Serotonergic psychedelics and personality: A systematic review of contemporary research 5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers The paradoxical psychological effects of lysergic acid diethylamide (LSD). A Review of Vilazodone, Serotonin, and Major Depressive Disorder Seeing with the eyes shut: neural basis of enhanced imagery following Ayahuasca ingestion. Pharmacological modulation of the neural basis underlying inhibition of return (IOR) in the human 5-HT2A agonist and NMDA antagonist model of psychosis Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors Effects of dopaminergic and serotonergic manipulation on emotional processing: A pharmacological fMRI study Psychological and Cardiovascular Effects and Short-Term Sequelae of MDMA (“Ecstasy”) in MDMA-Naïve Healthy Volunteers Serotonergic and Noradrenergic Modulation of Emotion Processing by Single Dose Antidepressants Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Cognitive Improvement in Schizophrenic Patients does not Require a Serotonergic Mechanism: Randomized Controlled Trial of Olanzapine vs Amisulpride Clonidine decreases intraoperative bleeding in middle ear microsurgery PET analysis of the 5-HT2A receptor inverse agonist ACP-103 in human brain. Are serotonergic reuptake inhibitors more potent in reducing suicidality? An empirical study on paroxetine Serotonergic targets in the treatment of antidepressant induced sexual dysfunction: a pilot study of granisetron and sumatriptan Administration of clonazepam in the treatment of TMD and associated myofascial pain: a double-blind pilot study. Effects of the South American Psychoactive Beverage Ayahuasca on Regional Brain Electrical Activity in Humans: A Functional Neuroimaging Study Using Low-Resolution Electromagnetic Tomography Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers. Gender differences in the subjective effects of MDMA Neural correlates of working memory in pure and polyvalent ecstasy (MDMA) users
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 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 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 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 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 Objective : To review the mechanism of selective serotonin reuptake inhibitor (SSRI)–mediated serotonergic neurotransmission , focusing on serotonin 1A ( 5-HT1A ) autoreceptors , which are proposed to be involved in delaying therapeutic efficacy . Vilazodone was specifically design ed to function both as an SSRI and a partial agonist at 5-HT1A receptors . This combined mechanism is proposed to decrease time to efficacy , minimize sexual side effects , and provide concomitant anxiolytic properties . Data Sources : A PubMed search of all English- language articles from January 1990 to January 2013 was conducted using the search terms depression and 5-HT1A , depression and buspirone , depression and pindolol , and vilazodone . Study Selection : We found 47 articles and abstract s that were selected for inclusion on the basis of information about the pharmacology of 5-HT1A receptors and the clinical data on pindolol , buspirone , and vilazodone in depression . Data Extraction : This review summarizes current literature involving antidepressant activity , the role of 5-HT1A autoreceptors , and clinical trials involving serotonin reuptake inhibition in conjunction with 5-HT1A agonists and partial agonists , with a focus on vilazodone . Results : Vilazodone has demonstrated efficacy in 2 large , r and omized , double-blind , placebo-controlled trials in major depressive disorder . Results suggest that vilazodone has a low incidence of sexual side effects and is effective in patients with high levels of anxiety . A pooled analysis shows evidence of significant symptom reduction after only 1 week of therapy . Conclusions : If future studies corroborate the clinical benefits attributed to its mechanism of action , vilazodone may show potential advantages in terms of onset of action , sexual side effects , and anxiolytic activity in patients with major depressive disorder 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 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 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 Recent neuroimaging studies have demonstrated abnormal central emotional processing in psychiatric disorders . The dopamine ( DA ) systems and serotonin ( 5-HT ) systems are the main target of psychopharmacotherapy . DA D2 receptor antagonists and selective serotonin reuptake inhibitors ( SSRIs ) are widely used in psychiatric practice . Investigating the effects of these drugs on emotional processing should lead to a better underst and ing of the pathophysiology and pharmacotherapy of neuropsychiatric disorders . We aim ed to examine effects of dopaminergic and serotonergic manipulation on neural responses to unpleasant pictures in healthy volunteers using pharmacological fMRI .  Thirteen healthy male subjects participated in a single-blind , r and omized , placebo-controlled design study . Each subject participated in three fMRI sessions . In each session , participants were orally administered either 25 mg of sultopride or 50 mg of fluvoxamine or placebo prior to scanning , and neural responses to unpleasant and neutral pictures were recorded . Despite no significant differences being found in the subjective ratings of affective pictures across three sessions , compared to placebo , acute treatments of DA D2 receptor antagonists and SSRIs commonly attenuated the amygdala activity , although both treatments had slightly different modulatory effects on other components of the neural circuit of emotional processing . This study has shown that even acute treatment of drugs that manipulate neurotransmitter systems could affect brain activation associated with emotional processing in human brain . At the same time , our findings suggest that pharmacological fMRI could be a powerful tool for investigating the neurophysiological properties of drugs targeting neuropsychiatric disorders 3,4-methylenedioxymethamphetamine ( MDMA , “ Ecstasy ” ) is a recreational drug reported to produce a different psychological profile than that of classic hallucinogens and stimulants . It has , therefore , been tentatively classified into a novel pharmacological class termed entactogens . This double-blind placebo-controlled study examined the effects of a typical recreational dose of MDMA ( 1.7 mg/kg ) in 13 MDMA-naıuml;ve healthy volunteers .  MDMA produced an affective state of enhanced mood , well-being , and increased emotional sensitiveness , little anxiety , but no hallucinations or panic reactions . Mild depersonalization and derealization phenomena occurred together with moderate thought disorder , first signs of loss of body control , and alterations in the meaning of percepts . Subjects also displayed changes in the sense of space and time , heightened sensory awareness , and increased psychomotor drive .  MDMA did not impair selective attention as measured by the Stroop test . MDMA  increased blood pressure moderately , with the exception of one subject who showed a transient hypertensive reaction . This severe increase in blood pressure indicates that the hypertensive effects of MDMA , even at recreational doses , should not be underestimated , particularly in subjects with latent cardiovascular problems . Most frequent acute somatic complaints during the MDMA challenge were jaw clenching , lack of appetite , impaired gait , and restless legs . Adverse sequelae during the following 24 hours included lack of energy and appetite , feelings of restlessness , insomnia , jaw clenching , occasional difficulty concentrating , and brooding . The present findings are consistent with the hypothesis that MDMA produces a different psychological profile than classic hallucinogens or psychostimulants Serotonergic and noradrenergic pathways are the main targets of antidepressants . Their differential effects on emotion processing-related brain activation are , however , to be further characterized . We aim ed at elucidating the neural sites of action of an acute differential serotonergic and noradrenergic influence on an emotion-processing task , which was earlier shown to be associated with depressiveness . In a single-blind pseudo-r and omized crossover study , 21 healthy subjects ( 16 subjects finally included in the analysis ) participated to ingest a single dose at three time points of either 40 mg citalopram , a selective serotonin-reuptake inhibitor , 8 mg reboxetine , a selective noradrenaline-reuptake inhibitor , or placebo 2–3 h before functional magnetic resonance imaging ( fMRI ) . During fMRI , subjects performed a task comprising the anticipation and perception of pictures of either ‘ known ’ ( positive , negative , neutral ) or ‘ unknown ’ valence ( r and omly 50 % positive or negative ) . In direct comparison with citalopram and with placebo , reboxetine increased brain activity in the medial thalamus . Citalopram modulated certain prefrontal and insular areas more prominently . Other frontal and parieto-occipital areas were modulated by both drugs . In conclusion , the functional network involved in emotional information processing could be modulated by the acute application of selective noradrenergic and serotonergic drugs revealing a noradrenergic effect in thalamic and frontal areas , and a prefrontal and insular focus of serotonergic modulation . These findings could have implication s for future selection criteria concerning personalized antidepressant medication in depression 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 Combined serotonin-2A ( 5-HT2A ) and dopamine-2 ( D2 ) receptor blockade has been proposed as a c and i date mechanism by which second-generation antipsychotics ( SGAs ) improve both cognition and negative symptoms in schizophrenic patients , in contrast to antipsychotics of the first generation . The SGA amisulpride , however , only binds to D2/D3 receptors , which makes it an interesting tool to test this assumption . In a r and omized controlled trial , 52 schizophrenic patients were allocated to treatment with either olanzapine ( 10–20 mg/day ) or amisulpride ( 400–800 mg/day ) . A comprehensive neuropsychological test battery and clinical ratings were used to assess participants at inclusion and after 4 and 8 weeks . Cognitive improvements of moderate size were observed , with effect sizes similar to those obtained in previous studies on the cognitive effects of SGAs . Importantly , amisulpride was not inferior to olanzapine for any cognitive domain . Combined 5-HT2A/D2 receptor blockade is probably not necessary for cognitive improvement by SGAs Background : The antihypertensive drug clonidine is a central ly acting α2 agonist useful as a premedicant because of its sedative , anxiolytic , and analgesic properties . We examined the effect of clonidine given as an oral preanesthetic medication in producing a bloodless surgical field in patients undergoing middle ear microsurgery . We also evaluated whether the administration of clonidine would alter the reflex cardiovascular response to laryngoscopy and endotracheal intubation , anesthetic requirement , postoperative pain intensity and consumption of analgesics , and pre‐ and postoperative sedation and anxiety The mechanisms underlying the clinical properties of atypical antipsychotics have been postulated to be mediated , in part , by interactions with the 5-HT2A receptor . Recently , it has been recognized that clinical ly effective antipsychotic drugs are 5-HT2A receptor inverse agonists rather than neutral antagonists . In the present study , which is part of the clinical development of the novel , selective 5-HT2A receptor inverse agonist ACP-103 , we applied positron emission tomography ( PET ) with the radiolig and [11C]N-methylspiperone ( [11C]NMSP ) to study the relationship between oral dose , plasma level , and uptake of ACP-103 in living human brain . The safety of drug administration was also assessed . Four healthy volunteers were examined by PET at baseline , and after the oral administration of various single doses of ACP-103 . Two subjects each received 1 , 5 , and 20 mg doses , and two subjects each received 2 , 10 , and 100 mg doses , respectively . ACP-103 was well tolerated . Detectable receptor binding was observed at very low ACP-103 serum levels . Cortical [11C]NMSP binding was found to be dose-dependent and fitted well to the law of mass action . A reduction in binding was detectable after an oral dose of ACP-103 as low as 1 mg , and reached near maximal displacement following the 10 - 20 mg dose . In conclusion , administration of ACP-103 to healthy volunteers was found to be safe and well tolerated , and single oral doses as low as 10 mg were found to fully saturate 5-HT2A receptors in human brain as determined by PET There is some empirical evidence that selective serotonin reuptake inhibitors reduce suicidal ideas faster than other antidepressants . These findings are well in line with the theory of a serotonergic hypofunction in suicidal patients . To test this hypothesis the data of a 6-week double-blind control-group study comparing paroxetine versus amitriptyline were analyzed with respect to suicidality .  The global antidepressive efficacy was comparable under dosages of 30 mg paroxetine or 150 mg amitriptyline per day . A differentiated analysis failed to confirm the hypothesis of a faster reduction of suicidal cognitions by paroxetine & NA ; Antidepressant induced sexual dysfunction is a common adverse event that is particularly evident with serotonergic antidepressants . There is a paucity of clinical trial evidence on the treatment of this problem . While there is some evidence of involvement of the serotonin ( 5‐HT2 ) receptor subtype in this phenomenon , other serotonergic receptor systems are not well studied . In this trial , 35 patients on maintenance therapy with a variety of serotonergic antidepressants , who reported antidepressant induced sexual dysfunction , were enrolled . Patients were given both granisetron 1 mg , and sumatriptan 100 mg , in a crossover design , to be used 1 h before intercourse . Sexual dysfunction was measured using the Feiger scale . There was a high dropout rate in the trial , reflecting both embarrassment with the pharmacological treatment of sexual dysfunction and difficulties with planning and timing the medication . Nevertheless , there was a significant effect of granisetron in this study , with scores decreasing from 23.7 ( SD 2.52 ) to 16.0 ( SD 6.42 ) on the Feiger scale ( n = 14 , P = 0.001 , Wilcoxon sign rank test  ) . Sumatriptan failed to show a significant change from baseline at the 0.01 level of significance . While the small sample size , high dropout rates and open label design are limitations to this study , it suggests efficacy of the granisetron in antidepressant induced sexual dysfunction and the role of the 5‐HT3 receptor in this phenomenon A double-blind pilot study was undertaken to test the administration of low doses of the long-acting benzodiazepine drug clonazepam in the management of chronic intractable temporom and ibular disorder/myofascial pain patients who were not responsive to occlusal splint , behavioral , and physical therapy .  Clonazepam was selected for its long duration and its cholinergic/GABA-ergic/serotonergic , anxiolytic , muscle relaxant , and sedative properties .  Clonazepam appears to be effective when compared to a placebo . However , caution must be observed with long-term administration of clonazepam because of potential side effects such as depression and liver dysfunction . Indiscriminate administration of clonazepam may be harmful to the patient 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 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 Abstract . Rationale : 3,4-Methylenedioxymethamphetamine ( MDMA ) mainly releases serotonin ( 5-HT ) and is contained in the recreational drug Ecstasy . 5-HT is known to play an important role in mood and anxiety disorders , for which there is a female preponderance . To date , there are no systematic data on gender differences in the subjective effects of MDMA . Objectives : The present work analyzed the pooled data from three controlled studies on the psychological and physiological effects of MDMA in healthy volunteers with no or minimal MDMA experience . A particular focus of the analyses were possible gender differences . Methods : A total of 74 subjects ( 54 male , 20 female ) participated in all three studies .  MDMA in oral doses ranging from 70–150 mg ( 1.35–1.8 mg/kg ) was administered under double-blind placebo-controlled conditions . Subjective peak changes were assessed by st and ardized psychometric rating scales . Physiological measures were blood pressure , heart rate , and peripheral body temperature . Adverse drug effects were assessed during the experimental session and after 24 h. Results : Psychoactive effects of MDMA were more intense in women than in men . Women especially had higher scores for  MDMA-induced perceptual changes , thought disturbances , and fear of loss of body control . The dose of MDMA positively correlated with the intensity of perceptual changes in women . Acute adverse effects and sequelae were also more frequent in female than in male subjects . In contrast , men showed higher increases in blood pressure than woman . Conclusions : The fact that equal doses of MDMA per kilogram body weight produce stronger responses in women compared to men is consistent with an increased susceptibility of women to the 5-HT-releasing effects of MDMA . Our results also indicate that increasing doses of MDMA produce more hallucinogen-like perceptual alterations , particularly in women Poor cognitive performance in ecstasy ( 3,4-methylenedioxymethamphetamine ; MDMA ) users has been related to the well-recognized neurotoxic effects of the drug upon central serotonergic and possibly also dopaminergic systems . However , concomitant use of other drugs has been a critical confound in most investigations . In this study we used an n-back task and fMRI to investigate working memory performance and related cerebral activation in eight , currently abstinent pure MDMA users and two matched groups of polyvalent MDMA users and non-users . Pure MDMA users presented lower activations than controls and /or polyvalent users , most notably in inferior temporal regions , the angular gyrus and the striate cortex , whereas polyvalent users did not differ from controls . Our results suggest that altered brain activation patterns during cognitive processing in ecstasy users may be mainly associated with prior MDMA use . Concomitant use of other drugs may modify this effect
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
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 .