|
|
Psilocybin: the mechanism of action and therapeutic potential
Mintálová, Tímea ; Novotný, Jiří (advisor) ; Vejmola, Čestmír (referee)
Psilocybin is a psychoactive molecule derived from tryptamine precursors that is present in some mushrooms, especially those belonging to the Psilocybe genus. Its pharmacologically active metabolite, produced by dephosphorylation, is psilocin, which can cross the blood-brain barrier. It is believed that the psychedelic effects of psilocin result from its partial agonistic activities on 5-HT2A receptors, the main receptor subtype among serotonin G-protein-coupled receptors (GPCRs). Psilocin also binds to a number of other subtypes of these receptors, but the effects it has on these receptors have not been fully explored yet. Psilocybin has been studied for its potential use in treating anxiety, depression, and disorders caused by addictive substances when administered in concentrations sufficient to produce psychedelic effects. The pharmacological potential of psilocybin is without the risks of potential addiction or overdose compared to other psychoactive drugs such as cocaine, alcohol, methamphetamine, and others. Due to the increasing worldwide trend of addiction, overdose, and suicidal deaths, it is necessary to seek new therapeutic alternatives. However, it is also necessary to assess various contraindications that may limit the possibility of using psilocybin as a pharmacological therapy....
|
|
|
Antidepressant potential of serotonergic psychedelics in preclinical research
Dušková, Valentýna ; Vejmola, Čestmír (advisor) ; Skálová, Kateřina (referee)
The treatments for depression available in contemporary medicine have a number of drawbacks. Modern antidepressants, despite fewer side effects than conventional ones, have a slow onset of action and their effectiveness is often individual. Recent studies of psychedelics have indicated their promising to extraordinary potential in the treatment of depression. Clinical research has made significant progress in this direction, as have a growing number of preclinical studies. Psychedelics potentiate signaling pathways and protein expression related to neurogenesis and cell viability and induce an increase in dendritic spines and dendritic branching. At the behavioural level, psychedelics have been shown to attenuate depressive behavioural changes, suppressing anxiety and anhedonia. This paper summarizes the effects of psychedelics in preclinical in vitro and in vivo studies, taking into account the neurobiology of depression, i.e., mainly at the level of neuroplasticity and observed behavioural changes. The first part of the thesis is devoted to the general characteristics of depression and psychedelics, followed by an introduction to preclinical experimental approaches. The central part then describes and discusses individual studies. Keywords: depression; animal models; psychedelics; LSD;...
|
|
|
EEG correlates of the effect of serotonergic hallucinogens in the rat
Vejmola, Čestmír ; Tylš, Filip (advisor) ; Stuchlík, Aleš (referee)
Serotonergic hallucinogens (ie. the classic psychedelics), including psilocybin, lysergic acid diethylamide (LSD), mescaline and DOB, represent a group of psychoactive substances that profoundly affect human perception, thinking, affectivity and cognitive functions. All known agents of such origin are agonists of the serotonin 5-HT2A receptors and induce large changes in the psyche due to the wide distribution of these receptors throughout the brain. The similarities between psychotic state and the state induced by these substances were noticed sixty years ago. Today, an abnormal function of serotonergic system is one of the explanations of psychotic disorders and serotonergic hallucinogens are therefore used in animal models as a model of schizophrenia. Modern neurobiological methods slowly reveal the ways in which serotonin system interacts with other neurotransmitter systems and contributes to such complex function as a human consciousness is. Although changes in the activity of the human brain in a psychotic state and the state of intoxication with psychedelics were largely theoretically unraveled, the animal experimental evidence fitting into this theoretical framework is still missing. The first part of this thesis summarizes the findings regarding phenomenology, neurobiology and...
|
|
|
Serotonergic hallucinogenes and their therapeutic use
Bouberl, David ; Novotný, Jiří (advisor) ; Vejmola, Čestmír (referee)
Serotonergic hallucinogens are a group of substances that induce changes in consciousness based on their affinity for some of the serotonin receptors - especially 5-HT2A. The best known substances in this group include LSD, psilocybin or mescaline. During the 1950's and 1960's, initial research into the therapeutic uses of these substances took place, but studies from this period did not meet today's methodological standards. However, the results of recent studies point to the potential therapeutic use of psilocybin or LSD in the treatment of depression / anxiety, addiction and OCD. The aim of this work is to summarize current knowledge about selected serotonergic hallucinogens, their chemical properties, mechanisms of action and especially about the possibilities of using these substances in psychotherapy.
|
|
|
Neurobiology of visual hallucinations.
Dodoková, Alica ; Vejmola, Čestmír (advisor) ; Hejnová, Lucie (referee)
Hallucination is a clinically significant qualitative disorder of perception that can be characterized as a sensation without a proper physical stimulus. Visual hallucinations are among the most serious symptoms in a range of psychiatric disorders such as schizophrenia, Parkinson's disease, or Lewy body dementia, but can also occur during drug intoxication or under normal physiological conditions. Based on visual image processing principles and higher thalamocortical circuits, several recent explanations of the visual hallucinations phenomenon are summarized in this thesis. Although there may be many possible causes, the most important are neurobiological disorders of the inhibition processes in the cortical areas of visual association, lesions in the brain stem cores and thus the malfunctioning of the reticular activation system, neurochemical dysregulation on the thalamic sensory interface, or dysfunction of the recurrent top-down and bottom-up mechanism. There are several theoretical models summarizing the mentioned aberrations (Perception and Attention Deficit, Bayesian Heruism), which provide a more comprehensive overview of the issue of visual hallucinations. Further research and unification of individual models could provide new possibilities for diagnosis and treatment of visual...
|
|
|
Neurobiology of visual hallucinations.
Dodoková, Alica ; Vejmola, Čestmír (advisor) ; Hejnová, Lucie (referee)
Hallucination is a clinically significant qualitative disorder of perception that can be characterized as a sensation without a proper physical stimulus. Visual hallucinations are among the most serious symptoms in a range of psychiatric disorders such as schizophrenia, Parkinson's disease, or Lewy body dementia, but can also occur during drug intoxication or under normal physiological conditions. Based on visual image processing principles and higher thalamocortical circuits, several recent explanations of the visual hallucinations phenomenon are summarized in this thesis. Although there may be many possible causes, the most important are neurobiological disorders of the inhibition processes in the cortical areas of visual association, lesions in the brain stem cores and thus the malfunctioning of the reticular activation system, neurochemical dysregulation on the thalamic sensory interface, or dysfunction of the recurrent top-down and bottom-up mechanism. There are several theoretical models summarizing the mentioned aberrations (Perception and Attention Deficit, Bayesian Heruism), which provide a more comprehensive overview of the issue of visual hallucinations. Further research and unification of individual models could provide new possibilities for diagnosis and treatment of visual...
|
|
|
EEG correlates of the effect of serotonergic hallucinogens in the rat
Vejmola, Čestmír ; Tylš, Filip (advisor) ; Stuchlík, Aleš (referee)
Serotonergic hallucinogens (ie. the classic psychedelics), including psilocybin, lysergic acid diethylamide (LSD), mescaline and DOB, represent a group of psychoactive substances that profoundly affect human perception, thinking, affectivity and cognitive functions. All known agents of such origin are agonists of the serotonin 5-HT2A receptors and induce large changes in the psyche due to the wide distribution of these receptors throughout the brain. The similarities between psychotic state and the state induced by these substances were noticed sixty years ago. Today, an abnormal function of serotonergic system is one of the explanations of psychotic disorders and serotonergic hallucinogens are therefore used in animal models as a model of schizophrenia. Modern neurobiological methods slowly reveal the ways in which serotonin system interacts with other neurotransmitter systems and contributes to such complex function as a human consciousness is. Although changes in the activity of the human brain in a psychotic state and the state of intoxication with psychedelics were largely theoretically unraveled, the animal experimental evidence fitting into this theoretical framework is still missing. The first part of this thesis summarizes the findings regarding phenomenology, neurobiology and...
|
|
|
Psychedelics and mechanisms of their effect on the CNS
Vejmola, Čestmír ; Novotný, Jiří (advisor) ; Páleníček, Tomáš (referee)
Psychedelics represent the group of psychotropics, which induce characteristic cognitive, perceptual and emotional symptoms. They are represented by simple indolamines (psilocybin or DMT), ergoline derivatives (LSD), and substituted phenylethylamines (mescaline). This work with a systematic approach to the problem attempts to characterize the underlying basis of physiological effects of psychedelics in brain. After the general characterization of hallucinogens, among which psychedelics belong to, the first part is focused on the common psychological and physiological actions and risks associated with them. Follows the pharmacological characterization of selected representatives especially with regard to their origin, ways of administration, effects, distribution and metabolization in body. A large part is devoted to the description of G-protein-coupled receptors functioning. The principal part is the last one, which describes mechanisms of action of psychedelics at the cellular level such as well as in different brain regions.
|
guest ::
