Acute and enduring adverse effects of psilocybin have been reported anecdotally, but have not been well characterized. For this study, 1993 individuals (mean age 30 yrs; 78% male) completed an online survey about their single most psychologically difficult or challenging experience (worst “bad trip”) after consuming psilocybin mushrooms. Thirty-nine percent rated it among the top five most challenging experiences of his/her lifetime. Eleven percent put self or others at risk of physical harm; factors increasing the likelihood of risk included estimated dose, duration and difficulty of the experience, and absence of physical comfort and social support. Of the respondents, 2.6% behaved in a physically aggressive or violent manner and 2.7% received medical help. Of those whose experience occurred >1 year before, 7.6% sought treatment for enduring psychological symptoms. Three cases appeared associated with onset of enduring psychotic symptoms and three cases with attempted suicide. Multiple regression analysis showed degree of difficulty was positively associated, and duration was negatively associated, with enduring increases in well-being. Difficulty of experience was positively associated with dose. Despite difficulties, 84% endorsed benefiting from the experience. The incidence of risky behavior or enduring psychological distress is extremely low when psilocybin is given in laboratory studies to screened, prepared, and supported participants.
: Psychoactive drugs of fungal origin, psilocin, ibotenic acid, and muscimol among them have been proposed for recreational use and popularized since the 1960s, XX century. Despite their well-documented neurotoxicity, they reached reputation of being safe and nonaddictive. Scientific efforts to find any medical application for these hallucinogens in psychiatry, psychotherapy, and even for religious rituals support are highly controversial. Even if they show any healing potential, their usage in psychotherapy is in some cases inadequate and may additionally harm seriously suffering patients. Hallucinogens are thought to reduce cognitive functions. However, in case of indolealkylamines, such as psilocin, some recent findings suggest their ability to improve perception and mental skills, what would motivate the consumption of “magic mushrooms.” The present article offers an opportunity to find out what are the main symptoms of intoxication with mushrooms containing psilocybin/psilocin, muscimol, and ibotenic acid. The progress in analytical methods for detection of them in fungal material, food, and body fluids is reviewed. Findings on the mechanisms of their biologic activity are summarized. Additionally, therapeutic potential of these fungal psychoactive compounds and health risk associated with their abuse are discussed.
Despite the general consensus that synaesthesia emerges at an early developmental stage and is only rarely acquired during adulthood, the transient induction of synaesthesia with chemical agents has been frequently reported in research on different psychoactive substances. Nevertheless, these effects remain poorly understood and have not been systematically incorporated. Here we review the known published studies in which chemical agents were observed to elicit synaesthesia. Across studies there is consistent evidence that serotonin agonists elicit transient experiences of synaesthesia. Despite convergent results across studies, studies investigating the induction of synaesthesia with chemical agents have numerous methodological limitations and little experimental research has been conducted. Cumulatively, these studies implicate the serotonergic system in synaesthesia and have implications for the neurochemical mechanisms underlying this phenomenon but methodological limitations in this research area preclude making firm conclusions regarding whether chemical agents can induce genuine synaesthesia.
In a large-scale ( N = 1487) general population online study, we investigated the relationship between past experience with classic psychedelic substances (e.g. LSD, psilocybin, mescaline), nature relatedness, and ecological behavior (e.g. saving water, recycling). Using structural equation modeling we found that experience with classic psychedelics uniquely predicted self-reported engagement in pro-environmental behaviors, and that this relationship was statistically explained by people’s degree of self-identification with nature. Our model controlled for experiences with other classes of psychoactive substances (cannabis, dissociatives, empathogens, popular legal drugs) as well as common personality traits that usually predict drug consumption and/or nature relatedness (openness to experience, conscientiousness, conservatism). Although correlational in nature, results suggest that lifetime experience with psychedelics in particular may indeed contribute to people’s pro-environmental behavior by changing their self-construal in terms of an incorporation of the natural world, regardless of core personality traits or general propensity to consume mind-altering substances. Thereby, the present research adds to the contemporary literature on the beneficial effects of psychedelic substance use on mental wellbeing, hinting at a novel area for future research investigating their potentially positive effects on a societal level. Limitations of the present research and future directions are discussed.
Psilocybin is the psychotropic tryptamine-derived natural product of Psilocybe carpophores, the so-called “magic mushrooms”. Although its structure has been known for 60 years, the enzymatic basis of its biosynthesis has remained obscure. We characterized four psilocybin biosynthesis enzymes. These include i) PsiD which represents a new class of fungal l-tryptophan decarboxylases, ii) PsiK, that catalyzes the phosphotransfer step, iii) the methyl transferase PsiM, catalyzing iterative N-methyltransfer as terminal biosynthetic step, and iv) PsiH, a monooxygenase. In a combined PsiD/PsiK/PsiM reaction, psilocybin was synthesized enzymatically in a step-economic route from 4-hydroxy-l-tryptophan. Given the renewed pharmaceutical interest in psilocybin, our results may lay the foundation for its biotechnological production.
Treatment resistant cluster headache and migraine patients are exploring alternative treatments online. The aim of this study was to improve comprehension regarding the use of non-established or alternative pharmacological treatments used by sufferers of cluster headaches and migraines.
Though synesthesia research has seen a huge growth in recent decades, and tremendous progress has been made in terms of understanding the mechanism and cause of synesthesia, we are still left mostly in the dark when it comes to the mechanistic commonalities (if any) among developmental, acquired and drug-induced synesthesia. We know that many forms of synesthesia involve aberrant structural or functional brain connectivity. Proposed mechanisms include direct projection and disinhibited feedback mechanisms, in which information from two otherwise structurally or functionally separate brain regions mix. We also know that synesthesia sometimes runs in families. However, it is unclear what causes its onset. Studies of psychedelic drugs, such as psilocybin, LSD and mescaline, reveal that exposure to these drugs can induce synesthesia. One neurotransmitter suspected to be central to the perceptual changes is serotonin. Excessive serotonin in the brain may cause many of the characteristics of psychedelic intoxication. Excessive serotonin levels may also play a role in synesthesia acquired after brain injury. In brain injury sudden cell death floods local brain regions with serotonin and glutamate. This neurotransmitter flooding could perhaps result in unusual feature binding. Finally, developmental synesthesia that occurs in individuals with autism may be a result of alterations in the serotonergic system, leading to a blockage of regular gating mechanisms. I conclude on these grounds that one commonality among at least some cases of acquired, developmental and drug-induced synesthesia may be the presence of excessive levels of serotonin, which increases the excitability and connectedness of sensory brain regions.
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Published about 5 years ago
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.
Perturbing a system and observing the consequences is a classic scientific strategy for understanding a phenomenon. Psychedelic drugs perturb consciousness in a marked and novel way and thus are powerful tools for studying its mechanisms. In the present analysis, we measured changes in resting-state functional connectivity (RSFC) between a standard template of different independent components analysis (ICA)-derived resting state networks (RSNs) under the influence of two different psychoactive drugs, the stimulant/psychedelic hybrid, MDMA, and the classic psychedelic, psilocybin. Both were given in placebo-controlled designs and produced marked subjective effects, although reports of more profound changes in consciousness were given after psilocybin. Between-network RSFC was generally increased under psilocybin, implying that networks become less differentiated from each other in the psychedelic state. Decreased RSFC between visual and sensorimotor RSNs was also observed. MDMA had a notably less marked effect on between-network RSFC, implying that the extensive changes observed under psilocybin may be exclusive to classic psychedelic drugs and related to their especially profound effects on consciousness. The novel analytical approach applied here may be applied to other altered states of consciousness to improve our characterization of different conscious states and ultimately advance our understanding of the brain mechanisms underlying them.
This paper presents original research on prevalence, user characteristics and effect profile of N,N-dimethyltryptamine (DMT), a potent hallucinogenic which acts primarily through the serotonergic system. Data were obtained from the Global Drug Survey (an anonymous online survey of people, many of whom have used drugs) conducted between November and December 2012 with 22,289 responses. Lifetime prevalence of DMT use was 8.9% (n=1980) and past year prevalence use was 5.0% (n=1123). We explored the effect profile of DMT in 472 participants who identified DMT as the last new drug they had tried for the first time and compared it with ratings provided by other respondents on psilocybin (magic mushrooms), LSD and ketamine. DMT was most often smoked and offered a strong, intense, short-lived psychedelic high with relatively few negative effects or “come down”. It had a larger proportion of new users compared with the other substances (24%), suggesting its popularity may increase. Overall, DMT seems to have a very desirable effect profile indicating a high abuse liability that maybe offset by a low urge to use more.