Text představí ketaminem asistovanou psychoterapii (KAP) jako novou léčebnou modalitu v psychiatrii pro široké diagnostické spektrum. Tato metoda má odlišné charakteristiky i indikace od použití esketaminu či racemického ketaminu v off-label use u deprese. Je unikátní kombinací farmakologického i psychoterapeutického přístupu tím, že aktivně využívá změněný stav vědomí vyvolaný ketaminem k zásadní akceleraci a prohloubení psychoterapeutického procesu. Podkladem této akcelerace je indukce neuroplastického procesu, zvýšená schopnost učení, a tím pádem efektivnější psychoterapie. Metoda částečně navazuje jednak na objev rychlého antidepresivního a anxiolytického účinku ketaminu z přelomu tisíciletí, jednak na metodiku psychedelické psychoterapie 50. a 60. let 20. století. V současné době se rychle rozvíjí především v USA; v ČR implementuje tento model do zdravotní péče Psyon – Psychedelická klinika, ale v poslední době vznikají i další takto specializovaná pracoviště. Text je krátkým přehledem využití ketaminu v psychiatrii a souhrnem dosavadního výzkumu o použití ketaminu v psychoterapii, představí východiska KAP a odliší KAP od jiných přístupů práce s ketaminem.

The text introduces Ketamine-Assisted Psychotherapy (KAP) as a new therapeutic modality in psychiatry for a broad diagnostic range. This method has distinct characteristics and indications compared to the use of esketamine or racemic ketamine off-label for depression. KAP uniquely combines pharmacological and psychotherapeutic approaches by actively utilizing the altered state of consciousness induced by ketamine to significantly accelerate and deepen the psychotherapeutic process. The foundation of this acceleration lies in the induction of neuroplastic processes, enhanced learning capacity, and thereby more effective psychotherapy. The method partially builds on the discovery of ketamine's rapid antidepressant and anxiolytic effects from the turn of the millennium, as well as on the methodology of psychedelic psychotherapy from the 1950s and 1960s. Currently, it is rapidly developing, especially in the United States. In the Czech Republic, this model is being implemented into healthcare by Psyon – Psychedelic Clinic, and recently, other specialized centers have also emerged. The text is a brief overview of the use of ketamine in psychiatry and a summary of the current research on the application of ketamine in psychotherapy. It introduces the principles of KAP and distinguishes KAP from other approaches to working with ketamine.

• MeSH
• Depression drug therapy   therapy   MeSH
• Mental Disorders drug therapy   classification   therapy   MeSH
• Hallucinogens pharmacology   therapeutic use   MeSH
• Ketamine * pharmacology   therapeutic use   MeSH
• Combined Modality Therapy methods   MeSH
• Humans MeSH
• Obsessive-Compulsive Disorder drug therapy   therapy   MeSH
• Feeding and Eating Disorders drug therapy   therapy   MeSH
• Psychotherapy * methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Psychedelika jsou psychoaktivní látky, které bezprostředně po užití typicky vyvolávají změny vnímání, myšlení, emotivity a kognitivních procesů. V poslední době se intenzivně zkoumá jejich antidepresivní a anxiolytický efekt. Hlavní výhodou těchto látek je rychlý nástup účinku s dlouhodobým účinkem po podání jedné či jen několika málo dávek. Mají také dobrý bezpečnostní profil. Další využití mohou mít tyto látky v léčbě chronických bolestí u neuropatie a primárních bolestí hlavy, například cluster headache. Cluster headache neboli syndrom nakupených bolestí hlavy je vzácné onemocnění projevující se epizodami intenzivních bolestí hlavy s vegetativním doprovodem, které mohou pacienty výrazně limitovat. I když je konvenční léčba u většiny pacientů dostatečně účinná a bezpečná, existuje určitá skupina pacientů, u kterých tomu tak není. Proto se nadále pátrá po nových léčebných možnostech. Nový potenciální zdroj terapie cluster headache může na základě recentních dat představovat právě i skupina tryptaminových a ergolinových psychedelik, například psilocybin a diethylamid kyseliny lysergové (LSD) a některé jejich deriváty. Jedná se však zatím pouze o léčbu experimentální.

Psychedelics are psychoactive substances that typically cause changes in perception, thinking, emotionality, and cognitive processes immediately after use. Recently, their antidepressant and anxiolytic effects have been intensively investigated. The main advantage of these substances is the rapid onset and long-lasting effect after administration of one or only a few doses. They also have a good safety profile. These substances can also be used to treat chronic neurogenic pain and primary headaches, e.g. cluster headache. Cluster headache is a rare disease, manifested by episodes of intense headaches with vegetative accompaniment, which can significantly limit patients. Although conventional treatment is sufficiently effective and safe for most patients, there is a certain group for whom this is not the case. Therefore, the search for new treatment options continues. Based on recent data, a group of tryptamine and ergoline psychedelics, for example psilocybin and lysergic acid diethylamide (LSD), and some of their derivatives, may represent a new potential source of cluster headache therapy. This treatment is still experimental.

• MeSH
• Cluster Headache * diagnosis   drug therapy   pathology   MeSH
• Hallucinogens * adverse effects   therapeutic use   MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

5-MeO-DMT is a short-acting psychedelic that is anecdotally reported to induce a radical disruption of the self and a paradoxical quality of aroused, waking awareness that is nevertheless devoid of any specific perceptual contents. Here, we conducted an exploratory observational study of the phenomenological and neuronal effects of this compound. We collected micro-phenomenological interviews, psychometric questionnaires, and electroencephalography (EEG) in naturalistic ceremonial settings where 5-MeO-DMT was ingested. Results revealed that the 5-MeO-DMT experience followed a dynamic progression that-only in the most extreme cases-manifested as a complete absence of self-experience and other phenomenal content with preserved awareness. Furthermore, visual imagery, bodily self-disruption, narrative self-disruption, and reduced phenomenal distinctions occurred in a variable fashion. EEG analyses revealed the 5-MeO-DMT experience was characterised by (global) alpha and (posterior) beta power reductions, implying a mode of brain functioning where top-down models are inhibited. Our preliminary phenomenological findings confirm the potential utility of 5-MeO-DMT as a pharmacological model for deconstructed consciousness while noting the limitations of employing retrospective questionnaires for this purpose. Considering the exploratory nature of this study and its limitations inherent to its naturalistic nature, further research employing real-time experience sampling and phenomenologically trained participants in controlled environments could expand our findings to meaningfully inform the potential of this tool for the scientific study of consciousness.

• Publication type
• Journal Article MeSH

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

Hlavním cílem tohoto textu je představit nové psychoaktivní látky zahrnující širokou a různorodou skupinu látek, většinou syntetického původu, zejména se stimulačními, sedativními a halucinogenními účinky. Tyto látky byly vyvinuty nebo znovu uvedeny na trh, aby na jedné straně nahradily tradiční návykové látky, jejichž výroba a zejména distribuce často cílí na obcházení legislativy. Na druhé straně se jedná o velký obchodní potenciál pro výrobce a distributory těchto látek. V textu jsou představeny různé podskupiny těchto látek, jako jsou syntetické kanabinoidy a opioidy, a jejich závažná zdravotní rizika, včetně neurotoxických a kardiovaskulárních komplikací. Dále se zaměřuje na specifické skupiny uživatelů, které tyto látky preferují, na jejich důvody pro užívání, včetně snahy vyhnout se detekci drog nebo zlepšit sexuální prožitek. Zvláštní pozornost je věnována i novým psychedelickým látkám a kratomu, včetně jejich farmakologických vlastností a zdravotních rizik. Článek zdůrazňuje složitost fenoménu nových psychoaktivních látek a nutnost zvýšené pozornosti zdravotnických pracovníků při identifikaci a léčbě intoxikací těmito látkami.

The main objective of this text is to introduce new psychoactive substances, which encompass a broad and diverse group of substances, mostly of synthetic origin, with primarily stimulating, sedative, and hallucinogenic effects. These substances were developed or reintroduced to the market to replace traditional addictive substances, and their production often aims to circumvent legislation. The text discusses various subgroups of these substances, such as synthetic cannabinoids and opioids, and their serious health risks, including neurotoxic and cardiovascular complications. It also focuses on specific user groups who prefer these substances and their reasons for use, including attempts to avoid drug detection or enhance sexual experiences. Special attention is also given to new psychedelic substances and kratom, including their pharmacological properties and health risks. The article emphasizes the complexity of the phenomenon of new psychoactive substances and the need for increased attention from healthcare professionals in identifying and treating intoxications with these substances.

• MeSH
• Dimethoxyphenylethylamine administration & dosage   pharmacology   MeSH
• Cannabinoids pharmacology   adverse effects   MeSH
• Ketamine administration & dosage   pharmacology   adverse effects   MeSH
• Humans MeSH
• Mitragyna chemistry   adverse effects   MeSH
• Analgesics, Opioid adverse effects   MeSH
• Psychotropic Drugs * pharmacology   classification   adverse effects   MeSH
• Wakefulness-Promoting Agents pharmacology   adverse effects   MeSH
• Drug Users MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Psilocybe cubensis, a widely recognized psychoactive mushroom species, has played a significant role in both historical and modern therapeutic practices. This review explores the complex interplay between genetic diversity, strain variability and environmental factors that shape the biosynthesis of key psychoactive compounds, including psilocybin and psilocin. With many strains exhibiting substantial variability in their phenotypic characteristics and biochemical content, understanding and documenting this diversity is crucial for optimizing therapeutic applications. The review also highlights advances in cultivation techniques, such as submerged fermentation of the mycelium, and innovative analytical methodologies that have improved the precision of compound quantification and extraction. Although there is limited scientific information on P. cubensis due to nearly four decades of regulatory restrictions on psychedelic research, recent developments in genetic and biochemical studies are beginning to provide valuable insights into its therapeutic potential. Furthermore, this review emphasizes key knowledge gaps and offers insights into future research directions to advance the cultivation, scientific documentation of strain diversity, regulatory considerations and therapeutic use of P. cubensis.

• Publication type
• Journal Article MeSH
• Review 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

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

Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. To test this, we applied our recently developed biocompatible neuroprosthesis to measure prefrontal neural function in a well-established rat model of alcohol addiction and relapse. We monitored neural oscillations and event-related potentials in awake alcohol-dependent rats during abstinence and following treatment with psilocybin or LY379268, agonists of the serotonin 2A receptor (5-HT2AR), and the metabotropic glutamate receptor 2 (mGluR2), that are known to reduce prefrontal dysfunction and relapse. Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. Psilocybin and LY379268 were able to restore these impairments. Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract. In summary, we provide prefrontal markers indicative of relapse and treatment response, especially for psychedelic drugs.

• MeSH
• Alcoholism * drug therapy   physiopathology   MeSH
• Amino Acids MeSH
• Bridged Bicyclo Compounds, Heterocyclic * pharmacology   MeSH
• Biomarkers MeSH
• Evoked Potentials drug effects   MeSH
• Rats MeSH
• Disease Models, Animal * MeSH
• Prefrontal Cortex * drug effects   physiopathology   metabolism   MeSH
• Psilocybin * pharmacology   MeSH
• Receptors, Metabotropic Glutamate MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH