“Rationale: 5-methoxy-n,n-dimethyltryptamine is a psychotropic substance found in various plant and animal species and is synthetically produced. 5-methoxy-n,n-dimethyltryptamine is used in naturalistic settings for spiritual exploration, recreation, or to address negative affect and mood problems. however, scientific knowledge on the effects of 5-methoxy-n,n-dimethyltryptamine in humans is scarce. objectives: the first objective was to assess the effects of inhalation of vaporized synthetic 5-methoxy-n,n-dimethyltryptamine on neuroendocrine markers. the second objective was to assess effects of the substance on affect and mindfulness. in addition, we assessed whether ratings of subjective measures were associated with changes in stress biomarkers (i.e., cortisol) and immune response (i.e., il-6, crp, il-1β), as well as the acute psychedelic experience. methods: assessments (baseline, immediately post-session, and 7-day follow-up) were made in 11 participants. salivary samples were collected at baseline and post-session and analyzed by high-sensitivity enzyme-linked immunosorbent assay (elisa). results: 5-methoxy-n,n-dimethyltryptamine significantly increased cortisol levels and decreased il-6 concentrations in saliva immediately post-session. these changes were not correlated to ratings of mental health or the psychedelic experience. relative to baseline, ratings of non-judgment significantly increased, and ratings of depression decreased immediately post-session and at follow-up. ratings of anxiety and stress decreased from baseline to 7-day follow-up. participant ratings of the psychedelic experience correlated negatively with ratings of affect and positively with ratings of non-judgment. conclusion: inhalation of vaporized synthetic 5-methoxy-n,n-dimethyltryptamine produced significant changes in inflammatory markers, improved affect, and non-judgment in volunteers. future research should examine the effect of 5-methoxy-n,n-dimethyltryptamineamine with healthy volunteers in a controlled laboratory setting.”

“Research on psychedelics has seen a recent revival, with many clinical trials focused on their therapeutic potential to treat a range of mental health conditions. the purpose of this systematic review was to evaluate clinical trials of psychedelic-assisted psychotherapy for mental health conditions from the present wave of psychedelic research (1990s to present). a total of 43 studies met criteria and were included. the conditions reviewed were substance use disorders; anxiety and/or depression, often associated with terminal illness; posttraumatic stress disorder; and obsessive-compulsive disorder. quantitative results indicate that psychedelics can significantly reduce clinical outcomes associated with these mental health conditions. common themes identified from qualitative reports included increased acceptance and processing of emotions, connectedness to others, forgiveness, self-compassion, insights into the self, peak or mystical experiences, ego dissolution, positive changes in worldview, motivation and commitment to change, changes in the relationship to the substance of abuse for those with substance use disorder, and acceptance of death for those with terminal illness. no serious, long-term adverse events were reported directly attributable to drug ingestion. we discuss the strengths and limitations of the research base, along with suggestions for clinical practice, potential therapeutic mechanisms, and directions for future research. despite promising results, further work is needed to determine which psychedelic is best suited for diverse mental health conditions, the most appropriate type of psychotherapy to employ, and the psychological and neurobiological mechanisms underlying clinical benefits.”

“This review illustrates the relevance of shamanism and its evolution under effects of psilocybin as a framework for identifying evolved aspects of psychedelic set and setting. effects of 5ht2 psychedelics on serotonin, stress adaptation, visual systems and personality illustrate adaptive mechanisms through which psychedelics could have enhanced hominin evolution as an environmental factor influencing selection for features of our evolved psychology. evolutionary psychology perspectives on ritual, shamanism and psychedelics provides bases for inferences regarding psychedelics’ likely roles in hominin evolution as exogenous neurotransmitter sources through their effects in selection for innate dispositions for psychedelic set and setting. psychedelics stimulate ancient brain structures and innate modular thought modules, especially self-awareness, other awareness, ‘mind reading,’ spatial and visual intelligences. the integration of these innate modules are also core features of shamanism. cross-cultural research illustrates shamanism is an empirical phenomenon of foraging societies, with its ancient basis in collective hominid displays, ritual alterations of consciousness, and endogenous healing responses. shamanic practices employed psychedelics and manipulated extrapharmacological effects through stimulation of serotonin and dopamine systems and augmenting processes of the reptilian and paleomammalian brains. differences between chimpanzee maximal displays and shamanic rituals reveal a zone of proximal development in hominin evolution. the evolution of the mimetic capacity for enactment, dance, music, and imitation provided central capacities underlying shamanic performances. other chimp-human differences in ritualized behaviors are directly related to psychedelic effects and their integration of innate modular thought processes. psychedelics and other ritual alterations of consciousness stimulate these and other innate responses such as soul flight and death-and-rebirth experiences. these findings provided bases for making inferences regarding foundations of our evolved set, setting and psychology. shamanic setting is eminently communal with singing, drumming, dancing and dramatic displays. innate modular thought structures are prominent features of the set of shamanism, exemplified in animism, animal identities, perceptions of spirits, and psychological incorporation of spirit others. a shamanic-informed psychedelic therapy includes: a preparatory set…”

“Background: observational data and preliminary studies suggest serotonin 2a agonist psychedelics may hold potential in treating a variety of substance use disorders (suds), including opioid use disorder (oud). aims: the study aim was to describe and analyze self-reported cases in which naturalistic psychedelic use was followed by cessation or reduction in other substance use. methods: an anonymous online survey of individuals reporting cessation or reduction in cannabis, opioid, or stimulant use following psychedelic use in non-clinical settings. results: four hundred forty-four respondents, mostly in the usa (67%) completed the survey. participants reported 4.5 years of problematic substance use on average before the psychedelic experience to which they attributed a reduction in drug consumption, with 79% meeting retrospective criteria for severe sud. most reported taking a moderate or high dose of lsd (43%) or psilocybin-containing mushrooms (29%), followed by significant reduction in drug consumption. before the psychedelic experience 96% met sud criteria, whereas only 27% met sud criteria afterward. participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced substance misuse. greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with greater reduction in drug consumption. conclusions: while these cross-sectional and self-report methods cannot determine whether psychedelics caused changes in drug use, results suggest the potential that psychedelics cause reductions in problematic substance use, and support additional clinical research on psychedelic-assisted treatment for sud.”

“Background: recent studies have suggested therapeutic benefits of psychedelics for a variety of mental health conditions. the understanding of how single psychedelic administrations can induce long-lasting effects are, in large, still lacking. however, recent studies in both healthy and clinical populations suggest a role for personality changes. aim: to test support for some of these plausible mechanisms we evaluated (cross-sectional) associations between recreational use of psychedelics and 3,4-methylene-dioxymethamphetamine (mdma) and (a) personality measures and (b) key markers of cerebral serotonergic signalling (serotonin transporter and serotonin-2a-receptor binding). methods: in 10 psychedelic-preferring recreational users, 14 mdma-preferring users and 21 non-using controls, personality was assessed using the ‘big five‘ instrument revised neo personality inventory (neo-pi-r). frontal serotonin transporter and serotonin-2a-receptor binding potentials were quantified using [11c]dasb and [18f]altanserin positron emission tomography, respectively. results: of the five neo-pi-r traits, only openness to experience scores differed between the three groups; psychedelic-preferring recreational users showing higher openness to experience scores when compared with both mdma-preferring users and controls. openness to experience scores were positively associated with lifetime number of psychedelic exposures, and among all mdma-preferring user/psychedelic-preferring recreational user individuals, frontal serotonin transporter binding – but not frontal serotonin-2a-receptor binding – was positively associated with openness to experience. conclusion: our findings from this cross-sectional study support increasing evidence of a positive association between psychedelic experiences and openness to experience, and (a) expands this to the context of “recreational” psychedelics use, and (b) links serotonergic neurotransmission to openness to experience. a modulation of personality induced by psychedelic experiences may have important therapeutic implications via its impact on peoples’ value systems, cognitive flexibility, and individual and social behaviour.”