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1.
Compr Psychoneuroendocrinol ; 13: 100163, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36545240

RESUMO

Rationale: Psilocybin is a serotonergic psychedelic that has gained prominent attention recently as a potential therapeutic for neuropsychiatric disorders including Major Depressive Disorder. Pre-clinical and initial studies in humans suggest that serotonin 2A receptor agonists, including serotonergic psychedelics, have anti-inflammatory effects. This may contribute to its therapeutic effects as previous studies indicate a link between neuropsychiatric disorders and inflammatory processes. However, the effect of psilocybin on biomarkers of inflammation has not been evaluated in humans. Objectives: Investigate the effect of a single dose of psilocybin on peripheral biomarkers of inflammation in healthy humans. Methods: Blood samples were collected from 16 healthy participants before and one day after the administration of a single oral dose of psilocybin (mean dose: 0.22 mg/kg) and subsequently analyzed for concentrations of high-sensitivity C-reactive protein (hsCRP), tumor-necrosis-factor (TNF) and soluble urokinase plasminogen activator receptor (suPAR). Change in inflammatory markers was evaluated using a paired t-test where p < 0.05 was considered statistically significant. Results: We did not observe statistically significant changes in any of the above biomarkers of inflammation (all Cohen's d ≤ 0.31; all p ≥ 0.23). Conclusions: Our data do not support that a single dose of psilocybin reduces biomarkers of inflammation in healthy individuals one day after administration. Nevertheless, we suggest that future studies consider additional markers of inflammation, including markers of neuroinflammation, and evaluate potential anti-inflammatory effects of psilocybin therapy in clinical cohorts where more prominent effects may be observable.

2.
Ugeskr Laeger ; 183(47)2021 11 22.
Artigo em Dinamarquês | MEDLINE | ID: mdl-34851261

RESUMO

A significant proportion of patients with depression do not respond to classic antidepressants addressing serotonergic or noradrenergic neurotransmission. Certain clinical features of depression seem to involve dopaminergic neurotransmission. Although medications with specific dopaminergic actions are used in the treatment of depression in other countries (e.g. the United States), these drugs are rarely mentioned in Danish treatment guidelines. This review aims at comprehending current dopaminergic treatment strategies and future directions in this field.


Assuntos
Antidepressivos , Depressão , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Dopamina , Dopaminérgicos , Humanos , Norepinefrina
3.
J Psychopharmacol ; 35(4): 459-468, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33501857

RESUMO

BACKGROUND: Psilocybin is a serotonergic psychedelic with psychoactive effects mediated by serotonin 2A receptor (5-HT2AR) activation. It produces an acute psychedelic altered state of consciousness with a unique phenomenology that can be temporally characterized by three intensity phases: onset of psychoactive effect, a peak plateau and return to normal consciousness. AIMS: We evaluated whether pre-drug brain 5-HT2AR binding predicted the three phases of psilocybin subjective drug intensity (SDI) and retrospective self-report of mystical type experiences in healthy individuals. METHOD: Sixteen participants completed a pre-drug [11C]Cimbi-36 positron emission tomography scan to assess 5-HT2AR binding. On a separate day, participants completed a single psilocybin session (oral dose range 0.2-0.3 mg/kg), during which SDI was assessed every 20 min. The Mystical Experience Questionnaire (MEQ) was completed at the end of the session. The three SDI phases were modelled using segmented linear regressions. We evaluated the associations between neocortex 5-HT2AR binding and SDI/MEQ outcomes using linear regression models. RESULTS: Neocortex 5-HT2AR was statistically significantly negatively associated with peak plateau duration and positively with time to return to normal waking consciousness. It was also statistically significantly negatively associated with MEQ total score. CONCLUSION: This is the first study to investigate how individual brain 5-HT2AR binding predicts subjective effects of a single dose of psilocybin. Our findings reinforce the role of cerebral 5-HT2AR in shaping the temporal and mystical features of the psychedelic experience. Future studies should examine whether individual brain levels of 5-HT2AR have an impact on therapeutic outcomes in clinical studies.


Assuntos
Encéfalo , Misticismo/psicologia , Psilocibina , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Estado de Consciência/efeitos dos fármacos , Estado de Consciência/fisiologia , Feminino , Alucinógenos/administração & dosagem , Alucinógenos/farmacocinética , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Tomografia por Emissão de Pósitrons/métodos , Psilocibina/administração & dosagem , Psilocibina/farmacocinética , Psicotrópicos/administração & dosagem , Psicotrópicos/farmacocinética , Receptores 5-HT2 de Serotonina/metabolismo , Autoimagem , Agonistas do Receptor 5-HT2 de Serotonina/administração & dosagem , Agonistas do Receptor 5-HT2 de Serotonina/farmacocinética
4.
Eur Neuropsychopharmacol ; 33: 71-80, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32146028

RESUMO

A single dose of the serotonin 2A receptor (5-HT2AR) agonist psilocybin can have long-lasting beneficial effects on mood, personality, and potentially on mindfulness, but underlying mechanisms are unknown. Here, we for the first time conduct a study that assesses psilocybin effects on cerebral 5-HT2AR binding with [11C]Cimbi-36 positron emission tomography (PET) imaging and on personality and mindfulness. Ten healthy and psychedelic-naïve volunteers underwent PET neuroimaging of 5-HT2AR at baseline (BL) and one week (1W) after a single oral dose of psilocybin (0.2-0.3 mg/kg). Personality (NEO PI-R) and mindfulness (MAAS) questionnaires were completed at BL and at three-months follow-up (3M). Paired t-tests revealed statistically significant increases in personality Openness (puncorrected = 0.04, mean change [95%CI]: 4.2[0.4;∞]), which was hypothesized a priori to increase, and mindfulness (pFWER = 0.02, mean change [95%CI]: 0.5 [0.2;0.7]). Although 5-HT2AR binding at 1W versus BL was similar across individuals (puncorrected = 0.8, mean change [95%CI]: 0.007 [-0.04;0.06]), a post hoc linear regression analysis showed that change in mindfulness and 5-HT2AR correlated negatively (ß [95%CI] = -5.0 [-9.0; -0.9], pFWER= 0.046). In conclusion, we confirm that psilocybin intake is associated with long-term increases in Openness and - as a novel finding - mindfulness, which may be a key element of psilocybin therapy. Cerebral 5-HT2AR binding did not change across individuals but the negative association between changes in 5-HT2AR binding and mindfulness suggests that individual change in 5-HT2AR levels after psilocybin is variable and represents a potential mechanism influencing long-term effects of psilocybin on mindfulness.


Assuntos
Alucinógenos/administração & dosagem , Alucinógenos/farmacologia , Atenção Plena , Neocórtex/efeitos dos fármacos , Neocórtex/metabolismo , Psilocibina/administração & dosagem , Psilocibina/farmacologia , Receptor 5-HT2A de Serotonina/efeitos dos fármacos , Receptor 5-HT2A de Serotonina/metabolismo , Adulto , Benzilaminas , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neocórtex/diagnóstico por imagem , Testes Neuropsicológicos , Personalidade/efeitos dos fármacos , Testes de Personalidade , Fenetilaminas , Tomografia por Emissão de Pósitrons , Adulto Jovem
5.
Neuropsychopharmacology ; 44(7): 1336-1337, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30846853

RESUMO

The original version of this article contained an error in the labelling of Figures 2 and 3. While the captions and figures themselves are correct, in order to correspond with the in-text references, they have now been re-numbered in both the PDF and HTML versions of the article.

6.
Neuropsychopharmacology ; 44(7): 1328-1334, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30685771

RESUMO

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 [11C]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.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Alucinógenos/farmacologia , Psilocibina/sangue , Psilocibina/farmacologia , Receptor 5-HT2A de Serotonina/metabolismo , Adulto , Benzilaminas , Radioisótopos de Carbono , Feminino , Humanos , Masculino , Fenetilaminas , Tomografia por Emissão de Pósitrons , Ligação Proteica , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia
7.
Hum Brain Mapp ; 40(7): 2117-2124, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30633430

RESUMO

Recent research found lasting increases in personality trait Openness in healthy individuals and patients after administration of the serotonin 2A receptor (5-HT2A R) agonist psilocybin. However, no studies have investigated whether 5-HT2A R availability as imaged using positron emission tomography (PET) is associated with this trait. In 159 healthy individuals (53 females), the association between 5-HT2A R binding in neocortex imaged with [18 F]altanserin or [11 C]Cimbi-36 PET and personality trait Openness was investigated using linear regression models. In these models the influence of sex on the association was also investigated. Trait Openness was assessed with the NEO Personality Inventory-Revised. No significant associations between neocortical 5-HT2A R binding and trait Openness were found for [18 F]altanserin (p = 0.5) or [11 C]Cimbi-36 (p = 0.8). Pooling the data in a combined model did not substantially change our results (p = 0.4). No significant interactions with sex were found (p > 0.35). Our results indicate that differences in 5-HT2A R availability are not related to variations in trait Openness in healthy individuals. Although stimulation of the 5-HT2A R with compounds such as psilocybin may contribute to long-term changes in trait Openness, there is no evidence in favor of an association between 5-HT2A R and trait Openness.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Inventário de Personalidade , Personalidade/fisiologia , Tomografia por Emissão de Pósitrons/métodos , Receptor 5-HT2A de Serotonina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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