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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
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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“Comparison of the two scans revealed a global 20% decline in [11C]-raclopride (41) binding in the striatum, which is similar to the displacements evoked by amphetamine or other strong releasers of dopamine.”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [96]
In the citing paper
“Furthermore, the decline in the ventral striatum correlated with individual ratings for euphoria and depersonalization.”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [96]
In the citing paper
“The other explanation of psychedelics' ability to facilitate altered states of consciousness characterized by heightened introspection and diminished ego boundaries is their influence on 5-HT1A [64] and 5-HT2B [65], and interacting with the dopaminergic [66] and glutamatergic systems [67].”
From Mindfulness meditation and psychedelics: potential synergies and commonalities (2023) · cites this paper as [66]
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Jóźwiak-Bębenista, M., Stasiak, A., Sienkiewicz, M., Kwiatkowski, P. A., & Kowalczyk, E. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27104229 · Cited by 1
“…with this, indirect dopaminergic modulation, including increased extracellular dopamine in frontal and limbic regions, has been reported following psilocybin administration, potentially enhancing reward processing and motivational drive, both of which may be blunted in late-life depression [50–52].”
Brar, P. S., Price, R. B., Ross, S., Tofighi, B., & Sarpal, D. K. (2026) · Journal of Psychopharmacology · doi:10.1177/02698811261456191
“A similar diverse array of actions is observed for mescaline and DMT, while a diverse pharmacologic profile is also implicated for psilocybin (Pierce and Peroutka, 1989; Ray, 2010; Vamvakopoulou et al., 2023; Vollenweider et al., 1999).”
Psychedelics and Reward Processing: Before and After the 1970 Controlled Substances Act
Lifshitz, D. J., Sawaya, M. F., & Murnane, K. S. (2026) · Psychedelic Medicine · doi:10.1177/28314425261472614
Classic Psychedelics for Treating Chronic Pain: Mechanism and Clinical Translation
Chen, H., Ke, B., & Jiang, R. (2026) · Molecules · doi:10.3390/molecules31152611
“For instance, a seminal human positron emission tomography (PET) study demonstrated that low-dose psilo-cybin (0.25 mg/kg), mediated by the activation of 5-HT1A/2A receptors, provokes a robust release of dopamine within the striatum [109].”
Influential
Metadata
- Authors
- Vollenweider, F.
- Affiliations
- University Hospital Zurich (CH)
- Corresponding author
- Vollenweider, F
- Venue
- Neuropsychopharmacology
- Published
- 1999-05
- Volume
- 20
- Issue
- 5
- Pages
- 424-433
- ISSN
- 0893-133X (ISSN-L)
- 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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