Tomas Palenicek

• MD, PhD
• Prague Psychiatric Center

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. W...

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 unders...

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 a...

Psilocybin is a classic psychedelic and a novel treatment for mood disorders. Psilocybin induces dose-dependent transient (4-6 hours) usually pleasant changes in perception, cognition, and emotion by non-selectively agonizing the 5-HT2A receptors and negatively regulating serotonin reuptake, and long-term positive antidepressant effect on mood and...

Rationale: Mescaline is a classical psychedelic compound with a phenylethylamine structure that primarily acts on serotonin 5-HT2A/C receptors, but also binds to 5-HT1A and 5-HT2B receptors. Despite being the first psychedelic ever isolated and synthesized, the precise role of different serotonin receptor subtypes in its behavioral pharmacology is...

Background Recent studies have intensively explored the potential antidepressant effects of psilocybin. However, important variables such as previous experience, repeated administration, setting and sex remain underexplored. This study describes the acute psilocybin experience and long-term effects in a small sample of healthy individuals. Methods...

Background: Recent evidence suggests that psychedelics are able to induce rapid and long-lasting antidepressant effects. The generally acknowledged explanation for these traits is the phenomenon of neuroplasticity, although exact underlying molecular mechanisms remain unclear. Aims: This study investigates selected neuroplastic effects of psilocin,...

This scientific paper addresses the potential risk of spurious responses in neuroscientific auditory steady-state response (ASSR) experiments attributed to transduction artifacts. The focus is particularly on click train stimuli, given their spectral content in the frequency range of interest (e.g., 40 Hz). Building upon a pilot experiment demonstr...

Psilocybin is investigated as a fast-acting antidepressant used in conjunction with psychotherapy. Intact cognitive functions, including memory, are one of the basic conditions of effective psychedelic-assisted therapy. While cognitive and memory processing is attenuated on various domains during psilocybin intoxication, the effect of psilocybin on...

The present study investigated whether neonatal exposure to the proinflammatory endotoxin lipopolysaccharide (LPS) followed by an antibiotic (ATB)-induced dysbiosis in early adulthood could induce neurodevelopmental disorders-like behavioral changes in adult male rats. Combining these two stressors resulted in decreased weight gain, but no signific...

Introduction: N-2-methoxy-benzylated (“NBOMe”) analogues of phenethylamine are a group of new psychoactive substances (NPS) with reported strong psychedelic effects in sub-milligram doses linked to a number of severe intoxications, including fatal ones. In our present work, we provide a detailed investigation of pharmacokinetics and acute behaviour...

Background: COMP360 is a proprietary, synthetic formulation of psilocybin being developed for treatment-resistant depression (TRD), a burdensome, life-threatening illness with high global impact. Here, we expand upon the previous report of primary outcomes from a phase 2 study of COMP360 in individuals with TRD-the largest randomised controlled cl...

N-(2-methoxybenzyl)phenethylamines (NBOMes) are a family of potent 5-HT2A agonists containing substances emerging on the illicit drug market as a replacement for N,N-diethyllysergamide (LSD). Despite the increasing use of NBOMes for diagnostic, research and recreational purposes, only a limited number of studies have focussed on their in vivo effec...

Aim Deschloroketamine (DCK), a structural analogue of ketamine, has recently emerged on the illicit drug market as a recreational drug with a modestly long duration of action. Despite it being widely used by recreational users, no systematic research on its effects has been performed to-date. For this reason, we investigated the pharmacokinetic, ph...

Psilocybin is a classical serotoninergic psychedelic that induces cognitive disruptions similar to psychosis. Gamma activity is affected in psychosis and is tightly related to cognitive processing. The 40 Hz auditory steady-state responses (ASSR) are frequently used as indicators to test the ability to generate gamma activity. Based on previous lit...

In this paper we deal with a simplified anisotropic rat head phantom development and the investigation of the influence of the anisotropic white matter on electroencephalogram source localization. The proposed phantom is based on the cubic cross cell composition combined with agar mixture to set desired electrical conductivity anisotropic ratio. Fo...

In spite of use of cannabidiol (CBD), a non-psychoactive cannabinoid, in pediatric patients with epilepsy, preclinical studies on its effects in immature animals are very limited. In the present study we investigated anti-seizure activity of CBD (10 and 60 mg/kg administered intraperitoneally) in two models of chemically induced seizures in infanti...

Naphyrone, also known as NRG-1, is a novel psychoactive substance (NPS), a cathinone with stimulatory properties available on the grey/illicit drug market for almost a decade. It is structurally related to infamously known powerful stimulants with the pyrovalerone structure, such as alpha-pyrrolidinovalerophenone (α-PVP) or methylenedioxypyrovalero...

Compounds from the N-benzylphenethylamine (NBPEA) class of novel psychoactive substances are being increasingly utilized in neurobiological and clinical research, as diagnostic tools, or for recreational purposes. To understand the pharmacology, safety, or potential toxicity of these substances, elucidating their metabolic fate is therefore of the...

Background and purpose Deschloroketamine (DCK), a structural analogue of ketamine, has recently emerged on the illicit drug market as a recreational drug with a modestly long duration of action. Despite it being widely used by recreational users, no systematic research on its effects has been performed to date. Experimental approach Pharmacokineti...

Serotonergic psychedelics are recently gaining a lot of attention as a potential treatment of several neuropsychiatric disorders. Broadband desynchronization of EEG activity and disconnection in humans have been repeatedly shown; however, translational data from animals are completely lacking. Therefore, the main aim of our study was to assess the...

N-Benzylphenethylamines are novel psychedelic substances increasingly used for research, diagnostic, or recreational purposes. To date, only a few metabolism studies have been conducted for N-2-methoxybenzylated compounds (NBOMes). Thus, the available 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe) metabolism data are lim...

This work presents and evaluates a 12-electrode intracranial electroencephalography system developed at the National Institute of Mental Health (Klecany, Czech Republic) in terms of an electrical source imaging (ESI) technique in rats. The electrode system was originally designed for translational research purposes. This study demonstrates that it...

Serotonergic agonist psilocybin is a psychedelic with antidepressant potential. Sleep may interact with psilocybin’s antidepressant properties like other antidepressant drugs via induction of neuroplasticity. The main aim of the study was to evaluate the effect of psilocybin on sleep architecture on the night after psilocybin administration. Regard...

Naphthylpyrovalerone (naphyrone) is a pyrovalerone cathinone that potently inhibits monoamine transporters and provides stimulatory‐entactogenic effects. Little is known about the safety of naphyrone or its effects in vivo, and more research is needed to acquire knowledge about its fundamental effects on physiology and behaviour. Our objective was...

A single dose of the serotonin 2A receptor (5-HT2AR) agonist psilocybin can have long-lasting beneficial effects on mood, personality, and potentially on mindfulness, but underlying mechanisms are unknown. Here, we for the first time conduct a study that assesses psilocybin effects on cerebral 5-HT2AR binding with [¹¹C]Cimbi-36 positron emission to...

Deschloroketamine (2‐(methylamino)‐2‐phenyl‐cyclohexanone) is a ketamine analogue belonging to a group of dissociative anaesthetics, which have been distributed within the illicit market since 2015. However, it was also being sold as ‘ketamine’ misleading people to believe that they were getting genuine ketamine. Dissociative anaesthetics have also...

Background: Cannabis, and specifically one of its active compounds delta-9-tetrahydrocannabinol in recreational doses, has a variety of effects on cognitive processes. Most studies employ resting state functional magnetic resonance imaging techniques to assess the stationary effects of cannabis and to-date one report addressed the impact of delta-...

Brain mapping is a topographical method that is frequently used in human scalp electroencephalogram (EEG) for two-dimensional (2D) or three-dimensional (3D) visualisation of electrical potentials distributed across the surface of the brain. In human research, accepted standards for EEG recording and mapping exist, however to date, no such standards...

All known psychedelics are 5-HT2A receptor agonists and induce extensive psychological changes. Abnormal function of serotonergic transmission is seen today as one of the etiopathogenetic factors of schizophrenia. Therefore, psychedelics are used to model this disease. The representatives of two main classes – tryptamines (psilocin, LSD) and phenet...

Synthetic cannabinoid compounds are marketed as “legal” marijuana substitutes, even though little is known about their behavioral effects in relation to their pharmacokinetic profiles. Therefore, in the present study we assessed the behavioral effects of systemic treatment with the two synthetic cannabinoids JWH-073 and JWH-210 and the phytocannabi...

Synthetic cannabinoid compounds are marketed as "legal" marijuana substitutes, even though little is known about their behavioral effects in relation to their pharmacokinetic profiles. Therefore, in the present study we assessed the behavioral effects of systemic treatment with the two synthetic cannabinoids JWH-073 and JWH-210 and the phytocannabi...

Measurements of brain electrical activity in animals are essential for the validation of the pharmaco-effect of drugs. The way to evaluate these recordings should be comparable to that of EEG in humans. Methods that visualize the results of the measured EEG recording include brain mapping in two-dimensional or three-dimensional space. The most comm...

Chronic methamphetamine (meth) abuse often turns into a compulsive drug-taking disorder accompanied by persistent cognitive deficits and re-occurring psychosis. Possible common neurobiological substrates underlying meth-induced deficits and schizophrenia remain poorly understood. Serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptors...

The adipokinetic and red pigment‐concentrating hormone (AKH/RPCH) family of peptides controls fat, carbohydrate and protein metabolism in insects. In our previous study, we showed that AKH possesses antidepressant, anxiolytic, and analgesic effects, causes hyperlocomotion and exerts neuroprotective effects and increased brain neurotrophic factors i...

3,4-methylenedioxypyrovalerone (MDPV) is a potent pyrovalerone cathinone that is substituted for amphetamines by recreational users. We report a comprehensive and detailed description of the effects of subcutaneous MDPV (1–4 mg/kg) on pharmacokinetics, biodistribution and metabolism, acute effects on thermoregulation under isolated and aggregated c...

After a hiatus of several decades, there has been a resurgence of studies into the therapeutic potential of serotonergic psychedelics. When administered in controlled settings, they have been reported to induce a wide variety of long-lasting positive psychological changes. However, the mechanisms by which psychedelics impart these long-lasting bene...

Objective Time-course of ketamine effect was assessed in depressive patients by QEEG to elucidate changes associated with treatment and to assess potential predictors of response. Methods The analysis was completed from data of two double-blind, cross-over, placebo-controlled studies, assessing the effect of ketamine infusion (0.54 mg/kg) in 51 in...

Electroencephalography (EEG) is a method that reflects the electrical activity of the brain. Changes in electrical activity can be reflected also in 2D or 3D maps Measurements of brain electrical activity in animals are essential for the validation of the pharmaco-effect on the brain. The translational approach using similar methods for quantitativ...

Short-term moderate doses of serotonergic and dissociative hallucinogens can be useful in the treatment of anxiety. Recently, a trend has developed for long-term intermittent 'microdosing' (usually one-tenth of a 'full' active dose), with reports of long-lasting relief from anxiety and related disorders; however, there is no scientific evidence for...

Rationale: Disruption of auditory event-related evoked potentials (ERPs) P300 and mismatch negativity (MMN), electrophysiological markers of attentive and pre-attentive cognitive processing, is repeatedly described in psychosis and schizophrenia. Similar findings were observed in a glutamatergic model of psychosis, but the role of serotonergic 5-H...

Mephedrone (MEPH) is a synthetic cathinone derivative with effects that mimic MDMA and/or cocaine. Our study in male Wistar rats provides detailed investigations of MEPH’s and its primary metabolite nor-mephedrone’s (nor-MEPH) pharmacokinetics and bio-distribution to four different substrates (serum, brain, lungs, and liver), as well as comparative...

Methylone (3,4-methylenedioxy-N-methylcathinone) is a synthetic cathinone analog of the recreational drug ecstasy. Although it is marketed to recreational users as relatively safe, fatalities due to hyperthermia, serotonin syndrome, and multi-organ system failure have been reported. Since psychopharmacological data remain scarce, we have focused ou...

Objectives Aminoindanes (“bath salts,” a class of novel psychoactive substances, NPSs) increased rapidly in popularity on the recreational drug market, particularly after mephedrone and other synthetic cathinones were banned in the UK in 2010. Novel aminoindanes continue to emerge, but relatively little is known about their effects and risks. Their...

Metabolic and behavioural effects of, and interactions between Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are influenced by dose and administration route. Therefore we investigated, in Wistar rats, effects of pulmonary, oral and subcutaneous (sc.) THC, CBD and THC+CBD. Concentrations of THC, its metabolites 11-OH-THC and THC-COOH, and CBD...

Chronic methamphetamine (METH) abuse has been shown to elicit strong neurotoxic effects. Yet, with an increasing number of children born to METH abusing mothers maturing into adulthood, one important question is how far do the neurotoxic effects of METH alter various neurotransmitter systems in the adult METH-exposed offspring. The purpose of this...

Rationale: Self-report studies indicate that cannabis could increase sexual desire in some users. We hypothesized that intoxication increases activation of brain areas responsive to visual erotica, which could be useful in the treatment of hypoactive sexual desire disorder, a condition marked by a lack of sexual desire. Objectives: The aim of th...

1. Methylone (3,4-methylenedioxy-N-methylcathinone, MDMC), which appeared on the illicit drug market in 2004, is a frequently abused synthetic cathinone derivative. Known metabolic pathways of MDMC include N-demethylation to normethylone (3,4-methylenedioxycathinone, MDC), aliphatic chain hydroxylation and oxidative demethylenation followed by mono...

OBJECTIVES The serotonergic hallucinogen psilocybin, has profound effects on the human mind, which can be characterized by alteration in perception, thinking disorder and strong emotional salience. The character of the altered state of consciousness induced by hallucinogens is hardly predictable; while an important role has the environment in which...

1. 5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs. 2. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body wei...

Comparison of human and rat data of quantitative analysis of EEG signal.

Mephedrone (4-methylmethcathinone, MEPH) is a novel recreational drug that has rapidly increased in popularity in recent years, especially in the UK. MEPH produces similar effect to MDMA, amphetamines or cocaine. MEPH has a potential to induce compulsive patterns of use as well as toxicity in overdose. Here we examined effects of three subcutaneous...

Methoxetamine (MXE) is a novel psychoactive compound (NPS) that emerged in 2010 as a substitute for the dissociative anaesthetic ketamine. MXE has a reputation of carrying a lower risk of harm than ketamine, however a number of deaths have been reported. Currently very little is known about the psychopharmacological effects of this compound or its...

This chapter focuses on the potential use of serotonergic hallucinogen psilocybin in clinical as well as experimental psychiatry, addictology, and neurology. It presents the results of recent clinical studies with psilocybin and summarizes the psychological and neurobiological aspects of its effect in specific therapeutic indications. In addition,...

A new designer drug, a dissociative anesthetic and a putative N-methyl-D-aspartate receptor antagonist, methoxetamine (MXE) noted by the EU Early Warning System has been already identified as a cause of several fatalities worldwide. The primary objective of this work was to develop a suitable sample preparation method allowing for isolation of MXE...