title: Psychedelics not linked to mental health problems or suicidal behavior: A population study LSD‐induced entropic brain activity predicts subsequent personality change Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Serotonergic psychedelics and personality: A systematic review of contemporary research Psilocybin with psychological support for treatment-resistant depression: six-month follow-up Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. Anxiety and depression in Nepal: prevalence, comorbidity and associations Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction The paradoxical psychological effects of lysergic acid diethylamide (LSD). Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects Cessation and reduction in alcohol consumption and misuse after psychedelic use Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Long-term follow-up of psilocybin-facilitated smoking cessation Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer
abstract: A recent large population study of 130,000 adults in the United States failed to find evidence for a link between psychedelic use ( lysergic acid diethylamide , psilocybin or mescaline ) and  mental health problems . Using a new data set consisting of 135,095 r and omly selected United States adults , including 19,299 psychedelic users , we examine the associations between psychedelic use and mental health . After adjusting for sociodemographics , other drug use and childhood depression , we found no significant associations between lifetime use of  psychedelics  and increased likelihood of past year serious psychological distress , mental health treatment , suicidal thoughts , suicidal plans and suicide attempt , depression and anxiety . We failed to find evidence that psychedelic use is an independent risk factor for mental health problems .  Psychedelics are not known to harm the brain or other body organs or to cause addiction or compulsive use ; serious adverse events involving psychedelics are extremely rare . Overall , it is difficult to see how prohibition of psychedelics can be justified as a public health measure Personality is known to be relatively stable throughout adulthood . Nevertheless , it has been shown that major life events with high personal significance , including experiences engendered by psychedelic drugs , can have an enduring impact on some core facets of personality . In the present , balanced‐order , placebo‐controlled study , we investigated biological predictors of post‐lysergic acid diethylamide ( LSD ) changes in personality . Nineteen healthy adults underwent resting state functional MRI scans under LSD ( 75 µg , I.V. ) and placebo ( saline I.V. ) . The Revised NEO Personality Inventory ( NEO‐PI‐R ) was completed at screening and 2 weeks after LSD/placebo . Scanning sessions consisted of three 7.5‐min eyes‐closed resting‐state scans , one of which involved music listening . A st and ardized preprocessing pipeline was used to extract measures of sample entropy , which characterizes the predictability of an fMRI time‐series . Mixed‐effects models were used to evaluate drug‐induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2‐week follow‐up . Overall , LSD had a pronounced global effect on brain entropy , increasing it in both sensory and hierarchically higher networks across multiple time scales . These shifts predicted enduring increases in trait openness . Moreover , the predictive power of the entropy increases was greatest for the music‐listening scans and when “ ego‐dissolution ” was reported during the acute experience . These results shed new light on how LSD‐induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality . Hum Brain Mapp 37:3203–3213 , 2016 . © 2016 Wiley Periodicals , Abstract A double-blind , r and omized , active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases . Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart . The participants received either 200 & mgr;g of LSD ( n = 8) or 20 & mgr;g of LSD with an open-label crossover to 200 & mgr;g of LSD after the initial blinded treatment was unmasked ( n = 4 ) . At the 2-month follow-up , positive trends were found via the State-Trait Anxiety Inventory ( STAI ) in reductions in trait anxiety ( p = 0.033 ) with an effect size of 1.1 , and state anxiety was significantly reduced ( p = 0.021 ) with an effect size of 1.2 , with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events . STAI reductions were sustained for 12 months . These results indicate that when administered safely in a method ologically rigorous medically supervised psychotherapeutic setting , LSD can reduce anxiety , suggesting that larger controlled studies are warranted HighlightsSerotonergic psychedelics act as agonists at cortical 5‐HT2A receptors.5‐HT2A receptors are expressed in fronto‐temporo‐parieto‐occipital areas .Some personality traits seem to be related to 5‐HT2A receptor expression . Acute and long‐term use of psychedelics is associated with personality changes  . Personality changes induced by psychedelics may have therapeutic effects . & NA ; Serotonergic psychedelics act as agonists at cortical 5‐HT2A receptors and seem to induce personality changes . We conducted a systematic review of studies assessing the effects of these drugs on personality . Papers published from 1985–2016 were included from PubMed , LILACS , and SciELO data bases . Three hundred and sixty‐nine studies were identified , and 18 were included . Specific personality traits , such as Absorption and Self‐Transcendence , seem to influence the effects of psychedelics , and  psychedelic drug users and nonusers appear to differ in some personality traits . Psychedelics administered in controlled setting s may induce personality changes , such as increased Openness and Self‐Transcendence . Increases in global brain entropy induced by acute psychedelic administration predicted changes in Openness , and Self‐Transcendence was negatively correlated with cortical thinning of the posterior cingulate cortex in long‐term religious ayahuasca users . Acute and long‐term use of psychedelics is associated with personality changes that appear to be modulated by 5‐HT2A receptors . These changes seem to induce therapeutic effects that should be further explored in r and omized controlled studies Rationale Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy . Objectives Here , we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression . Methods Twenty patients ( six females ) with ( mostly ) severe , unipolar , treatment-resistant major depression received two oral doses of psilocybin ( 10 and 25 mg , 7 days apart ) in a supportive setting . Depressive symptoms were assessed from 1 week to 6 months post-treatment , with the self-rated QIDS-SR16 as the primary outcome measure . Results Treatment was generally well tolerated . Relative to baseline , marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment ( Cohen ’s d = 2.2 at week 1 and 2.3 at week 5 , both p < 0.001 ) ; nine and four patients met the criteria for response and remission at week 5 . Results remained positive at 3 and 6 months ( Cohen ’s d = 1.5 and 1.4 , respectively , both p < 0.001 ) . No patients sought conventional antidepressant treatment within 5 weeks of psilocybin . Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience . Conclusions Although limited conclusions can be drawn about treatment efficacy from open-label trials , tolerability was good , effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort . Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind r and omised control trials Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior , attitudes , and values , and increases in the personality domain of openness . In an open-label pilot- study of psilocybin-facilitated smoking addiction treatment , 15 smokers received 2 or 3 doses of psilocybin  in the context of cognitive behavioral therapy ( CBT ) for smoking cessation . Twelve of 15 participants ( 80 % ) demonstrated biologically verified smoking abstinence at 6-month follow-up . Participants who were abstinent at 6 months ( n=12 ) were compared to participants still smoking at 6 months ( n=3 ) on measures of subjective effects of psilocybin . Abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience . No significant differences in general intensity of drug effects were found between groups , suggesting that mystical-type subjective effects , rather than overall intensity of drug effects , were responsible for smoking cessation . Nine of 15 participants ( 60 % ) met criteria for " complete " mystical experience . Smoking cessation outcomes were significantly correlated with measures of mystical experience on session days , as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions . These results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment Several lines of evidence suggest that classic ( 5HT2A agonist ) hallucinogens have clinical ly relevant effects in alcohol and drug addiction . Although recent studies have investigated the effects of psilocybin in various population s , there have been no studies on the efficacy of psilocybin for alcohol dependence . We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data . Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions . Participants ’ responses to psilocybin were qualitatively similar to those described in other population s. Abstinence did not increase significantly in the first 4 weeks of treatment ( when participants had not yet received psilocybin ) , but increased significantly following psilocybin administration ( p < 0.05 ) . Gains were largely maintained at follow-up to 36 weeks . The intensity of effects in the first psilocybin session ( at week 4 ) strongly predicted change in drinking during weeks 5–8 ( r = 0.76 to r = 0.89 ) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5 . There were no significant treatment-related adverse events . These preliminary findings provide a strong rationale for controlled trials with larger sample s to investigate efficacy and mechanisms . TRIAL REGISTRATION : Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being . However , little research has examined enduring changes in traits . This study administered psilocybin to participants who undertook a program of meditation/spiritual practice s. Healthy participants were r and omized to three groups ( 25 each ) : ( 1 ) very low-dose ( 1 mg/70 kg on sessions 1 and 2 ) with moderate-level ( “ st and ard ” ) support for spiritual- practice ( LD-SS ) ; ( 2 ) high-dose ( 20 and 30 mg/70 kg on sessions 1 and 2 , respectively ) with st and ard support ( HD-SS ) ; and ( 3 ) high-dose ( 20 and 30 mg/70 kg on sessions 1 and 2 , respectively ) with high support for spiritual practice ( HD-HS ) .  Psilocybin was administered double-blind and instructions to participants /staff minimized expectancy confounds . Psilocybin was administered 1 and 2 months after spiritual- practice initiation . Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin .  Compared with low-dose , high-dose psilocybin produced greater acute and persisting effects . At 6 months , compared with LD-SS , both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness , gratitude , life meaning/ purpose , forgiveness , death transcendence , daily spiritual experiences , religious faith and coping , and community observer ratings . Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practice s. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning . Trial Registration Clinical Trials.gov Identifier Rationale Although psilocybin has been used for centuries for religious purpose s , little is known scientifically about its acute and persisting effects . Objectives This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable , supportive conditions . Material s and methods The participants were hallucinogen-naïve adults reporting regular participation in religious or spiritual activities . Two or three sessions were conducted at 2-month intervals . Thirty volunteers received orally administered psilocybin ( 30 mg/70 kg ) and methylpheni date hydrochloride ( 40 mg/70 kg ) in counterbalanced order . To obscure the study design , six additional volunteers received methylpheni date in the first two sessions and unblinded psilocybin in a third session . The 8-h sessions were conducted individually . Volunteers were encouraged to close their eyes and direct their attention inward . Study monitors rated volunteers ’ behavior during sessions . Volunteers completed question naires assessing drug effects and mystical experience immediately after and 2 months after sessions . Community observers rated changes in the volunteer ’s attitudes and behavior . Results Psilocybin produced a range of acute perceptual changes , subjective experiences , and labile moods including anxiety .  Psilocybin also increased measures of mystical experience . At 2 months , the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers . Conclusions When administered under supportive conditions , psilocybin occasioned experiences similar to spontaneously occurring mystical experiences . The ability to occasion such experiences prospect ively will allow rigorous scientific investigations of their causes and consequences Background : Clinical ly significant anxiety and depression are common in patients with cancer , and are associated with poor psychiatric and medical outcomes . Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression .  Methods : In this double-blind , placebo-controlled , crossover trial , 29 patients with cancer-related anxiety and depression were r and omly assigned and received treatment with single-dose psilocybin ( 0.3 mg/kg ) or niacin , both in conjunction with psychotherapy . The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks . Results : Prior to the crossover , psilocybin produced immediate , substantial , and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness , improved spiritual wellbeing , and increased quality of life . At the 6.5-month follow-up , psilocybin was associated with enduring anxiolytic and anti-depressant effects ( approximately 60–80 % of participants continued with clinical ly significant reductions in depression or anxiety ) , sustained benefits in existential distress and quality of life , as well as improved attitudes towards death . The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression . Conclusions : In conjunction with psychotherapy , single moderate-dose psilocybin produced rapid , robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress . Trial Registration : Clinical Trials.gov Identifier : Cancer patients often develop chronic , clinical ly significant symptoms of depression and anxiety . Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients . The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and /or anxiety . This r and omized , double-blind , cross-over trial investigated the effects of a very low ( placebo-like ) dose ( 1 or 3 mg/70 kg ) vs. a high dose ( 22 or 30 mg/70 kg ) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up . Instructions to participants and staff minimized expectancy effects . Participants , staff , and community observers rated participant moods , attitudes , and behaviors throughout the study . High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety , along with increases in quality of life , life meaning , and optimism , and decreases in death anxiety . At 6-month follow-up , these changes were sustained , with about 80 % of participants continuing to show clinical ly significant decreases in depressed mood and anxiety . Participants attributed improvements in attitudes about life/self , mood , relationships , and spirituality to the high-dose experience , with > 80 % endorsing moderately or greater increased well-being/life satisfaction . Community observer ratings showed corresponding changes . Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes . Trial Registration Clinical Trials.gov identifier : BACKGROUND Anecdotal reports suggest that psychedelic agents may relieve symptoms of  obsessive-compulsive disorder ( OCD ) . This modified double-blind study investigated the safety , tolerability , and clinical effects of psilocybin , a potent 5-HT(1A ) and 5-HT(2A/2C ) agonist , in patients with OCD . METHOD Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic . Low ( 100 microg/kg ) , medium ( 200 microg/kg ) , and high ( 300 microg/kg ) doses were assigned in that order , and a very low dose ( 25 microg/kg ) was inserted r and omly and in double-blind fashion at any time after the first dose . Testing days were separated by at least 1 week . Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic ; subjects were then transferred to a psychiatric inpatient unit for overnight observation . The Yale-Brown Obsessive Compulsive Scale ( YBOCS ) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0 , 4 , 8 , and 24 hours post-ingestion . The Hallucinogen Rating Scale was administered at 8 hours , and vital signs were recorded at 0 , 1 , 4 , 8 , and 24 hours after ingestion . The study was conducted from November 2001 to November 2004 . RESULTS Nine subjects were administered a total of 29 psilocybin doses . One subject experienced transient hypertension without relation to anxiety or somatic symptoms , but no other significant adverse effects were observed . Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions ( 23%-100 % decrease in YBOCS score ) . Repeated- measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda ( F = 9.86 , df = 3,3 ; p = .046 ) , but no significant effect of dose ( F = 2.25 , df = 3,3 ; p = .261 ) or interaction of time and dose ( F = 0.923 , df = 9,45 ; p = .515 ) . Improvement generally lasted past the 24-hour timepoint . CONCLUSIONS In a controlled clinical environment , psilocybin was safely used in subjects with OCD and was associated with acute reductions in core  OCD symptoms in several subjects Background Anxiety and depression are two important contributors to the global burden of disease . In many developing countries , including Nepal , their prevalences are yet to be assessed . Methods A nationwide cross-sectional study was conducted among a representative sample of Nepalese adults aged 18–65 years ( N = 2100 ) , selected by multistage r and om cluster sampling  and interviewed at home during unannounced visits . The vali date d question naires included the Hospital Anxiety and Depression Scale ( HADS ) , to detect cases of anxiety ( HADS-A ) , depression ( HADS-D ) and comorbid anxiety and depression ( HADS-cAD ) , the Eysenck Personality Question naire Revised Short Form-Neuroticism ( EPQRS-N ) , and the World Health Organization Quality of Life 8- question scale ( WHOQOL-8 ) . Logistic regression analyses were used to explore associations of caseness with four groups of variables : demographic , domicile , substance use , and behavioural and health . Results Age- and gender-adjusted point prevalences of HADS-A , HADS-D and HADS-cAD were 16.1 , 4.2 and 5.9 % respectively . In a multivariate model , HADS-A was positively associated with urban residence ( AOR = 1.82 ; p < 0.001 ) and neuroticism ( AOR = 1.32 ; p < 0.001 ) , and negatively with alcohol consumption ( AOR = 0.71 ; p = 0.041 ) . HADS-D was positively associated with marijuana use ( AOR = 3.61 ; p = 0.017 ) and negatively with quality of life ( QoL ) ( AOR = 0.86 ; p < 0.001 ) . HADS-cAD was positively associated with widowhood ( AOR = 2.71 ; p = 0.002 ) , urban residence ( AOR = 2.37 ; p = 0.001 ) , living at altitude ≥2000 m ( AOR = 2.32 ; p = 0.002 ) and neuroticism ( AOR = 1.26 ; p < 0.001 ) , and negatively with alcohol use ( AOR = 0.56 ; p = 0.026 ) and QoL ( AOR = 0.79 ; p < 0.001 ) . Conclusion Depression and anxiety are important mental health conditions in Nepal , and major contributors to public ill health , being very highly prevalent , comorbid and associated with psychosocial burden . They are also linked to the unique topography , habitation and social structure of the country . High prevalence coupled with the disabling nature of these disorders establishes their health-care priority and their importance in national health policy BACKGROUND Validation of animal models of hallucinogenic drugs ' subjective effects requires human data . Previous human studies used varied groups of subjects and assessment methods . Rating scales for hallucinogen effects emphasized psychodynamic principles or the drugs ' dysphoric properties . We describe the subjective effects of grade d doses of N , N-dimethyltryptamine ( DMT ) , an endogenous hallucinogen and drug of abuse , in a group of experienced hallucinogen users . We also present preliminary data from a new rating scale for these effects . METHODS Twelve highly motivated volunteers received two doses ( 0.04 and 0.4 mg/kg ) of intravenous ( IV ) dimethyltryptamine fumarate " nonblind , " before entering a double-blind , saline placebo-controlled , r and omized study using four doses of IV DMT . Subjects were carefully interviewed after resolution of drug effects , providing thorough and systematic descriptions of DMT 's effects . They also were administered a new instrument , the Hallucinogen Rating Scale ( HRS ) . The HRS was drafted from interviews obtained from an independent sample of 19 experienced DMT users , and modified during early stages of the study . RESULTS Psychological effects of IV DMT  began almost immediately after administration , peaked at 90 to 120 seconds , and were almost completely resolved by 30 minutes . This time course paralleled DMT  blood levels previously described . Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate , and included a rapidly moving , brightly colored visual display of images . Auditory effects were less common . " Loss of control , " associated with a brief , but overwhelming " rush , " led to a dissociated state , where euphoria alternated or coexisted with anxiety . These effects completely replaced subjects ' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness . Lower doses , 0.1 and 0.05 mg/kg , were primarily affective and somaesthetic , while 0.1 mg/kg elicited the least desirable effects . Clustering of HRS items , using either a clinical , mental status method or principal components factor analysis provided better resolution of dose effects than did the biological variables described previously . CONCLUSIONS These clinical and preliminary quantitative data provide bases for further psychopharmacologic characterization of DMT 's properties in humans . They also may be used to compare the effects of other agents affecting relevant brain receptors in volunteer and psychiatric population Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders , rigorous follow-up has not been conducted . To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate ( 20 mg/70 kg ) and high ( 30 mg/70 kg ) doses of psilocybin within a structured 15-week smoking cessation treatment protocol . Participants were 15 psychiatrically healthy nicotine-dependent smokers ( 10 males ; mean age of 51 years ) , with a mean of six previous lifetime quit attempts , and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake . Biomarkers assessing smoking status , and self-report measures of smoking behavior demonstrated that 12 of 15 participants ( 80 % ) showed seven-day point prevalence abstinence at 6-month follow-up . The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and /or pharmacological therapies ( typically < 35 % ) . Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin , these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models . The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction BACKGROUND Lysergic acid diethylamide ( LSD ) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way . This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study . METHOD A total of 20 healthy volunteers participated in this within-subjects study . Participants received LSD ( 75 µg , intravenously ) on one occasion and placebo ( saline , intravenously ) on another , in a balanced order , with at least 2 weeks separating sessions . Acute subjective effects were measured using the Altered States of Consciousness question naire and the Psychotomimetic States Inventory ( PSI ) . A measure of optimism ( the Revised Life Orientation Test ) , the Revised NEO Personality Inventory , and the Peter 's Delusions Inventory were issued at baseline and 2 weeks after each session . RESULTS LSD produced robust psychological effects ; including heightened mood but also high scores on the PSI , an index of psychosis-like symptoms . Increased optimism and trait openness were observed 2 weeks after LSD ( and not placebo ) and there were no changes in delusional thinking . CONCLUSIONS The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term . It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition , and that increased cognitive flexibility subsequent to serotonin 2A receptor ( 5-HT2AR ) stimulation promotes emotional lability during intoxication and leaves a residue of ' loosened cognition ' in the mid to long term that is conducive to improved psychological wellbeing & NA ; Recent evidence indicates that psilocybin with psychological support may be effective for treating depression . Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses ( Ma , 2015 ) . We hypothesised that amygdala responses to emotional faces would be altered post‐treatment with psilocybin . In this open‐label study , 20 individuals diagnosed with moderate to severe , treatment‐resistant depression , underwent two separate dosing sessions with psilocybin . Psychological support was provided before , during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last . Neutral , fearful and happy faces were presented in the scanner and analyses focused on the amygdala . Group results revealed rapid and enduring improvements in depressive symptoms  post psilocybin .  Increased responses to fearful and happy faces were observed in the right amygdala post‐treatment , and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1‐week . Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli , an opposite effect to previous findings with SSRIs . This suggests fundamental differences in these treatments ' therapeutic actions , with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them . Based on the present results , we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression , enabling patients to reconnect with their emotions . Trial registration : IS RCT N , number IS RCT N14426797 . This article is part of the Special Issue entitled ‘ Psychedelics : New Doors , Altered Perceptions ’ . HighlightsPsilocybin with psychological support was used successfully to treat depression . Amygdala responses to fearful faces were increased one day after psilocybin session . Increased amygdala responses predicted positive clinical outcomes .Psilocybin assisted therapy treats depression by reviving emotional responsiveness 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 r and omized to receive the four active doses in either ascending or descending order ( nine participants each ) . Placebo was scheduled quasi-r and omly . During sessions , volunteers used eyeshades and were instructed to direct their attention inward . Volunteers completed question naires 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 . Implication s for therapeutic trials are discussed Objective : A recently published study showed the safety and efficacy of LSD-assisted psychotherapy in patients with anxiety associated with life-threatening diseases . Participants of this study were included in a prospect i ve follow-up . Method : 12 months after finishing LSD psychotherapy , 10 participants were tested for anxiety ( STAI ) and participated in a semi-structured interview . A Qualitative Content Analysis ( QCA ) was carried out on the interviews to elaborate about LSD effects and lasting psychological changes . Results : None of the participants reported lasting adverse reactions . The significant benefits as measured with the STAI were sustained over a 12-month period . In the QCA participants consistently reported insightful , cathartic and interpersonal experiences , accompanied by a reduction in anxiety ( 77.8 % ) and a rise in quality of life ( 66.7 % ) . Evaluations of subjective experiences suggest facilitated access to emotions , confrontation of previously unknown anxieties , worries , re sources and intense emotional peak experiences à la Maslow as major psychological working mechanisms . The experiences created led to a restructuring of the person ’s emotional trust , situational underst and ing , habits and world view . Conclusions : LSD administered in a medically supervised psychotherapeutic setting can be safe and generate lasting benefits in patients with a life-threatening disease . Explanatory models for the therapeutic effects of LSD warrant further study ABSTRACT Background : A recent epidemiological study suggested that 5-methoxy-N , N-dimethyltryptamine ( 5-MeO-DMT ) used for spiritual and recreational reasons is associated with subjective improvement in depression and anxiety . Further exploration of the potential psychotherapeutic effects of 5-MeO-DMT could inform future clinical trials . Objectives : We examined self-reported improvement in  depression and anxiety among people who use 5-MeO-DMT  in a group setting with structured procedures guiding dose and administration of 5-MeO-DMT . Such procedures also include activities for the preparation of , and support during/following sessions , which are similar to procedures used in clinical trials of hallucinogen administration . Next , we examined whether depression or anxiety were improved following use , and whether the acute subjective effects ( mystical/challenging ) or beliefs about the 5-MeO-DMT experience were associated with improvements in these conditions . Methods : Respondents ( n = 362 ; Mage = 47.7 ; Male = 55 % ; White/Caucasian = 84 % ) completed an anonymous web-based survey . Results : Of those reporting having been diagnosed with depression ( 41 % ) or anxiety ( 48 % ) , most reported these conditions were improved ( depression = 80 % ; anxiety = 79 % ) following 5-MeO-DMT use , and fewer reported they were unchanged ( depression = 17 % ; anxiety = 19 % ) or worsened ( depression = 3 % ; anxiety = 2 % ) . Improvement in depression/anxiety conditions were associated with greater intensity of mystical experiences and higher ratings of the spiritual significance and personal meaning of the 5-MeO-DMT experience . There were no associations between depression or anxiety improvement and the intensity of acute challenging physical/psychological effects during the 5-MeO-DMT experience . Conclusions : Future prospect i ve controlled clinical pharmacology studies should examine the safety and efficacy of 5-MeO-DMT administration for relieving depression and anxiety Both psychedelics and meditation exert profound modulatory effects on consciousness , perception and cognition , but their combined , possibly synergistic effects on neurobiology are unknown . Accordingly , we conducted a r and omized , double-blind , placebo-controlled study with 38 participants following a single administration of the psychedelic psilocybin ( 315 μg/kg p.o . ) during a 5-day mindfulness retreat .  Brain dynamics were quantified directly pre- and post-intervention by functional magnetic resonance imaging during the resting state and two meditation forms . The analysis of functional connectivity identified psilocybin-related and mental state-dependent alterations in self-referential processing regions of the default mode network ( DMN ) . Notably , decoupling of medial prefrontal and posterior cingulate cortices , which is thought to mediate sense of self , was associated with the subjective ego dissolution effect during the psilocybin-assisted mindfulness session . The extent of ego dissolution and brain connectivity predicted positive changes in psycho-social functioning of participants 4 months later . Psilocybin , combined with meditation , facilitated neurodynamic modulations in self-referential networks , subserving the process of meditation by acting along the anterior-posterior DMN connection . The study highlights the link between altered self-experience and subsequent behavioral changes . Underst and ing how interventions facilitate transformative experiences may open novel therapeutic perspectives . Insights into the biology of discrete mental states foster our underst and ing of non-ordinary forms of human self-consciousness and their concomitant brain substrate Background : Meta- analysis of r and omized studies using lysergic acid diethylamide ( LSD ) for alcohol use disorder ( AUD ) showed large , significant effects for LSD efficacy compared to control conditions . Clinical studies suggest potential anti-addiction effects of LSD and mechanistically-related classic psychedelics for alcohol and other substance use disorders . Aims : To supplement clinical studies , reports of psychedelic use in naturalistic setting s can provide further data regarding potential effects of psychedelics on alcohol use . Methods : An anonymous online survey of individuals with prior AUD reporting cessation or reduction in alcohol use following psychedelic use in non- clinical setting s. Results : 343 respondents , mostly White ( 89 % ) , males ( 78 % ) , in the USA ( 60 % ) completed the survey . Participants reported seven years of problematic alcohol use on average before the psychedelic experience to which they attributed reduced alcohol consumption , with 72 % meeting retrospective criteria for severe AUD . Most reported taking a moderate or high dose of LSD ( 38 % ) or psilocybin ( 36 % ) , followed by significant reduction in alcohol consumption . After the psychedelic experience 83 % no longer met AUD criteria . Participants rated their psychedelic experience as highly meaningful and insightful , with 28 % endorsing psychedelic-associated changes in life priorities or values as facilitating reduced alcohol misuse . Greater psychedelic dose , insight , mystical-type effects , and personal meaning of experiences were associated with a greater reduction in alcohol consumption , controlling for prior alcohol consumption and related distress . Conclusions : Although results can not demonstrate causality , they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use , supporting further investigation of psychedelic-assisted treatment for AUD BACKGROUND Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species . Recent studies have assessed the therapeutic potential of psilocybin for various conditions , including end-of-life anxiety , obsessive-compulsive disorder , and smoking and alcohol dependence , with promising preliminary results . Here , we aim ed to investigate the feasibility , safety , and efficacy of psilocybin in patients with unipolar treatment-resistant depression . METHODS In this open-label feasibility trial , 12 patients ( six men , six women ) with moderate-to-severe , unipolar , treatment-resistant major depression received two oral doses of psilocybin ( 10 mg and 25 mg , 7 days apart ) in a supportive setting . There was no control group . Psychological support was provided before , during , and after each session . The primary outcome measure for feasibility was patient-reported intensity of psilocybin 's effects . Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up . Depressive symptoms were assessed with st and ard assessment s from 1 week to 3 months after treatment , with the 16-item Quick Inventory of Depressive Symptoms ( QIDS ) serving as the primary efficacy outcome . This trial is registered with IS RCT N , number IS RCT N14426797 . FINDINGS Psilocybin 's  acute psychedelic effects typically became detectable 30 - 60 min after dosing , peaked 2 - 3 h after dosing , and subsided to negligible levels at least 6 h after dosing . Mean self-rated intensity ( on a 0 - 1 scale ) was 0·51 ( SD 0·36 ) for the low-dose session and 0·75 ( SD 0·27 ) for the high-dose session . Psilocybin was well tolerated by all of the patients , and no serious or unexpected adverse events occurred . The adverse reactions we noted were transient anxiety during drug onset ( all patients ) , transient confusion or thought disorder ( nine patients ) , mild and transient nausea ( four patients ) , and transient headache ( four patients ) . Relative to baseline , depressive symptoms were markedly reduced 1 week ( mean QIDS difference -11·8 , 95 % CI -9·15 to -14·35 , p=0·002 , Hedges ' g=3·1 ) and 3 months ( -9·2 , 95 % CI -5·69 to -12·71 , p=0·003 , Hedges ' g=2 ) after high-dose treatment . Marked and sustained improvements in anxiety and anhedonia were also noted . INTERPRETATION This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials , with more rigorous design s , to better examine the therapeutic potential of this approach . FUNDING Medical Research Council ABSTRACT Background : A recent open-label pilot study ( N = 15 ) found that two to three moderate to high doses ( 20 and 30 mg/70 kg ) of the serotonin 2A receptor agonist , psilocybin , in combination with cognitive behavioral therapy ( CBT ) for smoking cessation , result ed in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone . Objectives : To assess long-term effects of a psilocybin-facilitated  smoking cessation program at ≥12 months after psilocybin administration . Methods : The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months , and related data on subjective effects of psilocybin . Results : All 15 participants completed a 12-month follow-up , and 12 ( 80 % ) returned for a long-term ( ≥16 months ) follow-up , with a mean interval of 30 months ( range = 16–57 months ) between target-quit date ( i.e. , first psilocybin session ) and long-term follow-up . At 12-month follow-up , 10 participants ( 67 % ) were confirmed as smoking abstinent . At long-term follow-up , nine participants ( 60 % ) were confirmed as smoking abstinent . At 12-month follow-up 13 participants ( 86.7 % ) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives . Conclusion : These results suggest that in the context of a structured treatment program , psilocybin holds considerable promise in promoting long-term smoking abstinence . The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction . Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted Background : A recently published r and omized controlled trial compared single-dose psilocybin with single-dose niacin in conjunction with psychotherapy in participants with cancer-related psychiatric distress . Results suggested that psilocybin-assisted psychotherapy facilitated improvements in psychiatric and existential distress , quality of life , and spiritual well-being up to seven weeks prior to the crossover . At the 6.5-month follow-up , after the crossover , 60–80 % of participants continued to meet criteria for clinical ly significant antidepressant or anxiolytic responses . Methods : The present study is a long-term within-subjects follow-up analysis of self-reported symptomatology involving a subset of participants that completed the parent trial . All 16 participants who were still alive were contacted , and 15 participants agreed to participate at an average of 3.2 and 4.5 years following psilocybin administration .  Results : Reductions in anxiety , depression , hopelessness , demoralization , and death anxiety were sustained at the first and second follow-ups . Within-group effect sizes were large . At the second ( 4.5 year ) follow-up approximately 60–80 % of participants met criteria for clinical ly significant antidepressant or anxiolytic responses . Participants overwhelmingly ( 71–100 % ) attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives . Conclusion : These findings suggest that psilocybin-assisted psychotherapy holds promise in promoting long-term relief from cancer-related psychiatric distress . Limited conclusions , however , can be drawn regarding the efficacy of this therapy due to the crossover design of the parent study . Nonetheless , the present study adds to the emerging literature base suggesting that psilocybin-facilitated therapy may enhance the psychological , emotional , and spiritual well-being of patients with life-threatening cancer
target: Enduring changes in personality/attitudes , depression , spirituality , anxiety , wellbeing , substance misuse , meditative practice s , and mindfulness were documented .
  Mystical experiences , connectedness , emotional breakthrough , and increased neural entropy were related to these long-term changes in psychological functioning .
  Finally , with proper screening , preparation , supervision , and integration , limited aversive side effects were noted by study participants .
background: Research into the basic effects and therapeutic applications of  psychedelic drugs  has grown considerably in recent years .
  Yet , pressing questions remain regarding the substances ' lasting effects .
  Although individual studies have begun monitoring sustained changes , no study to- date has synthesized this information .