Kombinace sumatriptanu s naproxenem sodným v jedné kombinované tabletě (Frimig Duo) přináší relativně novou možnost pro akutní léčbu migrény, zejména u jedinců s nedostatečným efektem krátce působících triptanů. V textu jsou uvedeny teoretické patofyziologické a farmakologické informace s implementací do klinické praxe.
The combination of sumatriptan with sodium naproxen in a single tablet (Frimig Duo) offers a relatively new option for the acute treatment of migraine, particularly in individuals with insufficient efficacy from short-acting triptans. The text presented provides theoretical pathophysiological and pharmacological information with implementation into clinical practice.
- MeSH
- Serotonin 5-HT1 Receptor Agonists MeSH
- Anti-Inflammatory Agents, Non-Steroidal MeSH
- Drug Combinations MeSH
- Drug Evaluation MeSH
- Humans MeSH
- Migraine Disorders * drug therapy physiopathology MeSH
- Naproxen * pharmacokinetics pharmacology therapeutic use MeSH
- Sumatriptan * pharmacokinetics pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Spánek je základní lidskou potřebou, jeho poruchou trpí téměř polovina lidské populace. Bolest hlavy je jedním z nejčastějších zdravotních problémů. Dle WHO jí trpí 50-75 % dospělých. Oba tyto fenomény mají charakter globální zdravotní zátěže. Vztah mezi bolestí hlavy a poruchou spánku je mnohoznačný a komplexní, komorbidita těchto dvou syndromů vede k chronifikaci obou onemocnění, zvyšuje zátěž a vede ke zhoršení obou poruch, snížení kvality života, zvýšení frekvence komplikací a snižuje účinnost léčby.
Sleep is a basic human need, almost half of the human population suffers from its disorder. Headache is one of the most common health problems. According to the WHO, 50-75 % of adults suffer from it. Both of these phenomena have the character of a global health burden. The relationship between headache and sleep disorder is multifaceted and complex, the comorbidity of these two syndromes leads to the chronification of both diseases, increases the burden and leads to the worsening of both disorders, a decrease in the quality of life, an increase in the frequency of complications and a decrease in the effectiveness of treatment.
Psilocybin, a naturally occurring psychedelic compound in magic mushrooms, shows promise as a novel intervention with a single administration inducing rapid and long-lasting antidepressant effects. However, there are limited studies on the optimal dosing required for the beneficial effects of psilocybin given its side effects. To address this gap, we investigated in Wistar rats whether a single psilocybin administration (0.1, 0.32, 1.0, and 3.2 mg/kg) had antidepressant-like effects in the forced swim test (FST), a pro-social effect in the social interaction test (SIT), and the ability to alter pleasure using the sucrose preference test (SPT). We also examined the dose-response relationships of psilocybin on the head-twitch response (HTR), locomotor activity, body temperature, and weight gain. Furthermore, we explored whether the brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex (PFC) paralleled the behavioral changes observed after psilocybin. In the FST, psilocybin induced dose-dependent inverted-U-shaped responses with only the intermediate dose of 0.32 mg/kg producing short and long-term antidepressant-like effects. A similar pattern was observed for the SIT, the SPT, and the HTR. In contrast, the high doses of psilocybin (1.0 and 3.2 mg/kg), while deprived of anti-depressant-like activity, significantly reduced body temperature, locomotor activity, and body weight gain. BDNF levels in the hippocampus and PFC increased dose-dependently after psilocybin, but linearly suggesting a dissociation between high BDNF levels and the observed antidepressant-like behaviors. Our results indicated that there is a narrow window for the therapeutic potential of psilocybin, with 0.32 mg/kg effectively producing antidepressant-like effects without the accompanying adverse effects observed only at higher doses.
- MeSH
- Antidepressive Agents * pharmacology therapeutic use MeSH
- Hallucinogens * pharmacology MeSH
- Hippocampus drug effects metabolism MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Brain-Derived Neurotrophic Factor metabolism MeSH
- Swimming psychology MeSH
- Motor Activity drug effects MeSH
- Rats, Wistar MeSH
- Prefrontal Cortex drug effects metabolism MeSH
- Psilocybin * pharmacology therapeutic use MeSH
- Body Temperature drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
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
- Hallucinogens * pharmacology MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Glutamic Acid * metabolism MeSH
- Lysergic Acid Diethylamide pharmacology MeSH
- Cerebral Cortex * drug effects metabolism cytology MeSH
- Neurons * drug effects metabolism MeSH
- Rats, Sprague-Dawley MeSH
- Psilocybin pharmacology MeSH
- Serotonin Agents pharmacology MeSH
- Synaptic Vesicles drug effects metabolism MeSH
- Tryptamines pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The intestine hosts the largest immune system and peripheral nervous system in the human body. The gut‒brain axis orchestrates communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Here, using a human three-dimensional in vitro culture model, we investigated the effects of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Serotonin attenuated the tumor necrosis factor-induced proinflammatory response, mostly by affecting the expression of chemokines. Serotonin affected the phenotype and distribution of tissue-migrating monocytes, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, our results show that serotonin plays a crucial role in communication among gut-brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of inflammation. In vivo studies focused on the role of neuromodulators in gut inflammation have shown controversial results, highlighting the importance of human experimental models. Moreover, our results emphasize the importance of human health research in human cell-based models and suggest that the serotonin signaling pathway is a new therapeutic target for inflammatory bowel disease.
- MeSH
- Humans MeSH
- Monocytes metabolism immunology MeSH
- Cell Movement MeSH
- Serotonin * metabolism MeSH
- Signal Transduction MeSH
- Intestinal Mucosa * metabolism pathology MeSH
- Tumor Necrosis Factor-alpha metabolism MeSH
- Inflammation metabolism pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Recent years show an exponential increased interest ("renaissance") in the use of psychedelics for the treatment of mental disorders and broader. Some of these treatments, such as psilocybin for depression, are in the process of formal regulation by regulatory bodies in the US (FDA) and Europe (EMA), and as such on the brink of real-world implementation. In the slipstream of these developments increasing commercial initiatives are taking shape. The European Psychiatric Association (EPA) acknowledges both the therapeutic potential of psychedelic substances and the challenges for both research and clinical implementation. Steps need to be taken toward a well-balanced policy based upon sound scientific evidence and research, aiming at safe, ethical responsible integration of psychedelic therapy available for all patients who can potentially benefit. METHODS: In this EPA policy paper, we highlight the potential benefits, and also the challenges of psychedelic treatments, which can be relevant for the future real-world implementation of these treatments. RESULTS: In addition to an overview of the current evidence and hypotheses of working mechanisms of psychedelic treatment, this policy paper specifically highlights the importance of the psychosocial components of the treatment as well as the ethical and professional aspects playing a role in real-world implementation. CONCLUSIONS: Four recommendations are formulated for further research and clinical implementation.
- MeSH
- Mental Disorders * drug therapy MeSH
- Hallucinogens * therapeutic use MeSH
- Humans MeSH
- Psilocybin therapeutic use pharmacology MeSH
- Psychiatry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
Migréna je časté invalidizující onemocnění. Celosvětová prevalence migrény se odhaduje mezi 10-15 %. Migréna často propuká již v dětském věku, kdy je poměr dívek a chlapců kloněn k vyššímu počtu u chlapců, během puberty se pak počty vyrovnávají. S pokračujícím věkem se poměr kloní více k ženskému pohlaví. Nejvíce však postihuje dospělé v produktivním věku, kde již výrazně převažují ženy nad muži. V České republice je více než milion migreniků. Většina z nich trpí migrénou epizodickou, nejméně dvacet procent z nich pak trpí formou chronickou, která se významně odráží na kvalitě života nemocného i jeho rodiny. V léčbě migrény zažíváme v posledních letech revoluci. Máme k dispozici specifickou medikaci akutní i profylaktickou v různých formách podání.
Migraine is a frequent disabling disease. The worldwide prevalence of migraine is estimated to be between 10-15 %. Migraines often start already in childhood, when the ratio of girls to boys tends to be higher in boys, and during puberty the numbers even out. As age continues, the ratio leans more towards the female sex. However, it mostly affects adults of working age, where women already significantly outnumber men. There are more than a million migrainers in the Czech Republic. Most of them suffer from episodic migraine, while at least twenty percent of them suffer from the chronic form, which significantly affects the quality of life of the patient and her/his family. In recent years, we have experienced a revolution in the treatment of migraine. We have available specific acute and prophylactic medication in various forms of administration.
- Keywords
- atogepant, rimegepant,
- MeSH
- Calcitonin Gene-Related Peptide Receptor Antagonists * pharmacology classification therapeutic use MeSH
- Anti-Inflammatory Agents, Non-Steroidal pharmacology therapeutic use MeSH
- Humans MeSH
- Migraine Disorders * diagnosis drug therapy physiopathology MeSH
- Tryptamines pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro. OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717). METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using TEAE data from participants with relapsing multiple sclerosis who entered DAYBREAK from phase 3 studies (cutoff February 1, 2022). Incidences of TEAEs matching terms from each search were stratified by SSRI/SNRI use. RESULTS: Of 2257 DAYBREAK participants, 274 (12.1%) used an SSRI/SNRI. No participants had TEAEs matching the SA narrow search terms. There was no significant difference in the percentage of participants with ⩾1 TEAE matching the SA broad search for those on versus off SSRIs/SNRIs (on: 12.4%, n = 34/274; off: 15.6%, n = 310/1982, nominal p = 0.1630). CONCLUSION: MedDRA searches showed no increase in TEAEs potentially associated with SA with concomitant SSRI/SNRI and ozanimod use.
- MeSH
- Antidepressive Agents adverse effects MeSH
- Indans * MeSH
- Serotonin and Noradrenaline Reuptake Inhibitors * adverse effects MeSH
- Humans MeSH
- Oxadiazoles * MeSH
- Multiple Sclerosis * chemically induced MeSH
- Selective Serotonin Reuptake Inhibitors adverse effects MeSH
- Serotonin MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Keywords
- atogepant,
- MeSH
- Calcitonin Gene-Related Peptide Receptor Antagonists administration & dosage adverse effects therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Migraine Disorders * drug therapy MeSH
- Antibodies, Monoclonal administration & dosage therapeutic use MeSH
- Calcitonin Gene-Related Peptide MeSH
- Piperidines administration & dosage adverse effects therapeutic use MeSH
- Pyridines administration & dosage adverse effects therapeutic use MeSH
- Pyrroles administration & dosage adverse effects therapeutic use MeSH
- Spiro Compounds administration & dosage adverse effects therapeutic use MeSH
- Tryptamines administration & dosage adverse effects therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Newspaper Article MeSH
OBJECTIVE: To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression. METHODS: For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support. The resulting psychedelic experience (Five-Dimensional Altered States of Consciousness questionnaire [5D-ASC] and Emotional Breakthrough Inventory [EBI]) were measured. These proximal variables and outcome 3 weeks post-administration (change in Montgomery-Åsberg Depression Rating Scale [MADRS]) were explored using correlation analysis. RESULTS: The mean intensity of psychedelic effects was dose-related, but distributions of scores for different doses overlapped considerably. Depression response correlated with select aspects of the psychedelic experience overall and for individual doses. At the 25 mg dose, 5D-ASC dimensions Oceanic Boundlessness (Pearson correlation coefficient r = -0.508) and Visual Restructuralization (r = -0.516), and EBI (r = -0·637) were the variables with the strongest correlation to the Week 3 change from Baseline in MADRS score. LIMITATIONS: The existence of correlation does not establish causation and exploratory findings require further replication, preferably in larger independent samples. CONCLUSIONS: The intensity of psychedelic experience overlaps widely across doses and mitigates the risk of unblinding to dose. Correlations between psychedelic experience and outcome suggest specificity in psilocybin's mechanism of action. Quality and intensity of psychedelic experience may be a measure of pharmacodynamic effect and reveal an effective dose response phenomenon for single oral doses.
- MeSH
- Depressive Disorder, Treatment-Resistant * drug therapy MeSH
- Depressive Disorder, Major drug therapy MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Hallucinogens * administration & dosage pharmacology MeSH
- Middle Aged MeSH
- Humans MeSH
- Psilocybin * pharmacology administration & dosage MeSH
- Psychiatric Status Rating Scales MeSH
- Treatment Outcome MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
