Mechanisms of action of LSD-like substances

Mechanisms of action of LSD-like substances

The mechanisms of action by which LSD and similar substances are capable of producing such impressive effects as visual hallucinations and changes in consciousness in such small doses remain mysterious, but more and more scientists agree that an important role in this process is played by changes in the activity of brain systems associated with serotonin. The first part of this evidence arose from the analysis of the chemical structure of the main hallucinogens. LSD, psilocybin, harmalin are classified according to their chemical structure as indolalkylamines. The same chemical structure has a natural substance serotonin.

The proximity of the chemical structure prompted the assumption that LSD and others like it can imitate serotonin and therefore activate the serotonin receptors of the brain. Currently, this hypothesis has received significant support. For example, it has been proven that LSD and other hallucinogens envelop serotonin receptors and that the force with which this occurs is strictly dependent on the power of the hallucinogen.

One of the problems associated with the above hypothesis is mescaline. The chemical structure of mescaline is very different from all other hallucinogens. By chemical nature, it is more like amphetamines than LSD. For this reason, it was thought that its mechanism of action was different from LSD. However, unlike amphetamines (as well as methyl amphetamines such as MDA), mescaline has a pronounced hallucinogenic effect, virtually identical to LSD. Another evidence in favor of a common mechanism of action for LSD and mescalin appeared in the study of tolerance. Tolerance to all effects of LSD develops very quickly. The same applies to mescaline. In addition, there is cross-tolerance between LSD, mescaline, and other drugs of this group. And, finally, recent data suggest that mescaline (or perhaps one of the mescaline metabolites) also envelop serotonin receptors.

As noted in Chapter 3, serotonin is everywhere in the brain. That is why the effects of LSD-like hallucinogens are so diverse. Serotonin is believed to play an important role in changing mood, which is the reason for the powerful emotional impact of these drugs. However, it is not known which parts of the brain are responsible for the hallucinogenic effect of these drugs.

Pharmacokinetics of LSD-like substances

Pharmacokinetics of LSD-like substances

As noted above, since all the hallucinogens act on serotonin receptors, their effects are very similar. However, these drugs vary greatly in their effectiveness, duration of action, and other pharmacological parameters. The most powerful drug of this class is LSD. For the manifestation of its action enough 25 mg.

The drug sold on the street, packaged in the range of 75-250 mg is either paper soaked with a small amount of LSD solution (“mark”, “napkin”), or gel, or a pill. LSD is quickly absorbed and a noticeable effect occurs within 20-60 minutes after ingestion. The drug is quickly spread throughout the body and, overcoming the blood-brain barrier, enters the brain. The action of LSD lasts from 8 to 12 hours, it is quickly processed and removed from the body. Even with the most powerful equipment, traces of LSD or its metabolites can be detected no later than 72 hours after ingestion. Although the hallucinogens found in the seeds of the bindweed (ergin and isoergin) are completely identical to LSD, their action is much weaker – about 5-10% of the strength of the LSD action.

Psilocybin is usually taken orally: either by eating mushrooms, or in the form of a drink made from the same mushrooms. It is very difficult to determine the dose of this substance, because different types of mushrooms contain different amounts of psilocybin. Usually, 5-10 g of mushrooms containing from 10 to 20 mg of psilocybin are consumed. Thus, the effectiveness of psilocybin is about 1% of the effectiveness of LSD. Duration of action is approximately 4 to 6 hours. Just like all other serotonergic hallucinogens, psilocybin develops tolerance and exhibits cross-tolerance to all members of this group. Mescaline is usually taken in the form of peyote “pads”, as described above. As a rule, from 5 to 20 of these “pads” are eaten, containing about 200-800 mg of mescaline. Mescaline is about 3000 times weaker than LSD, its minimum effective dose is 200 mg. Duration of action from 8 to 12 hours.

Much less is known about other serotonergic hallucinogens, but most of them resemble those described above. The exception is dimethyltryptamine (DMT), which is contained in the bark of the tree Virola and is used in the form of powder or smoked. Its action occurs within a few minutes, but it lasts only about 30 minutes.

Psychotherapeutic use

Psychotherapeutic use

Historically, it was assumed that LSD and others like it should have two uses in psychotherapy, but at present they are not used for these purposes. First, since it was believed that LSD mimics psychosis, by taking LSD, the psychotherapist could learn more about the patient’s subjective sensations. Indeed, hallucinations, unusual sensations, a breakdown in communication with reality are also characteristic of people with schizophrenia and those who receive hallucinogens. But there are cardinal differences.

Hallucinogens usually cause visual hallucinations, while schizophrenia is characterized by hearing. Thus, the subjective sensations of a person suffering from psychosis and using a hallucinogen are not identical. However, the fact that LSD-like compounds can mimic psychosis can be confirmed by the fact that chlorpromazine and other antipsychotics used in the treatment of schizophrenia effectively eliminate the effects of LSD. Thus, hallucinogens can help to better understand the biochemistry of mental disorders.

Secondly, hallucinogens were supposed to be used as an addition to psychotherapy. The idea was that the psychotherapist could find out the most essential thing about the patient if he was taking LSD, moreover, it helped the patient himself to better understand himself, since hallucinogens reduced the resistance of the ego. Many extravagant statements have been made regarding the beneficial effects of LSD on the treatment of mental illness, but gradually the use of LSD in psychotherapy has been markedly reduced. One of the reasons for this was the political environment, the other is that many psychotherapists thought the potential risk of LSD outweighed its benefits. Indeed, it has not been scientifically proven that, as an adjunct to psychotherapy, LSD is more effective than harmless medication prescribed to calm the patient. Some psychotherapists believe that these compounds deserve to be re-evaluated as possible psychotherapeutic agents, but now attention has shifted to the compounds of the MDA group and MDMA.

Effects of serotonergic hallucinogens

Effects of serotonergic hallucinogens

The effects of LSD and the like on the body are similar to amphetamines and cocaine. This is due to the fact that they are sympathomimetic. They cause pupil dilation, increase the pulse and blood pressure, body temperature, cause increased sweating.
It is more difficult to characterize their effect on the psyche. Individual responses to LSD vary greatly. However, common to all serotonergic hallucinogens is a violation of visual perception, although there is some constancy in the types of visual changes. Many of these have been listed in Albert Hofmann’s first use LSD report. Hofmann wrote:

“Kaleidoscopic fantastic images flooded over me, they changed, shimmered in different colors, turned into moving spirals and circles, exploded in color fountains, moved and intermingled with each other in constant motion. Each acoustic perception, such as the sound of a closed door or the noise of a passing car was transformed into a visual one. Each sound produced a very mobile visual image having a form and color. “

The spiral explosions and vortex-like images described by Hofmann are the most typical hallucinations. They are called constant forms because they were observed very often. Another constant form is lattice images resembling a chessboard that appear on a smooth surface. The transformation of sound signals into visuals described by Hofmann is called synesthesia; this is also a frequently mentioned phenomenon. Other visual effects are flashes of light, enhancing the brightness or intensity of color, framing various objects with tails and curls, a sense of movement of stationary objects (when it seems that the wall is breathing or the flowers start to move, grow, wallpaper).

However, trips are more than just a light show. Other perceptions are changing. The mood becomes extremely unstable, the cognitive processes change in a very strange way. Despite the fact that the descriptions of experienced sensations are very different from each other, they still show some similarities. All of them are united by the presence of a very strong affect, although the nature of the emotional state is different. They all include “magical” thinking, and, especially in the last two examples, events are filled with cosmic meaning. If the visions are frightening, then the person can behave like a mental patient, usually referred to as a bad trip. Intuitions, concepts, insights, coming during the trip, seem to be very significant, and later turn out to be banal or false. For example, a person, under the influence of a drug, often thinks that he has telepathic or prophetic abilities, but when checked it turns out that they are absent. Nevertheless, thanks to this, it is easy to understand why in cultures with undeveloped science, hallucinogens were given mystical and religious significance.

Side Effects of Serotonergic Hallucinogens

Side Effects of Serotonergic Hallucinogens

The most important part of the discussion about LSD concerned the adverse effects of its use. The main danger lies in the fact that, apparently, LSD causes chromosomal abnormalities. Therefore, men or women who use this drug are at risk of having inferior children. This finding is based on the discovery that LSD disrupts chromosomes in leukocytes that are artificially cultured in a laboratory. Based on this, there is a fear that LSD can damage human gametes. Although the fact that chromosomes are disturbed in leukocytes in a laboratory test tube under the influence of high doses of LSD does not prove that the same should occur in natural conditions. In the course of a serious study of this issue did not appear convincing evidence that LSD (as well as any other serotonergic hallucinogen) increases the number of descendants with congenital disorders, if taken in moderate doses. Although some risks are still possible when taking high doses, the ability of LSD to cause hereditary disorders is no stronger than that of aspirin under normal circumstances. However, as with other substances, there is a risk of damage to the fetus if the drug is taken during pregnancy.

Other adverse effects of LSD deserve a closer look. An important problem is acute panic or paranoid drug-induced reactions. These bad trips leave a person in a state of acute mental disorder in which he can hurt himself or others. It is difficult to establish the frequency of bad trips, but there were enough of them to be in the 60s. there was an extensive network of accessible crisis centers, where LSD victims could receive psychological help and, if necessary, referral to a hospital. Currently, bad trips are becoming less common, because it is better known how to prevent them. The psychological state of the drug user and his environment is important. For example, there was a case of suicide of a person who took LSD during one experiment conducted by the CIA in the 50s, but did not know about it. Being under the influence of a drug without prior knowledge of its capabilities is very dangerous, there can be disastrous consequences. A quiet, calm environment, low doses of LSD reduce the likelihood of bad trips, although they can occur under the most favorable circumstances.

Another problem that is associated with hallucinogens, similar to LSD, is the phenomenon of the “return of the past.” It consists in a sudden, unexpected re-experience of fragments from hallucinogenic trips that occurred weeks, months, years before that moment. Although, as in the case of bad trips, it is difficult to establish the frequency of this phenomenon, according to one study, 53.5% of those who use LSD experienced a “return to the past” syndrome. Although the majority do not consider them particularly destructive, but 12.9% of those who have experienced this, sought medical help. Although little is known about the causes of their occurrence, they are triggered by anxiety, fatigue, the consumption of marijuana, or sudden changes in the environment, such as at nightfall.

LSD also causes long-term mental disorders. Perhaps the most famous and terrifying example of this is Charles Manson and his “family.” In the “family” of Manson, LSD was used in large doses, but it is not known exactly what role, if any, this use played in their psychopathology, which led to mass murder. When you meet with an insane person taking LSD, it is difficult to establish whether a mental disorder has occurred as a result of taking LSD, or if this person has already been ill, and LSD has more acutely manifested these symptoms. The matter is further complicated by the fact that LSD users have previously dealt with many other drugs and it is not known what role those in turn played. It is believed that hallucinogens can aggravate or exacerbate psychosis or emotional disturbances in some sensitive individuals. LSD also causes other adverse effects. For example, there are few but alarming cases of persistent visual disturbances caused by LSD. LSD also causes long-lasting or permanent changes in the biochemistry of the brain and affects the behavior of animals in the laboratory. Thus, although LSD is not addictive, it is a potentially dangerous drug.

Subjective descriptions of the effects of LSD

Subjective descriptions of the effects of LSD

Many attempts have been made to describe the LSD experience. These descriptions are different from each other, often confusing, sometimes contradictory, although there are some common features. The following excerpts, written by the most well-known supporters of LSD, demonstrate the diversity of this experience:

I looked into a glass of water. In the depths of his whirlpool there was a whirlwind that went down to the center of the world and to the heart of time … The dog barked and its piercing howl could be like all the wolves of Tartarus … At one point I was a giant in a tiny closet, and in another dwarf in a huge hall. I was lying on my back on the floor. Then my room disappeared and I was sinking, sinking and sinking. From afar, I heard the subtle word death. I began to sink faster, moving away millions of light years from Earth. The word grew louder and more insistent, surrounding me, including me. “DEATH … DEATH … DEATH …” I remembered the horror in my father’s eyes in his last moments. In the last moments before my own death, I shouted “no.” Absolute all-consuming horror. A series of visions began. A number of images appeared in sync with the music … I saw myself at the Mongol Khan’s court … at a concert that was held in front of a huge audience … in a fantastic place … at Versailles … near the Lincoln statue … I felt swallowed by the chaotic sea …

There were several boats worn by an agitated sea … I was on one of these ships … we sailed past a huge figure, standing in foamy water to the waist … His features were full of compassion of love and participation. We knew that it was the image of God. We realized that God was also captured by the storm.

Anticholinergic hallucinogens

Anticholinergic hallucinogens

Atropine and scopolamine are acetylcholine receptor blocking agents in the brain. Although in low doses they are used for medical purposes, in high doses they have a hallucinogenic effect. They can be found in many plants growing throughout the world, they have a long history of use. A few – centuries BC plants containing scopolamine were used by the ancient Greeks in the process of divination in Delphi. In the Middle Ages, healers cooked their drugs from them. Such plants as belladonna, mandragora, henbane, growing in Europe, as well as representatives of the genus Datura, growing in America, are eaten because of their hallucinogenic properties. Although now these substances are not consumed by healers, they apparently continue to form part of the powder that makes man zombies in Haiti.

Anticholinergic hallucinogens have a multifaceted effect on the body, causing dry mouth, loss of clarity of vision, motor control, increase pulse and body temperature. They can cause death, causing respiratory depression at doses slightly higher than the minimum effective. Psychologically, they can cause a hypnotic trance or stupor. The recipients of these substances seem to be delirious, unconscious, but they are able to describe their feelings if they are asked about it. A distinctive feature of drugs of this class is that after taking them, a person remembers almost nothing, he is not able to recall a single detail in his memory. Perhaps this is one of the reasons that these substances are almost not sold on the street.

Another plant worthy of consideration in this part is the red mushroom. The red fly agaric contains several different chemical compounds with a hallucinogenic effect, one of which is muscarin, which is a cholinergic agonist, and muscimol, a hallucinogen similar to LSD-like drugs. Although it is rarely used now, since it is nothing special, it is the first attempts to use hallucinogens that are associated with it. The red fly agaric is widespread in Europe and Asia, and it is possible that the mysterious drink “Soma”, described in the Indian “Rigveda” more than 2 thousand years ago, was made from it. “Rig Veda” describes a rather extravagant way of resuming the action of this substance by pouring out the urine of a poisoned person. Mustsimol is the only hallucinogen, whose properties do not change when passing through the body and are stored in the urine. Eating red amanita usually causes numbness, lasting several hours, during which a person is visited by visions, and then comes euphoria, a surge of energy, accompanied by visual hallucinations.

Methyl Amphetamines

Methyl Amphetamines

Recently, much attention has been paid to drugs of this group, in particular MDMA, better known as Ecstasy. MDMA belongs to a group of substances known as methyl amphetamines, so named because of their chemical structure (there are many drugs in this category, but the most famous are presented in table 11-2). These drugs are often combined with serotonin hallucinogens. Indeed, their chemical structure resembles that of mescaline. In addition, they affect the transmission of serotonin (as well as norepinephrine and dopamine). DOM resembles mescalin in chemical nature and causes similar effects, including visual hallucinations. However, others (MDA, MDMA, DOET) differ from the serotonergic hallucinogens discussed above in that they do not cause or cause visual hallucinations, but not to a large extent. Laboratory studies, including experiments on animals, allowed MDA, MDMA, DOET to be classified as amphetamines and to distinguish them from LSD. This is confirmed by observations of people.

MDA, MDMA produce a slight euphoria, accompanied by openness and helplessness. These properties encourage some psychotherapists to recommend the use of these substances, in particular MDMA, as an addition to therapy. Thus, these drugs can be considered as a unique category among hallucinogens. Anyway, there are reports that these substances can damage the serotonergic neurons of the brain.

History and epidemiology

For the first time, DOM was talked about in the late 60s, when its powerful hallucinogenic effects and rather long duration of action (about 24 hours) caused many bad trips. MDA also attracted attention at about the same time, but met a warmer welcome. He was called the Soft American Drug because he had a weaker effect and less pronounced sensory effects than LSD. He was also called the Drug of Love, because his use evoked positive feelings for others, developed sympathy. The use of MDA as well as LSD decreased in the 70s, while another drug, MDMA, became popular. It is estimated that in 1976 about 10,000 doses of MDMA were sold on the street. In 1985, the DEA estimated that only 30,000 doses were sold in Texas in a month. What explains such a significant increase in consumption? The spread of information about its beneficial therapeutic effects made it attractive. His use did not disturb the public and he received the nickname “Ecstasy”. Moreover, until 1985 he remained a legal drug. Although MDA was a drug of Group N1 (see Appendix N1), MDMA, which is very similar in structure, was not classified according to this system. Thus, drug dealers preferred the least risk and began to sell ecstasy. Anyway, in the face of the growing use of MDMA, followed by animal studies proving brain damage, in 1985, MDMA was classified as a Group N1 drug. As soon as MDMA came under control, distributors started selling DOET, a very similar drug to MDMA, which is now also controlled by the DEA Act of 1986. These decisions are controversial because they prohibit further testing of MDMA and similar compounds in psychiatry.

Effects of PCP

Effects of PCP

The effects of PCP are rather peculiar. A moderate dose (1-10 mg) causes euphoria and numbness, resembling alcoholic intoxication. Speech becomes slurred and usually a lack of coordination of movements. The object can become inhibited and numb, with a blank look, or become aggressive and overly active. Observed sweating, increased heartbeat, increased blood pressure, rapid, involuntary movements of the eyeballs, called nystagmus. Blurred vision is often tested, the recipient of a drug begins to double in the eyes, but visual hallucinations are rare. Tactile sensations are much more common.

The most frequently experienced hallucination is that parts of the body appear to be either very small or very large. You can imagine yourself small enough to go through a keyhole, or suddenly it seems that the arm is twice as long as the whole body. The following fragment gives a brief description of the condition of a person who has taken ketamine:

“In Donna’s ketamine eyes, the corridor leading to the toilet looked like a tunnel stretching for miles. The matter was complicated by the fact that Donna felt no more than two feet tall …”
These effects usually last from two to eight hours, but they are quite diverse and, especially after high doses, can last for several days or weeks. Overdose (more than 20 mg) can cause an attack, prolonged coma, and sometimes death from suffocation. PCP often causes bad trips, which occur in 50% – 80% of cases of use. Toxic psychosis caused by PCP is most often characterized by paranoia, a flash of rage, and can last for several days. In addition, PCP often exacerbates long-term attacks of psychosis and depression, which last from seven to thirty days or more. In these cases, physical limitations and intensive medical treatment are often necessary. More often than all the other hallucinogens, PCP causes medical and psychiatric complications. Often, psychosis caused by PCP numerically exceeds the number of psychosis caused by schizophrenia or alcoholism.

Drug Abuse Prevention

Posted on November 3, 2018  in Medical news

Information about alcohol and drugs, their effects, their use and abuse. This led us to our last chapter on drug abuse prevention.
Unfortunately, historically, neither the efforts of professionals, nor directed funding could make the prohibition of drugs the main public task. The reasons for this are not determined, but there are two possible explanations. One is that the efforts to prevent abuse in the past have brought only modest results. The second explanation for this is that currently the abuse of various substances is particularly noticeable and finds a faster response in human and financial resources. Whether such an approach is short-sighted is a very controversial issue.

Although prevention has always received less attention than treatment, now is the time when the study and development of prevention is on the rise. Perhaps the most significant factor that caused this change is the association of the problem of drug addiction with the problem of AIDS. Intravenous drug users constitute the second largest group of people infected with HIV in the United States and Europe. In addition, the influence of drugs in some cases can provoke promiscuous sex, increasing the risk of contracting AIDS.
Most still agree that prevention should be an important component in the modern approach to solving the problem of abuse of various substances. The first step in this chapter is a review of definitions related to prevention. Then the main models of prevention and the associated difficulties are discussed. There will also be considered several examples of preventive programs and their results.