What most fear those who defend a non-working Luddit solution like “just say no ” is a world in which all traditional social values ​​will dissolve in a clash with individuals and populations obsessed with psychoactive substances and an endless search for self-satisfaction. We should not rule out this too real possibility. But one should reject the idea that such a worrisome, in general opinion, future can be avoided by witch-hunts, a ban on research and the hysterical spread of misinformation and lies.

Since time immemorial, psychoactive substances have been part of the galaxy culture. And only with the advent of technologies capable of purifying and concentrating the active components of plants and herbal preparations, these substances are separated from the common fabric of culture and become a kind of scourge instead.

In a sense, our problem is not a problem of psychoactive substances, but a problem of managing our technology. Are new synthetic substances, one hundred or even a thousand times more likely to cause addiction than heroin or crack, awaiting us in the future? The answer will be an absolute “yes” if we do not realize and do not investigate the inherent human need for chemical dependence, and then we will not find and approve any ways of expressing this need. We discover that human beings are creatures of chemical habits, with the same terrible distrust with which the Victorians discovered that people are creatures of sexual fantasy and obsession. This process of meeting with oneself as a species is a necessary precondition for creating a more humane social and natural order. Important to remember,that the adventure of such a meeting with oneself does not begin with Freud and Jung and does not end with them. The argument diligently developed in this book is that the next step in understanding ourselves can arise only when we take into account our innate and legitimate need to live in an atmosphere rich in mental states caused by our own will. I am confident that we can begin this process by revising our sources of origin. Indeed, I made great efforts to show that in the environment of Archaic, in which self-reflection first arose, we find the keys to the sources of our troubled history.when we take into account our innate and legitimate need to live in an atmosphere rich in mental states caused by our will. I am confident that we can begin this process by revising our sources of origin. Indeed, I made great efforts to show that in the environment of Archaic, in which self-reflection first arose, we find the keys to the sources of our troubled history.when we take into account our innate and legitimate need to live in an atmosphere rich in mental states caused by our will. I am confident that we can begin this process by revising our sources of origin. Indeed, I made great efforts to show that in the environment of Archaic, in which self-reflection first arose, we find the keys to the sources of our troubled history.


Hallucinogenic indoles, unexplored and prohibited by law, are presented here as agents of evolutionary change. These are biochemical agents, whose final impact is carried out not on the direct experience of the individual, but on the genetic constitution of the species. In the first chapters, attention was paid to the fact that improving visual acuity, improving the ability of reproduction and enhancing the stimulation of the protolinguistic functions of the brain are logical consequences of the inclusion of psilocybin in the food of an ancient person. If it were possible to prove the idea of ​​the emergence of human consciousness in connection with the mediated indoles synergy of neurodevelopment, then our image of ourselves, our attitude to nature, and the current dilemma regarding the consumption of psychoactive substances in society would change.

We cannot solve neither the “drug problem”, nor the problem of the destruction of the environment, nor the problem of stocks of nuclear weapons, until our image of ourselves as a species is again associated with the Earth. This case, in the first place, begins with an analysis of the unique combination of conditions that are necessary for the organization of the animal, in order to make a leap towards conscious self-reflection. When the main meaning of the hallucinogen-mediated symbiosis “man-plant” in the scenario of our origins is understood, we are able to understand our present state of neurosis. Learning the lessons contained in those long-standing and formative events can lay the foundation for making decisions not only about the need to control the consumption and abuse of substances in society, but also about our deep and growing need for a spiritual dimension of life.


Earlier in this blog, DMT was noted as a particularly interesting compound. What can be said about DMT experience and DMT in connection with our spiritual emptiness? Does he offer us any answers? Do the short-term tryptamines provide any analogy to the ecstasy of a partnership society before Eden became just a memory? And if they represent, what can be said about this?

Every time one thing impressed me in many of my breakthroughs into the world of hallucinogenic indoles, which, in general, remains unmentioned: the transformation of the ability to present and the language itself. The experience, exciting the whole being, slipping under the cover of ecstasy DMT, is felt as penetration through some kind of membrane. Mind and “I” literally unfold before our eyes. It feels as if it has been renewed, although it has not changed, as if it were made of gold and simply reforged into a new form in the crucible of its birth. The breathing is normal, the heartbeat is even, the mind is clear and observant. But what kind of world is this? What do feelings perceive?

Under the influence of DMT, the world becomes an Arab labyrinth, a palace, some more than possible Martian treasure, filled with motifs flooding the amazed mind with polysyllabic wordless delight. The color and sensation of the mystery that reveals reality literally permeates the whole experience. There is a feeling of other times, as well as their own childhood, miracle, miracle and miracle again. This is an audience with a stranger-nuncio. In the midst of this experience, obviously, at the end of human history, guard gates, which seem to open under the roaring whirlwind of an inexpressible interstellar void into Eternity.

Eternity, as Heraclitus remarked shrewdly, is a child playing with colored balls. “There are a lot of mini-entities – kids, self-transforming mechanical elves of hyperspace. Maybe these are children who are meant to be human to fathers? The impression of entering the ecology of souls hiding behind the portals of what we naively call death? I do not know. Perhaps they are the synesthetic embodiment of us as the Other or the Other as us? Or maybe elves lost to us with the extinction of the magical light of childhood? Here is a shock, which can hardly be expressed, an epiphany beyond our wildest dreams. Here is the kingdom of what is weirdest of all that we can to assume. Here the secret, alive, unscathed, is still as new to us as it was when our ancestors experienced it fifteen thousand years ago. Tryptamine essences offer the gift of a new language: they sing with pearl voices that are scattered with colored petals and spread in the air like hot metal to become toys and such gifts, which, probably, the gods gave to their children. The sensation of emotional connection is awesome and creepy. The revealed sacraments are real and, if one expresses in whole, they will not leave a stone unturned in that small world in which we have become so sick.

This is not some changeable world of UFOs caused by distant peaks; This is not the song of the sirens of the deceased Atlantis, sounding on the grounds of crazed America. DMT is not one of our irrational illusions. I am sure that what we perceive in the presence of DMT is genuine news. This is some kind of neighboring dimension, frightening, transformative, beyond the limits of our imagination and, nevertheless, accessible to ordinary research. We have to send fearless experts – whatever that implies – to research everything they find and make a report about it.

DMT, as mentioned earlier, is found as part of normal human neurometabolism and is the strongest of the naturally occurring indole hallucinogens. The extraordinary ease with which the DMT completely destroys all borders and transfers it to the inconceivable and irresistible dimension of the Other – this is literally one of the wonders of life itself. And the second is followed by this first miracle: the extraordinary ease and simplicity with which the system of enzymes of the human brain is recognized by DMT molecules in synapses. In just a few hundred seconds, these enzymes completely and without any harm deactivate DMT. The fact that normal levels of amines in the brain are restored so quickly after taking the strongest of all hallucinogenic indoles suggests that, perhaps,There was a long-standing joint evolutionary relationship between humans and hallucinogenic tryptamines.

Although psilocybin and psilocin, hallucinogenic indoles active in the fungus Stropharia cubensis related to cattle are not considered directly metabolized in DMT before they become active in the brain, nevertheless their pathway is more related to the neural pathway of DMT activity . And indeed, they can be active in the same synapses as DMT, although with a higher reactivity of the latter. The source of this difference is probably pharmacokinetic, that is, DMT can pass the blood-brain barrier more easily and, therefore, reach the site of activity in a shorter time. The affinity of these two compounds to the site of communication is approximately equal.

As mentioned earlier, the DMT study, especially in humans, was generally inadequate. When DMT was studied, it was administered by injection. This is the preferred procedure with the experimental substance, since you can know the exact dosage. However, in cases with DMT, this approach masked the unusual effect of “time reversal” that occurs when smoking DMT. Experiencing DMT with an intramuscular injection lasts about an hour. The peak of the experience, achieved when smoking, comes somewhere in a minute. In the Amazon, some tribes have a tradition of consuming DMT-containing plants. They consume the sap of Virola trees , related to nutmeg, or the ground and roasted seeds of the huge Anadenanthera peregrina. A commonly used method of activating indole is to inhale powdered plant material through the nose. This procedure is not done by yourself. The consumer has an assistant who blows the powder through a hollow, powder-filled reed, first into one, then into the other nostril. The apparent deliberation of this process leaves no doubt that the shamans of Amazonia learned what modern DMT researchers did not know, namely that the most effective way of consumption is adsorption through the nasal mucosa.


Perhaps you will protest: “But isn’t DMT prohibited by law?”

Yes, today DMT in the USA is on the list No 1. The list No 1 is a list of substances without any indications for medical use at all. Even cocaine does not apply here. Psilocybin and DMT have been added to this list without any scientific evidence providing evidence of the benefits or harms of their use. In the paranoid atmosphere of the late 60s, the mere fact that these substances cause hallucinations was sufficient reason to classify them so restrictive that it discouraged even medical research.

Faced with such a hysterical “I don’t want to know anything”, we would not hurt to recall that at one time the anatomy of corpses was also forbidden by the church and declared sorcery. Modern anatomy was created by medical students visiting the battlefields or stealing corpses from the gallows. For the sake of improving the knowledge of the human body, they ran the risk of arrest and imprisonment. Shouldn’t we be just as bold in trying to push the boundaries of the known and the possible?

The mood of dominion was always rejected by change, as if they felt the possibility of such a change that would once and for all deprive them of their power. In the phenomenon of indole hallucinogens, this presumptive fear has generated abundant fruit – downright fruit from the Tree of Knowledge. To taste of him is to become like gods, and this will obviously mean the decline of the style of dominion. Any revival of the Archaic will hope for this.


The softening of Western rationalism has gone very far, as anyone can easily see by reading some popular modern book on cosmology or quantum physics. Nevertheless, I also want to lightly throw a little heat through introducing the idea of ​​some connection between measurements, which is achieved most reliably and directly by using indole hallucinogens with their long history of human consumption and their joint evolution. Such compounds, obviously, act as regulators of culture change and can be a means of gaining access to the presumption of some very large self-regulating system. Perhaps this is the Supermind of our whole species or some kind of “mind of the planet”, or maybe we were too limited in our search for an inhuman mind, and some completely differentfundamentally different from us, a reasonable view shares with us our stay on Earth.

I offer these ideas in terms of speculative. I do not have solid personal knowledge as to what is happening here. I just think that I have a sufficient understanding of the customs, expectations, criteria of evidence and the “common knowledge” of human beings to be able to note that what happens when DMT is intoxicated is much more distinctive than anything that could be called “intoxication”. Under the influence of DMT, the mind finds itself in a convincingly real, clearly coexisting alien world. Not in the world, concerning our thoughts, hopes, fears, but rather in the world of kids – their joys, dreams, their poetry. Why? I have not the foggiest idea. These are just facts: this is how it happens to us.

Among the main schools of thought of the twentieth century, only Jung’s psychology sought to examine certain phenomena that are so important for shamanism. Alchemy, which Jung studied very thoroughly, was the heir to a long tradition of shamanic and magical methods, as well as more practical chemical procedures, such as metal working and embalming. The literature on alchemy shows that the vortex billowing contents of the alchemical vessel were fertile ground for projecting the contents of the naive pre-scientific mind. Jung insisted that alchemical allegories and emblems were the product of the unconscious and can be analyzed in exactly the same way as dreams.From the point of view of Jung, the discovery of the same motives in the fantastic speculations of the alchemists and in the dreams of his patients was a strong support for his theory of the collective unconscious and the universal general archetypes of the latter.

During his study of alchemy, Jung was confronted with reports of Kabiri – similar to the elves of alchemical children, whose appearance or tangible presence is an integral part of the last stages of the alchemical creation. These alchemical children are like those little helpers who are called upon by a shaman. Jung viewed them as certain autonomous sides of the psyche that temporarily got out of control of the ego. Unfortunately, the explanation that these alchemical geniuses are “autonomous aspects of the psyche” is not an explanation at all. It is like describing an elf as a small non-physical entity of indeterminate origin. Such explanations only postpone the need to get in touch with the deeper nature of the experience itself.

Science was not useful in the case of elusive human contacts with other kinds of mind. She prefers to direct her attention somewhere else, noting that subjective perceptions, although unusual, are not her area. What a pity, because subjective experience is all that any of us have. In any case, the largely subjective nature of the so-called objective universe is now confirmed by the most objective science — physics. In the new physics, the subjective observer is inextricably linked with the observed phenomena. Interesting, but this is a return to the shamanic point of view. The true intellectual legacy of quantum physics may be the new respect and priority that it attaches to subjectivity. Turning us to subjectivity means imparting tremendous new power to the language, since language is that material,from which the subjective world is made.

Thanks to psychedelics, we learn that God is not an idea, God is a lost continent in the mind of man. This continent was reopened during a time of great danger to us and our world. What is it? Coincidence, synchronicity, or cruelly meaningless neighborhood of hope and doom? A few years ago, I turned the work of my life to an understanding of the mystery of the experience caused by tryptamine hallucinogens. In the end, this mystery is not one that can be explained by science. I, of course, understand that a person spreads his obsessive ideas, trying to fill the whole space. But in the critical events accompanying the emergence of cattle breeding and the language of human beings, I found an ancient echo of those moments that I felt and witnessed personally.

Today it is necessary to stand face to face with the desired and found answer. In front of us, a measurement is flickering, so huge that its contours can hardly be accommodated in the focus of the human coordinate system. Our animal existence, our planetary existence ends. In geological time, this end is just in a few moments. The great dying, the great extinction of many species has occurred at least since the climax of the partnership in prehistoric Africa. Our future is in the mind; the only hope for the survival of our weary planet is that we will find ourselves in our mind and make a friend of it who can reunite us with the Earth again, at the same time taking us to the stars. The change, which is more radical in significance than all the former, immediately looms ahead.Shamans preserved the gnosis of the availability of the Other for millennia; today is planetary knowledge. The consequences of this situation are just beginning to manifest.

Naturally, I do not expect my words to be taken seriously. However, these conclusions are based on the experience available to anyone who only takes the time to explore DMT. The experience itself lasts less than fifteen minutes. I do not foresee criticism from people who did not bother to conduct this simple and unconditional experiment. After all, how seriously can critics deal with a problem if they are not inclined to devote a few minutes of their time to experience this phenomenon for themselves?

Deep psychedelic experience does not just offer the possibility of living in the world of sensible people, in harmony with the Earth and with each other. He also promises an excellent adventure, a meeting with something completely unexpected – with some other neighboring world filled with life and beauty. Do not ask where he is; at the moment we can only say – not here, not there. We are still obliged to recognize our own ignorance about the nature of the mind and about exactly what the world has to be and what it is. For several millennia, and even more, our dream was to understand these issues, and we were defeated. Yes, defeat, if we don’t think of another possibility – the possibility of a “completely different”.

Some lost souls scan the heavens in search of a friendly “flying saucer” that will penetrate the earthly sphere and take us to Paradise; others offer to seek salvation at the feet of various rishis, roshi, geisha, and gurus. It would be better for researchers to look into the work of the botanists, anthropologists, and chemists who located, identified and characterized the shamans’ hallucinogens. Thanks to them, we got our hands on a tool to save the souls of men. This is a great tool, but it is a tool that should be used. All our addictions over the centuries — from sugar to cocaine and television — have been a tireless search for something taken from us on Paradise. The answer was found. Search for nothing more. He found.


Using plants of the type described above will help us understand the valuable gift of partnership with plants that was lost at the dawn of time. Many people are eager to get acquainted with the facts concerning their true identity. Plant hallucinogens are clearly directed to this essential identity. Not to know your true identity means to be some kind of insane deluded thing, a golem. And, undoubtedly, this image, painfully Orwellian, is applicable to the mass of human beings, now living in societies of highly developed industrial democracy. Their authenticity lies in the ability to obey and follow the changes in mass style that are transmitted by the media. Engaged in the use of narcotics, absurd communications and the policy of disguised fascism,they are doomed to a poisoned life at a low level of consciousness. Put to sleep by the daily TV program, they are the living dead, lost for all but the act of consumption.

I believe that the failure of our civilization to resolve issues related to the problem of psychoactive substances and habitual destructive behavior is an unlucky legacy for all of us. But if we had sufficiently restructured the image of ourselves and the image of the world, we could make of pharmacology a means of giving us the most ambitious hopes and dreams. Instead, pharmacology has become a devilish maid of rampant rolling toward regulativeness and the destruction of civil liberties.

Most people have a predilection for certain substances and, more importantly, they all have a predilection for certain standards of behavior. Attempting to see the difference between habits and addictions threatens the indissoluble merging of mental and physical energies that shape the behavior of each of us. People who are not involved in the relationship of food stimulation or stimulation of psychoactive substances are rare, and by their adherence to dogma and the intentional narrowing of their horizon, it can be judged that they failed to create some viable alternative to substance involvement.

Here I tried to explore our biological history and our more modern cultural history in search of something that could be missed. My theme was human agreements with plants, created and torn over thousands of years. These relationships shaped every aspect of our identity as self-reflecting beings — our language, our cultural values, our sexual behavior, what we remember and what we forget in our past. Plants are a lost link in search of an understanding of the human mind and its place in nature.


In the United States, the zeal of the federal government, which looks like a desire to eradicate drugs, is directly related to the extent to which the government is co-opted by the values ​​of fundamentalist Christianity. We harbor the illusion of a constitutional separation of church and state in the United States. But in fact, the federal government, by encouraging the prohibition of alcohol during the period of prohibitions, interfering with the rights to freedom of childbearing or consumption of peyote in America’s Aboriginal religious rituals, foolishly trying to regulate the consumption of food and certain substances, acts as a pressure lever in favor of the values ​​of the right wing fundamentalists .

In the end, the right to determine for oneself food and the preferences of certain psychoactive substances will be considered as a natural consequence of human dignity as long as it is done in such a way that it does not restrict the rights of others. The signing of the Magna Carta Charter, the abolition of slavery, the granting of voting rights to women – these are cases in which the evolving definition of what constitutes justice has been swept away by ossified social structures that have increasingly begun to rely on the “fundamentalist” reading of their first principles. The war on drugs is schizophrenic carried out by governments that consider trafficking to be reprehensible, while they themselves are nevertheless the main guarantors and patrons of the international drug business. Such an approach is doomed to failure.

The war on drugs was not meant to be victorious. On the contrary, it will continue as long as possible to allow various intelligence agencies to conduct their operations and squeeze out the remaining hundreds of millions of dollars in illegal profits from a planetary sale of narcotic substances, and then it will be declared defeat. And “defeat” will mean, as in the case of the Vietnam War, that the media faithfully portray the situation and name its real participants and that the public’s aversion to crime, stupidity and venality of the establishment will force them to reconsider the policy. In this cynical manipulation of people and entire nations in connection with drugs and stimulants, modern governments have tied themselves up with an ethical catastrophe,comparable with the revival of the slave trade in the XVIII century or with the recently rejected provisions of Marxism-Leninism.


The conclusion seems obvious: only legalization can lay the foundation for a sound policy on psychoactive substances. In fact, even the most disinterested commentators on this issue came to this opinion, although the political consequences of upholding legalization only contributed to slowing down its discussion. In his latest book The Great War on Drugs, Arnold Trebach formulated convincing arguments for a revolution in substance-related politics.

Another guiding model for dealing with the abuse of relevant substances can be found in how America historically dealt with different conflicting religions; in fact, they are all accepted as a suitable moral choice, which should be available to those who believe in it. The problem of psychoactive substances should be approached in the same way – more like religion than science. I would like law and medicine to recognize the personal, unscientific nature of the sphere of substance abuse, the introduction of some form of First Amendment of the guarantee of freedom to choose a personal doctrine of adherence to certain substances, but somewhat limited by reasonable medical principles. / Arnold S. Trebach. The Great Drug War (New York: Macmillan. 1987), p. 363 /

What he doesn’t discuss, he doesn’t even mention at all, these are the roles that hallucinogens will play in the public scenario after the period of their suppression. In fact, psychedelics seem to be insignificant, if only a measure of the social impact of substances is estimated in the millions of dollars from street sales. Only LSD continues to sometimes distinguish among psychedelics as a possible large-scale problem. However, estimates of the amount of psychedelics produced and consumed in the United States have been politicized, and therefore unreliable and meaningless.

But another measure of the social significance of substances shows that we neglect, at first, at least, the discussion of the social impact of psychedelic consumption when we consider the issue of legalization of psychoactive substances. The key to this other measure lies in the interest shown to the psychedelics of the CIA and military intelligence in the 60s in projects such as MK (“brain control” – mind control) and MK — ULTRA. The widespread belief that the conclusion of these studies was that television is the drug of choice for mass hypnosis, although reasonable, but it should not be taken at face value. I am sure that if psychoactive substances were legalized, fears of a cocaine epidemic or a general addiction to heroin would have been unfounded. I am also convinced that the interest in psychedelics would increase,and their consumption would increase, and that this possibility is of great importance for the ruling circles. This new interest in psychedelics should be foreseen and foreseen. If the use of psychedelics makes it easier to understand the social attitudes and assumptions of the original cultures of the partnership style, then ultimately the public nurturing institutions may wish to support this awareness.

It seems that some new planetary consensus is being built. What was previously in its infancy and unconsciously, now becomes conscious and at the same time logically built. The collapse of the Marxist alternative to a democratic consumer society for compact media and high technology was quick and complete. For the first time in the entire history of the planet, there is some definite, albeit dimly definable consensus regarding “democratic values”. This trend will meet the real resistance of various forms of monotheistic religious fundamentalism in the 90s. All this is a phenomenon of expanded consciousness caused by an information explosion. Democracy is an expression of the Archaic idea of ​​an equal group of nomads. In its purest terms, she is psychedelic through and through, and her triumph seems ultimately unmistakable.

The “Drug Problem” acts against the tendency of a planetary expansion of consciousness through the spread of democratic values. There is no doubt that a society that intends to control the consumption of psychoactive substances by its citizens is heading for the slippery slope of totalitarianism. No arbitrariness by the police, no supervision or interference in people’s lives will be enough to influence the “drug problem”. Therefore, there will be no limit to repressions that frightened public institutions and their brainwashing specialists can cause.

Humble offer

A policy of respect for democratic values ​​in the matter of psychoactive substances would be to educate people so that they could make an intelligent choice based on their own needs and ideals. This kind of simple prescription is necessary and, unfortunately, already late. A general plan for those who are seriously seeking to come to terms with the American drug problem might contain several choice points, including those listed below.

1. A 200% federal tax on tobacco and alcohol should be introduced. All government tobacco subsidies need to be stopped. More serious warnings should be printed on the packages. Twenty percent of the federal sales tax must be levied on sugar and its substitutes; it is necessary to stop all support for sugar production. On sugar packs, there should also be cautions, and sugar should be a mandatory topic in the school education program.

2. It is necessary to legalize all types of cannabis and introduce a 200% federal tax on the sale of hemp products. Information on the content of “THC” products (tetrahydrocannabiol) and current information on its effect on health should be printed on the package.

3. The lending activities of the International Monetary Fund and the World Bank should be closed in countries that produce hard drugs. Only an international inspection and a certificate stating that the country is not engaged in such activities will restore the right to receive a loan.

4. Strict control should be established, both for manufacturers and for owners of weapons. It was the wide availability of firearms that led to the close intertwining of the problems of violent crime and drug abuse.

5. The legality of nature, and therefore the legality of all plants for their cultivation and use, must be recognized.

6. Psychedelic therapy should be made legal and included in the existing insurance system.

7. It is necessary to strengthen the legislation on currency and banking operations. Today, a secret agreement between banks and criminal cartels allows for large-scale money laundering.

8. There is a direct need for serious support for research related to all aspects of substance use and abuse, as well as for serious public education.

9. One year after the implementation of the above, it is necessary to legalize psychoactive substances that are still considered illegal in the United States. The mediation is eliminated, the government can sell the substances at their price plus 200%, and this money can be placed in a special fund to pay the social, medical and educational costs of the legalization program. Money from taxation on alcohol, tobacco, sugar and hemp can also be placed in this fund.

10. At the end of this year, all drug offenders who did not use firearms and did not display criminal acts should also be pardoned.

If these proposals seem too radical, it is only because we have moved far from the ideals that were originally the most American. The basis of the American theory of social policy is the notion that the right to “life, liberty, and the search for happiness” belongs to our undivided rights. To declare that the right to seek happiness does not include the right to experiment with psychoactive plants and substances is to put forward an argument, narrow at best, at worst, ignorant and primitive. The only religions that are more than the traditionally sanctioned moral code are the religions of trance, dance ecstasy, and intoxication with hallucinogens. This is a living fact of the secret of being, and an inherent religious right is the opportunity to approach it in our own way.A civilized society will make this principle a law.

The interaction of different drugs

Posted on July 13, 2019  in Pain

In order to somewhat simplify the presentation, cases were considered with the use of only one drug. Pharmacology also studies the effects of taking two or more psychoactive substances. Several drugs may be taken at the same time, or some next drug may be taken before the previous one is removed from the body.
Taking two or more drugs at once complicates the nature of the end result, since several drugs can interact with each other while being administered into the body. An interaction occurs when the action of one drug affects the action of another. Such interaction can be considered qualitatively and quantitatively. In pharmacology, the quantitative aspect is much better studied, that is, the strength of action of substances. In this sense, there are two types of interaction: the reinforcing effect of drugs and reducing it.
Combinations that enhance the effect. The term “synergism” is used to denote the interaction between drugs, which enhances their effect. If two specific drugs are synergistic, then the effect of their joint use will be greater than the sum of the effects of their separate use. In practice, it is difficult to determine whether certain drugs are synergistic, that is, whether the final effect is the simple result of adding the effects of two substances, or whether the drugs somehow reinforce each other.

In quantitative studies, drug interactions are presented as changes in the line of action of the dose. The case of synergism between the two drugs A and B is presented in Figure 4-7. The solid line is a typical dose response curve for a drug, which was analyzed in Figure 4-2. Drug synergism shifts this curve to the left (dashed line in the figure). It can be seen that if there is a drug B, drug A has a stronger effect.
Combinations that reduce the effect. The weakening of the effect of one drug in the presence of another in the body is indicated by the term “antagonism”. It is easy to guess that in case of antagonism of two drugs, the line of action of the dose in Figure 4-7 will move to the right. For example, amphetamines that stimulate the nervous system, are antagonists of alcohol and reduce its depressive effects. However, they do not interfere with alcohol to impair coordination of movements.

Importance of drug interaction. Knowledge of the nature of the interaction of substances is very important in medicine, since many drugs can be used in combination with others for more effective treatment of diseases. Thus, this interaction plays into the hands of medicine. On the other hand, it can create doctors and problems. Difficulties usually arise in the case when the doctor, prescribing the patient the medicine, does not know what other medicines he takes. One substance may negate the therapeutic effects of another. Moreover, the combination of certain drugs can have unhealthy or even deadly effects.
The interaction of substances in the body creates problems with the combination of drugs taken for treatment and other drugs. The most common situations of this kind are the mixing of substances that suppress the nervous system (depressants). For example, the simultaneous intake of alcohol and barbiturates can be fatal, since these substances enhance the sleeping effect of each other. This combination is often used for suicide, but sometimes death occurs as a result of careless mixing of these substances.

Drug interactions significantly affect the causes and nature of their use. People can deliberately mix drugs with the same or similar effect to get a “super effect”. It happens, on the contrary, used drugs with opposite effects to weaken the action of one of them. In rehabilitation centers, you can often meet people who have used alcohol with its depressive effects to overcome excessive stimulation caused by cocaine. Often they drink a lot of black coffee after drinking. Caffeine is an antagonist of alcohol, and it partly relieves the depressive effect of the latter on the central nervous system. These examples show actions related to the quantitative effect of drugs: people try to change the power of their actions. By mixing drugs, one can also achieve qualitative interaction between them. So,if a person takes a depressant (say, some of the benzodiazepines) along with LSD, then as a result he will experience complete peace of mind combined with a change in perception that will cause LSD.


Effective and lethal doses

These are the last two terms that are introduced here to describe the effects of drugs. They arose from the fact that individual reactions to the same dose of the drug are very diverse. As a result, to determine the effect produced by a given dose, it is not enough to examine one person. The effect is often described in comparative terms or in a quantitative ratio of people who have this effect at a certain dose.
Figure 4-6 shows the dose lines of action for two effects. The difference of this graph from the previous ones is that on the vertical axis is not the magnitude of the effect of the drug, but the percentage of people who have this effect. This change is made to better illustrate effective and lethal doses. These terms clearly define the effect. We consider the change in the percentage of people experiencing this effect, with an increase in the dose of the drug.

The effective dose (ED) is the percentage of people who have the desired effect at a given dose. This can also be expressed as the dose at which a given number of people have an effect of interest to us. To find the ED on our graph, you need to draw a line from a certain percentage of people to the dose curve and then lower the other line to the horizontal axis. The point of intersection will give us an ED for a given percentage of people. Figure 4-6 shows the standard pharmacological term ED 50, in this case for the sedative effect of a certain drug. ED 50 means that 50% of people who have received a given dose of a drug will be sleepy. Similarly, you can define an ED for any other percentage. Figure 4-6 shows two more such effective doses.

Lethal dose (LD) is a specific case of an effective dose. As the name implies, the effect of interest in this case is death, and thus, LD represents the percentage of animals (people in experiments with lethal doses, of course, are not used) who die from a given dose of a drug over time. Pharmacological standard and here 50%. LD 50 is the dose at which 50% of the animals that received it die during a given time. The dose of LD 50 for humans is determined by extrapolating data obtained from animals. In Figure 4-6, the LD 50 of our imaginary drug is presented on the right line.
Knowledge of these two doses is very important. For example, medical institutions need to know what the discrepancy is between the ED and LD of a given substance. If the discrepancy is small, then the risk of unintentional suicides of people who use these substances not in therapeutic purposes. For some drugs, say caffeine and marijuana, the difference between ED and LD is large. But other drugs pose big problems. Occasional death from a heart attack while taking cocaine. Another example is alcohol. If a person weighing 70 kg and has an average tolerance for alcohol, drink 100 grams per hour on an empty stomach, he will feel relaxed. LD 50 for such a person will be 0.75 liters of whiskey per hour. Such doses are used much more often than you can imagine, and lead to severe poisoning and death. Moreover, if you mix drugs (say, alcohol and barbiturates), then the total ED and LD get very close together and the risk of death increases.

And the last note: the divergence of these doses is always taken into account when prescribing drugs for medical purposes. Doctors are looking for substances, a certain dose of which would produce the desired therapeutic effect (that is, was an effective dose) for all patients, did not give side effects and thus was not fatal. The therapeutic index is displayed: this is the LD 50 / ED 50 ratio for the drug. The most common ED is to relieve the symptoms of any illness or poisoning. You see, the higher the therapeutic index of a substance, the bolder it can be used in medicine. As a rule, the steeper the slope of the dose line, the lower the therapeutic index of the substance. Knowing the therapeutic index of the drug, the doctor can easily determine whether to prescribe it in this case.