Hallucinogens

Distortions of perception, such as hallucinations or illusions, as well as thinking disorders (for example, paranoia) can be caused by many drugs if they are taken in toxic doses. Distortions of perception and hallucinations can also occur during the period of the withdrawal syndrome when you stop using sedatives (for example, alcohol or barbiturates). Nevertheless, some substances cause impaired perception, thinking and affective disorders, even in low doses, which do not have a significant effect on memory and orientation. Such substances are often called hallucinogens (psychedelics). However, their use does not always lead to the appearance of hallucinations. In the USA, the most commonly used psychedelics include lysergic acid diethylamide (LSD), phencyclioin (PCP), methylene-dioxime methamphetamine (MDMA, ecstasy) and various cholinolytic agents (atropine, benzotropin). The use of these substances attracted public attention in the 60's and 70's, but then, in the 80's, their use declined. In 1989, the use of hallucinogens in the United States began to increase again. In 1993, 11.8% of college students reported using one of these substances at least once. The tendency to increase in consumption was especially pronounced in adolescents, beginning with the 8th grade.

Although the psychedelic effect can be caused by various substances, the basic psychedelic drugs belong to two groups. Indoleamine hallucinogens include LSD, DMT (N, N-dimethyltryptamine), psilocybin. Fenetylamines include mescaline, dimethoxymethylamphetamine (HOME), methyleneenedioxy amphetamine (MDA), and MDMA. Preparations of both groups have a strong affinity for serotonin 5-HT 2 receptors (Titeler et al., 1988), but differ in their affinity for other subtypes of 5-HT receptors. There is a strong correlation between the relative affinity of these compounds for 5-HT2 receptors and their ability to cause hallucinations in humans. The role of 5-HT 2 -receptors in the development of hallucinations is also confirmed by the fact that antagonists of these receptors, for example, ritanserin, effectively block the behavioral and electrophysiological reactions caused by hallucinogens in experimental animals. Recent binding studies conducted with cloned 5-HT receptors have shown that LSD interacts with most of the 14 subtypes of these receptors at nanomolar concentrations. Thus, it is doubtful whether the psychedelic effect was associated with an effect on any one of the subtypes of serotonin receptors.

LSD is the most active drug of this group, which causes a significant psychedelic effect even at such a low dose as 25-50 μg. Consequently, LSD is 3,000 times more active than mescaline.

LSD is sold in the underground market in various forms. One of these popular modern forms is postage stamps, which are coated with an adhesive containing a different dose of LSD (50 to 300 mg or more). Although most samples sold as LSD do contain LSD, samples of poisonous fungi and other plant substances sold as psilocybin and other psychedelics rarely contain a hallucinogen.

In humans, the action of hallucinogens is variable, even for the same person at different times. In addition to the dose of the substance, its effect depends on individual sensitivity and external conditions. LSD after oral administration is rapidly absorbed and begins to act for 40 minutes. The effect peaks after 2-4 hours and then regresses for 6-8 hours. At a dose of 100 μg, LSD causes distortion of perception and hallucinations, as well as affective changes, including euphoria or depression, paranoia, intense arousal and sometimes a sense of panic. Signs of LSD use include: wide pupils, high blood pressure, rapid pulse, skin flushing, salivation, lacrimation, revitalization of reflexes. Distortion of visual perception is especially pronounced when using LSD. Colors seem more intense, the shape of objects can be distorted, a person pays attention to unusual nuances, for example, to a drawing of hair growth on the back of a brush. It has been reported that these substances can increase the effectiveness of psychotherapy and contribute to the treatment of addiction and other mental disorders. However, these reports are not supported by controlled studies. At present, there is no reason to consider these drugs curative.

The so-called "bad trip" is characterized by intense anxiety, although sometimes severe depression and suicidal ideation are noted. Visual disorders are usually expressed. The "bad journey" associated with the use of LSD is difficult to distinguish from the reaction to cholinolytic agents and phencyclidine. To date, there have been no documented deaths caused by the use of LSD, but there have been reports of fatalities and suicides occurring against the background of LSD or soon after its termination. Prolonged psychotic reactions, lasting two days or more, can occur after taking a hallucinogen inside. In predisposed persons, these substances can provoke schizophreniform episodes. In addition, according to some sources, prolonged use of these substances can lead to the development of persistent psychotic disorder. Frequent use of psychedelic substances is rare, and therefore tolerance usually does not develop. To behavioral changes caused by LSD, tolerance develops if the substance is consumed 3-4 times a day, but the withdrawal syndrome does not develop. Experimental models demonstrated cross-tolerance between LSD, mescaline and psilocybin.

[1], [2], [3], [4]

Treatment of abuse of hallucinogens

Because of the unpredictability of the action of psychedelic substances, each application carries a certain risk. Although addictions and addictions do not develop, medical care may be required for "bad travel". Sometimes it seems that heavy excitement requires the use of drugs, but the necessary effect in this situation can have a usual soothing conversation. Antipsychotic agents (dopamine receptor antagonists) can enhance unpleasant experiences. Diazepam, 20 mg orally, may be effective. A particularly adverse aftereffect of LSD and other similar drugs is the occurrence of episodic visual disorders, which are observed in a small part of people who used LSD in the past. This phenomenon was called "flashback" and reminds the sensations that arose against the background of the action of LSD. Currently, in official classifications, it is referred to as a persistent perception disorder caused by hallucinogens. This phenomenon manifests itself as false images on the periphery of the field of view, the flow of color geometric pseudo-hallucinations, and positive trace images. In half of cases, this visual impairment remains stable and, thus, constitutes a persistent impairment in the functioning of the visual analyzer. To provoking factors include stress, fatigue, being in a dark room, taking marijuana, neuroleptics, anxiety.

MDMA (Ecstasy)

MDMA and MDA are phenylethylamines, which have both a stimulating and a psychedelic effect. MDMA gained popularity in the 1980s in some campuses due to the ability to exacerbate sensory abilities and reflections. This substance has been recommended by some psychotherapists to improve the effectiveness of treatment, but there is no evidence to support this opinion. The acute effect of the substance depends on the dose and is characterized by tachycardia, dry mouth, jaw-reduction, muscle pain and, with higher doses, visual hallucinations, agitation, hyperthermia and panic attacks.

MDA and MDMA cause degeneration of serotonergic neurons and their axons in rats. Although this effect was not shown in humans, a low level of serotonin metabolites was noted in the cerebrospinal fluid of persons with long-term use of MDA. Thus, this substance may have neurotoxic effects, while the prospective benefits of MDMA are not proven.

Fenzyclidine

By its pharmacological action is different from other psychedelics, the prototype of which is LSD. Initially, phencyclidine was suggested as an anesthetic in the 1950s, but was not used because of the high frequency of delirium and hallucinations in the postoperative period. He was referred to dissociative anesthetics, because in the state of anesthesia the patients retain consciousness, they have a blinking look, a frozen face and rigid muscles. Abuse of this drug began with the 70-ies. Initially, it was taken orally, and then it was smoked, which provided better control over the dose. The effect of the drug was investigated in healthy volunteers. At a dose of 0.05 mg / kg, phencyclidine causes emotional dulling, impoverishment of thinking, bizarre reactions in projective tests. Fenziliklidin can also cause a catatonic pose and a schizophreniform syndrome. Persons using high doses of the drug can actively react to hallucinations, show hostility and aggressive behavior. The anesthetic effect increases with increasing dose. They may have a sopor or coma, accompanied by muscle rigidity, rhabdomyolysis, hyperthermia. At intoxication in patients, there can be a progressive deterioration of the state from aggressive behavior to the development of coma with the presence of wide non-responsive pupils and high arterial pressure.

Fenzyclidine has a high affinity for the structures of the cortex and the limbic system, resulting in blockade of N-methyl-D-acapatotal (NMDA) -type glutamate receptors. Some opioids and other agents have the same effect as phencyclidine on laboratory models and specifically bind to these same receptors. According to some reports, the stimulation of NMDA receptors by a large number of excitatory amino acids is one of the links in the "ischemic cascade", leading to the death of neurons. In this regard, there is an interest in the creation of fenpiclidine analogs, which would also block NMDA receptors, but did not have psychotogenic effects.

Fenzyclidine causes a phenomenon of reinforcement in primates, as evidenced by experiments with self-introduction of substances that lead to intoxication. People most often use phencyclidine occasionally, but about 7% of cases, according to some studies, there is daily use. According to some data, the animals develop tolerance to the behavioral effects of PCP, but this phenomenon has not been systematically studied in humans. In primates after interruption of daily administration, abstinence symptoms are observed - drowsiness, tremor, epileptic seizures, diarrhea, piloerection, bruxism, vocalization.

[5], [6], [7], [8], [9], [10], [11]

Treatment of abuse of phencyclidine

When overdosing, only supportive measures are needed, since there is no drug blocking the effects of phencyclidine, and the effectiveness of measures to accelerate the excretion of phencyclidine is not proven. Although there are recommendations for acidifying urine. Coma with an overdose of phencyclidine can last from 7 to 10 days. Excitation or a psychotic condition caused by phencyclidine can be doped with diazepam. Persistent psychotic disorders require the appointment of neuroleptics, for example, haloperidol. Since phencyclidine has a holinolitic effect, neuroleptics with a similar effect, for example, chlorpromazine, should be avoided.

Inhalants

Inhalants include several different categories of chemicals that evaporate at room temperature and can cause sudden changes in mental status when inhaled. Examples are toluene, kerosene, gasoline, carbon tetrahydrochloride, amyl nitrate, nitrous oxide. Solvents (for example, toluene) are usually used by children from the age of 12 years. The substance is usually placed in a plastic bag, and it is inhaled. After a few minutes, dizziness and intoxication occur. Aerosols containing fluorocarbon solvents are also widely used. Prolonged or daily use can lead to damage to several systems of the body: violation of the heart rate, bone marrow depression, brain degeneration, damage to the liver, kidneys, peripheral nerves. A lethal outcome is possible, probably associated with a heart rhythm disturbance, especially with physical exertion or upper airway obstruction.

Amyl nitrate (poppers) causes relaxation of smooth muscles and was used in the past to treat angina pectoris. It is a yellow volatile flammable liquid with a fruity smell. In recent years, amyl nitrate and butyl nitrate have been used to relax smooth muscles and enhance orgasm, especially male homosexuals. It is purchased in the form of room deodorants. It can cause agitation, a sensation of blood rush, dizziness. Side effects include heart beat, orthostatic hypotension, headache, in severe cases, loss of consciousness is possible.

Gaseous anesthetics, for example, nitrous oxide or halothane, are sometimes used to get intoxication by medical personnel. Nitrous oxide is also abused by public catering workers, since it is produced in disposable small aluminum containers used for whipping cream. Nitrous oxide causes euphoria, analgesia, and then loss of consciousness. Compulsive use and chronic intoxication are rarely reported, but there is a risk of overdose associated with the abuse of this anesthetic.

Treatment of dependence

The treatment of substance abuse and dependence should depend on the nature of the substance and the individual characteristics of each individual patient. The algorithm takes into account various therapeutic possibilities. For each category of psychoactive substances, available medical treatment is provided. Treatment is impossible without knowing the pharmacological features of the substances used by the patient, or a combination thereof. This is especially important in the treatment of overdose or detoxification in a patient with an abstinence syndrome. It is important to understand that treatment of dependence requires many months and years of rehabilitation. Behavioral stereotypes developed during the thousand-fold injections of the drug will not disappear after detoxification and even after a typical 28-day in-patient rehabilitation program. Long-term outpatient treatment is needed. Although it is preferable to strive for complete abstinence, in practice many patients are tempted to re-start using the drug, which may require repeated courses of treatment. In this case, maintenance therapy may be effective, such as long-term methadone treatment in opioid dependence. This process can be compared with the treatment of other chronic diseases, for example, diabetes mellitus, bronchial asthma or arterial hypertension, which require long-term use of medications, and complete recovery is unlikely. If we consider dependence in the context of a chronic disease, then the existing treatment of dependence can be considered quite effective. Long-term treatment is accompanied by an improvement in physical and mental status, as well as social and professional activities. Unfortunately, due to the general pessimism in the medical community regarding the effectiveness of the treatment, the therapeutic efforts are mainly aimed at correcting the complications of pulmonary, cardiovascular, hepatic, and not correction of behavioral changes associated with dependence. Meanwhile, directing efforts to treat the dependence itself, it is possible to prevent somatic complications, and this requires a long rehabilitation program.