Hallucinogenic Agents Research Articles

1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents - A Review.

1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI, or DOX where X = -I) was first synthesized in 1973 in a structure-activity study to explore the effect of various aryl substituents on the then newly identified, and subsequently controlled, hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM, or DOX where X = -CH3). Over time, DOI was found to be a serotonin (5-HT) receptor agonist using various peripheral 5-HT receptor tissue assays and later, following the identification of multiple families of central 5-HT receptors, an agonist at 5-HT2 serotonin receptors in rat and, then, human brain. Today, classical hallucinogens, currently referred to as serotonergic psychedelic agents, are receiving considerable attention for their potential therapeutic application in various neuropsychiatric disorders including treatment-resistant depression. Here, we review, for the first time, the historical and current developments that led to DOI becoming a unique, perhaps a landmark, agent in 5-HT2 receptor research.

Psychedelic Therapy: A Primer for Primary Care Clinicians-Lysergic Acid Diethylamide (LSD).

Lysergic acid diethylamide (LSD) is a hallucinogenic agent. In the mid-20th century, it was used to augment psychoanalysis and to treat alcohol use disorder. However, LSD was banned in 1970 in part because of concerns that it could bring about or exacerbate mental illness. Its therapeutic potential remains incompletely understood. While uncontrolled recreational use of LSD can, in rare instances, lead to long-term psychosis, adverse events in clinical trials of LSD, such as anxiety, headache, and nausea, have almost always been mild and transient. Serious adverse events, such as intense panic, suicidal ideation, and psychosis, were reported in either none or very few of the participants. However, patient selection criteria, optimal dosing strategy, and appropriate clinical follow-up guidelines remain to be established. Preliminary data suggest that LSD may be effective for the management of alcohol use disorder, anxiety, and depression. In trials of LSD for treating anxiety and depression associated with life-threatening illnesses, 77% of participants demonstrate durable relief at 1 year post-treatment. Top-line data from a large-scale phase IIb trial (n = 198) indicate that 50% of participants experience remission from generalized anxiety disorder after a single 100 μg dose of LSD. According to a meta-analysis of RCTs on LSD from the mid-20th century, single-dose regimens of LSD significantly improve alcohol use disorder (P < 0.0003) with an odds ratio (OR) of 1.96. Only one large-scale clinical trial (>50 participants) has been conducted on LSD in the contemporary era of psychedelic research. Further studies with large sample sizes are needed to explore potential clinical applications. Preliminary data suggest that LSD may be one of the most potent treatments for anxiety in patients both with and without a life-threatening illness. LSD may also be beneficial for treating depression and substance use disorders.

Pharmacology and Therapeutic Effects of Psilocybin

Psilocybin, a psychoactive alkaloid with hallucinogenic properties, exists in a variety of hallucinogenic mushrooms. As a study tool to imitate psychosis, psilocybin has aroused a lot of interest in the biological community due to its various possible therapeutic benefits. It is also a very popular and widely misused natural hallucinogens with distinct metabolism pathways and toxicity. In this paper, the metabolism and mechanism of psilocybin were summarized, and the toxicology and pharmacology of psilocybin were discussed in detail, and the positive effects of psilocybin on psychological illnesses like depression, addiction, anxiety, and obsessive-compulsive disorder were gathered and sorted out, and the drug's therapeutic potential for mental and psychological illnesses was systematically clarified. Understanding the mechanism and therapeutic ability of psilocybin is of great significance to its potential development. As a hallucinogenic agent with low toxicity and no side effects, its effective application in the treatment of psychological and mental diseases can provide new ideas for the treatment of various diseases.

Chemical Characterization and Molecular Dynamics Simulations of Bufotenine by Surface-Enhanced Raman Scattering (SERS) and Density Functional Theory (DFT).

Bufotenine (5-hydroxy-N,N-dimethyltryptamine) is a natural tryptamine derivative with hallucinogenic activity. In this paper, we present novel chemical and molecular conformational analyses of bufotenine based on an experimental and theoretical approach integrating surface-enhanced Raman scattering (SERS) and density functional theory (DFT). For the first time, low concentrations of bufotenine in acetonitrile solutions were analyzed by SERS using two types of silver nanoparticle substrates synthesized via one- or two-step reduction processes. The vibrational characteristics of this molecule were verified by molecular dynamics simulations of Raman bands based on DFT. Here we demonstrate the potential of this integrated approach for the identification of bufotenine, a prominent hallucinogenic agent, establishing an innovative rapid and accurate sensing and characterization method of the identification of controlled substances at trace amounts.

Abstract- Poster

BACKGROUND:Oculocutaneous albinism (OCA) is an autosomal recessive disorder defined by little to no melanin production in the eyes, skin, and hair, and is extremely rare, affecting 0.005% of the world’s population.Schizophrenia is a mental illness affecting approximately 1% of the world’s population, and is characterized by behavior such as disorganized thinking and speech, delusions, hallucinations,etc.It was previously hypothesized that Schizophrenia could be caused by a defect in melatonin metabolism, leading to increased melanin production and the production of hallucinogenic agent. However, this implies that albinos would be protected against schizophrenia (since they have little to no melanin production).AIM:To discuss coexistence of Schizophrenia in a albino female.METHODOLOGY: (Case Report)A 38yr old married albino female presented to OPD with poor personal care,suspiciousness towards family members,irritability,frequent anger outbursts, sleep disturbances for past 3yrs.On detailed exploration,patient was found to have Delusion of persecution and reference.Her routine blood investigations and neuroimaging were within normal limits.She was diagnosed as a case of Paranoid Schizophrenia by the treating consultant and was started on Oral Olanzapine 20mg/day and Tab Clonazepam 0.5 mg hs.Her symptoms improved (PANSS decreased from 83 to 40) within span of 3 months.CONCLUSION:Based on our case report and previous case reports in the literature we have reviewed, we can reject the schizophrenia-melatonin hypothesis, as it has been shown on multiple occasions that albinos can be schizophrenic.

“Ritual” mushrooms in the traditional culture of the Ob Ugrians

Introduction. In the traditional culture of the Ob Ugrians, certain types of mushrooms have received a special mythological “status” that reveals their place in the traditional picture of the world and explains the power of their impact on humans. The purpose of the study is to present the role of mushrooms in folk medicine and ritual practices of the Khanty and Mansi. These interconnected areas have not been sufficiently studied at the moment, which reflects the relevance of the work. Materials and Methods. The article uses the published data and field materials of the author, as well as folklore sources. The study was carried out on the basis of an interdisciplinary and systematic approach using the structural-functional method. Results and Discussion. In the treatment and cleansing rituals of the Khanty and Mansi, the use of birch tinder fungi has become widespread. Their healing properties have been known since antiquity, since image of the Tree of Life was associated with this tree. Another representative of the mushroom kingdom, the fly agaric, was used sporadically, primarily as a hallucinogenic agent used in ritual practices. The properties of this mushroom allow researchers to make an ambiguous conclusion that the secret of soma, the drink of the gods, lies in the portion made from the fly agaric. Conclusion. Changes in living conditions led to the gradual disappearance of the traditions of folk medicine and ritual practices of the Ob Ugrians, which significantly complicates their study at the present period.

Do Hallucinogens Have a Role in the Treatment of Addictions? A Review of the Current Literature

The utility of hallucinogenic drugs within psychiatry is an emerging topic, although not entirely a novel idea. After their introduction to western society in the mid-twentieth century, psychologists and psychiatrists studied their properties for use as adjunctive therapy in the treatment of psychiatric illness. Unfortunately, their classification as Schedule 1 drugs by the Drug Enforcement Administration in the 1970s put an end to this research. In the past decade, however, interest in hallucinogens has been reignited. The psychiatric community has begun to reinvestigate their role in mental health treatment, with addiction being one focus. Though there is a growing pool of research surrounding the use of hallucinogens in addiction treatment, there have been few reviews focusing on this topic. This paper will serve to summarize this data, focusing specifically on the following hallucinogenic agents: lysergic acid diethylamide, psilocybin, ketamine, ibogaine, and ayahuasca. It will review both the basic pharmacology of each of these chemicals and studies assessing their use in treating various addictions including alcoholism, nicotine addiction, opioid use disorder, and cocaine use disorder. Though more robust research is needed before use of these drugs can be effectively adopted into clinical practice, the current data is promising and suggests the potential for a new and unique avenue for the treatment of addiction.

Psilocybin exerts distinct effects on resting state networks associated with serotonin and dopamine in mice

Hallucinogenic agents have been proposed as potent antidepressants; this includes the serotonin (5-HT) receptor 2A agonist psilocybin. In human subjects, psilocybin alters functional connectivity (FC) within the default-mode network (DMN), a constellation of inter-connected regions that displays altered FC in depressive disorders. In this study, we investigated the effects of psilocybin on FC across the entire brain with a view to investigate underlying mechanisms. Psilocybin effects were investigated in lightly-anaesthetized mice using resting-state fMRI. Dual-regression analysis identified reduced FC within the ventral striatum in psilocybin- relative to vehicle-treated mice. Refinement of the analysis using spatial references derived from both gene expression maps and viral tracer projection fields revealed two distinct effects of psilocybin: it increased FC between 5-HT-associated networks and cortical areas, including elements of the murine DMN, thalamus, and midbrain; it decreased FC within dopamine (DA)-associated striatal networks. These results suggest that interactions between 5-HT- and DA-regulated neural networks contribute to the neural and therefore psychological effects of psilocybin. Furthermore, they highlight how information on molecular expression patterns and structural connectivity can assist in the interpretation of pharmaco-fMRI findings.

Effects of chronic methamphetamine abuse on the retinal nerve fiber layer, ganglion cell layer and Bruch’s membrane opening minimum rim width

BackgroundMethamphetamine (Meth) is a highly addictive and hallucinogenic agent which is used as the second most common illicit drug globally. Meth could affect the retina and optic nerve by inducing the release of vasoconstrictive agents such as endothelin 1 and induction of severe oxidative stress with accumulation of reactive oxygen species. AimTo evaluate the effects of chronic Meth abuse on the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) and the Bruch’s membrane opening minimum rim width (MRW). MethodIn this case-control study, we recruited 55 Meth abusers and 49 healthy individuals with mean age of 44.63 ± 0.97 and 43.08 ± 0.91 years, respectively. RNFL thickness, GCL thickness and MRW were evaluated using optical coherence tomography. ResultsWe found statistically significant decrease in RNFL, MRW thickness in Meth abusers (P: 0.002 and P: 0.006, respectively). We did not detect statistically significant difference regarding GCL thickness between the groups (P = 0.320). Our results showed a weak but statistically significant correlation of Meth dose increment and decrement of RNFL thickness ((P: 0.005, r = -0.193) and MRW (P: 0.013, r = -0.174). We found no correlation between duration of Meth consumption with RNFL and MRW thickness (P: 0.205, r= -0.124; P: 0.771, r= -0.029, respectively). ConclusionWe found a statistically significant adverse association in meth abusers with RNFL thickness and MRW. These two parameters were also statistically associated with the meth dose as measured by daily dose of Meth. Although we found a decrease in the GCL thickness, it did not reach statistical significance.

Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions.

Mescaline (3,4,5-trimethoxyphenethylamine), mainly found in the Peyote cactus (Lophophora williamsii), is one of the oldest known hallucinogenic agents that influence human and animal behavior, but its psychoactive mechanisms remain poorly understood. This article aims to fully review pharmacokinetics and pharmacodynamics of mescaline, focusing on the in vivo and in vitro metabolic profile of the drug and its implications for the variability of response. Mescaline pharmacokinetic and pharmacodynamic aspects were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period. Biological effects of other compounds found in peyote were also reviewed. Although its illicit administration is less common, in comparison with cocaine and Cannabis, it has been extensively described in adolescents and young adults, and licit consumption often occurs in religious and therapeutic rituals practiced by the Native American Church. Its pharmacodynamic mechanisms of action are primarily attributed to the interaction with the serotonergic 5-HT2A-C receptors, and therefore clinical effects are similar to those elicited by other psychoactive substances, such as lysergic acid diethylamide (LSD) and psilocybin, which include euphoria, hallucinations, depersonalization and psychoses. Moreover, as a phenethylamine derivative, signs and symptoms are consistent with a sympathomimetic effect. Mescaline is mainly metabolized into trimethoxyphenylacetic acid by oxidative deamination but several minor metabolites with possible clinical and forensic repercussions have also been reported. Most reports concerning mescaline were presented in a complete absence of exposure confirmation, since toxicological analysis is not widely available. Addiction and dependence are practically absent and it is clear that most intoxications appear to be mild and are unlikely to produce lifethreatening symptoms, which favors the contemporary interest in the therapeutic potential of the drugs of the class.

Exploring Hallucinogen Pharmacology and Psychedelic Medicine with Zebrafish Models.

After decades of sociopolitical obstacles, the field of psychiatry is experiencing a revived interest in the use of hallucinogenic agents to treat brain disorders. Along with the use of ketamine for depression, recent pilot studies have highlighted the efficacy of classic serotonergic hallucinogens, such as lysergic acid diethylamide and psilocybin, in treating addiction, post-traumatic stress disorder, and anxiety. However, many basic pharmacological and toxicological questions remain unanswered with regard to these compounds. In this study, we discuss psychedelic medicine as well as the behavioral and toxicological effects of hallucinogenic drugs in zebrafish. We emphasize this aquatic organism as a model ideally suited to assess both the potential toxic and therapeutic effects of major known classes of hallucinogenic compounds. In addition, novel drugs with hallucinogenic properties can be efficiently screened using zebrafish models. Well-designed preclinical studies utilizing zebrafish can contribute to the reemerging treatment paradigm of psychedelic medicine, leading to new avenues of clinical exploration for psychiatric disorders.

A novel 3D method of locomotor analysis in adult zebrafish: Implications for automated detection of CNS drug-evoked phenotypes

BackgroundExpanding the spectrum of organisms to model human brain phenotypes is critical for our improved understanding of the pathobiology of neuropsychiatric disorders. Given the clear limitations of existing mammalian models, there is an urgent need for low-cost, high-throughput in-vivo technologies for drug and gene discovery. New methodHere, we introduce a new automated method for generating 3D (X,Y,Z) swim trajectories in adult zebrafish (Danio rerio), to improve their neurophenotyping. ResultsBased on the Track3D module of EthoVision XT video tracking software (Noldus Information Technology), this tool enhances the efficient, high-throughput 3D analyses of zebrafish behavioral responses. Applied to adult zebrafish behavior, this 3D method is highly sensitive to various classes of psychotropic drugs, including selected psychostimulant and hallucinogenic agents. Comparison with existing MethodsOur present method offers a marked advance in the existing 2D and 3D methods of zebrafish behavioral phenotyping, minimizing research time and recording high-resolution, automatically synchronized videos with calculated, high-precision object positioning. ConclusionsOur novel approach brings practical simplicity and ‘integrative’ capacity to the often complex and error-prone quantification of zebrafish behavioral phenotypes. Illustrating the value of 3D swim path reconstructions for identifying experimentally-evoked phenotypic profiles, this method fosters innovative, ethologically relevant, and fully automated small molecule screens using adult zebrafish.

(421) CR845, a novel peripherally-acting kappa opioid receptor agonist, has low abuse potential compared with pentazocine

CR845, a potent, peripherally-acting, selective kappa opioid receptor agonist, is being developed for the treatment of acute and chronic pain. This study examined the relative abuse potential of CR845 compared to placebo or pentazocine, a schedule IV opioid analgesic. Recreational polydrug users with experience with opioids and hallucinogenic agents were enrolled in this single-center, randomized, double-blind, active- and placebo-controlled study. Thirty-nine subjects received a single bolus IV dose of the following 4 treatments in random order: CR845 5 mcg/kg (therapeutic dose), CR845 15 mcg/kg (supra-therapeutic dose), placebo, and pentazocine 0.5 mg/kg. Treatments were separated by 48-hour washout period. Drug liking bipolar Visual Analog Scale (VAS) was the primary measurement, and was assessed periodically between 5 minutes and 8 hours after dosing. This trial met the primary endpoint with drug liking scores for pentazocine significantly greater than that of placebo and either doses of CR845 (P<0.0001 for each comparison to pentazocine). The least squares (LS) mean for the maximum drug liking VAS (Emax) scores (±standard error of LS mean) were 87.6±1.9 for pentazocine, 65.3±1.9 for CR845 5 mcg/kg, 66.9±1.9 for CR845 15 mcg/kg, and 52.4±1.9 for placebo, indicating that both doses of CR845 had significantly lower drug liking response compared to pentazocine. Additional bipolar VAS measurements were lower for CR845 compared with pentazocine for “overall drug liking” (P<0.0001 for both doses of CR845) and “take drug again” (P<0.0003 for CR845 5 mcg/kg and P<0.0001 for CR845 15 mcg/kg). These VAS scores for CR845 were equivalent for both doses and were similar to those of placebo. These results suggest that the novel and selective peripherally acting kappa agonist CR845 may present a low risk for abuse liability in humans. Sponsored by Cara Therapeutics. CR845, a potent, peripherally-acting, selective kappa opioid receptor agonist, is being developed for the treatment of acute and chronic pain. This study examined the relative abuse potential of CR845 compared to placebo or pentazocine, a schedule IV opioid analgesic. Recreational polydrug users with experience with opioids and hallucinogenic agents were enrolled in this single-center, randomized, double-blind, active- and placebo-controlled study. Thirty-nine subjects received a single bolus IV dose of the following 4 treatments in random order: CR845 5 mcg/kg (therapeutic dose), CR845 15 mcg/kg (supra-therapeutic dose), placebo, and pentazocine 0.5 mg/kg. Treatments were separated by 48-hour washout period. Drug liking bipolar Visual Analog Scale (VAS) was the primary measurement, and was assessed periodically between 5 minutes and 8 hours after dosing. This trial met the primary endpoint with drug liking scores for pentazocine significantly greater than that of placebo and either doses of CR845 (P<0.0001 for each comparison to pentazocine). The least squares (LS) mean for the maximum drug liking VAS (Emax) scores (±standard error of LS mean) were 87.6±1.9 for pentazocine, 65.3±1.9 for CR845 5 mcg/kg, 66.9±1.9 for CR845 15 mcg/kg, and 52.4±1.9 for placebo, indicating that both doses of CR845 had significantly lower drug liking response compared to pentazocine. Additional bipolar VAS measurements were lower for CR845 compared with pentazocine for “overall drug liking” (P<0.0001 for both doses of CR845) and “take drug again” (P<0.0003 for CR845 5 mcg/kg and P<0.0001 for CR845 15 mcg/kg). These VAS scores for CR845 were equivalent for both doses and were similar to those of placebo. These results suggest that the novel and selective peripherally acting kappa agonist CR845 may present a low risk for abuse liability in humans. Sponsored by Cara Therapeutics.

Determination of Safrole in Ethanol Extract of Nutmeg (Myristica fragrans Houtt) Using Reversed-Phase High Performance Liquid Chromatography

Dehydrodiisoeugenol (DDIE), myristicin, and safrole are chemical compounds contained in fruit and seed of nutmeg (Myristica fragrans Houtt). DDIE shows antidiabetic activity on PPARγ receptor, while myristicin is hallucinogenic agent. Of the three compounds, safrole is the most toxic substance due to its carcinogenic activity. In this work, we developed an analytical method to determine safrole in ethanol extract of nutmeg. Reversed-Phase High Performance Liquid Chromatography (Dionex Ultimate 3000) using C-18 LiChroCART 250-4, LiChrospher 100 RP 18e (5 µm) 250 mm column as stationary phase, was selected as the method of analysis. A mixture of methanol:water (73:27) at flow rate 1 mL/min was used as mobile phase. Detection was done at 282 nm. Using such conditions, retention time for safrole was 10.45 minutes. The recovery was 101.421%, while the value of CV was 0.838%. LOD and LOQ were 0.668 µg/mL and 2.023 µg/mL, respectively. Mean concentration of safrole in the nutmeg seed extract was 10.979%.

Perspectives on Zebrafish Models of Hallucinogenic Drugs and Related Psychotropic Compounds

Among different classes of psychotropic drugs, hallucinogenic agents exert one of the most prominent effects on human and animal behaviors, markedly altering sensory, motor, affective, and cognitive responses. The growing clinical and preclinical interest in psychedelic, dissociative, and deliriant hallucinogens necessitates novel translational, sensitive, and high-throughput in vivo models and screens. Primate and rodent models have been traditionally used to study cellular mechanisms and neural circuits of hallucinogenic drugs' action. The utility of zebrafish ( Danio rerio ) in neuroscience research is rapidly growing due to their high physiological and genetic homology to humans, ease of genetic manipulation, robust behaviors, and cost effectiveness. Possessing a fully characterized genome, both adult and larval zebrafish are currently widely used for in vivo screening of various psychotropic compounds, including hallucinogens and related drugs. Recognizing the growing importance of hallucinogens in biological psychiatry, here we discuss hallucinogenic-induced phenotypes in zebrafish and evaluate their potential as efficient preclinical models of drug-induced states in humans.

Structure–activity relationships of serotonin 5‐HT2A agonists

AbstractOf the 14 known types of serotonin receptors one of the most extensively studied is the 5‐HT2A (5‐hydroxytryptamine) receptor. In the brain, this receptor plays a key role in regulation of cortical function and cognition, appears to be the principal target for the hallucinogenic/psychedelic drugs such as lysergic acid diethylamide (LSD), and also is a target for the newest atypical antipsychotic agents, which are antagonists or inverse agonists at this site. Among the structure–activity relationships that are known for this receptor type, there are three chemical classes of agonists: tryptamines, ergolines, and phenethylamines. Important structural features are identified for agonist activity and some of these agonists have features in common. In addition to effects at the receptor will be the focus, these drugs are also hallucinogenic (psychedelic) agents, and much of the SAR was developed on the basis of effects in humans, before modern pharmacological techniques were available. A certain amount of our knowledge therefore relies on those human studies. WIREs Membr Transp Signal 2012, 1:559–579. doi: 10.1002/wmts.42For further resources related to this article, please visit the WIREs website.

Effects of hallucinogenic agents mescaline and phencyclidine on zebrafish behavior and physiology

Mescaline and phencyclidine (PCP) are potent hallucinogenic agents affecting human and animal behavior. As their psychotropic effects remain poorly understood, further research is necessary to characterize phenotypes they evoke in various animal models. Zebrafish (Danio rerio) are rapidly emerging as a new model organism for neuroscience research. Here, we examine the effects of mescaline (5-20mg/l) and PCP (0.5-3mg/l) in several zebrafish paradigms, including the novel tank, open field and shoaling tests. Mescaline and PCP dose-dependently increased top activity in the novel tank test, also reducing immobility and disrupting the patterning of zebrafish swimming, as assessed by ethograms. PCP, but not mescaline, evoked circling behavior in the open field test. At the highest doses tested, mescaline markedly increased, while PCP did not affect, zebrafish shoaling behavior. Finally, 20mg/l mescaline did not alter, and 3mg/l PCP elevated, whole-body cortisol levels. Overall, our studies indicate high sensitivity of zebrafish models to hallucinogenic compounds with complex behavioral and physiological effects.

Effects of MDMA on Extracellular Dopamine and Serotonin Levels in Mice Lacking Dopamine and/or Serotonin Transporters

3,4-Methylendioxymethamphetamine (MDMA) has both stimulatory and hallucinogenic properties which make its psychoactive effects unique and different from those of typical psychostimulant and hallucinogenic agents. The present study investigated the effects of MDMA on extracellular dopamine (DAex) and serotonin (5-HTex) levels in the striatum and prefrontal cortex (PFC) using in vivo microdialysis techniques in mice lacking DA transporters (DAT) and/or 5-HT transporters (SERT). subcutaneous injection of MDMA (3, 10 mg/kg) significantly increased striatal DAex in wild-type mice, SERT knockout mice, and DAT knockout mice, but not in DAT/SERT double-knockout mice. The MDMA-induced increase in striatal DAex in SERT knockout mice was significantly less than in wildtype mice. In the PFC, MDMA dose-dependently increased DAex levels in wildtype, DAT knockout, SERT knockout and DAT/SERT double-knockout mice to a similar extent. In contrast, MDMA markedly increased 5-HTex in wildtype and DAT knockout mice and slightly increased 5-HTex in SERT-KO and DAT/SERT double-knockout mice. The results confirm that MDMA acts at both DAT and SERT and increases DAex and 5-HTex.

Use and Accidental Exposure to Hallucinogenic Agents Reported to the Czech Toxicological Information Centre From 1995 to 2008

Intoxication by hallucinogenic agents is relatively common in the Czech Republic, with most cases of the use of these agents being by adolescents and young people. The objective of the study was to evaluate the number, trends, gender and age of the subjects, and the severity of exposure in intoxication by hallucinogenic plant and mushroom substances, in comparison with synthetic drugs, brought to the attention of the Toxicological Information Centre (TIC) through inquiries over the past 14 years (1995–2008) (from total 3,702 calls concerning the use of both natural and synthetic drugs, 917 calls were due to the use of hallucinogenic plants and mushrooms).

Introduction: Coding of high-order cognition grounded onto spatial representation

Hallucinogenic agents have been proposed as potent antidepressants; this includes the serotonin (5-HT) receptor 2A agonist psilocybin. In human subjects, psilocybin alters functional connectivity (FC) within the default-mode network (DMN), a constellation of inter-connected regions that displays altered FC in depressive disorders. In this study, we investigated the effects of psilocybin on FC across the entire brain with a view to investigate underlying mechanisms. Psilocybin effects were investigated in lightly-anaesthetized mice using resting-state fMRI. Dual-regression analysis identified reduced FC within the ventral striatum in psilocybin- relative to vehicle-treated mice. Refinement of the analysis using spatial references derived from both gene expression maps and viral tracer projection fields revealed two distinct effects of psilocybin: it increased FC between 5-HT-associated networks and cortical areas, including elements of the murine DMN, thalamus, and midbrain; it decreased FC within dopamine (DA)-associated striatal networks. These results suggest that interactions between 5-HT- and DA-regulated neural networks contribute to the neural and therefore psychological effects of psilocybin. Furthermore, they highlight how information on molecular expression patterns and structural connectivity can assist in the interpretation of pharmaco-fMRI findings.