Matrix-assisted laser-desorption/ionization-mass spectrometric imaging of psilocybin and its analogues in psychedelic mushrooms using a cesium chloride-coated target plate.

Fungi with hallucinogenic properties and neurotoxicity have been listed as prohibited drugs in recent years, but there is a lack of in situ quantification of psilocybin and analogues in these samples to avoid the decomposition of these psychoactive tryptamines in time-consuming sample preparation. In this study, matrix-assisted laser-desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FT ICR) mass spectrometric imaging (MSI) was used to analyze the distribution of psilocybin and its analogues in hallucinogenic Psilocybe mushrooms. A cesium chloride (CsCl)-coated target plate was prepared to improve the detection sensitivity and reduce the interference of other compounds or decomposition products with very similar m/z values in MALDI-FT ICR MS analysis. Psilocybin and other tryptamines with structurally similar compounds, including psilocin, baeocystin, tryptophan, tryptamine, and aeruginascin, were identified and imaged in the psilocybe tissue section; the semiquantitative analysis of the distribution of psilocybin was also investigated using a homemade 75-well CsCl-coated plate; and the target plate can be placed on the mass spectrometry target carrier along with the indium-tin oxide (ITO) conductive slide, which can simultaneously carry out matrix vapor deposition, thus ensuring the parallelism between the standards and samples in the pretreatment experiment and MSI. The contents of psilocybin and its analogues in the psilocybe tissue section can be evaluated from the color changes corresponding to different concentration standard curves. Furthermore, a comprehensive comparison between MALDI-FT ICR MS and ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-Q/TOF MS) analysis was performed for quantification and validation. This study reduces the decomposition in time-consuming sample pretreatment and provides a powerful tool for drug abuse control and forensic analysis.

The dilemma of new psychoactive substances: A growing threat.

New psychoactive substances (NPS) pose a major public threat and are a growing problem worldwide. They were designed to replace banned or controlled drugs while escaping quality control measures. Their chemical structure is constantly changed which imposes a major forensic challenge, and makes it difficult for law enforcement measures to track and ban them. Hence, they are called "legal highs" as they replicate illicit drugs whilst remaining legal. Low cost, easy accessibility and less legal liability are the main factors that contribute to the popularity of NPS among the public. This is particularly with the lack of knowledge of the health risks and harms associated with NPS not only amongst the public, but healthcare professionals as well, which further constitutes a challenge for preventative and treatment measures. Further medico-legal investigation, extensive laboratory and non-laboratory analyses, and advanced forensic measures are necessary to identify, schedule and control new psychoactive substances. Besides, additional efforts are required to educate the public and increase their awareness regarding NPS and their potential harms.

Gs signaling pathway distinguishes hallucinogenic and nonhallucinogenic 5-HT2AR agonists induced head twitch response in mice.

5- HT2A receptor is a member of the family A G-protein-coupled receptor. It is involved in many psychiatric disorders, such as depression, addiction and Parkinson's disease. 5-HT2AR targeted drugs play an important role in regulating cognition, memory, emotion and other physiological function by coupling G proteins, and their most notable function is stimulating the serotonergic hallucination. However, not all 5-HT2AR agonists exhibit hallucinogenic activity, such as lisuride. Molecular mechanisms of these different effects are not well illustrated. This study suggested that 5-HT2AR coupled both Gs and Gq protein under hallucinogenic agonists DOM and 25CN-NBOH stimulation, but nonhallucinogenic agonist lisuride and TBG only activates Gq signaling. Moreover, in head twitch response (HTR) model, we found that cAMP analogs 8-Bromo-cAMP and PDE4 inhibitor Rolipram could increase HTR, while Gs protein inhibitor Melittin could reduce HTR. Collectively, these results revealed that Gs signaling is a key signaling pathway that may distinguish hallucinogenic agonists and nonhallucinogenic agonists.

Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids.

Since not only psilocybin (PSB) but also PSB-containing mushrooms are used for psychedelic therapy and microdosing, it is necessary to know their concentration variability in wild-grown mushrooms. This article aimed to determine the PSB, psilocin (PS), baeocystin (BA), norbaeocystin (NB), and aeruginascin (AE) concentrations in a large sample set of mushrooms belonging to genera previously reported to contain psychotropic tryptamines. Ultra-high performance liquid chromatography coupled with tandem mass spectrometry was used to quantify tryptamine alkaloids in the mushroom samples. Most mushroom collections were documented by fungarium specimens and/or ITS rDNA/LSU/EF1-α sequencing. Concentrations of five tryptamine alkaloids were determined in a large sample set of 226 fruiting bodies of 82 individual collections from seven mushroom genera. For many mushroom species, concentrations of BA, NB, and AE are reported for the first time. The highest PSB/PS concentrations were found in Psilocybe species, but no tryptamines were detected in the P. fuscofulva and P. fimetaria collections. The tryptamine concentrations in mushrooms are extremely variable, representing a problem for mushroom consumers due to the apparent risk of overdose. The varied cocktail of tryptamines in wild mushrooms could influence the medicinal effect compared to therapy with chemically pure PSB, posing a serious problem for data interpretation.

Nanosensor for Sensitive Detection of the New Psychedelic Drug 25I-NBOMe.

This work reports the synthesis, characterization, and sensing behavior of a hybrid nanodevice for the detection of the potent abuse drug 25I-NBOMe. The system is based on mesoporous silica nanoparticles, loaded with a fluorescent dye, functionalized with a serotonin derivative and capped with the 5-HT2A receptor antibody. In the presence of 25I-NBOMe the capping antibody is displaced, leading to pore opening and rhodamine B release. This delivery was ascribed to 5-HT2A receptor antibody detachment from the surface due to its stronger coordination with 25I-NBOMe present in the solution. The prepared nanodevice allowed the sensitive (limit of detection of 0.6 µm) and selective recognition of the 25I-NBOMe drug (cocaine, heroin, mescaline, lysergic acid diethylamide, MDMA, and morphine were unable to induce pore opening and rhodamine B release). This nanodevice acts as a highly sensitive and selective fluorometric probe for the 25I-NBOMe illicit drug in artificial saliva and in sweets.

In vivo production of psilocybin in E. coli.

Psilocybin, the prodrug of the psychoactive molecule psilocin, has demonstrated promising results in clinical trials for the treatment of addiction, depression, and post-traumatic stress disorder. The development of a psilocybin production platform in a highly engineerable microbe could lead to rapid advances towards the bioproduction of psilocybin for use in ongoing clinical trials. Here, we present the development of a modular biosynthetic production platform in the model microbe, Escherichia coli. Efforts to optimize and improve pathway performance using multiple genetic optimization techniques were evaluated, resulting in a 32-fold improvement in psilocybin titer. Further enhancements to this genetically superior strain were achieved through fermentation optimization, ultimately resulting in a fed-batch fermentation study, with a production titer of 1.16 g/L of psilocybin. This is the highest psilocybin titer achieved to date from a recombinant organism and a significant step towards demonstrating the feasibility of industrial production of biologically-derived psilocybin.

Screening of Hallucinogenic Compounds and Genomic Characterisation of 40 Anatolian Salvia Species.

INTRODUCTION: Salvia, an important and widely available member of Lamiaceae family. Although comparative analysis on secondary metabolites in several Salvia species from Turkey has been reported, their hallucinogenic chemicals have not been screened thoroughly. OBJECTIVE: This study provides LC-MS/MS analysis of 40 Salvia species for screening their psychoactive constituents of salvinorin A and salvinorin B. 5S-rRNA gene non-coding region of Salvia plants was sequenced, aligned and compared with that sequence of Salvia divinorum plant. METHODOLOGY: Targeted molecules of salvinorin A and salvinorin B were quantified, using LC-MS/MS, from all aerial parts of 40 Salvia species, collected from different parts of Turkey. Regions of 5S-rRNA gene from different species were amplified by polymerase chain reaction and DNA sequences were aligned with Salvia divinorum DNA sequences. RESULTS: Very few of the Salvia species (S. recognita, S. cryptantha and S. glutinosa) contained relatively high levels of salvinorin A (212.86 ± 20.46 µg/g, 51.50 ± 4.95 µg/g and 38.92 ± 3.74 µg/g, respectively). Salvinorin B was also found in Salvia species of S. potentillifolia, S. adenocaulon and S. cryptantha as 2351.99 ± 232.22 µg/g, 768.78 ± 75.90 µg/g and 402.24 ± 39.71 µg/g, respectively. The sequences of 5S-rRNA gene of 40 different Salvia species were presented and it was found that none of the Salvia species in Turkey had similar DNA sequence to Salvia divinorum plant. CONCLUSION: This is the first report of screening 40 Salvia species in Turkey according to their psychoactive constituents, salvinorin A and salvinorin B and their genomic structures. It is possible that some of these Salvia species may exhibit some psycho activity. Thus, they need to be screened further. Copyright © 2017 John Wiley & Sons, Ltd.

Hallucinogenic drugs in pre-Columbian Mesoamerican cultures.

INTRODUCTION: The American continent is very rich in psychoactive plants and fungi, and many pre-Columbian Mesoamerican cultures used them for magical, therapeutic and religious purposes. OBJECTIVES: The archaeological, ethno-historical and ethnographic evidence of the use of hallucinogenic substances in Mesoamerica is reviewed. RESULTS: Hallucinogenic cactus, plants and mushrooms were used to induce altered states of consciousness in healing rituals and religious ceremonies. The Maya drank balché (a mixture of honey and extracts of Lonchocarpus) in group ceremonies to achieve intoxication. Ritual enemas and other psychoactive substances were also used to induce states of trance. Olmec, Zapotec, Maya and Aztec used peyote, hallucinogenic mushrooms (teonanacatl: Psilocybe spp) and the seeds of ololiuhqui (Turbina corymbosa), that contain mescaline, psilocybin and lysergic acid amide, respectively. The skin of the toad Bufo spp contains bufotoxins with hallucinogenic properties, and was used since the Olmec period. Jimson weed (Datura stramonium), wild tobacco (Nicotiana rustica), water lily (Nymphaea ampla) and Salvia divinorum were used for their psychoactive effects. Mushroom stones dating from 3000 BC have been found in ritual contexts in Mesoamerica. Archaeological evidence of peyote use dates back to over 5000 years. Several chroniclers, mainly Fray Bernardino de Sahagún, described their effects in the sixteenth century. CONCLUSIONS: The use of psychoactive substances was common in pre-Columbian Mesoamerican societies. Today, local shamans and healers still use them in ritual ceremonies in Mesoamerica.

Phylogenetic and chemical studies in the potential psychotropic species complex of Psilocybe atrobrunnea with taxonomic and nomenclatural notes.

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.

Less is more? A review of psilocybin microdosing.

BACKGROUND: The applications of psilocybin, derived from 'magic mushrooms,' are vast, including a burgeoning practice known as microdosing, which refers to the administration of sub-hallucinogenic doses of psychedelic substances to obtain benefits without experiencing significant cognitive and perceptual distortion. However, current research is fairly new with several limitations and gaps that hinder adequate conclusions on its efficacy. AIMS: This semi-structured review aimed to identify and highlight research gaps in the field of psilocybin microdosing for future research. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses based strategy was employed, utilizing a chain of keywords and key phrases across multiple databases, augmented by a cross-sectional Google search for relevant grey literature in the form of the top 10 search results. A total of 40 studies and 8 unique websites were identified, summarized and tabulated into four distinct categories, namely non-clinical, clinical, observational and anecdotal evidence. RESULTS: The majority of available evidence originates from observational studies, while non-clinical and clinical study findings remain comparatively sparse and inconsistent. Web-based findings were consistent with current research findings. Key research gaps were highlighted: the imperative for more randomized placebo-controlled trials, exploration of dose-response ranges, psychological and personality testing of participants, utilization of active placebos, greater diversity in study populations, an increase in psilocybin-exclusive microdosing studies and the refinement of animal models. CONCLUSION: Definitive conclusions regarding the efficacy of psilocybin microdosing remain elusive, emphasizing the need for further study. Numerous research gaps necessitate consideration for future investigations.

Feasibility and effectiveness study of applying a hallucinogen harm reduction and integration model to a mindfulness thinking intervention using virtual reality: A randomized controlled trial.

Objective: The purpose of this study was to investigate whether a virtual reality (VR) program designed and developed based on the hallucinogenic harm reduction and integration (PHRI) clinical model could be more effective in guiding positive thinking training, improving positive thinking awareness and ability, and, to some extent, facilitating personal efficacy and emotional state compared to a traditional VR program that places users in a virtual natural ecological environment to guide positive thinking training. We also sought to understand the factors that may influence the effectiveness of VR interventions and user experience. Method: Seventy-six randomly recruited participants were divided into a control group and an experimental group of 38 participants, each according to a random number table, and were trained in VR meditation for eight weeks. The experimental group used a PHRI-based mindfulness program, while the control group used a traditional mindfulness meditation program. We used The Mindful Attention Awareness Scale and the PAD emotional three-dimensional scale to assess the level of state mindfulness and changes in the emotional state before and at the end of the experiment. The Immersive Tendencies Questionnaire measured the user's sense of presence and immersion in the virtual environment. The Five Facet Mindfulness Questionnaires and the Depression Anxiety and Stress Scale (DASS-21) were used at the baseline assessment stage before and at the 4-week follow-up after the experiment to assess the change in trait mindfulness levels due to the mindfulness training. The Five Facet Mindfulness Questionnaires and the DASS-21 were used to assess changes in mindfulness and mental health trait levels. Results: At the end of the experiment, the MMSQ score was significantly lower in the control group than in the experimental group, while the ITQ score was significantly higher than in the experimental group, and both scores were statistically significant (p < 0.05). In the follow-up assessment four weeks after the end of the experiment, the FFMQ-15 score and the DASS-21 were significantly and statistically higher in the experimental group than in the control group (p < 0.05). Since the scores of the PAD scale did not obey a normal distribution, we used the Wilcoxon signed-rank test to assess the results, which proved that the experimental group had higher levels of emotional activation and arousal. Conclusion: The VR positive thinking program developed based on PHRI can significantly increase the positive thinking state and emotional arousal and activation of the general population participants but does not directly lead to the growth of positive emotions. Moreover, this detached psychedelic scene brings users a weaker sense of presence and presence than traditional natural space scenes. Furthermore, it does not bring any intense simulator motion sickness symptoms. These findings suggest that VR programs developed based on PHRI have a more positive facilitation effect on the positive state and that this increase lasts longer than conventional VR-positive programs.

Predicting the Hallucinogenic Potential of Molecules Using Artificial Intelligence.

The development of new drugs addressing serious mental health and other disorders should avoid the psychedelic experience. Analogs of psychedelic drugs can have clinical utility and are termed "psychoplastogens". These represent promising candidates for treating opioid use disorder to reduce drug dependence, with rarely reported serious adverse effects. This drug abuse cessation is linked to the induction of neuritogenesis and increased neuroplasticity, a hallmark of psychedelic molecules, such as lysergic acid diethylamine. Some, but not all psychoplastogens may act through the G-protein coupled receptor (GPCR) 5HT2A whereas others may display very different polypharmacology making prediction of hallucinogenic potential challenging. In the process of developing tools to help design new psychoplastogens, we have used artificial intelligence in the form of machine learning classification models for predicting psychedelic effects using a published in vitro data set from PsychLight (support vector classification (SVC), area under the curve (AUC) 0.74) and in vivo human data derived from books from Shulgin and Shulgin (SVC, AUC, 0.72) with nested five-fold cross validation. We have also explored conformal predictors with ECFP6 and electrostatic descriptors in an effort to optimize them. These models have been used to predict known 5HT2A agonists to assess their potential to act as psychedelics and induce hallucinations for PsychLight (SVC, AUC 0.97) and Shulgin and Shulgin (random forest, AUC 0.71). We have tested these models with head twitch data from the mouse. This predictive capability is desirable to reliably design new psychoplastogens that lack in vivo hallucinogenic potential and help assess existing and future molecules for this potential. These efforts also provide useful insights into understanding the psychedelic structure activity relationship.

Vaccinium uliginosum L. (bog bilberry) and the search for its alleged toxicity: a review.

Bog bilberry (Vaccinium uliginosum L.) is a wild-growing berry native to all circumboreal regions. There is however a significant discrepancy in the uses of bog bilberry fruits around the world. There exists a strong prejudice against the use of these berries in many European countries as well as a few incidences of poisoning reported between 1906 and 1944. In Asia and North America, this fear is completely absent from the local knowledge and the bog bilberry is valued as an excellent food and medicinal plant. There has been a lack of research on the topic in the last 50 years and thus the presumed toxicity remains unproven. This review aims to gather the conflicting information from all regions where bog bilberry grows and present them in a critical way to elucidate the possible explanations for the discrepancies. There are several possible explanations for the alleged toxicity of the bog bilberry, including a fungal infection of the fruits, individual intolerance or accidental poisoning by a different plant species; the local names meaning "drunk, inebriating, vomit-inducing berry" may be related to the alcoholic drinks made from them. This review highlights the gap in knowledge and serves as a theoretical framework for future research.

Presence of abnormal otoliths in hallucinogenic fish and their comparison with normal otoliths using light and scanning electron digital imaging.

The otolith organs located in the inner ear of the fish are responsible for vital activities such as balance and hearing. Abnormalities in these organs can adversely affect the vital activities of the fish species. The main purpose of the study is to analyze the abnormalities in the otoliths of Sarpa salpa, known as the hallucinogenic fish. For that, 372 individuals of S. salpa are collected from the North Aegean Sea. As a result of the abnormality analyses in S. salpa otoliths, anomalies were detected such as various prominence structures on the surface of the otolith caused by accumulation and a more transparent appearance due to the different crystal structures in some parts of the otolith. These abnormalities were found in the left and/or right otoliths of male and female individuals in different total lengths. The percentage of individuals with abnormal otoliths of S. salpa is calculated as 52.42%. It was determined that there are statistical differences between the left and right otolith measurements of male and female individuals with abnormal and normal otoliths(p < 0.05). There is no relationship between the percentage of individuals showing abnormality and total length and sex. The current study presents for the first time abnormal otolith information on left and right otoliths in male and female S. salpa. It is thought that abnormalities in hallucinogenic fish otoliths could be related to genetic predisposition as well as stress due to nutritional preference, pollutants, and environmental factors. RESEARCH HIGHLIGHTS: The presence of abnormalities in the otoliths of Sarpa salpa, a hallucinogenic fish, was revealed for the first time. Abnormalities in the otoliths of S. salpa were identified, such as the presence of various prominence structures on the otolith's surface, loss of parts as well as a more transparent appearance in the outlines or surface of the otolith. Normal and abnormal otoliths of female and male hallucinogenic fish from different size groups were examined using light and scanning electron microscopy. Abnormality detected in the otoliths of hallucinogenic fish is not related to the gender and size of the fish.

The novel psychoactive substance 25E-NBOMe induces reward-related behaviors via dopamine D1 receptor signaling in male rodents.

Novel psychoactive substances (NPSs) are new psychotropic drugs designed to evade substance regulatory policies. 25E-NBOMe (2-(4-ethyl-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine) has recently been identified as an NPS, and its recreational misuse has been reported to be rapidly increasing. However, the psychopharmacological effects and mechanisms of 25E-NBOMe have not been studied. We examined the abuse potential of 25E-NBOMe using the conditioned place preference in male mice and self-administration paradigms in male rats. Additionally, immunoblot assay, enzyme-linked immunosorbent assay, and microdialysis were used to determine the molecular effects of 25E-NBOMe in the nucleus accumbens (NAc). Our data demonstrated that 25E-NBOMe induces conditioned place preference, and the dopaminergic signaling in the NAc mediates these. Following 25E-NBOMe administration, expression of dopamine transporter and dopamine D1 receptor (D1DR) were enhanced in the NAc of male mice, and NAc dopamine levels were reduced in both male mice and rats. Induction of intracellular dopaminergic pathways, DARPP32, and phosphorylation of CREB in the NAc of male mice was also observed. Significantly, pharmacological blockade of D1DR or chemogenetic inhibition of D1DR-expressing medium spiny neurons in the NAc attenuated 25E-NBOMe-induced conditioned place preference in male mice. We also examined the hallucinogenic properties of 25E-NBOMe using the head twitch response test in male mice and found that this behavior was mediated by serotonin 2A receptor activity. Our findings demonstrate that D1DR signaling may govern the addictive potential of 25E-NBOMe. Moreover, our study provides new insights into the potential mechanisms of substance use disorder and the improvement of controlled substance management.

Why are plants named after witches and devils in north-western Europe?

ETHNOPHARMACOLOGICAL RELEVANCE: Witches in Western Europe are associated with the use of medicinal, abortifacient, hallucinogenic, and toxic plants. Curiously, these associations are not backed up by first-hand evidence and historians are unconvinced that people convicted as witches were herbalists. Local plant names provide an untapped source for analysing witchcraft-plant relationships. AIM OF THE STUDY: We analysed vernacular plant names indicating an association with witches and devils to find out why these species and witchcraft were linked. MATERIALS AND METHODS: We constructed a database with vernacular names containing the terms witch and devil in related north-west European languages. The devil was added because of its association with witchcraft. The plant species' characteristics (e.g., medicinal use, toxicity) were assessed to determine if there were non-random associations between these traits and their names. RESULTS: We encountered 1263 unique vernacular name-taxa combinations (425 plant taxa; 97 families). Most species named after witches and/or devils were found within the Asteraceae, Ranunculaceae, and Rosaceae. For Dutch, German and English we confirmed associations between witchcraft names and toxicity. Hallucinogenic plants do not appear to be associated with witch-names. For Dutch, we found significant associations between plant names and medicinal and apotropaic uses, although we did not find any association with abortifacient qualities. CONCLUSIONS: This study demonstrates that there is a wide variety of plants associated with witches and the devil in north-western Europe. Plant names with the terms witch and devil were likely used in a pejorative manner to name toxic and weedy plants, and functioned as a warning for their harmful properties. Our study provides novel insights for research into the history of witchcraft and its associated plant species.

A fatal case of aspiration due to consumption of the hallucinogenic tryptamine derivative dipropyltryptamine (DPT).

BACKGROUND AND AIM: This case involves a 20-year-old man with prior hallucinogen-use experience, who sniffed an unknown amount of dipropyltryptamine in an apartment. Dipropyltryptamine, a hallucinogenic compound belonging to the tryptamine class is recognized for inducing effects similar to dimethyltryptamine (DMT) but with a longer duration. Ten to fifteen minutes later he experienced visual hallucinations, followed by increasing apathy. Two hours post consumption he developed abdominal pain, leading to collapse, seizure, and vomiting. Despite emergency medical resuscitation on site, transport to hospital 2.5 hours post consumption and extracorporeal life support he died 21 hours later. Relevant toxicological and morphological findings are presented. METHODS: A serum sample was collected four hours post consumption. Autopsy was performed six days after death. Antemortem serum, as well as postmortem cardiac blood and urine were analyzed for alcohol and psychoactive drugs by systematic toxicological analyses employing gas chromatography-mass spectrometry (Maurer/Pfleger/Weber library among others), liquid chromatography-ion trap mass spectrometry (LC-MSn, Toxtyper™), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Dipropyltryptamine was quantified by LC-MS/MS after solid-phase extraction. RESULTS: Autopsy revealed a state after deep aspiration of gastric contents with consecutive brain edema due to oxygen deprivation. Dipropyltryptamine concentrations were approximately 210 ng/ml, 110 ng/ml and 180 ng/ml in antemortem serum, postmortem cardiac blood and urine, respectively. To the best of our knowledge, these are the first reported concentrations of dipropyltryptamine in a fatal case. CONCLUSION: Unlike typical tryptamine overdose reports, this case did not present with agitation, hyperthermia, or tachycardia. Despite the individual's prior experience with tryptamines and the generally low toxicity associated with this class of hallucinogens, death in this case was an indirect consequence of the nasal consumption of a high dose of dipropyltryptamine.

Salvia divinorum: from Mazatec medicinal and hallucinogenic plant to emerging recreational drug.

Salvia divinorum is a sage endemic to a small region of Mexico and has been traditionally used by the Mazatec Indians for divination and spiritual healing. Recently, it has gained increased popularity as a recreational drug, used by adolescents and young adults as an alternative to marijuana and LSD. Salvinorin A, the major active ingredient of the plant, is considered to be the most potent known hallucinogen of natural origin. This review surveys the current state of knowledge on the neurochemical, pharmacokinetic, and pharmacological properties of salvinorin A, the trends and motivation behind S. divinorum use, and the health problems among users of the plant's products. S. divinorum induces intense, but short-lived, psychedelic-like changes in mood and perception, with concomitant hallucinations and disorientation. Many websites have misinterpreted the limited existing research-based information on the side effects of salvia as evidence for its safety. However, data accumulated over the last few years indicate that potential health risks are associated with the use of S. divinorum, especially by teenagers, users of other substances of abuse, and individuals with underlying psychotic disturbances. Taken together, the data presented in this review point to the need for further basic and clinical studies to create a basis for the development of well-addressed prevention and treatment strategies.

Psychedelics as Transformative Therapeutics.

Over the past decade, psychedelic compounds have emerged as potentially transformative therapeutics for a variety of intractable neuropsychiatric conditions. However, historically most of the basic science has utilized these compounds as probes to interrogate various endogenous neurotransmitter systems-mainly the serotonin 5-HT2A receptor. With the renewed interest in utilizing these compounds as therapeutics and the explosion in clinical trials, psychedelics have been purported to treat many neuropsychiatric disorders, including depression, cluster headaches, migraines, anxiety, and obsessive-compulsive disorder. It is therefore imperative to understand the biology and pharmacology behind their therapeutic mechanisms as well as expose any potential pitfalls in their widespread use as treatments. This review covers the latest advances in understanding the biological mechanisms, the newest efforts in drug discovery, and potential pitfalls when it comes to utilizing this class of compounds as emerging therapeutics.

Underground ibogaine use for the treatment of substance use disorders: A qualitative analysis of subjective experiences.

INTRODUCTION: Ibogaine is one of the alkaloids naturally found in plants such as Tabernanthe iboga, which has been traditionally used by members of the Bwiti culture. Since the discovery of its anti-addictive properties by Howard S. Lotsof in 1962, ibogaine has been used experimentally to treat substance use disorders (SUD), especially those involving opioids. We aim to provide a detailed understanding of the underlying psychological aspects of underground ibogaine use for the treatment of SUD. METHODS: Semi-structured interviews were carried out with 13 participants with SUD, which motivated their self-treatment with ibogaine. The data were analysed using the grounded theory approach and considered the context of the treatment, and the nature of the occurring hallucinogenic and cognitive phenomena during the treatment experience. RESULTS: We identified several psychological effects that the study respondents experienced, which seem to play a substantial role in the therapeutic process concerning SUD. The evoking of interpersonal and transpersonal experiences, autobiographical memories, and preparation, integration and motivation for a lifestyle change are important components that participants reported during and after ibogaine intake. DISCUSSION AND CONCLUSION: Ibogaine is increasingly being used for the treatment of SUD, due in part to the limited treatment options currently available. Its beneficial effects seem to be related not only to its complex pharmacology but also to the subjective experience that ibogaine induces. The main aspects of this experience are related to autobiographical memories and valuable personal insights, which together appear to help individuals cope with their SUD.