Ede Frecska - Academia.edu (original) (raw)
Papers by Ede Frecska
Current Neuropharmacology, 2017
Background: Widespread protein aggregation occurs in the living system under stress or during agi... more Background: Widespread protein aggregation occurs in the living system under stress or during aging, owing to disturbance of endoplasmic reticulum (ER) proteostasis. Many neurodegenerative diseases may have a common mechanism: the failure of protein homeostasis. Perturbation of ER results in unfolded protein response (UPR). Prolonged chronical UPR may activate apoptotic pathways and cause cell death. Methods: Research articles on Sigma-1 receptor were reviewed. Results: ER is associated to mitochondria by the mitochondria-associated ER-membrane, MAM. The sigma-1 receptor (Sig-1R), a well-known ER-chaperone localizes in the MAM. It serves for Ca 2+-signaling between the ER and mitochondria, involved in ion channel activities and especially important during neuronal differentiation. Sig-1R acts as central modulator in inter-organelle signaling. Sig-1R helps cell survival by attenuating ER-stress. According to sequence based predictions Sig-1R is a 223 amino acid protein with two transmembrane (2TM) domains. The X-ray structure of the Sig-1R [1] showed a membrane-bound trimeric assembly with one transmembrane (1TM) region. Despite the in vitro determined assembly, the results of in vivo studies are rather consistent with the 2TM structure. The receptor has unique and versatile pharmacological profile. Dimethyl tryptamine (DMT) and neuroactive steroids are endogenous ligands that activate Sig-1R. The receptor has a plethora of interacting client proteins. Sig-1R exists in oligomeric structures (dimer-trimer-octamer-multimer) and this fact may explain interaction with diverse proteins. Conclusion: Sig-1R agonists have been used in the treatment of different neurodegenerative diseases, e.g. Alzheimer's and Parkinson's diseases (AD and PD) and amyotrophic lateral sclerosis. Utilization of Sig-1R agents early in AD and similar other diseases has remained an overlooked therapeutic opportunity.
![Research paper thumbnail of [Spirituality in medicine] Spiritualitás a medicinában](https://a.academia-assets.com/images/blank-paper.jpg)
](![Research paper thumbnail of A szocializáció szerepe a pszichoszexuális fejlődésben [The role of socialization in psychosexual development. In Hungarian]](https://attachments.academia-assets.com/104545544/thumbnails/1.jpg)
](Psychiatria Hungarica, 2022
Introduction: In the recent research and interpretation of the genetical-biological and environ... more Introduction:
In the recent research and interpretation of the genetical-biological and environmental-social factors shaping psychosexual development, in addition to scientific arguments, more and more ideological and political aspect have received unfortunate emphasis.
Objective:
Since the literature investigating the development of gender identity and gender orientation has not only increased, but also polarized, it is timely to look at the scientific exchange of ideas and debates among the differing positions.
Method:
Exploring the significance of genetic, biological and social factors involved in the development of gender identity and gender orientation based on international literature data.
Results:
Based on the current state of science it can be concluded that, in addition to the indisputably marked genetic-biological factors, education and social patterns, as well as the extremely complex environmental and media-related influence with its variable intensity and diverse emotional content also play a significant role in the psychosexual development. This is supported, among other observations, by the data indicating that homoerotic behavior is more common in people raised by same-sex couples.
Conclusion:
As psychosexual development is determined jointly by both genetic-biological and social factors (like education, media etc), belonging to a sexual minority group is not a choice, not the result of a personal decision. Therefore, any kind of discrimination in this regard is unacceptable. Further scientific studies are necessary to answer a large number of questions that still remain open.
![Research paper thumbnail of Rögös út a sokoldalú kibontakozás felé [Rocky road toward recovery. In Hungarian].](https://attachments.academia-assets.com/104545348/thumbnails/1.jpg)
](Psychiatria Hungarica, 2020
Demográfiai és távoli anamnesztikus adatok Gizella jelenleg 41 éves, egyedülálló, szüleivel élő, ... more Demográfiai és távoli anamnesztikus adatok Gizella jelenleg 41 éves, egyedülálló, szüleivel élő, érettségizett, majd három és fél éves számviteli szakot végzett logisztikus, tíz éve munka nélkül, szkizofrénia diagnózissal élő nőbeteg. Első alkalommal 2004-ben (25 éves korában) jelent meg a Pszichiátriai Gondozóban alkalmazkodási problémákkal. Akkor labilis hangulat, feszültség, alacsony frusztrációs tolerancia jellemezte, munkahelyét otthagyta. Alkoholt alkalmanként fogyasztott, nem drogozott, akkor még naponta egy doboz cigarettát szívott. Premorbid vonásai alapján szociábilis, sokoldalúan érdeklődő, mentálisan élénk, derűs, nyitott személyiségűként jellemezhető. Családi anamnézise pszichiátriai vonatkozásban negatív. 2010-ig pszichiátriai szempontból gyógyszermentes volt.
Open Medicine, 2020
The objective of this research is to identify the relationship between the neuropsychiatric sympt... more The objective of this research is to identify the relationship between the neuropsychiatric symptoms (NPSs) of patients with major neurocognitive disorder (mNCD), their quality of life, illness intrusiveness and the caregiver's burden. We assessed 131 patients with mNCD. Examination methods included WHO well-being index short version, illness intrusiveness rating scale, Alzheimer's Disease Assessment Scale-Cog, Mini Mental State Examination and neuropsychiatric inventory. The results were analysed using standard statistical tests. In our sample, the prevalence of NPSs is 100%. A significant correlation (p < 0.0001) was observed with quality of life and illness intrusiveness. Additionally, a strong relationship was observed between NPSs and the caregiver's burden (r = 0.9). The result is significantly twice as much stronger in comparison to the relationship between NPS and cognitive symptoms (r = 0.4). This is the first study in Hungary to assess the impact of NPS on the burden of relatives and quality of life. NPS had twice stronger impact on caregivers' burden than cognitive decline. However, further studies are needed to assess the sub-syndromes in mNCD in relation to NPS.
Neuropsychopharmacologia Hungarica, 2020
Discovery and development of the selective serotonin reuptake inhibitors mark a milestone in neur... more Discovery and development of the selective serotonin reuptake inhibitors mark a milestone in neuro-pharmacology. Drugs from this class alter the functioning of the serotonin system by the potentiation of serotonin through the negative allosteric modulation of its neuronal uptake by the human serotonin transporter. Selective serotonin reuptake inhibitors show few side effects compared to those caused by traditional antidepressants and they vary in the binding interactions formed during binding. Gener-ally, their binding involves three specific regions of the drug structures, each participating in vital inter-actions, such as salt bridge formation and additional hydrophobic interactions with conserved resi-dues in the central binding site of the target protein. Side effects, however, such as the initial lack of response to treatment, or drowsiness, nausea, and sexual dysfunction occasionally may arise. Addi-tional binding studies, furthermore, highlighted the importance of enantioselectivity in the binding of these compounds, raising concerns about the beneficial application of racemate mixtures of some of these compounds. Therefore, additional characterisation of binding and further structural improve-ment of this class of drugs is necessary. The recently synthesized sertraline salts, and functional deriv-atives of fluoxetine and citalopram show promising results in delivering antidepressant activity as well as in effectively overcoming anorexigenic side-effects in rodent models. Hence, despite certain non-desired effects associated with selective serotonin reuptake inhibitor applications, this class of drugs is considered as first-line medication in the management of major depression, and is carrying an excel-lent potential for the development and refinement of the currently available and novel antidepressant therapies.
Experimental Neurology , 2020
Background and purpose: N,N-dimethyltryptamine (DMT) is an endogenous ligand of the Sigma 1 recep... more Background and purpose: N,N-dimethyltryptamine (DMT) is an endogenous ligand of the Sigma 1 receptor (Sig-1R) with documented in vitro cytoprotective properties against hypoxia. Our aim was to demonstrate the in vivo neuroprotective effect of DMT following ischemia-reperfusion injury in the rat brain. Methods: Transient middle cerebral occlusion (MCAO) was induced for 60 min in male Wistar rats using the filament occlusion model under general anaesthesia. Before the removal of the filament the treatment group (n = 10) received an intra-peritoneal (IP) bolus of 1 mg/kg-body weight (bw) DMT dissolved in 1 ml 7% ethanol/saline vehicle, followed by a maintenance dose of 2 mg/Kg-bw/h delivered over 24 h via osmotic minipumps. Controls (n = 10) received a vehicle bolus only. A third group (n = 10) received a Sig-1R antagonist (BD1063, 1 mg/kg-bw bolus +2 mg/kg-bw/h maintenance) in parallel with the DMT. Lesion volume was measured by MRI 24 h following the MCAO. Shortly after imaging the animals were terminated, and the native brains and sera were removed. Four rats were perfusion fixed. Functional recovery was studied in two separate group of pre-trained animals (n = 8-8) using the staircase method for 30 days. The expression levels of proteins involved in apoptosis, neuroplasticity and inflammatory regulation were assessed by real-time qPCR and ELISA. Results: DMT treated rats were characterized by lower ischemic lesion volume (p = .0373), and better functional recovery (p = .0084) compared to the controls. Sig-1R was expressed both in neurons and in microglia in the peri-infarct cortex, and the DMT induced change in the lesion volume was hindered by BD1063. Lower APAF1 expression (mRNA and protein) and higher BNDF levels were documented on DTM, while decreased TNF-α, IL1β, IL-6 and increased IL-10 expressions indicated the compound's anti-inflammatory potential. Conclusion: Our results indicate a Sig-1R dependent reduction of the ischemic brain injury following exogenous DMT administration in rats, presumably through a combined anti-apoptotic, pro-neurotrophic and anti-inflammatory treatment effect.
Neuropharmacology , 2021
Dimethyltryptamine (DMT), an endogenous ligand of sigma-1 receptors (Sig-1Rs), acts against syste... more Dimethyltryptamine (DMT), an endogenous ligand of sigma-1 receptors (Sig-1Rs), acts against systemic hypoxia, but whether DMT may prevent cerebral ischemic injury is unexplored. Here global forebrain ischemia was created in anesthetized rats and aggravated with the induction of spreading depolarizations (SDs) and subsequent short hypoxia before reperfusion. Drugs (DMT, the selective Sig-1R agonist PRE-084, the Sig-1R antagonist NE-100, or the serotonin receptor antagonist asenapine) were administered intravenously alone or in combination while physiological variables and local field potential from the cerebral cortex was recorded. Neuroprotection and the cellular localization of Sig-1R were evaluated with immunocytochemistry. Plasma and brain DMT content was measured by 2D-LC-HRMS/MS. The affinity of drugs for cerebral Sig-1R was evaluated with a radioligand binding assay. Both DMT and PRE-084 mitigated SDs, counteracted with NE-100. Further, DMT attenuated SD when co-administered with asenapine, compared to asenapine alone. DMT reduced the number of apoptotic and ferroptotic cells and supported astrocyte survival. The binding affinity of DMT to Sig-1R matched previously reported values. Sig-1Rs were associated with the perinuclear cytoplasm of neurons, astrocytes and microglia, and with glial processes. According to these data, DMT may be considered as adjuvant pharmacological therapy in the management of acute cerebral ischemia.
![Research paper thumbnail of Szorongászavarok és kezelési nehézségeik a hazai tapasztalatok függvényében [Anxiety disorders and their treatment problems in Hungarian praxis. In Hungarian]](https://attachments.academia-assets.com/104540508/thumbnails/1.jpg)
](Háziorvos Továbbképző Szemle, 2022
A félelem es a szorongás egymáshoz hasonló, adaptív hátterű pszichés állapot. Mindkettő normális ... more A félelem es a szorongás egymáshoz hasonló, adaptív hátterű pszichés állapot. Mindkettő normális reakció lehet fenyegető helyzetben vagy más kihívó stresszorral szemben úgy, hogy hatása pozitív, óvó-védő funkciót tölt be a jobb teljesítőképességet és a túlélés esélyeit szolgálva. Figyelmeztet a veszélyre, fókuszálja a figyelmet és segít a felkészülésben. Amíg a félelem egy aktuális fenyegető helyzetre adott testi-érzelmi reakció, addig a szorongás egy jövőre irányuló, fokozott éberséggel és fizikális tünetekkel járó, izgalmi állapot. Patalógás a szorongás, ha nincs tárgya az aggálynak, vagy ha túlméretezetten nem segít a megküzdésben, sőt a hétköznapokban való helytállást is akadályozza vagy beszűkíti a szociális kapcsolatokat. Szorongászavarokban a félelemnek, aggályoskodásnak maladaptiv formájáról, az érintett korához nem illő, azzal inkongruens megjeleneseről van szó.
![Research paper thumbnail of Alvászavarok és kezelési nehézségeik a hazai tapasztalatok függvényében [Sleep disorders and their treatment problems in Hungarian praxis. In Hungarian]](https://attachments.academia-assets.com/104540139/thumbnails/1.jpg)
](Gyógyszerész Továbbképzés, 2022
Nem szükséges hangsúlyozni – csak kiindulópontként említem – hogy az alvás mennyire lényeges rész... more Nem szükséges hangsúlyozni – csak kiindulópontként említem – hogy az alvás mennyire lényeges része életünknek. Publikációkban, prezentációkban gyakran fordul elő, hogy valami leírva vagy kimondva közhelynek hangzik, ám mennyire közhely az, amelynek megvalósítása tartósan csorbát szenved és alig úszik be a figyelem fókuszába, csak lebeg a tudatosság perifériáján. Valahogy így állunk az alvászavarok kezelésével is. Az alvászavarok népegészségügyi kihatása jelentős, mégis az erre szakosodott alvásmedicina egyelőre nem nyert kellő teret a hazai szakellátásban, és ebből kifolyólag kezelésük gyakran nem a szakmai irányelveknek megfelelően történik.
![Research paper thumbnail of A mikrobiom-asszociált gyulladás és a migrén: A bél–agy tengely újabb állomása? [Microbiome-associated inflammation and migraine: A new link in the brain-gut axis? In Hungarian]](https://attachments.academia-assets.com/104539698/thumbnails/1.jpg)
](Central European Journal of Gastroenterology and Hepatology , 2022
Bél–agy tengelynek nevezzük az emésztőrendszer és a központi idegrendszer működése közötti funkci... more Bél–agy tengelynek nevezzük az emésztőrendszer és a központi idegrendszer működése közötti funkcionális kapcsolatot. A humán mikrobiom ezen a területen is nagy áttörést hozott, és új perspektívába helyezte a migrén kóroktanának tényezőit is, amelyek ma a klinikai agykutatás és a farmakológia fontos kutatási területei. Jelen összefoglaló a környezeti tényezők hosszú távú hatásait – a mikrobiom-változással kialakuló gyulladásos és anyagcsere-eltéréseket – helyezi el a migrén patofiziológiájának legújabb eredményei mellé. Gyakorlati támpontokat kíván adni a betegellátásban a tüneti és oki tényezők feltérképezéséhez, illetve ezekkel kapcsolatos életmódtényezők azonosításához. Ez lehetővé teszi ezen környezeti oki tényezők változtatását és a célzott gyógyszeres kezelés kiegészítését a krónikus fejfájásban szenvedő, migrénre is hajlamos betegek sikeres preventív kezelése érdekében. Ennek a jelentősége óriási a migrén nagy prevalenciája miatt a nyugati világban, illetve a kezelésére széles körben alkalmazott fájdalomcsillapító (tüneti) kezelések hosszú távú szövődményei miatt.
Neuroscience Chronicles, 2021
The article entitled “N,N-Dimethyltryptamine [DMT] attenuates spreading depolarization and restra... more The article entitled “N,N-Dimethyltryptamine [DMT] attenuates spreading depolarization and restrains neurodegeneration by sigma-1 receptor activation in the ischemic rat brain” by Szabo et al. published recently in Neuropharmacology [192:108612] is the last one in the series of studies on the potential benefits of DMT administration in different clinical forms of ischemia-reperfusion injury (IRI). The larger scope of the project – initiated and organized by Ede Frecska – is to collect support for a hypothesized biological function of this and related endogenous hallucinogen compounds such as 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), 5-hydroxy-N,N-dimethyl-tryptamine (bufotenine). Establishing beneficial effects of these naturally occurring components of the mammalian body is a necessary but not satisfactory criterion for a physiological role. We wish to mention here early on, that regard-less of the fulfilment of this second bold aim, if accumulating evidence with independent replications support our findings on the tissue (especially neuro-) protective effects of DMT and its analogues, than ways may open for therapeutic applications and their current classification as Schedule I agents may change for better. The latter carries a stigma and impedes scientific research of these neurochemically very potent and enigmatic molecules.
Biomedicines, 2022
Ischemic eye diseases are major causes of vision impairment. Thus, potential retinoprotective eff... more Ischemic eye diseases are major causes of vision impairment. Thus, potential retinoprotective effects of N’N-dimethyltryptamine (DMT) were investigated. To inhibit its rapid breakdown by monoamine-oxidase A (MAO-A) enzyme, DMT was co-administered with harmaline, a –carboline in the Amazonian Ayahuasca brew. Using ligation, 60 min of ischemia was provoked in eyes of rats, followed by 7 days of reperfusion whilst animals received harmaline alone, DMT + harmaline, or vehicle treatment. After 1 week of reperfusion, electroretinographical (ERG) measurements, histological analysis, and Western blot were performed. Harmaline alone exhibited retinoprotection in ischemia–reperfusion (I/R) which was, surprisingly, counterbalanced by DMT in case of co-administration. As both MAO-A inhibition and DMT increase serotoninergic tone synergistically, communicated to be anti-ischemic, thus, involvement of other pathways was investigated. Based on our experiments, DMT and harmaline exert opposite effects on important ocular proteins such as PARP1, NF B, MMP9, or HSP70, each having a critical role in a different mechanism of eye-ischemia-related pathologies, e.g., cell death, inflammation, tissue destruction, and oxidative stress. Since DMT is proclaimed to be a promising drug candidate, its potentially undesirable effect on eye-ischemia should be further investigated. Meanwhile, this experiment revealed the potential therapeutic effect of MAO-A inhibitor harmaline in I/R-related eye diseases.
Journal of Consciousness Studies, 2023
Soul belief is a universal of human culture and belief in multiple souls is common, especially in... more Soul belief is a universal of human culture and belief in multiple souls is common, especially in pre-modern traditions. This essay illustrates how a three-folded structure appears in the soul concepts of Mongolian shamanistic traditions. The reported accounts of the three souls among various Mongolian ethnic groups are somewhat divergent-especially in their consciousness-related attributeswhich may reflect the cultural bias of data collectors, inconsistencies between data providers, and the evolution of these concepts due to historical events, socioeconomic changes, and external cultural influences. Despite these confounding effects, the soul concept of Mongolian shamanism is similar in its pluralism to the beliefs of many other cultures. Mongolian Indigenous concepts and their descriptions reveal key elements of consciousness. Although these soul concepts evoke spiritual interpretations, they nevertheless reflect aspects of an
European Neuropsychopharmacology, 2023
Alzheimer's Disease (AD) is a currently incurable but increasingly prevalent fatal and progressiv... more Alzheimer's Disease (AD) is a currently incurable but increasingly prevalent fatal and progressive neurodegenerative disease, demanding consideration of therapeutically relevant natural products and their synthetic analogues. This paper reviews evidence for effectiveness of natural and synthetic psychedelics in the treatment of AD causes and symptoms. The plastogenic effects of serotonergic psychedelics illustrate that they have efficacy for addressing multiple facets of AD pathology. We review findings illustrating neuroplasticity mechanisms of classic (serotonergic) and non-classic psychedelics that indicate their potential as treatments for AD and related dementias. Classic psychedelics modulate glutamatergic neurotransmission and stimulate synaptic and network remodeling that facilitates synaptic, structural and behavioral plasticity. Up-regulation of neurotrophic factors enable psychedelics to promote neuronal survival and glutamate-driven neuroplasticity. Muscimol modulation of GABA A R reduces A βinduced neurotoxicity and psychedelic Sig-1R agonists provide protective roles in A β toxicity. Classic psychedelics also activate mTOR intracellular effector pathways in brain regions that show atrophy in AD. The potential of psychedelics to treat AD involves their ability to induce structural and functional neural plasticity in brain circuits and slow or reverse brain atrophy. Psychedelics stimulate neurotrophic pathways, increase neurogenesis and produce long-lasting neural changes through rewiring pathological neurocircuitry. Psychedelic effects on 5-HT receptor target genes and induction of synaptic, structural, and functional changes in neurons
Journal of Psychedelic Studies, 2017
In contemporary phenomenology, Dieter Lohmar has suggested that the new task of phenomenological ... more In contemporary phenomenology, Dieter Lohmar has suggested that the new task of phenomenological research is to analyze the “alternative representational systems” of fantasy. In line with this program, we propose that psychedelic experience could also be suitable subject to this project subsumed under the wider category of fantasy activity. The aim of this paper is to show that psyche-delic experiences offer a favorable situation to study the imagination. Method: The paper applies the conceptual framework of the late Merleau-Ponty, developed in The Visible and the Invisible, using his mescaline analyses which have been elaborated in The Phenomenology of Perception. Results: We demonstrate that psychedelic visions and emotional states can be discussed within the Merleau-Pontian framework of “wild world.” From the viewpoint of phenomenology, we suggest that psychedelic visions represent an ongoing sense-making and Gestalt-formation process in which the role of the elaborative activity of the subject is crucial. These – often unsettling – visions show the basic volatility and ambiguity of perception and fantasy, which also sheds light to the hidden schemes of perception, thinking, and emotion of normal consciousness. Conclusions: Freud claimed that dreams are “the royal road” to the unconscious. In an analogous manner, while dreams were the primary psychoscope to the unconscious of psychoanalysis, in contemporary phenomenology psychedelic experiences may show a possible way to an another kind of unconscious, the phenome-nological unconscious. This unconscious comprises the hidden schemes and basic affective emotional attitudes of the knowing sub-ject.
Acta Agraria Debreceniensis, 2021
With the increasing attention to the health promoting activities of the bioactive compounds from ... more With the increasing attention to the health promoting activities of the bioactive compounds from some plants, many researchers are focusing on the biological potential and mechanisms of certain cultivated plant species. In this review, we survey the olive and almond based extracts specific phytoconstituents and their associated health promoting effects that have been evaluated in experimental and clinical studies.
NeuroQuantology, 2016
Healing methods based on the altered states of consciousness common to spiritual or shamanic trad... more Healing methods based on the altered states of consciousness common to spiritual or shamanic traditions escape neuroscientific explanations based on classical physics and classical cognition–denoted here as ‘perceptual- cog-nitive’ (characteristic of the ordinary state of consciousness) information processing. A second foundation of knowledge–named as ‘nonlocal-intuitive’ approach–with another way for making representation of the environ-ment is recommended to be introduced for better understanding of the shaman’s reintegrative role in their com-munity and for an improved interpretation of the shamanic state of consciousness with the ‘soul flight’ in its cen-ter. This essay offers terminology for translating some common elements of indigenous world views into a frame closer to the contemporary Western mindset. The proposed model suggests that when the coping capacity of the ‘perceptual-cognitive’ mode of processing is exhausted in a stressful or unmanageable situation, or its dominance is eliminated by the use of hallucinogens or contemplation, a frame shift occurs, and an alternate source of envi-ronmental information is opened through a ‘nonlocal-intuitive’ channel. Consequently, the core activity of sha-manic practice, the shamanic journey, occurs in a field of quantum connections and is not restricted by space-time constrains, but limited by the uncertainty principle.
![Research paper thumbnail of A Covid-19-fertőzés neuropszichiátriai szövődményei [The neuropsychiatric complications of COVID-19 infection. In Hungarian]](https://attachments.academia-assets.com/104540883/thumbnails/1.jpg)
](Lege Artis Medicinae, 2021
Initially, the studies of COVID-19 infection focused primarily on the acute and subacute somatic ... more Initially, the studies of COVID-19 infection focused primarily on the acute and subacute somatic symptoms of limited duration, but later on with the spread of the pandemic the scope was extended to prolonged symptoms recognized as complications. Data are mounting about after-effects in circulation, respiration, coagulation, problematic outcomes in rheumatology, dermatology, ophthalmology, as well as about the acute and prolonged symptoms of the dysfunctional central nervous system. Initially, sporadic case reports, later results of population based studies and animal models were available, and the first systematic review articles were emerging during preparation of our survey. Lesions of the central nervous system may manifest themselves both in neurological symptoms and diseases or psychiatric complaints and syndromes. The scale of symptoms is broad, the pathomechanisms are not perfectly mapped thus all therapeutic approaches are in their infancy yet. Epidemiological data of neuropsychiatric complications are incomplete for the time being though they have been rapidly becoming more accurate. Conservative estimates assume tens of millions of people affected worldwide. More time is necessary to assess the persistence or improvement of the prolonged symptoms. Besides every efforts to block the spread of the virus, the utmost importance is to analyze the effects of the virus on the central nervous system and to develop effective treatment strategies. According to our current knowledge, the pathomechanism of neuropsychiatric complications is multifactorial. Beyond the direct deleterious effect of the virus on neuronal and glial functions, more important is that the serious consequences of cerebrovascular dysfunction and poor oxygenation have to be taken into consideration together with extended and prolonged systemic immunological processes, which markedly harm the brain tissue, notably neurons, axons, synapses and glia cells. Based on a non-systematic literature review our work details these mechanisms and addresses therapeutic options as well.
Current Neuropharmacology, 2017
Background: Widespread protein aggregation occurs in the living system under stress or during agi... more Background: Widespread protein aggregation occurs in the living system under stress or during aging, owing to disturbance of endoplasmic reticulum (ER) proteostasis. Many neurodegenerative diseases may have a common mechanism: the failure of protein homeostasis. Perturbation of ER results in unfolded protein response (UPR). Prolonged chronical UPR may activate apoptotic pathways and cause cell death. Methods: Research articles on Sigma-1 receptor were reviewed. Results: ER is associated to mitochondria by the mitochondria-associated ER-membrane, MAM. The sigma-1 receptor (Sig-1R), a well-known ER-chaperone localizes in the MAM. It serves for Ca 2+-signaling between the ER and mitochondria, involved in ion channel activities and especially important during neuronal differentiation. Sig-1R acts as central modulator in inter-organelle signaling. Sig-1R helps cell survival by attenuating ER-stress. According to sequence based predictions Sig-1R is a 223 amino acid protein with two transmembrane (2TM) domains. The X-ray structure of the Sig-1R [1] showed a membrane-bound trimeric assembly with one transmembrane (1TM) region. Despite the in vitro determined assembly, the results of in vivo studies are rather consistent with the 2TM structure. The receptor has unique and versatile pharmacological profile. Dimethyl tryptamine (DMT) and neuroactive steroids are endogenous ligands that activate Sig-1R. The receptor has a plethora of interacting client proteins. Sig-1R exists in oligomeric structures (dimer-trimer-octamer-multimer) and this fact may explain interaction with diverse proteins. Conclusion: Sig-1R agonists have been used in the treatment of different neurodegenerative diseases, e.g. Alzheimer's and Parkinson's diseases (AD and PD) and amyotrophic lateral sclerosis. Utilization of Sig-1R agents early in AD and similar other diseases has remained an overlooked therapeutic opportunity.
Psychiatria Hungarica, 2022
Introduction: In the recent research and interpretation of the genetical-biological and environ... more Introduction:
In the recent research and interpretation of the genetical-biological and environmental-social factors shaping psychosexual development, in addition to scientific arguments, more and more ideological and political aspect have received unfortunate emphasis.
Objective:
Since the literature investigating the development of gender identity and gender orientation has not only increased, but also polarized, it is timely to look at the scientific exchange of ideas and debates among the differing positions.
Method:
Exploring the significance of genetic, biological and social factors involved in the development of gender identity and gender orientation based on international literature data.
Results:
Based on the current state of science it can be concluded that, in addition to the indisputably marked genetic-biological factors, education and social patterns, as well as the extremely complex environmental and media-related influence with its variable intensity and diverse emotional content also play a significant role in the psychosexual development. This is supported, among other observations, by the data indicating that homoerotic behavior is more common in people raised by same-sex couples.
Conclusion:
As psychosexual development is determined jointly by both genetic-biological and social factors (like education, media etc), belonging to a sexual minority group is not a choice, not the result of a personal decision. Therefore, any kind of discrimination in this regard is unacceptable. Further scientific studies are necessary to answer a large number of questions that still remain open.
Psychiatria Hungarica, 2020
Demográfiai és távoli anamnesztikus adatok Gizella jelenleg 41 éves, egyedülálló, szüleivel élő, ... more Demográfiai és távoli anamnesztikus adatok Gizella jelenleg 41 éves, egyedülálló, szüleivel élő, érettségizett, majd három és fél éves számviteli szakot végzett logisztikus, tíz éve munka nélkül, szkizofrénia diagnózissal élő nőbeteg. Első alkalommal 2004-ben (25 éves korában) jelent meg a Pszichiátriai Gondozóban alkalmazkodási problémákkal. Akkor labilis hangulat, feszültség, alacsony frusztrációs tolerancia jellemezte, munkahelyét otthagyta. Alkoholt alkalmanként fogyasztott, nem drogozott, akkor még naponta egy doboz cigarettát szívott. Premorbid vonásai alapján szociábilis, sokoldalúan érdeklődő, mentálisan élénk, derűs, nyitott személyiségűként jellemezhető. Családi anamnézise pszichiátriai vonatkozásban negatív. 2010-ig pszichiátriai szempontból gyógyszermentes volt.
Open Medicine, 2020
The objective of this research is to identify the relationship between the neuropsychiatric sympt... more The objective of this research is to identify the relationship between the neuropsychiatric symptoms (NPSs) of patients with major neurocognitive disorder (mNCD), their quality of life, illness intrusiveness and the caregiver's burden. We assessed 131 patients with mNCD. Examination methods included WHO well-being index short version, illness intrusiveness rating scale, Alzheimer's Disease Assessment Scale-Cog, Mini Mental State Examination and neuropsychiatric inventory. The results were analysed using standard statistical tests. In our sample, the prevalence of NPSs is 100%. A significant correlation (p < 0.0001) was observed with quality of life and illness intrusiveness. Additionally, a strong relationship was observed between NPSs and the caregiver's burden (r = 0.9). The result is significantly twice as much stronger in comparison to the relationship between NPS and cognitive symptoms (r = 0.4). This is the first study in Hungary to assess the impact of NPS on the burden of relatives and quality of life. NPS had twice stronger impact on caregivers' burden than cognitive decline. However, further studies are needed to assess the sub-syndromes in mNCD in relation to NPS.
Neuropsychopharmacologia Hungarica, 2020
Discovery and development of the selective serotonin reuptake inhibitors mark a milestone in neur... more Discovery and development of the selective serotonin reuptake inhibitors mark a milestone in neuro-pharmacology. Drugs from this class alter the functioning of the serotonin system by the potentiation of serotonin through the negative allosteric modulation of its neuronal uptake by the human serotonin transporter. Selective serotonin reuptake inhibitors show few side effects compared to those caused by traditional antidepressants and they vary in the binding interactions formed during binding. Gener-ally, their binding involves three specific regions of the drug structures, each participating in vital inter-actions, such as salt bridge formation and additional hydrophobic interactions with conserved resi-dues in the central binding site of the target protein. Side effects, however, such as the initial lack of response to treatment, or drowsiness, nausea, and sexual dysfunction occasionally may arise. Addi-tional binding studies, furthermore, highlighted the importance of enantioselectivity in the binding of these compounds, raising concerns about the beneficial application of racemate mixtures of some of these compounds. Therefore, additional characterisation of binding and further structural improve-ment of this class of drugs is necessary. The recently synthesized sertraline salts, and functional deriv-atives of fluoxetine and citalopram show promising results in delivering antidepressant activity as well as in effectively overcoming anorexigenic side-effects in rodent models. Hence, despite certain non-desired effects associated with selective serotonin reuptake inhibitor applications, this class of drugs is considered as first-line medication in the management of major depression, and is carrying an excel-lent potential for the development and refinement of the currently available and novel antidepressant therapies.
Experimental Neurology , 2020
Background and purpose: N,N-dimethyltryptamine (DMT) is an endogenous ligand of the Sigma 1 recep... more Background and purpose: N,N-dimethyltryptamine (DMT) is an endogenous ligand of the Sigma 1 receptor (Sig-1R) with documented in vitro cytoprotective properties against hypoxia. Our aim was to demonstrate the in vivo neuroprotective effect of DMT following ischemia-reperfusion injury in the rat brain. Methods: Transient middle cerebral occlusion (MCAO) was induced for 60 min in male Wistar rats using the filament occlusion model under general anaesthesia. Before the removal of the filament the treatment group (n = 10) received an intra-peritoneal (IP) bolus of 1 mg/kg-body weight (bw) DMT dissolved in 1 ml 7% ethanol/saline vehicle, followed by a maintenance dose of 2 mg/Kg-bw/h delivered over 24 h via osmotic minipumps. Controls (n = 10) received a vehicle bolus only. A third group (n = 10) received a Sig-1R antagonist (BD1063, 1 mg/kg-bw bolus +2 mg/kg-bw/h maintenance) in parallel with the DMT. Lesion volume was measured by MRI 24 h following the MCAO. Shortly after imaging the animals were terminated, and the native brains and sera were removed. Four rats were perfusion fixed. Functional recovery was studied in two separate group of pre-trained animals (n = 8-8) using the staircase method for 30 days. The expression levels of proteins involved in apoptosis, neuroplasticity and inflammatory regulation were assessed by real-time qPCR and ELISA. Results: DMT treated rats were characterized by lower ischemic lesion volume (p = .0373), and better functional recovery (p = .0084) compared to the controls. Sig-1R was expressed both in neurons and in microglia in the peri-infarct cortex, and the DMT induced change in the lesion volume was hindered by BD1063. Lower APAF1 expression (mRNA and protein) and higher BNDF levels were documented on DTM, while decreased TNF-α, IL1β, IL-6 and increased IL-10 expressions indicated the compound's anti-inflammatory potential. Conclusion: Our results indicate a Sig-1R dependent reduction of the ischemic brain injury following exogenous DMT administration in rats, presumably through a combined anti-apoptotic, pro-neurotrophic and anti-inflammatory treatment effect.
Neuropharmacology , 2021
Dimethyltryptamine (DMT), an endogenous ligand of sigma-1 receptors (Sig-1Rs), acts against syste... more Dimethyltryptamine (DMT), an endogenous ligand of sigma-1 receptors (Sig-1Rs), acts against systemic hypoxia, but whether DMT may prevent cerebral ischemic injury is unexplored. Here global forebrain ischemia was created in anesthetized rats and aggravated with the induction of spreading depolarizations (SDs) and subsequent short hypoxia before reperfusion. Drugs (DMT, the selective Sig-1R agonist PRE-084, the Sig-1R antagonist NE-100, or the serotonin receptor antagonist asenapine) were administered intravenously alone or in combination while physiological variables and local field potential from the cerebral cortex was recorded. Neuroprotection and the cellular localization of Sig-1R were evaluated with immunocytochemistry. Plasma and brain DMT content was measured by 2D-LC-HRMS/MS. The affinity of drugs for cerebral Sig-1R was evaluated with a radioligand binding assay. Both DMT and PRE-084 mitigated SDs, counteracted with NE-100. Further, DMT attenuated SD when co-administered with asenapine, compared to asenapine alone. DMT reduced the number of apoptotic and ferroptotic cells and supported astrocyte survival. The binding affinity of DMT to Sig-1R matched previously reported values. Sig-1Rs were associated with the perinuclear cytoplasm of neurons, astrocytes and microglia, and with glial processes. According to these data, DMT may be considered as adjuvant pharmacological therapy in the management of acute cerebral ischemia.
Háziorvos Továbbképző Szemle, 2022
A félelem es a szorongás egymáshoz hasonló, adaptív hátterű pszichés állapot. Mindkettő normális ... more A félelem es a szorongás egymáshoz hasonló, adaptív hátterű pszichés állapot. Mindkettő normális reakció lehet fenyegető helyzetben vagy más kihívó stresszorral szemben úgy, hogy hatása pozitív, óvó-védő funkciót tölt be a jobb teljesítőképességet és a túlélés esélyeit szolgálva. Figyelmeztet a veszélyre, fókuszálja a figyelmet és segít a felkészülésben. Amíg a félelem egy aktuális fenyegető helyzetre adott testi-érzelmi reakció, addig a szorongás egy jövőre irányuló, fokozott éberséggel és fizikális tünetekkel járó, izgalmi állapot. Patalógás a szorongás, ha nincs tárgya az aggálynak, vagy ha túlméretezetten nem segít a megküzdésben, sőt a hétköznapokban való helytállást is akadályozza vagy beszűkíti a szociális kapcsolatokat. Szorongászavarokban a félelemnek, aggályoskodásnak maladaptiv formájáról, az érintett korához nem illő, azzal inkongruens megjeleneseről van szó.
Gyógyszerész Továbbképzés, 2022
Nem szükséges hangsúlyozni – csak kiindulópontként említem – hogy az alvás mennyire lényeges rész... more Nem szükséges hangsúlyozni – csak kiindulópontként említem – hogy az alvás mennyire lényeges része életünknek. Publikációkban, prezentációkban gyakran fordul elő, hogy valami leírva vagy kimondva közhelynek hangzik, ám mennyire közhely az, amelynek megvalósítása tartósan csorbát szenved és alig úszik be a figyelem fókuszába, csak lebeg a tudatosság perifériáján. Valahogy így állunk az alvászavarok kezelésével is. Az alvászavarok népegészségügyi kihatása jelentős, mégis az erre szakosodott alvásmedicina egyelőre nem nyert kellő teret a hazai szakellátásban, és ebből kifolyólag kezelésük gyakran nem a szakmai irányelveknek megfelelően történik.
Central European Journal of Gastroenterology and Hepatology , 2022
Bél–agy tengelynek nevezzük az emésztőrendszer és a központi idegrendszer működése közötti funkci... more Bél–agy tengelynek nevezzük az emésztőrendszer és a központi idegrendszer működése közötti funkcionális kapcsolatot. A humán mikrobiom ezen a területen is nagy áttörést hozott, és új perspektívába helyezte a migrén kóroktanának tényezőit is, amelyek ma a klinikai agykutatás és a farmakológia fontos kutatási területei. Jelen összefoglaló a környezeti tényezők hosszú távú hatásait – a mikrobiom-változással kialakuló gyulladásos és anyagcsere-eltéréseket – helyezi el a migrén patofiziológiájának legújabb eredményei mellé. Gyakorlati támpontokat kíván adni a betegellátásban a tüneti és oki tényezők feltérképezéséhez, illetve ezekkel kapcsolatos életmódtényezők azonosításához. Ez lehetővé teszi ezen környezeti oki tényezők változtatását és a célzott gyógyszeres kezelés kiegészítését a krónikus fejfájásban szenvedő, migrénre is hajlamos betegek sikeres preventív kezelése érdekében. Ennek a jelentősége óriási a migrén nagy prevalenciája miatt a nyugati világban, illetve a kezelésére széles körben alkalmazott fájdalomcsillapító (tüneti) kezelések hosszú távú szövődményei miatt.
Neuroscience Chronicles, 2021
The article entitled “N,N-Dimethyltryptamine [DMT] attenuates spreading depolarization and restra... more The article entitled “N,N-Dimethyltryptamine [DMT] attenuates spreading depolarization and restrains neurodegeneration by sigma-1 receptor activation in the ischemic rat brain” by Szabo et al. published recently in Neuropharmacology [192:108612] is the last one in the series of studies on the potential benefits of DMT administration in different clinical forms of ischemia-reperfusion injury (IRI). The larger scope of the project – initiated and organized by Ede Frecska – is to collect support for a hypothesized biological function of this and related endogenous hallucinogen compounds such as 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), 5-hydroxy-N,N-dimethyl-tryptamine (bufotenine). Establishing beneficial effects of these naturally occurring components of the mammalian body is a necessary but not satisfactory criterion for a physiological role. We wish to mention here early on, that regard-less of the fulfilment of this second bold aim, if accumulating evidence with independent replications support our findings on the tissue (especially neuro-) protective effects of DMT and its analogues, than ways may open for therapeutic applications and their current classification as Schedule I agents may change for better. The latter carries a stigma and impedes scientific research of these neurochemically very potent and enigmatic molecules.
Biomedicines, 2022
Ischemic eye diseases are major causes of vision impairment. Thus, potential retinoprotective eff... more Ischemic eye diseases are major causes of vision impairment. Thus, potential retinoprotective effects of N’N-dimethyltryptamine (DMT) were investigated. To inhibit its rapid breakdown by monoamine-oxidase A (MAO-A) enzyme, DMT was co-administered with harmaline, a –carboline in the Amazonian Ayahuasca brew. Using ligation, 60 min of ischemia was provoked in eyes of rats, followed by 7 days of reperfusion whilst animals received harmaline alone, DMT + harmaline, or vehicle treatment. After 1 week of reperfusion, electroretinographical (ERG) measurements, histological analysis, and Western blot were performed. Harmaline alone exhibited retinoprotection in ischemia–reperfusion (I/R) which was, surprisingly, counterbalanced by DMT in case of co-administration. As both MAO-A inhibition and DMT increase serotoninergic tone synergistically, communicated to be anti-ischemic, thus, involvement of other pathways was investigated. Based on our experiments, DMT and harmaline exert opposite effects on important ocular proteins such as PARP1, NF B, MMP9, or HSP70, each having a critical role in a different mechanism of eye-ischemia-related pathologies, e.g., cell death, inflammation, tissue destruction, and oxidative stress. Since DMT is proclaimed to be a promising drug candidate, its potentially undesirable effect on eye-ischemia should be further investigated. Meanwhile, this experiment revealed the potential therapeutic effect of MAO-A inhibitor harmaline in I/R-related eye diseases.
Journal of Consciousness Studies, 2023
Soul belief is a universal of human culture and belief in multiple souls is common, especially in... more Soul belief is a universal of human culture and belief in multiple souls is common, especially in pre-modern traditions. This essay illustrates how a three-folded structure appears in the soul concepts of Mongolian shamanistic traditions. The reported accounts of the three souls among various Mongolian ethnic groups are somewhat divergent-especially in their consciousness-related attributeswhich may reflect the cultural bias of data collectors, inconsistencies between data providers, and the evolution of these concepts due to historical events, socioeconomic changes, and external cultural influences. Despite these confounding effects, the soul concept of Mongolian shamanism is similar in its pluralism to the beliefs of many other cultures. Mongolian Indigenous concepts and their descriptions reveal key elements of consciousness. Although these soul concepts evoke spiritual interpretations, they nevertheless reflect aspects of an
European Neuropsychopharmacology, 2023
Alzheimer's Disease (AD) is a currently incurable but increasingly prevalent fatal and progressiv... more Alzheimer's Disease (AD) is a currently incurable but increasingly prevalent fatal and progressive neurodegenerative disease, demanding consideration of therapeutically relevant natural products and their synthetic analogues. This paper reviews evidence for effectiveness of natural and synthetic psychedelics in the treatment of AD causes and symptoms. The plastogenic effects of serotonergic psychedelics illustrate that they have efficacy for addressing multiple facets of AD pathology. We review findings illustrating neuroplasticity mechanisms of classic (serotonergic) and non-classic psychedelics that indicate their potential as treatments for AD and related dementias. Classic psychedelics modulate glutamatergic neurotransmission and stimulate synaptic and network remodeling that facilitates synaptic, structural and behavioral plasticity. Up-regulation of neurotrophic factors enable psychedelics to promote neuronal survival and glutamate-driven neuroplasticity. Muscimol modulation of GABA A R reduces A βinduced neurotoxicity and psychedelic Sig-1R agonists provide protective roles in A β toxicity. Classic psychedelics also activate mTOR intracellular effector pathways in brain regions that show atrophy in AD. The potential of psychedelics to treat AD involves their ability to induce structural and functional neural plasticity in brain circuits and slow or reverse brain atrophy. Psychedelics stimulate neurotrophic pathways, increase neurogenesis and produce long-lasting neural changes through rewiring pathological neurocircuitry. Psychedelic effects on 5-HT receptor target genes and induction of synaptic, structural, and functional changes in neurons
Journal of Psychedelic Studies, 2017
In contemporary phenomenology, Dieter Lohmar has suggested that the new task of phenomenological ... more In contemporary phenomenology, Dieter Lohmar has suggested that the new task of phenomenological research is to analyze the “alternative representational systems” of fantasy. In line with this program, we propose that psychedelic experience could also be suitable subject to this project subsumed under the wider category of fantasy activity. The aim of this paper is to show that psyche-delic experiences offer a favorable situation to study the imagination. Method: The paper applies the conceptual framework of the late Merleau-Ponty, developed in The Visible and the Invisible, using his mescaline analyses which have been elaborated in The Phenomenology of Perception. Results: We demonstrate that psychedelic visions and emotional states can be discussed within the Merleau-Pontian framework of “wild world.” From the viewpoint of phenomenology, we suggest that psychedelic visions represent an ongoing sense-making and Gestalt-formation process in which the role of the elaborative activity of the subject is crucial. These – often unsettling – visions show the basic volatility and ambiguity of perception and fantasy, which also sheds light to the hidden schemes of perception, thinking, and emotion of normal consciousness. Conclusions: Freud claimed that dreams are “the royal road” to the unconscious. In an analogous manner, while dreams were the primary psychoscope to the unconscious of psychoanalysis, in contemporary phenomenology psychedelic experiences may show a possible way to an another kind of unconscious, the phenome-nological unconscious. This unconscious comprises the hidden schemes and basic affective emotional attitudes of the knowing sub-ject.
Acta Agraria Debreceniensis, 2021
With the increasing attention to the health promoting activities of the bioactive compounds from ... more With the increasing attention to the health promoting activities of the bioactive compounds from some plants, many researchers are focusing on the biological potential and mechanisms of certain cultivated plant species. In this review, we survey the olive and almond based extracts specific phytoconstituents and their associated health promoting effects that have been evaluated in experimental and clinical studies.
NeuroQuantology, 2016
Healing methods based on the altered states of consciousness common to spiritual or shamanic trad... more Healing methods based on the altered states of consciousness common to spiritual or shamanic traditions escape neuroscientific explanations based on classical physics and classical cognition–denoted here as ‘perceptual- cog-nitive’ (characteristic of the ordinary state of consciousness) information processing. A second foundation of knowledge–named as ‘nonlocal-intuitive’ approach–with another way for making representation of the environ-ment is recommended to be introduced for better understanding of the shaman’s reintegrative role in their com-munity and for an improved interpretation of the shamanic state of consciousness with the ‘soul flight’ in its cen-ter. This essay offers terminology for translating some common elements of indigenous world views into a frame closer to the contemporary Western mindset. The proposed model suggests that when the coping capacity of the ‘perceptual-cognitive’ mode of processing is exhausted in a stressful or unmanageable situation, or its dominance is eliminated by the use of hallucinogens or contemplation, a frame shift occurs, and an alternate source of envi-ronmental information is opened through a ‘nonlocal-intuitive’ channel. Consequently, the core activity of sha-manic practice, the shamanic journey, occurs in a field of quantum connections and is not restricted by space-time constrains, but limited by the uncertainty principle.
Lege Artis Medicinae, 2021
Initially, the studies of COVID-19 infection focused primarily on the acute and subacute somatic ... more Initially, the studies of COVID-19 infection focused primarily on the acute and subacute somatic symptoms of limited duration, but later on with the spread of the pandemic the scope was extended to prolonged symptoms recognized as complications. Data are mounting about after-effects in circulation, respiration, coagulation, problematic outcomes in rheumatology, dermatology, ophthalmology, as well as about the acute and prolonged symptoms of the dysfunctional central nervous system. Initially, sporadic case reports, later results of population based studies and animal models were available, and the first systematic review articles were emerging during preparation of our survey. Lesions of the central nervous system may manifest themselves both in neurological symptoms and diseases or psychiatric complaints and syndromes. The scale of symptoms is broad, the pathomechanisms are not perfectly mapped thus all therapeutic approaches are in their infancy yet. Epidemiological data of neuropsychiatric complications are incomplete for the time being though they have been rapidly becoming more accurate. Conservative estimates assume tens of millions of people affected worldwide. More time is necessary to assess the persistence or improvement of the prolonged symptoms. Besides every efforts to block the spread of the virus, the utmost importance is to analyze the effects of the virus on the central nervous system and to develop effective treatment strategies. According to our current knowledge, the pathomechanism of neuropsychiatric complications is multifactorial. Beyond the direct deleterious effect of the virus on neuronal and glial functions, more important is that the serious consequences of cerebrovascular dysfunction and poor oxygenation have to be taken into consideration together with extended and prolonged systemic immunological processes, which markedly harm the brain tissue, notably neurons, axons, synapses and glia cells. Based on a non-systematic literature review our work details these mechanisms and addresses therapeutic options as well.