Cited by 305Psychedelics and Drug StudiesNeurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatment

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5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride

Vollenweider, F·1999·Neuropsychopharmacology

DOI 10.1016/s0893-133x(98)00108-0

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Abstract

The modulating effects of serotonin on dopamine neurotransmission are not well understood, particularly in acute psychotic states. Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psilocybin (n = 7). Psilocybin is a potent indoleamine hallucinogen and a mixed 5-HT2A and 5-HT1A receptor agonist. Psilocybin administration (0.25 mg/kg p.o.) produced changes in mood, disturbances in thinking, illusions, elementary and complex visual hallucinations and impaired ego-functioning. Psilocybin significantly decreased [11C]raclopride receptor binding potential (BP) bilaterally in the caudate nucleus (19%) and putamen (20%) consistent with an increase in endogenous dopamine. Changes in [11C]raclopride BP in the ventral striatum correlated with depersonalization associated with euphoria. Together with previous reports of 5-HT receptor involvement in striatal dopamine release, it is concluded that stimulation of both 5-HT2A and 5-HT1A receptors may be important for the modulation of striatal dopamine release in acute psychoses. The present results indirectly support the hypothesis of a serotonin-dopamine dysbalance in schizophrenia and suggest that psilocybin is a valuable tool in the analysis of serotonin-dopamine interactions in acute psychotic states.

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BackgroundResult
A Research Domain Criteria (RDoC)-Guided Dashboard to Review Psilocybin Target Domains: A Systematic Review
Pouyan, N., Khankahdani, Z. H., Sisi, F. Y., Lee, Y. L., Rosenblat, J. D., Teopiz, K. M., Lui, L. M. W., Subramaniapillai, M., Lin, K., Nasri, F., et al. (2022) · CNS Drugs · doi:10.1007/s40263-022-00944-y · Cited by 18
The Neurobiological Correlates of Meditation and Mindfulness
Edwards, J. E., Peres, J., Monti, D., & Newberg, A. B. (2011) · Springer eBooks · doi:10.1007/978-1-4614-0647-1_6 · Cited by 16
Neurocognitive effects of psilocybin: A systematic and comprehensive review of neuroimaging studies in humans
Berkovitch, L., Fauvel, B., Preller, K. H., & Gaillard, R. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106239 · Cited by 16
The Algorithmic Agent Perspective and Computational Neuropsychiatry: From Etiology to Advanced Therapy in Major Depressive Disorder
Ruffini, G., Castaldo, F., Lopez-Sola, E., Sanchez-Todo, R., & Vohryzek, J. (2024) · Entropy · doi:10.3390/e26110953 · Cited by 20
Natural psychedelics in the treatment of depression; a review focusing on neurotransmitters
Jahanabadi, S., Amiri, S., Karkeh-abadi, M., & Razmi, A. (2023) · Fitoterapia · doi:10.1016/j.fitote.2023.105620 · Cited by 15
[Cross-cultural adaptation and validation of the Cambridge Depersonalisation Scale].
Castillo, J. J. M., de la Iglesia, J. M., Colomer, C. A., Berríos, G. E., Sierra, M., & Luque, R. L. (2006) · Actas Españolas de Psiquiatría · Cited by 14
Probing the antidepressant potential of psilocybin: integrating insight from human research and animal models towards an understanding of neural circuit mechanisms
Meccia, J., Lopez, J., & Bagot, R. C. (2022) · Psychopharmacology · doi:10.1007/s00213-022-06297-0 · Cited by 13
Neurobiology of the Effects of Psilocybin in Relation to Its Potential Therapeutic Targets
Tylš, F., Páleníček, T., & Horáček, J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800212-4.00073-x · Cited by 14
Anatomical relationships between serotonin 5-HT2A and dopamine D2 receptors in living human brain
Ishii, T., Kimura, Y., Ichise, M., Takahata, K., Kitamura, S., Moriguchi, S., Kubota, M., Zhang, M.-R., Yamada, M., Higuchi, M., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0189318 · Cited by 12
Imaging addiction with PET: is insight in sight?
Schiffer, W. K., Lee, D. E., Brodie, J. D., & Dewey, S. L. (2005) · Drug Discovery Today · doi:10.1016/s1359-6446(05)03412-4 · Cited by 13
Plasma levels of dopamine metabolite correlate with mismatch negativity in patients with schizophrenia
Shiga, T., Horikoshi, S., Kanno, K., Kanno‐Nozaki, K., Hikita, M., Itagaki, S., Miura, I., & Yabe, H. (2020) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12984 · Cited by 12
Microdosing psychedelics as cognitive and emotional enhancers.
Rifkin, B. D., Maraver, M. J., & Colzato, L. S. (2020) · Psychology of Consciousness Theory Research and Practice · doi:10.1037/cns0000213 · Cited by 15
Exploring the effect of microdosing psychedelics on creativity in an open-label natural settingPreprint
Prochazkova, L., Lippelt, D. P., Colzato, L. S., Kuchař, M., Sjoerds, Z., & Hommel, B. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/384412 · Cited by 12
Depression and Prefrontal Cortex: All Roads Lead to Dopamine
Moghaddam, B., & Abbas, A. I. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.02.015 · Cited by 11
Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats
Tylš, F., Vejmola, Č., Koudelka, V., Piorecká, V., Kadeřábek, L., Bochin, M., Novák, T., Kuchař, M., Bendová, Z., Brunovský, M., et al. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1152578 · Cited by 11
A continuum hypothesis of psychotomimetic rapid antidepressants
Haarsma, J., Harmer, C. J., & Tamm, S. (2021) · Brain and Neuroscience Advances · doi:10.1177/23982128211007772 · Cited by 13
“Indeed, following the intake of psilocybin, increases in dopamine levels in the striatum, which correlated to euphoria and depersonalisation, have been shown (Vollenweider et al., 1999).”
Background
The possible place for psychedelics in pharmacotherapy of mental disorders
Wojtas, A. (2023) · Pharmacological Reports · doi:10.1007/s43440-023-00550-9 · Cited by 12
“Quite similar to LSD, modern studies concerning psilocybin originated also in Switzerland, with the drug being used in research of psychotic disorders [136, 137]; which then evolved into basic studies describing the effects of psilocybin in healthy volunteers [138].”
Result
Untitled work
(2000) · doi:10.1002/1099-1077(200010)15:7
The Circumplex Structure of Depersonalization/Derealization
Sacco, R. (2010) · International Journal of Psychological Studies · doi:10.5539/ijps.v2n2p26 · Cited by 12
“The most common psychoactive drugs to cause DP/DR are cannabis (Melges, Tinklenberg, Hollister, & Gillespie, 1970b) and hallucinogens (Vollenweider et al., 1999), but DP/DR episodes can also be precipitated by ketamine (“special K”) and MDMA (“ecstasy”) (Medford et al.”
Bioactive Alkaloids from Fungi: Psilocybin
Mahmood, Z. (2013) · Springer eBooks · doi:10.1007/978-3-642-22144-6_19 · Cited by 11
Measurement of psychological state changes at low dopamine transporter occupancy following a clinical dose of mazindol
Kimura, Y., Maeda, J., Yamada, M., Takahata, K., Yokokawa, K., Ikoma, Y., Seki, C., Ito, H., Higuchi, M., & Suhara, T. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4464-x · Cited by 11
Psychedelic research in Australia: Breaking through the stigma
Puspanathan, P. (2017) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867417701580 · Cited by 10
“Suggestions of possible risks have been made (Vollenweider et al., 1999) but not explored in depth and insufficient safety data, small sample sizes and so on remain a barrier to confidence in the literature.”
Background
Dopamine, Serotonin, and Structure/Function Brain Defects as Biological Bases for Treatment Response in Delusional Disorder: A Systematic Review of Cases and Cohort Studies
Guàrdia, A., González-Rodríguez, A., Seeman, M. V., Pedrero, A. Á., Estrada, F., Acebillo, S., Labad, J., & Monreal, J. A. (2021) · Behavioral Sciences · doi:10.3390/bs11100141 · Cited by 10
“The results of our literature search indirectly support the hypothesis of a serotonin-dopamine dysregulation in DD and help to explain the fact that antidepressants as well as antipsychotics show efficacy in this disorder [25,58].”
Result
Classical psychedelics’ action on brain monoaminergic systems
Butler, J. J., Ricci, D., Aman, C., Beyeler, A., & Deurwaerdère, P. D. (2024) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2024.106669 · Cited by 12
Psychedelics and fNIRS neuroimaging: exploring new opportunities
Scholkmann, F., & Vollenweider, F. X. (2022) · Neurophotonics · doi:10.1117/1.nph.10.1.013506 · Cited by 9
Self-citation
Derivatives of 3, 4, 5-Trimethoxycinnamic Acid Ameliorate Stress-Induced Anxiety in Mice and Rats
Hong, E., Min, H. K., Lim, H., Gu, S. M., Jabborov, A., Yayeh, T., Kim, M., Park, W., Jung, J., Yun, J., et al. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03240-y · Cited by 9
Biology and recent brain imaging studies in affective psychoses
Wang, P. W., & Ketter, T. A. (2000) · Current Psychiatry Reports · doi:10.1007/s11920-000-0071-x · Cited by 9
Dissociable effects of psilocybin and escitalopram for depression on processing of musical surprises
Harding, R., Singer, N., Wall, M. B., Hendler, T., Erritzøe, D., Nutt, D., Carhart-Harris, R. L., & Roseman, L. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03035-8 · Cited by 11
Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats
Fuini, E., Chang, A., Ortiz, R. J., Nasseef, M. T., Edwards, J., Latta, M., Gonzalez, E., Woodward, T. J., Bradshaw, H. B., Axe, B., et al. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1554049 · Cited by 11
Hypothesis: a promising effect of 5-HT1A receptor agonists in alleviating motor symptoms of Parkinson's disease.
Nayebi, A. M. (2010) · African Journal of Pharmacy and Pharmacology · doi:10.5897/ajpp.9000172 · Cited by 8
Trapped in a Glass Bell Jar: Neural Correlates of Depersonalization and Derealization in Subjects at Clinical High-Risk of Psychosis and Depersonalization–Derealization Disorder
Büetiger, J. R., Hubl, D., Kupferschmid, S., Schultze‐Lutter, F., SCHIMMELMANN, B. G., Federspiel, A., Hauf, M., Walther, S., Kaess, M., Michel, C., et al. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.535652 · Cited by 8
Interactive effects of cholecystokinin-8S and various serotonin receptor agonists onthe firing activity of neostriatal neuronesin rats
Wilms, K., Vierig, G., & Davidowa, H. (2001) · Neuropeptides · doi:10.1054/npep.2001.0875 · Cited by 8
Transformation of Brain Structure and Spiritual Experience
Newberg, A. B. (2012) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780199729920.013.0031 · Cited by 8
Light therapy for sleep disturbance comorbid depression in relation to neural circuits and interactive hormones—A systematic review
Chen, Y., Zhang, Y., Feng, G., Lei, Y., Liu, Q., & Liu, Y. (2023) · PLoS ONE · doi:10.1371/journal.pone.0286569 · Cited by 8
“It is reported that 5-HT modulation of DA release in the basal ganglia is correlated with acute psychoses [112].”
Background
New frontiers in the biosynthesis of psychoactive specialized metabolites
Li, G., & Facchini, P. J. (2024) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2024.102626 · Cited by 7
Psychedelics as pharmacotherapeutics for substance use disorders: A scoping review on clinical trials and perspectives on underlying neurobiology
Wittenkeller, L. M., Gudelsky, G. A., Winhusen, T. M., & Amato, D. (2025) · British Journal of Pharmacology · doi:10.1111/bph.70181 · Cited by 7
“In line with our interpretations, it has been demonstrated that 17.5 mg/70 kg psi-locybin, a dose lower than that of clinical trials, is capable of elevating extracellular dopamine in healthy individuals (Vollenweider et al., 1999).”
Influential
The Effectiveness of Microdosed Psilocybin in the Treatment of Neuropsychiatric Lyme Disease: A Case Study
Kinderlehrer, D. A. (2023) · International Medical Case Reports Journal · doi:10.2147/imcrj.s395342 · Cited by 7

Authors: Vollenweider, F.
Affiliations: University Hospital Zurich (CH)
Corresponding author: Vollenweider, F
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 1999-05
Volume: 20
Issue: 5
Pages: 424-433
ISSN: 0893-133X (ISSN-L)
DOI: 10.1016/s0893-133x(98)00108-0
OpenAlex: W1986425243
Cited by: 305
References: 73
Citations by year: 2026: 15 · 2025: 18 · 2024: 28 · 2023: 28 · 2022: 20 · 2021: 18 · 2020: 19 · 2019: 6 · 2018: 13 · 2017: 7 · 2016: 14 · 2015: 7 · 2014: 6 · 2013: 9 · 2012: 11
FWCI: 8.62
Type: journal article
Language: en
Open access: closed
Locations: Neuropsychopharmacology (publishedVersion)
PubMed (publishedVersion)
DORA PSI (Paul Scherrer Institute) (submittedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Topics: Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords: psilocybin, psychosis, serotonin, dopamine release, dopamine D2 receptor, [11C]raclopride, striatum, caudate nucleus, putamen, 5-HT2A receptor, 5-HT1A receptor, serotonin-dopamine interaction, hallucinations, depersonalization, schizophrenia
MeSH terms: Adult, Basal Ganglia, Dopamine, Hallucinogens, Humans, Male, Psilocybin, Psychometrics, Psychoses, Substance-Induced, Salicylamides, Serotonin, Tomography, Emission-Computed, Antipsychotic Agents, Dopamine Antagonists, Raclopride

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5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride

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