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Psychoactives
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Natural Hallucinogens in Mental Health
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Natural Hallucinogens in Mental Health

A special issue of Psychoactives (ISSN 2813-1851).

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 44771

Special Issue Editors

Dr. Rafael Guimarães Dos Santos

E-Mail Website
Guest Editor
1. Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
2. National Institute of Science and Technology—Translational Medicine, São Paulo, Brazil
3. ICEERS—International Center for Ethnobotanical Education, Research, and Service, Barcelona, Catalunya, Spain
Interests: psychoactive drugs; hallucinogens; cannabinoids; serotonin; glutamate; depressive disorders; anxiety disorders; substance-related disorders; mental health
Dr. Jaime Eduardo Cecílio Hallak

E-Mail Website
Guest Editor
Department of Neurosciences and Behavior, Ribeirao PretoSchool of Medicine, University of Sao Paulo, Av Bandeirantes 3900, Ribeirao Preto CEP14049-900, Brazil
Interests: psychopharmacology; psychiatric rating scales; psychiatry at general hospital; schizophrenia; neuropsychiatry; neuroimaging; neuro-pathology; neuro-psychology; electroconvulsive therapy

Special Issue Information

Dear Colleagues,

Natural hallucinogenic substances, such as ayahuasca/dimethyltryptamine and psilocybin-containing fungi, have been used for generations for healing in several cultures in the Americas. Interest in these drugs in psychiatry dates to the 1950–60s and, in recent years, there has been a renewed interest in the possible use of some of these compounds as therapeutics in mental health. Classic serotonergic hallucinogens or psychedelics, such as ayahuasca and psilocybin, have shown promising antidepressant and anxiolytic effects in small trials with patients with Major Depressive Disorder, depressive and anxious symptoms associated with cancer or other life-threatening diseases, and in alcohol and tobacco use disorders. Remarkably, these drugs induce therapeutic effects within hours/days and beneficial effects remain significant for weeks to months. Nevertheless, these promising results are still preliminary and much remains to be investigated in this field. For instance, it is still unknown if whole preparations (mushroom, ayahuasca) are more effective or better tolerated compared to isolated compounds or the role of psychotherapy in the treatments. Therefore, the objective of this Special Issue is to collect reviews and original articles dealing with the administration and uses of natural hallucinogens as therapeutics in psychiatric disorders and in mental health in general.

Dr. Rafael Guimarães Dos Santos
Dr. Jaime Eduardo Cecílio Hallak
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Psychoactives is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • natural psychoactives
  • psychopharmacology
  • mental health
  • psychiatry
  • therapeutics
  • hallucinogens
  • psychedelics
  • tryptamines

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Published Papers (9 papers)

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Editorial

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2 pages, 211 KiB  
Editorial
Natural Hallucinogens in Mental Health
by Rafael Guimarães Dos Santos and Jaime Eduardo Cecilio Hallak
Psychoactives 2022, 1(2), 87-88; https://doi.org/10.3390/psychoactives1020009 - 21 Nov 2022
Viewed by 1965
Abstract
In the last two decades, an increasing trend has unfolded toward the possible beneficial uses of natural hallucinogenic substances for treating mental health disorders [...] Full article
(This article belongs to the Special Issue Natural Hallucinogens in Mental Health)

Research

Jump to: Editorial, Review, Other

15 pages, 2976 KiB  
Article
Minorities’ Diminished Psychedelic Returns: Gender, Perceived Stigma, and Distress
by Sean Matthew Viña
Psychoactives 2024, 3(2), 303-317; https://doi.org/10.3390/psychoactives3020019 - 2 Jun 2024
Cited by 1 | Viewed by 1711
Abstract
Because psychedelics have been found to increase psychological traits like openness, mental flexibility, and interpersonal perceptiveness, some researchers believe that psychedelics could help individuals cope with the psychological effects of discrimination. However, it is still unclear whether psychedelic use can help manage the [...] Read more.
Because psychedelics have been found to increase psychological traits like openness, mental flexibility, and interpersonal perceptiveness, some researchers believe that psychedelics could help individuals cope with the psychological effects of discrimination. However, it is still unclear whether psychedelic use can help manage the internalized stigma that deters formal mental health treatment. This study investigates the impact of six measures of psychedelic use (MDMA, psilocybin, DMT, ayahuasca, peyote/mescaline, and LSD) on psychological distress (Kessler Psychological Distress Scale) and internalized stigma. The study used data from the National Survey of Drug Use and Health (NSDUH) from 2008 to 2019, with a sample size of 458,372 participants. Ordinary least square regression models were conducted using Stata 18. Gender analysis found that among men, ayahuasca use was linked to reduced stigma perception associated with higher distress. For women, DMT use was linked to reduced stigma perceptions when experiencing higher distress. However, results find that individuals who have used MDMA and psilocybin reported heightened perceptions of stigma associated with increased psychological distress. Among women, MDMA and psilocybin use was associated with a higher perception of stigma when they experienced distress. These findings suggest that, overall, psychedelics may not reduce the impact of distress on the perception of stigma, especially for women. Full article
(This article belongs to the Special Issue Natural Hallucinogens in Mental Health)
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17 pages, 1507 KiB  
Article
Self-Rated Effectiveness of Ayahuasca and Breathwork on Well-Being, Psychological Resilience, Self-Compassion, and Personality: An Observational Comparison Study
by Rishma S. I. Khubsing, Martin van Leerdam, Eline C. H. M. Haijen and Kim P. C. Kuypers
Psychoactives 2024, 3(2), 167-183; https://doi.org/10.3390/psychoactives3020011 - 31 Mar 2024
Cited by 1 | Viewed by 2138
Abstract
Background: In recent years, there has been a growing interest in the therapeutic potential of classical psychedelics like ayahuasca for mental health improvement. Naturalistic studies at ayahuasca retreats have shown (short-term) improvements in mental well-being but understanding the psychological mechanisms is crucial. We [...] Read more.
Background: In recent years, there has been a growing interest in the therapeutic potential of classical psychedelics like ayahuasca for mental health improvement. Naturalistic studies at ayahuasca retreats have shown (short-term) improvements in mental well-being but understanding the psychological mechanisms is crucial. We are interested in psychological processes such as resilience, self-compassion, and personality traits. Additionally, it is unclear whether changes are solely due to ayahuasca or influenced by the social setting. To address this, a control group participating in a breathwork session, similar to ayahuasca retreats, was included. Methods: In this observational study, individuals who attended an ayahuasca retreat (n = 69) and individuals who participated in a breathwork session (n = 30) completed an online survey one week before (baseline) and one, six, and twelve weeks after they entered the retreat/session. The survey included a series of questionnaires, i.e., the World Health Organisation-Five Well-Being Index, 14-item Resilience Scale, Self-Compassion Scale–Short Form, and Big Five Inventory-10. A linear mixed model (LMM) was used to analyze the outcome data. Results: It was shown that well-being, resilience, and self-compassion increased and remained stable over 12 weeks compared to baseline, regardless of group (ayahuasca or breathwork). Older participants generally reported higher resilience and self-compassion. Self-compassion was also higher in the ayahuasca group overall. Neuroticism decreased in both groups, with lower scores in the ayahuasca group. Agreeableness increased over time, also not influenced by group membership, while there were no changes in extraversion, conscientiousness, or openness. Discussion: Both interventions improved well-being, aligning with prior research. Importantly, this study unveils a novel finding: both interventions enhance resilience and self-compassion for up to three months, offering promise for conditions marked by low well-being, resilience, and self-compassion like depression and anxiety-related disorders. While acknowledging its limitations (e.g., self-selected sample, no specific information of the ayahuasca brew or the breathwork technique), it emphasizes the need for controlled studies with control groups, attention to social contexts in research on these interventions, and to assess other variables like depth of altered states of consciousness that might explain improvement in psychological processes and wellbeing. Full article
(This article belongs to the Special Issue Natural Hallucinogens in Mental Health)
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13 pages, 310 KiB  
Article
Subjective Effects of a Single Dose of Ayahuasca among College Students with Harmful Alcohol Use: Qualitative Analysis of Participant Accounts
by Anna Beatriz Vicentini, Lucas Silva Rodrigues, Giordano Novak Rossi, Juliana Mendes Rocha, Lorena T. L. Guerra, José Augusto Silva Reis, Renan Massanobu Maekawa, Flávia de Lima Osório, José Carlos Bouso, Fabiana Pereira Santos, Beatriz Aparecida Passos Bismara Paranhos, Mauricio Yonamine, Jaime Eduardo Cecilio Hallak and Rafael Guimarães dos Santos
Psychoactives 2023, 2(4), 346-358; https://doi.org/10.3390/psychoactives2040022 - 17 Nov 2023
Cited by 1 | Viewed by 2862
Abstract
Alcohol is the recreational drug most frequently consumed, and its high frequency of use can lead to worsening social, psychological, and domestic issues. The age group most susceptible to alcohol dependence is 18- to 24-year-old youths, demanding interventional tools to target early involvement [...] Read more.
Alcohol is the recreational drug most frequently consumed, and its high frequency of use can lead to worsening social, psychological, and domestic issues. The age group most susceptible to alcohol dependence is 18- to 24-year-old youths, demanding interventional tools to target early involvement risks. Ayahuasca seems to be a promising therapeutic tool since evidence suggests it presents potential for the treatment of depression, anxiety, and substance abuse, among other disorders. This study aimed to analyze subjective reports of university students with harmful alcohol use participating in a single-blind study evaluating the effects of one ayahuasca dose (1 mL/kg). Twenty-one days after ayahuasca administration, semi-structured interviews were conducted (n = 6) to identify peer psychological elements linked to its therapeutic potential. Subsequently, content analysis methodology was employed to define the main categories: Self-perception of experience, Positive Impacts (PI), Substances Use Pattern (SUP), Insights (I), Visual Effects, Transient Derealization, and Sleep Pattern. Among these, the most pertinent categories for this study were PI, SUP, and I, as, together, they suggest a potential link between insights and/or positive emotions and reduced alcohol consumption due to their internal transformation potential, which could be linked to a decrease in consumption. Full article
(This article belongs to the Special Issue Natural Hallucinogens in Mental Health)
21 pages, 328 KiB  
Article
Life after Ayahuasca: A Qualitative Analysis of the Psychedelic Integration Experiences of 1630 Ayahuasca Drinkers from a Global Survey
by Tessa Cowley-Court, Richard Chenhall, Jerome Sarris, José Carlos Bouso, Luís Fernando Tófoli, Emérita Sátiro Opaleye, Violeta Schubert and Daniel Perkins
Psychoactives 2023, 2(2), 201-221; https://doi.org/10.3390/psychoactives2020014 - 13 Jun 2023
Cited by 4 | Viewed by 12586
Abstract
Ayahuasca is an Amazonian psychoactive plant medicine being explored for its potential therapeutic uses in Western contexts. Preliminary studies link ayahuasca use with improvements across a range of mental health indicators, but studies have not yet explored qualitative aspects of the post-treatment process [...] Read more.
Ayahuasca is an Amazonian psychoactive plant medicine being explored for its potential therapeutic uses in Western contexts. Preliminary studies link ayahuasca use with improvements across a range of mental health indicators, but studies have not yet explored qualitative aspects of the post-treatment process known in the psychedelic literature as “integration”. This includes how participants make sense of their ayahuasca experiences and minimise harm/maximise benefits after ayahuasca use. A global online survey, conducted between 2017 and 2019, collected responses from 1630 ayahuasca drinkers (50.4% male, mean age = 43 years) to an open-ended question about their integration experiences after consuming ayahuasca. Inductive codebook thematic analysis was used to identify themes in participants’ integration experiences. Participants described integration experiences in three main ways. First, was an overall appraisal of the integration experience (e.g., as easy, challenging, or long-term/ongoing). Second, was describing beneficial tools which facilitated integration (e.g., connecting with a like-minded community and ongoing practice of yoga, meditation, journaling, etc.). Third, was describing integration challenges (e.g., feeling disconnected, going back to “old life” with new understandings, etc.). These findings suggest that integrating ayahuasca experiences can be challenging and take considerable time, though working through integration challenges may facilitate positive growth. Findings also challenge the role of individual psychotherapy as the primary integration tool in Western psychedelic therapy, suggesting that communal and somatic elements may also be useful. An expanded definition of psychedelic integration is proposed which includes working with integration challenges and adjusting to life changes. Full article
(This article belongs to the Special Issue Natural Hallucinogens in Mental Health)

Review

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26 pages, 474 KiB  
Review
‘Mind-Revealing’ Psychedelic States: Psychological Processes in Subjective Experiences That Drive Positive Change
by Rúna F. E. Walther and Hein T. van Schie
Psychoactives 2024, 3(3), 411-436; https://doi.org/10.3390/psychoactives3030026 - 18 Sep 2024
Viewed by 1911
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Natural Hallucinogens in Mental Health)
20 pages, 2027 KiB  
Review
Mind the Psychedelic Hype: Characterizing the Risks and Benefits of Psychedelics for Depression
by Daniel Meling, Rebecca Ehrenkranz, Sandeep M. Nayak, Helena D. Aicher, Xaver Funk, Michiel van Elk, Marianna Graziosi, Prisca R. Bauer, Milan Scheidegger and David B. Yaden
Psychoactives 2024, 3(2), 215-234; https://doi.org/10.3390/psychoactives3020014 - 16 Apr 2024
Cited by 3 | Viewed by 5910
Abstract
Rationale: Psychedelic research re-emerged from a period of suppression into the so-called psychedelic renaissance. In parallel, most media reporting has shifted from the overstatement of the risks of psychedelics to overly positive hype. As the empirical evidence is more equivocal than frequently portrayed, [...] Read more.
Rationale: Psychedelic research re-emerged from a period of suppression into the so-called psychedelic renaissance. In parallel, most media reporting has shifted from the overstatement of the risks of psychedelics to overly positive hype. As the empirical evidence is more equivocal than frequently portrayed, the conclusions about the effectiveness of psychedelics should be considered preliminary. Poor science communication about psychedelics’ therapeutic potential may lead potential participants or patients to feel misled and policy decisions to be misinformed. An evidence-informed characterization of their risks and benefits is needed. Objectives: This article assesses the state of psychedelic research for treating depression and the effect sizes of psychedelics on therapeutic outcomes, the risk of bias, and the prevalence of adverse effects. We review research on the risks and benefits of psychedelics and discuss how the following depression treatments have shown decreasing effect sizes over time: (1) cognitive behavioral therapy, (2) mindfulness interventions, (3) selective serotonin reuptake inhibitors, and (4) ketamine. We speculate that a similar trend may occur for psychedelic treatments. Results and conclusions: It is likely that larger and better-controlled psychedelic trials will demonstrate smaller effect sizes that are more comparable to other conventional and emerging treatments for mood disorders. Clear science communication is critical for setting public expectations and psychedelic policy. With this evidence-based assessment, we aim to cut through the misinformation about the benefits, risks, and future prospects of psychedelic treatments. Full article
(This article belongs to the Special Issue Natural Hallucinogens in Mental Health)
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30 pages, 865 KiB  
Review
The Clinical Potential of Dimethyltryptamine: Breakthroughs into the Other Side of Mental Illness, Neurodegeneration, and Consciousness
by Frankie A. Colosimo, Philip Borsellino, Reese I. Krider, Raul E. Marquez and Thomas A. Vida
Psychoactives 2024, 3(1), 93-122; https://doi.org/10.3390/psychoactives3010007 - 26 Feb 2024
Cited by 1 | Viewed by 9026
Abstract
The human brain is an extraordinarily complex organ responsible for all aspects of cognition and control. Billions of neurons form connections with thousands of other neurons, resulting in trillions of synapses that create a vast and intricate network. This network is subjected to [...] Read more.
The human brain is an extraordinarily complex organ responsible for all aspects of cognition and control. Billions of neurons form connections with thousands of other neurons, resulting in trillions of synapses that create a vast and intricate network. This network is subjected to continuous remodeling that adapts to environmental and developmental changes. The resulting neuroplasticity is crucial to both healthy states and many forms of mental illness and neurodegeneration. This narrative review comprehensively examines N,N-dimethyltryptamine (DMT), a naturally occurring hallucinogen and psychedelic compound, focusing on its implications in promoting neuroplasticity via neuritogenesis. We examine DMT’s pharmacology, including its interaction with serotonergic, sigma-1, and trace amine-associated receptors and their associated signaling pathways. The therapeutic potential of DMT in both animal models and clinical trials is discussed with impacts on perception, cognition, emotion, and consciousness. We uniquely focus on current directions centered on unveiling the direct mechanisms of DMT’s therapeutic effects that demonstrate transformative effects on mental well-being, particularly for conditions like depression, anxiety, and post-traumatic stress disorder. We discuss the connection between DMT and neuroplasticity, offering the potential for forming new neural connections, improving learning, memory, and aiding recovery from brain injuries, including neurorehabilitation and neuroregeneration. The ultimate potential of DMT’s therapeutic efficacy to enhance neurogenesis, especially for neurodegenerative conditions, is also discussed. Full article
(This article belongs to the Special Issue Natural Hallucinogens in Mental Health)
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Other

16 pages, 1138 KiB  
Systematic Review
Neural Network Modulation of Ayahuasca: A Systematic Review of Human Studies
by Guilherme Henrique de Morais Santos, Lucas Silva Rodrigues, Juliana Mendes Rocha, Giordano Novak Rossi, Genís Ona, José Carlos Bouso, Jaime Eduardo Cecilio Hallak and Rafael Guimarães dos Santos
Psychoactives 2023, 2(1), 76-91; https://doi.org/10.3390/psychoactives2010006 - 20 Mar 2023
Cited by 1 | Viewed by 4832
Abstract
Background: Ayahuasca is a serotoninergic hallucinogen that plays a central role in the Amazonian traditional medicine. Its psychoactive effects are associated with the presence of N,N-dimethyltryptamine (DMT), and monoamine oxidase inhibitors (MAO-A). Advances in neuroimaging investigations have provided insight into [...] Read more.
Background: Ayahuasca is a serotoninergic hallucinogen that plays a central role in the Amazonian traditional medicine. Its psychoactive effects are associated with the presence of N,N-dimethyltryptamine (DMT), and monoamine oxidase inhibitors (MAO-A). Advances in neuroimaging investigations have provided insight into ayahuasca’s neurobiological mechanisms of action. Methods: Selecting only studies with neuroimaging results related to human ayahuasca consumption, we included six articles from a previous systematic review of serotoninergic hallucinogen neuroimaging studies up to 2016. Furthermore, we updated the data with a new systematic search from 2016 to 2022. We searched the PubMed, SciELO, and LILACS databases using the search terms “(ayahuasca OR DMT) AND (MRI OR fMRI OR PET OR SPECT OR imaging OR neuroimaging)”. Results: Our updated search provided five new articles for a total of 11 included in this review. The results on the Default Mode Network (DMN) are evident and may indicate a path to short term neuromodulation. Acutely, local neural networks appeared to become expanded, while overall brain connectivity declined. On chronic consumers, anatomical changes were reported, most notably related to cingulate cortex. Conclusion: Ayahuasca seems to change acute brain connectivity similarly to other psychedelics. The results are preliminary and further studies are warranted. Full article
(This article belongs to the Special Issue Natural Hallucinogens in Mental Health)
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