PREFACE

The first time I came in contact with psychedelic drugs, I knew instantly that my life had changed. I knew I was embarking on a journey of no return, on a caravel sailing towards unknown territories, and I would never find a port in which to rest, since few mysteries resist the advancement of knowledge as much as the characteristic alterations of consciousness induced by these substances. However, despite this certainty, I suppose that one feels the call and follows it, without looking back. And it is paradoxical, to say the least, that some substances called «psychedelics» (a word formed by psykhe, soul, breath, and dēlos, show, reveal) contain mysteries that are so complicated to unravel. Nevertheless, although this contradiction seems evident here, the truth is that a large part of what concerns the human organism and the action external molecules can exert on it, still lives in buried treasures that await, unhurriedly, to be discovered.

Personally, I began to study psychedelic drugs from a psychological point of view, obviously thinking that the most important thing about them would be their psychological effects. However, it did not take long for me to realize that, in order to approach them, it was necessary to widen the scope a little more. I then became interested in what anthropologists and ethnologists had to say about them, through descriptions of exotic journeys and literally mind-blowing adventures. Learning this perspective seemed one of the fundamental pillars for anyone who approaches these drugs, since it is of course necessary to place them in their historical context and understand the ways in which different cultures have used them, especially with regard to their communal and spiritual use. Later on, I drifted into a much more biomedical trend, for various reasons, although I would highlight the fact that I perceived the need to study these drugs from as serious and respectable a perspective as possible. I was also aware that there was much more to be done in medical-scientific settings that, despite their robustness and seriousness, were actually the most backward in the field. In this way, I studied neurotoxicology and neuropsychopharmacology applied to animal research, and later pursued studies on human pharmacology, subsequently undertaking my doctorate in Health, Psychology and Psychiatry. Thus, at the time of this writing, I believe I have some experience and expertise in the fields of psychology, anthropology, and pharmacology that should allow me to better understand what psychedelic drugs do to our minds. However, I still don't understand anything.

Despite not understanding anything, I dared to write this book, perhaps so that others could also reach the same conclusion. In fact, I wish we could all get there…! One comes across many books on neuroscience, psychopharmacology or popular science in general, launching bold statements without foundation or proclaiming supposed absolute certainties on issues that are still not very well understood. Nevertheless, we must not forget that science is a method of obtaining knowledge that works with provisional knowledge, where hypotheses or theories are generated that often have nothing to do with reality. We often settle for these simplistic or reductionist explanations of complex phenomena, and there is a reason for this: we need certainties. Our brain is prepared to build schemes, models of our environment, with the intention of predicting, as much as possible, future situations in which our life may be in danger. But sometimes this gets out of hand. We cannot understand everything. Let the person holding this book know that they will not find those certainties here. In this book we will navigate together through uncertainty, which should be the true defining characteristic of the scientific enterprise and the flag of our caravel. It is only when we position ourselves in the awareness of not knowing that we begin to learn. We should cultivate this state more.

Certainly, when we talk about the pharmacology of psychedelic drugs, we find ourselves in a highly complex field. This discipline should answer questions such as: Why does this molecule cause this primate to think of itself as God? To answer, you must first ask yourself: How does the human brain convert chemicals into thoughts? The answer to this question is still as far as the horizon itself. However, despite these limitations, the pharmacological knowledge of these drugs has advanced extraordinarily in recent decades, and although we cannot answer essential questions, we can answer other tangential ones, which is not trivial.

The rise of psychedelic drugs not only as possible therapeutic tools, but also as valuable tools to better understand functions as complex as consciousness itself, is already unstoppable. Researchers from all over the world are immersed in this search like never before, and the many possibilities are not even imaginable. What was unthinkable just 15 or 20 years ago is not only happening today, but is exceeding all expectations. Ambitious research programs financed by governments, billionaire investments in the development of medicines based on psychedelic drugs, the approval of the most important regulatory agencies, etc. It would not be surprising that shortly after this book is published, the use of psilocybin or MDMA for the treatment of certain psychological disorders is approved, nor that some decisive step is taken in basic research in neuroscience thanks to some psychedelic compound. Not even the most powerful psychedelic drug would make us see the exciting future that awaits us.

It is foreseeable that all this new wave of studies and research with psychedelics will also lead to advances in the knowledge of adjacent fields. From ICEERS, the organization in which I work, we organized the third international conference on ayahuasca in 2019, and to my surprise, in most of the congress, everything was discussed except ayahuasca. There were conferences on the sustainability of ecosystems like the Amazon, on art, biodiversity, indigenous communities, history, human rights, colonialism, etc. For me, personally, the intellectual interest in psychedelic drugs has also aroused a voracious interest in the pharmacology of natural products or in the general functioning of the nervous system or our mind. That is why I invite all the people who can read these lines to enter this field with all the enthusiasm and openness possible, because it is very likely that they will end up getting hooked on other fields that have nothing to do, at first glance, with psychedelic drugs. This transdisciplinarity that defines these drugs is perhaps the best of their attributes, and the new information that we receive almost daily about them is a nectar that we must take advantage of and exploit to its fullest.

I remember that when I went to high school, I must have been about 12 or 13 years old, I had not tried any drugs, except for a little glass of wine or quinquina with the family, and a puff here and there out of a cigarette that someone had procured – without even knowing how. However, I had already read Antonio Escohotado, Thomas Szasz, Albert Hofmann, Stanislav Grof, Aldous Huxley, Kerouac, etc. So the subject of "drugs" was beginning to look like a pretty fascinating world to me. Back then, in my high school Natural Sciences textbook, I found a couple of pages that talked about drugs. As soon as I started reading the content I started to freak out. It was nothing but alarmist information or directly implausible fallacies. I was stunned. Much more than that: I was deeply incensed at the thought that my generation, and many others before and perhaps after, would be confronted with this pack of lies and thus exposed to information that simply wasn't true. How was that possible? It took less than a few hours, I think, for me to get to work. I made a list of all the statements that were wrong, false or required some nuance, adding the correct information to each and the sources from which I had obtained the information. I attached the list to a letter addressed to Santillana Publishers, in which I strongly suggested that they correct those contents in future editions of the book on Natural Sciences, and I sent it by post to their headquarters. A couple of weeks later I was summoned to the office of the headmaster. There, with him, were also two lawyers from Santillana Publishers. They let me know that they had not liked the aforementioned letter very much and that they could even report me to the authorities (truth be told, I do not remember why, but I may have asked them to modify the content of the books a little too emphatically). In short, they forced me to write another letter in which I retracted what I had said in the previous one. Right there and then, handwritten. And the matter was settled. I was a scared kid who didn't know anything about life, I didn't do things right, and at the time, I had no other choice. But now I'm not a kid anymore.

This book is, in part, a crystallization of that premature desire to combat disinformation. I hope that it can help many people receive the upcoming future of psychedelic drugs in a way that is informed, safe, free from prejudice and, of course, open to what we do not yet know.

I would not like, nor would I forgive myself, for ending this text without thanking all the people who have made it possible. First of all, I would like to thank the fantastic team at Argonowta, for their enthusiasm and for this unique opportunity. It has been a pleasure to be accompanied by your team and collaborators.

It is inevitable to remember all the teachers or, rather, educators (my father told me that teachers teach, but from educators, you learn) who have accompanied me in my academic stage. To Pepita, Salvador Escudé, Manel, Rocaspana, Pere Joan, Inés, Teresa, Santafé, Jordi, thanks for everything.

I’d also like to thank my mother and father, for giving their all, loving me to the best of their ability and always being there.

Thanks to the fantastic team at ICEERS, my second family, who have always believed in me and offered me so many opportunities and unforgettable moments. And, gosh, thanks for every month's salary, too. What a nice gesture.

Thank you, Bou, for being my mentor and friend; and for being such an inspiration. To work by your side is a dream come true and an honor. Thank you for being someone from whom I always learn, who always surprises me and who is always there.

Thank you Mer, for being the beacon that sheds a little light in this world and that has guided many of my steps. Also, I probably wouldn't know how important this book is without you.

Thank you Eva, for joining me in the writing process of this book, for your careful reading of the proofs and your wise suggestions and corrections, but above all, thank you for accompanying me in this life and for your love. T'estimo, preciosa.

My regards and gratitude also to those who are no longer here, for teaching me what is really important.

FOREWORD

Unbounded love. Full acceptance. Absolute understanding. Transformation. Connection. Integrity. Astonishment. Ecstasy… These are some of the most common experiences shared by those who return from a psychedelic adventure which, experienced in moderation, does not seem to leave anyone indifferent. Far from being a contemporary passing fad, after emerging from a few decades of ostracism to which international drug policies had condemned it, the psychedelic experience has been a common practice in the cultural context of humanity, and of radical importance in the cultural construction of the West. The main philosophers of classical Greece participated in the Eleusinian rites, which were celebrated for some two thousand years until the temple of Eleusis, near Athens, was destroyed by Christian fundamentalism, determined from its origins to placate, with force and fierceness if necessary, all spiritual manifestations other than their own. In Eleusis, the ritual involved the drinking of kykeon, a hallucinogen whose precise composition has not yet been identified, although recognized experts compare it to modern LSD. It seems that the Eleusinian rites were practiced throughout the entire Greek cultural environment, outside of Greece, and this seems to be attested by a small chalice found in the area of Empuries, province of Girona, which was supposedly used to drink the kykeon. We can go back even further, to prehistoric times, and find the case of Selva Pascuala, a Neolithic shelter located in the mountains of Cuenca, Spain. The cave contains a parietal mural in which, according to experts, some psilocybin fungi are depicted, which the primitive inhabitants of the region would use to carry out their explorations of non-ordinary ontological territories.

But the use of psychedelics is not exclusive to our cultural tradition. The greatest known diversity of plant hallucinogens is found in South America, in Central America there are numerous archaeological records of the use of numerous hallucinogenic plants and mushrooms. The same occurs in Africa and Asia, although with less diversity. The anomaly of prosecuting users of hallucinogens (the war on drugs is really a war against those who use them) has been very limited in space (the countries that are signatories to the International Drug Conventions, but not their untamed indigenous lands) and in time (from 1971 to the present day). Just a few decades in what is surely tens of thousands of years of use. A mere hiccup in the history of humanity.

And it seems that this situation is reversing. On the one hand, in most countries, including Spain, only the active ingredients of hallucinogenic plants are controlled, not the plants themselves. And in countries where they are, like the United States, a social movement is emerging that calls for decriminalization, something that has already been adopted, in fact, in some states and that, as happened with marijuana before, is producing a chain reaction spreading to other states. Psilocybin mushrooms are already sold in stores in Canada, and the government has authorized the compassionate use of hallucinogens (for patients who have had other treatments fail). For the rest of the planet, ceremonies with ayahuasca, psilocybin mushrooms or peyote are in the process of global expansion (with their pros and cons, like everything else). Cheap and homemade cultivation methods are easily accessible to everyone, and the array of non-controlled substances available in informal trafficking networks (thanks to prohibition, which has sharpened the ingenuity of society, new drugs were created when the old ones started being controlled), is the largest in the entire history of mankind. So, on that front, although there are still occasional arrests and persecutions, things have gotten so out of hand that, in reality, there is no turning back. What will happen in this race ahead remains to be seen, for at least in the case of ayahuasca, peyote and iboga, plant resources are limited and may not be enough to supply all the people interested in them. It is an element for reflection.

On the other hand, we find that the active ingredients controlled in the most restrictive lists, such as LSD, psilocybin, mescaline, DMT or MDMA, to give the most notorious examples, are being the subject of scientific research. Some of them, such as psilocybin for the treatment of depression, or MDMA for post-traumatic stress disorder, are in such advanced stages of development that they are expected to be available for clinical use by 2023/24. We will then find ourselves in the paradox that for the same substance one can grow at home or buy on the deep web at absurdly low prices, one will have to pay a fortune for a psychiatrist to administer it. We are already seeing this in the case of ketamine for the treatment of depression. A vial of ketamine or S-ketamine (the racemic one that is also used in clinics) costs just 2 euros, and contains several dozen therapeutic doses. Its equivalent as an authorized medication for depression costs about 5,000 euros. The same active ingredient, with a different pharmaceutical preparation and a higher price. For this reason, the majority of ketamine treatment centers, at least in Spain, continue to use “run of the mill” ketamine, for obvious reasons. A third option is beginning to emerge in the case of easily accessible drugs, such as MDMA, psilocybin or ketamine itself: centers that allow patients to bring the substance, purchased by themselves, and take it at the consultation under supervision.

It will be interesting to see how all these tensions are resolved: on the one hand, as has already been said, the globalization of ceremonies with traditional plants; on the other, the medicalization of controlled hallucinogens and, finally, a possible use of the same active ingredients that are authorized but obtained on the illicit market because of their lower price. In a rational world, we would expect these tensions to be resolved rationally, generating as many possibilities as there are phenomena, and where the safety of patients or participants in ceremonies takes precedence. In a world like the one we live in, in other words, irrational, possibilities may include groups asking for the criminal prosecution of other groups, corporatism establishing itself as hegemonic against other groups (whichever group the hegemonic decide should not be hegemonic), sensationalism in the media attacking certain ways of doing things and recognizing other ways as the only legitimate ones, and politicians incapable of understanding the complexity of these problems, forcefully applying solutions that are too simple to complex issues, generating more harm than good. In short, nothing that we do not already know, having seen the management of similar problems that is happening in Spain, from the legalization of cannabis for medical use to the management of the COVID-19 pandemic. Be that as it may, whatever the future holds, its impact will of course be fascinating in the social field. It remains to be seen whether the political-administrative field will be up to the task. And how many victims will there be before that happens, when it happens, if it happens.

That is why a book like this is so pertinent at this time. It does not deal with social issues, but rather brings us up to date on the current scientific knowledge of the functioning of all these substances, for which so many names have been sought, without consensus. In this book about such an arduous discipline as pharmacology, the young psychologist and pharmacologist Genís Ona makes an informative, entertaining and, as far as the subject allows, understandable approach to the pharmacology, psychopharmacology and neuropharmacology of hallucinogens. To understand the pharmacology of hallucinogens is to understand the essence of what makes us human: beings capable of experiencing those ineffable sensations with which this prologue began. Hallucinogens allow us to access unusual spaces of reality, thus becoming a source of knowledge, not of psychopathology. This is how they have been used since time immemorial, and this is also the most interesting way of contemporary use. It is still paradoxical that when the therapeutic value of hallucinogens is recognized (once their safety and efficacy as drugs to treat mental health problems have been demonstrated), what is being implicitly recognized is the therapeutic value of hallucinations. And, perhaps, parallel to this, a less pathological view of some human psychological experiences that are currently considered diseases will begin to emerge, despite the lack of evidence on their physiopathogenesis.

In this sense, Genís Ona also wonderfully guides us along the path of pharmacological research and its direction. How, in the years when psychedelics were considered psychopathology-inducing substances, the mechanisms by which they produced aberrant psychological effects were sought in their neuropharmacology (the interest back then being the cause of diseases such as schizophrenia). Today the outlook is quite different and we find studies where hallucinogens have been shown to improve prosocial behavior or counteract the neurobiological mechanisms of anxiety. So we have gone from looking for the bases of human psychopathology, to exploring the bases of its healing mechanisms. The curious thing about the matter is that the mechanisms are the same and, what varies, is the way in which they are viewed. Before, they were viewed as the mechanisms by which our brain developed schizophrenia and today they are viewed as the ones that can cure depression. The scientific investigation of hallucinogens is the best example of how science is not as objective as some claim it to be but is as imbricated in social context as any other human activity. Social context will decides what hallucinogens are useful for, and that is what will guide their pharmacological research, yielding a better insight into their neurobiological bases.

But why a book on the pharmacology of hallucinogens? What is so interesting about pharmacology to dedicate a popular science book to it? Beyond what the author already comments in his introduction, that is, that although we do not talk about the mechanism of action of drugs in our everyday life, medicines are in fact part of that daily life, and it never hurts knowing something about what they do to our body (and what our body does with medicines). In the case of hallucinogenic drugs, the interest, in my opinion, is enormous. We are talking about substances with a minimal effect on the body that induce a maximum state of consciousness. Hallucinogenic drugs are that link between the extremely material (our body) and the extremely spiritual (our conscience absolutely exposed). In a way, hallucinogens are a kind of philosophers’ stone that, when in contact with a series of brain receptors, produces an amazing transformation of reality, in which, on the subjective plane, the spiritual is separated from the physical. The subjective experience with hallucinogens is therefore extremely spiritual: in its peak effect, the body disappears and only the spirit remains, at the mercy of transformation, in its most radical essence -a sentient, knowing and understanding spirit. A sentient, knowing and understanding spirit. For indigenous cultures, hallucinogens are the vehicle to enter a spiritual territory that is as real, if not more so, than reality itself, from which rise myths, cosmogonies and the knowledge of the origins of the disease and its sources for correction, where the shamans carry out their medical acts. Their concepts of health and disease have nothing to do with ours. And, Westerners being so spiritually illiterate, these substances allow us to access understandings about the nature of reality that can later serve us in our daily lives, as much therapeutically, as ontologically and transcendentally (one of the uses of psychedelics being recovered is precisely in patients with terminal illnesses, preparing them to face death). If this is so, then knowledge of the pharmacology of hallucinogens consists in trying to understand the mechanisms by which this knowledge itself is produced. It could be said that the pharmacology of hallucinogens is actually a philosophical discipline that is studied through scientific methods commonly used in psychology and biology.

Pharmacology is the science that studies the effects of drugs on the body. In the case of hallucinogenic drugs, there are two subdisciplines of particular interest: psychopharmacology, which is the study of effects on behavior, and neuropharmacology, which is the study of effects on the nervous system. In the first, the study is carried out using tools developed by psychology such as psychometric questionnaires, and in the latter, with tools from neurology (study of receptors and mechanisms of action). It is a complex science, since relating psychological processes with neurobiological mechanisms is not an easy task. All this aside from the risk of trying to explain phenomena belonging to different levels of analysis, one with the other's categories. The most current example is that of the famous Default Neural Network construct, so popular in current neuroscience in general, and in that of hallucinogens in particular. I leave it to the readers to get to the corresponding part in this book, to see how easy it is to fall into this type of bias, and how the author solves it so accurately. And similarly, many other examples which only a person with mixed training in psychology and pharmacology, together with great experience in the empirical field, can draw our attention to and clarify.

In this sense, Genís has been able to place each explanation at its corresponding level of analysis, thus avoiding the reductionisms that are so typical of this field. In a context in which biomedicine is dominating research agendas and budgets, even though its clinical application is extremely limited compared to other approaches, based mainly on public health or social and community practices, the author wanted to reflect on its scope and limitations and devote some final chapters to the reduction of risks in the use of hallucinogens and the recognition that should be given to traditional societies, which are ultimately the discoverers of many of these compounds. If in our society we establish mind-brain relationships in accordance with the parallel advances of both neurobiology and psychology, a field of extremely interesting value will be one to connect these disciplines with traditional indigenous knowledge in relation to hallucinogenic plants and compounds. In his essential book Consilience, the Unity of Knowledge, the recently deceased biologist Edward O. Wilson already pointed in that direction, precisely using ayahuasca and one of its best-known cultural expressions, the art of the Peruvian mestizo painter Pablo Amaringo, as an example.

In short, what we have here is an a priori arduous field, which becomes attractive when we understand that its concepts reveal the keys that will allow us to go deeper and deeper into the knowledge of what is the essence of the human being. Hallucinogens, as writers like Aldous Huxley or chemists like Alexander Shulgin have said, are incomparable tools for learning about mind-brain relationships. And the discipline that deals with this study is pharmacology. The last twenty years have been vertiginous in terms of the development and progress in knowledge of the pharmacology of hallucinogens, but this knowledge is only present in scientific journals; it has not reached the general public. That is why this book is so pertinent at this time. We needed a translator, a compiler who could bring what is in that inaccessible world of scientific literature down to earth, a feat that can only be achieved satisfactorily if the one doing it can masterfully combine scientific knowledge and humanistic sensibility in such a way that scientific abstraction can be understood in its social context. In the case of Genís Ona, these two knowledges co-exist, allowing him to move away from literal and reductionist explanations, without avoiding the complexity of the phenomenon and making precise interpretations of the data.

Writing a book like this was no easy task, if one did not want to betray the goal of making it for all audiences. My congratulations to the author. I think he can feel satisfied with the result. At first glance, this book may not be the most attractive title in this collection. A headline with a technical “nonword” can put off a distracted reader. But if an intellectually restless person seeks to know the processes that mediate between matter and spirit, how these processes have been discovered, what philosophical and therapeutic implications they have and, above all, update on the level of knowledge that is now available about them and their relationship to hallucinogenic or psychedelicdrugs, this is your book. I can be nothing but proud of having been asked to preface it by the author, the only independent researcher in Spain who is currently administering hallucinogens in clinical settings to study their pharmacology and therapeutic potential. And someone who, in addition to being a tireless collaborator, is a good friend. Genís' resume, by the way, in terms of scientific publications in impactful journals, exceeds the average researcher, and more so in a field as complicated as psychedelicresearch, until relatively recently, has been. This book is therefore another small success in his already brilliant career, of which I am sure we will all feel proud in the future, even more than we are now. Researchers like him are role models for this coming generation, which is his own, to take over in psychedelic research.

Jose Carlos Bouso

Scientific Director of ICEERS -

International Center for Ethnobotanical Education, Research & Service.