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A fatal case of magic mushroom' ingestion in a heart transplant recipient

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... Case reports describe patients who died after ingestion of psilocybin (Lim et al., 2012;van Amsterdam et al., 2011) or LSD (Mardal et al., 2017). These cases usually involve accidental deaths (e.g. ...
... It was unclear how much the psilocybin mushroom ingestion contributed to death. Traumatic deaths have been reported after psilocybin mushroom use (van Amsterdam et al., 2011) along with a single overdose in a heart transplant recipient, possibly due to a sympathetic surge (Lim et al., 2012). Authors have reported that psilocybin mushrooms contain phenylethylamine, which has sympathomimetic action, which is consistent with reported effects (van Amsterdam et al., 2011). ...
Article
Background: Lysergic acid diethylamide (LSD) and psilocybin are serotonergic hallucinogens that are used primarily for recreational abuse. Small studies evaluated the efficacy of LSD and psilocybin for several psychiatric conditions. There are limited safety or toxicity data for either of these substances, especially in large populations. Methods: This was a retrospective analysis of single-substance exposures of LSD or psilocybin-containing mushrooms (PcMs) reported to United States poison centers from 1 January 2000 to 31 December 2016. The study describes the most frequent toxicities, management sites, and medical outcomes. Results: A total of 5883 PcM and 3554 LSD exposures were included. Most patients were between 13 and 29 years of age (83.9% PcM, 88.9% LSD) and primarily male (77.9% PcM, 74.1% LSD). Most common clinical effects were hallucinations (45.8% PcM, 37.4% LSD), agitation (24.1% PcM, 42.4% LSD), and tachycardia (18.0% PcM, 38.6% LSD). Serious clinical effects were infrequent, but included hyperthermia, seizures, coma, increased serum creatinine, and cardiac arrest. Most patients were treated and released from the emergency department. More LSD patients were admitted to critical care and non-critical care units than PcM patients. Moderate effect was the most frequent outcome for both substances (61.0% PcM, 62.3% LSD). Conclusion: These data find that LSD and PcM use occurs primarily in adolescents and young adults, who experience mild to moderate adverse effects. Serious effects are infrequent but can occur. While most LSD and PcM users require only emergency department management, LSD use is more likely to require medical admission.
... Psychedelics are physiologically safe in humans when ingested at standard doses (Dos Santos et al., 2012;Gasser et al., 2014;Nichols, 2004;Nichols and Grob, 2018). Overdose deaths have occurred due to ingestion of very large doses, that is, more than 23 times the previously recommended LSD human dose (Lim et al., 2012;Nichols and Grob, 2018;Van Amsterdam et al., 2011) or by mixing psychedelics with other drugs and/or alcohol (Gable, 2004;Van Amsterdam et al., 2011). For a summary of overdose and toxicity events reported in the literature, please see Table 3. ...
... LSD has also been shown to be safe with very low physiological toxicity (Nichols, 2016). However, there have been cases of death by overdose of psychedelics with the majority from LSD (Fysh et al., 1985;Nichols and Grob, 2018) and psilocybin (Lim et al., 2012;Van Amsterdam et al., 2011) -probably because these are the most widely used. Supplemental Appendix 1 provides a summary of these and other case reports. ...
Article
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Background: Despite an increasing body of research highlighting their efficacy to treat a broad range of medical conditions, psychedelic drugs remain a controversial issue among the public and politicians, tainted by previous stigmatisation and perceptions of risk and danger. Objective: This narrative review examines the evidence for potential harms of the classic psychedelics by separating anecdotes and misinformation from systematic research. Methods: Taking a high-level perspective, we address both psychological and psychiatric risks, such as abuse liability and potential for dependence, as well as medical harms, including toxicity and overdose. We explore the evidence base for these adverse effects to elucidate which of these harms are based largely on anecdotes versus those that stand up to current scientific scrutiny. Results: Our review shows that medical risks are often minimal, and that many - albeit not all - of the persistent negative perceptions of psychological risks are unsupported by the currently available scientific evidence, with the majority of reported adverse effects not being observed in a regulated and/or medical context. Conclusions: This highlights the importance for clinicians and therapists to keep to the highest safety and ethical standards. It is imperative not to be overzealous and to ensure balanced media reporting to avoid future controversies, so that much needed research can continue.
... Cases of life-threatening toxidrome associated with psilocybin-containing mushrooms are extremely rare. Toxicologically confirmed cases or cases involving mycological identification of psilocybin-containing mushrooms in the patient's possession include those of a 23 year old man who suffered a seizure and transient expressive aphasia, 43 a 25 year old man who experienced renal failure, rhabdomyolysis and posterior encephalopathy with cortical blindness, 44 a 24year old female heart transplant recipient who died from cardiac arrest 45 and an 18 year old man who suffered a myocardial infarction. 46 An alleged, but unconfirmed case of a 17 year old man who experienced cardiac contractile dysfunction has also been reported. ...
Article
Background Psychedelic compounds such as LSD, psilocybin and MDMA share a long and complex history with psychiatry. A half century ago psychedelics were widely employed by psychiatrists in investigational and clinical settings, with studies demonstrating promising findings for their use in the treatment of mental illness and substance use disorders. However, concerns were also raised about their abuse potential, as well as other adverse effects. Due to these worries and psychedelics’ association with the counterculture movement, psychedelics were largely outlawed in the United States in 1970, bringing research on their therapeutic potential to a halt. However, in recent years a resurgence of psychedelic research has revealed compelling, though early, evidence for the use of psychedelic-assisted therapy in treating alcohol use disorder, nicotine use disorder, posttraumatic stress disorder and depression. Objective Here we provide an overview of psychiatry’s complicated relationship with psychedelics, while reviewing contemporary findings on psychedelic-assisted therapy, safety of psychedelic-assisted therapy and risks of non-medical use. We also make the case that psychiatry should consider preparing now for the possibility of Food and Drug Administration (FDA) approval of psychedelic-assisted therapies in the near future. We conclude by discussing how growing societal interest in psychedelics could impact the work of C-L psychiatrists, while also exploring how C-L psychiatrists might contribute to future delivery of psychedelic treatments. Conclusions Despite past concerns about psychedelics, current data indicate psychedelic-assisted therapy may potentially reduce suffering due to mental illness and addiction if administered thoughtfully and cautiously by trained professionals in medical settings.
... In one case, a person died after ingestion of an 275 extremely high dose of Psilocybe semilanceata, resulting psilocybin plasma levels of 4 µg/mL [48]. In another case, a heart transplant recipient appeared to have plasma psilocin levels of 30 µg/mL [49]. Despite the mild physiological effects, including hypertension and tachycardia, it cannot be excluded that extre-280 mely high doses of psilocybin cause LSD-overdose-like effects such as hyperthermia, respiratory failure, or even coma [50]. ...
Article
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Introduction: Evidence based treatment for Substance use disorders (SUD) includes psychotherapy and pharmacotherapy. However, these are only partially effective. Hallucinogens, such as psilocybin, may represent potential new treatment options for SUD. This review provides a summary of (human) studies on the putative therapeutic effects of psilocybin, and discusses the receptor systems, brain regions and cognitive and emotional processes mediating psilocybin's effects. Psilocybin's chemical structure is similar to that of serotonin. Dysregulations in the serotonin system are associated with alterations in stress hormones, such as cortisol, and mood disorders. After psilocybin administration cortisol levels spike and activate the executive control network, with subsequent increased control over emotional processes, and relief of negative thinking and persistent negative emotions. Preliminary data of ongoing alcohol and smoking addiction studies in humans shows promising effects of psilocybin administration on substance use. Importantly, psilocybin has a low risk of toxicity and dependence and can be used safely under controlled clinical conditions. Areas covered: This paper is a narrative review based on the search terms: psilocybin, substance use disorder, addiction, depression, serotonin. Literature on potential efficacy and mechanisms of action of psilocybin in SUD is discussed. Expert commentary: Recent positive findings with psilocybin need confirmation in well-designed placebo controlled randomized trials employing a large sample size.
... Its lethal dose in humans has been theoretically estimated at approximately 1000 times an effective dose (Gable, 2004), which is an amount that is likely not possible for an individual to consume when in the form of psilocybin-containing mushrooms. The authors are aware of only one documented case of acute overdose poisoning death likely caused by psilocybin (Lim et al., 2012). Specifically, a 24-year old female, who had received a heart transplant 10 years prior due to end-stage rheumatic heart disease, experienced cardiac arrest 2e3 hr after consuming psilocybincontaining mushrooms, and subsequently died. ...
Article
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Conclusions: (1) psilocybin has an abuse potential appropriate for CSA scheduling if approved as medicine; (2) psilocybin can provide therapeutic benefits that may support the development of an approvable New Drug Application (NDA) but further studies are required which this review describes; (3) adverse effects of medical psilocybin are relatively low and manageable when administered according to risk management approaches; and (4) although further study is required, this review suggests that placement in Schedule IV may be appropriate if a psilocybin-containing medicine is approved.
... hallucinogènes sont extrêmement rares et dues à une association avec d'autres drogues, souvent l'alcool (Lim et al, 2012 ;Van Amsterdam et al, 2011 Des effets neurotoxiques ont été rapportés, comme une perte de connaissance associée à des convulsions Heim et al, 1966 ;Pierrot et al, 2000). Un cas de rhabdomyolyse, ayant entraîné une insuffisance rénale aiguë, a été décrit suite à l'ingestion de Psilocybe cubensis chez un homme consommant de multiples drogues et présentant une hépatite virale de type C (Bickel et al, 2005). ...
Thesis
Panaeolus cinctulus et Panaeolus cyanescens sont les deux champignons possédant un caractère hallucinogène certain et poussant en Normandie. Rarement trouvés, ils contiennent de la sérotonine, mais surtout de la psilocybine et de la psilocine leur conférant des propriétés hallucinogènes. Ces composés appartenant à la famille des alcaloïdes indoliques sont dosés par diverses méthodes chromatographiques. Les panéoles bleuissants possèdent d’ailleurs de forts taux de psilocybine. Après absorption, cette molécule est transformée en psilocine, psychodysleptique. Elle induit des perturbations sensorielles, mais aussi des modifications profondes de la pensée et de l’humeur dont certaines demeurent après l’élimination de la psilocine. Le mécanisme d’action de la psilocine, agoniste des récepteurs sérotoninergiques 5-HT2A principalement, n’est que partiellement élucidé. La psilocine agit notamment au niveau des circuits corticaux et module la transmission de nombreux neuromédiateurs. Certaines études portent sur l’utilisation de la psilocybine pour explorer et soigner certaines pathologies psychiatriques et sur son intérêt dans la prise en charge de certaines addictions. Tous ces développements thérapeutiques potentiels sont limités par la difficulté d’entreprendre des études cliniques mesurant son efficacité dans de tels domaines. La psilocybine est consommée dans un cadre festif. Les champignons hallucinogènes, placés sous la réglementation des substances stupéfiantes, sont souvent considérés comme une drogue « naturelle » et donc inoffensive, mais des accidents mortels ont été reportés. Les confusions avec des espèces plus toxiques présentent des risques plus grands encore.
... There are only three known deaths attributed to magic mushroom toxicity (Gerault and Picart, 1996;Lim et al., 2012). The estimated lethal dose of psilocybin is approximately 6 g of psilocybin drug substance, in essence 1000 times more than the threshold dose of 6 mg (Gable, 2004) and equivalent to about 10 kg of fresh mushrooms. ...
Article
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Background Psilocybin-containing mushrooms are used for recreational, spiritual, self-development and therapeutic purposes. However, physiologically relatively nontoxic, adverse reactions are occasionally reported. Aims This study investigated the 12-month prevalence and nature of magic mushroom-related adverse reactions resulting in emergency medical treatment seeking in a global sample of people reporting magic mushroom use. Methods We use data from the 2017 Global Drug Survey – a large anonymous online survey on patterns of drug use conducted between November 2016 and January 2017. Results Out of 9233 past year magic mushroom users, 19 (0.2%) reported having sought emergency medical treatment, with a per-event risk estimate of 0.06%. Young age was the only predictor associated with higher risk of emergency medical presentations. The most common symptoms were psychological, namely anxiety/panic and paranoia/suspiciousness. Poor ‘mindset’, poor ‘setting’ and mixing substances were most reported reasons for incidents. All but one respondent returned back to normality within 24 h. Conclusions The results confirm psilocybin mushrooms are a relatively safe drug, with serious incidents rare and short lasting. Providing harm-reduction information likely plays a key role in preventing adverse effects. More research is needed to examine the detailed circumstances and predictors of adverse reactions including rarer physiological reactions.
... In one case, a person died after ingestion of an extremely high dose of Psilocybe semilanceata, resulting psilo- cybin plasma levels of 4 µg/mL [48]. In another case, a heart transplant recipient appeared to have plasma psilocin levels of 30 µg/mL [49]. Despite the mild physiological effects, including hypertension and tachycardia, it cannot be excluded that extre- mely high doses of psilocybin cause LSD-overdose-like effects such as hyperthermia, respiratory failure, or even coma [50]. ...
... More severe adverse events include hallucinogen persisting perception disorder (Orsolini et al., 2017), seizures (Jo et al., 2014), and a hypothetical risk of the development of stiffening of cardiac valves with frequent long-standing use (Löfdahl et al., 2016). Related to the latter, there has been one anecdotal case of a psilocybin-related death of a heart transplant patient (Lim et al., 2012). In addition, some fatal cases have been reported as a result of severe emotional destabilization or hallucinations leading to suicidal behaviour, such as the conviction of the ability to fly (Müller et al., 2013). ...
Article
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Classical psychedelics represent a family of psychoactive substances with structural similarities to serotonin and affinity for serotonin receptors. A growing number of studies have found that psychedelics can be effective in treating various psychiatric conditions, including post-traumatic stress disorder, major depressive disorder, anxiety, and substance use disorders. Mental health disorders are extremely prevalent in the general population constituting a major problem for the public health. There are a wide variety of interventions for mental health disorders, including pharmacological therapies and psychotherapies, however, treatment resistance still remains a particular challenge in this field, and relapse rates are also quite high. In recent years, psychedelics have become one of the promising new tools for the treatment of mental health disorders. In this review, we will discuss the three classic serotonergic naturally occurring psychedelics, psilocybin, ibogaine, and N, N-dimethyltryptamine, focusing on their pharmacological properties and clinical potential. The purpose of this article is to provide a focused review of the most relevant research into the therapeutic potential of these substances and their possible integration as alternative or adjuvant options to existing pharmacological and psychological therapies.
... These transient and moderate elevations in SBP and HR have not been associated with any serious adverse cardiac events in these supervised experimental studies. Despite the cardiac safety in controlled clinical trials, there have been a couple of rare recreational psilocybin mushroom case reports of myocardial infarction, with one resulting in the death of 24-year-old heart transplant recipient (Lim, Wasywich, & Ruygrok, 2012). ...
Chapter
In an attempt to comprehensively review the adverse effects of psychedelics, toxicology literature associated with unsafe recreational environments was also selectively reviewed for reports of adverse effects that may be generalizable to a therapeutic setting, but more robust evidence from clinical trial research is emphasized in this chapter.
... Psilocybin overdose is very rare [241,242]. One such report of psilocybin overdose and subsequent fatality was specifically due to cardiac arrest, some 2-3 h after psilocybin ingestion, in a 24-year-old female who, 10 years prior, had a heart transplant due to end-stage rheumatic heart disease [243]. ...
Article
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The psychedelic effects of some plants and fungi have been known and deliberately exploited by humans for thousands of years. Fungi, particularly mushrooms, are the principal source of naturally occurring psychedelics. The mushroom extract, psilocybin has historically been used as a psychedelic agent for religious and spiritual ceremonies, as well as a therapeutic option for neuropsychiatric conditions. Psychedelic use was largely associated with the “hippie” counterculture movement, which, in turn, resulted in a growing, and still lingering, negative stigmatization for psychedelics. As a result, in 1970, the U.S. government rescheduled psychedelics as Schedule 1 drugs, ultimately ending scientific research on psychedelics. This prohibition on psychedelic drug research significantly delayed advances in medical knowledge on the therapeutic uses of agents such as psilocybin. A 2004 pilot study from the University of California, Los Angeles, exploring the potential of psilocybin treatment in patients with advanced-stage cancer managed to reignite interest and significantly renewed efforts in psilocybin research, heralding a new age in exploration for psychedelic therapy. Since then, significant advances have been made in characterizing the chemical properties of psilocybin as well as its therapeutic uses. This review will explore the potential of psilocybin in the treatment of neuropsychiatry-related conditions, examining recent advances as well as current research. This is not a systematic review.
... There have been cases of acute cardiac failure including Takotsubo cardiomyopathy, cardiac ischemia, and myocardial infarction in patients with preexisting cardiac conditions following the ingestion of psilocybin, 5-MeO-DIPT, MDMA, and ibogaine. [111][112][113][114] Ibogaine has also been implicated in fatal cases of cardiomyopathy, QT prolongation, and ventricular arrhythmias, and cardiac hypertrophy, mostly in patients with preexisting cardiac issues, which has limited its use in the United States in the treatment of opioid use disorder. 115,116 Additional fatal cases of cardiotoxicity have been identified following the ingestion of MDMA in patients both with and without preexisting cardiac conditions. ...
Article
Hallucinogens constitute a unique class of substances that cause changes in the user's thoughts, perceptions, and mood through various mechanisms of action. Although the serotonergic hallucinogens such as lysergic acid diethylamide, psilocybin, and N,N‐dimethyltryptamine have been termed the classical hallucinogens, many hallucinogens elicit their actions through other mechanisms such as N‐methyl‐D‐aspartate receptor antagonism, opioid receptor agonism, or inhibition of the reuptake of monoamines including serotonin, norepinephrine, and dopamine. The aim of this article is to compare the pharmacologic similarities and differences among substances within the hallucinogen class and their impact on physical and psychiatric effects. Potential toxicities, including life‐threatening and long‐term effects, will be reviewed.
... In terms of human being, we may be able to tolerate a higher dose. Despite some studies had emphasized the reported acute toxic effects associated with the exposure of psilocybin at low dose (Isbell et al., 1961;Lim et al., 2012;van Amsterdam et al., 2011), results from Davis et al. suggest that no severe adverse events occurred. Meanwhile, a relatively large dose of psilocybin (i.e., 30-35mg/70 kg, the highest dose among all included studies) treatment accompanied with psychotherapy Davis. ...
Article
Background: Previous studies have shown that psilocybin has antidepressant effects. In the current study, we aim to explore the dose effects of psilocybin on primary (major depression patients) and secondary depression (depressed cancer patients). Methods: Published studies concerning psilocybin for depression were retrieved. In accordance with PRISMA guidelines, 6 databases (PubMed, Embase, Web of Science, Cochrane Library, Clinicaltrials.gov 2.3 and WanFang database) were searched for research studies published or still in progress from inception to 30 November, 2020, with language restricted to English and Chinese. Hedges' g of Beck Depression Inventory (BDI) score changes was calculated as the primary outcome. Results: 7 articles were finally included, with a total of 136 participants. In terms of efficacy, Hedges' g was 1.289 (95%CI=[1.020, 1.558], heterogeneity I2=50.995%, p<0.001). As psilocybin dose increases within a certain range, the antidepressive effect declines and then increases, with 30-35 mg/70 kg achieving the optimal therapeutic effect. Subgroup analysis suggested that the antidepressive effect of psilocybin was extremely significant at a relatively high dose (30-35mg/70kg: Hedges' g=3.059, 95%CI=[2.269, 3.849], p<0.001), long-term (>1month: Hedges' g=1.123, 95%CI=[0.861, 1.385], p<0.001) and when used in primary depression patients (Hedges' g=2.190, 95%CI=[1.423, 2.957], p<0.001). Limitations: Only a small number of studies can be identified of variable quality, thus our conclusions remain preliminary. Conclusions: Our preliminary results have shown that psilocybin exerts a rapid effect in reducing depressive symptom on primary and secondary depression. The optimal dose of psilocybin may be 30-35mg/70kg or higher; future clinical trials are warranted for further evaluation on its effect.
... Individuals with significant underlying cardiovascular, neurologic, hepatic, or renal conditions have largely been excluded from recent studies, and it is unclear whether medical complications will be more common in these populations. Life-threatening medical complications have occurred in individuals taking unregulated classical psychedelics (including psilocybin-containing mushrooms) in uncontrolled settings, though even in these settings, medical fatalities are extremely rare and likely multifactorial (Bickel et al. 2005;Raval et al. 2008;Berrens et al. 2010;Aakeroy et al. 2020;Borowiak et al. 1998;Nichols and Grob 2018;Lim et al. 2012;Leonard et al. 2018). Though classical psychedelics have overlapping neurophysiological mechanisms, their adverse effect profile may not be uniform. ...
Article
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Rationale A broad reassessment of the potential benefits of psychedelic drugs has led to the initiation of multiple major clinical trials in an effort to advance their status to become FDA-approved medications, as well as local legislative efforts to legalize or decriminalize their use. Objectives To use recently published data to assess potential risks and benefits of psychedelic drugs as therapeutics, as well as to synthesize what is currently known in order to generate fruitful future research directions. Methods A review of studies conducted since 1991 identified 14 clinical trials of classical psychedelics, including 11 of psilocybin (N = 257 participants), 1 of lysergic acid diethylamide (N = 12 participants), and 2 of ayahuasca (N = 46 participants). Other published studies (e.g., of healthy volunteers, survey studies, case reports, neuroimaging) were also considered for review. Results Published studies since 1991 largely support the hypothesis that small numbers of treatments with psychedelic-assisted psychotherapy can offer significant and sustained alleviation to symptoms of multiple psychiatric conditions. No serious adverse events attributed to psychedelic therapy have been reported. Existing studies have several limitations, including small sample sizes, inherent difficulty in blinding, relatively limited follow-up, and highly screened treatment populations. Conclusions Substantial data have been gathered in the past 30 years suggesting that psychedelics are a potent treatment for a variety of common psychiatric conditions, though the ideal means of employing these substances to minimize adverse events and maximize therapeutic effects remains controversial. Unique factors related to study design are vital for clinical researchers in the field to address.
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Various amphetamine-like designer drugs including MDMA, and MDA are abused. Although abuse of MDA and MDMA can be detected by urine analysis using amphetamine/methamphetamine immunoassay or immunoassay specifically designed to detect MDMA, other amphetamine-like designer drugs have low cross-reactivity with amphetamine immunoassay and may not be detected in urine if abused. Bath salts are synthetic cathinone. Cathinone is a natural product found in khat plant. Synthetic cannabinoids are also widely abused. These products are not structurally related to THC but interact with cannabinoid receptors which also bind THC. Date rape drugs such as Rohypnol, GHB and to less extent ketamine are also encountered in rave parties. Fentanyl and its analogs are also abused. Although less frequently abused, magic mushroom and peyote cactus abuse are also reported. After abuse of many of these products, toxicology screen could be negative because these compounds are not routinely targeted in drugs-of-abuse analysis.
Article
Psilocybin is found in a family of mushrooms commonly known as “magic mushrooms” that have been used throughout history to induce hallucinations. In the late 1950s Albert Hofmann, of Sandoz Laboratories, identified and synthesized the psychoactive compounds psilocybin and psilocin which are found in psilocybe mushrooms. Psilocybin was marketed by Sandoz as Indocybin for basic psychopharmacological and therapeutic clinical research. Psilocybin saw a rapid rise in popularity during the 1960s and was classed as a schedule I drug in 1970. This led to a significant decrease in psilocybin research. Recently, however, preliminary studies with psilocybin have shown promise as potential for the treatment of obsessive compulsive disorder, alcohol addiction, tobacco addiction, major depressive disorder, and the treatment of depression in terminally ill cancer patients. This review describes in detail the synthesis, metabolism, pharmacology, ADRs and importance of psilocybin to neuroscience in the past and present.
Article
Porpuse: Sudden cardiac death (SCD) is an important post-transplant problem being responsible for approximately 10% of deaths. We conducted a systematic review and meta-analysis to evaluate incidence and predictors of post-heart transplant SCD, and use of implantable cardiac defibrillator (ICD). Methods: Citations were identified in electronic databases and references of included studies. Observational studies on adults reporting on incidence and predictors of post-transplant SCD and ICD use were selected. We meta-analyzed SCD in person-years using random effect models. We qualitatively summarized predictors. Results: This study includes 55 studies encompassing 47,901 recipients. The pooled SCD incidence SCD was 1.30 per 100 person-years (95%CI 1.08-1.52). Cardiac allograft vasculopathy (CAV) was associated with higher SCD risk (2.40 per 100 patient-years, 95%CI 1.46-3.34). Independent predictors of SCD identified by 2 moderate quality studies were older donor and younger recipient age, non-Caucasian race, reduced left ventricular ejection fraction, rejection, infection and cancer. Authors rarely reported on ICD use. Conclusion: This meta-analysis found that post-transplant SCD risk in heart transplant recipients is higher than in the general population. CAV was associated with increased SCD risk. Observational studies reporting on absolute risk of SCD are needed to better identify populations at a clinically significant increased risk. This article is protected by copyright. All rights reserved.
Thesis
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BACKGROUND Novel or new psychoactive substances (NPS), also known as designer drugs and research chemicals, represent a relatively recent phenomenon which can be traced back to the last decade or even earlier. The growth of this phenomenon and its electronic trade (e-trade) has been logarithmic and alarming; its aftermaths are not limited to; the economy, individual and public health, or illicit drug trade. The discipline of NPS has been extensively studied since 2010. However, there are still deficits in; data from the Middle East and the developing world including Arabic countries (1), application of data science and inferential hypothesis testing (2), implementation of the principles and theories of social science (3), utilization of experimental designs including randomised controlled trials (RCT) and quasi-experimental studies (4), and ultimately the enactment of real-time web analysis and the realization of tools of knowledge discovery in databases (5). AIM AND OBJECTIVES This study will implement an innovative research approach by combining observational analyses and data science; the aim is to provide generalizable (inferential) data in relation to NPS e-commerce activities on both divisions of the web, surface and deep. The pinnacle objective is to; assess the proportional magnitude of NPS e-commerce activity in the Middle East (1), provide a thorough analysis of the e-vendors on the darknet, both globally and regionally (Middle East) (2), correlate change in trends of e-commerce with time (3), provide recommendations for future studies in relation to the e-commerce activity in the Middle East (4), and to discuss the colossal potential of data mining technologies (5). MATERIALS AND METHODS This dissertation embodies the integrative and combinatorial approach towards the investigation of the e-trade (e-commerce) of NPS; it is made of integrated studies allocated into eleven results chapters. The utilised investigative tools represent a mixed-breed of observational web analytics including; literature review (1), cross-sectional studies and surveys (2, 3), internet snapshots (4), retrospective analyses (5), and critical appraisal (6). These analyses took place in both appendices of the web (surface web and the anonymous deep web); the analyses specifically involved; Google Trends database (1), literature databases (2), drug fora (3), social communication e-media (3), news and media networks (4), Grams search engine of the deep web (5), the darknet and its e-marketplace (6), Alphabay, Agora, Valhalla, Hansa, other dedicated e-markets for NPS e-trade (7). Additional extrapolations were concluded via the use of surveys and e-surveys in a population of medical students from Iraq. The potentials for knowledge discovery in databases (KDD) were also discussed in all chapters. Each chapter was thoroughly investigated via; data science tools (I), inferential statistics and hypothesis testing (II). The latter was dependent on using the Microsoft Excel 2016, the Statistical Package for the Social Sciences (SPSS), and some online tools of data science. RESULTS AND DISCUSSION A systematic review of approximately 600 PubMed-indexed articles of NPS literature showed; attempts of NPS research started to evolve after 2010, almost one-third of the research output (36%) was of relevance to toxicology and analytic chemistry, while reviews and cross-sectional studies were less common (15%, 18%). The analysis of the individual basis of power showed that NPS researchers, legislators, and policymakers are lagging behind, whereas terrorist possesses the highest possible power. Power scores of e-vendors scored highest in the UK, US, and eastern Europe, while being almost absent in the Middle East. The complimentary usage of PubMed, drug fora, and Google Trends was successful in extrapolating the most trending and high-risk NPS; the contribution from the Middle East to incidents of intoxications and fatalities was absent except for Israel. Deep web analysis, including the darknet e-marketplace, has shown that the contribution of the Middle East never exceeded 7% of the total e-trade, data were limited to; Iran, Israel, Turkey, Afghanistan, Oman, United Arab Emirates, and Saudi Arabia. Other Arabic countries included; Egypt, Morocco, and Algeria. It was interesting to observe the e-vendors of NPS operating in the Middle East were highly involved in e-trade activities in other nations, primarily; the UK, Western Europe and Scandinavia, US, Canada, Australia, and New Zealand. Surveys and internet snapshots unveiled the lack of awareness and very low prevalence of (ab)use of NPS within the selected Iraqi population. Captagon was highly prevalent in the Middle East, unlike NBOMe and octodrine. In summary, the contribution from the Middle East was microscopic when compared to the developed world; it did not exceed 7% of the entire NPS phenomenon e-trade. Similarly, the NPS research in the region of the Middle East can be described to be in its infancy. The overall level-of-evidence of this dissertation is assumed to be of level-2b according to the classification system imposed by the Oxford Center for Evidence-Based Medicine (2009). CONCLUSION The growth of the NPS phenomenon, including the e-commerce and its links to terrorism, are reaching unprecedented levels. Unless some reasonable efforts and ingenious upgrades of the current research methodologies, the NPS trade and e-trade will continue to prevail rendering all its counter-attempts fade into dust; these attempts are not only limited to NPS research but also into; legislative actions, policy planning, and counter-terrorism. Upgrades should affect these front lines; increasing the quality and quantity of studies in developed countries including Middle Eastern and Arabic countries (1), incorporation of efficient use of data science and advanced web analytics (2), compulsory training of data science, biostatistics, and basic neuroscience for all NPS researchers, chemists, and toxicologists (3), validation and incorporation of data mining and real-time analyses (4), inclusion of the rarely-used experimental studies including RCTs, pragmatic RCTs, and animal modelling (5), enhancement and potentiation of internet snapshot techniques (6), and full exploitation of trends databases of the surface web (7). Perhaps, the integration of real-time data mining and data crunching, and inferential data science technique will represent the climax armament to antagonise the alarming e-trade.
Article
Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT)2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites. Psilocybin is primarily a pro-drug that is dephosphorylated by alkaline phosphatase to active metabolite psilocin. This last is then further metabolized, psilocin-O-glucuronide being the main urinary metabolite with clinical and forensic relevance in diagnosis.
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Drug abuse is a worldwide problem. Although commonly abused drugs can be identified during routine urine drug testing, less commonly abused drugs may escape detection. These less commonly abused drugs not only include some designer drugs such as synthetic cannabinoid but also include abuse of psychedelic magic mushroom (active ingredients: psilocybin and psilocin), peyote cactus (active ingredient: mescaline), and khat plants (active ingredient: cathinone). Moreover, solvent and glue abuse is gaining popularity among teenagers and young adults which may even cause fatality. Amphetamine/methamphetamine immunoassay has a low cross-reactivity with psilocin. Cathinone, if present in the urine, can be detected by amphetamine/methamphetamine immunoassay due to cross-reactivity of cathinone with assay antibody. Currently there is one commercially available immunoassay which is capable of detecting synthetic cathinone known as bath salts as well as mescaline. However, gas chromatography combined with mass spectrometry as well as liquid chromatography combined with tandem mass spectrometry (LC/MS/MS)-based method is available for confirmation of the active ingredients present in magic mushroom, peyote cactus, and khat plant. Such chromatography-based methods also offer more sensitivity and specificity compared to an immunoassay.
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Methods applicable to the detection of hallucinogenic indole compounds, namely psilocybin, psilocin, and related molecules, that have been developed so far for purposes of mycological research, toxicological studies, or forensic investigations are described in this chapter. The most current literature as well as some interesting older publications are cited, providing a historical overview of the subject. Methods of qualitative and quantitative analysis are presented. Additionally, preliminary purification steps and sample treatment before the exact quantitative determination are proposed. The methods described utilized various analytical techniques for the measurement of psilocybin/psilocin content in the analyzed material, including capillary electrophoresis, chemiluminescence detection systems, high-performance liquid chromatography with electrochemical, ultraviolet, or fluorescence detection systems, gas chromatography, and liquid chromatography coupled with mass spectrometry. The methods developed for simultaneous determination of several commonly abused psychoactive substances along with psilocin/psilocybin are also mentioned.
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The aim of our chapter is to review recent developments in a group of medicinally important natural products-alkaloids, with reference to the structure-activity studies in respect of certain diseases. Alkaloids covered by our review come from mushrooms called "hallucinogenic." Hallucinogenic compounds have been chemically identified in mushrooms belonging to various genera, e.g., Agrocybe, Amanita, Conocybe, Galerina, Gymnopilus, Hypholoma, Inocybe, Panaeolus, Psilocybe, Pholiotina, Pluteus, and Weraroa [J.W. Allen, Ethnomycol. J. Sacred Mushroom Stud. 9 (2012) 130-175]. One of the largest classes of alkaloids is indole alkaloids. Indoles are probably the most widely distributed heterocyclic compounds in nature having medicinal importance [K.N. Kumar et al., Molecules 18 (2013) 6620-6662]. Two of simple indole alkaloids: psilocin (3-[2 (dimethylamino)ethyl]-4-indolol) and psilocybin ([3-(2-dimethylaminoethyl)-1H-indol-4-yl] dihydrogen phosphate) are present in most psychedelic mushrooms. Psilocin is a serotonin agonist - psilocybin/psilocin caused effects are thought to be mediated mainly by activation of 5-HT2A receptor. Ligands for the 5-HT2A receptor may be extremely useful tools for future cognitive neuroscience research [D.E. Nichols, Pharmacol. Ther. 101 (2004) 131-181]. They are also other analogs of psilocybin: baeocystin, norbaeocystin, bufotenin, and aeruginascin that are found in hallucinogenic mushrooms. Bufotenin occur also in some animal species (genus Bufo) and plants. Some of the mushroom belonging to genera Gymnopilus and Pholiota were shown to possess bisnoryangonin and hispidin, alkaloids with antimicrobial [K. Shinto et al., J. Home Econ. Jpn. 58 (9) (2007) 563-568] and antioxidant [Lee In-K et al., Mycobiology, 36 (1) (2008) 55-59] activity. Also psychoactive species of genus Amanita, contain the alkaloids (muscimol, ibotenic acid, and muscazone) that react with neurotransmitter receptors in the central nervous system. Isoxazoles, to which these alkaloids belong, have been found to inhibit voltage-gated sodium channels to control pain, enable the construction of tetracycline antibiotic derivatives, and as treatments for depression. The information within this review is intended to serve as a reference tool to better enable future research into important and fascinating area of pharmacognostic science as well as other parts of medical science.
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In 2007, the Minister of Health of the Netherlands requested the CAM (Coordination point Assessment and Monitoring new drugs) to assess the overall risk of magic mushrooms. The present paper is an updated redraft of the review, written to support the assessment by CAM experts. It summarizes the literature on physical or psychological dependence, acute and chronic toxicity, risk for public health and criminal aspects related to the consumption of magic mushrooms. In the Netherlands, the prevalence of magic mushroom use was declining since 2000 (last year prevalence of 6.3% in 2000 to 2.9% in 2005), and further declined after possession and use became illegal in December 2008. The CAM concluded that the physical and psychological dependence potential of magic mushrooms was low, that acute toxicity was moderate, chronic toxicity low and public health and criminal aspects negligible. The combined use of mushrooms and alcohol and the quality of the setting in which magic mushrooms are used deserve, however, attention. In conclusion, the use of magic mushrooms is relatively safe as only few and relatively mild adverse effects have been reported. The low prevalent but unpredictable provocation of panic attacks and flash-backs remain, however, a point of concern.
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Case report: Intentional intoxication with natural hallucinogenic substances such as hallucinogenic mushrooms continues to be a major problem in the US and Europe, particularly in the harbor complex of northwest Poland (Pomerania). A case is described of Psilocybe intoxication in an 18-year-old man resulting in Wolff-Parkinson-White syndrome, arrhythmia, and myocardial infarction. The indole concentrations of hallucinogenic mushrooms may predict the risk for adverse central nervous system and cardiac toxicity.
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We report the case of a 25-year-old, hepatitis C-infected man, who presented with severe rhabdomyolysis and acute renal failure, and later developed posterior encephalopathy with cortical blindness after the ingestion of magic mushrooms. Conventional respiratory and cardiovascular support including mechanical ventilation, continuous veno-venous hemodialysis and corticosteroids led to improvement and the patient recovered completely over the following months. Magic mushrooms are becoming increasingly fashionable among drug users, as they are believed to be more harmless than other hallucinogenic designer drugs. So far, little is known about their possible severe side effects.
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Consumption of natural hallucinogenic substances continues to be a problem. In this case we report from a young male patient presenting with an acute coronary syndrome with significant ST-elevation after the abuse of psychoactive fungi, commonly referred to as "magic mushrooms". Coronary angiography excludes relevant coronary artery disease. In ventriculography contractile dysfunction with hypokinesia in the apical segments could be documented reminiscent to wall motion abnormalities in Tako-Tsubo cardiomyopathy (TTC). Cardiovascular magnetic resonance imaging showed no pathological signal activity in the late-enhancement sequences ruling out myocardial infarction or inflammatory processes. Ventricular function normalized within several days. The active metabolite of psychoactive fungi psilocybin is known to interact with several different dopaminergic, adrenergic and serotonergic receptors. Thus, the pathomechanisms leading to contractile dysfunction after consumption of psychoactive fungi are reminiscent to those documented in TTC.