Magic Mushrooms Research Articles

P03-21 Magic mushrooms and psilocybin: pharmacokinetics, pharmacodynamics, and clinical applications

P03-21 Magic mushrooms and psilocybin: pharmacokinetics, pharmacodynamics, and clinical applications

SPECIAL ISSUE: Do Biofeedback, Neurofeedback, and Neuromeditation Have a Role in Psychedelic-Assisted Therapies?

SPECIAL ISSUE: Do Biofeedback, Neurofeedback, and Neuromeditation Have a Role in Psychedelic-Assisted Therapies?

Psilocybin and the Meaning Response: Exploring the Healing Process in a Retreat Setting in Jamaica

ABSTRACTIn the past decade, the consumption of psilocybin mushrooms has become a popular therapeutic tool for people looking to deal with mental and emotional health issues. The emerging interest in psilocybin therapy in the global north has led to the development of retreat centers in locations where psilocybin is legal or unregulated. Drawing on ethnographic research at a psilocybin retreat center in Jamaica, this article examines the emotional and somatic reactions attributed to psilocybin that influence the social interactions and the mental and emotional state of the guests at this retreat center. We argue that guests go through a symbolic healing process that involves the construction of a meaning response based on internal and collective experiences of altered consciousness via psilocybin. Additionally, we emphasize how both attending the retreat and the psychedelic experience there can be considered a liminal state that leads to different modes of relation while in Jamaica.

Insights for Modern Applications of Psilocybin Therapy from a Case Study of Traditional Mazatec Medicine

ABSTRACTThe "people of knowledge" of traditional Mazatec medicine have preserved until today the ritual use of psilocybin mushrooms as part of their health care systems. The renewed interest in the effect of psilocybin on human consciousness for both therapeutic and recreational purposes usually obviates the historical and cultural background of indigenous peoples, as well as the legitimation of their practices and knowledge. In this article, through the case study of a foreign person who attended a Mazatec ritual specialist to participate in a ritual night ceremony known as velada, we show the importance of approaching research on psychoactive plants and mushrooms from a transdisciplinary and intercultural perspective, so that we can appreciate the profound complexity of the healing processes that take place in traditional indigenous contexts, as well as the limits of recreational uses or exclusively neopositivist and clinical approaches.

Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study

The use of low sub-perceptual doses of psychedelics (“microdosing”) has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies severely limits our knowledge of microdosing and its effects. Moreover, research conducted in standard laboratory settings could fail to capture the motivation of individuals engaged or planning to engage in microdosing protocols, thus underestimating the likelihood of positive effects on creativity and cognitive function. We recruited 34 individuals starting to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled experimental design, we investigated the acute and short-term effects of 0.5 g of dried mushrooms on subjective experience, behavior, creativity (divergent and convergent thinking), perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, but only for participants who correctly identified their experimental condition. These changes were accompanied by reduced EEG power in the theta band, together with preserved levels of Lempel-Ziv broadband signal complexity. For all other measurements there was no effect of microdosing except for few small changes towards cognitive impairment. According to our findings, low doses of psilocybin mushrooms can result in noticeable subjective effects and altered EEG rhythms, but without evidence to support enhanced well-being, creativity and cognitive function. We conclude that expectation underlies at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.

Magic Mushrooms – an exploratory look at how mental health professionals feel and think about Psilocybin

Psilocybin recently received breakthrough status by the FDA for its use in treatment of depression. We therefore investigated mental health professionals’ (MHPs) opinions on Psilocybin (n = 155). Overall, attitudes were neutral but self-rated knowledge of Psilocybin was low. The term used in the survey, ‘Psilocybin’ or ‘Magic Mushrooms’, did not significantly affect their responses. Some variables (i.e., gender, attitudes towards medical cannabis, and personal history of psychedelic usage) were associated with ratings of Psilocybin. These results provide a baseline of MHPs' thoughts on Psilocybin and what should be considered in the future if it is FDA-approved.

Magic truffle intoxication: A case report

Unusual forms of hallucinogenic mushrooms are emerging, which may delay diagnosis and compromise optimal management. Here, we discuss clinical and biological findings in a case of “magic mushroom” intoxication in a 20-year-old man who was brought to hospital emergency department in a state of euphoria, disorientation, intense visual hallucinations, episodic amnesia and agitation requiring physical restraint. The patient’s family brought intact specimens of the consumed product, without any health professional being able to identify it. Toxicological screening detected psilocin in urine and in the unknown mushrooms, allowing guiding the mushroom identification towards the Psilocybes genus. Ten hours post-ingestion, the patient was discharged asymptomatic. We believe that recognition of the unusual form of hallucinogenic mushroom presented here by emergency physicians might contribute to better diagnosis and subsequent optimal management, especially since hallucinogenic substances are not routinely tested in toxicological analyses.

Genetic Survey of Psilocybe Natural Products.

Psilocybe magic mushrooms are best known for their main natural product, psilocybin, and its dephosphorylated congener, the psychedelic metabolite psilocin. Beyond tryptamines, the secondary metabolome of these fungi is poorly understood. The genomes of five species (P. azurescens, P. cubensis, P. cyanescens, P. mexicana, and P. serbica) were browsed to understand more profoundly common and species‐specific metabolic capacities. The genomic analyses revealed a much greater and yet unexplored metabolic diversity than evident from parallel chemical analyses. P. cyanescens and P. mexicana were identified as aeruginascin producers. Lumichrome and verpacamide A were also detected as Psilocybe metabolites. The observations concerning the potential secondary metabolome of this fungal genus support pharmacological and toxicological efforts to find a rational basis for yet elusive phenomena, such as paralytic effects, attributed to consumption of some magic mushrooms.

Natural language signatures of psilocybin microdosing.

Serotonergic psychedelics are being studied as novel treatments for mental health disorders and as facilitators of improved well-being, mental function, and creativity. Recent studies have found mixed results concerning the effects of low doses of psychedelics ("microdosing") on these domains. However, microdosing is generally investigated using instruments designed to assess larger doses of psychedelics, which might lack sensitivity and specificity for this purpose. Determine whether unconstrained speech contains signatures capable of identifying the acute effects of psilocybin microdoses. Natural speech under psilocybin microdoses (0.5g of psilocybin mushrooms) was acquired from thirty-four healthy adult volunteers (11 females: 32.09 ± 3.53years; 23 males: 30.87 ± 4.64years) following a double-blind and placebo-controlled experimental design with two measurement weeks per participant. On Wednesdays and Fridays of each week, participants consumed either the active dose (psilocybin) or the placebo (edible mushrooms). Features of interest were defined based on variables known to be affected by higher doses: verbosity, semantic variability, and sentiment scores. Machine learning models were used to discriminate between conditions. Classifiers were trained and tested using stratified cross-validation to compute the AUC and p-values. Except for semantic variability, these metrics presented significant differences between a typical active microdose and the inactive placebo condition. Machine learning classifiers were capable of distinguishing between conditions with high accuracy (AUC [Formula: see text] 0.8). These results constitute first evidence that low doses of serotonergic psychedelics can be identified from unconstrained natural speech, with potential for widely applicable, affordable, and ecologically valid monitoring of microdosing schedules.

Psychedelic Psychiatry

The last decade has seen a remarkable resurgence of interest in psychedelic drugs such as psilocybin (from magic mushrooms) LSD and DMT (dimethyl tryptamine – the active ingredient of ayahuasca). This has been driven by the discovery that these psychedelics all act agonists of 5-HT2A receptors. Human imaging studies have revealed this action leads to profound alterations in brain measures of activity particularly in terms of increased entropy of EEG MEG and fMRI signals and reduced within-network, but increased between-network, connectivity. In addition they all can increase synaptic growth and brain plasticity. These findings not only explain the subjective nature of the psychedelic experience but also have implications for the treatment of internalising disorders such as depression addiction anorexia and OCD that are characterised by increased within network connectivity especially of the default mode network. Subsequent trials, particularly of psilocybin, in these disorders has revealed significant clinical benefits from even just a single administration. A number of companies have now been set up to extend these discoveries with regulatory-level trials that could result in market authorisations within a few years. My talk will explore these brain mechanisms and clinical data and discuss the potential place of psychedelic medicine in the future of psychiatry.DisclosureI am an advisor to Compass pathways and Beckley Psytec two companies that are developing psychedelics for depression and other psychiatric indications. Several members of my research group receive support from these companies and also from Small Pharma.

Association of Psilocybin Use in Adolescents with Major Depressive Episode

IntroductionPsilocybin is a psychedelic drug found in mushrooms, often referred to as magic mushrooms due to its visual and auditory hallucinations effects upon ingestion. It is a Schedule I drug per DEA, and the FDA has not approved psilocybin for medicinal purposes. However, recent studies have shown promising therapeutic use to treat depression.ObjectivesTo identify current use, prevalence, and its association with depression in adolescents.MethodsThe National Survey on Drug Use and Health survey data from 2008-18 studied adolescent data (12-17 years), who responded, “ever used psilocybin (mushrooms)” and “lifetime major depressive episode (MDE).” The association between the psilocybin use and MDE status was analyzed in SAS 9.4 through multivariate logistic regression for odds ratio (OR) and 95% confidence interval (CI).ResultsA total of 172745 adolescents were included in this study, of which 2469 ever used psilocybin in their lifetime, and 170276 responded no lifetime use. The psilocybin ever lifetime users were 17 years old (42%vs.17%,p<0.001), male (60%vs.51%,p<0.001), and non-Hispanic White (71%vs.55%,p<0.001) in comparison to non-users. Among psilocybin user group, 31% of respondents had lifetime MDE, compared to 16% of the lifetime psilocybin non-user group participants (p<0.001). The odds of association of psilocybin use among participants with MDE were 2.17 times compared to those without MDE (CI: 1.93-2.44,p<0.001).ConclusionsWe identified a significant association between psilocybin use and MDE among adolescents, which raises public health concerns about its illegal use, abuse, and toxicity potential. Future clinical studies should assess its clinical safety, efficacy, and addictive properties.DisclosureNo significant relationships.

New Paradigms of Old Psychedelics in Schizophrenia.

Psychedelics such as lysergic acid diethylamide (LSD), psilocybin (magic mushrooms), and mescaline exhibit intense effects on the human brain and behaviour. In recent years, there has been a surge in studies investigating these drugs because clinical studies have shown that these once banned drugs are well tolerated and efficacious in medically supervised low doses called microdosing. Psychedelics have demonstrated efficacy in treating neuropsychiatric maladies such as difficult to treat anxiety, depression, mood disorders, obsessive compulsive disorders, suicidal ideation, posttraumatic stress disorder, and also in treating substance use disorders. The primary mode of action of psychedelics is activation of serotonin 5-HT2A receptors affecting cognition and brain connectivity through the modulation of several downstream signalling pathways via complex molecular mechanisms. Some atypical antipsychotic drugs (APDs) primarily exhibit pharmacological actions through 5-HT2A receptors, which are also the target of psychedelic drugs. Psychedelic drugs including the newer second generation along with the glutamatergic APDs are thought to mediate pharmacological actions through a common pathway, i.e., a complex serotonin–glutamate receptor interaction in cortical neurons of pyramidal origin. Furthermore, psychedelic drugs have been reported to act via a complex interplay between 5HT2A, mGlu2/3, and NMDA receptors to mediate neurobehavioral and pharmacological actions. Findings from recent studies have suggested that serotoninergic and glutamatergic neurotransmissions are very closely connected in producing pharmacological responses to psychedelics and antipsychotic medication. Emerging hypotheses suggest that psychedelics work through brain resetting mechanisms. Hence, there is a need to dig deeply into psychedelic neurobiology to uncover how psychedelics could best be used as scientific tools to benefit psychiatric disorders including schizophrenia.

Alternative Options for Complex, Recurrent Pain States Using Cannabinoids, Psilocybin, and Ketamine: A Narrative Review of Clinical Evidence.

With emerging information about the potential for morbidity and reduced life expectancy with long-term use of opioids, it is logical to evaluate nonopioid analgesic treatments to manage pain states. Combinations of drugs can provide additive and/or synergistic effects that can benefit the management of pain states. In this regard, tetrahydrocannabinol (THC) and cannabidiol (CBD) modulate nociceptive signals and have been studied for chronic pain treatment. Psilocybin, commonly known as “magic mushrooms”, works at the serotonin receptor, 5-HT2A. Psilocybin has been found in current studies to help with migraines since it has a tryptamine structure and works similarly to triptans. Psilocybin also has the potential for use in chronic pain treatment. However, the studies that have looked at alternative plant-based medications such as THC, CBD, and psilocybin have been small in terms of their sample size and may not consider the demographic or genetic differences in the population because of their small sample sizes. At present, it is unclear whether the effects reported in these studies translate to the general population or even are significant. In summary, additional studies are warranted to evaluate chronic pain management with alternative and combinations of medications in the treatment of chronic pain.

Assessment of Bioactivity-Modulating Pseudo-Ring Formation in Psilocin and Related Tryptamines.

Psilocybin (1) is the major alkaloid found in psychedelic mushrooms and acts as a prodrug to psilocin (2, 4‐hydroxy‐N,N‐dimethyltryptamine), a potent psychedelic that exerts remarkable alteration of human consciousness. In contrast, the positional isomer bufotenin (7, 5‐hydroxy‐N,N‐dimethyltryptamine) differs significantly in its reported pharmacology. A series of experiments was designed to explore chemical differences between 2 and 7 and specifically to test the hypothesis that the C‐4 hydroxy group of 2 significantly influences the observed physical and chemical properties through pseudo‐ring formation via an intramolecular hydrogen bond (IMHB). NMR spectroscopy, accompanied by quantum chemical calculations, was employed to compare hydrogen bond behavior in 4‐ and 5‐hydroxylated tryptamines. The results provide evidence for a pseudo‐ring in 2 and that sidechain/hydroxyl interactions in 4‐hydroxytryptamines influence their oxidation kinetics. We conclude that the propensity to form IMHBs leads to a higher number of uncharged species that easily cross the blood‐brain barrier, compared to 7 and other 5‐hydroxytryptamines, which cannot form IMHBs. Our work helps understand a fundamental aspect of the pharmacology of 2 and should support efforts to introduce it (via the prodrug 1) as an urgently needed therapeutic against major depressive disorder.

Magic mushroom extracts in lipid membranes

The active hallucinogen of magic mushrooms, psilocin, is being repurposed to treat nicotine addiction and treatment-resistant depression. Psilocin belongs to the tryptamine class of psychedelic compounds which include the hormone serotonin. It is believed that psilocin exerts its effect by binding to the serotonin 5-HT2A receptor. However, recent in-vivo evidence suggests that psilocin may employ a different mechanism to exert its effects. Membrane-mediated receptor desensitization of neurotransmitter receptors is one such mechanism. We compare the impact of the neutral and charged versions of psilocin and serotonin on the properties of zwitterionic and anionic lipid membranes using molecular dynamics simulations and calorimetry. Both compounds partition to the lipid interface and induce membrane thinning. The tertiary amine in psilocin, as opposed to the primary amine in serotonin, limits psilocin's impact on the membrane although more psilocin partitions into the membrane than serotonin. Calorimetry corroborates that both compounds induce a classical melting point depression like anesthetics do. Our results also lend support to a membrane-mediated receptor-binding mechanism for both psilocin and serotonin and provide physical insights into subtle chemical changes that can alter the membrane-binding of psychedelic compounds.

Combining FTIR-ATR and OPLS-DA methods for magic mushrooms discrimination

Magic mushrooms are naturally occurring fungi that are considered hallucinogenic drugs because they contain psilocybin and psilocin. These substances are controlled in almost every country in the world, so the use, possession, cultivation, and sale of magic mushrooms are prohibited in whole or in part. Despite this, the abuse of magic mushrooms continues and can put at risk the life of the consumer and society in general if the consumer behaves in an unsafe manner.The number of mushroom species is very high, making it difficult to correctly identify them based only on physical and morphological characteristics. Therefore, there is a need to develop non-destructive mushrooms analysis methods that have less response time and higher discrimination ability. The present work used Attenuated Total Reflectance Fourier Transform Infrared (FTIR-ATR) Spectroscopy to study 64 mushroom samples from different genera including hallucinogenic, edible, and toxic species. In addition, this study used Orthogonal Partial Least Squares - Discriminant Analysis (OPLS-DA), using SIMCA chemometric software to analyse the obtained infrared (IR) spectra. The main molecular vibrations of the components of the fungus were successfully identified by IR spectroscopy. Although the specific bands corresponding to psilocybin or psilocin could not be assigned in the spectra, the regression method was able to discriminate the various species. Hallucinogenic mushrooms were well separated from other species, allowing the method to be used as an initial screening technique to determine whether or not the seized mushrooms are of forensic interest.

Adverse experiences resulting in emergency medical treatment seeking following the use of magic mushrooms.

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.

Magic Mushroom Use: A Qualitative Interview Study of Post-Trip Impacts and Strategies for Optimizing Experiences

ABSTRACT The field of psychedelic research is undergoing a revival, yet research focused on non-clinical psychedelic use remains relatively limited. The current qualitative study sheds light on how people use magic mushrooms, what they perceive the effects of such use to be, and the meanings that users attach to their magic mushroom experiences. To be eligible to participate in the study, participants were required to be young adults who had used magic mushrooms within the past three months and residents of Victoria, Canada. Semi-structured, one-on-one in-person interviews regarding magic mushroom use habits, culture, knowledge and other factors were conducted with each participant and subsequently analyzed thematically. Participants associated magic mushroom use with lasting impacts on their lives including transformation and learning experiences. Additionally, participants described strategies to optimize their magic mushroom experiences, including engaging in research regarding magic mushrooms as well as making use of peer supports. Furthermore, aspects of magic mushroom experiences conceptualized as harmful in previous studies were described by participants as associated with learning experiences and few harms. Participants’ perceived positive outcomes and relatively low risk profile warrants further research to inform how magic mushroom users can maximize potential positive outcomes and also minimize harms.

Ministry of the Mushroom

Recently there has been a surge of renewed interest in the psychedelic compound psilocybin. In particular, psilocybin is being studied in clinical settings as a potential breakthrough treatment for depression. Alongside this growing therapeutic interest, there has been a rise in the religious use of psilocybin, as evidenced by the creation of a number of psilocybin mushroom churches in the United States. While the dominant popular discourse surrounding psilocybin is currently clinical, psilocybin churches offer an alternative form of meaning making regarding the psychedelic experience. Specifically, this article argues that psilocybin churches enable their followers to participate in a dynamic social process of “sacred sensemaking,” whereby psilocybin mushrooms are considered to be a sacrament, church members follow a ritual-based psychopharmacological practice, and the psychedelic experience is interpreted in terms of a direct encounter with the divine. Different psilocybin churches have unique approaches, ritual practices and cosmologies, nonetheless this article suggests that they may be united by this common process of sacred sensemaking.

The mushroom, the frog, and the rainbow of desire: A participatory-psychedelic spiritual emergence.

This article will explore a spiritual emergency through a myth or fairy tale that emerged at the same time I had a frightening brush with death. Two days before the accident I had ingested psilocybin mushrooms. Michael Washburn, among other transpersonal theorists, will be used to interpret, amplify and re-frame this potential ‘psychotic episode’ with ‘borderline features’ into something more, perhaps, on the threshold of a shamanic initiation in a liminal state. The mythic sequence in my story anticipates the death-rebirth (perinatal pattern) and evolution of consciousness in the LSD research of Stanislav Grof; an evolution given epic participatory elucidation by Richard Tarnas; and an evolution consummated in the erotic desire for nature found in the panpsychism of Freya Mathews.