From information to innovation for mental health

In Europe, 75% of depression cases do not receive adequate treatment, up to 50% of treated patients experience treatment resistance, and almost a third of these attempt suicide (WHO-MSD-MER 2017). In addition, according to the Organisation for Economic Co-operation and Development (OECD), one in two people will face a mental illness during their lifetime.

In recent decades, mental health has become one of the most urgent global challenges. According to the World Health Organization (WHO), conditions such as depression, anxiety and post-traumatic stress disorder (PTSD) affect hundreds of millions of people, often with serious consequences for their quality of life. Despite the clear need, innovation in mental health is lagging behind. Current estimates suggest that by 2040 we will be able to prevent only 14% of the burden of mental health conditions. The pharmaceutical sector has made limited progress in developing new treatments, leaving many patients without viable options. “Treatment resistance” is a common phenomenon in several psychiatric conditions. In this context, a debate is opening up on the need for new ways to address these conditions effectively and safely.

Psychedelic-assisted therapies in Western medicine have their roots in the 1950s, when substances such as LSD began to be explored for their therapeutic potential. In 1938, Swiss chemist Albert Hofmann synthesized LSD, unexpectedly discovering its applications for mental health. Between 1950 and 1965, LSD was administered to more than 40,000 patients and generated more than a thousand scientific papers, showing promising results in the treatment of depression, alcoholism and end-of-life anxiety.

In the 1970s, chemist Alexander Shulgin brought MDMA, first synthesized in 1912 by the pharmaceutical company Merck, back into the spotlight, discovering its potential in psychotherapy thanks in part to his collaboration with psychologist Leo Zeff, who in the 1960s had supervised thousands of psychedelic-assisted therapy sessions.
In the 1970s, the use of psychedelics began to slip out of the scientific community's control: cases of recreational use increased, stories about the potential dangers of psychedelics multiplied, and they came to be associated less with scientific discoveries and more with an emerging counterculture and the decline of classic American values. In 1971 this climate led to LSD being placed in the UN's Schedule I, the category associated with substances at high risk of abuse, dangerous to public health and without any therapeutic value, with consequent restrictions on scientific research into the therapeutic use of these substances. Similarly, in 1985, in response to the widespread recreational use of MDMA, which was becoming popular in rave culture, the US Drug Enforcement Administration (DEA) placed the substance in Schedule I. After MDMA was scheduled, Rick Doblin founded the nonprofit MAPS in 1986, and it is partly through figures like him that the last 20 years have seen renewed scientific interest in the therapeutic use of psychedelics in mental health. With the founding of MAPS, Rick Doblin launched a regulatory pathway for these substances, highlighting the effective use of MDMA in therapy, raising more than $300 million for evidence-based research and reopening the way to the therapeutic use of psychedelics in mental health.

Psychedelic-assisted therapy uses substances such as psilocybin, MDMA or ketamine, integrated into a psychotherapeutic process, to treat conditions such as treatment-resistant depression, post-traumatic stress disorder (PTSD), anxiety and addiction.

These substances induce altered states of consciousness that may facilitate deep emotional reprocessing and support the therapeutic process, but at the same time they may pose risks if not administered correctly. For this reason, it is essential that this takes place in an appropriate, controlled environment under the supervision of qualified therapists.

In recent years, research on psychedelic-assisted therapy has produced promising results, highlighting both the potential opportunities and the challenges associated with this therapeutic approach.

Opportunities

• An additional treatment option: Psychedelic medicine offers an alternative for patients who do not respond to conventional treatments; it does not replace existing ones.
• Less frequent dosing: Compared with traditional antidepressants, psychedelic-assisted therapy involves only a few doses during the course of treatment, reducing or eliminating the need for long-term daily medication.
• Supporting brain activation and neuroplasticity: The use of psychedelic substances may not only encourage the patient's emotional openness, making the psyche more receptive to targeted psychotherapeutic interventions, but also stimulate neuroplasticity. This ability to reopen brain plasticity facilitates neural reorganization, supporting lasting improvements in the management of depression, anxiety and addiction

Challenges

• Dependence on “set and setting”: Set refers to mindset, that is, the psychological state and attitude with which one approaches the experience. Adequate mental preparation is essential to ensure an open, receptive and intentional state of mind. The setting, on the other hand, is the physical environment in which the experience takes place. This space should be safe, comfortable and positively stimulating, while also professional and controlled to ensure the highest scientific rigor.
• High administration costs: Treatments require complex infrastructure and highly qualified staff, limiting large-scale adoption.
• Regulatory bodies and guidelines: regulatory bodies have only been involved in developing guidelines for clinical studies with psychedelic substances in recent years. This leaves little clarity on how to assess certain elements, including maintaining the double blind: participants may infer which treatment they received from its effects, compromising blinding (so-called “functional unblinding”), and the limited measurability of outcomes linked to the psychotherapeutic process. These challenges hinder the approval process by institutional bodies such as the FDA.

Over the last 20 years, the scientific community has once again become interested in psychedelic-assisted therapy, in particular by conducting clinical trials on MDMA to address PTSD and on psilocybin as an innovative treatment for treatment-resistant depression. This progress has led to significant developments in several countries, where research and regulation are advancing at different speeds.

United States
In 2017, the Food and Drug Administration (FDA) granted MDMA-assisted therapy for PTSD Breakthrough Therapy designation, speeding up its development; psilocybin received the same designation in 2018 for treatment-resistant depression and in 2019 for major depressive disorder. In 2019, esketamine (an isomer of ketamine) was approved as a nasal spray for treatment-resistant depression. After the FDA's negative response in 2024, in July 2026 Resilient (formerly Lykos Therapeutics) resubmitted its application for approval of MDMA-assisted therapy, which is currently under FDA review: a potentially historic step toward the clinical integration of these therapies.

Australia
In February 2023, Australia's Therapeutic Goods Administration (TGA) announced that, starting July 1, 2023, psychiatrists would be authorized to prescribe psilocybin for treatment-resistant depression and MDMA for PTSD. Although no specific products containing these substances have yet been approved, authorized psychiatrists may legally provide them to patients under their care, subject to approval by an ethics committee and specific authorization from the TGA.

Canada
Since 2020, Canada has made significant progress in the therapeutic use of psilocybin, with a focus on patients with terminal illnesses. Thanks to the mobilization of a coalition of terminally ill patients, healthcare professionals and experts, Health Canada began granting individual exemptions that allow legal access to experimental psilocybin treatments to relieve the anxiety and depression associated with incurable illnesses. In January 2022, Health Canada restored the ability of physicians to request, case by case, through its “Special Access Program,” access to restricted drugs such as psilocybin for patients with serious or life-threatening conditions when other therapies have failed, are unsuitable or are not available; this is not a general approval.

Europe
In Europe, psychedelic research is advancing with clinical studies in countries such as the United Kingdom, Germany, the Netherlands and Switzerland. Through programs such as Horizon 2020 and Horizon Europe, the European Union is investing in mental health projects that include the study of psychedelic compounds such as psilocybin. Although regulatory approvals are still limited, these investments represent a significant step toward the clinical integration of psychedelics in the treatment of mental illness. In March 2024, the European Medicines Agency (EMA) updated its guidelines on the development of medicines for Major Depressive Disorder (MDD) to include psychedelic therapy. In January 2025, the first European Citizens’ Initiative (ECI), Psychedelicare.eu, was launched: a request submitted by citizens of several member states calling on the European Commission to propose new laws and recommendations to support research into, and the therapeutic use of, psychedelic substances.

Clinical trials are experimental studies that evaluate the efficacy and safety of new treatments, including psychedelic-assisted ones. Divided into three phases, trials begin with safety studies in small groups of volunteers and then expand to larger numbers of patients with specific conditions.

Only after passing through these phases can a treatment be approved for large-scale clinical use. The trials currently under way on psychedelic-assisted therapies are helping to define the most appropriate doses, methods of administration and target populations. To date, the countries with ongoing clinical trials are: the United States, Canada, Australia, the United Kingdom, Germany, Spain, Portugal, the Czech Republic, the Netherlands, Norway and Switzerland.

Below is a selection of some of the most recent scientific articles on psychedelic-assisted therapy, organized by substance.

Pending health regulations that take into account all the studies carried out in this field and revise the drug schedules, MAPS Italia promotes practices that care for the mind, the body and the environment, creating and promoting opportunities to meet and work on these topics, raising awareness and preparing fertile, receptive ground for the institutional opening to psychedelic treatments.

Breathwork

The therapeutic processes of altering and expanding consciousness triggered by psychedelic substances can also be achieved, always within controlled therapeutic settings, through other practices. Czech psychiatrist Stanislav Grof, one of the fathers of LSD therapy, developed an alternative to the use of substances in the 1970s through Holotropic Breathwork sessions, a structured method of accelerated breathing accompanied by evocative music and therapeutic integration.

In recent years, similar practices such as conscious connected breathing have attracted growing interest from the scientific community for their ability to induce non-ordinary states of consciousness (NOSC) and to facilitate deep processes of emotional and psychospiritual integration.

In a safe, facilitated and well-integrated context, breathwork is a transformative and accessible way to explore consciousness and support deep healing processes.

In Florence, these practices can be experienced in collaboration with Inbodhi Breath Firenze, an active partner in training and in leading experiential sessions focused on inner exploration and mind-body integration.

The most recent research confirms that breathwork can trigger experiences similar to those induced by psychedelic substances, such as ego dissolution, mystical states and emotional catharsis, while also offering significant therapeutic benefits.

A 2025 study published in Communications Psychology found that circular breathwork induces altered states comparable to those of psilocybin, with measurable improvements in well-being and depressive symptoms after a single session:
Havenith et al., 2025, Communications Psychology

Another study published in Current Psychology in 2023 showed how conscious connected breathing alters brain activity and generates subjective mystical-type experiences, accompanied by an increase in self-esteem and a reduction in negative moods:
Bahi et al., 2023, Current Psychology

Finally, a meta-analysis published in Scientific Reports gathered data from 12 randomized controlled trials, confirming that breathwork is effective in reducing anxiety, depression and stress, strengthening its validity as a clinical tool:
Fincham et al., 2023, Scientific Reports