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PSYCHEDELICS IN THE TREATMENT OF MENTAL DISORDERS:
ADVANCES AND CHALLENGES
Eduardo d’Avila Lins Lacerda1
Bianca Medeiros Ferraz da Nóbrega2
Yasmin Mesquita Dias Franca Gadelha3
Lara Ribeiro Fernandes Teixeira4
Manolo Altieri Espinar5
Bruna Trigueiro Carlini6
Gabriel Santa Cruz Lins7
Ana Rafaela Souza dos Santos Lima8
Izabela Maria Medeiros Azevedo9
Paulo Heinrich Soares Bomtempo10
Abstract: Psychedelics have emerged as a promising approach to treating mental disorders,
challenging traditional paradigms in psychiatry. This study conducted an integrative literature
review to investigate the advances, challenges, and implications of the therapeutic use of these
substances, addressing the guiding question: “What are the current scientic perspectives on the
use of psychedelics in the treatment of mental disorders?” The methodology followed the steps
proposed by Mendes, Silveira, and Galvão (2008), covering the selection of articles from the LILACS,
1 University Center of João Pessoa, https://orcid.org/0009-0000-4154-2306
2 University Center of João Pessoa, https://orcid.org/0009-0005-7229-8744
3 Nova Esperança College of Medicine, https://orcid.org/0009-0007-9216-4908
4 Nova Esperança College of Medicine, https://orcid.org/0009-0003-3746-8635
5 University Center of João Pessoa, https://orcid.org/0009-0008-4282-4418
6 Nova Esperança College of Medicine, https://orcid.org/0009-0001-3670-2173
7 University Center of João Pessoa, https://orcid.org/0009-0009-7942-9654
8 University Center of João Pessoa https://orcid.org/0009-0008-5303-5203
9 University Center of João Pessoa, https://orcid.org/0009-0007-3868-2106
10 Federal University of Pernambuco, https://orcid.org/0000-0002-2515-6146
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SCIELO, and MEDLINE databases. Descriptors in Portuguese and English, such as “Psychedelics,”
“Mental Disorders,” and “Therapeutic Advances,” were used, and inclusion criteria favored recent
and complete publications. The results indicated signicant advances in the use of psychedelics, such
as psilocybin, in treating resistant depression and MDMA for post-traumatic stress disorder (PTSD).
Studies showed rapid and sustained improvements in depressive symptoms, while MDMA, combined
with assisted psychotherapy, signicantly reduced PTSD symptoms. These effects are attributed to
the interaction with serotonergic receptors, promoting neuroplasticity and reorganization of neural
networks, enabling profound psychological transformation. Despite the progress, ethical, legal, and
operational challenges remain. Many psychedelics are still classied as high-risk substances, hindering
their regulation and clinical use. Additionally, training specialized professionals and ensuring safety
in therapeutic settings are crucial aspects to expand the application of these substances. In conclusion,
psychedelics represent an innovative frontier in the treatment of mental disorders, with the potential to
revolutionize psychiatry. However, overcoming regulatory and societal barriers, as well as investing in
long-term research and professional training, is essential for their full integration into health systems.
Keywords: Psychedelics, Mental Disorders, Therapeutic Advances, Depression.
INTRODUCTION
Psychedelics have been the subject of growing interest in the area of mental health, emerging
as a promising approach for the treatment of various mental disorders. Substances such as psilocybin,
LSD, ayahuasca and MDMA have demonstrated, in recent studies, therapeutic potential in conditions
such as treatment-resistant depression, post-traumatic stress disorder (PTSD), anxiety and chemical
dependency. These advances have challenged traditional paradigms and sparked a resurgence of
scientic interest in previously marginalized substances.
Historically, psychedelics have been associated with both the counterculture of the 1960s
and social stigma and legal prohibition, which has hindered systematic research on their effects and
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medical applications. However, in recent decades, a psychedelic renaissance has allowed scientists
and health professionals to explore its benets in controlled and therapeutically oriented contexts.
This renaissance reects a transition of perspective: from recreational drugs to potent tools in the
arsenal of modern psychiatry.
The biological basis of psychedelics involves their interaction with serotonergic receptors
in the brain, particularly the 5-HT2A receptor, which plays a crucial role in regulating mood,
perception, and cognition. Neuroimaging studies show that these substances can induce altered states
of consciousness, reduce the rigidity of neural networks, and promote greater connection between
different brain areas. These effects have been linked to ego dissolution, an experience that many
patients report as deeply therapeutic.
The clinical outcomes obtained in controlled studies have been promising. Research indicates
that administering psilocybin, under professional supervision, can reduce symptoms of depression
for months after a single dose. Similarly, MDMA has shown signicant efcacy in treating PTSD,
especially in patients who have not responded to conventional treatments. These results point to a
revolution in the eld of psychiatry, with both clinical and social implications.
Despite these advances, the use of psychedelics in the treatment of mental disorders faces
considerable challenges. Ethical, legal, and regulatory issues limit its expansion and integration into
health systems. In addition, there is a pressing need for more long-term studies that evaluate the
safety and efcacy of these substances in diverse populations. The risk of abuse and the possibility of
adverse experiences also require strict protocols and expert supervision.
Another relevant aspect is the need to prepare health professionals to deal with the specics
of psychedelic treatment. This includes both technical training and the development of interpersonal
skills to conduct therapeutic sessions that often involve intense and emotionally charged experiences.
Patient support, before, during, and after the use of the substance, is essential to maximize benets
and minimize risks.
The integration of psychedelics into clinical practice also requires a review of public health
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policies. This includes regulating access to substances, establishing specialized centers, and including
psychedelic treatments in health systems, respecting the cultural and social particularities of each
region. It is essential that this incorporation is guided by scientic evidence and a commitment to
ethics and equity.
In short, psychedelics represent an exciting frontier in psychiatry and neuroscience, offering
new hope for patients and professionals in the eld. However, the path to its full acceptance and
utilization is fraught with challenges that require interdisciplinary collaboration, investment in
research, and a cautious and responsible approach. This study aims to carry out an integrative review
to understand the advances, challenges and implications of the use of psychedelics in the treatment
of mental disorders, contributing to the scientic debate and to the elaboration of future therapeutic
guidelines.
METHODOLOGY
This research was carried out through an integrative literature review, with an exploratory
approach, whose objective was to investigate, through articles already published, relevant information
that answered the guiding question. The methodology adopted followed the steps proposed by
Mendes, Silveira and Galvão (2008): 1) choice of the theme and denition of the research question; 2)
delimitation of inclusion and exclusion criteria; 3) extraction and limitation of information from the
selected studies; 4) analysis of the studies included in the review; 5) analysis and interpretation of the
results; and 6) presentation of the review or synthesis of knowledge.
The guiding question dened was: What are the current scientic perspectives on the use of
psychedelics in the treatment of mental disorders?
The integrative literature review aims to gather and synthesize the scientic knowledge
produced on the topic investigated, allowing the search, evaluation and consolidation of the available
evidence, contributing to the development of knowledge on the subject (Marconi; Lakatos, 2010). This
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type of study promotes the synthesis of knowledge by compiling ideas on the same topic, incorporating
the results obtained in practice. It is an important method in the eld of evidence-based practice,
as it involves dening a problem, conducting a systematic search for studies, critical analysis, and
applying the results. It is a broad method of review, allowing the inclusion of experimental and non-
experimental studies, which makes the study more complete (Souza; Silva; Carvalho, 2010).
To reach robust answers, searches were carried out in the following scientic databases:
Latin American and Caribbean Literature on Health Sciences (LILACS), Scientic Electronic Library
Online (SCIELO) and Medical Literature Analysis and Retrieval System Online (MEDLINE). For
the research, Descriptors in Health Sciences (DeCS) and Medical Subject Headings (MeSH) were
used, combined with the Boolean operator AND: “Psychedelics,” AND, “Mental Disorders,” AND,
“Therapeutic Advances”. In English, the descriptors were as follows: “Psychedelics,” AND, “Mental
Disorders,” AND, “Therapeutic Advances.”
The inclusion criteria adopted for the selection of articles were: free publications, available
in full, in Portuguese, English or Spanish, published in the last 5 years and that met the objective of
the research. The exclusion criteria, in turn, included: incomplete articles, duplicates in more than one
database, monographs, dissertations and theses.
RESULTS AND DISCUSSION
The results presented in the recent scientic literature on the therapeutic use of psychedelics
in the treatment of mental disorders reveal signicant advances. Controlled clinical studies have
demonstrated the effectiveness of substances such as psilocybin in the treatment of resistant depression,
showing response rates superior to those obtained with conventional antidepressants. Carhart-Harris
et al. (2018) observed that psilocybin administration, accompanied by psychotherapeutic support,
promoted rapid and sustained improvement in depressive symptoms, even in patients who had not
responded to other approaches. These ndings reinforce the potential of psychedelics as a promising
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tool in the psychiatric therapeutic arsenal.
In addition to depression, psychedelics have also been shown to be effective in treating post-
traumatic stress disorder (PTSD). A notable example is the use of MDMA in assisted psychotherapy,
which has shown positive results in phase 3 studies. According to Mithoefer et al. (2019), patients
undergoing this approach have reported signicant reductions in PTSD symptoms, often achieving
complete remission. These results highlight not only the neurochemical effects of the substance, but
also the impact of guided therapeutic sessions, which enable a resignication of traumatic memories.
Neuroscience offers explanations about the mechanisms behind these effects. Classic
psychedelics, such as psilocybin and LSD, act as agonists of serotonin 5-HT2A receptors, promoting
a reorganization of neural networks. This results in greater functional connectivity between different
regions of the brain, facilitating neuroplasticity and breaking rigid thought patterns associated with
mental disorders (Nichols, 2016). In this sense, psychedelics not only treat the symptoms, but also
offer an opportunity for deep psychological transformation, which represents an innovative paradigm
in psychiat r y.
However, the challenges associated with the therapeutic use of psychedelics are signicant.
One of the main obstacles is legal regulation. Many of these substances remain classied as high-risk
drugs, which limits their availability for research and clinical use. Despite advances in countries such
as the United States and Canada, where psilocybin has received special research designations, most
nations still face legal barriers and social stigmas that hinder the implementation of these therapies
(Nutt et al., 2020).
Another relevant aspect is the need to ensure safety and efcacy in the therapeutic use of
psychedelics. Although rates of serious adverse effects are low in controlled settings, there are reports
of negative experiences, such as intense anxiety or exacerbation of psychotic symptoms, especially
in predisposed individuals. This reinforces the importance of strict patient selection protocols and the
presence of trained professionals during therapeutic sessions (Johnson et al., 2008).
The training of qualied professionals is also a central challenge. Psychotherapists working
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with psychedelics need specialized training to deal with altered states of consciousness and facilitate the
integration of patients’ lived experiences. Institutions such as MAPS (Multidisciplinary Association
for Psychedelic Studies) have developed training programs, but the demand for specialists still exceeds
the supply, indicating the need for additional investments in this eld (Doblin et al., 2019).
The ethical implications of psychedelic use are also worth mentioning. The creation of a
therapeutic market for these substances raises questions about accessibility and equity. As psychedelic
treatments are often expensive and complex, there is a risk that only a limited portion of the
population could benet, increasing mental health inequalities. In addition, the potential for excessive
commercialization can divert the focus from therapeutic benets to purely for-prot purposes
(Schenberg, 2020).
The literature also points to the importance of considering cultural and historical perspectives
in the use of psychedelics. In many indigenous cultures, substances such as ayahuasca and peyote have
been used for centuries in ceremonial and healing contexts. Integrating these traditional practices
into the Western therapeutic model requires a careful balance between cultural respect and scientic
evidence, avoiding misappropriations or simplications of complex practices (Labate & Cavnar, 2014).
While there are signicant challenges, the renaissance of psychedelic research has the
potential to transform the treatment of mental disorders. Future studies should focus on expanding
samples, long-term follow-up, and comparing them with conventional interventions. In addition, it is
crucial that public policies advance in parallel, allowing these innovative therapies to be accessible
and regulated in a responsible way (Rucker et al., 2017).
In conclusion, psychedelics offer new hope for the treatment of mental disorders by combining
neuroscientic advances with innovative psychotherapeutic practices. However, the effective
implementation of these therapies requires a collective effort, involving researchers, clinicians,
policymakers, and communities, ensuring that the potential of these substances is fully realized for
the benet of global mental health (Grifths et al., 2016).
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CONCLUSION
Psychedelics have emerged as a promising tool in the treatment of mental disorders,
offering new perspectives for conditions such as resistant depression, post-traumatic stress disorder,
and chemical dependency. Scientic advances have shown that these substances, when used in a
controlled manner and accompanied by psychotherapeutic support, can provide signicant benets,
including symptom remission and improved quality of life. These ndings indicate a transformation
in the paradigm of mental health care, shifting the focus from simple symptom management to the
possibility of deep psychological and neurobiological reorganization.
Despite the advances, the limitations in the eld are evident. Restricted access to research,
due to regulatory barriers, still prevents a broader expansion of knowledge and clinical use.
Additionally, the ethical and legal challenges related to the commercialization and accessibility of
treatments highlight the need for a greater balance between innovation and equity. Other issues, such
as the lack of trained professionals, the high costs of therapies, and the possibility of adverse effects
in inappropriate settings, require cautious approaches and further studies to ensure the safety and
efcacy of interventions.
To overcome these barriers, it is crucial that future research focuses on broadening the
understanding of the neurobiological mechanisms of psychedelics and identifying specic populations
that may benet from these treatments. Further investigations into the long-term impacts and possible
interactions with other therapies are equally needed. Multicenter studies that explore cultural and
historical variations in the use of these substances are also recommended, promoting a more holistic
integration between science, ethics, and traditional practices.
Thus, the adoption of collaborative approaches, involving researchers, health professionals,
public policy makers, and communities, can contribute to a more balanced regulation and the
dissemination of evidence-based practices. The development of accessible and culturally sensitive
therapeutic models is essential if the transformative potential of psychedelics is to be fully realized,
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offering a viable and innovative alternative for mental health care.
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