Almost everyone knows the story of the discovery of one of the most famous psychedelics, lysergic acid diethylamide. In 1938, Swiss chemist Albert Hofmann researched a number of lysergic acid compounds, and only five years later the psychotropic properties of the compound LSD-25, which has now become simply LSD, were discovered. The pharmaceutical company Sandoz supported the research, and in the 1960s the substance found its way to psychologist Timothy Leary, after which the "psychedelic boom" began. In the 1970s, psychedelics were banned. Now, after 50 years of "scientific" silence, researchers are beginning to return to the subject of psychedelics in a variety of neuroscience fields: studies of brain function, treatment of anxiety and post-traumatic syndrome.
A bit of history
The history of psychedelics predates the synthesis of LSD by Albert Hoffman. Substances remarkably resembling the neurotransmitter serotonin (Figure 2) and having similar effects to LSD on the nervous system can be found in certain species of mushrooms and plants. The hallucinogenic properties of the peyote cactus have been known to various Native American tribes for a long time, and only in the late 19th century was mescaline isolated from it, which is now banned in most countries. Another example is the use of psilocybin mushrooms by the Aztecs, which is confirmed in the form of fairly large stone monuments to these mushrooms. And isolated psilocybin in pure form in 1958, already familiar to the inhabitant of our forum Albert Hoffman. The shamans of the Amazon Indian tribes used the drink Ayahuasca, prepared from the liana Banisteriopsis caapi ("spirit liana"), the active substance of which is dimethyltryptamine (DMT). In many countries, the preparation of ayahuasca is forbidden. Interestingly, DMT is contained not only in the decoction of the "spirit liana", but is also an endogenous hallucinogen and is synthesized in the brain of each of us.
A bit of history
The history of psychedelics predates the synthesis of LSD by Albert Hoffman. Substances remarkably resembling the neurotransmitter serotonin (Figure 2) and having similar effects to LSD on the nervous system can be found in certain species of mushrooms and plants. The hallucinogenic properties of the peyote cactus have been known to various Native American tribes for a long time, and only in the late 19th century was mescaline isolated from it, which is now banned in most countries. Another example is the use of psilocybin mushrooms by the Aztecs, which is confirmed in the form of fairly large stone monuments to these mushrooms. And isolated psilocybin in pure form in 1958, already familiar to the inhabitant of our forum Albert Hoffman. The shamans of the Amazon Indian tribes used the drink Ayahuasca, prepared from the liana Banisteriopsis caapi ("spirit liana"), the active substance of which is dimethyltryptamine (DMT). In many countries, the preparation of ayahuasca is forbidden. Interestingly, DMT is contained not only in the decoction of the "spirit liana", but is also an endogenous hallucinogen and is synthesized in the brain of each of us.
And chemically synthesized LSD is also a derivative of ergot alkaloids (a fungus that parasitizes on cereal plants), a hallucinogen known to mankind since the time of the Eleusinian Mysteries - ancient Greek initiation rituals (1500 BC).
But the real "boom" in the use of psychedelics in Europe and America began after the synthesis of LSD: experiments in the use of this substance began in laboratories around the world. In the late 1960s, the first experiments on the use of LSD in the treatment of alcohol addiction and chronic depression were conducted at the Spring Grove Clinic (Maryland, USA). The results of the first studies were impressive, and the use of LSD in clinical trials was encouraged by the U.S. government. From the 1950s through the 1960s, six international conferences and thousands of articles were devoted to the use of LSD in the clinic. What could have happened to make such a promising drug not just banned from clinical trials, but listed as illegal in most parts of the globe?
In the 1960s, the LSD trip became an element of hippie culture, thanks in large part to the disgraced Harvard lecturer Timothy Leary, whose words "Turn on, tune in and drop out" became the slogan of the generation. The cult of psychedelics among young people horrified older generations and governments, resulting in the demonization of psychedelics in the mass media. In the U.S., for example, where LSD was synthesized and widely used in clinical trials, hippie drugs (psychedelics and cannabinoids) were delegitimized and Timothy Leary was sent to prison. Of course, with the total ban on the use of psychedelics, scientific research in this area came to naught (Figure 3).
But the real "boom" in the use of psychedelics in Europe and America began after the synthesis of LSD: experiments in the use of this substance began in laboratories around the world. In the late 1960s, the first experiments on the use of LSD in the treatment of alcohol addiction and chronic depression were conducted at the Spring Grove Clinic (Maryland, USA). The results of the first studies were impressive, and the use of LSD in clinical trials was encouraged by the U.S. government. From the 1950s through the 1960s, six international conferences and thousands of articles were devoted to the use of LSD in the clinic. What could have happened to make such a promising drug not just banned from clinical trials, but listed as illegal in most parts of the globe?
In the 1960s, the LSD trip became an element of hippie culture, thanks in large part to the disgraced Harvard lecturer Timothy Leary, whose words "Turn on, tune in and drop out" became the slogan of the generation. The cult of psychedelics among young people horrified older generations and governments, resulting in the demonization of psychedelics in the mass media. In the U.S., for example, where LSD was synthesized and widely used in clinical trials, hippie drugs (psychedelics and cannabinoids) were delegitimized and Timothy Leary was sent to prison. Of course, with the total ban on the use of psychedelics, scientific research in this area came to naught (Figure 3).
The Age of the «Psychedelic Renaissance»
While psychedelics remained a taboo subject, courageous scientists in laboratories around the world proved that this group of substances not only has no toxic effects on the brain, but also does not cause physical dependence when used in a controlled manner. The first clinical studies were not approved until 30 years after the prohibition of psychedelics. Expectedly, this event and the first research results were a turning point in psychedelics research. Roland Griffiths and colleagues proved for the first time since criminalization that taking psychedelics contributes to the personal growth of volunteers and improves their quality of life. Thus, since 2006, the study of psychedelics has become popular again: as of this writing, 30,695 articles mentioning the term psychedelic are indexed in PubMed, of which only about 12% are literature reviews. "The point of no return" becomes the publication on the effects of MDMA on the serotonergic system of octopuses in the highly ranked journal Cell. The authors of this work showed that ecstasy, by interacting with the serotonin transporter protein SERT, turns sociopathic octopuses into friendly neighbors (Figure 4).
While psychedelics remained a taboo subject, courageous scientists in laboratories around the world proved that this group of substances not only has no toxic effects on the brain, but also does not cause physical dependence when used in a controlled manner. The first clinical studies were not approved until 30 years after the prohibition of psychedelics. Expectedly, this event and the first research results were a turning point in psychedelics research. Roland Griffiths and colleagues proved for the first time since criminalization that taking psychedelics contributes to the personal growth of volunteers and improves their quality of life. Thus, since 2006, the study of psychedelics has become popular again: as of this writing, 30,695 articles mentioning the term psychedelic are indexed in PubMed, of which only about 12% are literature reviews. "The point of no return" becomes the publication on the effects of MDMA on the serotonergic system of octopuses in the highly ranked journal Cell. The authors of this work showed that ecstasy, by interacting with the serotonin transporter protein SERT, turns sociopathic octopuses into friendly neighbors (Figure 4).
Briefly and simplistically about the mechanism of action of psychedelics
What happens to the brain when a person takes psychedelics?
The mechanism of action of psychedelics was well described by Professor Michael Pollan in an interview with Joe Rogan:
What happens to the brain when a person takes psychedelics?
The mechanism of action of psychedelics was well described by Professor Michael Pollan in an interview with Joe Rogan:
Indeed, as can be seen in scientific publications (Figures 5 and 6), the brain of a person who has taken psychedelics is literally transformed. Psychedelics, which alter serotonin signaling between brain neurons at the microlevel, change the connections between different areas of the brain at the global level. One such zone is the resting neural network (or default mode network), which appears to play a key role in the therapeutic effects of psychedelics.
The resting neural network is our internal storyteller. It is this area of the brain that is responsible for the very flow of thoughts during meditation, for the inner voice reasoning about what to make for dinner, or for our memories. We will define the operant resting neural network as the physical home of the "ego" in our brain. When using psychedelics, this network is almost completely shut down, which is a critical point of therapy. The silencing of the ego allows the patient to distance himself and look at the traumatic event or addiction from a "safe distance.
It is worth noting that a similar mechanism underlies the amazing insights associated with the use of psychedelics. Many have heard that James Watson and Francis Crick's use of psychedelics helped them understand the structure of DNA. Disconnecting the Operational Rest Network allows one to feel part of something bigger and to pay attention to the mundane patterns that are hidden from the washed-out gaze and consciousness drowned in the unresolved problems of the inner ego.
About psychedelic therapy
Now that we have tried to look at psychedelics from a scientific point of view, let's discuss why the famous American drug regulatory agency, the FDA, called psychedelics «Breakthrough Therapy», and allowed the use of MDMA in clinical trials as a treatment for post-traumatic stress disorder (PTSD). PTSD is an individual response to a traumatic event. Such an event is the death of a loved one, violence, participation in hostilities, hostage-taking, abuse of ideals, and more.
About psychedelic therapy
Now that we have tried to look at psychedelics from a scientific point of view, let's discuss why the famous American drug regulatory agency, the FDA, called psychedelics «Breakthrough Therapy», and allowed the use of MDMA in clinical trials as a treatment for post-traumatic stress disorder (PTSD). PTSD is an individual response to a traumatic event. Such an event is the death of a loved one, violence, participation in hostilities, hostage-taking, abuse of ideals, and more.
After having experienced violence in childhood, a person with PTSD can be observed by a psychologist for a long time. PTSD is accompanied by depression, avoidance of human society, constant mental experience of a tragic situation, increased anxiety, withdrawal, and a sense of numbness. The patient is unable to focus on the traumatic events in detail, often developing amnesia while continuing to have nightmares. In its severe form, PTSD leads to suicide. The person experiencing PTSD hesitates to go to specialists, because he or she believes that only a person with similar experiences can understand him or her. Existing therapy for PTSD is a comprehensive treatment of symptoms and co-occurring disorders. For example, if a patient develops depression, the physician prescribes continuous administration of antidepressants, often accompanied by the development of unpleasant side effects. And, after withdrawal of antidepressants, PTSD can return. In addition, some patients simply do not respond to traditional medication.
In contrast to classical antidepressants, the use of MDMA to treat PTSD has shown promising results in clinical trials. Patients were given 2-3 sessions, each of which lasted eight hours. Sessions were necessarily conducted in the presence of two physicians. Each session was accompanied by a one-week break, when the doctor consulted the patient by telephone if necessary. During the session, the therapists supported the patients by talking to them nonstop and allowing them to feel the presence of the other person nearby. Taking a small dose of MDMA does not induce a sense of euphoria, but allows the patient to relive the tragic event, focus on it, reflect, and as a result, accept the experience. There is evidence that after several sessions after 1-6 years, PTSD has not returned to patients' lives.
Of course, it must be understood that MDMA is not a magic bullet - like any therapy, psychedelics can cause a number of side effects, which tend to be corrected by changing the dose. There are also a number of limitations to the use of psychedelics, particularly the presence of a predisposition to develop psychosis in patients. This is why the prescription of psychedelics must be strictly monitored and accompanied by specialist supervision. In addition to treating post-traumatic stress disorder, psychedelics have proven effectiveness in treating depression and alcoholism, chronic anxiety and nicotine addiction.
In contrast to classical antidepressants, the use of MDMA to treat PTSD has shown promising results in clinical trials. Patients were given 2-3 sessions, each of which lasted eight hours. Sessions were necessarily conducted in the presence of two physicians. Each session was accompanied by a one-week break, when the doctor consulted the patient by telephone if necessary. During the session, the therapists supported the patients by talking to them nonstop and allowing them to feel the presence of the other person nearby. Taking a small dose of MDMA does not induce a sense of euphoria, but allows the patient to relive the tragic event, focus on it, reflect, and as a result, accept the experience. There is evidence that after several sessions after 1-6 years, PTSD has not returned to patients' lives.
Of course, it must be understood that MDMA is not a magic bullet - like any therapy, psychedelics can cause a number of side effects, which tend to be corrected by changing the dose. There are also a number of limitations to the use of psychedelics, particularly the presence of a predisposition to develop psychosis in patients. This is why the prescription of psychedelics must be strictly monitored and accompanied by specialist supervision. In addition to treating post-traumatic stress disorder, psychedelics have proven effectiveness in treating depression and alcoholism, chronic anxiety and nicotine addiction.
Perspective on psychedelic therapy
Once again, I want to point out that familiar things are not always what they seem, and stereotypical thinking greatly hinders the development of science. Research on psychedelics literally "stopped" for decades, during which time thousands of PTSD patients could have been cured. At this point, the scientific evidence for the effectiveness of psychedelics has not changed the opinion of the United Nations, and in 170 countries, psychedelics are still illegal substances, not even approved for medical use. This ambivalence between scientists and the UN has led to the fact that psychedelics are still the culture of the underground and "small labs. When it comes to psychedelics, in today's world the words "openness," "freedom," and "self-discovery" sound the same as "drugs" and "black market," and the topic of psychedelic use remains largely taboo.
I believe that psychedelics can be used for the good of humanity to treat people suffering from mental disorders, and I take the liberty of inspiring those who read this publication to follow the news of the Multidisciplinary Association for Psychedelic Studies (MAPS), which is fighting for legalization of psychedelic-associated therapy for patients with PTSD.
Once again, I want to point out that familiar things are not always what they seem, and stereotypical thinking greatly hinders the development of science. Research on psychedelics literally "stopped" for decades, during which time thousands of PTSD patients could have been cured. At this point, the scientific evidence for the effectiveness of psychedelics has not changed the opinion of the United Nations, and in 170 countries, psychedelics are still illegal substances, not even approved for medical use. This ambivalence between scientists and the UN has led to the fact that psychedelics are still the culture of the underground and "small labs. When it comes to psychedelics, in today's world the words "openness," "freedom," and "self-discovery" sound the same as "drugs" and "black market," and the topic of psychedelic use remains largely taboo.
I believe that psychedelics can be used for the good of humanity to treat people suffering from mental disorders, and I take the liberty of inspiring those who read this publication to follow the news of the Multidisciplinary Association for Psychedelic Studies (MAPS), which is fighting for legalization of psychedelic-associated therapy for patients with PTSD.
It is important for our guests to understand that "dirty" psychedelics in the form of drugs sold on the black market with admixtures of toxic chemicals and other drugs, as well as in conditions of uncontrolled use, are extremely dangerous. LSD, DMT, mescaline and psilocybin, like any other drugs, must be synthesized and tested under proper conditions, sold only in pharmacies and taken only in the presence of a qualified professional. Suffice it to recall the history of psychedelics: each of them was used in ancient rituals, which were always conducted under the guidance of an experienced shaman.