Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

Palhano-Fontes, Fernanda; Barreto, Dayanna Patrícia de Carvalho; Onias, Heloisa; Andrade, Kátia C.; Novaes, Morgana Menezes; Pessoa, Jessica A.; Mota-Rolim, Sérgio A.; Osório, Flávia L.; Sanches, Rafael Faria; Santos, Rafael G. dos; Tófoli, Luís Fernando; Silveira, Geraldo; Yonamine, Maurı́cio; Riba, Jordi; Santos, Francisco R.; Silva-Junior, Antonio A.; Alchieri, João Carlos; Galvão-Coelho, Nicole Leite; Lobão-Soares, Bruno; Hallak, Jaime Eduardo Cecílio; Arcoverde, Emerson; Maia‐de‐Oliveira, João Paulo; Araújo, Dráulio Barros de

doi:10.1017/s0033291718001356

Cited by 519 publications

(537 citation statements)

References 52 publications

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“…Moreover, SPECT imaging showed that ayahuasca administration was associated with increased blood perfusion in the left nucleus accumbens, right insula, and left subgenual area, brain regions associated with emotional processing and the therapeutic effects of traditional antidepressants. These results were partially replicated by our group in a recent parallel arm, double-blind, randomized, placebo-controlled trial in which 35 patients with treatment-resistant major depression received a single dose of ayahuasca or placebo 43 . Compared with patients that received placebo, patients that received ayahuasca had lower depressive symptoms seven days after drug administration.…”

Section: Therapeutic Potentialsmentioning

confidence: 74%

“…In our open-label study involving the administration of a single ayahuasca dose to 17 patients with treatment-resistant major depressive disorder, vomiting was the only adverse effect reported and occurred in 47% of the volunteers 42 . In our subsequent randomized controlled trial, the most common adverse reaction were nausea (71%), vomiting (57%), transient anxiety (50%), transient headache (42%), and restlessness (50%) 43 .…”

Section: Safety and Toxicitymentioning

confidence: 93%

“…Evidence from uncontrolled studies 42,48,49 Anxiolytic Antidepressive Antiaddictive Evidence from controlled studies 41,43 Anxiolytic Antidepressive…”

Section: Table 3 Main Therapeutic Potentials Of Ayahuascamentioning

confidence: 99%

“…The most common adverse reactions to ayahuasca are nausea and vomiting, which is often accompanied by other somatic-dysphoric effects such as feeling heat and/or cold and gastrointestinal discomfort (Table 4) 18,19,24,42,43 . In ritual contexts, vomiting is not interpreted as negative, being understood as a cleansing process 2,16,35 .…”

Section: Safety and Toxicitymentioning

confidence: 99%

“…Although ayahuasca administration in the experimental or clinical setting may induce anxiety and psychotic/psychotomimetic or dissociative symptoms, these effects are usually mild and short-lived, and most participants consider the experience pleasant 18,20,21,42,43,60 . Its important to highlight that individuals with a personal or family history of psychotic illness or nonpsychotic mania are usually not enrolled in these studies, which could explain the absence of reports of prolonged dysphoric or psychotic reaction in the experimental and clinical settings 5,14,[18][19][20][21]23,24,[27][28][29]32,33,36,[41][42][43]60 .…”

Section: Safety and Toxicitymentioning

confidence: 99%

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Ayahuasca: what mental health professionals need to know

Santos

Bouso²,

Hallak

2017

Arch. Clin. Psychiatry (São Paulo)

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Background: Ayahuasca is a psychoactive ethnobotanical concoction that has been used for decades by indigenous groups of the Northwestern Amazon and by syncretic religious organizations for ritual and therapeutic purposes. In the last two decades, it is being used worldwide in evolving practices. Ayahuasca seem to therapeutic effects, but controlled studies are lacking. Moreover, its safety and toxicity are not completely understood. Objectives: To present an overview of the effects of ayahuasca based on the most recent human studies. Methods: Narrative review. Results: Ayahuasca administration in controlled settings appears to be safe from a subjective and physiological perspective, with few adverse reactions being reported. More frequent adverse reactions occur in non-controlled settings. Prolonged psychotic reactions are rare and seem to occur especially in susceptible individuals. Ayahuasca showed antidepressive, anxiolytic, and antiaddictive effects in animal models, observational studies, and in open-label and controlled studies. Discussion: Ayahuasca administration in controlled settings appear to be safe. Moreover, ayahuasca seem to have therapeutic effects for treatment-resistant psychiatric disorders that should be further investigated in randomized controlled clinical trials. However, medical complications and cases of prolonged psychotic reactions have been reported, and people with personal or family history of psychotic disorders should avoid ayahuasca intake.

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Section: Therapeutic Potentialsmentioning

confidence: 74%

Section: Safety and Toxicitymentioning

confidence: 93%

“…Evidence from uncontrolled studies 42,48,49 Anxiolytic Antidepressive Antiaddictive Evidence from controlled studies 41,43 Anxiolytic Antidepressive…”

Section: Table 3 Main Therapeutic Potentials Of Ayahuascamentioning

confidence: 99%

Section: Safety and Toxicitymentioning

confidence: 99%

Section: Safety and Toxicitymentioning

confidence: 99%

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Ayahuasca: what mental health professionals need to know

Santos

Bouso²,

Hallak

2017

Arch. Clin. Psychiatry (São Paulo)

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Magnitude of the Placebo Response Across Treatment Modalities Used for Treatment-Resistant Depression in Adults

et al. 2021

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IMPORTANCEThe placebo effect in depression clinical trials is a substantial factor associated with failure to establish efficacy of novel and repurposed treatments. However, the magnitude of the placebo effect and whether it differs across treatment modalities in treatment-resistant depression (TRD) is unclear.OBJECTIVE To examine the magnitude of the placebo effect in patients with TRD across different treatment modalities and its possible moderators. DATA SOURCESSearches were conducted on MEDLINE, Web of Science, and PsychInfo from inception to June 21, 2021. STUDY SELECTION Randomized clinical trials (RCTs) were included if they recruited patients with TRD and randomized them to a placebo or sham arm and a pharmacotherapy, brain stimulation, or psychotherapy arm. DATA EXTRACTION AND SYNTHESIS Independent reviewers used standard forms for data extraction and quality assessment. Random-effects analyses and standard pairwise meta-analyses were performed. MAIN OUTCOMES AND MEASURES The primary outcome was the Hedges g value for the reported depression scales. Secondary outcomes included moderators assessed via meta-regression and response and remission rates. Heterogeneity was assessed with the I 2 test, and publication bias was evaluated using the Egger test and a funnel plot. Cochrane Risk of Bias Tool was used to estimate risks. RESULTS Fifty RCTs were included involving various types of placebo or sham interventions with a total of 3228 participants (mean [SD] age, 45.8 [6.0] years; 1769 [54.8%] female). The pooledplacebo effect size for all modalities was large (g = 1.05; 95% CI, 0.91-1.1); the placebo effect size in RCTs of specific treatment modalities did not significantly differ. Similarly, response and remission rates associated with placebo were comparable across modalities. Heterogeneity was large. Three variables were associated with a larger placebo effect size: open-label prospective treatment before double-blind placebo randomization (β = 0.35; 95% CI, 0.11 to 0.59; P = .004), later year of publication (β = 0.03; 95% CI, 0.003 to 0.05; P = .03), and industry-sponsored trials (β = 0.34; 95% CI, 0.09 to 0.58; P = .007). The number of failed interventions was associated with the probability a smaller placebo effect size (β = −0.12; 95% CI, −0.23 to −0.01, P = .03). The Egger test result was not significant for small studies' effects. (continued) Key Points Question What is the placebo effect magnitude in different treatment modalities used for management of patients with treatment-resistant depression? Findings In this systematic review and meta-analysis of 3228 patients with treatment-resistant depression in 50 randomized clinical trials, the placebo effect size was large and consistent across treatment modalities. Response and remission rates associated with placebo effect were comparable across modalities.Meaning The findings of this study suggest a placebo effect size benchmark may be used to interpret the findings of past and future clinical trials.

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Hallucinogenic Drugs

Bonson¹

2020

Encyclopedia of Life Sciences

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Hallucinogens constitute one of the oldest classes of drugs used by humanity, often in the context of spiritual practices. Classic hallucinogens such as lysergic acid diethylamide (LSD), psilocybin, N , N ‐dimethyltryptamine (DMT), mescaline and 2,5‐dimethoxy‐4‐methylamphetamine (DOM) produce complex psychological and physical effects, including perceptual changes, cognitive shifts in reality, and emotional alterations. These drugs primarily act on serotonin systems through 5‐hydroxytryptamine 2A (5HT 2A ) receptors, with additional activity through 5HT 1A receptors, as well as dopamine and glutamate systems. Investigations into the neurochemical and behavioural effects of this class of drugs have provided important insights into pharmacology and psychiatric conditions. Given their popularity as recreational drugs, investigation of their actions and effects continues to be an important endeavour. In the past 30 years, there has been a renewed interest in conducting clinical studies with these drugs in healthy individuals and in patients with psychiatric conditions in laboratories around the world. Key Concepts Hallucinogens have been used for thousands of years by various societies, often in conjunction with spiritual practices. In the present day, hallucinogens remain highly popular as recreational drugs. The chemical structure of hallucinogens consists of tryptamines (LSD and psilocybin) and phenethylamines (mescaline and DOM). The potency of hallucinogens is directly correlated to their ability to act as agonists at the serotonin receptor subtype, 5‐HT 2A . Drugs that act at sites other than 5‐HT 2A receptors can also produce hallucinogen‐like effects (e.g. ketamine, MDMA, salvinorin A, nitrous oxide, GHB). The signature effects of hallucinogens include perceptual changes, alterations in effect and shifts in cognitive ability. Negative responses associated with hallucinogens include ‘bad trips’ (severe anxiety and a disconnection with reality) as well as rare instances of ‘flashbacks’ and psychotic breaks. Human research with hallucinogens has recently been revitalised, augmenting the scientific advances made previously with animal and human studies.

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Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

Cited by 519 publications

References 52 publications

Ayahuasca: what mental health professionals need to know

Ayahuasca: what mental health professionals need to know

Magnitude of the Placebo Response Across Treatment Modalities Used for Treatment-Resistant Depression in Adults

Hallucinogenic Drugs

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