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Psychedelics, such as psilocybin represent one of the most promising current therapeutic approaches in psychiatry.Psychedelics seem to have not only potent antidepressant effects. Do they also work particularly quickly, i.e. within one day?The available literature on clinical studies of psychedelics in depressive syndromes is presented both from the period up to the prohibition of these substances in the late 1960s as well as after the resumption of research in the 2000s. One focus is the speed of onset of antidepressant action.Only the clinical studies published since 2016 that meet modern methodological standards have also systematically examined the speed of the antidepressant onset of action. The published studies, which were almost exclusively carried out with psilocybin, so far show small sample sizes (the total number of patients with depression treated in published clinical studies is 200) and some of them have methodological weaknesses; however, they suggest a pronounced and very rapid onset of action within one day for depression, treatment-resistant depression and depression in the context of life-threatening cancer.The available studies indicate a potent, rapid onset and in many cases long-lasting antidepressant effect over several months. The currently conducted studies with three-digit patient numbers will provide final information about the potential of psilocybin for depression.HINTERGRUND: Psychedelika wie Psilocybin stellen einen der vielversprechendsten aktuellen Therapieansätze in der Psychiatrie dar.Psychedelika scheinen nicht nur eine potente antidepressive Wirkung zu haben. Setzt ihre Wirkung auch besonders schnell, d. h. innerhalb eines Tages, ein?Die verfügbare Literatur über klinische Studien mit Psychedelika bei depressiven Syndromen wird dargestellt, und zwar sowohl aus der Zeit bis zu dem Verbot dieser Substanzen Ende der 1960er-Jahre als auch nach der Wiederaufnahme der Forschung in den 2000er-Jahren. Ein Fokus liegt auf der Schnelligkeit des Eintritts der antidepressiven Wirkung.Nur die seit 2016 publizierten klinischen Studien, die modernen methodischen Standards genügen, haben auch die Schnelligkeit des antidepressiven Wirkeintritts systematisch untersucht. Die publizierten Studien, die fast ausnahmslos mit Psilocybin durchgeführt wurden, weisen bisher allerdings noch kleine Fallzahlen auf (die Gesamtzahl der in publizierten klinischen Studien behandelten Patienten mit Depression ist 200), z. T. haben sie methodische Schwächen. Sie legen jedoch eine ausgeprägte und sehr rasch – innerhalb eines Tages – einsetzende Wirkung bei Depression, therapieresistenter Depression und Depression im Rahmen lebensbedrohlicher Krebserkrankungen nahe.Die verfügbaren Studien weisen auf eine potente, schnell einsetzende und in vielen Fällen lang – mehrere Monate – anhaltende antidepressive Wirkung hin. Endgültigen Aufschluss über das Potenzial der Substanz werden die aktuell durchgeführten Studien mit dreistelligen Patientenzahlen geben.

First tested und used for therapeutic purposes in psychiatry, LSD entered the sub- und counter-cultural field of the beatnik and hippie movement in the 1950s and 1960s as a chemical promise of individual liberation from societal restrictions. In this process, “psychedelic” movies emerged as a new genre, picking up narratives of the substance-induced freeing of the mind and developing cinematic stagings of being “high” on LSD. The article compares a selection of “psychedelic” movies produced since the 1960s, including “The Trip”, “Easy Rider”, “Altered States” and “Fear and Loathing in Las Vegas”. It focusses on the question of how narratives of the chemical transgression of the mind, understood as part of the counter-cultural movement, transformed into representations of intoxication as expression of individual fragmentation and pointless escapism at the mercy of societal constraints.

The goal of this doctoral thesis was the close examination of the biosynthesis of different indole alkaloides produced by different species of the fungal genus Psilocybe. This included the first characterization of the biosynthesis of psilocybin as the main psychotropic agent and the first discovery of the simultaneous production of β-carbolines. In the first step, the genome of P. cyanescens was sequenced and analyzed for characteristic genes and clusters or modifying enzymes. After the detection of the psilocybin biosynthesis cluster in Psilocybe, the cluster was expressed heterologous in E. coli and A. niger and an in vitro characterization of the psilocybin biosynthesis was done. Because of the raised pharmaceutical interest as well as some collaboration with the company Promega and the non-profit organization Usona, an expanded biocatalytic route for the in vitro production of psilocybin was established. The solution was the development of a continuous in vitro synthesis through a connection of the tryptophan synthase (TS) out of the basidiomycete P. cubensis with the biosynthesis route of psilocybin. Additionally, the substrate specifity of the TS were tested against different other halogenated indoles and for the first time different analogues of psilocybin could be produced biocatalytically with the same set of enzymes (Blei, Baldeweg et al. 2018). The generation of another derivate the 6-methylpsilocybin succeeded through an exchange with the TS of S. enterica (Fricke, Sherwood et al. 2019). Furthermore, the biosynthesis of the indole alkaloid l-Hypaphorin was characterized using the methyltransferase TrpM. Surprisingly no interference occured between the substrates of TrpM and the methyltransferase from the psilocybin biosynthesis PsiM because of strict substrate specifics. Supplemental to the already addressed indole alkaloides my work could identify further natural products out of the β-carboline class in the fruiting bodies and mycelia of different Psilocybe species. This was a big discovery in regards to the possible synergistic effects this could have on the psychoactive effect of Psilocybin through an inhibition of the monoaminoxidase enzyme (Blei, Dörner et al. 2019).

In der gegenwärtigen Arbeit wurden die Strukturvielfalt und die genetischen und enzymatischen Grundlagen der Indolalkaloidbiosynthese in Basidiomyceten in Psilocybe spp. untersucht. Durch in silico-Analysen und heterologe Expression ist es gelungen, die Biosynthese des Psilocybins aufzuklären, die verantwortlichen Gene zu identifizieren und die resultierenden Enzyme biochemisch und phylogenetsich zu charakterisieren. Die Psilocybin-Biosynthese wird dabei durch vier Enzyme katalysiert, nämlich die L-Tryptophan-Decarboxylase PsiD, die Cytochrom-P450-Monooxygenase PsiH, die Kinase PsiK und die N-Methyltransferase PsiM, die einzigartige Sekundärmetabolit-Enzyme darstellen und deren Substratspezifitäten eine zu der bisher postulierten Biosynthese abweichenden Abfolge belegte. Aufbauend auf dem erlangten Wissen aus der Psilocybin-Biosynthese konnte die erfolgreiche Entwicklung mehrerer in vitro- und in vivo-Routen für das Psilocybin sowie den drei nicht-natürlichen Derivaten Isonorbaeocystin, 5-Methylpsilocybin und 6-Methylpsilocybin beschrieben werden. Dies könnte die Grundlage für die Weiterentwicklung von kostengünstigen und umweltfreundlichen Herstellungsverfahren für den pharmazeutisch höchstrelevanten Naturstoff sein. Die erzeugten Derivate könnten zudem helfen, die serotonerge Neurotransmission im Menschen besser zu verstehen. Die in dieser Arbeit erzielten Ergebnisse könnten bei der Sicherstellung der Versorgung von Psilocybin helfen, was das Durchführen weiterer klinischer Studien unterstützen könnte. Bei einer erneuten Sekundärmetabolom-Analyse verschiedener Psilocybe-Arten konnten, neben weiteren Indolalkaloiden, verschiedene β-Carboline identifiziert werden, die als potente Monoaminooxidase-Hemmer möglicherweise einen bisher unentdeckten synergistischen Effekt auf die Wirkung des Psilocybins haben könnten.

Psilocybin/psilocin from so-called psychoactive mushrooms causes hallucinogenic effects. Especially for people with mental or psychiatric disorders ingestion of magic mushrooms may result in horror trips combined with the intention of self-destruction and suicidal thoughts. Automutilation after consumption of hallucinogenic mushrooms has already been described. Our case report demonstrates the suicide of a man by self-inflicted cut and stab injuries. A causal connection between suicidal behaviour and previous ingestion of psychoactive mushrooms is discussed.

The purpose of this article is to provide an overview of the current research on hallucinogen induced psychiatric disorders. In addition to LSD and psilocybin hallucinogens of biologic origin are increasingly used by adolescents and young adults.Relevant literature and related articles were identified by means of a computerized MEDLINE search including the years 1997 - 2007. As keywords "hallucinogen induced psychosis", "hallucinogen induced flashback", "hallucinogen persisting perception disorder (HPPD)" were used. Finally, 64 journal articles and books out of 103 were included in the review.Acute psychotic syndromes in adolescents are rarely due to intoxications with hallucinogenic drugs. However, clinical relevance of flashback phenomena as post-hallucinogenic psychiatric disorder has to be disputed. Because of the high popularity of biogenic hallucinogens and LSD knowledge of intoxications and resulting psychiatric disorders as well as medical complications and therapeutical approaches are clinically important. Especially intoxications with drugs of herbal origin like tropanalcaloids play an important role in emergency situations.

Psychoactive mushrooms ("magic mushrooms") have been consumed in northern Europe since the late seventies. Recently, the use of hallucinogenic fungi has become popular among young people again. In autumn, psychoactive mushrooms can be collected from their natural habitats throughout Europe. Some species are cultivated in the Netherlands and are sold in "smart-shops" or via Internet. In Germany, dried specimens are sold as "Duftkissen" (aroma pads). The article reviews the common psychoactive species and illustrates medical risks.

The paper presents simple methods for microscopic examination and basic microchemical testing for the identification of suspect mushroom powders. The microscopic features of the most commonly cultivated and trafficked hallucinogenic genus Psilocybin are described and may serve for the decision whether any suspect material consists of such mushroom powder (and is therefore to be subjected to further analysis) or not.

Music is a structure ('Gestalt') in time. The recognition of disturbances of the perception of music enhances the knowledge of disorders of perception of time. Disturbances of perception of music and time in experimental psychoses (psilocybine) are discussed in relation to the studies by Piaget on the development of the notion of time in childhood. The results allow a new interpretation of the disturbances of the perception of time in diencephalic disorders as described in the literature.

We tested dried East-Asian mushrooms that have only recently appeared on the German drug "scene". They were impregnated with lysergic acid diethylamide (LSD) but sold as Mexican sacred hallucinogenic mushrooms, containing psilocybine. For the safe identification of psilocybine in mushrooms, TASmethod is proposed. Successful identification of LSD in mushrooms is done by tartaric acid extraction with subsequent TLC of the free base. The modified van Urk reaction in connection with hRf-values is best suited for the detection of psilocybine, psilocine and LSD.