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Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study
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 randomized, double-blind, placebo-controlled trials.
... There are other active trials with DMT (intravenous and vaporized) for major depressive disorder and TRD, with promising results that have yet to be published. 87 In the case of ayahuasca, two trials (one open-label 88 and one placebo-controlled 89 ) have assessed the antidepressant potential of a single ayahuasca dose in patients with TRD, one placebocontrolled trial evaluated the effects of a single ayahuasca dose in a public-speaking test in individuals with social anxiety disorder, 90 and one single-blind trial assessed the effects of a single dose of ayahuasca in college students with harmful alcohol use. 91 In all these trials, volunteers were informed about the experimental procedures and ayahuasca general effects before drug sessions, ayahuasca (or placebo) was administered in a comfortable laboratory setting with psychological support (no psychotherapy was used), and follow-ups were performed after the drug sessions. ...
... In the open-label trial with 17 TRD patients, a single ayahuasca dose (2.2 mL/kg; 0.8 mg/mL DMT) induced significant reductions in depressive symptoms from the first hours after ayahuasca intake until 21 days afterwards (61% reduction in the Hamilton Rating Scale for Depression). 88 Ayahuasca was well tolerated, producing mainly transient nausea and vomiting. These positive results were replicated in a placebo-controlled trial with 29 TRD patients, where a single dose of ayahuasca (1 mL/kg; 0.36 mg/mL DMT), compared to an active, but nonpsychoactive, placebo (designed to simulate the organoleptic properties of ayahuasca: bitter and sour taste with a brownish color), produced significant reductions in depressive symptoms after seven days (57% reduction in the Montgomery-Asberg Depression Rating Scale). ...
... In experimental studies involving the administration of ayahuasca to healthy volunteers 36,55-66 and patients, [88][89][90][91] ayahuasca was generally well tolerated, and the most common adverse effects reported included nausea, gastrointestinal discomfort and vomiting, transient anxiety, drowsiness, difficulty in concentrating, fear, dissociation/ depersonalization and confusion, moderate and transient increases in blood pressure and heart rate, and headaches. 61,100 Most of these effects were transient and did not need any kind of intervention to be managed, and there were few cases where more intense psychological support was needed. ...
Ayahuasca is a botanical hallucinogen traditionally used for therapeutic and ritual purposes by indigenous groups from Northwestern Amazonian countries such as Brazil, Peru, Colombia, and Ecuador. Ayahuasca is made by the decoction of two plants, which are rich in the 5-HT1A/2A partial agonist dimethyltryptamine or DMT (from the leaves of the Psychotria viridis bush) and β-carbolines such as harmine, from the stalks of the Banisteriopsis caapi vine. There is an increasing interest in the possible therapeutic effects of ayahuasca, especially for psychiatric disorders (major depression, posttraumatic stress disorder, and substance use disorder). This review summarizes information on the pharmacology, safety, and therapeutic potentials of ayahuasca. Although human experimental and naturalist studies published until now suggest a good safety and tolerability profile, often associated with improvements in depressive and anxious symptoms, there are few controlled studies, with small sample sizes, using only single doses, and with short follow-ups. Potential benefits of ayahuasca should be evaluated in larger samples in both experimental and observational studies and using different doses in controlled trials.
... 54 In controlled therapeutic and clinical settings where participants are meticulously screened for risk factors, both DMT and ayahuasca seem to be psychologically and physiologically safe, and they are not considered drugs of dependence. 38,55,56 In the only RCT on ayahuasca to date, ayahuasca did not induce any significant increases in manic symptoms, as measured by the Young Mania Rating Scale, nor did it have a significant effect on responses to the Brief Psychiatric Rating Scale, which captures symptoms of psychosis, or the Clinician-Administered Dissociative States Scale. 38 Another open-label trial of ayahuasca did not report any adverse effects other than vomiting. ...
... 38 Another open-label trial of ayahuasca did not report any adverse effects other than vomiting. 56 Indeed, vomiting is the most common adverse effect that is unique to ayahuasca. In total, 47%-57% of participants vomited in clinical trials of ayahuasca for depression. ...
... In total, 47%-57% of participants vomited in clinical trials of ayahuasca for depression. 38,56 The recent Global Ayahuasca Survey of 10,836 ayahuasca users reported that 62% of respondents vomited at least once during past sessions. 57 The MAO inhibitors in ayahuasca cause high levels of unmetabolized serotonin to accumulate in the gut. ...
Background
N,N -dimethyltryptamine (DMT) is a naturally occurring serotonergic psychedelic found in natural plants around the globe. As the main psychoactive component in ayahuasca, which also contains monoamine oxidase inhibitors, DMT has been consumed as plant-based brew by indigenous peoples for centuries. Further research is required to delineate the therapeutic utility of DMT.
Areas of Uncertainty
Although previous research has shown that DMT is synthesized endogenously, it may not be produced at physiologically relevant concentrations. Additionally, the phenomenological similarities between the DMT-induced state and near-death experiences led to the popular hypothesis that endogenous DMT is released during the dying process. However, this hypothesis continues to be debated. Generally, DMT and ayahuasca seem to be physiologically and psychiatrically safe, although ayahuasca is known to cause transient vomiting.
Therapeutic Advances
A double-blind, randomized controlled trial showed that, within 1 week, ayahuasca causes remission in 36% of patients with treatment-resistant depression. According to top-line results from a recent phase IIa trial, 57% of patients with major depressive disorder experienced remission 12 weeks after receiving a single intravenous dose of DMT.
Limitations
There has only been a single published double-blind randomized controlled trial on ayahuasca and 2 on DMT. All clinical trials have had small sample sizes (≤34 participants). DMT requires further research to understand its therapeutic and clinical potential as a psychedelic.
Conclusions
Preliminary evidence indicates that ayahuasca and DMT may be more effective than existing antidepressants for treating major depressive disorder and treatment-resistant depression.
... Although DMT degrades rapidly, the β-carbolines allow it to be orally active by inhibiting monoamine oxidase A (MAO-A). Like psychedelics such as psilocybin and lysergic acid diethylamide (LSD), activation of 5-HT 2A receptors largely contributes to ayahuasca's psychoactive effects (Valle et al., 2016), and DMT (D'Souza et al., 2022) and ayahuasca (Palhano-Fontes et al., 2019;Sanches et al., 2016) are showing promise for the treatment of depression. Nevertheless, DMT possesses a unique pharmacology including σ receptor activation that may induce hippocampal neurogenesis (Morales-Garcia et al., 2020) and therefore impact episodic memory. ...
... Regardless, the present study would suggest that ayahuasca does not increase susceptibility to false memory when an event takes place and is remembered all under acute effects in frequent ayahuasca users (but note that the findings here cannot generalize to inexperienced populations, and our sample was relatively homogenous). Considering that ayahuasca is being explored for its therapeutic potential (Palhano-Fontes et al., 2019;Sanches et al., 2016), it will be important to examine whether inexperienced users are also not more susceptible to memory distortion under the acute effects of ayahuasca. Future work with delays between memory phases (for drug clearance) and precisely timed drug administrations (i.e., preencoding, immediately post-encoding, pre-misinformation, immediately post-misinformation, and just prior to a delayed memory test) will delineate the temporal dependency of drug effects on encoding, consolidation, retrieval, and memory distortion. ...
Background
Ayahuasca is an Amazonian brew with 5-HT 2A -dependent psychedelic effects taken by religious groups globally. Recently, psychedelics have been shown to impair the formation of recollections (hippocampal-dependent episodic memory for specific details) and potentially distort memory while remembering. However, psychedelics spare or enhance the formation of familiarity-based memory (cortical-dependent feeling of knowing that a stimulus has been processed).
Aims
Given the growing literature on the plasticity-promoting effects of psychedelics, we investigated the acute impact of ayahuasca on recollection, familiarity, and false memory in an observational study of 24 Santo Daime members with >500 lifetime ayahuasca uses on average.
Methods
Participants completed a false memory task at baseline and after they consumed a self-selected dose of ayahuasca prepared by their church (average dose contained 3.36 and 170.64 mg of N,N-dimethyltryptamine and β-carbolines, respectively).
Results
Surprisingly, pre-encoding administration of ayahuasca enhanced hit rates, memory accuracy, and recollection but had no impact on familiarity or false memory. Although practice effects cannot be discounted, these memory enhancements were large and selective, as multiple measures of false memory and metamemory did not improve across testing sessions. β-carboline activity potentially accounted for this recollection enhancement that diverges from past psychedelic research. Although ayahuasca did not impact familiarity, these estimates were generally elevated across conditions compared to past work, alluding to a consequence of frequently driving cortical plasticity.
Conclusions
When encoding and retrieval took place under acute ayahuasca effects in experienced ayahuasca users, susceptibility to memory distortions did not increase, potentially owing to enhancements in memory accuracy.
... Similarly to what have been happening to other psychedelic substances, AYA properties have been investigated as treatment for numerous psychiatric disorders, such as depression, anxiety, and substance use disorder (7)(8)(9)(10)(11). Additionally, preclinical studies have suggested a possible action of AYA on fear processing circuits, which could support possible mechanism for therapeutic effects on anxiety and posttraumatic stress disorder (PTSD) (12,13). ...
... Another SPECT study, this time evaluating depressive patients, compared rCBF prior to and 8 h after AYA intake (2.2 mL/kg). The treatment increased rCBF on left nucleus accumbens, right insula and left subgenual anterior cingulate cortex (11). ...
Ayahuasca is a hallucinogenic substance currently being investigated for the treatment of mood, anxiety, and trauma-related disorders.
Evidence from animal and human studies suggest that the effects of ayahuasca involve modulation of neural substrates relevant for emotional processing, especially in regions rich in serotonergic receptors.Moreover, preclinical studies also show that ayahuasca has specific effects on fear-relatedmemories. The serotonergic system has been classically associated to anxiety and fear responses, with selective serotonin reuptake inhibitors being first-classmedication to treat mood, anxiety, and stress-related disorders. Here we review currently available data regarding ayahuasca (and its main components) behavioral and functional effects on anxiety and fear-related responses through its modulation of serotoninergic signaling.
... Ayahuasca is a traditional Amazonian brew made from the Banisteriopsis caapi vine and the Psychotria viridis leaf, which contain β-carboline alkaloids acting as MAO-inhibitors and DMT, respectively. Ayahuasca is used in shamanic and spiritual rituals of indigenous tribes and communities and is known for its intense introspective visionary experiences and reported therapeutic benefits [17,[70][71][72]. Among outcomes observed after consumption of ayahuasca are lower hopelessness and improvement of depression [17,[72][73][74], as well as beneficial personality changes [75]. ...
... Ayahuasca is used in shamanic and spiritual rituals of indigenous tribes and communities and is known for its intense introspective visionary experiences and reported therapeutic benefits [17,[70][71][72]. Among outcomes observed after consumption of ayahuasca are lower hopelessness and improvement of depression [17,[72][73][74], as well as beneficial personality changes [75]. ...
This narrative review explores the utilization of psychedelic states in therapeutic contexts, deliberately shifting the focus from psychedelic substances back to the experiential phenomena they induce, in alignment with the original meaning of the term "mind-manifesting." The review provides an overview of various psychedelic substances used in modern therapeutic settings and ritualistic indigenous contexts, as well as non-pharmacological methods that can arguably induce psychedelic states, including breathwork, meditation, and sensory deprivation. While the occurrence of mystical experiences in psychedelic states seems to be the strongest predictor of positive outcomes, the literature of the field yields several other psychological processes, such as awe, perspective shifts, insight, emotional breakthrough, acceptance, re-experiencing of memories, and certain aspects of challenging experiences, that are significantly associated with positive change. We additionally discuss in detail mystical experience related changes in metaphysical as well as self-related beliefs and their respective contributions to observed outcomes. We conclude that a purely medical and neurobiological perspective on psychological health is reductive and should not overshadow the significance of phenomenological experiences in understanding and treating psychological issues that manifest in subjective realities of human individuals.
... Ayahuasca has been explored in therapeutic settings with promising results for several mental health disorders and symptoms, including depression [42,43], social anxiety [44] and grief [45]. ...
... Secondly, the individual studies included in the meta-analysis were underpowered and had methodological issues, including insufficient details on participant populations, limited diversity in LSD doses and treatment variables, the use of low-dose LSD as an active placebo in some trials, potential publication bias, blinding issues and variations in outcome measures for alcohol use improvement [48]. In the context of the heroin study [43], the experimental design allows no meaningful inferences regarding the relative efficacy of LSD. In summary, the challenges in designing placebo-controlled and doubleblind trials were underscored in these clinical studies, given ethical considerations and the inherent nature of the psychoactive intervention [12]. ...
Mental health disorders and substance use disorders (SUDs) in particular, contribute greatly to the global burden of disease. Psychedelics, including entactogens and dissociative substances, are currently being explored for the treatment of SUDs, yet with less empirical clinical evidence than for other mental health disorders, such as depression or post-traumatic stress disorder (PTSD). In this narrative review, we discuss the current clinical research evidence, therapeutic potential and safety of psilocybin, lysergic acid diethylamide (LSD), ketamine, 3,4-methylenedioxymethamphetamine (MDMA) and ibogaine, particularly in the context of the SUD treatment. Our aim was to provide a balanced overview of the current research and findings on potential benefits and harms of psychedelics in clinical settings for SUD treatment. We highlight the need for more clinical research in this particular treatment area and point out some limitations and challenges to be addressed in future research.
... Two days following psilocybin treatment, we identified decreased insula and putamen activity, along with increased functional connectivity between the caudate and ACC, potentially reflecting enhanced goal-directed action [96]. Post-acute effects in non-AUD populations have also been observed with psilocybin, including increased SN-DMN, SN-CEN, and striatal connectivity, as well as decrease glutamate and NAA levels in the ACC [61,97,98]. Ayahuasca has also been reported to increase insula activity, within-SN connectivity (ACC), and SN-DMN connectivity [64,98,99]. ...
... Post-acute effects in non-AUD populations have also been observed with psilocybin, including increased SN-DMN, SN-CEN, and striatal connectivity, as well as decrease glutamate and NAA levels in the ACC [61,97,98]. Ayahuasca has also been reported to increase insula activity, within-SN connectivity (ACC), and SN-DMN connectivity [64,98,99]. Interestingly, increased SN-DMN connectivity predicted long-term enhancements in mindfulness traits, creative thinking, and the generation of novel ideas, which may be related to frequently reported enhancements in openness [99,100]. ...
Purpose of review
This article utilizes a pre-existing framework in the field of addiction to comprehensively capture the effects of classic psychedelics (psilocybin, lysergic acid diethylamide, dimethyltryptamine, and mescaline) for the treatment of alcohol use disorder (AUD).
Recent findings
Basic science, preclinical, and clinical studies support the influence of psychedelics on all 3 core domains of addiction, comprising negative emotionality (including depression and anxiety), incentive salience (including craving and compulsive use) and executive functioning (including impulsivity and cognitive flexibility). However, systematic investigation using objective measures to evaluate these domains in AUD is needed.
Summary
We close by discussing limitations and challenges in the field of psychedelic science, and propose future research directions to advance our understanding of the psychological and neurobiological basis of clinical improvement. Conceptualizing future research under this 3-domain framework may assist the refinement of psychedelic-assisted treatments and the development of personalized medicine approaches for AUD.
... Данные исследований показывают, что псилоцибин, принимаемый в рамках двух сессий, способен вызывать долгосрочные улучшения, которые сохраняются на протяжении нескольких месяцев. Подобные эффекты наблюдаются и у других психоделиков: в Бразилии исследования действия аяуаски на пациентов с депрессией и ПТСР показали улучшение симптомов через неделю после приёма и их сохранение на протяжении трёх недель [8,9]. Рандомизированные исследования также выявили устойчивое снижение тревожных симптомов у пациентов с онкологическими заболеваниями после приёма LSD [10]. ...
MDMA, DMT и LSD, применяемых при депрессии, посттравматическом стрессовом расстройстве, тревожных и обсессивно-компульсивных расстройствах. Перечисленные вещества предлагают иную парадигму лечения благодаря быстрому наступлению те-рапевтического эффекта и способности стимулировать долгосрочные изменения психического состояния, поддер-жанные определённым психотерапевтическим сопровождением. В то же время многие исследования, восхваляющие психоделики, остаются методологически слабыми, что препятствует интеграции этих средств в медицинскую практику. Данная статья предлагает обсуждение современных представлений о психоделиках, а также критическое рассмотре-ние существующих научных данных. Анализируется исторический контекст использования психоделических средств, включая ранние исследования, в том числе методику психоделической терапии кетамином, разработанную в России профессором Е.М. Крупицким. Подробно рассматриваются существующие сложности, такие как отсутствие адекват-ных плацебо и стандартов дозирования, малые размеры выборок и сильное влияние контекстуальных факторов, ко-торые могут исказить результаты. На основе этого автор призывает российских психиатров к критичному осмыслению данных и к готовности выработать взвешенное отношение к применению психоделиков в терапии, исходя из качества доказательной базы и особенностей российской нормативно-правовой базы. Ключевые слова: псилоцибин; ЛСД; серотониновые рецепторы, лекарственная терапия.
... Despite these important advancements, there remains a need for research examining the immediate post-retreat period and the relationship between acute experiences and affect and mindfulness skills in everyday life. While several prospective studies have examined the subacute effects of ayahuasca (e.g., de Lima Osório et al. 2015;Sanches et al. 2016;Uthaug et al. 2019Uthaug et al. , 2021Jiménez-Garrido et al. 2020;van Oorsouw et al. 2021van Oorsouw et al. , 2022, many have relied primarily on retrospective self-reports administered at a limited number of time points. These seminal studies have provided valuable insights, but are constrained by the limitations of retrospective reporting over a limited number of observations over time. ...
Rationale
To examine the acute effects of ayahuasca use and their relationship to sub-acute changes in affect and mindfulness in a non-clinical sample, addressing the need for a better understanding of ayahuasca’s immediate and short-term impacts as interest in its use grows.
Objectives
Using prospective ecological assessment, this study investigates how ayahuasca used at a 4-day retreat affects positive/negative affect and mindfulness skills in daily living compared to pre-retreat. Additionally, we explore acute psychedelic experiences during the ayahuasca retreat, assessed retrospectively 1–2 days post-retreat, as potential mechanisms for theorized effects in daily living post-retreat.
Methods
Thirty-six participants reported positive/negative affect and mindfulness skills three times daily for 5 days before and after the retreat. Baseline assessments included lifetime psychedelic experience, and post-retreat assessments covered acute ayahuasca experiences. Mixed-effect linear models were used to analyze the data.
Results
Post-retreat, we observed reduced negative affect, increased positive affect, and enhanced mindfulness skills in daily living. Ayahuasca-induced acute experiences, such as time/space transcendence, emotional breakthrough and challenging experiences predicted greater subacute positive affect. Notably, none of these experiences were linked to subacute improvements in negative affect or mindfulness. No participants showed clinically significant adverse responses post-retreat, and only 5.5% exhibited some degree of potentially clinically significant deterioration in affect.
Conclusions
Ayahuasca use may lead to improvement in mood and mindfulness skills, and key acute psychedelic experiences induced by ayahuasca may be important to some of these salutary effects, positive affect in particular.
... Recentemente, a ayahuasca (ou seu principal componente psicoativo, a DMT) tem sido investigada como um potencial terapêutico para vários transtornos mentais, especialmente a depressão resistente ao tratamento e a dependência química. Os testes em fase inicial são promissores, tanto em termos de segurança quanto de eficácia (Nunes et al., 2016;Osório et al., 2015;Palhano-Fontes et al., 2019;Sanches et al., 2016). No entanto, a DMT continua na Lista I de substâncias controladas nos Estados Unidos. ...
On February 2023, the Drug Enforcement Administration (DEA) released a document to the legal team representing the Church of the Eagle and the Condor (“CEC”). This disclosure came two years after the church, in conjunction with Chacruna Institute, submitted two FOIA requests to the DEA and the Department of Justice requesting all records pertaining to ayahuasca. This report, titled “Ayahuasca: Risks to Public Health and Safety,” was issued in July 2020. In the present article, we challenge a number of claims made in the DEA report and highlight significant factual omissions, theoretical biases, and misinterpretations of existing data. We will demonstrate that the DEA report severely downplays the safety profile and therapeutic potential of ayahuasca and overemphasizes the risks. It also fails to include current research on ayahuasca demonstrating its potential benefits.
... 2,5 Notably, ayahuasca shows equally rapid but more sustainable antidepressant effects than ketamine. 2,[8][9][10] While the exact pharmacological mechanisms have not yet been fully revealed, a drug-drug interaction between the indole alkaloid DMT and the β-carboline alkaloids harmine, harmaline, and tetrahydroharmine is likely mediating its therapeutic effects. DMT shows no oral bioavailability due to excessive metabolic firstpass degradation by the enteric monoamine oxidase A (MAO-A) enzyme. ...
Background
Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects in various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) and β-carboline alkaloids such as harmine. However, its use is often accompanied by distressing effects like nausea, vomiting, and intense hallucinations, possibly due to complex pharmacokinetic/pharmacodynamic (PK-PD) interactions and lack of dose standardization.
Methods
This study addresses these limitations by testing a novel pharmaceutical formulation containing pure forms of DMT and harmine in a double-blind, randomized, placebo-controlled trial with 31 healthy male volunteers. We evaluated PK-PD by monitoring drug and metabolite plasma levels, subjective effects, adverse events, and cardiovascular parameters. Each participant received 3 randomized treatments: (1) 100 mg buccal harmine with 100 mg intranasal DMT, (2) 100 mg buccal harmine with intranasal placebo, and (3) full placebo, using a repeated-intermittent dosing scheme, such that 10 mg of DMT (or placebo) was administered every 15 minutes.
Results
N,N-dimethyltryptamine produced consistent PK profiles with Cmax values of 22.1 ng/mL and acute drug effects resembling the psychological effects of ayahuasca with a duration of 2–3 hours. Likewise, buccal harmine produced sustained-release PK profiles with Cmax values of 32.5 ng/mL but lacked distinguishable subjective effects compared to placebo. All drug conditions were safe and well tolerated, indicating the formulation’s suitability for clinical applications.
Conclusions
This study underscores the potential of a patient-oriented pharmaceutical formulation of DMT and harmine to reduce risks and improve therapeutic outcomes in treating mental health disorders.
Clinical trial registration number
Neurodynamics of prosocial emotional processing following serotonergic stimulation with N,N-dimethyltryptamine (DMT) and harmine in healthy subjects (NCT04716335) https://clinicaltrials.gov/ct2/show/NCT04716335
... Psychedelic drugs have been successfully used to treat multiple neuropsychiatric disorders, including major depressive disorder, post-traumatic stress disorder, and substance use disorders (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). These neuropsychiatric disorders are precipitated by chronic stress, which leads to both structural and functional changes in the prefrontal cortex (PFC) in humans and rodents (15)(16)(17)(18)(19)(20)(21)(22). ...
Psychedelic drugs have shown therapeutic potential for the treatment of multiple neuropsychiatric disorders chiefly by promoting long-lasting plasticity in the prefrontal cortex (PFC). A critical function of the PFC is the ability to apply previously learned rules to novel scenarios, a skill known as cognitive flexibility. Here, we show that a single dose of 25CN-NBOH, a serotonin 2A receptor-preferring psychedelic, improves performance on a relatively complex flexible reversal learning task in mice, measured 2-3 weeks after the dose. This effect was seen in both male and female mice. This behavioral finding complements previous cellular results showing that a single psychedelic dose induces long-term structural changes in the PFC and uniquely demonstrates sustained improvements in cognitive flexibility in a novel behavioral paradigm weeks after the initial psychedelic dose in mice. This high throughput task also provides a rapid, automated way to assess other candidate psychedelics for their impact on cognitive flexibility in mice.
... There is growing interest in Ayahuasca, partially due to recent findings showing that it may be effective in treating mental disorders, such as depression [24] and behavioral addiction [25][26][27]. Similar therapeutic potential has also been pointed out for other psychedelics [9,21,[28][29][30][31]. ...
The entropic brain hypothesis holds that the key facts concerning psychedelics are partially explained in terms of increased entropy of the brain's functional connectivity. Ayahuasca is a psychedelic beverage of Amazonian indigenous origin with legal status in Brazil in religious and scientific settings. In this context, we use tools and concepts from the theory of complex networks to analyze resting state fMRI data of the brains of human subjects under two distinct conditions: (i) under ordinary waking state and (ii) in an altered state of consciousness induced by ingestion of Ayahuasca. We report an increase in the Shannon entropy of the degree distribution of the networks subsequent to Ayahuasca ingestion. We also find increased local and decreased global network integration. Our results are broadly consistent with the entropic brain hypothesis. Finally, we discuss our findings in the context of descriptions of "mind-expansion" frequently seen in self-reports of users of psychedelic drugs.
... Existing studies of people who consume it ceremonially have found have better psychological functioning, and lower hopelessness, substance abuse, and depression rates, in comparison to the general population Santos et al., 2007). At the moment of writing this report, a series of randomised controlled studies has found ayahuasca to be potentially epective for treatment-resistant depression (Osório et al., 2015;Palhano-Fontes et al., 2019;Sanches et al., 2016), and non-controlled studies suggest it may be epective for the treatment of addiction (Nunes et al., 2016;Thomas et al., 2013). ...
This paper focuses on a single case of ayahuasca-assisted grief therapy for the prevention of complicated grief, conducted within a clinical trial. The participant, a woman in her thirties who lost her father to cancer, completed a 9-session process of Meaning Reconstruction Therapy (MRT) organised around two ayahuasca sessions. Following each psychedelic experience, she also completed a psychedelic integration session. The case study investigates the effect of the intervention, the observed changes in the participant, and the potential processes of change which may account for this improvement. The analysis relies on a qualitative narrative approach to examine the content of each therapy session, as well as on the psychometric measures completed at baseline, post-treatment, and at the three-month follow-up. These results are linked to emerging theories in the field, with a particular focus on the role of meaning reconstruction, psychological flexibility, and a continuing bond with the deceased.
... In 2015, Favaro and colleagues [67] demonstrated that chronic administration (30 days) of AYA at the very high doses of 120, 240, and 480 mg/kg modulated contextual emotional association in rats, while Pic-Taylor and coauthors [68] reported that a single administration of AYA in Wistar rats at much lower doses corresponding to 4.5 mg/ kg and 9 mg/kg of DMT promoted a decrease in locomotor and exploratory activities in the OFT and in the EPM test, similar to the fluoxetine-treated control group. According to Sanches and colleagues [16], a dose of 1.76 mg/kg of DMT in humans is effective for the clinical treatment of patients with depression. Here, the lowest dose tested corresponds [69]. ...
The psychoactive decoction Ayahuasca (AYA) used for therapeutic and religious purposes by indigenous groups and peoples from Amazonian regions produces anti-inflammatory and neuroprotective effects. Thus, it may be useful to attenuate the neuroinflammation and related anxiety- and depressive-like symptoms elicited by inflammatory insults such as sepsis. Rats were pretreated for 3 days with different doses of AYA. Twenty-four hours after, cecal ligation and puncture (CLP) was performed. On days 1–4, post-CLP behavioral tests to assess anxiety-like behavior were performed. After 24-h, neuroinflammation, oxidative stress, myeloperoxidase activity, and mitochondrial metabolism were assessed in the prefrontal cortex (PFC), hippocampus (HP), and cortex. AYA pretreatment increased the time spent in the open arms of the elevated plus maze and prevented the sepsis-induced hyper-grooming and -rearing behavior, suggesting an anxiolytic effect. AYA pretreatment increased the levels of the anti-inflammatory interleukin 4, in the PFC and the cortex, and brain-derived neurotrophic factor in the cortex. Moreover, AYA pretreatment increased myeloperoxidase activity in the PFC and the HP and decreased nitrite/nitrate concentration in the PFC, HP, and cortex of septic rats, suggesting enhanced neutrophil activation and decreased nitric oxide signaling. Furthermore, AYA pretreatment prevented lipid peroxidation in the PFC, HP, and cortex of septic rats as measured by decreased levels of thiobarbituric acid reactive substances. Levels of protein carbonyls and activity of superoxide dismutase, citrate synthase, succinate dehydrogenase, and mitochondrial respiratory chain were not affected. Together, AYA represents a promising approach to prevent sepsis-induced neuroinflammatory and oxidative stress and associated anxiety-like symptoms.
... Este interés ha llegado a la investigación biomédica, que hoy día la estudia por su potencial para el tratamiento de numerosas dolencias: como antiinflamatorio (Santos, Moreira, Borges y Caldas, 2022), neuroprotector (Katchborian-Neto et al., 2020), para enfermedades neurodegenerativas (Samoylenko et al., 2010), en el tratamiento de la depresión mayor (Sanches et al., 2016), el duelo (González et al., 2020), los trastornos de ansiedad (Dos Santos et al., 2021;Dos Santos et al., 2022), la regulación emocional (Domínguez-Clavé et al., 2019), la dependencia de drogas (Rodrigues et al., 2022) o el trauma (Weiss et al., 2023). ...
The International Center for Ethnobotanical Education, Research & Service (ICEERS) is a non-profit and public utility Foundation that navigates the challenges of the globalization of psychoactive plants such as ayahuasca or iboga. This article will review the 12 years of research by the ICEERS scientific team, building a narrative about the basic notions that should be had about ayahuasca, based largely on our publications. A “deobjectify” view of ayahuasca is proposed and inserted into a medical system where the most important focus is the system, not the ayahuasca itself.
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ICEERS (International Center for Ethnobotanical Education, Research & Service) es una Fundación sin ánimo de lucro y de utilidad pública que navega los desafíos de la globalización de las plantas psicoactivas como la ayahuasca o la iboga. En este artículo se hará un repaso a los 12 años de inves-tigación del equipo científico de ICEERS, construyendo una narrativa sobre las nociones básicas que se deben tener sobre la ayahuasca, basada mayormente en nuestras publicaciones. Se propone una mirada de la ayahuasca “descosificante” e inserta en un sistema médico donde lo importante es el sistema, no la ayahuasca en sí.
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https://transpersonaljournal.com/en/component/edocman/jtr-all-root-en/cat-jtr-2024-16-1/cat-jtr-2024-16-1-theoretical-studies/ayahuasca-nociones-basicas.html?Itemid=528
... Serotonergic psychedelics such as psilocybin have long been employed by diverse cultures for spiritual and medicinal purposes 1 , producing profound alterations in perception and long-term changes in mood and cognition 2 . Promising results from several clinical trials have accelerated clinical interest in psychedelics to treat conditions such as depression 3-6 , addiction 7-10 and anxiety 3,[11][12][13][14] . A number of animal studies have identified a rapid induction of enhanced neuroplasticity with psychedelics, facilitating structural and functional remodeling of neural circuitry [15][16][17][18][19] . ...
Psilocybin, a psychoactive substance derived from fungi, has been utilized historically by diverse cultures for both medicinal and non-medicinal purposes, owing to its ability to elicit profound sensory and cognitive alterations and sustain long-term changes in mood and cognition. Promising results from recent clinical studies have generated a wave of interest in employing psilocybin to treat neuropsychiatric and neuro-degenerative conditions. How psychedelics cause acute perceptual effects, and how these relate to long-lasting alterations is still debated. Whereas it is thought that perceptual disturbances may be caused by disrupted flow of information between sensory and higher order areas, in vivo studies have focused mostly on the latter. In particular, there has been little study of how psilocybin affects sensory representations in primary auditory cortex (A1). We used two-photon microscopy and wide field calcium imaging to examine how psilocybin affects A1 neuron response properties in the mouse. Administration of 1 mg/kg psilocybin prevented habituation of sound-evoked responses to repeated stimuli, maintaining overall responsiveness, bandwidth, and sound-level response thresholds after repeated stimulation. This was in contrast to marked habituation of responses and narrowing of tuning in controls. We observed no effect on overall distribution of best frequencies at the cortical level, suggesting psilocybin in A1 disrupts normal sensory gating, rather than tonotopic organization. This supports models of psychedelic action in which perceptual disturbances are driven by disrupted hierarchical sensory gating. With further research, influences of psychedelics on sensory representations could be harnessed to target maladaptive sensory processing in conditions such as tinnitus.
Significance Statement
Despite its role in altering auditory sensory perception, the impact of psilocybin on modulating neuronal activity in the auditory cortex remains understudied. This study is the first to identify an inhibition of normal auditory habituation to repeated stimuli with single-neuron resolution. We identify a role for psilocybin in the targeted, context-dependent modulation of auditory sensory neural tuning properties, which may help to explain how disruption of hierarchical control of sensory representations leads to perceptual disturbances. With further work, this influence on sensory representations could be used to target conditions where maladaptive sensory processing leads to deleterious health outcomes.
... Psychedelics have also been studied for the treatment of depression. In an open-label pilot study, 17 patients with major depressive disorder received a single dose of ayahuasca 1 and showed significant reductions in depressive symptoms lasting three weeks (Osório et al., 2015;Sanches et al., 2016). Meanwhile, in a double-blind randomized controlled trial involving 35 patients with treatment-resistant depression, half of the patients showed significant antidepressant effects lasting up to a week after a single dose of ayahuasca (Palhano-Fontes et al., 2019). ...
A recent wave of research in psychiatry and neuroscience has re-examined the properties of ‘classic’ psychedelic substances—also known as serotonergic hallucinogens—such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT). Evidence to date suggests that psychedelics can be given safely in controlled conditions, at moderate to high doses, and may have potential as therapeutic agents in the treatment of various addictive and mood disorders. The main mechanism of action appears to be the induction of a dramatically altered state of consciousness, but the details of how psychedelic-assisted psychotherapy works are hotly debated, as are the relations between psychedelic experiences themselves and the neural changes induced by the drugs. The chapters collected in this volume address the fascinating philosophical questions raised by the renewed psychiatric use of psychedelics. The topics of these chapters cluster around three main themes, in terms of which the volume is organized. Chapters in Section One, ‘Self and Mind’, ask: what can we learn about the self and the mind from psychedelic science? Chapters in Section Two, ‘Science and Psychiatry’, address methodological, theoretical, and clinical questions concerning how psychedelics can best be studied scientifically and used therapeutically, and how they might work to relieve psychiatric suffering. Finally, chapters in Section Three, ‘Ethics and Spirituality’, address broader questions about the interpretation of psychedelic experience, its ethical implications, and its possible role(s) in the broader culture.
... Nausea and vomiting are traditionally not considered to be negative side effects of ayahuasca, as it is part of the ritualistic process where purgation is important (Palhano-Fontes et al. 2019;Zeifman et al. 2020;Durante et al. 2021). The clinical trial by Sanches et al. (2016) indicated that ayahuasca is well tolerated by volunteers, as there was no significant increase in blood pressure, heart rate or any other cardiovascular indicator, and no dysphoric effect was reported. ...
Ayahuasca is a psychoactive decoction originally used in indigenous Amazonian culture. It consists of a dense brown liquid that most frequently results from the decoction of two plants native to the Amazon rainforest, Psychotria viridis (Rubiaceae) and Banisteriopsis caapi (Malpighiaceae). The composition of the decoction is variable, as several plant species can be used in its preparation. Its psychoactive effect occurs due to the presence of N,N-dimethyltryptamine (DMT), an agonist at serotonergic receptors (5-HT1A/2A/2C) that is metabolized by the enzyme monoamine oxidase type A (MAO-A), and also the presence of β-carbolines, which are reversible MAO-A inhibitors. This joint interaction promotes a sequence of psychedelic neurochemical effects. Due to the current expansion of research on psychedelic substances and the growing public interest in the benefits of ayahuasca beyond its traditional use in the Amazon, academic research on its therapeutic capacity has been increasing. This study aimed to carry out a literature review on the scientific evidence for the therapeutic potential of ingesting ayahuasca. The review covered the period 2012-2022, and resulted in evidence on the therapeutic effects of ayahuasca on depression/anxiety, chemical dependency/alcoholism and Parkinson’s disease, as well as neuropsychological effects, and possible toxic effects on reproduction/embryonic development, among other adverse effects. The highest number of publications in the searched period dealt with the effects of ayahuasca on depression and anxiety. Further studies need to address the detailed mechanism of action of ayahuasca, as well as its potential toxicity, in order to demonstrate its safety.
... Serotonergic psychedelics have been reported to mitigate anxiety and mood disorders symptoms after just a single dose [1][2][3][4][5][6][7][8] with long-lasting effects likely due to structural plasticity [9][10][11][12][13][14][15][16][17]. Psychedelics treatment leads to dendritic spine growth, increases dendritic arbor complexity, and stimulates synapse formation, although results vary among studies [9,18]. ...
Serotonergic psychedelics have potential therapeutic effects in treating anxiety and mood disorders, often after a single dose, and are suggested to have plasticity-inducing action. However, a comprehensive mechanism of action is still lacking. Here, we investigated how a single dose of the short-acting 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) acts on gene expression from microdissected brain regions (anterior cingulate cortex - ACC; basolateral amygdala - BLA; ventral hippocampus CA1 region - vCA1 and dentate gyrus—DG) of naive and stressed mice. Specifically, we compared gene expression of Arc, Zif268, BDNF, CREB, mTORC1, NR2A, TRIP8b, and NFkB in mice injected with 5-MeO-DMT or saline at different time points (1 h, 5 h, or 5 days prior). 5-MeO-DMT altered mRNA expression of immediate early genes Arc and ZiF268 in the ACC, BLA, and vCA1, while NR2A expression was decreased after 5 h in the vCA1. We also found a long-term increase in TRIP8b, a gene related to the modulation of neuronal activity, in the vCA1 after 5 days. Behaviorally, 5-MeO-DMT treated mice showed mixed anxiolytic and anxiogenic effects in the elevated plus maze and open field test 24 h or 5 days after treatment. However, pre-treated mice subjected to acute stress showed both lower corticosterone levels and robust anxiolytic effects of 5-MeO-DMT administration. Together, our findings provide insights into the molecular actions of 5-MeO-DMT in the brain related to anxiolytic effects of behavior.
... A renewed focus on these drugs in psychiatric research has led to a revisiting of their applications, with encouraging findings emerging for conditions such as substance use disorders (Armstrong et al., 2023;Bogenschutz et al., 2015;Hendricks et al., 2014;Johnson et al., 2014;Tap, 2024), depression and anxiety (including in individuals with serious and terminal medical conditions) (Carhart- Griffiths et al., 2016;Grob et al., 2011;Ross et al., 2016;Sanches et al., 2016), obsessive-compulsive disorder (OCD) (Buot et al., 2023;Moreno et al., 2006), and challenging personality traits (leading to a heightening of prosocial, anti-materialist, and pro-ecological attitudes) (Halpern, 2003;Hendricks et al., 2014;Isham et al., 2022;Timmermann et al., 2021). Beyond these, further applications for psychedelics (e.g., for eating disorders, traumatic brain injuries, and neurocognitive disorders) are being explored (Allen et al., 2024;Cherian et al., 2024;Harris, 2024;Peck et al., 2023;Pilozzi et al., 2023;Saeger & Olson, 2022). ...
... There were five studies that investigated the use of ayahuasca for the treatment of depression and one investigating its effect on grief. Sanches et al. (2016) demonstrated significant clinical reduction of symptoms, in a study of good quality, and a five-year qualitative follow-up, rated moderate, demonstrated that ayahuasca was well tolerated and symptom reductions were limited to a few weeks (Santos, Sanches, Osório, & Hallak, 2018). Palhano-Fontes et al. (2019) conducted an RCT of good quality, which demonstrated a significant reduction in depression in the ayahuasca group. ...
Background and aims
Psychedelics show promise for treatment of mental health conditions (MHCs). But there is relatively little research on indigenous psychedelics conducted in the Global South (GS). Much research is carried out in the Global North, where there are different cultural perceptions of mental health and psychedelics. Therefore, this paper appraises research on psychedelics for treatment or therapy where research was carried out in the GS.
Method
A systematic review of research literature was conducted from 1st January 2010 to 31st July 2023. Medline, PsychINFO and Global Health databases were searched for studies of patients undergoing treatment for MHCs with psychedelics.
Results
Data from 27 papers were extracted and narratively synthesized. A total of 984 participants were included suffering from depression, obsessive-compulsive disorder, substance use disorder, post-traumatic stress disorder and eating disorders. The studies investigated the feasibility of psychedelic treatments and presented evidence for their safety. There was preliminary efficacy data for ayahuasca, iboga, 5-MeO-DMT, psylocibin, and MDMA in the treatment of some MHCs. All studies were conducted in line with ethical and medical guidelines, and no serious adverse events were reported.
Conclusion
A renaissance of clinical psychedelic research on substances that have been used as traditional medicines in the GS presents promising evidence for treatment efficacy and safety across a range of MHCs. Psychedelics present an exciting new treatment approach for people in the GS, in a health area with considerable unmet need. Moreover, research demonstrated cost-effectiveness, while results suggested no significant safety concerns or side effects.
... Psychedelics have made an impressive comeback in mental health care. In the last decade, an increasing number of studies have investigated the therapeutic effects of classic serotonergic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT). 1 The present results are promising and suggest efficacy in the treatment of major depressive disorder (Carhart- Carhart-Harris et al., 2018, 2021Goodwin et al., 2022;Palhano-Fontes et al., 2019;Raison et al., 2023;Reiff et al., 2020;Rotz et al., 2023;Sanches et al., 2016), anxiety with and without a life-threatening illness (Gasser et al., 2014;Griffiths et al., 2016;Holze et al., 2023;Reiff et al., 2020;Ross et al., 2016), and alcohol and smoking cessation (Bogenschutz et al., 2015;Garcia-Romeu et al., 2019;Krebs & Johansen, 2012). Meta-analyses and systematic reviews underscore the potential benefits of psychedelics in mental health care and suggest that psychedelics can be safely used in the clinical context (Andersen et al., 2021;Bender & Hellerstein, 2022;Haikazian et al., 2023;Ko et al., 2023;Maia et al., 2022;Romeo et al., 2020;Roscoe & Lozy, 2022;Simonsson et al., 2023;Wheeler & Dyer, 2020). ...
... En pacientes internados en una unidad psiquiátrica con depresión recurrente, una sola dosis de ayahuasca (2.2 ml/kg) disminuyó significativamente la depresión desde los 80 minutos posingestión hasta los subsecuentes 21 días que fueron evaluados y se observó una mayor perfusión sanguínea en el núcleo accumbens izquierdo, la ínsula derecha y el área subgenual izquierda, estructuras relacionadas con el estado de ánimo y las emociones (Sanches et al., 2016). Por otra parte, se ha reportado que el DMT facilita la aceptación de la muerte en pacientes oncológicos terminales. ...
Los enteógenos han surgido en la investigación clínica como un tratamiento alternativo para la Depresión Resistente al Tratamiento (DRT). Tienen efectos antidepresivos rápidos y duraderos, son ansiolíticos, y mitigan la ideación suicida. Además, inducen emociones positivas y provocan experiencias místicas o espirituales, atributos que pueden contribuir a su eficacia terapéutica, dada la influencia protectora del misticismo y la religiosidad contra la depresión. Esta revisión narrativa tiene como objetivo discutir la evidencia existente sobre la utilización de enteógenos en la DRT, proporcionar una comprensión actualizada del panorama de la investigación y discutir los mecanismos de acción de compuestos como la psilocibina, DMT, LSD, ketamina, esketamina y cannabinoides. La eficacia de los enteógenos en el manejo de la depresión ha sido validada consistentemente en los ensayos clínicos. No obstante, es imperativo reconocer nuestra limitada comprensión de los posibles efectos adversos, especialmente a largo plazo, a pesar de los datos que sustentan su tolerabilidad aguda.
... Ceremonial ayahuasca use is associated with benefits to mental health Accumulating evidence from cross-sectional, preclinical, and experimental studies suggest that ayahuasca has both antidepressant and anxiolytic effects (72). Robust evidence from controlled and open-label trials shows reduced depression scores following the administration of ayahuasca (20,73,74). Similarly, although anxiety studies show mixed results [see (33)], some studies suggest ayahuasca may have therapeutic potential in the treatment of anxiety [e.g., (75,76)]. ...
Background
Refugees and immigrants can experience complex stressors from the process of immigration that can have lasting and severe long-term mental health consequences. Experiences after ayahuasca ingestion are shown to produce positive effects on psychological wellbeing and mental health, including anecdotal reports of improved symptoms of trauma and related disorders. However, data on the longitudinal health impact of naturalistic ayahuasca use in Middle Eastern and North African (MENA) immigrant and refugee populations is limited.
Aims
The current longitudinal online survey study was conducted to gather prospective data on ceremonial ayahuasca use in a group (N = 15) of primarily female MENA immigrants and refugees and to provide further insight into the patterns and outcomes surrounding that use. The study sought to assess self-reported changes in physical and mental health, well-being, and psychological functioning, examine relationships between aspects of individual mindset (e.g., psychedelic preparedness) prior to ayahuasca use and observed outcomes during (e.g., subjective drug effects) and afterwards (i.e., persisting effects), characterize risks and negative experiences, and describe trauma exposure and personal history.
Results/Outcomes
Our findings revealed ceremonial use of ayahuasca is associated with significant improvements in mental health, well-being, and psychological functioning, including reductions in depression, anxiety, and shame, and increases in cognitive reappraisal and self-compassion. Most participants reported no lasting adverse effects and experienced notable positive behavioral changes persisting months after ingestion.
Conclusion/Interpretation
While preliminary, results suggest naturalistic ayahuasca use might hold therapeutic potential for MENA populations exposed to trauma prior to and during the process of migration.
... In recent decades, the effects of ayahuasca in the treatment of depression and anxiety have been studied [75, [87][88][89][90]. In a study of patients suffering from depressive disorder, symptoms and signs of depression decreased immediately after ingestion of ayahuasca, and the effect lasted for 14 days. ...
The Amazon region is the world’s largest river basin and rainforest ecosystem. The
vast area belongs to nine South American nations: Bolivia, Brazil, Colombia, Ecuador,
French Guiana, Guyana, Peru, Suriname, and Venezuela. Amazonia has one of the
largest amounts of surface freshwater and the highest average annual precipitation in
the world
... Psychedelics have emerged as promising treatments for not only depression [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] but also a wide range of other psychiatric conditions, including substance use disorder, 29,30 post-traumatic stress disorder, [31][32][33][34][35][36] and end-of-life anxiety. [37][38][39][40][41] However, there is little emphasis on psychedelics in medical education, and many physicians just feel unprepared to manage patients taking psychedelic medications in the setting of other acute and chronic conditions. ...
Background
Psychedelic drugs have recently emerged as plausibly effective pharmacological agents for the management of depression, anxiety, and other neuropsychiatric conditions, including those that are treatment-resistent. The latter half of the 20th century marked a revolution in the treatment of mental illnesses, exemplified by the introduction of selective serotonin reuptake inhibitors and other pharmacological agents. Nevertheless, mental illness remains a major public health crisis, affecting nearly one billion individuals worldwide.
Areas of Uncertainty
Because of the decades-long status of several psychedelics as Schedule I drugs, there have not been very many large, double-blind, randomized controlled trials of psychedelics. Owing to small sample sizes, there may be rare yet serious adverse events that have not been reported in the clinical trials thus far.
Therapeutic Advances
Esketamine, a dissociative hallucinogen drug, was approved for the management of major depressive disorder by the Food and Drug Administration in 2019. As of January 2024, two Phase III trials of 3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug that inhibits the serotonin transporter, have been completed; the results indicate that MDMA is superior to existing pharmacological treatments for post-traumatic stress disorder. A phase III trial of psilocybin, a naturally occurring serotonin receptor partial agonist, is currently underway. The following series details the current state of research in psychedelic therapeutics, including lysergic acid diethylamide (LSD), N-N-dimethyltryptamine (DMT) and ayahuasca, psilocybin, ibogaine, MDMA, and ketamine.
Limitations
While initial clinical trials of psychedelics for depression were very promising, trials of psilocybin with larger sample sizes (100+ participants) suggest that its remission rate is 25%–29%. This is about the same as the remission rate of antidepressants, which is roughly 30% according to the landmark STAR*D trial.
Conclusions
Psychedelic drugs and structural derivatives offer a great deal of promise for the management of a wide range of psychiatric morbidities. It is imperative that clinicians become familiar with these novel agents and learn how to integrate psychedelic therapy with the rest of their care through open communication and referral.
... In recent decades, the effects of ayahuasca in the treatment of depression and anxiety have been studied [75, [87][88][89][90]. In a study of patients suffering from depressive disorder, symptoms and signs of depression decreased immediately after ingestion of ayahuasca, and the effect lasted for 14 days. ...
This book includes six chapters describing the anthropological, biological and industrial problems facing the Amazon region. It highlights a new risk, that of historic drought caused by El Nino. The book seeks also positive examples of sustainable development possibilities.
... After a period of more curbed and negative attention in the Global North, partially due to various governmental interventions (Giffort, 2020), the past two decades have witnessed a revival of scientific and public interest in the use of psychedelics for therapeutic purposes (Carhart-Harris & Goodwin, 2017). A fast-growing number of studies indicate that psychedelics, when used with certain conducts and frames, can alleviate a wide range of conditions such as major and treatment-resistant depression Gukasyan et al., 2022;Sanches et al., 2016;van Oorsouw et al., 2022), eating disorders (Spriggs et al., 2021), endof-life psychological distress (Gasser et al., 2014;Griffiths et al., 2016;Ross et al., 2016), alcohol, tobacco and opioid addiction (Bogenschutz et al., 2015;dos Santos et al., 2017;Johnson et al., 2014;Noorani et al., 2018), cluster headaches (Andersson et al., 2017) and improve general wellbeing (Griffiths et al., 2006;Haijen et al., 2018). These research results have been accompanied by a prosperous psychedelics industry and tourism and a rocketing amount of organisations, businesses, citizens' initiatives and media coverage trying to either ride, profit from or steer the wave (Chabloz, 2009;Psychedelic Invest, 2024;Steinhardt & Noorani, 2020). ...
Within recent years, an increasing number of people and researchers in the Global North have become interested in psychedelic substances and their therapeutic application. While much of the current media attention and research effort mainly concentrate on the therapeutic potential and actions of the individual's acute psychedelic experience, this article explores the user‐perceived, therapeutic dynamics of psychedelics in a more long‐term perspective by charting the lived experiences and practices of ‘integration’ among psychedelic users in Denmark. Based on ethnographic fieldwork from November 2020 to June 2021, I offer a dual typology of self‐related integration as narrative and experiential‐somatic . Combining the two, I argue that psychedelic integration in contemporary Denmark can be viewed as a processual self‐transformation of the users' experiential orientation where understandings and/or modes of being from the acute psychedelic experience are woven into, prolonged, and/or embodied in their everyday existence .
... Early studies evidenced a series of positive psychotropic effects of ayahuasca in religious users [61], an effect that was confirmed by a similar observational study years later [62]. Following studies evidenced a rapid antidepressant effect [63]. Then a randomized placebo-controlled trial confirmed a very rapid effect in treatment resistant depression since day 1, with an impressive effect size of d = 1.49 at day 6 of treatment, with a remission of 36% after 7 days [64]. ...
For the first time after many decades, many new antidepressants have been approved and many more are under various stages of development and will soon be available in the market. The new drugs present a range of new mechanisms of action with benefits in terms of speed of action, tolerability and range of treatable disorders. Neurosteroids have been recently approved and their rapid benefit may extend from postpartum depression to anxious depression and bipolar depression, dextromethorphan and bupropion combination may prove useful in major depression but also in treatment resistant depression, dextromethadone is a possible augmentation in partial antidepressant response, psychedelic drugs have the potential of long lasting benefits after a single administration, though are still experimental treatments. Botulinum has the same advantage of psychedelics of a single administration and its antidepressant effects may last for weeks or more. Further potentially interesting new antidepressant mechanisms include new drug targets, drug repurposing and genetic or epigenetic manipulations. It is therefore important that clinicians are kept up to date with new evidence so that new evidence can be rapidly translated into clinical practice.
... Psychedelics are back on stage in mental healthcare [1]. Over the past decade, a growing number of studies have examined the therapeutic effects of classic serotonergic psychedelics, including psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT). 1 So far, the results are promising, suggesting effectiveness in treating cancer-related depression and anxiety [6][7][8][9][10], (treatment-resistant) depression [6,[11][12][13][14][15][16][17], and alcohol and smoking cessation [18][19][20][21][22][23]. But even though psychedelics have been ascribed great potential to have a major impact on mental healthcare in the coming decades, caution is still in order. ...
A psychedelic renaissance is currently taking place in mental healthcare. The number of psychedelic-assisted therapy trials is growing steadily, and some countries already grant psychiatrists special permission to use psychedelics in non-research contexts under certain conditions. These clinical advances must be accompanied by ethical inquiry. One pressing ethical question involves whether patients can even give informed consent to psychedelic-assisted therapy: the treatment’s transformative nature seems to block its assessment, suggesting that patients are unable to understand what undergoing psychedelic-assisted therapy actually means for them and whether it aligns with their values. The present paper argues that patients often have sufficient knowledge to give informed consent because they know that they want to change their negative status quo and that psychedelic-assisted therapy offers an effective way to do so. Accordingly, patients can understand what the transformative nature of psychedelic-assisted therapy means for them and a make a value-aligned choice even if they are unable to anticipate the manifestation of a psychedelic experience.
Rationale
In our ongoing battle against the coronavirus 2019 (COVID-19) pandemic, a major challenge is the enduring symptoms that continue after acute infection. Also known as Long COVID, post-COVID-19 syndrome (PCS) often comes with debilitating symptoms like fatigue, disordered sleep, olfactory dysfunction, and cognitive issues (“brain fog”). Currently, there are no approved treatments for PCS. Recent research has uncovered that the severity of PCS is inversely linked to circulating serotonin levels, highlighting the potential of serotonin-modulating therapeutics for PCS. Therefore, we propose that serotonergic psychedelics, acting mainly via the 5-HT2A serotonin receptor, hold promise for treating PCS.
Objectives
Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS.
Results
Potential mechanisms through which serotonergic psychedelics may alleviate PCS symptoms are discussed, with emphasis on their effects on inflammation, neuroplasticity, and gastrointestinal function. Additionally, this review explores the potential of serotonergic psychedelics in mitigating endothelial dysfunction, a pivotal aspect of PCS pathophysiology implicated in organ dysfunction. This review also examines the potential role of serotonergic psychedelics in alleviating specific PCS symptoms, which include olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges.
Conclusions
Emerging evidence suggests that serotonergic psychedelics may alleviate PCS symptoms. However, further high-quality research is needed to thoroughly assess their safety and efficacy in treating patients with PCS.
Introduction:
After a long period of obscurantism, a possible role of psychedelics in clinical practice has progressively become a tangible perspective during the last two decades. However, the resounding enthusiasm linked to such 'psychedelic renaissance' runs the risk to unduly minimize the possible hazards associated with these compounds, while expanding their alleged benefits to improbable panacea-like proportions. In order to avoid mystifying or demonizing the properties of 5-HT2a agonists on emotional grounds, this subject requires a strictly unprejudiced and cautious approach to the evidence.
Areas covered:
In this article, the authors attempted to comprehensively analyze the available literature to provide a balanced overview of the possible benefits of psychedelics in healthcare, taking into account their potential risks.
Expert opinion:
To date, psychedelics have shown a therapeutic potential in a wide range of conditions, with a seemingly limited risk of inducing adverse reactions, including abuse and dependence, when administered in a controlled environment by specialized personnel. In any case, although several questions remain unanswered before drawing firm conclusions, further studies are needed to establish which conditions and subjects could benefit from psychedelics and which patients bear the greater risk of adversities.
CITATION Chaves C, dos Santos RG, Dursun SM, Tusconi M, Carta MG, Brietzke E and Hallak JEC (2024) Why N,N-dimethyltryptamine matters: unique features and therapeutic potential beyond classical psychedelics.
Background
Harmine is a component of the hallucinogenic brew, Ayahuasca, which also contains the psychoactive compound, N, N-dimethyltryptamine. Whether pharmaceutical-grade harmine hydrochloride (HCl) has psychoactive effects, the doses at which these might occur, and the dose-response relationship to side effects and safety in humans are unknown.
Methods
We conducted a Phase 1, open-label single ascending dose trial in healthy adults with normal body mass index and no prior psychiatric illness. The primary goal was to determine the maximum tolerated dose (MTD) of oral pharmaceutical-grade harmine HCl and to characterize safety and tolerability. A secondary goal was to ascertain whether any oral dose has psychoactive effects.
Results
Thirty-four adult participants, aged 18–55 years, were screened for study eligibility. Twenty-five participants met eligibility criteria and were randomized to a single dose of 100, 200, 300, or 500 mg of harmine HCl, respectively, using a continuous reassessment method. The most common adverse events (AEs) observed were gastrointestinal and/or neurological, dose-related, and of mild to moderate severity. The MTD was determined to be between 100 and 200 mg and is weight-based, with 90% of those participants receiving >2.7 mg/kg experiencing a dose-limiting toxicity. No serious AEs of harmine HCl were identified.
Conclusions
Harmine HCl can be orally administered to healthy participants in doses <2.7 mg/kg with minimal or no AEs. Doses >2.7 mg/kg are associated with vomiting, drowsiness, and limited psychoactivity. This study is the first to systematically characterize the psychoactive effects of pharmaceutical quality harmine in healthy participants.
This narrative review explores the utilization of psychedelic states in therapeutic contexts, deliberately shifting the focus from psychedelic substances back to the experiential phenomena which they induce, in alignment with the original meaning of the term “mind-manifesting”. This review provides an overview of various psychedelic substances used in modern therapeutic settings and ritualistic indigenous contexts, as well as non-pharmacological methods that can arguably induce psychedelic states, including breathwork, meditation, and sensory deprivation. While the occurrence of mystical experiences in psychedelic states seems to be the strongest predictor of positive outcomes, the literature of this field yields several other psychological processes, such as awe, perspective shifts, insight, emotional breakthrough, acceptance, the re-experiencing of memories, and certain aspects of challenging experiences, that are significantly associated with positive change. Additionally, we discuss in detail mystical experience-related changes in metaphysical as well as self-related beliefs and their respective contributions to observed outcomes. We conclude that a purely medical and neurobiological perspective on psychological health is reductive and should not overshadow the significance of phenomenological experiences in understanding and treating psychological issues that manifest in the subjective realities of human individuals.
Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, associated with substantial burden and large economical costs. Notwithstanding various conventional antidepressant treatment options, a large portion of depressed people (ca. 30%) fails to respond to first-line treatment, resulting in treatment-resistant depression (TRD). Although non-response to multiple antidepressant interventions is a common outcome, a consensus definition of TRD is not yet available. In practice, TRD is applied when two or more successive treatments with different antidepressants are not working. The last decade’s intense research into new medicines for TRD has led to two developments, using typical or serotonergic (psilocybin, ayahuasca) and atypical (glutamatergic) psychedelics (ketamine, esketamine). Both approaches, although via different entrance mechanism, exhibit a fast onset but also long-lasting antidepressant effect far beyond the biological presence of the drug in the body, strongly indicating that downstream mechanisms activated by signaling cascades in the brain are involved. The present chapter describes the clinical development of psilocybin and esketamine for TRD and discusses the problems involved in the use of a proper placebo because of the psychotomimetic (psilocybin) or dissociative (ketamine) effects that interfere with performing “blind” studies. Nevertheless, intranasal esketamine was developed and approved for TRD, whereas psilocybin has shown positive results. Adverse effects and tolerability of both drugs in the dose ranges used are generally acceptable. The emergence of anti-TRD medicines for treatment of a very severe disease is a breakthrough in psychiatry.
The potent hallucinogen N,N-dimethyltryptamine (DMT) has garnered significant interest in recent years due to its profound effects on consciousness and its therapeutic psychopotential. DMT is an integral (but not exclusive) psychoactive alkaloid in the Amazonian plant-based brew ayahuasca, in which admixture of several β-carboline monoamine oxidase A (MAO-A) inhibitors potentiate the activity of oral DMT, while possibly contributing in other respects to the complex psychopharmacology of ayahuasca. Irrespective of the route of administration, DMT alters perception, mood, and cognition, presumably through agonism at serotonin (5-HT) 1A/2A/2C receptors in brain, with additional actions at other receptor types possibly contributing to its overall psychoactive effects. Due to rapid first pass metabolism, DMT is nearly inactive orally, but co-administration with β-carbolines or synthetic MAO-A inhibitors (MAOIs) greatly increase its bioavailability and duration of action. The synergistic effects of DMT and MAOIs in ayahuasca or synthetic formulations may promote neuroplasticity, which presumably underlies their promising therapeutic efficacy in clinical trials for neuropsychiatric disorders, including depression, addiction, and post-traumatic stress disorder. Advances in neuroimaging techniques are elucidating the neural correlates of DMT-induced altered states of consciousness, revealing alterations in brain activity, functional connectivity, and network dynamics. In this comprehensive narrative review, we present a synthesis of current knowledge on the pharmacology and neuroscience of DMT, β-carbolines, and ayahuasca, which should inform future research aiming to harness their full therapeutic potential.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00018-024-05353-6.
Background
Previous international clinical trials have indicated that mystical experiences resulting from the consumption of classic psychedelic drugs, such as psilocybin, may represent a subjective psychological mechanism of action associated with therapeutic effects for various mental disorders. The revised 30-item Mystical Experience Questionnaire is one of several psychometric scales designed to evaluate such subjective experiences induced by psychedelic drugs. The field of psychedelic research is growing in Scandinavian countries, yet there is currently a lack of translated and culturally adapted Norwegian versions of rating scales for assessing psychedelic drug-induced states of consciousness. With planned and upcoming psychedelic research projects in Norway, there is a need for a Norwegian version of the MEQ30.
Aims
We aimed to translate and adapt the Revised Mystical Experiences Questionnaire (MEQ30) from English to Norwegian.
Methods
We used rigorous translation methods, including two independent forward translations, one back-translation, pilot testing on a small psychedelic user group (n = 6) and cognitive debriefing in an expert-panel (n = 6) to ensure a culturally adapted Norwegian translation.
Results
Our translation and adaptation procedure resulted in a final Norwegian version of the MEQ30.
Conclusion
The Norwegian MEQ30 is ready to be implemented in future Norwegian trials. Its psychometric properties have not yet been assessed.
Psychedelic substances have demonstrated promising therapeutic effects across a wide range of mental health conditions including depression (1-13) anxiety disorders including generalized anxiety (14-16) and social anxiety (17, 18) and autism (19), post-traumatic stress disorder (PTSD) (6, 20-23), and substance use disorders such as tobacco addiction (24) and alcoholism (25-30). These therapeutic effects are hypothesized to work through various mechanisms operating at different levels of analysis. At the cellular and molecular level, these include increased stimulation of the 5-HT2A serotonin receptor, increased cortical glutamatergic transmission, increased neuroplasticity, and decreased inflammation (31). At the network and circuit levels, the proposed mechanisms involve decreased brain modularity, changes in network functional connectivity, and increased neural entropy (32, 33). Psychologically and behaviorally, the effects are thought to involve increased cognitive and psychological flexibility, experiences of psychological insight, heightened emotional acceptance, and peak experiences or mystical-type states (34, 35). By further examining the neurobiological and psychological mechanisms of psychedelic substances, we can gain a deeper understanding of how these substances interact with the brain and influence behavior and help alleviate suffering in various psychopathologies.
Serotoninergic psychedelics or hallucinogens such as lysergic acid diethylamide (LSD), ayahuasca/dimethyltryptamine, and psilocybin are currently being investigated as possible therapeutics in psychiatry. Preliminary clinical trials with promising results have been performed in major depressive disorder (MDD) (including treatment-resistant major depressive disorder), substance use disorders (alcohol and tobacco), anxiety disorders (social anxiety disorder, generalized anxiety disorder), and cancer-related depression and/or anxiety. These trials use single or few doses of these drugs, and suggest rapid (hours/days) and sustained (weeks/months) antidepressive, anxiolytic, and antiaddictive effects. Agonism at cortical layer V 5-HT2A receptors present in the frontal and limbic regions seems to be the main mechanism of action of these drugs, which appears to lead to an increase in glutamatergic tone, neuroplasticity, and cognitive flexibility (especially social cognition). Other effects include increases in introspection, positive mood, openness to new experiences, and improvements in emotional regulation. The most relevant of these trials is critically discussed in this chapter, highlighting their promising (but preliminary) results, limitations, and the challenges associated with the possible use of these drugs in psychiatry.
The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of preclinical, clinical, epidemiological, and pharmacovigilance data (as well as pertinent reviews and case studies) was conducted for articles using the electronic databases of PubMed and Web of Science (to 6 July 2023) and PsycINFO, ClinicalTrials.gov , and Embase (to 21 September 2022) and included articles in English in peer-reviewed journals. Additionally, reference lists were searched. Due to the breadth of the area covered, we presented the relevant data in a thematic format. Our searches revealed 78 relevant articles. Data showed that ayahuasca or DMT is generally safe; however, some adverse human events have been reported. Animal models using higher doses of ayahuasca have shown abortifacient and teratogenic effects. Isolated harmala alkaloid studies have also revealed evidence of potential toxicity at higher doses, which may increase with co-administration with certain medications. Harmaline revealed the most issues in preclinical models. Nevertheless, animal models involving higher-dose synthetic isolates may not necessarily be able to be extrapolated to human use of therapeutic doses of plant-based extracts. Serious adverse effects are rarely reported within healthy populations, indicating an acceptable safety profile for the traditional use of ayahuasca and DMT in controlled settings. Further randomized, controlled trials with judicious blinding, larger samples, and longer duration are needed.
Objective:
To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline).
Methods:
Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection.
Results:
Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression.
Conclusion:
Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.
This book presents a series of perspectives on the therapeutic potential of the ritual and clinical use of the Amazonian hallucinogenic brew ayahuasca in the treatment and management of various diseases and ailments, especially its role in psychological well-being and substance dependence. Biomedical and anthropological data on the use of ayahuasca for treating depression, PTSD, and substance dependence in different settings, such as indigenous contexts, neo-shamanic rituals, contemporary therapeutic circles, and in ayahuasca religions, in both South and North America, are presented and critiqued. Though multiple anecdotal reports on the therapeutic use of ayahuasca exist, there has been no systematic and dense reflection on the topic thus far. The book brings the therapeutic use of ayahuasca to a new level of public examination and academic debate. The texts in this volume stimulate discussion on methodological, ethical, and political aspects of research and will enhance the development of this emergent field of studies. © 2014 Springer-Verlag Berlin Heidelberg. All rights are reserved.
Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode.
Open-label trial conducted in an inpatient psychiatric unit.
Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement.
These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.
There is an increasing use of ayahuasca for recreational purposes. Furthermore, there is a growing evidence for the antidepressant properties of its components. However, there are no reports on the effects of this substance in the psychiatric setting. Harmaline, one of the main components of ayahuasca, is a selective and reversible MAO-A inhibitor and a serotonin reuptake inhibitor.
We present the case of a man with bipolar disorder who had a manic episode after an ayahuasca consumption ritual. This patient had had at least one hypomanic episode in the past and is currently depressed. We discuss the diagnostic repercussion of this manic episode.
There is lack of specificity in the diagnosis of substance-induced mental disorder. The knowledge of the pharmacodynamic properties of ayahuasca consumption allows a more physiopathological approach to the diagnosis of the patient.
This article offers critical sociological and philosophical reflections on ayahuasca and other psychedelics as objects of research in medicine, health and human sciences. It situates 21stcentury scientific inquiry on ayahuasca in the broader context of how early modern European social trends and intellectual pursuits translated into new forms of empiricism and experimental philosophy, but later evolved into a form of dogmatism that convenienced the political suppression of academic inquiry into psychedelics. Applying ideas from the field of science and technology studies, we consider how ayahuasca’s myriad ontological representations in the 21stcentury — for example, plant teacher, traditional medicine, religious sacrament, material commodity, cognitive tool, illicit drug — influence our understanding of it as an object of inquiry. We then explore epistemological issues related to ayahuasca studies, including how the indigenous and mestizo concept of “plant teacher” or the more instrumental notion of psychedelics as “cognitive tools” may impact understanding of knowledge. This leads to questions about whether scientists engaged in ayahuasca research should be expected to have personal experiences with the brew, and how these may be perceived to help or hinder the objectivity of their pursuits. We conclude with some brief reflections on the politics of psychedelic research and impediments to academic knowledge production in the field of psychedelic studies.
The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.
New World indigenous peoples are noted for their sophisticated use of psychedelic plants in shamanic and ethnomedical practices. The use of psychedelic plant preparations among New World tribes is far more prevalent than in the Old World. Yet, although these preparations are botanically diverse, almost all are chemically similar in that their active principles are tryptamine derivatives, either DMT or related constituents. Part 1 of this paper provides an ethnopharmacological overview of the major tryptamine-containing New World
hallucinogens
.
After no research in humans for >40 years, there is renewed interest in using lysergic acid diethylamide (LSD) in clinical psychiatric research and practice. There are no modern studies on the subjective and autonomic effects of LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse inhibition (PPI) of the acoustic startle response, and patients with schizophrenia exhibit similar impairments in PPI. However, no data are available on the effects of LSD on PPI in humans.
In a double-blind, randomized, placebo-controlled, crossover study, LSD (200 μg) and placebo were administered to 16 healthy subjects (8 women, 8 men). Outcome measures included psychometric scales; investigator ratings; PPI of the acoustic startle response; and autonomic, endocrine, and adverse effects.
Administration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours. The predominant effects induced by LSD included visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization phenomena. Subjective well-being, happiness, closeness to others, openness, and trust were increased by LSD. Compared with placebo, LSD decreased PPI. LSD significantly increased blood pressure, heart rate, body temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine. Adverse effects produced by LSD completely subsided within 72 hours. No severe acute adverse effects were observed.
In addition to marked hallucinogenic effects, LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy. LSD altered sensorimotor gating in a human model of psychosis, supporting the use of LSD in translational psychiatric research. In a controlled clinical setting, LSD can be used safely, but it produces significant sympathomimetic stimulation.
Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
N,N-dimethyltryptamine (DMT) is a widely distributed plant alkaloid that displays partial agonist activity at the 5-HT2A receptor and induces intense psychedelic effects in humans when administered parenterally. However, self-administration studies have reported a total lack of activity following oral intake. This is thought to be due to extensive degradation by monoamine oxidase (MAO). Despite increased use of DMT and DMT-containing preparations, such as the plant tea ayahuasca, the biotransformation of DMT in humans when administered alone is relatively unknown. Here we used high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry (MS/MS) to characterize the metabolism and disposition of oral and smoked DMT. Twenty-four-hour urine samples were obtained from 6 DMT users before and after intake of 25 mg DMT doses on two separate sessions. In one session, DMT was taken orally and in another it was smoked. After oral ingestion, no psychotropic effects were experienced and no DMT was recovered in urine. MAO-dependent indole-3-acetic acid (IAA) represented 97% of the recovered compounds, whereas DMT-N-oxide (DMT-NO) accounted for only 3%. When the smoked route was used, the drug was fully psychoactive, unmetabolized DMT and DMT-NO rose to 10% and 28%, respectively, and IAA levels dropped to 63%. An inverse correlation was found between the IAA/DMT-NO ratio and subjective effects scores. These findings show that in the smoked route a shift from the highly efficient MAO-dependent to the less efficient CYP-dependent metabolism takes place. This shift leads to psychoactivity and is analogous to that observed in ayahuasca preparations combining DMT with MAO inhibitors. Copyright © 2014 John Wiley & Sons, Ltd.
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, randomized, 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.
A double-blind, randomized, 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 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg 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 methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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 designed 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.
Interactions between glutamatergic and endocannabinoid systems may contribute to schizophrenia, dissociative states, and other psychiatric conditions. Cannabidiol (CBD), a cannabinoid-1/2 (CB1/2) receptor weak partial agonist or antagonist, may play a role in the treatment of schizophrenia.
This study tested the hypothesis that CBD would attenuate the behavioral effects of the NMDA receptor antagonist, ketamine, in healthy human subjects.
Ten male healthy volunteers were evaluated twice in a randomized order. In both sessions they received ketamine (bolus of 0.26 mg/kg/1 min followed by IV infusion of 0.25mg/kg over 30 min) preceded by either CBD (600 mg) or placebo. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS) and the CADSS (Clinician Administered Dissociative States Scale) at regular intervals from 30 min before to 90 min after ketamine administration.
CBD significantly augmented the activating effects of ketamine, as measured by the activation subscales of the BPRS. However, CBD also showed a non-significant trend to reduce ketamine-induced depersonalization, as measured by the CADSS.
These data describe a complex pattern of psychopharmacologic interactions between CBD and ketamine at the doses of each agent studied in this experiment.
OBJETIVOS: Verificar a confiabilidade da "Entrevista Clínica Estruturada para o DSM-IV - Versão Clínica (SCID-CV)" traduzida para o português. MÉTODOS: Foram submetidos, a duas entrevistas independentes (teste-reteste), 45 pacientes psiquiátricos em seguimento no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC-FMRP/USP). Os dados foram analisados pelo Coeficiente Kappa (K). RESULTADOS: O Kappa ponderado foi excelente (Kw=0,83). A confiabilidade foi estatisticamente significante em transtorno do humor (K=0,87); transtornos psicóticos (K=0,90); transtornos relacionados ao uso de substância (K=0,76); transtornos de ansiedade (K=0,61); e nas categorias diagnósticas específicas analisadas, exceto em agorafobia sem história de transtorno do pânico (K=-0,04). CONCLUSÕES: A SCID-CV traduzida e adaptada para o português apresenta, em geral, boa confiabilidade, mas a ausência de questões e critérios diagnósticos específicos no próprio instrumento em diagnósticos, como agorafobia sem história de transtorno de pânico, diminuiu sua confiabilidade.
Major depressive disorder is characterized by impaired reward processing, possibly due to dysfunction in the basal ganglia. However, few neuroimaging studies of depression have distinguished between anticipatory and consummatory phases of reward processing. Using functional MRI (fMRI) and a task that dissociates anticipatory and consummatory phases of reward processing, the authors tested the hypothesis that individuals with major depression would show reduced reward-related responses in basal ganglia structures.
A monetary incentive delay task was presented to 30 unmedicated individuals with major depressive disorder and 31 healthy comparison subjects during fMRI scanning. Whole-brain analyses focused on neural responses to reward-predicting cues and rewarding outcomes (i.e., monetary gains). Secondary analyses focused on the relationship between anhedonic symptoms and basal ganglia volumes.
Relative to comparison subjects, participants with major depression showed significantly weaker responses to gains in the left nucleus accumbens and the caudate bilaterally. Group differences in these regions were specific to rewarding outcomes and did not generalize to neutral or negative outcomes, although relatively reduced responses to monetary penalties in the major depression group emerged in other caudate regions. By contrast, evidence for group differences during reward anticipation was weaker, although participants with major depression showed reduced activation to reward cues in a small sector of the left posterior putamen. In the major depression group, anhedonic symptoms and depression severity were associated with reduced caudate volume bilaterally.
These results suggest that basal ganglia dysfunction in major depression may affect the consummatory phase of reward processing. Additionally, morphometric results suggest that anhedonia in major depression is related to caudate volume.
The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this "subgenual" ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended "visceromotor network" of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.
The objective of the present study was to evaluate the factor structure of Bech's version of the Brief Psychiatric Rating Scale (BPRS), translated into Portuguese. The BPRS was administered to a heterogeneous group of psychiatric inpatients (N = 98) and outpatients (N = 62) in a University Hospital. Each patient was evaluated from one to eight times. The interval between consecutive interviews was one week for the inpatients and one month for the outpatients. The results were submitted to factorial analysis. The internal consistency of the total scale and of each factor was also estimated. Factorial analysis followed by normalized orthogonal rotation (Varimax) yielded four factors: Withdrawal-Retardation, Thinking Disorder, Anxious-Depression and Activation. Internal consistency measured by Cronbach's alpha coefficient ranged from 0.766 to 0.879. The data show that the factor structure of the present instrument is similar to that of the American version of the BPRS which contains 18 items, except for the absence of the fifth factor of the latter scale, Hostile-Suspiciousness.
The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine2A agonist activity, with monoamine oxidase (MAO)-inhibiting beta-carboline alkaloids (harmine, harmaline, and tetrahydroharmine). Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. Tmax (median) was observed at 1.5 h after both doses. The Tmax for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.
DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] displays a high affinity for the rat 5-HT2A, 5-HT2B and 5-HT2C receptors (pKi 7.3, 7.4 and 7.8, respectively) and acts as an agonist. DOI (0.5-4 mg/kg, i.p. 30 min pre-test) increased the number of punished passages in the mouse four plates test (FPT). The anti-punishment action of DOI (1 mg/kg, i.p. 30 min pre-test) was abolished by prior treatment with the selective 5-HT2A receptor antagonist SR 46949B (0.1 and 1 mg/kg, i.p. 45 min pre-test) but not by the selective 5-HT2C receptor antagonist RS 10-2221 (0.1 and 1 mg/kg, i.p. 45 min pre-test) nor the selective 5-HT2C/2B receptor antagonist SB 206553 (0.1 and 1 mg/kg, i.p. 45 min pre-test). An anxiolytic-like action was also observed for DOI (1 mg/kg) in the elevated plus maze (EPM). The anxiolytic-like action of DOI (1 mg/kg, i.p. 30 min pre-test) was antagonised by pre-treatment with SR 46949B (0.125 and 0.5 mg/kg, i.p. 45 min pre-test) but not by RS 10-2221 (0.1 and 1 mg/kg, i.p. 45 min pre-test) nor SB 206553 (0.1 and 1 mg/kg, i.p. 45 min pre-test). In conclusion, DOI produced an anxiolytic-like profile in the mouse FPT and EPM. These effects are likely to be 5-HT2A receptor mediated.
The reliability and validity of a Portuguese version of the Young Mania Rating Scale were evaluated. The original scale was translated into and adapted to Portuguese by the authors. Definitions of clinical manifestations, a semi-structured anchored interview and more explicit rating criteria were added to the scale. Fifty-five adult subjects, aged 18 to 60 years, with a diagnosis of Current Manic Episode according to DSM-III-R criteria were assessed using the Young Mania Rating Scale as well as the Brief Psychiatric Rating Scale in two sessions held at intervals from 7 to 10 days. Good reliability ratings were obtained, with intra-class correlation coefficient of 0.97 for total scores, and levels of agreement above 0.80 (P < 0.001) for all individual items. Internal consistency analysis resulted in an alpha = 0.67 for the scale as a whole, and an alpha = 0.72 for each standardized item (P < 0.001). For the concurrent validity, a correlation of 0.78 was obtained by the Pearson coefficient between the total scores of the Young Mania Rating Scale and Brief Psychiatric Rating Scale. The results are similar to those reported for the English version, indicating that the Portuguese version of the scale constitutes a reliable and valid instrument for the assessment of manic patients.
Ayahuasca is a South American psychoactive plant tea which contains the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and monoamine-oxidase inhibitors that render DMT orally active. Previous investigations with ayahuasca have highlighted a psychotropic effect profile characterized by enhanced introspective attention, with individuals reporting altered somatic perceptions and intense emotional modifications, frequently accompanied by visual imagery. Despite recent advances in the study of ayahuasca pharmacology, the neural correlates of acute ayahuasca intoxication remain largely unknown.
To investigate the effects of ayahuasca administration on regional cerebral blood flow.
Fifteen male volunteers with prior experience in the use of psychedelics received a single oral dose of encapsulated freeze-dried ayahuasca equivalent to 1.0 mg DMT/kg body weight and a placebo in a randomized double-blind clinical trial. Regional cerebral blood flow was measured 100-110 min after drug administration by means of single photon emission tomography (SPECT).
Ayahuasca administration led to significant activation of frontal and paralimbic brain regions. Increased blood perfusion was observed bilaterally in the anterior insula, with greater intensity in the right hemisphere, and in the anterior cingulate/frontomedial cortex of the right hemisphere, areas previously implicated in somatic awareness, subjective feeling states, and emotional arousal. Additional increases were observed in the left amygdala/parahippocampal gyrus, a structure also involved in emotional arousal.
The present results suggest that ayahuasca interacts with neural systems that are central to interoception and emotional processing and point to a modulatory role of serotonergic neurotransmission in these processes.
A meta-analytic study of changes in brain activation in depression - Volume 18 Issue 6 - P Fitzgerald, J Maller, K Hoy, T Oxley, Z Daskalakis, A Laird
While most patients with depression respond to combinations of pharmacotherapy, psychotherapy, and electroconvulsive therapy (ECT), there are patients requiring other treatments. Deep brain stimulation (DBS) allows modulation of brain regions that are dysfunctional in depression. Since anhedonia is a feature of depression and there is evidence of dysfunction of the reward system, DBS to the nucleus accumbens (NAcc) might be promising.
Ten patients suffering from very resistant forms of depression (treatment-resistant depression [TRD]), not responding to pharmacotherapy, psychotherapy, or ECT, were implanted with bilateral DBS electrodes in the NAcc. The mean (+/-SD) length of the current episode was 10.8 (+/-7.5) years; the number of past treatment courses was 20.8 (+/-8.4); and the mean Hamilton Depression Rating Scale (HDRS) was 32.5 (+/-5.3).
Twelve months following initiation of DBS treatment, five patients reached 50% reduction of the HDRS (responders, HDRS = 15.4 [+/-2.8]). The number of hedonic activities increased significantly. Interestingly, ratings of anxiety (Hamilton Anxiety Scale) were reduced in the whole group but more pronounced in the responders. The [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography data revealed that NAcc-DBS decreased metabolism in the subgenual cingulate and in prefrontal regions including orbital prefrontal cortex. A volume of interest analysis comparing responders and nonresponders identified metabolic decreases in the amygdala.
We demonstrate antidepressant and antianhedonic effects of DBS to NAcc in patients suffering from TRD. In contrast to other DBS depression studies, there was also an antianxiety effect. These effects are correlated with localized metabolic changes.
The effects of the indolehallucinogen psilocybin, a mixed 5-HT2 and 5-HT1 agonist, on regional cerebral glucose metabolism were investigated in 10 healthy volunteers with PET and [F-18]-fluorodeoxyglucose (FDG) prior to and following a 15- or 20-mg dose of psilocybin. Psychotomimetic doses of psilocybin were found to produce a global increase in cerebral metabolic rate of glucose (CMRglu) with significant and most marked increases in the frontomedial and frontolateral cortex (24.3%), anterior cingulate (24.9%), and temporomedial cortex (25.3%). Somewhat smaller increases of CMRglu were found in the basal ganglia (18.5%), and the smallest increases were found in the sensorimotor (14.7%) and occipital cortex (14.4%). The increases of CMRglu in the prefrontal cortex, anterior cingulate, temporomedial cortex, and putamen correlated positively with psychotic symptom formation, in particular with hallucinatory ego disintegration. The present data suggest that excessive 5-HT2 receptor activation results in a hyperfrontal metablic pattern that parallels comparable metabolic findings associated with acute psychotic episodes in chronic schizophrenics and contrasts with the hypofrontality in chronic schizophrenic patients.
We investigated the late effects of serotonergic drugs on mouse forced swimming and found that serotonin 1A antagonist NAN-190 hydrobromide (NAN-190) and serotonin 2 agonist R(-)-DO1 hydrochloride (DO1) increase the typical anti-depressive behavior climbing 6 hours after the intraperitoneal injection. With the use of ion exchanger, ultra filtration and chemical extraction methods, a substance having remarkable anti-depressive activity on mouse forced swimming was extracted from the serums of the mice treated with the drugs. The substance was strongly suggested to be a glycolipid having a specific sugar chain structure GalNAcalpha1-3GalNAc in its terminal. In fact, globopentaosylceramide, another glycolipid having the structure in the terminal also showed marked anti-depressive activity on mouse forced swimming, but globotetraosylceramide lacking the sugar chain structure did not. The GalNAcalpha1-3GalNAc-lipid reactivity in the serum and typical anti-depressive behavior climbing increased corresponding to the doses of NAN-190 and DO1. These findings clearly indicate that the terminal structure GalNAcalpha1-3GalNAc has the essential role in the anti-depressive activity of globopentaosylceramide, and that serotonin 1A antagonism and serotonin 2 agonism increase the production of an anti-depressive glycolipid having the terminal structure in mouse serum.
Objective:
A large number of studies with considerably variable methods have been performed to investigate brain regions involved in the pathophysiology of major depressive disorder. The aim of this study was to use a quantitative meta-analytic technique to synthesise the results of much of this research.
Methods:
Three separate quantitative meta-analytical studies were conducted using the Activation Likelihood Estimation technique. Analysis was performed on three types of studies: (1) those conducted at rest comparing brain activation in patients with depression and controls; (2) those involving brain changes following antidepressant treatment; and (3) those comparing brain activation patterns induced by the induction of positive or negative emotion in patients with depression compared with controls.
Results:
There appears to be a complex series of areas of the brain implicated in the pathophysiology of depression although limited overlap was found across imaging paradigms. This included a network of regions including frontal and temporal cortex as well as the insula and cerebellum that are hypoactive in depressed subjects and in which there is increase in activity with treatment. There was a corresponding set of subcortical and limbic regions in which opposite changes were found.
Conclusions:
There is limited overlap between the brain regions identified using differing imaging methods. The most consistently identified regions include areas of the anterior cingulate, dorsolateral, medial and inferior prefrontal cortex, insula, superior temporal gyrus, basal ganglia and cerebellum. Further research is required to identify if different imaging methods are identifying complementary networks that are equally involved in the disorder.
Reliability of the structured clinical interview for DSM-IV-clinical version translated into Portuguese
- C M Del-Ben
- Jaa Vilela
- Jas Crippa
Del-Ben CM, Vilela JAA, Crippa JAS, et al. Reliability of the structured
clinical interview for DSM-IV-clinical version translated into Portuguese.
Rev Bras Psiquiatr. 2001;23:156-159.
- Sanches
Sanches et al
Journal of Clinical Psychopharmacology @BULLET Volume 36, Number 1, February 2016
Reliability of the structured clinical interview for DSM-IVclinical version translated into Portuguese.
- Del-Ben
A meta-analytic study of changes in brain activation in depression.
- Fitzgerald
Hamilton (HAM-D) Montgomery Asberg (MADRS) depression rating scales.
- Moreno