• The pharmacology of psilocybin (Passie et al., 2002)
  
  Lainaus

  Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocybin were known until recently. Because of its still growing capacity for abuse and the widely dispersed data this review presents all the available pharmacological data about psilocybin.

  
  
• Increased activation of indirect semantic associations under psilocybin (Spitzer et al., 1996)
  
  Lainaus

  The spread of activation in semantic networks can be measured using semantic and indirect semantic priming effects in lexical decision tasks (Spitzer et al 1993a and b). For example, in thought-disordered schizophrenic patients, activation spreads faster and farther than in non-thought-disordered patients and normal subjects, which results in an increased direct and indirect semantic priming effect (see below). This has been interpreted as the result of a decreased signal-to-noise ratio in cortical neural networks that process semantic information. Such a decreased signal-to-noise ratio has been related to a decreased dopaminergic modulation (Servan-Schreiber et al. 1990; Cohen and Servan- Schreiber 1992, 1993), which we recently were able to confirm directly in a study on the effects of L-dopa on semantic and indirect semantic priming (Kischka et al 1995).
  
  As dopamine was found to have a focusing effect on the activity in semantic networks, i.e., it increases the signal-to-noise ratio and reduces the spread of activation (measured as reduced indirect semantic priming), we set out to investigate the effect of the hallucinogenic agent psilocybin on this task. Since psilocybin is known to act on the serotonin (5-HT) system and has effects of "broadening" conscious experiences, we hypothesized that it might exert a defocusing effect on semantic networks (i.e., decrease the signal-to-noise ratio), which should lead to an increased indirect semantic priming effect.
  
  To test this hypothesis directly, we conducted a double-blind, placebo-controlled study on the effects of psilocybin on semantic and indirect semantic priming as part of a larger project that was designed to assess the behavioral effects and pharmacokinetic properties of this hallucinogenic agent (the results will be reported elsewhere; cf. Holzmann 1995).

  
  
• Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans. (Carter et al., 2007)
  
  Lainaus

  RATIONALE: Binocular rivalry occurs when different images are simultaneously presented to each eye. During continual viewing of this stimulus, the observer will experience repeated switches between visual awareness of the two images. Previous studies have suggested that a slow rate of perceptual switching may be associated with clinical and drug-induced psychosis.
  
  OBJECTIVES: The objective of the study was to explore the proposed relationship between binocular rivalry switch rate and subjective changes in psychological state associated with 5-HT2A receptor activation.
  
  MATERIALS AND METHODS: This study used psilocybin, the hallucinogen found naturally in Psilocybe mushrooms that had previously been found to induce psychosis-like symptoms via the 5-HT2A receptor. The effects of psilocybin (215 microg/kg) were considered alone and after pretreatment with the selective 5-HT2A antagonist ketanserin (50 mg) in ten healthy human subjects.
  
  RESULTS: Psilocybin significantly reduced the rate of binocular rivalry switching and increased the proportion of transitional/mixed percept experience. Pretreatment with ketanserin blocked the majority of psilocybin's "positive" psychosis-like hallucinogenic symptoms. However, ketanserin had no influence on either the psilocybin-induced slowing of binocular rivalry or the drug's "negative-type symptoms" associated with reduced arousal and vigilance.
  
  CONCLUSIONS: Together, these findings link changes in binocular rivalry switching rate to subjective levels of arousal and attention. In addition, it suggests that psilocybin's effect on binocular rivalry is unlikely to be mediated by the 5-HT2A receptor.

  
  
• The 5-HT2A/1A Agonist Psilocybin Disrupts Modal Object Completion Associated with Visual Hallucinations (Kometer et al., 2011)
  
  Lainaus

  Background: Recent findings suggest that the serotonergic system and particularly the 5-HT2A/1A receptors are implicated in visual processing and possibly the pathophysiology of visual disturbances including hallucinations in schizophrenia and Parkinson's disease.
  
  Methods: To investigate the role of 5-HT2A/1A receptors in visual processing the effect of the hallucinogenic 5-HT2A/1A agonist psilocybin (125 and 250 μg/kg vs. placebo) on the spatiotemporal dynamics of modal object completion was assessed in normal volunteers (n = 17) using visual evoked potential recordings in conjunction with topographic-mapping and source analysis. These effects were then considered in relation to the subjective intensity of psilocybin-induced visual hallucinations quantified by psychometric measurement.
  
  Results: Psilocybin dose-dependently decreased the N170 and, in contrast, slightly enhanced the P1 component selectively over occipital electrode sites. The decrease of the N170 was most apparent during the processing of incomplete object figures. Moreover, during the time period of the N170, the overall reduction of the activation in the right extrastriate and posterior parietal areas correlated positively with the intensity of visual hallucinations.
  
  Conclusions: These results suggest a central role of the 5-HT2A/1A-receptors in the modulation of visual processing. Specifically, a reduced N170 component was identified as potentially reflecting a key process of 5-HT2A/1A receptor–mediated visual hallucinations and aberrant modal object completion potential.

  
  
• The Occurrence of Psilocybin and Psilocin in Finnish Fungi (Ohenoja et al., 1987)
  
  Lainaus

  The use of hallucinogenic fungi containing psilocybin and or psilocin has, during the past few decades, spread from Central America to the whole western world. Psilocybin (4-phosphoryloxy- N, N-dimethyltryptamine) and psilocin (4-hydroxy-N,N-dimethyltryptamine) were first isolated from Psilocybe mexicana but have later been reported from more than 30 species of the genus and from several species of other genera. In the Scandinavian countries, the most common psilocybin-containing fungus is Psilocybe semilancuta; in all, about ten active species have been reported from Norway and Denmark. In this study, a variety of Finnish fungi were screened for their psilocybin and psilocin content using two methods of hplc.

  
  
• Timothy Leary, Richard Alpert (Ram Dass) and the changing definition of psilocybin (Warka & Galliherb, 2010)
  
  Lainaus

  Background: This research focuses on the events leading to the 1968 U.S. federal prohibition of psilocybin. It is a study of duelling moral entrepreneurs—Timothy Leary and Richard Alpert vs. the Harvard University Administration. The goal is to show how the primary active compound in an ostensibly harmless fungus (the psilocybin mushroom) became controversial in less than a decade.
  
  Methods: We used books, newspapers, magazine articles and previously unpublished materials (including documents from the Harvard Archives) to analyze Leary and Alpert's lives and careers through the early 1970s.
  
  Results: The prohibition of psilocybin in the U.S. was largely a product of Leary and Alpert's involvement in the “Harvard drug scandal” and their transformation from Harvard professors to countercultural icons. They tested the substance on a variety of human subjects and in doing so piqued the interest of Harvard undergraduates while drawing condemnation from other faculty and Harvard administrators. This case is theoretically interesting because unlike most illegal drugs, psilocybin was never linked to a threatening minority group, but to some of the nation's most privileged youth.
  
  Conclusion: The Harvard administrators were not really moral entrepreneurs but Leary and Alpert clearly were. Although they were far from being prohibitionists, they were self-righteous crusaders on different but equally holy missions for the good of young and minority Americans. Ironically, due to their successes the possession of psilocybin was criminalized under United States federal law in 1968 (Pub. L. No. 90-639, Stat. 1361 1968 and Boire, 2002). This case study demonstrates that crusaders can be successful in changing culture even when laws are passed in futile attempts to control their behaviour, just as Leary predicted.

  
  
• Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects (Griffiths et al., 2011)
  
  Lainaus

  RATIONALE: This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior.
  
  OBJECTIVES: This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions.
  
  METHODS: Participants were 18 adults (17 hallucinogen-naïve). Five 8-h sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up.
  
  RESULTS: Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects.
  
  CONCLUSIONS: Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.

  
  
• A Prehistoric Mural in Spain Depicting Neurotropic Psilocybe Mushrooms (Akers et al., 2011)
  
  Lainaus

  The Selva Pascuala mural, a work of post-Paleolithic rock art in Spain, contains fungoid figures herein hypothesized to depict neurotropic fungi, especially Psilocybe hispanica, a species that occurs in a neighboring region. This hypothesis is based on features of these figures related to fungal morphology, along with ethnographic analogy, and shamanistic explanations of rock art. If correct, this interpretation would support inference of prehistoric utilization of this fungus in the region. The mural represents the first direct evidence for possible ritual use of Psilocybe in prehistoric Europe.

  
  
• A worldwide geographical distribution of the neurotropic fungi, an analysis and discussion (Guzman, Allen & Gartz, 1998)
  
  Lainaus

  In this paper, the world distribution of 216 known species of neurotropic fungi is discussed. The neurotropic fungi considered are divided into the following four groups: 1) species with psilocybin and related indoles, or those likely to contain these substances, 2) species with ibotenic acid, 3) ergot fungi, and 4) species used as sacred fungi for which no reliable chemical studies have been found. In the first group are Psilocybe (116 species), Gymnopilus (14 species), Panaeolus (13 species), Copelandia (12 species), Hypholoma (6 species), Pluteus (6 species), Inocybe (6 species), Conocybe (4 species), Panaeolina (4 species), Gerronema (2 species) and Agrocybe, Galerina and Mycena (each with one species), although in several species of this group, mainly in the Panaeoloideous fungi, there are no known chemical studies. In the second group are Amanita muscaria, A. pantherina and A. regalis; in the third group are Claviceps purpurea and allies: 5 species of Claviceps and 2 of Cordyceps; in the fourth group are bolets (two genera with 8 species), Russula (6 species), and 6 species of gasteromycetes (Lycoperdales y Phallales) in 3 genera. Concerning the distribution of Psilocybe, the majority of the species are found in or near the Austral hemisphere, mainly in the subtropical humid forests. Within these forests reside the most most well documented ethnic groups that use neurotropic fungi, such as the native peoples of Mexico and New Guinea. Mexico has the highest number of neurotropic species of fungi, with 76 species, of which 44 belong to Psilocybe (39 % of the world). More than 450 bibliographic references were considered.

  
  
• Biotransformation of Tryptamine Derivatives in Mycelial Cultures of Psilocybe (Gartz, 1988)
  
  Lainaus

  Mycelial cultures of Psilocybe cubensis capable of forming psilocybin and psilocin de novo display a high capacity for hydroxylation of tryptamine derivatives at the 4-position. A specific biotransformation of added synthetic N,N-diethyl-tryptamine was found. Thus high amounts of 4-hydroxy-N,N-diethyltryptamine (up to 3.3%) and a minor quantity of 4-phosphoryloxy-N,N-diethyltryptamine (0.01-0.8%) were isolated from fruiting bodies of Psilocybe cubensis in corresponding experiments. This is the first example of a directed biosynthesis of tryptamine substances by fungi. An effective biotransformation of N-methyltryptamine was also demonstrated with surface cultures of Psilocybe semilanceata. Baeocystin, a possible natural precursor of psilocybin, was detected and quantified in the biomasses. No alkaloids could be found in the culture medium.

  
  
• Ethnobotany of Psilocybin Mushrooms, especially Psilocybe cubensis (Badham, 1983)
  
  Lainaus

  Mushrooms containing psilocybin have been used for millennia in primative societies for religious/medical purposes. However, today these fungi are used in Western countries primarily as a form of recreation. Although this use does not seem to be causing significant health problems, more study is needed to evaluate the significance of this phenomenon. Essentially all the ethnobotanical use of Psilocybe cubensis (Earle.) Sing. rests on the fact that it contains the compounds psilocybin and psilocin, both of which are hallucinogenic. The most complete interdisciplinary study of this and other “psilocybin” mushrooms is that of Heim and Wasson (1958). Singer (1958), Singer and Smith (1958), Pollock (1975, 1976), Ott (1976), Lincoff and Mitchel(1977), Ott and Bigwood (1978), Rumack and Salzman (1978), Schultes and Hofmann (1980) and Stamets (1978) have also published works on various aspects of hallucinogenic fungi. Because Psilocybe cubensis grows commonly in the southeastern United States and is easily cultivated (Stamets, 1978), it is probably the most commonly eaten hallucinogenic mushroom in this area today. The unauthorized possession, sale, or use of psilocybin or psilocin is a crime in the United States (Public Law 91-513) although few, if any, people have been convicted of possession of mushrooms. The purpose of this paper is to review the literature of man’s past and present use of psilocybin mushrooms, especially P. cubensis.

  
  
• Further investigations on psychoactive mushrooms of the genera Psilocybe, Gymnopilus and Conocybe (Gartz, 1991)
  
  Lainaus

  The analysis of three bluing species of the genera Psilocybe, Gymnopilus and Conocybe from Germany revealed psilocybin and baeocystin and in some cases psilocin as well. The content of the alkaloids in cultured basidiocarps of Psilocybe semilanceata and Gymnopilus purpuratus was in the same order of magnitude as that found in naturally grown mushrooms. For the first time, the psilocybin containing non-bluing mycelium of Conocybe cyanopus could be cultivated.

  
  
• Tryptamines as Ligands and Modulators of the Serotonin 5-HT2A Receptor and the Isolation of Aeruginascin from the Hallucinogenic Mushroom Inocybe aeruginascens (Jensen, 2004)
  
  Lainaus

  Aeruginascin is a natural product from the hallucinogenic mushroom Inocybe aeruginascens. This compound was isolated and identified as 4-phosphoryloxy-N,N,N-trimethyltryptamine. Aeruginascin is the quaternary trimethylammonium analog of the hallucinogenic compound psilocybin. Synthetic aeruginascin was identical in all aspects to the isolated sample. Additionally, the mushroom alkaloids norbaeocystin and baeocystin were synthesized and a new synthetic approach to 4‑hydroxy-tryptamines was investigated.

  
  
• The neurobiology of psychedelic drugs implications for the treatment of mood disorders (Vollenweider & Kometer, 2011)
  
  Lainaus

  After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.

  
  

• Broadband Cortical Desynchronization Underlies the Human Psychedelic State (Muthukumaraswamy et al., 2013)
  
  
  Lainaus

  Psychedelic drugs produce profound changes in consciousness, but the underlying neurobiological mechanisms for this remain unclear. Spontaneous and induced oscillatory activity was recorded in healthy human participants with magnetoencephalography after intravenous infusion of psilocybin—prodrug of the nonselective serotonin 2A receptor agonist and classic psychedelic psilocin. Psilocybin reduced spontaneous cortical oscillatory power from 1 to 50 Hz in posterior association cortices, and from 8 to 100 Hz in frontal association cortices. Large decreases in oscillatory power were seen in areas of the default-mode network. Independent component analysis was used to identify a number of resting-state networks, and activity in these was similarly decreased after psilocybin. Psilocybin had no effect on low-level visually induced and motor-induced gamma-band oscillations, suggesting that some basic elements of oscillatory brain activity are relatively preserved during the psychedelic experience. Dynamic causal modeling revealed that posterior cingulate cortex desynchronization can be explained by increased excitability of deep-layer pyramidal neurons, which are known to be rich in 5-HT2A receptors. These findings suggest that the subjective effects of psychedelics result from a desynchronization of ongoing oscillatory rhythms in the cortex, likely triggered by 5-HT2A receptor-mediated excitation of deep pyramidal cells.

• PSILOCYBIN – summary of knowledge and new perspectives (Tylš et al., 2013)
  
  Lainaus

  Psilocybin, a psychoactive alkaloid contained in hallucinogenic mushrooms, is nowadays given a lot of attention in the scientific community as a research tool for modeling psychosis as well as due to its potential therapeutic effects. However, it is also a very popular and frequently abused natural hallucinogen. This review summarizes all the past and recent knowledge on psilocybin. It briefly deals with its history, discusses the pharmacokinetics and pharmacodynamics, and compares its action in humans and animals. It attempts to describe the mechanism of psychedelic effects and objectify its action using modern imaging and psychometric methods. Finally, it describes its therapeutic and abuse potential.
  

  
  

• The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs (Carhart-Harris et al., 2014)
  
  Lainaus

  Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is [also] proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.
  

New study: Magic Mushrooms Repair Brain Damage From Extreme Trauma

• Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning (Sanchez‑Ramos et al., 2013)
  
  Lainaus

  Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear conditioning. PSOP, the 5-HT2A agonist 25I-NBMeO and the 5-HT2A/C antagonist ketanserin were administered via an acute intraperitoneal injection to mice. Trace fear conditioning was measured as the amount of time spent immobile in the presence of the conditioned stimulus (CS, auditory tone), trace (silent interval) and post-trace interval over 10 trials. Extinction was determined by the number of trials required to resume mobility during CS, trace and post-trace when the shock was not delivered. Neurogenesis was determined by unbiased counts of cells in the dentate gyrus of the HPC birth-dated with BrdU co-expressing a neuronal marker. Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice. Injection of PSOP, 25I-NBMeO or ketanserin resulted in significant dose-dependent decreases in number of newborn neurons in hippocampus. At the low doses of PSOP that enhanced extinction, neurogenesis was not decreased, but rather tended toward an increase. Extinction of "fear conditioning" may be mediated by actions of the drugs at sites other than hippocampus such as the amygdala, which is known to mediate the perception of fear. Another caveat is that PSOP is not purely selective for 5-HT2A receptors. PSOP facilitates extinction of the classically conditioned fear response, and this, and similar agents, should be explored as potential treatments for post-traumatic stress disorder and related conditions.
  

  Lainaus

  The data reported demonstrate that the administration of PSOP produced a biphasic response in hippocampal neurogenesis; a low dose (0.1 mg/kg) resulted in a trend toward increased neurogenesis, whereas the high dose of PSOP significantly decreased the formation of new neurons measured 2 weeks after drug exposure. In addition, all doses of the potent 5-HT2A receptor agonist 25I-NBMeO and the 5-HT2A/C receptor antagonist ketanserin decreased hippocampal neurogenesis.

• Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles (Baumeister et al., 2014)
  
  Lainaus

  Hallucinogens have been part of spiritual practice for millennia, but controversy surrounding their mind-manifesting effects led to their proscription by the mid-20th century, largely without evidence of harm or toxicity and despite nascent data suggesting therapeutic utility in treating depressive illnesses. This review explores their pharmacodynamic actions and the current limited data on their clinic effectiveness. These drugs appear to exert their psychedelic effects through their agonist or partial agonist activity at the serotonergic 5-HT2A receptor, though they also have affinity for other metabotropic serotonin receptors. Hallucinogen binding affects a wide range of intracellular signalling pathways, the precise nature of which remains incompletely understood. They alter the serotonergic tone of brainstem raphe nuclei that project through the brain; they interact with receptors in the prefrontal cortex altering connectivity patterns and intracellular functioning; and they disrupt inhibitory control of sensory input via the thalamus to the cortex. The serotonergic system has long been implicated in anxiety and depressive disorders, and is a major target of most existing antidepressants. Classical hallucinogens alter the functioning of this system, but not in the same way current medications do: whilst there are identified receptors and neurotransmitter pathways through which hallucinogens could therein produce therapeutic effects, the neurobiology of this remains speculative at this time. There is currently an extremely limited but growing literature on hallucinogen safety and clinical application. The drugs appear well tolerated by healthy controls and clinical populations, and the rapid tolerance to repeated administration might reduce the possibility of dependency. Clinical trials reported over the past decade have generally shown positive therapeutic potential, but they are notably few in number. Legislative policy has had a freezing effect on evaluation of these compounds, a better understanding of which might improve our knowledge of the processes involved in consciousness, the neuropathology of depression, and potentially open up new pharmacological therapies.

• Evolution of the Toxins Muscarine and Psilocybin in a Family of Mushroom-Forming Fungi (Kosentka et al., 2013)
  
  Lainaus

  Mushroom-forming fungi produce a wide array of toxic alkaloids. However, evolutionary analyses aimed at exploring the evolution of muscarine, a toxin that stimulates the parasympathetic nervous system, and psilocybin, a hallucinogen, have never been performed. The known taxonomic distribution of muscarine within the Inocybaceae is limited, based only on assays of species from temperate regions of the northern hemisphere. Here, we present a review of muscarine and psilocybin assays performed on species of Inocybaceae during the last fifty years. To supplement these results, we used liquid chromatography–tandem mass spectrometry (LC–MS/MS) to determine whether muscarine was present in 30 new samples of Inocybaceae, the majority of which have not been previously assayed or that originated from either the tropics or temperate regions of the southern hemisphere. Our main objective is to test the hypothesis that the presence of muscarine is a shared ancestral feature of the Inocybaceae. In addition, we also test whether species of Inocyabceae that produce psilocybin are monophyletic. Our findings suggest otherwise. Muscarine has evolved independently on several occasions, together with several losses. We also detect at least two independent transitions of muscarine-free lineages to psilocybin-producing states. Although not ancestral for the family as a whole, muscarine is a shared derived trait for an inclusive clade containing three of the seven major lineages of Inocybaceae (the Inocybe, Nothocybe, and Pseudosperma clades), the common ancestor of which may have evolved ca. 60 million years ago. Thus, muscarine represents a conserved trait followed by several recent losses. Transitions to psilocybin from muscarine-producing ancestors occurred more recently between 10–20 million years ago after muscarine loss in two separate lineages. Statistical analyses firmly reject a single origin of muscarine-producing taxa.

• Phylogenetic and chemical studies in the potential psychotropic species complex of Psilocybe atrobrunnea with taxonomic and nomenclatural notes (Borovička et al., 2015)
  
  Lainaus

  Five Psilocybe species with unresolved systematic position (P. atrobrunnea, P. laetissima, P. medullosa, P. pelliculosa, and P. silvatica)  were investigated using four molecular markers (EF1-α, ITS, LSU, and  IGS). Phylogenetic analysis revealed that with the exception of P. laetissima, which is now rightfully classified in the genus Leratiomyces, all investigated species belong to Psilocybe sect. Psilocybe. For the first time, psychotropic compounds psilocin and psilocybin were detected in P. medullosa using gas chromatography-mass spectrometry. On the contrary, neither psilocin, nor psilocybin was detected in P. atrobrunnea  and negative results were also obtained from mycelia grown in vitro on  tryptamine/tryptophan-amended media. These results strongly suggest that  biosynthesis of these alkaloids was lost in P. atrobrunnea. With the exception of minor differences detected in EF1-α marker, all sequences of American and European collections of P. atrobrunnea were identical. On the other hand, a thorough nomenclatural study revealed that the name P. atrobrunnea must be considered dubious; the oldest available candidate name, P. fuscofulva, was therefore adopted. The molecular data suggests that morphologically identical American P. silvatica and European P. medullosa likely represent distinct species; epitypes of both taxa were therefore designated.