plasticity in key circuits relevant to treating neuropsychiatric disorders, e.g.,. How Much Is ''Just Pharmacology''? Currently, psilocybin therapy for psychiatric disorders is given within a structured psychotherapeutic setting with a considerable therapist input. There is always a preparatory session before drug administration. There are always one, and in some studies two, therapists present during the psychedelic session-which lasts up to 6 h. The next day, and beyond, there are further integration sessions with the same therapists to help patients talk through and thereby ''ground'' their experiences. This amount of therapist exposure has significant cost implications and therefore naturally leads to the question-is the psychotherapy really necessary? Would just giving the drug alone produce the same clinical benefits? To some extent, this is a false dichotomy, because any effect on the brain is, by implication, an effect on the mind and vice versa, and so the question is more whether there can be an action on the brain and long-term therapeutic effect, without a noticeable mediating subjective experience. A question like this could be addressed either via sub-perceptual microdosing or via giving the psychedelic during sleep or under anesthesia. Although ethically challenging to implement, giving individuals a psychedelic under anesthesia and assessing its subsequent effect on a mental-health-relevant outcome might help resolve debate about the importance of the psychological components of psychedelic therapy, as well as the imperfection of current blinding procedures. Ours' and others' data do suggest that there is a positive interaction between the neuroplastic effects of 5-HT2A receptor agonism and what is done with that plasticity. Indeed, part of the core drug action seems to be to make people exceptionally sensitive to what lies beyond their (ego) boundaries, whether this be material percolating up from their inner world, e.g., in terms of emotions and memories, or coming into the brain from the outer world, e.g., in terms of the therapist(s) present and music heard.
There is great current interest from both neuroscience and clinical perspectives in understanding how psychedelics remedy psychiatry disorders. Knowing ''the answer'' would not only help reassure sceptics that psychedelics are more than just a powerful placebo but would also help maximize their therapeutic benefit-particularly in directing interventional processes to maintain wellness. This is the prime need right now because, despite the impressive immediate effects of psilocybin on depression, about half of patients relapse within 6 months. Why this is is presently unknown, but it supports the idea that, in some people, depression can become a persistent, intractable, problem that might influence thinking processes forever. In others, it might be a defense against a traumatic event or loss that psychedelics uncover and help the patient process and move on from. More work is needed to test our assumption that the most severe presentations might require more than just a single-dose treatment. As described above, the 5-HT2A receptor is likely the key molecular mediator of cases of major psychological change. This receptor seems to have a low level of basal activity in normal brain states because its complete blockade with 5-HT2A antagonists has almost no effect on daytime mind and brain functioning. Interestingly 5-HT2A antagonists do enhance deep (stages 3-4) sleep, a state of heightened brain synchronicity, the exact opposite of the entropic brain state seen with psychedelics (Carhart-Harris and Friston, 2019). We suggest that in states of extreme stress, when novel behavioral responses are vital, the 5-HT2A system might be activated to provide solutions to the crisis and also help lay down new, more adaptive behavioral and cognitive patterns. The ''resetting'' of normal functioning in intrinsic brain networks, like the default-mode network, might be related to this adaptive mechanism. When thinking in terms of brain regions and circuits underpinning clinical responses, a lot of work in recent years has focused on the role of the amygdala in unconscious threat processing, as well as prefrontal control of this. Amygdala response to threat cues (e.g., a fearful face) measured with fMRI is significantly increased in depressed people. A range of different drug treatments for depression have been shown to suppress this hyperresponsivity and this has become a prime theory for how these medicines work. Recently, psilocybin has been shown to do something similar in healthy volunteers 1 week after psilocybin, but an opposite effect was seen in treatment-resistant patients (TRDs) 1 day after psilocybin therapy, which potentially implies a complex, non-linear process of change. We also found evidence of decreased ''resting-state'' blood flow in the temporal cortex, which contains the amygdala, 1 day after psilocybin for TRDs that was predictive of positive outcomes. Our current trial of psilocybin versus the SSRIs escitalopram in major depressive disorder (U.S. National Library of Medicine, 2020c) aims to more comprehensively address this matter after a standard treatment with each.
Major hurdles facing research with psychedelics include the burden that their Schedule 1 status incurs and a lack of mainstream funding, and we suspect these things are related. The Schedule 1 status of psychedelics led to vastly increased regulations on research, associated costs, and damaging stigma that likely deterred governmental agencies, other reputable funding bodies, and companies from backing the relevant research. Before LSD was banned, the US NIH funded over 130 studies exploring its clinical utility; however, since the ban, it has funded none and until a few years ago, no company was committed to manufacturing medical grade psychedelics and thus procurement of the required drugs for clinical trials was almost impossible. Nowadays, both COMPASS Pathways and Usona are making psilocybin at scale with others starting. Natural plant-based products such as ayahuasca, peyote, and magic mushrooms are now legal in some South American countries and are becoming decriminalized in a few US cities. Moreover, magic mushrooms could be legalized in the US state of Oregon later this year. Magic truffles, which contain the same active compound, are legal in the Netherlands, and this loophole, combined with a growing interest in the therapeutic potential of psilocybin, has led to fast-growing industry in Dutch truffle retreats. Some finance journalists have begun predicting a ''shroom boom'' to rival the ''green rush'' seen with medicinal cannabis. This escalating recreational use presents an opportunity to collect ''Big Data'' for educational and harm-reduction purposes, and we have set-up an online It is possible to make new 5-HT2A receptor agonist ligands that would, at the time of synthesis, be outside national or UN Conventions. However, based on recent examples, the risk of them becoming restricted would be very high. In the UK, the ultrarestrictive 2016 Psychoactive Substances Act makes all novel psychoactive compounds illegal, and some of the newer 5-HT2A receptor agonists (e.g., the NBOMeS) have been found to be more toxic than the older ones, a situation similar to that seen with the growth of legal but more harmful synthetic cannabinoids. Overall, it seems the best way forward to fostering research and therapeutic application is to press for a rescheduling of psychedelics with proven therapeutic utility, especially psilocybin. That psilocybin was made Schedule 1 (i.e., having no medical value) on the shirt-tails of politically motivated banning of LSD has had an immense negative effect on treatment and research. A campaign to re-schedule psilocybin is now underway in the UK, led by the charity DrugScience.org.uk and has international, scientific support.
The resurrection of research into the neuroscience and therapeutic application of psychedelics represents one of the most important initiatives in psychiatry and brain science in recent decades. It rectifies decades of global research paralysis that emerged as collateral damage from the war on drugs and that has become one of the worst examples of censorship of human research in the history of science. The past ten years have seen the first green shoots of recovery with a number of teams across several continents beginning human neuroimaging and clinical trials that have delivered remarkable insights into brain function and instigated an exciting new approach to the treatment of a range of psychiatric disorders (Table). What is now needed is a combined, multi-level, multidisciplinary program of research into the mechanisms underpinning these findings.
Create a free account to open full-text PDFs.
Kuypers, K. P. C., Erritzoe, D., Knudsen, G. M. et al. · Journal of Psychopharmacology (2019)
Ly, C., Greb, A. C., Cameron, L. P. et al. · Cell Reports (2018)
Madsen, M. K., Fisher, P. M., Burmester, D. et al. · Neuropsychopharmacology (2019)
Preller, K. H., Herdener, M., Pokorny, T. et al. · Current Biology (2017)
Roseman, L., Demetriou, L., Wall, M. B. et al. · Neuropharmacology (2018)
Roseman, L., Nutt, D. J., Carhart-Harris, R. L. · Frontiers in Pharmacology (2018)
Rucker, J., Iliff, J., Nutt, D. J. · Neuropharmacology (2017)
Papers in Blossom that reference this study
Kuc, J., McAlpine, R. G., Sellers, A. et al. · Journal of Psychopharmacology (2026)
Davoudian, P. A., Jiang, Q., Knox, C. A. et al. · Biorxiv (2026)
Girn, M., Doss, M. K., Roseman, L. et al. · Nature Medicine (2026)
Kirlić, N., Atli, M., Mistry, S. et al. · Journal of Clinical Psychopharmacology (2025)
Martens, M. A. G., Cunha, B. G., Erritzoe, D. et al. · Translational Psychiatry (2025)
Pellegrini, L., Fineberg, N. A., O'Connor, S. et al. · Comprehensive Psychiatry (2025)
Blackburne, G., Mcalpine, R. G., Fabus, M. et al. · Cell Reports (2025)
Ludbrook, G., Bryson, N., Taylor, B. et al. · Journal of Clinical Psychopharmacology (2025)
Barta, S., Brooker, J., O’Callaghan, C. · Journal of Palliative Medicine (2025)
Wall, M. B., Demetriou, L., Giribaldi, B. et al. · American Journal of Psychiatry (2025)
Fink-Jensen, A., Jensen, M. E., Stenbæk, D. S. et al. · Journal of Psychopharmacology (2025)
Zeifman, R. J., Spriggs, M. J., Kettner, H. et al. · Scientific Reports (2025)
Nutt, D. J., Hunt, P., Schlag, A. K. et al. · British Journal of Clinical Pharmacology (2024)
Shinozuka, K., Jerotic, K., Mediano, P. A. M. et al. · Translational Psychiatry (2024)
Agnorelli, C., Spriggs, M. J., Godfrey, K. et al. · Preprints (2024)
Saha, D., Singh, A., Vaidya, V. A. et al. · ACS Chemical Neuroscience (2024)
Avram, M., Fortea, L., Wollner, L. et al. · Molecular Psychiatry (2024)
Palmisano, V. F., Agnorelli, C., Fagiolini, A. et al. · Biochemistry (2024)
Barba, T., Kettne, H., Radu, C. et al. · Scientific Reports (2024)
Siva, J. B., Barba, T., Kettner, H. et al. · Journal of Psychopharmacology (2024)
Szigeti, B., Weiss, B., Rosas, F. E. et al. · Psychological Medicine (2024)
Pizzi, S. D., Chiacchiaretta, P., Sestieri, C. et al. · NeuroImage (2023)
Jacobs, E., Murphy-Beiner, A., Rouiller, I. et al. · Neuroethics (2023)
Neubert, J. J., Anderson, K., Mason, N. L. · Psyarxiv (2023)
Zeifman, R. J., Wagner, A. C., Monson, C. M. et al. · Journal of Affective Disorders (2023)
Pizzi, S. D., Chiacchiaretta, P., Sestieri, C. et al. · Biological Psychiatry (2023)
Batievsky, D., Weiner, M., Kaplan, S. B. et al. · Frontiers in Pain Research (2023)
Mash, D. C. · Pharmacological Research (2023)
Timmermann, C., Roseman, L., Haridas, S. et al. · PNAS (2023)
Brasher, T., Rosen, D., Spinella, M. · International Journal of Wellbeing (2023)
Ruffini, G., Damiani, G., Lozano-Soldevilla, D. et al. · PLOS ONE (2023)
Ledwos, N., Rodas, J. D., Husain, M. I. et al. · Journal of Psychopharmacology (2022)
Giribaldi, B., Lyons, T., Rosas, F. E. et al. · Journal of Psychopharmacology (2022)
Baumann, S., Carhart-Harris, R. L., Nutt, D. J. et al. · Psyarxiv (2022)
Kaplan, A. L., Confair, D. N., Kim, K. et al. · Nature (2022)
Brys, I., Barrientos, S. A., Ward, J. et al. · Biorxiv (2022)
Fadahunsi, N., Lund, J., Breum, A. W. et al. · Translational Psychiatry (2022)
Glynos, N., Fields, C. W., Barron, J. et al. · Journal of Psychoactive Drugs (2022)
Hipólito, I., Mago, J., Rosas, F. E. et al. · Psyarxiv (2022)
Argento, E., Goldenberg, S., Deering, K. et al. · Drug and Alcohol Dependence (2022)
Daws, R. E., Timmermann, C., Giribaldi, B. et al. · Nature Medicine (2022)
Rodriguez, L., Lopez, A., Moyna, G. et al. · ACS Omega (2022)
Murphy, R., Murphy-Beiner, A., Kettner, H. et al. · Frontiers in Pharmacology (2022)
Timmermann, C., Watts, R., Dupuis, D. · Transcultural Psychiatry (2022)
Peill, J. M., Trinci, K. E., Kettner, H. et al. · Journal of Psychopharmacology (2022)
Polito, V., Liknaitzky, P. · Psyarxiv (2021)
Dursun, S. M., Kelly, J. R., Gillan, C. M. et al. · Frontiers in Psychiatry (2021)
Whitfield, H. J. · Frontiers in Psychiatry (2021)
Page, L., Rehman, A., Syed, H. et al. · Frontiers in Psychiatry (2021)
Strumila, R., Guillaume, S. · Pharmaceuticals (2021)
Nichols, C. D., Wiatr, K., Figiel, M. et al. · Journal of Neurochemistry (2021)
Ermakova, A. O., Dunbar, F., Rucker, J. et al. · Journal of Psychopharmacology (2021)
Verroust, V., Zafar, R., Spriggs, M. J. · Annales Médico-Psychologiques (2021)
Harding, F., Seynaeve, M., Keeler, J. et al. · Journal of Integrative Neuroscience (2021)
Zamani, A., Carhart-Harris, R. L., Christoff, K. · Neuropsychopharmacology (2021)
Hübner, S., Haijen, E. C. H. M., Kaelen, M. et al. · Journal of Medical Internet Research (2021)
Mans, K., Kettner, H., Erritzoe, D. et al. · Frontiers in Psychiatry (2021)
Corrigan, K., Haran, M., Mccandliss, C. et al. · Irish Journal of Medical Science (2021)
Daws, R. E., Timmermann, C., Giribaldi, B. et al. · Research Square (2021)
Lewis-Healey, E., Laukkonen, R., Van Elk, M. · Psyarxiv (2021)
Carhart-Harris, R. L., Wagner, A. C., Agrawal, M. et al. · Journal of Psychopharmacology (2021)
Carhart-Harris, R. L., Giribaldi, B., Watts, R. et al. · New England Journal of Medicine (2021)
Hesselgrave, N., Troppoli, T. A., Wulff, A. B. et al. · PNAS (2021)
Dos Santos, R. G., Hallak, J. E., Baker, G. et al. · Journal of Psychopharmacology (2021)
Zeifman, R. J., Singhal, N., Breslow, L. et al. · ACS Pharmacology and Translational Science (2021)
Kozłowska, U., Klimczak, A., Wiatr, K. et al. · Biorxiv (2021)
Szigeti, B., Kartner, L., Blemings, A. et al. · eLife (2021)
Olson, D. E. · ACS Pharmacology and Translational Science (2020)
Gandy, S., Forstmann, M., Carhart-Harris, R. L. et al. · Health Psychology Open (2020)
DiVito, A. J., Leger, R. F. · Molecular Biology Reports (2020)
Brouwer, A., Carhart-Harris, R. L. · Journal of Psychopharmacology (2020)
Andersen, K. A. A., Carhart-Harris, R. L., Nutt, D. J. et al. · Acta Psychiatrica Scandinavica (2020)
Gill, H., Gill, B., Chen-Li, D. et al. · Expert Review of Neurotherapeutics (2020)
Greb, A. C., Vargas, M. V., Duim, W. C. et al. · ACS Pharmacology and Translational Science (2020)
Rubin-Kahana, D. S., Hassan, A. N., Le Foll, B. · Journal of Addiction Medicine (2020)
Spriggs, M. J., Kettner, •. H., Carhart-Harris, •. R. L. · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity (2020)
Kim, K., Che, T., Panova, O. et al. · Cell (2020)
Kelly, J. R., Crockett, M. T., Alexander, L. et al. · Irish Journal of Psychological Medicine (2020)