human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
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
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    