The serotonergic psychedelics psilocybin, LSD and DMT hold great promise for the development of new treatments for psychiatric conditions such as major depressive disorder, addiction and end-of-life anxiety. Previous studies in both animals and humans have confirmed the effects of these drugs on neuronal activity and plasticity. However, the understanding of the mechanisms of action of these substances is limited. Here we show rapid effects of psychedelics on presynaptic properties, using live cell imaging at the level of single synapses in primary rat cortical neurons. Using the genetically encoded reporter of synaptic vesicle fusion synaptopHluorin, we detected a reduced fraction of synaptic vesicles that fused in response to mild or strong electrical stimulation 3-30 min after application of serotonergic psychedelics. These effects were transient and no longer present 24 h after treatment. While DMT only reduced the total recycling pool, LSD and psilocin also reduced the size of the readily releasable vesicle pool. Imaging with the sensors for glutamate, iGluSnFR, and presynaptic calcium, synGCaMP6, showed that while psilocin and DMT increased evoked glutamate release, LSD and psilocin reduced evoked presynaptic calcium levels. Interestingly, psilocin also affected short-term plasticity leading to a depression of responses to paired stimuli. The rapid and drug-specific modulation of glutamatergic neurotransmission described in this study may contribute to distinct anxiolytic and antidepressant properties of serotonergic psychedelics.
- MeSH
- halucinogeny * farmakologie MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- kyselina glutamová * metabolismus MeSH
- LSD farmakologie MeSH
- mozková kůra * účinky léků metabolismus cytologie MeSH
- neurony * účinky léků metabolismus MeSH
- potkani Sprague-Dawley MeSH
- psilocybin farmakologie MeSH
- serotoninové látky farmakologie MeSH
- synaptické vezikuly účinky léků metabolismus MeSH
- tryptaminy farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
RATIONALE: Cabergoline (CAB) is an ergot derivative typically prescribed for the treatment of hyperprolactinemia. It suppresses the release of prolactin through agonist actions on dopamine (DA) D2 receptors; however, it possesses binding affinity for other DA and 5-HT receptors. Side effects that exacerbate valvular heart disease can occur with high doses. OBJECTIVE: The present study examined the acute, subchronic, and chronic dose-response effects of CAB and a derivative dimethylcabergoline (DMC) which acts as an antagonist instead of agonist at 5-HT 2B receptors, on appetitive and consummatory sexual behaviors of male rats. METHODS: CAB (0, 0.03, 0.15, or 0.3 mg/kg/ml) was administered daily to sexually experienced male rats (N = 10/dose) by oral gavage for a total of 68 days. Sexual behavior was tested every 4 days during this period for a total of 16 trials. On the 17th trial, rats were administered their dose of CAB, and 4 h after were overdosed with sodium pentobarbital, perfused intracardially, and their brains processed for Fos immunohistochemistry. DMC (0, 0.03, 0.15, 0.3 mg/kg/ml) was administered daily to sexually experienced male rats (N = 10/dose) by oral gavage for a total of 36 days. Sexual behavior was tested every 4 days for a total of 9 trials. RESULTS: CAB increased anticipatory level changes, intromissions, and ejaculations significantly across all timepoints, with the medium and high doses being most potent. The medium and high doses also increased Fos protein significantly within the medial preoptic area, whereas in the nucleus accumbens shell, the low and medium doses decreased Fos protein but the high dose increased it significantly from control. Similar to CAB, the medium and high doses of DMC increased the number of ejaculations significantly. Rats in all drug dose groups appeared healthy for the duration of the experiments. CONCLUSIONS: Both CAB and DMC facilitate ejaculations, and CAB further facilitates measures of anticipatory sexual motivation and intromissions. These data suggest that both could be used as treatments for sexual arousal disorders and ejaculation/orgasm disorders with little or no untoward side effects at low doses.
- MeSH
- kabergolin farmakologie MeSH
- kopulace * MeSH
- krysa rodu rattus MeSH
- motivace MeSH
- mozek MeSH
- pohlavní steroidní hormony MeSH
- receptory dopaminu D2 MeSH
- sexuální chování zvířat * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Different psychoactive substances are widely used in today's society. So far limited data are available on the use of psychedelics in the general population. The main aim of this study is to estimate the numbers of users of substances with psychedelic properties (classical psychedelics, cannabis, ecstasy, and ketamine) in the Czech Republic. METHODS: Data from two samples enrolled in representative cross-sectional questionnaire surveys in the Czech adult population in 2016 (n = 2,785) and 2018 (n = 1,665) were analysed. Prevalence rates were extrapolated to estimate numbers of current, i.e., last-year, users of psychedelics, and their socio-demographic profiles were compared with non-users and users of cannabis. RESULTS: An estimated 5-6% of the Czech adult population (350-430 thousand people) used classical psychedelics (LSD, psilocybin mushrooms, ayahuasca) in their lifetime, increasing up to 28-30% when cannabis is included (1.9-2.1 million users). Current use of classical psychedelics reached 0.7-1.9% (50-130 thousand people), and 9-11% (590-750 thousand users) when cannabis was included. Users of psychedelics were more often males, of younger age and single. CONCLUSIONS: No significant socio-demographic differences were found between users of classical psychedelics and recreational cannabis users, however, differences were significant when compared to non-users and users of other illicit drugs. Findings should further serve to inform drug policy and social and healthcare systems in respect to the use of psychedelics.
- MeSH
- Cannabis * MeSH
- dospělí MeSH
- halucinogeny * terapeutické užití MeSH
- ketamin * MeSH
- lidé MeSH
- LSD MeSH
- poruchy spojené s užíváním psychoaktivních látek * epidemiologie MeSH
- průřezové studie MeSH
- psilocybin MeSH
- zakázané drogy * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
V minulosti sa predpokladalo, že hormonálne zmeny po pôrode spojené s dojčením sú rizikovým faktorom pre psychické zdravie žien a že dojčenie zhoršuje, či je priamo príčinou popôrodnej depresie či popôrodnej psychózy (dôkazom je napríklad zastaraný pojem "laktačná psychóza"). V súčasnosti však existuje veľa poznatkov v oblasti neuroendokrinológie, psychiatrie a psychológie, ktoré tento predpoklad nepodporujú, či dokonca priamo vyvracajú. Cieľom nášho článku bolo priniesť prehľad súčasných poznatkov k popôrodnej depresii a dojčeniu a porovnať odporúčania k liečbe dojčiacich žien na Slovensku a v zahraničí. Náš článok obsahuje súhrn aktuálnych výskumov v oblasti popôrodnej depresie a dojčenia v súvislosti so spánkom a s fungovaním hormonálneho systému a osi HPA žien po pôrode. Autori výskumov uvádzajú, že hormóny, ktoré sú po pôrode vylučované vďaka dojčeniu, majú stabilizačný účinok na psychiku žien a os HPA, čo naznačuje, že dojčenie môže mať ochranný účinok pred rozvojom popôrodnej depresie, či ju zmierňovať, ak sa napriek dojčeniu rozvinie. Nedojčenie je podľa našich zistení aj rizikovým faktorom pre kvalitu spánku žien po pôrode, čo môže ovplyvňovať ich psychické zdravie, a teda zvyšovať riziko, že sa popôrodná depresia rozvinie, či zhoršovať jej symptómy. V záverečnej kapitole článku sme zhrnuli slovenské a české odporúčania pri liečbe popôrodnej depresie a porovnali ich so zahraničnými, konkrétne v Spojených štátoch amerických. Zistili sme, že kým v zahraničí sa neodporúča ukončenie dojčenia a zastavenie tvorby mlieka v prípade diagnózy popôrodnej depresie, na Slovensku je to stále bežnou, odporúčanou praxou, ktorá v článkoch nebola podporená žiadnymi relevantnými výskumami či argumentmi.
In the past, postpartum hormonal changes associated with breastfeeding were thought to be a risk factor for women ́s mental health. It was assumed that breastfeeding either worsened or was the direct cause for postpartum depression or postpartum psychosis (as evidenced, for example, by the outdated term "lactation psychosis"). However, there is currently much knowledge in the field of neuroendocrinology, psychiatry and psychology that does not support or even refutes this assumption. The aim of this article is to provide an overview of current knowledge on postpartum depression and breastfeeding and to compare recommendations for the treatment of breastfeeding women in Slovakia and abroad. Our article contains a summary of current research in the field of postpartum depression and breastfeeding in connection with sleep and the functioning of the hormonal system and the HPA axis of women after childbirth. Researchers report that hormones secreted due to breastfeeding have a stabilizing effect on women ́s mental health and HPA axis, suggesting that breastfeeding may have a protective effect against the development of postpartum depression or alleviate it if it develops despite breastfeeding. According to our findings, bottle feeding is also a risk factor for the quality of women ́s sleep after childbirth, which can affect their mental health and thus increase the risk that postpartum depression will develop or worsen its symptoms afterwards. In the final chapter of the article, we summarize the Slovak and Czech recommendations for the treatment of postpartum depression and compare them with those from abroad, specifically from the United States. We found that while breastfeeding cessation and lactation suppression in the case of a diagnosis of postpartum depression is not recommended abroad, it is still a common, recommended practice in Slovakia. Though recommended, this practice isn ́t supported in Slovak articles by any relevant research or arguments.
Prolaktinomy jsou nejčastější hormonálně aktivní adenomy hypofýzy. U žen je obvyklým příznakem onemocnění amenorea či jiná porucha menstruace. Diagnostika je založena na zjištění hyperprolaktinemie s verifikací adenomu v oblasti tureckého sedla pomocí magnetické rezonance. Ve většině případů má dobrý efekt samostatná farmakoterapie kabergolinem. Léčbu makroprolaktinomů je nutné individuálně zvažovat, uplatňuje se kombinace více modalit, například operace nebo ozáření gama nožem následované farmakoterapií.
Prolactinomas are the most common hormonally active pituitary adenomas. For women, amenorrhea or other menstrual disturbances are common symptoms of the disease. Diagnosis is based on the detection of hyperprolactinaemia with verification of the adenoma in the region of the Turkish saddle using magnetic resonance imaging. In most cases, cabergoline alone has a good effect. The treatment of macroprolactinomas must be individually considered; a combination of several modalities, such as surgery or gamma-knife irradiation followed by drug therapy, is applied.
- MeSH
- agonisté dopaminu aplikace a dávkování farmakologie terapeutické užití MeSH
- amenorea MeSH
- galaktorea MeSH
- hyperprolaktinemie diagnóza etiologie MeSH
- kabergolin aplikace a dávkování farmakologie terapeutické užití MeSH
- léková rezistence MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mladý dospělý MeSH
- nádory hypofýzy chirurgie diagnóza farmakoterapie MeSH
- neúspěšná terapie MeSH
- prolaktin analýza krev účinky léků MeSH
- prolaktinom * chirurgie diagnóza farmakoterapie MeSH
- radiochirurgie MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
Článek poskytuje úvod do aktuálního stavu výzkumu psychedeliky asistované psychoterapie, se zaměřením na pacienty s život ohrožující nemocí. Předkládá přehled prací z 50.–70. let a detailněji se zabývá soudobými studiemi, které poukazují na bezpečnost a dlouhodobý antidepresivní a anxiolytický potenciál této metody u pacientů s depresí, úzkostí a tzv. existenciální tísní. Stručně je popsán terapeutický kontext, psychické a somatické účinky psychedelik včetně rizik, nastíněny jsou též možné mechanismy účinku psychedelik (zejména psilocybinu) z neurobiologické a psychologické perspektivy. Uvedeny jsou též hlavní limity dosavadního výzkumu s ohledem na možné využití psychedelik v paliativní péči.
The article provides an introduction to the existing research in psychedelics-assisted psychotherapy focused on patients with life-threatening illnesses. It overviews studies from the 1950s and 1970s and deals with recent studies that refer to the safety and long-term antidepressant and anxiolytic potential of this method in patients with depression, anxiety and so-called existential distress. Further, the therapeutic context, psychological and somatic effects of psychedelics, including their risks, are briefly described, as well as possible mechanisms of action of psychedelics (especially psilocybin) from neurobiological and psychological perspectives. The main limitations of the existing research with regard to the possible use of psychedelics in palliative care are also discussed.
Serotonergic psychedelics are recently gaining a lot of attention as a potential treatment of several neuropsychiatric disorders. Broadband desynchronization of EEG activity and disconnection in humans have been repeatedly shown; however, translational data from animals are completely lacking. Therefore, the main aim of our study was to assess the effects of tryptamine and phenethylamine psychedelics (psilocin 4 mg/kg, LSD 0.2 mg/kg, mescaline 100 mg/kg, and DOB 5 mg/kg) on EEG in freely moving rats. A system consisting of 14 cortical EEG electrodes, co-registration of behavioral activity of animals with subsequent analysis only in segments corresponding to behavioral inactivity (resting-state-like EEG) was used in order to reach a high level of translational validity. Analyses of the mean power, topographic brain-mapping, and functional connectivity revealed that all of the psychedelics irrespective of the structural family induced overall and time-dependent global decrease/desynchronization of EEG activity and disconnection within 1-40 Hz. Major changes in activity were localized on the large areas of the frontal and sensorimotor cortex showing some subtle spatial patterns characterizing each substance. A rebound of occipital theta (4-8 Hz) activity was detected at later stages after treatment with mescaline and LSD. Connectivity analyses showed an overall decrease in global connectivity for both the components of cross-spectral and phase-lagged coherence. Since our results show almost identical effects to those known from human EEG/MEG studies, we conclude that our method has robust translational validity.
Cíl studie: Shrnout současné možnosti prevence a terapie ovariálního hyperstimulačního syndromu (OHSS). Metodika: Výběr aktuálních prací a doporučených postupů. Výsledky: V pohledu bezpečnosti a prevence OHSS je výhodnější antagonistický protokol. Pacientky se syndromem polycystických ovarií mnohdy benefitují z pouhého podávání metforminu či letrozolu k indukci ovulace. V případě bezprostředně hrozícího OHSS se doporučuje podávat cabergolin v dávce 0,5 mg 1× denně per os, subkutánně nízkomolekulární heparin v profylaktické dávce a dbát na dostatečnou hydrataci. Za nevhodné lze naopak označit podávání diuretik. V případě punkce ascitu lze provést jeho reinstilaci do cévního řečiště. Závěr: Prezentujeme přehled současných doporučení a postupů v rámci prevence a terapie OHSS.
Objective: To present current possibilities of the prevention and therapy of ovarian hyperstimulation syndrome (OHSS). Methods: Literature and guidelines were researched. Results: From the view of safety and prevention of OHSS, antagonistic protocol is suitable. Patients with syndrome of polycystic ovaries benefit from the use of metformin or letrozole that can be sufficient to induce ovulation. As a treatment of imminent OHSS, it is recommended to administer 0.5 mg of cabergoline per os daily as well as low molecular weight heparin subcutaneously in prophylactic dose and to maintain sufficient fluid intake. Diuretics are strongly discouraged to use. To maintain intravascular volume, drained ascites can be reintroduced. Conclusion: We present a review of current literature and recommendations.
Práce se zabývá nejnovějšími pohledy na diagnostiku a léčbu neuroleptického maligního syndromu (NMS). NMS je vzácný antipsychotiky navozený, život ohrožující stav, charakterizovaný hyperpyrexií, svalovou rigiditou, kvalitativní změnou vědomí a deregulací autonomního nervového systému. Prevalence a mortalita se v průběhu posledních 30 let snížila, hlavně zřejmě díky časné diagnostice a vhodné intervenci. Recentní data uvádějí prevalenci 0,02-0,03 % a mortalitu 5,6 %. Léčba zahrnuje vysazení syndrom vyvolávajícího dopaminového antagonisty a podpůrnou léčbu, může dále zahrnovat specifickou farmakoterapii (benzodiazepiny, bromokriptin, amantadin, dantrolen) a elektrokonvulzivní léčbu. Nicméně klinici, a zvláště lékaři v primární péči, kteří často užívají antipsychotika jako přídatnou léčbu, by měli být s tímto syndromem obeznámeni.
The paper deals with recent aspects of diagnosis and treatment of neuroleptic malignant syndrome (NMS). NMS is an antipsychotic-induced, life-threatening condition, characterized by hyperpyrexia, muscle rigidity, qualitative alteration of consciousness and autonomic nervous system dys-regulation. NMS prevalence and mortality rates have declined over the past 30 years, most likely due to early recognition of the syndrome and appropriate intervention. Recent reports suggest a prevalence of 0.02-0.03%, and 5.6% mortality. Treatment includes withdrawal of the offending dopamine antagonist, supportive care and may include the use of specific pharmacotherapies (benzodiazepines, bromocriptine, amentadine, dantrolene) and electroconvulsive therapy. Nonetheless, clinicians, especially primary care clinicians who are using antipsychotics more often for adjunctive treatments, must be cognizant of this syndrome.
- MeSH
- amantadin terapeutické užití MeSH
- antipsychotika škodlivé účinky terapeutické užití MeSH
- benzodiazepiny terapeutické užití MeSH
- bromokriptin terapeutické užití MeSH
- dantrolen terapeutické užití MeSH
- diferenciální diagnóza MeSH
- farmakovigilance MeSH
- incidence MeSH
- lidé MeSH
- maligní neuroleptický syndrom * diagnóza farmakoterapie MeSH
- směrnice pro lékařskou praxi jako téma * MeSH
- Check Tag
- lidé MeSH
