Psychedelic Research: A Comprehensive Overview

Over the last couple of decades, the psychedelic world has experienced a true renaissance. The resurgence of psychedelic research, together with a more liberal attitude towards non-ordinary states, has ignited widespread interest in the potential of these substances for therapeutic, psychological, and spiritual healing. After a long and dispiriting period of prohibition, criminalization and stigma that began in the late 1960s, psychedelics are once again front and center in the research agenda of leading universities and medical institutions. Researchers from all fields, from the cutting edge neuroscience  and medicine, and all the way to psychology, sociology, medical anthropology and literary theory, are once again exploring the therapeutic applications of substances and compounds such as psilocybin, LSD, MDMA, and ayahuasca to treat a wide range of psycho-spiritual afflictions, including depression, anxiety, PTSD, and addiction. In addition to its therapeutic and medical applications, psychedelic research is also uncovering insights into consciousness, neuroplasticity, and the human condition. This blogpost explores the current state of psychedelic research, highlighting some of the most promising areas of study  in both medical and cultural contexts.

A Brief History of Psychedelic Research

Before we go any further, it is important to state that psychedelic plants and fungi have been used by indigenous cultures for millennia in diverse and well documented religious and magico-medical contexts. That is, although the Western scientific interest in these class of substances is relatively recent, this is not universally true. Science, as we know it, refers to a particular epistemic orientation and method for distilling knowledge through observation and manipulation of the natural world around us. Natural scientists exist and have existed throughout history all over the world. Indigenous traditions that include the use of psychoactive and psychedelic plants and fungi are traditions based on hundreds and possibly thousands of years of empirical knowledge, trial and error, deep listening to the guidance of nature and refined attunement to the ebbs and flows of the rhythms of the world. Generation of medicine men and women, shamans, medics, herbalists and people who performed all sorts of different spiritual or medical social roles adjacent to these wondrous plants and substances, meticulously encoding their findings in storytelling, songs, myths and other forms of oral lore (you can learn more about oral traditions in this previous blogpost).

From the Shipibo or the Huni Kuin in Western Amazonia, the Inga or the Kofán in the Colombian Putumayo basin, or the Bwiti in Western Africa, or the Mazatec or Zapotec people of the Oaxaca highlands and the Wirrarika (Huichol) or Raramuri (Tarahumara) of Western Mexico, indigenous wisdom keepers have kept this knowledge alive through light and dark, through conquest and inquisitions, displacements and ethnocides. To them we owe much of what we know today — and we carry the torch that they lit as we add layers of knowledge with the tools that we have today, microscopes and centirifuges and the modern magic of the  fMRI.

The academic-scientific study of psychedelics, however, only began in earnest in the mid-20th century, notably with Albert Hofmann’s discovery of LSD in 1938 and its psychoactive effects in 1943. In the 1950s and 1960s, psychedelics like LSD, psilocybin and mescaline became the focus of intense interest in psychiatric research. Early studies suggested their potential for treating mental illnesses, facilitating spiritual experiences, and even fostering creativity. The publication of books such as “The Doors of Perception”, by the British author Aldous Huxley, paved the way for wider interest in the effects of these substances. In the book, published in 1954, Huxley depicts his wondrous journeys under the influence of mescaline, the active ingredient in psychedelic cacti such as Peyote or Wachuma, also known as San Pedro. A few years later, philosopher Alan Watts explored the intersection between psychedelics and human consciousness in popular works such as “The New Alchemy” (1958) and “The Joyous Cosmology” (1962), helping spark  the curiosity of a whole generation of young seekers.

However, the growing countercultural association of psychedelics with anti-establishment movements and recreational use led to their criminalization in the late 1960s. Figures like Richard Alpert (Ram Dass), Ken Kesey or Timothy Leary, who exhorted the young disenchanted masses to “Turn on, tune in, and drop out”, tickled the repressive and authoritarian tendencies of the establishment a little too far. As a result, not only did the Hippie movement and the counterculture as a whole experienced a rude awakening from the psychedelic fever dream of the Summer of Love, but also the academic research came to a standstill for several decades, with these substances classified as Schedule I drugs in the United States and many other countries. It was not until the 1990s that interest in psychedelics began to rekindle, largely due to advancements in neuroscience and a renewed focus on mental health crises, coupled with the increasing awareness of the failure of the so called “war on drugs”.

Today, many decades later, we seem to be experiencing a “psychedelic renaissance”. The “psychedelic renaissance” refers to the renewed scientific and medical interest in psychedelics that began in the late 20th century and has accelerated in the 21st century, and also to the resurgence of a popular psychedelic culture no longer at the fringes of society. Transformational festivals, Netflix shows, popular books by bestselling mainstream authors — psychedelic drugs, or, at least, positive stories and media about psychedelic drugs are everywhere, and the narratives are decidedly different. Scientific journals report about the promising therapeutic applications of psilocybin mushrooms, MDMA and ayahuasca, while popular magazines and newspapers run stories highlighting the benefits of micro-dosing.

The cultural climate and the scientific momentum go hand in hand, shaping a new discourse about what psychedelics actually are and what they can become. Furthermore, psychedelic discourse addresses some of the most pressing issues of modern times, including an awareness of a looming mental health crisis affecting, more than anyone else, the younger generations. This renaissance is marked by rigorous research into how these substances can be used safely and effectively to address collective and individual mental health challenges, and benefit society as a whole. Now, lets take a look at some of the most important plants, fungi and substances being researched, and see how it is that they can help improve our quality of life.

Psilocybin

Psilocybin, the psychoactive compound in the mysterious fungi colloquially knows as “magic mushrooms,” has emerged as one of the most promising candidates for treating mental health disorders, especially depression. Research conducted at institutions like Johns Hopkins University (Lehto et al., 2021) and Imperial College London (Erritzoe et al., 2018) has shown that psilocybin, when administered in a controlled, therapeutic setting, can produce profound shifts in consciousness and emotional well-being.

One of the most groundbreaking studies published in 2016 (Griffiths et al.) found that a single dose of psilocybin produced significant reductions in depression and anxiety among patients with life-threatening cancer. Follow-up studies have demonstrated similar effects for individuals with treatment-resistant depression (Goodwin et al., 2022), a condition that has been notoriously difficult to treat with conventional antidepressants. The efficacy of psilocybin in these studies appears to be linked to its ability to induce mystical or transcendent experiences, which are often described as the most meaningful moments of a patients’ lives.

MDMA

MDMA, a synthetic compound colloquially known as “Molly” or “Ecstasy”, is another substance receiving significant attention for its potential to treat post-traumatic stress disorder (PTSD). In fact, MDMA-assisted psychotherapy, pioneered by organizations like the Multidisciplinary Association for Psychedelic Studies (MAPS), has been the flagship of the psychedelic renaissance, showing remarkable success in clinical trials and opening the doors to a wide range of research projects around the world. The reason why MDMA has been so successful as an adjunct to psychotherapy, is that it appears to facilitate emotional openness and empathy, allowing individuals to process traumatic memories without the fear or anxiety that typically accompanies such recollections. MDMA is not usually considered a classic psychedelic, as its effects are really most marked in the affective and emotional sides: for that reason, MDMA is sometimes classified as an entactogen or an empathogen: a class of substances defined by their ability to enhance sensitivity and increase empathy.  In fact, MDMA is also the drug of choice for another peculiar scenario: couples therapy. The ability of the substance to increase connectedness, reduce hostility and temporarily inhibit any emotional or psychological defense mechanisms, coupled with the increase in empathy, attunement and sensitivity, make it an ideal tool for therapists working with couples.

In 2021, results from Phase 3 clinical trials for MDMA-assisted therapy for PTSD were published (Mitchell et al., 2021), showing that 67% of participants no longer met the criteria for PTSD after three treatment sessions. Despite some recent setbacks, these findings have paved the way for MDMA to potentially become an FDA-approved treatment for PTSD in the near future, marking a significant milestone in the field of psychedelic medicine.

Ayahuasca and mental health

As we explore the therapeutic potential of psychedelic substances and plant medicines, our main focus, of course, will be on Ayahuasca. We have written extensively about our beloved, psychoactive brew in quite a few past blogposts, that you can find on our site. For example, you can learn more about the cultural history of ayahuasca here, or you can read about its diverse native uses here. The brew, made from the Banisteriopsis caapi vine and Psychotria viridis leaves, is a mixture of the powerful harmala alkaloids harmine and harmaline, and the psychedelic tryptamine DMT (dimethyltryptamine). With the resurgence of interest in psychedelics, particularly for their therapeutic potential, ayahuasca is increasingly studied in academic settings, both from a biomedical and a sociocultural perspective. Researchers are exploring its effects on mental health, addiction, social connection, consciousness, and even neurobiology and epigenetics.

Again, it is important to highlight that ayahuasca may be relatively “new” as a subject of research for academic science, yet it has a long history of use and meticulous study in many Amazonian cultures. Ayahuasca —also named Yagé, Natem, Oni or Nixi in different languages— is a sacred brew employed in healing ceremonies, used as a bridge for communication with the more-than-human-world, and as  a tool to enhance social cohesion within a group. Indigenous healers, known as vegetalistas, curanderos or ayahuasqueros, use ayahuasca to communicate and negotiate with plant spirits, diagnose illnesses, and guide participants through intricate processes of personal or communal healing. The brew’s ability to induce vivid visions, emotional catharsis, and feelings of connection with each other and the natural world is central to its spiritual and therapeutic significance.

In the 20th and 21st centuries, ayahuasca has moved beyond its indigenous roots and is now used in neo-shamanic practices all over the world. From Peru to Costa Rica, Mexico, London, Los Angeles or Bali, ayahuasca has become a global phenomenon. Although still illegal and quite misunderstood by many, the increasing popularity of ayahuasca ceremonies in urban centers and retreat settings worldwide has led to the rapid expansion of a global ayahuasca movement. As a result, academic research has expanded from focusing solely on ethnographic accounts of traditional contexts to include the observational study of ayahuasca’s effects on Western retreat participants seeking healing from mental health issues, and even controlled studies done in the clinical setting of universities and research centers.

Of course, one of the primary drivers of academic interest in ayahuasca is its potential to treat mental health conditions that are resistant to conventional therapies. With epidemics of loneliness, anxiety, alienation and disconnection sweeping over post-industrial societies, anything that holds promise to ameliorate human suffering deserves to be takes seriously. Several studies have explored the efficacy of ayahuasca in treating treatment-resistant depression and anxiety. A pioneering study published in 2018 in the journal Psychological Medicine conducted a randomized, placebo-controlled trial that showed a significant reduction in depressive symptoms after a single ayahuasca session (Palhano-Fontes et al., 2018). Participants reported rapid and lasting improvements in mood, with many attributing their positive outcomes to the emotional processing and insights gained during the experience.

The neurochemical mechanisms underlying these effects are also of interest to researchers. Ayahuasca is believed to affect serotonin receptors in the brain, much like traditional antidepressants, but with a faster onset of action. It also appears to promote neuroplasticity, allowing the brain to rewire itself by forming new neural connections (Mallaroni et al., 2023). These findings suggest that ayahuasca could offer a novel approach to treating mood disorders, especially for those who have not responded to conventional therapies.

Similar to MDMA (although very different medicines!), ayahuasca has shown promise in the treatment of PTSD, particularly for individuals who have experienced trauma and are struggling to find relief through standard therapeutic methods. In a recent study researchers found that participants who used ayahuasca in a supportive, ceremonial context experienced significant reductions in PTSD symptoms (Weiss et al., 2023). Many reported that the brew helped them revisit and process traumatic memories, often from a different perspective that facilitated emotional healing. This capacity to confront and process difficult memories is one of the key therapeutic features of ayahuasca. The brew’s visionary properties allow participants to access repressed emotions, revisit past experiences, and gain insights that can lead to profound psychological shifts. This ability to foster catharsis —emotional release— and catalyze deep transformation is an area of increasing interest in academic and clinical circles.

Furthermore, ayahuasca’s potential to treat addiction, particularly to alcohol and other substances, has also been a subject of growing research. A longitudinal study conducted in Canada, which followed participants over the course of several ayahuasca ceremonies, found significant reductions in addictive behaviors and improvements in overall well-being (Thomas et al., 2013). Participants often reported experiencing powerful insights about the root causes of their addiction, leading to increased self-awareness and a commitment to change. And this is an important point — psychedelics and plant medicine rarely “cure” us from what is ailing us on their own. They are not magic pills or panaceas. They can show us where we need to do the work — but we still need to walk to the walk.

Ayahuasca’s therapeutic effects on addiction are believed to be due to its ability to help dissolve the strong grip of the ego and facilitate a connection to a greater sense of purpose. By helping individuals confront their inner demons, traumas, and unresolved emotional pain, ayahuasca opens the door to healing and recovery. Researchers also highlight the importance of the ceremonial context, where the presence of a trained facilitator or shaman can provide guidance and emotional support during the intense experience.

Neurobiological Insights

A significant focus of academic research on ayahuasca is the study of its effects on the brain and consciousness. Using brain imaging technologies like fMRI and EEG, scientists are investigating how ayahuasca impacts brain function and promotes changes in perception, cognition, and mood. Ayahuasca’s active ingredients, particularly DMT, bind to serotonin receptors in the brain, leading to a non-ordinary, visionary state of consciousness characterized by vivid visions, ego dissolution, and altered perceptions of time and space. These effects are mediated by changes in the brain’s default mode network (DMN), a set of interconnected brain regions associated with self-referential thinking, memory, and the construction of personal identity. Research has shown that ayahuasca decreases activity in the DMN, which may explain why participants often report a sense of oneness with the universe or a connection to a higher power (Palhano-Fontes et al., 2015).

As we saw earlier, ayahuasca also promotes neuroplasticity, increasing the brain’s ability to form new neural connections (Mallaroni et al., 2023). This effect is particularly important for mental health, as it may help individuals break free from rigid patterns of thought and behavior that contribute to conditions like depression, anxiety, and addiction. Neuroplasticity may also account for the long-lasting therapeutic effects reported by many ayahuasca users, even after a single session.

The Future of Ayahuasca Research

The future of ayahuasca research looks promising, with growing interest from academic institutions, funding organizations, and policymakers. As the mental health crisis continues to escalate globally, there is an increasing recognition of the need for innovative approaches to treatment, and ayahuasca’s undeniable therapeutic potential is gaining attention. One of the primary obstacles, of course, is the legal status of the brew. While ayahuasca is legal in some South American countries and is protected as a sacrament by certain religious groups, it remains illegal in many parts of the world, including the United States and much of Europe. This has made it difficult for researchers to conduct large-scale clinical trials or obtain funding for their work.

Researchers are likely to continue investigating ayahuasca’s efficacy for treating mental health conditions like depression, PTSD, and addiction, with a focus on conducting larger, randomized controlled trials. There is also likely to be increased interest in understanding the neurobiological mechanisms underlying ayahuasca’s effects, particularly its ability to promote neuroplasticity, foster connectedness to each other and the world around us, help us redefine meaning and purpose and facilitate cathartic emotional releases.

At the same time, there must be a growing emphasis on ethical research practices, ensuring that the study of ayahuasca benefits indigenous communities and respects their traditions. Collaborative research projects that involve indigenous healers and researchers are likely to become more common, providing a more holistic understanding of the brew’s potential and truly honoring one of the key lessons this wonderful brew can teach us: the central importance of reciprocity and mutual responsibility as we strive for wholeness and happiness.

Lastly, it is important to learn a few lessons from the unfolding of this “psychedelic renaissance”. While the results of current psychedelic research are overwhelmingly positive and promising, it is crucial for researchers, practitioners and participants alike to remain grounded in the reality of these substances true power. While concerns can be minimized by adhering to best practices and choosing wisely where, when and with whom we want to wander into the depths of our own psyches, it is important to remain aware that risk still exists. Awareness of the set —our mental and emotional state— and the setting —the context for the experience— is very important. Psychedelics are generally considered physiologically safe, especially when compared to substances like alcohol or opioids, and they can induce intense psychological experiences that may be overwhelming for some individuals. Having the right support is crucial: being in an environment that inspires safety, comfort, professionalism and accountability.

As psychedelic research continues to advance, the future holds significant promise for the development of new therapies and treatments for mental health disorders. Several clinical trials are currently underway to further investigate the therapeutic potential of ayahuasca, psilocybin, MDMA, LSD, DMT and other substances. If these trials continue to produce positive results, we may see psychedelics become a mainstream treatment option within the next decade.

However, with increased access comes the need for better individual and collective integration. We have previously written a blogpost on integration that you can find here. Integration involves helping individuals and groups process and make sense of their psychedelic experiences, allowing them to apply the insights gained in a meaningful and constructive way. In essence, it is the practical step that ensures that the insights we gain during our ceremonies and our retreat are properly translated within our daily lives, helping us catalyze healing and positive transformation. Without a proper integration plan, the insights gained, no matter how life-changing they might appear, are likely to eventually evaporate in thin air, finding no fertile soil where to take root. This aspect of the psychedelic experience is essential for ensuring that the benefits of plant medicines are long-lasting and that any challenges or difficulties encountered during the experience are appropriately addressed. As the field of psychedelic research evolves, there will likely be a growing emphasis on developing insightful and replicable protocols for integration and support, which will be crucial for the responsible use of these substances.

Beyond therapy: Creativity, mysticism and consciousness

While medicalized psychedelics are really at the center of the psychedelic renaissance, and the framing of psychedelics as “medicines” and the highlighting of the therapeutic benefits have been crucial to their acceptance by mainstream academics and politicians, these aspects do not tell the whole picture.  For example, psychedelics —including ayahuasca— are also highly valued for their unmatched capacity to enhance creativity and problem-solving abilities. Historical evidence suggests that many artists, musicians, and scientists have used psychedelics to inspire their work and generate novel ideas. From Pink Floyd to the Doors, Star Wars or the timeless writings of Hunter S. Thompson, psychedelics and artistic expression go hand in hand. This can be true in science too— the famous chemist Kary Mullis, for example, credited his discovery of the polymerase chain reaction (PCR) technique, which revolutionized genetic research, in part to his experiences with LSD. Steve Jobs, the founder of Apple and creator of technologies that changed the world, was a vocal advocate of psychedelics as creativity adjuncts. Seeing familiar problems through a new set of eyes, gaining fresh insight and novel perspectives can make the whole difference in human innovation.

Furthermore, psychedelics are widely perceived to be powerful catalysts of “ego dissolution,” where individuals temporarily lose their sense of self-identity and feel a deep sense of unity with the universe or a higher power. These experiences, often described as mystical or transcendent, are characterized by feelings of awe, interconnectedness, and a loss of boundaries between the self and the external world — something that is sometimes called “cosmic consciousness”. Although research on intrinsically subjective experiences like these is tricky, researchers are increasingly able to find neural correlates and underlying mechanisms using advanced imaging technologies like fMRI.  Such states of consciousness are thought to have profound implications for our understanding of the mind, particularly in the context of spiritual and religious experiences, and will likely continue to be a fascinating field of base research, as psychedelics continue to be at the center of the time-old debate about the nature of reality and perception. The fact that psychedelics can dramatically alter how individuals perceive the world raises fundamental questions about the relationship between the brain, consciousness, and reality.

Are the visions and insights experienced during a psychedelic trip simply the result of altered brain chemistry, or do these substances allow individuals to access deeper layers of reality that are normally hidden from view? Are the entities that people encounter during their ayahuasca or DMT experiences just projections of our minds, or are these encounters with “real’ entities that exist independently of our perception of them, in parallel dimensions accessible only with the right neurochemical keys? Are these entities “plant spirits”, as argued by our indigenous teachers and mentors, are they intelligent alien beings or divine entities? Truly, reality is often stranger than fiction, and in matters of ontology, all we know is that we truly don’t know. These fascinating questions, however, keep driving interdisciplinary research that bridges neuroscience, psychology, philosophy, and spirituality.

References

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