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Background: Ayahuasca is a serotoninergic hallucinogen that plays a central role in the Amazonian traditional medicine. Its psychoactive effects are associated with the presence of N,N-dimethyltryptamine (DMT), and monoamine oxidase inhibitors (MAO-A). Advances in neuroimaging investigations have provided insight into ayahuasca’s neurobiological mechanisms of action. Methods: Selecting only studies with neuroimaging results related to human ayahuasca consumption, we included six articles from a previous systematic review of serotoninergic hallucinogen neuroimaging studies up to 2016. Furthermore, we updated the data with a new systematic search from 2016 to 2022. We searched the PubMed, SciELO, and LILACS databases using the search terms “(ayahuasca OR DMT) AND (MRI OR fMRI OR PET OR SPECT OR imaging OR neuroimaging)”. Results: Our updated search provided five new articles for a total of 11 included in this review. The results on the Default Mode Network (DMN) are evident and may indicate a path to short term neuromodulation. Acutely, local neural networks appeared to become expanded, while overall brain connectivity declined. On chronic consumers, anatomical changes were reported, most notably related to cingulate cortex. Conclusion: Ayahuasca seems to change acute brain connectivity similarly to other psychedelics. The results are preliminary and further studies are warranted.

Ayahuasca is a psychedelic brew originally used by Amazonian indigenous groups and in religious rituals. Pre-clinical and observational studies have demonstrated its possible potential as an antidepressant, and open- and placebo-controlled clinical trials corroborated these results. For it to become an approved treatment for depression, its safety and tolerability need to be assessed and documented.We have gathered data regarding the occurrence of adverse events (AEs) in all reported randomized, placebo-controlled trials with healthy and clinical populations involving ayahuasca administration (n = 108 ayahuasca administrations). We systematically categorized these results, recorded their prevalence, and discussed the possible mechanisms related to their emergence.There were no reports of serious AEs, indicating a relative safety of ayahuasca administration in controlled settings. Most common AEs included nausea, vomiting, headaches, and transient increases in cardiovascular measurements. Ayahuasca research is still in its infancy, especially concerning the absence of large and robust clinical trials to verify its antidepressant effects. Dose standardization, legal prohibition of the possession of its alkaloids and how traditional communities will be compensated if ayahuasca becomes an approved medicine are the biggest obstacles to overcome for its future use in the therapeutic context.

Ayahuasca is a hallucinogenic/psychedelic traditionally used for ritual and therapeutic purposes. One such therapeutic use is related to Substance Use Disorders (SUDs). A previous systematic review of preclinical and human studies published until 2016 suggested that ayahuasca and its alkaloids have therapeutic effects in the treatment of SUDs. To conduct an update of this previous review. A systematic review of quantitative studies which analyzed the effects of ayahuasca and its alkaloids on drug use (primary outcome) and other measures (secondary outcomes) related to SUDs was conducted, including articles from 2016 to 2020. Nine studies (four preclinical, five observational) were included in the review. Preclinical studies in rodents reported reductions in amphetamine self-administration and anxiety, and in alcohol- and methylphenidate-induced conditioned place preference. Observational studies among healthy ritual ayahuasca users and patients with SUDs reported reductions in drug use, anxiety, and depression, and increases in quality of life and well-being. We replicated the findings of the previous review suggesting that ayahuasca and its alkaloids have therapeutic effects in the treatment of SUDs. However, translation of preclinical data to humans is limited, observational studies do not allow us to infer causality, and there is a lack of standardization on ayahuasca doses. Although promising, randomized, controlled trials are needed to better elucidate these results. The PROSPERO ID for this study is CRD42020192046.

Although results are still preliminary, ketamine and classical hallucinogens have shown promise in recent years as novel, fast-acting antidepressants, especially for the treatment of unipolar treatment-resistant depression (TRD). Depression also seems to be related to abnormal levels of peripheral inflammatory and neurotrophic biomarkers, which may one day help to diagnose of this disorder. In this context, this systematic review of clinical trials evaluated the current evidence that relates the antidepressant effects of ketamine and classical hallucinogens on TRD with changes in inflammatory and neurotrophic biomarkers. Twelve studies were found (n = 587), 2 with oral ayahuasca (1 mL/kg) and 10 with ketamine (mostly intravenous 0.5 mg/kg) administration. Results for all biomarkers assessed were contradictory and thus inconclusive. Randomized controlled trials with bigger samples and higher statistical power are warranted to clarify if peripheral biomarkers can confidently be used to indicate and measure ketamine's and classical hallucinogens' antidepressant effect. The PROSPERO ID for this study is CRD42021249089.

To assess endocannabinoid (anandamide, AEA; 2-arachidonoylglycerol, 2-AG) plasma levels in healthy volunteers and in volunteers with social anxiety disorder (SAD) after a single oral dose of ayahuasca or placebo.Post hoc analysis of endocannabinoid plasma levels (baseline, 90 and 240 min after drug intake) from two parallel-group, randomized, placebo-controlled trials. In Study 1, 20 healthy volunteers ingested ayahuasca (average 1.58 mg/ml dimethyltryptamine (DMT)) or placebo, and in Study 2, 17 volunteers with SAD received ayahuasca (average 0.680 mg/ml DMT) or placebo.A significant difference was observed in AEA concentrations in Study 2 after ayahuasca intake (ΧAlthough our findings suggest that ayahuasca could modulate AEA levels in SAD patients, the high interindividual variability in both trials and the small samples preclude definitive conclusions. More research with larger samples is needed to better understand the effects of ayahuasca and other hallucinogens in the endocannabinoid system.

A limited number of preliminary open-label (We have analyzed all randomized, double-blind, and controlled trials that assessed the antidepressant effects of psilocybin and LSD in clinical populations to date, taking special attention to adverse events (AEs) related to their use. Prevalence, significance, and mechanisms of action related to AEs were systematically extracted, analyzed, and discussed.There were no serious AEs related to psilocybin and LSD administration. Most AEs were expected, manageable, and transient. Nevertheless, safety and tolerability concerns regarding some effects, such as dissociation, paranoia, and confusion, remain. Thus, randomized controlled trials with bigger samples are warranted to confirm their therapeutic effects and further investigate their safety and tolerability.

Background Ayahuasca is a classic hallucinogen with anxiolytic and antidepressive properties. Anecdotal evidence also suggests that it improves performance (eg, singing, speech). This controlled trial assessed the effects of ayahuasca on speech performance and anxiety in individuals with social anxiety disorder. Methods Seventeen volunteers with social anxiety disorder participated in a pilot, proof-of-concept, randomized, parallel-group trial. Self-perception of performance during a public-speaking test was assessed with the Self-statements During Public Speaking Scale primary outcome). Secondary outcomes included anxiety/subjective effects (Visual Analog Mood Scale; Bodily Symptoms Scale), recognition of emotions in facial expressions (REFE), tolerability measures (cardiovascular measures, self-reports), and brain-derived neurotrophic factor plasma levels. Effects on anxiety and REFE were assessed again 7, 14, and 21 days postdrug. Findings Compared with placebo, ayahuasca significantly improved self-perception of speech performance (Self-statements During Public Speaking Scale) and increased somatic symptoms (Bodily Symptoms Scale). There was also a significant time × group interaction in the cognitive deterioration Visual Analog Mood Scale factor and a significant effect of time in the REFE task, especially in reaction time. Other measures were not significantly modified. Ayahuasca was well tolerated, producing mainly nausea, gastrointestinal discomfort, and vomiting. Conclusions Ayahuasca improved self-perception of speech performance in socially anxious individuals. These effects occurred independent of task-related anxiety and REFE, suggesting that ayahuasca could specifically improve the cognitive aspect of speech performance. Further studies should try to unveil the mechanisms involved in the effects of ayahuasca and to better understand its effects on anxiety.

Background The recognition of emotions in facial expressions (REFE) is a core aspect of social cognition. Previous studies with the serotonergic hallucinogens lysergic acid diethylamide and psilocybin showed that these drugs reduced the recognition of negative (fear) faces in healthy volunteers. This trial assessed the acute and prolonged effects of a single dose of ayahuasca on the REFE. Methods Twenty-two healthy volunteers participated in a pilot, proof-of-concept, randomized trial. Study variables included a REFE task performed before and 4 hours after drug intake, subjective effects (self-reports/observer impressions), tolerability measures (cardiovascular measures, self-reports), and brain-derived neurotrophic factor plasma levels. The REFE task was applied again 1, 7, 14, and 21 days and 3 months after drug intake. Stability of ayahuasca alkaloids during the study was also assessed (room temperature, 18 months). Findings Compared with placebo, ayahuasca did not modify the REFE. No significant effects were observed on cardiovascular measures and brain-derived neurotrophic factor levels. Volunteers reported visual effects, tranquility/relaxation, and well-being, with few reports of transient anxiety/confusion. Ayahuasca was well tolerated, producing mainly nausea, gastrointestinal discomfort, and vomiting. A significant time-dependent deterioration of alkaloids was observed, especially for dimethyltryptamine. Conclusions Absence of significant effects on the REFE task could be due to lack of effects of ayahuasca (at the doses used), alkaloid degradation, learning effects, and the high educational level of the sample. Further trials with different samples are needed to better understand the effects of ayahuasca and other serotonergic hallucinogens on the REFE. Future trials should improve methods to guarantee the stability of ayahuasca alkaloids.

A ayahuasca é uma bebida psicoativa tradicionalmente utilizada por grupos indígenas da Amazônia com fins rituais e terapêuticos. Estudos em animais e humanos sugerem que a ayahuasca possui efeitos ansiolíticos e antidepressivos. O canabidiol (CBD) por sua vez é um fitocanabinoide produzido pela planta da maconha, e tem demonstrado diversas aplicações terapêuticas nos últimos anos, incluindo (mas não limitado a) efeito antipsicótico, ansiolítico e antiepilético. Tanto a ayahuasca quanto o CBD apresentam boa tolerabilidade. Os efeitos terapêuticos de ansiolíticos e antidepressivos tradicionais envolvem a modulação de processos da cognição social, como o reconhecimento de expressões faciais de emoções (REFE). Portanto, os efeitos terapêuticos da ayahuasca e do CBD poderiam estar relacionados com a modulação da cognição social. Dessa forma, o objetivo principal desse estudo randomizado, duplo-cego e controlado com placebo foi avaliar se a administração de ayahuasca combinada ou não ao CBD modula o REFE. Dezessete voluntários saudáveis participaram desse estudo. Durante os efeitos agudos da ayahuasca e do CBD (0 a 390 minutos) foram aplicadas tarefas de REFE (variável primária) e empatia (Teste de Empatia Multifacetada, TEM), bem como aferidas variáveis subjetivas (Escala Analógica Visual de Humor (VAMS), relatos dos voluntários e observações dos pesquisadores) e de segurança e tolerabilidade (enzimas hepáticas, pressão arterial e frequência cardíaca). Também medimos os níveis dos alcaloides da ayahuasca administrada e no plasma dos voluntários 5 horas após a administração de ayahuasca. Além disso, os voluntários retornaram ao laboratório para um acompanhamento no dia seguinte (D1), sete (D7) e 21 (D21) dias após administração das substâncias para verificar efeitos subagudos e prolongados. Um teste de personalidade (NEO-FFI) foi aplicado na linha de base e no D21. Os 17 voluntários participaram das sessões experimentais (100% de aderências), não havendo qualquer desistência ou retirada de voluntários devido a efeitos adversos graves. A administração de ayahuasca com ou sem CBD não produziu resultados significativos na acurácia geral e de cada emoção no teste de REFE. Também não foram encontrados resultados significativos na acurácia e intensidade da empatia emotiva e cognitiva, respectivamente, no TEM. Os resultados significativos se deram apenas nos tempos de reação (reduções) das duas tarefas de cognição social nos dois grupos, sugerindo aprendizagem. Em relação à personalidade, os resultados indicaram um aumento significativo nos escores do traço de Abertura à Experiência no grupo placebo combinado com ayahuasca. A ayahuasca produziu efeitos subjetivos típicos nos dois grupos, incluindo alterações visuais, bem-estar e tranquilidade. Efeitos significativos no fator Tempo foram observados nos quatro fatores avaliados pela VAMS (ansiedade, sedação, deterioração cognitiva e desconforto) nos dois grupos, mas não houve diferença entre grupos. Esses resultados sugerem que o CBD não modificou os efeitos subjetivos da ayahuasca, mas pode ter influenciado os efeitos da ayahuasca na personalidade. As variáveis de segurança demonstraram boa tolerabilidade para ayahuasca com ou sem CBD, sendo que o mal estar gastrointestinal, aumentos leves/moderados da frequência cardíaca e pressão arterial, e casos esparsos de sonolência e agitação foram os efeitos colaterais mais comuns, efeitos típicos da ayahuasca. Em suma, não foi encontrada evidência de modulação da cognição social pela ayahuasca com ou sem CBD nem de redução dos efeitos subjetivos da ayahuasca pelo CBD. A ayahuasca com ou sem o CBD foi bem tolerada e reduziu significativamente a ansiedade, além de produzir tranquilidade e bem-estar. Esses resultados sugerem que o protocolo é seguro e pode ser aplicado a populações clínicas com sintomas de ansiedade. Ayahuasca is a psychoactive drink traditionally used by indigenous groups in the Amazon Basin for ritual and therapeutic purposes. Animal and human studies suggest that ayahuasca has anxiolytic and antidepressant effects. Cannabidiol (CBD) is a phytocannabinoid produced by the cannabis plant, and has demonstrated several therapeutic applications in recent years, including (but not limited to) as an antipsychotic, anxiolytic and antiepileptic substance. Both ayahuasca and CBD have good tolerability. The therapeutic effects of traditional anxiolytics and antidepressants involve the modulation of social cognition processes, such as the recognition of emotions in facial expressions (REFE). Therefore, the therapeutic effects of ayahuasca and CBD could be related to the modulation of social cognition. Thus, the main objective of this randomized, double-blind, placebo- controlled study was to assess whether the administration of ayahuasca or ayahuasca combined with CBD modulates the REFE. Seventeen healthy volunteers participated in this study. During the acute effects of ayahuasca and CBD (0 to 390 minutes), REFE (primary variable) and empathy (Multifaceted Empathy Test, MET) tasks were applied. We also assessed subjective variables (Visual Analog Mood Scale (VAMS), volunteer\'s reports and researcher\'s observations) and safety and tolerability (liver enzymes, blood pressure and heart rate). Furthermore, we measured the alkaloid levels of the administered ayahuasca and in the volunteer\'s plasma 5 hours after the administration of ayahuasca. In addition, the volunteers returned to the laboratory for follow-up on the next day (D1), seven (D7) and 21 (D21) days after administration of the substances to verify subacute and prolonged effects. A personality test (NEO-FFI) was applied at baseline and D21. The 17 volunteers completed the experimental sessions (100% adherence), with no withdrawal of volunteers due to serious adverse effects. The administration of ayahuasca with or without CBD did not produce significant results in the general accuracy and for each emotion in the REFE task. There were also no significant results in the accuracy and intensity of emotional and cognitive empathy, respectively, as measured by the MET. The significant results occurred only in the reaction times (reductions) of the two tasks of social cognition in both groups, suggesting a learning effect. Regarding personality, the results indicated a significant increase in the scores of the trait of Openness to Experience in the placebo plus ayahuasca group. Ayahuasca produced typical subjective effects in both groups, including visual perception changes, well-being and tranquility. Significant effects on the Time factor were observed in the four factors assessed by VAMS (anxiety, sedation, cognitive deterioration, and discomfort) in the two groups, but there was no difference between groups. These results suggest that CBD did not modify the subjective effects of ayahuasca but may have influenced ayahuasca\'s effect on personality. The safety variables demonstrated good tolerability for ayahuasca with or without CBD, being gastrointestinal malaise, mild/moderate increases in heart rate and blood pressure and sparse cases of drowsiness and agitation the most common side effects, which are typical of ayahuasca ingestion. In short, there was no evidence of modulation of social cognition by ayahuasca with or without CBD or of a reduction in the subjective effects of ayahuasca by CBD. Ayahuasca with or without CBD was well tolerated and significantly reduced anxiety (VAMS), in addition to producing tranquility and well-being. These results suggest that the protocol is safe and can be applied to clinical populations with symptoms of anxiety.

Ayahuasca is a hallucinogenic/psychedelic traditionally used for ritual and therapeutic purposes. One such therapeutic use is related to Substance Use Disorders (SUDs). A previous systematic review of preclinical and human studies published until 2016 suggested that ayahuasca and its alkaloids have therapeutic effects in the treatment of SUDs. To conduct an update of this previous review. A systematic review of quantitative studies which analyzed the effects of ayahuasca and its alkaloids on drug use (primary outcome) and other measures (secondary outcomes) related to SUDs was conducted, including articles from 2016 to 2020. Nine studies (four preclinical, five observational) were included in the review. Preclinical studies in rodents reported reductions in amphetamine self-administration and anxiety, and in alcohol- and methylphenidate-induced conditioned place preference. Observational studies among healthy ritual ayahuasca users and patients with SUDs reported reductions in drug use, anxiety, and depression, and increases in quality of life and well-being. We replicated the findings of the previous review suggesting that ayahuasca and its alkaloids have therapeutic effects in the treatment of SUDs. However, translation of preclinical data to humans is limited, observational studies do not allow us to infer causality, and there is a lack of standardization on ayahuasca doses. Although promising, randomized, controlled trials are needed to better elucidate these results. The PROSPERO ID for this study is CRD42020192046.

Psychedelics or serotonergic hallucinogens are a group of substances that share the agonism of serotonergic 5-HT2A receptors as their main mechanism of action. Its main effects include changes in perception, cognitive process, and mood. Despite being used for centuries by different cultures in ritual contexts, these substances have currently aroused the interest of science and industry for their promising antidepressant, anxiolytic, and anti-addictive effects. Considering this evidence, this article aims to explore some of the possible health policy challenges to integrate these therapeutic tools into broad and heterogeneous health systems. As a main benefit, these substances produce rapid and enduring effects with the administration of single or few doses, which could lead to new treatment possibilities for patients with severe mental disorders resistant to the usual medications. The main challenge is associated with the fact that these substances remain scheduled in most countries and are associated with social stigma related to their recreational use (especially LSD and psilocybin). This situation makes it exceedingly difficult to conduct clinical trials, although international conventions allow such research. Ethically, this could be interpreted as a violation of human rights since thousands of people are prevented from having access to possible benefits. Interestingly, ritual ayahuasca use is more acceptable to the public than the use of psilocybin-containing mushrooms or LSD. The controlled, clinical use of LSD and psilocybin seems to be less criticized and is being explored by the industry. Rigorous scientific evidence coupled with industrial interests (LSD and psilocybin), together with respect for traditional uses (ayahuasca) and international conventions, seems to be the best way for these drugs to be integrated into health systems in the next years. Which highlights the need for an urgent dialogue between science, health system, society, and politics.

The present study describes the development of a novel solvent-free vortex-assisted dispersive liquid-liquid microextraction alternative based on a natural essential oil as extracting solvent (VA-EO-DLLME) for the determination of N,N-dimethyltryptamine (DMT), harmine (HRM), harmaline (HRL) and tetrahydroarmine (THH) (compounds found in the ayahuasca tea, a psychedelic plant preparation) in human plasma. After optimization through full factorial and Box-Behnken experimental designs, this VA-EO-DLLME followed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was completely validated and applied to authentic plasma specimens. Sample preparation consisted in the addition of 60 mg of NaCl, 100 μL of borate buffer and 100 μL of Eucalyptus globulus essential oil to a 200 μL aliquot of human plasma. After 30 s of vortex agitation followed by 5 min of centrifugation (10,000 rpm), 80 μL of the oil supernatant was dried and resuspended in mobile phase prior to injection into the UHPLC-MS/MS system. Once optimized, the validated method yielded LoDs ≤1.0 ng mL−1 for all analytes. LoQ was 1.0 ng mL−1 for DMT, HRL and HRM and 2.0 ng mL−1 for THH. The method has shown to be linear over the range of LoQ up to 150 ng mL−1 (r2 ≥ 0.9926). Intra/inter-day precision and accuracy met the acceptance criteria at three quality control (QC) levels. An additional intermediate precision study demonstrated that, except for THH and HRL at low and medium QCs, the overall method performance was similar for the three different oil sources. Matrix effect evaluation showed predominant ion suppression, ranging from 56% to 83%. Recovery varied from 33 up to 101% with an average of 50 ± 15.8%. Selectivity studies showed no interferences. Analysis of 13 authentic samples proved method feasibility. Finally, we believe that our novel VA-EO-DLLME approach offers a very simple, fast, cost-effective and eco-friendly alternative based on the use of an easily accessible and entirely green material as an extracting solvent. This may represent an incentive for researchers to investigate novel and creative alternatives, such as essential oils, as substitutes of organic solvents for microextraction methods in forensic and clinical contexts.

Recent trials using cannabidiol (CBD) have shown that most acute and prolonged adverse effects of CBD are mild to moderate, with rare serious adverse effects (SAEs). This review focused on analyzing SAEs of CBD and their possible relation to drug-drug interactions.We systematically analyzed the SAEs reported in randomized controlled trials (RCTs) involving the administration of oral CBD for at least 1 week in both healthy volunteers and clinical samples.SAEs related to CBD in RCT are rare and include mainly elevated transaminases, convulsion, sedation, lethargy, and upper respiratory tract infections. Elevated transaminases are related to concomitant valproate use, while sedation, lethargy, and upper respiratory tract infections are related to concomitant clobazam use. Epileptic patients should be monitored when using CBD concomitantly with these and other antiepileptic drugs for other possible drug-drug interactions.

Ayahuasca tea is a hallucinogenic beverage used for religious purposes in Brazil and many other countries that has therapeutic potential in the treatment of some mental health disorders. In the context of psychedelic research, quantification of the tea’s main alkaloids prior to its administration in animal or human studies is essential. For this reason, this study aims to provide information regarding the stability of the main ayahuasca alkaloids (dimethyltryptamine, DMT; harmine, HRM; tetrahydroharmine, THH; harmaline, HRL) in three different conditions: (1) A year stored in a refrigerator either in plastic or glass containers, (2) seven days at 37 °C to reproduce usual mail transportation, and (3) after three freeze–thaw cycles. Samples were quantified after a dilute-and-shoot procedure using liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS). There was no significant degradation of DMT concentration over time in all tested conditions. Harmala alkaloids (THH, HRL, and HRM) showed important variations after long-term and high-temperature storages. Although DMT has proven to be stable in all studied conditions, the harmala alkaloids revealed intense degradation and even concentration increment. This may be caused by degradation, alkaloid inter-conversion, and leaching from tea precipitate material. Therefore, ayahuasca quantification before administration in controlled sets is mandatory.

Tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids being linked with modulation of anxiety and depression. The recognition of emotions in facial expressions (REFE) is impaired in these disorders. Both drugs could modulate anxiety and mood by interfering with REFE. Thus, a systematic review of controlled trials assessing the effects of THC and CBD on REFE was performed. Ten studies describing seven distinct experiments were found (n = 170). THC (7.5-15 mg) did not alter REFE in three experiments, but reduced task performance in other three experiments. CBD did not alter REFE in two experiments, but improved task performance and counteracted the effects of THC in one experiment. THC (≥ 10 mg) and CBD (600 mg) showed opposite effects on brain activation, skin conductance, and anxiety measures with negative/threatening faces. The limited number of studies precludes firm conclusions on the effects of these substances on REFE. Further controlled trials are needed to elucidate the effects of THC and CBD on REFE. The PROSPERO ID for this study is CRD42019135085.

Background and aimsThe psychoactive capacity of the alkaloid N,N-dimethyltryptamine (DMT) has been known for decades, and its presence in beverages used in religious contexts around the world – suc...

Background: Recognition of emotions in facial expressions (REFE) is a key aspect of social cognition. Anxiety and mood disorders are associated with deficits in REFE, and anxiolytics and antidepressants reverse these deficits. Recent studies have shown that serotonergic hallucinogens (i.e. ayahuasca, dimethyltryptamine, psilocybin, lysergic acid diethylamide [LSD], and mescaline) have anxiolytic and antidepressant properties, but their effects on REFE are not well understood. The purpose of the study was to conduct a systematic review analyzing the effects of serotonergic hallucinogens on REFE in humans. Methods: Studies published in the PubMed, PsycINFO, and Web of Science databases until 19 October 2018 which analyzed the effects of serotonergic hallucinogens on REFE in humans were included. Results: Of the 62 studies identified, 8 studies were included. Included studies involved the administration of a single or a few doses of LSD or psilocybin, and most trials were randomized and controlled with placebo. LSD and psilocybin reduced the recognition of negative emotions in most studies and modulated amygdala activity to these stimuli, which was correlated with antidepressive effects in patients. Both drugs were well tolerated. Conclusions: Serotonergic hallucinogens reduced the recognition of negative emotions by modulating amygdala activity. Despite the small sample sizes, results suggest that serotonergic hallucinogens show promising beneficial effects on deficits in REFE.