title: 5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride Psychedelics not linked to mental health problems or suicidal behavior: A population study Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Effects of the South American Psychoactive Beverage Ayahuasca on Regional Brain Electrical Activity in Humans: A Functional Neuroimaging Study Using Low-Resolution Electromagnetic Tomography Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Pharmacological modulation of the neural basis underlying inhibition of return (IOR) in the human 5-HT2A agonist and NMDA antagonist model of psychosis Psychedelics and Mental Health: A Population Study Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers Increased frontal and paralimbic activation following ayahuasca, the pan-amazonian inebriant Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Seeing with the eyes shut: neural basis of enhanced imagery following Ayahuasca ingestion. Neuronal correlates of visual and auditory alertness in the DMT and ketamine model of psychosis Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans Psilocybin induces schizophrenia‐like psychosis in humans via a serotonin‐2 agonist action Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study
abstract: The modulating effects of serotonin on dopamine neurotransmission are not well understood , particularly in acute psychotic states .  Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo  and a  psychotomimetic dose of psilocybin ( n = 7 ) .  Psilocybin is a potent indoleamine hallucinogen and a mixed 5-HT2A and 5-HT1A receptor agonist . Psilocybin administration ( 0.25 mg/kg p.o . ) produced changes in mood , disturbances in thinking , illusions , elementary and complex visual hallucinations and impaired ego-functioning .  Psilocybin significantly decreased [11C]raclopride receptor binding potential ( BP ) bilaterally in the cau date nucleus ( 19 % ) and putamen ( 20 % ) consistent with an increase in endogenous dopamine . Changes in [11C]raclopride BP in the ventral striatum correlated with depersonalization associated with euphoria . Together with previous reports of 5-HT receptor involvement in striatal dopamine release , it is concluded that stimulation of both 5-HT2A and 5-HT1A receptors may be important for the modulation of striatal dopamine release in acute psychoses . The present results indirectly support the hypothesis of a serotonin-dopamine dysbalance in schizophrenia and suggest that psilocybin is a valuable tool in the analysis of serotonin-dopamine interactions in acute psychotic states 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 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 Ayahuasca , a South American psychotropic plant tea obtained from Banisteriopsis caapi and Psychotria viridis , combines monoamine oxidase-inhibiting β-carboline alkaloids with N , N-dimethyltryptamine ( DMT ) , a psychedelic agent showing 5-HT2A agonist activity . In a clinical research setting , ayahuasca has demonstrated a combined stimulatory and psychedelic effect profile , as measured by subjective effect self- assessment instruments and dose-dependent changes in spontaneous brain electrical activity , which parallel the time course of subjective effects . In the present study , the spatial distribution of ayahuasca-induced changes in brain electrical activity was investigated by means of low-resolution electromagnetic tomography ( LORETA ) . Electroencephalography recordings were obtained from 18 volunteers after the administration of a dose of encapsulated freeze-dried ayahuasca containing 0.85 mg DMT/kg body weight and placebo . The intracerebral power density distribution was computed with LORETA from spectrally analyzed data , and subjective effects were measured by means of the Hallucinogen Rating Scale ( HRS ) . Statistically significant differences compared to placebo were observed for LORETA power 60 and 90 min after dosing , together with increases in all six scales of the HRS . Ayahuasca decreased power density in the alpha-2 , delta , theta and beta-1 frequency b and s. Power decreases in the delta , alpha-2 and beta-1 b and s were found predominantly over the temporo-parieto-occipital junction , whereas theta power was reduced in the temporomedial cortex and in frontomedial regions . The present results suggest the involvement of unimodal and heteromodal association cortex and limbic structures in the psychological effects elicited by ayahuasca 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 Psychedelic drugs have a long history of use in healing ceremonies , but despite renewed interest in their therapeutic potential , we continue to know very little about how they work in the brain . Here we used psilocybin , a classic psychedelic found in magic mushrooms , and a task-free functional MRI ( fMRI ) protocol design ed to capture the transition from normal waking consciousness to the psychedelic state . Arterial spin labeling perfusion and blood-oxygen level-dependent ( BOLD ) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin .  Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD . As predicted , profound changes in consciousness were observed after psilocybin , but surprisingly , only decreases in cerebral blood flow and BOLD signal were seen , and these were maximal in hub regions , such as the thalamus and anterior and posterior cingulate cortex ( ACC and PCC ) . Decreased activity in the ACC/medial prefrontal cortex ( mPFC ) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects . Based on these results , a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed . Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC . These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain 's key connector hubs , enabling a state of unconstrained cognition 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 : 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 Rationale Attentional deficits are common symptoms in schizophrenia . Recent evidence suggests that schizophrenic patients show abnormalities in spatial orienting of attention , particularly a deficit of inhibition of return ( IOR ) . IOR is mostly thought to reflect an automatic , inhibitory mechanism protecting the organism from redirecting attention to previously scanned , insignificant locations . Pharmacologic challenges with hallucinogens have been used as models for psychosis . Objectives The aim of this study was to investigate the neural correlates underlying orienting of attention in the human N-methyl-d-aspartic acid antagonist and 5-HT2A agonist models of psychosis . Material s and methods Fourteen healthy volunteers participated in a r and omized , double-blind , cross-over event-related functional magnetic resonance imaging ( fMRI ) study with dimethyltryptamine ( DMT ) and S-ketamine . We administered a covert orienting of attention task with nonpredictive peripheral cues , and we scanned the subjects on two separate days at least 14 days apart with a placebo and a verum condition on each day . Results DMT , but not S-ketamine , slowed down reaction times significantly . IOR was blunted after DMT , but not after S-ketamine . Relative to placebo , S-ketamine increased activation in the IOR condition in the right superior frontal gyrus , left superior temporal gyrus , and right midfrontal frontal gyrus . Conclusions The discrepancy between the behavioral and functional imaging outcome indicates that pharmacological fMRI might be a sensitive tool to detect drug-modulated blood oxygenation level-dependent signal changes in the absence of behavioral abnormalities . Our findings might help to further clarify the contradictory findings of IOR in schizophrenic patients and might , thus , shed more light on possible differential pathomechanisms of schizophrenic symptoms Background The classical serotonergic psychedelics LSD , psilocybin , mescaline are not known to cause brain damage and are regarded as non-addictive . Clinical studies do not suggest that psychedelics cause long-term mental health problems .  Psychedelics have been used in the Americas for thous and s of years . Over 30 million people currently living in the US have used LSD , psilocybin , or mescaline . Objective To evaluate the association between the lifetime use of psychedelics and current mental health in the adult population . Method Data drawn from years 2001 to 2004 of the National Survey on Drug Use and Health consisted of 130,152 respondents , r and omly selected to be representative of the adult population in the United States . St and ardized screening measures for past year mental health included serious psychological distress ( K6 scale ) , mental health treatment ( inpatient , outpatient , medication , needed but did not receive ) , symptoms of eight psychiatric disorders ( panic disorder , major depressive episode , mania , social phobia , general anxiety disorder , agoraphobia , posttraumatic stress disorder , and non-affective psychosis ) , and seven specific symptoms of non-affective psychosis . We calculated weighted odds ratios by multivariate logistic regression controlling for a range of sociodemographic variables , use of illicit drugs , risk taking behavior , and exposure to traumatic events . Results 21,967 respondents ( 13.4 % weighted ) reported lifetime psychedelic use . There were no significant associations between lifetime use of any psychedelics , lifetime use of specific psychedelics ( LSD , psilocybin  , mescaline , peyote ) , or past year use of LSD and increased rate of any of the mental health outcomes . Rather , in several cases psychedelic use was associated with lower rate of mental health problems . Conclusion We did not find use of psychedelics to be an independent risk factor for mental health problems BACKGROUND The amygdala is a key structure in serotonergic emotion-processing circuits . In healthy volunteers , acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states . However , it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change . METHODS This study assessed the effects of acute administration of the hallucinogen psilocybin ( .16 mg/kg ) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging . Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory . A double-blind , r and omized , cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart . RESULTS Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration . The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state . CONCLUSIONS These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers . These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression Rationale Ayahuasca is a South American psychoactive plant tea which contains the serotonergic psychedelic N , N-dimethyltryptamine ( DMT ) and monoamine-oxidase inhibitors that render DMT orally active . Previous investigations with ayahuasca have highlighted a psychotropic effect profile characterized by enhanced introspective attention , with individuals reporting altered somatic perceptions and intense emotional modifications , frequently accompanied by visual imagery . Despite recent advances in the study of ayahuasca pharmacology , the neural correlates of acute ayahuasca intoxication remain largely unknown . Objectives To investigate the effects of ayahuasca administration on regional cerebral blood flow . Methods Fifteen male volunteers with prior experience in the use of psychedelics received a single oral dose of encapsulated freeze-dried ayahuasca equivalent to 1.0 mg DMT/kg body weight and a placebo in a r and omized double-blind clinical trial . Regional cerebral blood flow was measured 100–110 min after drug administration by means of single photon emission tomography ( SPECT ) . Results Ayahuasca administration led to significant activation of frontal and paralimbic brain regions . Increased blood perfusion was observed bilaterally in the anterior insula , with greater intensity in the right hemisphere , and in the anterior cingulate/frontomedial cortex of the right hemisphere , areas previously implicated in somatic awareness , subjective feeling states , and emotional arousal . Additional increases were observed in the left amygdala/parahippocampal gyrus , a structure also involved in emotional arousal . Conclusions The present results suggest that ayahuasca interacts with neural systems that are central to interoception and emotional processing and point to a modulatory role of serotonergic neurotransmission in these processes 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 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 The hallucinogenic brew Ayahuasca , a rich source of serotonergic agonists and reuptake inhibitors , has been used for ages by Amazonian population s during religious ceremonies . Among all perceptual changes induced by Ayahuasca , the most remarkable are vivid " seeings . " During such seeings , users report potent imagery . Using functional magnetic resonance imaging during a closed-eyes imagery task , we found that Ayahuasca produces a robust increase in the activation of several occipital , temporal , and frontal areas . In the primary visual area , the effect was comparable in magnitude to the activation levels of natural image with the eyes open . Importantly , this effect was specifically correlated with the occurrence of individual perceptual changes measured by psychiatric scales . The activity of cortical areas BA30 and BA37 , known to be involved with episodic memory and the processing of context ual associations , was also potentiated by Ayahuasca intake during imagery . Finally , we detected a positive modulation by Ayahuasca of BA 10 , a frontal area involved with intentional prospect i ve imagination , working memory and the processing of information from internal sources . Therefore , our results indicate that Ayahuasca seeings stem from the activation of an extensive network generally involved with vision , memory , and intention . By boosting the intensity of recalled images to the same level of natural image , Ayahuasca lends a status of reality to inner experiences . It is therefore underst and able why Ayahuasca was culturally selected over many centuries by rain forest shamans to facilitate mystical revelations of visual nature Deficits in attentional functions belong to the core cognitive symptoms in schizophrenic patients . Alertness is a nonselective attention component that refers to a state of general readiness that improves stimulus processing and response initiation . The main goal of the present study was to investigate cerebral correlates of alertness in the human 5HT2A agonist and N-methyl-D-aspartic acid ( NMDA ) antagonist model of psychosis . Fourteen healthy volunteers participated in a r and omized double-blind , cross-over event-related functional magnetic resonance imaging ( fMRI ) study with dimethyltryptamine ( DMT ) and S-ketamine . A target detection task with cued and uncued trials in both the visual and the auditory modality was used . Administration of DMT led to decreased blood oxygenation level-dependent response during performance of an alertness task , particularly in extrastriate regions during visual alerting and in temporal regions during auditory alerting . In general , the effects for the visual modality were more pronounced . In contrast , administration of S-ketamine led to increased cortical activation in the left insula and pre central gyrus in the auditory modality . The results of the present study might deliver more insight into potential differences and overlapping pathomechanisms in schizophrenia . These conclusions must remain preliminary and should be explored by further fMRI studies with schizophrenic patients performing modality-specific alertness tasks AIMS Ayahuasca is a traditional South American psychoactive beverage used in Amazonian shamanism , and in the religious ceremonies of Brazilian-based syncretic religious groups with followers in the US and several European countries . This tea contains measurable amounts of the psychotropic indole N , N-dimethyltryptamine ( DMT ) , and beta-carboline alkaloids with MAO-inhibiting properties . In a previous report we described a profile of stimulant and psychedelic effects for ayahuasca as measured by subjective report self- assessment instruments . In the present study the cerebral bioavailability and time-course of effects of ayahuasca were assessed in humans by means of topographic quantitative-electroencephalography ( q-EEG ) , a noninvasive method measuring drug-induced variations in brain electrical activity . METHODS Two doses ( one low and one high ) of encapsulated freeze-dried ayahuasca , equivalent to 0.6 and 0.85 mg DMT kg(-1 ) body weight , were administered to 18 healthy volunteers with previous experience in psychedelic drug use in a double-blind crossover placebo-controlled clinical trial . Nineteen-lead recordings were undertaken from baseline to 8 h after administration . Subjective effects were measured by means of the Hallucinogen Rating Scale ( HRS ) . RESULTS Ayahuasca induced a pattern of psychoactive effects which result ed in significant dose-dependent increases in all subscales of the HRS , and in significant and dose-dependent modifications of brain electrical activity . Absolute power decreased in all frequency b and s , most prominently in the theta b and . Mean absolute power decreases ( 95 % CI ) at a representative lead ( P3 ) 90 min after the high dose were -20.20+/-15.23 microV2 and -2.70+/-2.21 microV2 for total power and theta power , respectively . Relative power decreased in the delta ( -1.20+/-1.31 % after 120 min at P3 ) and theta ( -3.30+/-2.59 % after 120 min at P3 ) b and s , and increased in the beta b and , most prominently in the faster beta-3 ( 1.00+/-0.88 % after 90 min at P3 ) and beta-4 ( 0.30+/-0.24 % after 90 min at P3 ) subb and s. Finally , an increase was also seen for the centroid of the total activity and its deviation . EEG modifications began as early as 15 - 30 min , reached a peak between 45 and 120 min and decreased thereafter to return to baseline levels at 4 - 6 h after administration . CONCLUSIONS The central effects of ayahuasca could be objective ly measured by means of q-EEG , showing a time pattern which closely paralleled that of previously reported subjective effects . The modifications seen for the individual  q-EEG  variables were in line with those previously described for other serotonergic psychedelics and share some features with the profile of effects shown by pro-serotonergic and pro-dopaminergic drugs . The q-EEG profile supports the role of 5-HT2 and dopamine D2-receptor agonism in mediating the effects of ayahuasca on the central nervous system 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 After no research in humans for > 40 years , there is renewed interest in using lysergic acid diethylamide ( LSD ) in clinical psychiatric research and practice . There are no modern studies on the subjective and autonomic effects of LSD , and its endocrine effects are unknown . In animals , LSD disrupts prepulse inhibition ( PPI ) of the acoustic startle response , and patients with schizophrenia exhibit similar impairments in PPI . However , no data are available on the effects of LSD on PPI in humans . METHODS In a double-blind , r and omized , placebo-controlled , crossover study , LSD ( 200 μg ) and placebo were administered to 16 healthy subjects ( 8 women , 8 men ) . Outcome measures included psychometric scales ; investigator ratings ; PPI of the acoustic startle response ; and autonomic , endocrine , and adverse effects . RESULTS Administration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours . The predominant effects induced by LSD  included visual hallucinations , audiovisual synesthesia , and positively experienced derealization and depersonalization phenomena . Subjective well-being , happiness , closeness to others , openness , and trust were increased by LSD . Compared with placebo , LSD  decreased PPI  . LSD significantly increased blood pressure , heart rate , body temperature , pupil size , plasma cortisol , prolactin , oxytocin , and epinephrine . Adverse effects produced by LSD completely subsided within 72 hours . No severe acute adverse effects were observed . CONCLUSIONS In addition to marked hallucinogenic effects , LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy . LSD altered sensorimotor gating in a human model of psychosis , supporting the use of LSD in translational psychiatric research . In a controlled clinical setting , LSD can be used safely , but it produces significant sympathomimetic stimulation 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 BACKGROUND Serotonin ( 5-HT ) 1A and 2A receptors have been associated with dysfunctional emotional processing biases in mood disorders . These receptors further predominantly mediate the subjective and behavioral effects of psilocybin and might be important for its recently suggested antidepressive effects . However , the effect of psilocybin on emotional processing biases and the specific contribution of 5-HT2A receptors across different emotional domains is unknown . METHODS In a r and omized , double-blind study , 17 healthy human subjects received on 4 separate days placebo , psilocybin ( 215 μg/kg ) , the preferential 5-HT2A antagonist ketanserin ( 50 mg ) , or psilocybin plus ketanserin .  Mood states were assessed by self-report ratings , and behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal -directed behavior toward emotional cues . RESULTS Psilocybin enhanced positive mood and attenuated recognition of negative facial expression .  Furthermore , psilocybin increased goal -directed behavior toward positive compared with negative cues , facilitated positive but inhibited negative sequential emotional effects , and valence-dependently attenuated the P300 component . Ketanserin alone had no effects but blocked the psilocybin-induced mood enhancement and decreased recognition of negative facial expression . CONCLUSIONS This study shows that psilocybin shifts the emotional bias across various psychological domains and that activation of 5-HT2A receptors is central in mood regulation and emotional face recognition in healthy subjects . These findings may not only have implication s for the pathophysiology of dysfunctional emotional biases but may also provide a framework to delineate the mechanisms underlying psylocybin 's putative antidepressant effects 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 Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants , Banisteriopsis caapi and Psychotria viridis . It contains the psychedelic 5-HT2A and sigma-1 agonist N , N-dimethyltryptamine ( DMT ) plus β-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties . Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor , the molecular target of classical psychedelics , this has not been tested experimentally . Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans . We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind r and omized placebo-controlled study involving the oral administration of ayahuasca ( 0.75 mg DMT/kg body weight ) and the 5-HT2A antagonist ketanserin ( 40 mg ) . Twelve healthy , experienced psychedelic users ( 5 females ) participated in four experimental sessions in which they received the following drug combinations : placebo+placebo , placebo+ayahuasca , ketanserin+placebo and ketanserin+ayahuasca . Ayahuasca induced EEG power decreases in the delta , theta and alpha frequency b and s. Current density in alpha-b and oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca . Pretreatment  with ketanserin inhibited neurophysiological modifications , reduced the correlation between alpha and visual effects , and attenuated the intensity of the subjective experience . These findings suggest that despite the chemical complexity of ayahuasca , 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans PSILOCYBIN , an indoleamine hallucinogen , produces a  psychosis-like syndrome in humans that resembles first episodes of schizophrenia . In healthy human volunteers , the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone , but were increased by the dopamine antagonist and typical antipsychotic haloperidol . These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation , independently of dopamine stimulation . Thus , serotonin-2A overactivity may be involved in the pathophysiology of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics Abstract Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine , a 5-HT2A receptor agonist , and harmine , a monoamine-oxidase A inhibitor . Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients . The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow . In an open-label trial conducted in an inpatient psychiatric unit , 17 patients with recurrent depression received an oral dose of ayahuasca ( 2.2 mL/kg ) and were evaluated with the Hamilton Rating Scale for Depression , the Montgomery-Åsberg Depression Rating Scale , the Brief Psychiatric Rating Scale , the Young Mania Rating Scale , and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1 , 7 , 14 , and 21 days after drug intake . Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography . Ayahuasca administration was associated with increased psychoactivity ( Clinician Administered Dissociative States Scale ) and significant score decreases in depression-related scales ( Hamilton Rating Scale for Depression , Montgomery-Åsberg Depression Rating Scale , Brief Psychiatric Rating Scale ) from 80 minutes to day 21 . Increased blood perfusion in the left nucleus accumbens , right insula and left subgenual area , brain regions implicated in the regulation of mood and emotions , were observed after ayahuasca intake . Ayahuasca was well tolerated . Vomiting was the only adverse effect recorded , being reported by 47 % of the volunteers . Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties . These results should be replicated in r and omized , double-blind , placebo-controlled trials
target: Long-term use was associated with thinning of the posterior cingulate cortex , thickening of the anterior cingulate cortex , and decreased neocortical 5-HT2A receptor binding .
  Despite the high method ological heterogeneity and the small sample sizes , the results suggest that hallucinogens increase introspection and positive mood by modulating brain activity in the fronto-temporo-parieto-occipital cortex
background: Serotonergic hallucinogens produce alterations of perceptions , mood , and cognition , and have anxiolytic , antidepressant , and antiaddictive properties .
  These drugs act as agonists of frontocortical 5-HT2A receptors , but the neural basis of their effects are not well understood .
  Thus , we conducted a systematic review of neuroimaging studies analyzing the effects of serotonergic hallucinogens in man .