Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels
Open accessAbstract
The main psychedelic component of magic mushrooms is psilocybin, which shows promise as a treatment for depression and other mental disorders. Psychedelic effects are believed to emerge through stimulation of serotonin 2A receptors (5-HT2ARs) by psilocybin's active metabolite, psilocin. We here report for the first time the relationship between intensity of psychedelic effects, cerebral 5-HT2AR occupancy and plasma levels of psilocin in humans. Eight healthy volunteers underwent positron emission tomography (PET) scans with the 5-HT2AR agonist radioligand [11 C]Cimbi-36: one at baseline and one or two additional scans on the same day after a single oral intake of psilocybin (3-30 mg). 5-HT2AR occupancy was calculated as the percent change in cerebral 5-HT2AR binding relative to baseline. Subjective psychedelic intensity and plasma psilocin levels were measured during the scans. Relations between subjective intensity, 5-HT2AR occupancy, and plasma psilocin levels were modeled using non-linear regression. Psilocybin intake resulted in dose-related 5-HT2AR occupancies up to 72%; plasma psilocin levels and 5-HT2AR occupancy conformed to a single-site binding model. Subjective intensity was correlated with both 5-HT2AR occupancy and psilocin levels as well as questionnaire scores. We report for the first time that intake of psilocybin leads to significant 5-HT2AR occupancy in the human brain, and that both psilocin plasma levels and 5-HT2AR occupancy are closely associated with subjective intensity ratings, strongly supporting that stimulation of 5-HT2AR is a key determinant for the psychedelic experience. Important for clinical studies, psilocin time-concentration curves varied but psilocin levels were closely associated with psychedelic experience.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the Madsen PET study, cerebral 5HT2A receptor availability measured using agonist ligand [11C]-Cimbi-36 indicated dose-dependent brain receptor occupancy as high as 76%, which occurred when plasma psilocin concentration was about 100 nM.
“Results indicated a dose-dependent brain receptor occupancy as high as 76%, which occurred when the plasma psilocin (8) concentration was about 100 nM.”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [106]
The Discussion reports dose-dependent cerebral 5-HT2A receptor occupancy, and the ‘Psilocin levels and receptor occupancy relations’ section gives a model-estimated maximum of 76.6%. But 76.6% is a predicted maximum, not an occupancy observed at about 100 nM plasma psilocin; the Results report observed occupancies of 43–72% at the first PET scan. The cited passages do not establish the claimed concentration–occupancy pairing. (LLM, conf=0.89)
Experimental — accuracy not yet measuredData showed a rough relationship between the duration of the hallucinogenic experience (60-360 min) and the interval in which plasma psilocin concentration exceeded approximately 10 nM.
“Their data also showed a rough relationship between the duration of the hallucinogenic experience (60–360 min) and the interval in which the plasma psilocin (8) concentration exceeding approximately 10 nM.”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [106]
The ‘Psilocin levels and receptor occupancy relations’ section says subjective intensity ratings followed a qualitatively similar time course to plasma psilocin levels, supporting a rough temporal relationship. The copy does not establish a 60–360-minute duration or show that the experience lasted while plasma psilocin exceeded approximately 10 nM. In the Discussion, 10 nM is identified as the EC50 for receptor occupancy, not a threshold for the experience. (LLM, conf=0.86)
Experimental — accuracy not yet measuredA single dose of psilocybin provoked in healthy individuals a long-lasting increase in scores for the personality traits of openness to experience and mindfulness, which correlated inversely with reductions in [11C]-Cimbi-36 binding.
“However, a single dose of psilocybin (2) provoked in healthy individuals a long-lasting increase in scores for the personality traits of openness to experience and mindfulness, which correlated inversely with reductions in [11C]-Cimbi-36 (38) binding [106].”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [106]
The Abstract reports that eight healthy volunteers received a single psilocybin dose and had reduced [11C]Cimbi-36 binding measured by PET that same day. The Discussion describes long-term effects on personality as a subject for future study; this paper does not report lasting increases in openness or mindfulness, or an inverse correlation between those traits and binding reductions. Page numbers are unavailable in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe intensity of the psychedelic experience correlated with receptor occupancy, and with plasma psilocin concentration, assuming a single site model.
“Furthermore, the intensity of the psychedelic experience correlated with receptor occupancy, and with the plasma psilocin (8) concentration, assuming a single site model.”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [106]
The Results section ('Psilocin levels and receptor occupancy relations') reports positive associations of subjective intensity with both 5-HT2A receptor occupancy and plasma psilocin levels. The Discussion says the single-site binding model fits the relationship between plasma psilocin concentration and receptor occupancy—not the relationship between intensity and either measure. The intensity–occupancy relationship was described as quadratic. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLow doses of psilocybin may induce a therapeutic effect.
“and may therefore induce a therapeutic effect.”
From Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial (2024) · cites this paper as [116]
The Discussion says microdosing has been argued to improve mood and suggests 0.5–2 mg for future studies. The Introduction describes psilocybin as a promising treatment, but the paper does not establish that low doses have a therapeutic effect. (LLM, conf=0.83)
Experimental — accuracy not yet measured
The subjectively reported intensity of the psychedelic experience of psilocybin in humans correlates with 5-HT2AR occupancy and plasma psilocin levels.
“Since the subjectively reported intensity of the psychedelic experience of psilocybin in humans correlates with 5-HT 2A R occupancy and plasma psilocin levels (Madsen et al., 2019;Stenbæk et al. 2021)”
From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Madsen et al., 2019
Occupancy by psilocin at [11C]-Cimbi-36 agonist binding sites (circa 60%) was quite similar to the displacement of [18F]-altanserin by a similar dose of psilocybin reported by Hasler et al.
“Interestingly, the occupancy by psilocin (8) at [11C]-Cimbi-36 (38) agonist binding sites (circa 60%) was quite similar to the displacement of [18F]-altanserin (39) by a similar dose of psilocybin (2) reported by Hasler et al. [105].”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [106]
Pharmacokinetic research has shown dose-dependent increases in receptor occupancy and subjective effects of psilocybin across the dose range of 3 to 30 mg.
“Pharmacokinetic research has shown dose-dependent increases in receptor occupancy and subjective effects of psilocybin across the dose range of 3 to 30 mg. 18”
From Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression (2022) · cites this paper as [18]
Even low doses of psilocybin show considerable occupancy of cortical 5-HT2A receptors.
“even low doses of psilocybin show considerable occupancy of cortical 5-HT2ARs [116]”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
(1998) · The Journal of Clinical Psychiatry · Cited by 19,139 · see citing works
(1998) · PubMed · Cited by 10,216 · see citing works
Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., & Klinedinst, M. A. (2016) · Journal of Psychopharmacology · doi:10.1177/0269881116675513 · Cited by 2,201 · see citing works
Simplified Reference Tissue Model for PET Receptor Studies
Lammertsma, A. A., & Hume, S. P. (1996) · NeuroImage · doi:10.1006/nimg.1996.0066 · Cited by 2,025 · see citing works
Consensus Nomenclature for <i>in vivo</i> Imaging of Reversibly Binding Radioligands
Innis, R. B., Cunningham, V. J., Delforge, J., Fujita, M., Gjedde, A., Gunn, R. N., Holden, J., Houle, S., Huang, S.-C., Ichise, M., et al. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600493 · Cited by 1,955 · see citing works
Self-citationRoss, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., Mennenga, S. E., Belser, A., Kalliontzi, K., Babb, J., et al. (2016) · Journal of Psychopharmacology · doi:10.1177/0269881116675512 · Cited by 1,698 · see citing works
Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M. J., Erritzoe, D., Kaelen, M., Bloomfield, M., Rickard, J. A., Forbes, B., Feilding, A., et al. (2016) · The Lancet Psychiatry · doi:10.1016/s2215-0366(16)30065-7 · Cited by 1,540 · see citing works
Bunney, W. E., Hippius, H., Laakmann, G., & Schmauß, M. (1990) · Springer eBooks · doi:10.1007/978-3-642-74034-3 · Cited by 1,523 · see citing works
Human hallucinogen research: guidelines for safety
Johnson, M., Richards, W., & Griffiths, R. (2008) · Journal of Psychopharmacology · doi:10.1177/0269881108093587 · Cited by 1,203 · see citing works
Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin
Carhart-Harris, R. L., Erritzoe, D., Williams, T., Stone, J. M., Reed, L. J., Colasanti, A., Tyacke, R. J., Leech, R., Malizia, A. L., Murphy, K., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1119598109 · Cited by 1,172 · see citing works
Self-citationPsilocybin-assisted treatment for alcohol dependence: A proof-of-concept study
Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A., Wilcox, C. E., Barbosa, P., & Strassman, R. J. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881114565144 · Cited by 1,151 · see citing works
Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action
Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A., Vogel, H., & Hell, D. (1998) · NeuroReport · doi:10.1097/00001756-199812010-00024 · Cited by 1,018 · see citing works
González-Maeso, J., Weisstaub, N. V., Zhou, M., Chan, P., Ivic, L., Ang, R., Lira, A., Bradley-Moore, M., Ge, Y., Zhou, Q., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.008 · Cited by 925 · see citing works
Pilot study of the 5-HT <sub>2A</sub> R agonist psilocybin in the treatment of tobacco addiction
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., & Griffiths, R. R. (2014) · Journal of Psychopharmacology · doi:10.1177/0269881114548296 · Cited by 914 · see citing works
MacLean, K. A., Johnson, M. W., & Griffiths, R. R. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881111420188 · Cited by 895 · see citing works
Psychometric evaluation of the altered states of consciousness rating scale (OAV)
Studerus, E., Gamma, A., & Vollenweider, F. X. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012412 · Cited by 683 · see citing works
Psychedelics and the essential importance of context
Carhart-Harris, R. L., Roseman, L., Haijen, E., Erritzoe, D., Watts, R., Branchi, I., & Kaelen, M. (2018) · Journal of Psychopharmacology · doi:10.1177/0269881118754710 · Cited by 657 · see citing works
Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin
Barrett, F. S., Johnson, M. W., & Griffiths, R. R. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881115609019 · Cited by 637 · see citing works
Ego-dissolution and psychedelics: validation of the ego-dissolution inventory (EDI).
Nour, M. M., Evans, L., Nutt, D., & Carhart-Harris, R. L. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00269 · Cited by 470 · see citing works
Svarer, C., Madsen, K., Hasselbalch, S. G., Pinborg, L. H., Haugbøl, S., Frøkjær, V. G., Holm, S., Paulson, O. B., & Knudsen, G. M. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.10.017 · Cited by 383 · see citing works
Self-citationReceptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens
Rickli, A., Moning, O. D., Hoener, M. C., & Liechti, M. E. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2016.05.001 · Cited by 379 · see citing works
Prediction of Psilocybin Response in Healthy Volunteers
Studerus, E., Gamma, A., Kometer, M., & Vollenweider, F. X. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030800 · Cited by 369 · see citing works
A High-Resolution<i>In Vivo</i>Atlas of the Human Brain's Serotonin System
Beliveau, V., Ganz, M., Feng, L., Ozenne, B., Højgaard, L., Fisher, P. M., Svarer, C., Greve, D. N., & Knudsen, G. M. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2830-16.2016 · Cited by 368 · see citing works
Self-citationKometer, M., Schmidt, A., Bachmann, R., Studerus, E., Seifritz, E., & Vollenweider, F. X. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.04.005 · Cited by 298 · see citing works
Psilocybin, ein psychotroper Wirkstoff aus dem mexikanischen RauschpilzPsilocybe mexicana Heim
Hofmann, A., Heim, R., Brack, A., & Kobel, H. (1958) · Experientia · doi:10.1007/bf02159243 · Cited by 282 · see citing works
Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data
Greve, D. N., Svarer, C., Fisher, P. M., Feng, L., Hansen, A. E., Baare, W., Rosen, B., Fischl, B., & Knudsen, G. M. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2013.12.021 · Cited by 264 · see citing works
Self-citationMamo, D. C., Graff, A., Mizrahi, R., Shammi, C., Romeyer, F., & Kapur, S. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.06091479 · Cited by 241 · see citing works
Hasler, F., Bourquin, D., Brenneisen, R., Bär, T., & Vollenweider, F. X. (1997) · Pharmaceutica Acta Helvetiae · doi:10.1016/s0031-6865(97)00014-9 · Cited by 234 · see citing works
Specific Gravity of Blood and Plasma at 4 and 37 °C
TRUDNOWSKI, R. J., & Rico, R. (1974) · Clinical Chemistry · doi:10.1093/clinchem/20.5.615 · Cited by 211 · see citing works
Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes
McKenna, D. J., Repke, D. B., Lo, L., & Peroutka, S. J. (1990) · Neuropharmacology · doi:10.1016/0028-3908(90)90001-8 · Cited by 195 · see citing works
Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults
Brown, R. T., Nicholas, C. R., Cozzi, N. V., Gassman, M. C., Cooper, K. M., Muller, D., Thomas, C. D., Hetzel, S. J., Henriquez, K. M., Ribaudo, A. S., et al. (2017) · Clinical Pharmacokinetics · doi:10.1007/s40262-017-0540-6 · Cited by 188 · see citing works
Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines
Blair, J. B., Kurrasch-Orbaugh, D., Marona-Lewicka, D., Cumbay, M. G., Watts, V. J., Barker, E. L., & Nichols, D. E. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm000339w · Cited by 131 · see citing works
Comparison of psilocin with psilocybin, mescaline and LSD-25
Wolbach, A. B., Miner, E. J., & Isbell, H. (1962) · Psychopharmacology · doi:10.1007/bf00412109 · Cited by 123 · see citing works
Serotonin2 agonist administration down-regulates rat brain serotonin2 receptors
Buckholtz, N. S., Zhou, D., & Freedman, D. X. (1988) · Life Sciences · doi:10.1016/0024-3205(88)90342-6 · Cited by 106 · see citing works
Serotonin 2A Receptor Agonist Binding in the Human Brain with [ 11 C]Cimbi-36
Ettrup, A., da Cunha-Bang, S., McMahon, B., Lehel, S., Dyssegaard, A., Skibsted, A. P., Jørgensen, L. M., Hansen, M. A., Baandrup, A. O., Bache, S., et al. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2014.68 · Cited by 105 · see citing works
Self-citationSalinas, C. A., Searle, G. E., & Gunn, R. N. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2014.202 · Cited by 99 · see citing works
Lindenblatt, H., Krämer, E., Holzmann-Erens, P., Gouzoulis‐Mayfrank, E., & Kovar, K. (1998) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(98)00067-x · Cited by 90 · see citing works
Sex differences and serotonergic mechanisms in the behavioural effects of psilocin
Tylš, F., Páleníček, T., Kadeřábek, L., Fujáková-Lipski, M., Kubešová, A., & Horáček, J. (2015) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000198 · Cited by 86 · see citing works
Buckholtz, N. S., Zhou, D.-F., Freedman, D. X., & Potter, W. Z. (1990) · PubMed · Cited by 80 · see citing works
Karaki, S., Bécamel, C., Murat, S., la Cour, C. M., Millan, M. J., Prézeau, L., Bockaert, J., Marin, P., & Vandermoere, F. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.036558 · Cited by 74 · see citing works
Ettrup, A., Svarer, C., McMahon, B., da Cunha-Bang, S., Lehel, S., Møller, K., Dyssegaard, A., Ganz, M., Beliveau, V., Jørgensen, L. M., et al. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.02.001 · Cited by 72 · see citing works
Self-citationGründer, G. (1997) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00044-4 · Cited by 68 · see citing works
Fitzgerald, L. W., Conklin, D. S., Krause, C., et al. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0722127.x · Cited by 61 · see citing works
The mass action equation in pharmacology
Kenakin, T. (2015) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12810 · Cited by 57 · see citing works
Daily LSD administration selectively decreases serotonin2 receptor binding in rat brain
Buckholtz, N. S., Freedman, D. X., & Middaugh, L. D. (1985) · European Journal of Pharmacology · doi:10.1016/0014-2999(85)90407-8 · Cited by 57 · see citing works
PET analysis of the 5-HT2A receptor inverse agonist ACP-103 in human brain
Nordström, A., Månsson, M., Jovanovic, H., Karlsson, P., Halldin, C., Farde, L., Vanover, K. E., Hacksell, U., Brann, M. R., Davis, R. E., et al. (2007) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145707007869 · Cited by 49 · see citing works
Imaging in Central Nervous System Drug Discovery
Gunn, R. N., & Rabiner, E. A. (2016) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2016.09.001 · Cited by 49 · see citing works
López‐Giménez, J. F., Villazón, M., Brea, J. M., et al. (2001) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)12295-x · Cited by 47 · see citing works
Jørgensen, L. M., Weikop, P., Villadsen, J., Visnapuu, T., Ettrup, A., Hansen, H. D., Baandrup, A. O., Andersen, F. L., Bjarkam, C. R., Thomsen, C., et al. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16629483 · Cited by 44 · see citing works
Self-citationQuednow, B. B., Geyer, M. A., & Halberstadt, A. L. (2010) · Handbook of behavioral neuroscience · doi:10.1016/s1569-7339(10)70102-8 · Cited by 39 · see citing works
Johansen, A., Hansen, H. D., Svarer, C., Lehel, S., Leth-Petersen, S., Kristensen, J. L., Gillings, N., & Knudsen, G. M. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17746179 · Cited by 25 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Trial of Psilocybin versus Escitalopram for Depression
Carhart-Harris, R., Giribaldi, B., Watts, R., Baker-Jones, M., Murphy-Beiner, A., Murphy, R., Martell, J., Blemings, A., Erritzoe, D., & Nutt, D. J. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2032994 · Cited by 1,391 · see citing works
Self-citationREBUS and the anarchic brain: Toward a unified model of the brain action of psychedelics
Carhart-Harris, R. L., & Friston, K. J. (2019) · Pharmacological Reviews · doi:10.1124/pr.118.017160 · Cited by 1,180 · see citing works
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression
Goodwin, G. M., Aaronson, S. T., Alvarez, O., Arden, P. C., Baker, A., Bennett, J. C., Bird, C., Blom, R. E., Brennan, C., Brusch, D., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2206443 · Cited by 1,167 · see citing works
Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo
Shao, L.-X., Liao, C., Gregg, I., Davoudian, P. A., Savalia, N. K., Delagarza, K., & Kwan, A. C. (2021) · Neuron · doi:10.1016/j.neuron.2021.06.008 · Cited by 626 · see citing works
Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders
Vollenweider, F. X., & Preller, K. H. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0367-2 · Cited by 570 · see citing works
Psychedelics reopen the social reward learning critical period
Nardou, R., Sawyer, E., Song, Y. J., Wilkinson, M., Padovan-Hernandez, Y., de Deus, J. L., Wright, N., Lama, C., Faltin, S., Goff, L. A., et al. (2023) · Nature · doi:10.1038/s41586-023-06204-3 · Cited by 358 · see citing works
Andersen, K. A. A., Carhart‐Harris, R., Nutt, D. J., & Erritzoe, D. (2021) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.13249 · Cited by 347 · see citing works
Self-citationStructure-based discovery of nonhallucinogenic psychedelic analogs
Cao, D., Yu, J., Wang, H., Luo, Z., Liu, X., He, L., Qi, J., Fan, L., Tang, L., Chen, Z., et al. (2022) · Science · doi:10.1126/science.abl8615 · Cited by 312 · see citing works
Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics
Aleksandrova, L. R., & Phillips, A. G. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2021.08.003 · Cited by 276 · see citing works
Designer drugs: mechanism of action and adverse effects
Luethi, D., & Liechti, M. E. (2020) · Archives of Toxicology · doi:10.1007/s00204-020-02693-7 · Cited by 262 · see citing works
Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms
Inserra, A., De Gregorio, D., & Gobbi, G. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000056 · Cited by 232 · see citing works
Holze, F., Ley, L., Müller, F., Becker, A. M., Straumann, I., Vizeli, P., Kuehne, S. S., Roder, M. A., Duthaler, U., Kolaczynska, K. E., et al. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-022-01297-2 · Cited by 226 · see citing works
Pharmacological, neural, and psychological mechanisms underlying psychedelics: A critical review
van Elk, M., & Yaden, D. B. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104793 · Cited by 221 · see citing works
Mertens, L. J., Wall, M. B., Roseman, L., Demetriou, L., Nutt, D. J., & Carhart-Harris, R. L. (2020) · Journal of Psychopharmacology · doi:10.1177/0269881119895520 · Cited by 208 · see citing works
Raval, N. R., Johansen, A., Donovan, L. L., Ros, N. F., Ozenne, B., Hansen, H. D., & Knudsen, G. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020835 · Cited by 200 · see citing works
Self-citationMadsen, M. K., Fisher, P. M., Stenbæk, D. S., Kristiansen, S., Burmester, D., Lehel, S., Páleníček, T., Kuchař, M., Svarer, C., Ozenne, B., et al. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.02.001 · Cited by 183 · see citing works
Self-citationBecker, A. M., Holze, F., Grandinetti, T., Klaiber, A., Toedtli, V. E., Kolaczynska, K. E., Duthaler, U., Varghese, N., Eckert, A., Grünblatt, E., et al. (2022) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.2487 · Cited by 184 · see citing works
Sloshower, J., Skosnik, P. D., Safi-Aghdam, H., Pathania, S., Syed, S., Pittman, B., & D’Souza, D. C. (2023) · Journal of Psychopharmacology · doi:10.1177/02698811231154852 · Cited by 165 · see citing works
Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing
Kaertner, L. S., Steinborn, M. B., Kettner, H., Spriggs, M. J., Roseman, L., Buchborn, T., Balaet, M., Timmermann, C., Erritzoe, D., & Carhart-Harris, R. L. (2021) · Scientific Reports · doi:10.1038/s41598-021-81446-7 · Cited by 145 · see citing works
Jefsen, O. H., Elfving, B., Wegener, G., & Müller, H. K. (2021) · Journal of Psychopharmacology · doi:10.1177/0269881120959614 · Cited by 127 · see citing works
Bender, D., & Hellerstein, D. J. (2022) · Psychopharmacology · doi:10.1007/s00213-021-06049-6 · Cited by 88 · see citing works
Psychedelics and Neural Plasticity: Therapeutic Implications
Grieco, S. F., Castrén, E., Knudsen, G. M., Kwan, A. C., Olson, D. E., Zuo, Y., Holmes, T. C., & Xu, X. (2022) · The Journal of Neuroscience · doi:10.1523/jneurosci.1121-22.2022 · Cited by 82 · see citing works
“…reported intensity of the psychedelic experience of psilocybin in humans correlates with 5-HT 2A R occupancy and plasma psilocin levels (Madsen et al., 2019; Stenbæk et al. 2021), it will be informative to compare the behavioral effects of comparable drug exposures in humans and in…”
Self-citationPsilocybin‐assisted group therapy in patients with cancer diagnosed with a major depressive disorder
Agrawal, M., Richards, W., Beaussant, Y., Shnayder, S., Ameli, R., Roddy, K., Stevens, N., Richards, B., Schor, N., Honstein, H., et al. (2024) · Cancer · doi:10.1002/cncr.35010 · Cited by 88 · see citing works
Psychedelics therapeutics: What we know, what we think, and what we need to research
Nutt, D., Spriggs, M., & Erritzoe, D. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109257 · Cited by 84 · see citing works
Self-citationRomeo, B., Hermand, M., Pétillion, A., Karila, L., & Benyamina, A. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.03.002 · Cited by 76 · see citing works
Psilocybin in neuropsychiatry: a review of its pharmacology, safety, and efficacy
Dodd, S., Norman, T. R., Eyre, H. A., Stahl, S. M., Phillips, A., Carvalho, A. F., & Berk, M. (2023) · CNS Spectrums · doi:10.1017/s1092852922000888 · Cited by 73 · see citing works
Marschall, J., Fejer, G., Lempe, P., Prochazkova, L., Kuchar, M., Hajkova, K., & van Elk, M. (2022) · Journal of Psychopharmacology · doi:10.1177/02698811211050556 · Cited by 72 · see citing works
Gotvaldová, K., Hájková, K., Borovička, J., Jurok, R., Cihlářová, P., & Kuchař, M. (2021) · Drug Testing and Analysis · doi:10.1002/dta.2950 · Cited by 67 · see citing works
Psychedelic therapy's transdiagnostic effects: A research domain criteria (RDoC) perspective
Kelly, J. R., Gillan, C. M., Prenderville, J., Kelly, C., Harkin, A., Clarke, G., & O'Keane, V. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.800072 · Cited by 69 · see citing works
Sloshower, J., Zeifman, R. J., Guss, J., Krause, R., Safi-Aghdam, H., Pathania, S., Pittman, B., & D’Souza, D. C. (2024) · Scientific Reports · doi:10.1038/s41598-024-58318-x · Cited by 65 · see citing works
Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids
Gotvaldová, K., Borovička, J., Hájková, K., Cihlářová, P., Rockefeller, A., & Kuchař, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214068 · Cited by 53 · see citing works
Agin-Liebes, G., Ekman, E., Anderson, B., Malloy, M., Haas, A., & Woolley, J. (2024) · Journal of Humanistic Psychology · doi:10.1177/00221678211022949 · Cited by 51 · see citing works
Foldi, C. J., Liknaitzky, P., Williams, M., & Oldfield, B. J. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00043 · Cited by 51 · see citing works
Mechanisms of SSRI Therapy and Discontinuation
Sharp, T., & Collins, H. (2023) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2023_452 · Cited by 45 · see citing works
Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans.
Cumming, P., Scheidegger, M., Dornbierer, D., Palner, M., Quednow, B. B., & Martin-Soelch, C. (2021) · Molecules · doi:10.3390/molecules26092451 · Cited by 43 · see citing works
“However, a single dose of psilocybin (2) provoked in healthy individuals a long-lasting increase in scores for the personality traits of openness to experience and mindfulness, which correlated inversely with reductions in [11C]-Cimbi-36 (38) binding [106].”
BackgroundOnofrj, M., Russo, M., Delli Pizzi, S., De Gregorio, D., Inserra, A., Gobbi, G., & Sensi, S. L. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02691-0 · Cited by 43 · see citing works
Historic psychedelic drug trials and the treatment of anxiety disorders.
Weston, N. M., Gibbs, D., Bird, C. I. V., Daniel, A., Jelen, L. A., Knight, G., Goldsmith, D., Young, A. H., & Rucker, J. J. (2020) · Depression and Anxiety · doi:10.1002/da.23065 · Cited by 38 · see citing works
DellaCrosse, M., Pleet, M., Morton, E., Ashtari, A., Sakai, K., Woolley, J., & Michalak, E. (2022) · PLOS ONE · doi:10.1371/journal.pone.0279073 · Cited by 28 · see citing works
Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex <i>in vivo</i>
Shao, L.-X., Liao, C., Gregg, I., Davoudian, P. A., Savalia, N. K., Delagarza, K., & Kwan, A. C. (2021) · doi:10.1101/2021.02.17.431629 · Cited by 628 · see citing works
Uncovering psychedelics: from neural circuits to therapeutic applications
Melani, A., Bonaso, M., Biso, L., Zucchini, B., Conversano, C., & Scarselli, M. (2025) · Pharmaceuticals · doi:10.3390/ph18010130 · Cited by 17 · see citing works
Kurzbaum, E., Páleníček, T., Sharchaton, A., Azerrad, S., & Dekel, Y. (2025) · Journal of Fungi · doi:10.3390/jof11020099 · Cited by 15 · see citing works
Vanderijst, L., Hever, F., Buot, A., Dauré, C., Benoit, J., Hanak, C., Veeser, J., Morgiève, M., Campanella, S., Kornreich, C., et al. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-05502-y · Cited by 13 · see citing works
“Moreover, our approach might decrease the effect sizes pertaining to group differences, as even low doses of psilocybin show considerable occupancy of cortical 5-HT 2A Rs [116] and may therefore induce a therapeutic effect.”
BackgroundAssessing potential of psilocybin for depressive disorders
Kozak, Z., Johnson, M. W., & Aaronson, S. T. (2023) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2023.2273493 · Cited by 11 · see citing works
Scala, M., Fabbri, C., Fusar-Poli, P., Di Lorenzo, G., Ferrara, M., Amerio, A., Fusar-Poli, L., Pichiecchio, A., Asteggiano, C., Menchetti, M., et al. (2024) · CNS Spectrums · doi:10.1017/s1092852924002268 · Cited by 9 · see citing works
Serotonergic psychedelics for depression: A comprehensive overview
Wingert, A. M., Agnorelli, C., Peill, J., Reed, S., Nutt, D. J., & Erritzoe, D. (2025) · International Review of Neurobiology · doi:10.1016/bs.irn.2025.04.009 · Cited by 2 · see citing works
Self-citation
- Authors
- Madsen, M. K., Fisher, P. M., Burmester, D., Dyssegaard, A., Stenbæk, D. S., Kristiansen, S., Johansen, S. S., Lehel, S., Linnet, K., Svarer, C., Erritzoe, D., Ozenne, B., & Knudsen, G. M.
- Affiliations
- University of Copenhagen (DK)
- Copenhagen University Hospital (DK)
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2019-01-26
- Volume
- 44
- Issue
- 7
- Pages
- 1328-1334
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC6784978
- OpenAlex
- W2914255920
- Cited by
- 517
- References
- 51
- Citations by year
- 2026: 83 · 2025: 101 · 2024: 92 · 2023: 82 · 2022: 66 · 2021: 52 · 2020: 34 · 2019: 6
- FWCI
- 46.13
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-03-08)
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- Funders
- Innovationsfonden (4108‐00004B)
- National Institute for Health and Care Research (ACF-2013-21-501)
- Lundbeckfonden (R231-2016-3236)
- Rigshospitalet (R130A5324)
- H. Lundbeck A/S (R231-2016-3236)
- National Institute of Mental Health
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Keywords
- psilocybin, psilocin, 5-HT2A receptor, psychedelic effects, subjective intensity, dose-response relationship, magic mushrooms, depression treatment
- MeSH terms
- Adult, Benzylamines, Brain, Carbon Radioisotopes, Female, Hallucinogens, Humans, Male, Phenethylamines, Protein Binding, Psilocybin, Receptor, Serotonin, 5-HT2A, Positron-Emission Tomography, Serotonin 5-HT2 Receptor Agonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
