Mental and behavioral disorders due to psychoactive substance use [alcohol, opioids, cannabinoids, sedatives or hypnotics, cocaine, other stimulants (including caffeine), hallucinogens, tobacco, volatile solvents and multiple drug use]. Acute intoxication: clinical guidelines

List of Abbreviations

BP – blood pressure

HIV – human immunodeficiency virus

CNS – central nervous system

ANS – autonomic nervous system

WHO – World Health Organization

HPLC-MS — high-performance liquid chromatography with mass spectrometric detection

GC-MS – gas chromatography-mass spectrometry

CHD – coronary heart disease

IMV – invasive mechanical ventilation

EIA – enzyme immunoassay

IA — immunochromatographic assay

ABDS – acid-base balance status

pH — indicator reflecting the concentration of hydrogen ions in a solution (blood, urine, etc.)

BE — base excess in blood

medicines – medicinal products

VS – volatile solvents

GI – gastrointestinal tract

GIT – gastrointestinal bleeding

GHB – gamma-hydroxybutyric acid

S&H — sedatives and hypnotics

LSD — lysergic acid diethylamide

MDMA — 3,4-methylenedioxymethamphetamine

MDPV — methylenedioxypyrovalerone

α-PVP — alpha-pyrrolidinovalerophenone

CVA – cerebrovascular accident

psychoactive substance – psychoactive substance

SCs — synthetic cannabinoids

HR – heart rate

DMT — N,N-dimethyltryptamine

DOM — 2,5-dimethoxy-4-methylamphetamine (STP)

DOET — 2,5-dimethoxy-4-ethylamphetamine

DOB — 2,5-dimethoxy-4-bromoamphetamine

DMA — 3,4-dimethoxyamphetamine

GBL — gamma-butyrolactone

BDO — 1,4-butanediol

MDA — 3,4-methylenedioxyamphetamine

PCP — 1-(1-phenylcyclohexyl)piperidine (phencyclidine)

Russian Ministry of Health – Russian Ministry of Health

UN — United Nations

UNODC — United Nations Office on Drugs and Crime

ICD-10 – International Classification of Diseases, 10th Revision

MS – mass spectrometry

NA – noradrenaline

AI – acute intoxication

BV – blood volume

WEC — water-electrolyte balance

CD — compulsive drive

FPIA — fluorescence polarization immunoassay

US – ultrasound examination

TBI – traumatic brain injury

ECG – electrocardiogram

Echo-EG — echoencephalography

EEG – electroencephalography

CT – computed tomography

MRI – magnetic resonance imaging

X-ray — X-ray imaging

Terms and Definitions

Intoxication — impairment of vital functions caused by toxic substances of endogenous and exogenous origin.

Psychoactive substance (PAS) — a substance that, when ingested or introduced into the human body, affects mental processes, such as cognitive or affective spheres

Acute psychoactive substance intoxication — a transient condition that occurs following the administration of a psychoactive substance and results in disturbances of consciousness, cognitive function, perception, judgment, emotional state, or behavior, or other psychophysiological functions and responses

PAS tolerance — the degree of the body's resistance to the psychophysiological effects of a PAS.

Disorder of consciousness — a dysfunction of the brain accompanied by a temporary complete or partial loss of connection with reality, accompanied by a disturbance of environmental perception, disorientation in time and place, impaired thinking with difficulty in making judgments, and subsequent partial or total amnesia of the period of altered consciousness.

Obnubilation — a syndrome of impaired consciousness characterized by a significant increase in the perception threshold for all external stimuli and drowsiness.

Sopur — deep depression of consciousness with loss of voluntary activity and preservation of reflex activity.

Coma — a condition characterized by complete loss of consciousness, absence of active movements, impaired respiration and cardiac activity, lack of response to external stimuli, and fading of reflexes up to their complete disappearance.

Perceptual disorder — a disturbance of the mental process of reflecting objects and phenomena as a whole, in the totality of their properties, independent of the will of the subject with this disorder.

Behavioral disorder – a disturbance characterized by a persistent inability to control behavior in accordance with socially established norms.

Delirium – an exogenous mental disorder occurring with impaired consciousness (ranging from a clouded state to coma). It is characterized by true, predominantly visual, hallucinations and illusions, and, as a consequence, secondary delusions; affective disturbances, sleep and behavioral disorders, and disorientation in time and place with preserved orientation to one's own personality.

Convulsive seizure – an acute disturbance of consciousness accompanied by sensory disturbances and motor disorders or convulsions (involuntary contractions of muscles throughout the body).

Alcohol – various beverages whose main psychoactive ingredient is ethanol.

Alcohol substitutes – liquids consumed for the purpose of intoxication instead of conventional alcoholic beverages. These liquids may contain insufficiently purified ethanol and/or other substances as a base, most commonly various alcohols (methanol, propanol, butanol, ethylene glycol, etc.) and their esters.

Opioids – a group of opium poppy alkaloids and their derivatives of natural (parts and juice of the opium poppy, morphine, codeine, thebaine, noscapine) or semi-synthetic (heroin, hydrocodone, buprenorphine, oxycodone, ethylmorphine, etc.) origin. There are also synthetic opioids (methadone, butorphanol, tramadol, fentanyl, trimeperidine, etc.). All opioids are agonists of opioid receptors in the brain.

Cannabinoids – a group of active substances of hemp (Cannabis sativa) of natural origin (phytocannabinoids). Cannabinoids also include synthesized psychoactive substances that are agonists of cannabinoid receptors in the brain (synthetic cannabinoids [SCs] – "spices", "mixes", and other smoking blends, usually of complex composition).

Sedatives and hypnotics – a constantly expanding list of substances that, in addition to their primary sedative effect, possess euphorigenic (and consequently addicting) potential, united into a single group due to similarities in effects, targets of action, and clinical-dynamic features of addiction development. Sedatives and hypnotics traditionally include benzodiazepine derivatives (benzodiazepines) and barbiturates. Most of these agents are medicinal products (hereinafter – MPs). In recent years, the list of sedatives and hypnotics has expanded [1] to include:

Carbamates – Meprobamate;

Chloral derivatives – Chloral hydrate;

Carbinols – Ethchlorvynol;

Piperidines – Glutethimide, Methyprylon;

Quinazolinones – Methaqualone;

Imidazopyridines – Zolpidem, Zaleplon, Zopiclone;

Systemic antihistamines – Diphenhydramine, Hydroxyzine;

Gamma-hydroxybutyric acid (GHB), its analogues and precursors (Baclofen, Aminophenylbutyric acid, Pregabalin, Gabapentin, Propofol, Gamma-butyrolactone [GBL], 1,4-butanediol [BDO]).

Sedative-hypnotics vary widely in their ability to cause toxic effects; barbiturates and GHB precursors (gamma-butyrolactone, 1,4-butanediol) are the most dangerous in this regard, whereas GHB itself is less toxic.

Cocaine is a bio- and psychostimulant, a purified extract of the tropane alkaloid found in coca leaves (Erythroxylum coca), most commonly used as a water-soluble powdered hydrochloride (primarily intranasally and intravenously) and the more affordable crack – a free base with a higher decomposition temperature used for smoking.

Stimulants (psychostimulants) are a group of psychoactive substances that stimulate CNS activity and, to some extent, physical activity (amphetamine and amphetamine derivatives such as methamphetamine and 5-methoxy-3,4-methylenedioxyamphetamine [MDMA], cathinones and their derivatives). This list includes illicitly manufactured pervitin (methamphetamine) and ephedrone (methcathinone), produced from ephedrine-containing medications. In recent years, methcathinones have become widespread: alpha-pyrrolidinovalerophenone (α-PVP), methylenedioxypyrovalerone (MDPV), and mephedrone (4-methylmethcathinone), known as "salts", "crystals", "speed", etc. The list of stimulants is constantly expanding due to the development of designer variants (substances with similar psychotropic effects that are close in structure but not identical).

Hallucinogens (psychotomimetics, psychedelics) are a heterogeneous group of psychoactive substances of natural origin (mescaline, psilocybin, bufotenine, salvinorin A, ibogaine, etc.) and synthetic origin (lysergic acid diethylamide [LSD], phencyclidine [PCP], ketamine**, etc.) that bizarrely alter mental functions (consciousness, perception, emotions, thought). Substances in this group most frequently cause a short-term and reversible exogenous psychosis accompanied by obligate hallucinatory-delusional symptoms. Based on the characteristics of intoxication, hallucinogens are subdivided into serotonergic (LSD, N,N-dimethyltryptamine [DMT], mescaline, psilocybin, salvinorin A, etc.), anticholinergic (scopolamine, atropine**, and other drugs with anticholinergic activity), dissociative anesthetics (PCP, ketamine**), and amphetamine-class psychedelics (2,5-dimethoxy-4-methylamphetamine [DOM or STP], 2,5-dimethoxy-4-ethylamphetamine [DOET], 3,4-dimethoxyamphetamine [DMA], 3,4-methylenedioxyamphetamine [MDA], 2,5-dimethoxy-4-bromoamphetamine [DOB], etc.).

Nicotine is an alkaloid found in the leaves and stems of tobacco and certain other plants of the Solanaceae family. In the vast majority of cases, it is consumed by smoking, inhaling vapors of nicotine-containing liquids (in e-cigarettes and hookahs), or by chewing (chewing tobacco), buccal/sublingual absorption (snus, naswar), and intranasally (snuff).

Volatile solvents are a group of organic compounds that easily evaporate under normal conditions and are constituents of industrial and household chemicals. They are administered primarily via inhalation and less commonly via transcutaneous routes (solvents, aerosols).

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Acute intoxication (AI) is a transient condition following the administration of a psychoactive substance, characterized by disturbances in consciousness, cognitive function, perception, judgment, emotional state and/or behavior, or other psychophysiological functions and reactions. These disorders are caused by the acute pharmacological effects of the substance and conditioned reflexes to it. The intensity of acute intoxication decreases over time, and in the absence of further substance use, acute intoxication resolves. Symptoms of acute intoxication do not always reflect the primary action of the substance.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The cause of acute intoxication is the entry into the body—most commonly through self-administration—of a psychoactive substance in an amount sufficient to cause symptoms of acute intoxication. The pathogenesis of AI depends on the type of psychoactive substance. Acute intoxication correlates directly with dosage levels, with exceptions possible in patients with underlying conditions (e.g., renal or hepatic impairment), where small doses of a substance can produce a disproportionately severe intoxicating effect. In general, the observed disorders are associated with neurotransmitter metabolism disruption in the central nervous system (CNS) under the influence of psychoactive substances; however, intoxication with high doses brings toxic effects to the forefront, manifested, for example, in the depression of tissue respiration, heart rate, and other vital processes. The presence of toxic impurities in substances abused by dependent individuals—which are invariably present in surrogate alcohol and illicit street drugs—must also be taken into account [1, 4-6].

1.3 Epidemiology of the Disease or Condition

Special epidemiological studies focusing specifically on psychoactive substance-induced acute intoxication are lacking. Since acute intoxication is an absolute consequence of any psychoactive substance use, an understanding of the prevalence of this phenomenon can be derived from the overall prevalence of addictive disorders and the number of psychoactive substance users [7-9].

Alcohol is the most widespread psychoactive substance in the world; virtually the entire adult population consumes alcohol in some form, with average global consumption in 2019 standing at 5.8 liters per capita. Nicotine use is also ubiquitous; as of 2020, it is used by 22.3% of the global population aged 15 years and older [8].

The most common drugs in the world are cannabinoids. According to the United Nations Office on Drugs and Crime (UNODC), there were more than 209 million users in 2020. Opioids also remain a major global problem, with 61 million users. The growth in stimulant use continues: 21 million people used cocaine, about 20 million used "ecstasy" (MDMA), and 34 million used amphetamines. Despite the widespread consumption of caffeine worldwide, cases of acute caffeine intoxication do not occur. In the Russian Federation, according to 2021 data, mental and behavioral disorders due to psychoactive substance (PAS) use, including nicotine, were registered in 1,870,109 individuals, including 23,545 adolescents aged 15–17 years. The number of patients hospitalized in 2021 with acute alcohol intoxication was 40,863, and the number of individuals recorded as being in a state of alcohol intoxication was 532,122. The number of registered individuals in a state of drug intoxication in 2021 was 92,600, and from other PAS, 2,891 individuals [9].

1.4 Features of Coding the Disease or Condition

Diagnosis coding is performed using the International Classification of Diseases, 10th Revision (ICD-10). The ICD-10 variant adapted for Russia uses 7 characters to formalize the diagnosis of a disorder detected in a patient [1].

In ICD-10, acute intoxication (AI) caused by the use of various PAS (alcohol, opioids, cannabinoids, hypnotics and sedatives, cocaine, other psychostimulants including caffeine, hallucinogens, nicotine, volatile solvents) and poly-substance use is considered in the relevant sections according to the type of substance. The presence of AI is indicated by the fourth character 0 (F1x.0xx) (Table 1).

In the F13, F15, F16, and F19 categories, where a specific substance may belong either to narcotic or substance-abuse (toxicomania) agents, additional letter codes are introduced. If AI is caused by a narcotic substance, the Russian letter "H" is placed at the end of the code. A narcotic substance is a PAS included in schedules 1 and 2 of the official "List of Narcotic Drugs, Psychotropic Substances, and Their Precursors Subject to Control in the Russian Federation". If the PAS is not a narcotic, the substance is classified as a toxicomania agent, and the Russian letter "T" is placed at the end of the code.

Table 1. ICD-10 Diagnosis Formalization

The diagnosis of AI can be specified depending on the presence of complications. In this case, the diagnostic code is supplemented with a fifth character (Table 2).

Table 2. Specification of acute intoxication diagnosis in the presence of complications

The severity of AI is determined by the sixth character (mild – 1, moderate – 2, severe – 3) [10].

1.5 Classification of the disease or condition

Certain types of PAS-induced AI are classified depending on the substance that caused the intoxication. In addition, the severity of the intoxication course is taken into account. The severity of intoxication is assessed clinically. In cases of acute alcohol intoxication, its severity is additionally assessed using laboratory methods (blood alcohol concentration in the patient or in exhaled air).

Mild PAS-induced AI is generally not accompanied by significant changes in the patient's condition.

Moderate PAS-induced AI is accompanied by clinically significant changes in mental state and reversible impairment of internal organ function.

Severe PAS-induced AI is a life-threatening condition associated with impairment of central nervous system and vital organ function. Severe AI requiring specialized addiction care is characterized by psychomotor agitation, psychotic disorders, clouding of consciousness, as well as impaired consciousness not reaching the level of coma, with compensated vital organ dysfunction.

The extreme form of severe intoxication is poisoning. Poisoning with alcohol, opioids, hypnotics and sedatives, volatile organic solvents, and nicotine is accompanied by profound clouding of consciousness (amentia) or depression of consciousness to the level of coma, severe hemodynamic and respiratory depression. Poisoning with stimulants and hallucinogens is accompanied by pronounced psychomotor agitation, cardiac rhythm disturbances, and ischemia of vital organs (brain, heart, kidneys). In cases of PAS poisoning, patients require specialized toxicological care, and other ICD-10 codes are used (these conditions are not described in these clinical guidelines) [1].

1.6 Clinical presentation of the disease or condition

The clinical picture of AI is characterized by impairments in psychophysiological functions and reactions, posture, coordination, autonomic responses, consciousness, cognitive functions, perception, mood, and behavior that occur following PAS use. The nature of AI and the severity of the patient's condition largely depend on the PAS dose, individual tolerance level, the subject's baseline mental and physical condition, and other factors (e.g., the degree of purity of the consumed PAS). Behavioral manifestations of AI are noticeably influenced by cultural and personal expectations regarding the effects of PAS. The intensity of AI manifestations decreases over time, and in the absence of further PAS use, its effects diminish and completely disappear. Recovery is therefore complete, except in cases where tissue damage or other complications are present. The clinical picture of AI caused by various PAS differs [1].

1.6.1 Clinical presentation of acute alcohol intoxication

In acute alcohol intoxication (AI) of any severity caused by alcohol consumption, there is typically a smell of alcohol on the breath.

1.6.1.1 Mild acute alcohol intoxication (F10.0x1). Characterized by elevated mood, increased motor activity, and a sensation of psychic and physical comfort. A mild increase in parasympathetic activity may be observed, manifested as a decrease in heart rate and blood pressure, and skin hyperemia. External signs of intoxication are usually fully controlled and managed by willpower. Following mild AI, which lasts for an average of several hours, no unpleasant psychological or physical sensations are noted. Memories of the period of intoxication are preserved. Mild AI is most commonly recorded at blood alcohol concentrations from 0.5 to 1.5 g/L [1].

1.6.1.2 Moderate acute alcohol intoxication (F10.0x2) The behavior of intoxicated individuals gradually becomes increasingly disinhibited and is no longer controlled by willpower. Irritability, rudeness, aggressiveness, and obtrusiveness are frequently observed. Speech production becomes increasingly inadequate and uncontrolled. Control over the motivational sphere is also lost, and actions inappropriate to the situation may be committed. An acute exacerbation of individual character traits that remain hidden in a sober state is very characteristic. Movements become sweeping and repetitive. Gait becomes unsteady and uncertain. Activation of the sympathetic nervous system is characteristic, manifesting as tachycardia, increased respiratory rate, and elevated blood pressure. Tendon reflexes are usually diminished, and horizontal nystagmoid movements of the eyeballs appear Moderate AI is diagnosed at blood alcohol concentrations of 1.5–3 g/L [1].

1.6.1.3 Severe acute alcohol intoxication (F10.0x3) Motor activity is reduced; patients have difficulty standing on their feet and frequently fall. Physical weakness increases. Speech is largely unintelligible: intoxicated individuals utter fragments of words and phrases, mutter monotonously, and facial expressions are impoverished or absent. Productive verbal contact with such a subject is virtually impossible. Orientation in place and time is frequently lost. Severe AI is characterized by the appearance of varying depths of impaired consciousness symptoms, which may progress to the degree of coma (F10.05x). Vomiting, hiccups, and involuntary urination may be observed. The skin is pale, cold, and clammy. Heart sounds are muffled, palpitations are observed, and the pulse is rapid, with low volume and tension. Blood pressure decreases. Respiration is shallow, rapid, and may become pathological. Neurological symptoms are detected: diminished or absent conjunctival and pain reflexes, dilated pupils, weak reaction to light, and spontaneous horizontal nystagmus. Tendon reflexes are reduced or absent Severe acute alcohol intoxication is typically accompanied by complete or partial amnesia. Severe acute alcohol intoxication is diagnosed at blood alcohol concentrations of 3–5 g/L [1,5].

1.6.1.4 Complicated forms of acute alcohol intoxication

In addition to somatic complications (F10.02x) and seizure disorders (F10.06x), psychopathological complications may also be observed. Delirium (F10.03x) may develop in a state of intoxication (typically in individuals with concurrent somatic pathology such as acute pancreatitis, etc.). Pathological intoxication (F10.07x) is observed quite rarely. This condition represents a manifestation of a peculiar idiosyncrasy to alcohol—a brief acute psychosis occurring after the consumption of small doses of alcohol, sometimes insufficient to cause even mild intoxication in most people (below 0.40 g/L). The clinical picture is dominated by twilight clouding of consciousness with pronounced affective disorders (anxiety, fear, anger), hallucinations, transitory delusions, motor agitation, and aggression. The crisis culminates in deep sleep, and the period of psychosis is generally amnesized [1].

1.6.2 Clinical presentation of acute opioid intoxication

Since opioid-dependent patients typically use drugs parenterally, traces of intravenous injections can be found along the path of peripheral veins and sometimes over the projection of central veins.

Mild opioid AI is difficult to identify upon examination, especially in dependent individuals for whom such intoxication is habitual. The most pathognomonic sign is miosis and a decreased reaction to light. Frequently, in order to dissimulate narcotic intoxication, opioid-dependent individuals use solutions of anticholinergic drugs employed in ophthalmology, such as cyclopentolate, tropicamide**, etc.

In moderate AI, the subject is usually somewhat lethargic, complacent, and inactive. Contact may be difficult due to the patient's own dream-like experiences. Speech is quiet, and answers follow after pauses. At certain stages in the development of dependence, opioid addicts may exhibit a change in the intoxication picture, consisting of increased mental and physical activity against a background of complacency and euphoria. Somatovegetative and neurological disorders are of great importance for diagnosing opioid AI: miosis down to "pinpoint pupils", pallor, characteristic skin itching, dryness of mucous membranes, decreased blood pressure, hypothermia, decreased heart rate, diminished protective and tendon reflexes, and increased resistance to pain stimuli.

In severe opioid AI, depression of consciousness rapidly increases: obtundation is replaced by stupor, followed by superficial and then deep coma. Marked miosis ("pinpoint pupils"), cutaneous cyanosis, hypotension, bradycardia, bradypnea, shallow rare respiration or Cheyne-Stokes pathological respiration with the rapid development of hypoxemia and hypercapnia, and apnea are observed [1].

1.6.3 Clinical presentation of acute cannabinoid intoxication

AI caused by the use of naturally occurring cannabinoids is characterized by a specific odor of cannabis. An unusual odor (pungent, "chemical", the smell of "burnt leaves") can also be detected from patients who have smoked synthetic cannabinoids. Cannabinoid AI is characterized by various affective disorders (both euphoria and depression or dysphoria) and disturbances of consciousness, ranging from mild confusion to complete disorientation. Affect is generally unstable, and a shift between polar states is characteristic. AI is very frequently accompanied by various perceptual disorders: the color of surrounding objects may become more saturated; sounds may acquire a special timbre and tone. Phenomena of derealization and depersonalization are characteristic. The surrounding environment is perceived by the intoxicated subject as unusual and alien. Surrounding objects and one's own body may change in size and shape. Illusions, pseudo-hallucinations, or true hallucinations may be observed.

Thinking in a state of AI becomes illogical, inconsistent, and incoherent. Its pace is accelerated, less frequently slowed. Impairment of time perception is characteristic: it either accelerates or slows down. Statements are inconsistent, and comprehension of current events is impaired. Less frequently, thinking is slowed, with "thoughts freezing".

The state of cannabinoid AI is characterized by agitation and foolish behavior accompanied by uncontrollable laughter. Sexual arousal frequently occurs. Strong thirst is characteristic, and a sharply increased appetite often appears toward the end of intoxication.

Mild cannabinoid AI is characterized by facial flushing and conjunctival injection. As the severity of intoxication increases, the skin becomes pale and cold, and dryness of the mouth, increased ocular brilliance, and mydriasis are observed. Tachypnea, arterial hypertension, and tachycardia are usually noted.

Neurological examination reveals coordination disorders, tremor, and nystagmus. In severe cases, loss of skin sensitivity and paresthesias are observed.

In severe intoxication or heightened individual sensitivity to cannabinoids, psychotic forms of AI may develop with a predominance of delirious, oneiroid, or paranoid symptomatology.

Intoxication with synthetic cannabinoids is generally distinguished by a more severe clinical course, with the frequent development of seizure disorders, vomiting, and impairment of respiratory and cardiac activity [1].

1.6.4 Clinical presentation of acute sedative and hypnotic intoxication

The state of sedative-hypnotic AI generally resembles alcohol intoxication. Characteristic features are increasing lethargy, drowsiness, and motor incoordination. The affective sphere is characterized by emotional lability and a tendency toward "affect incontinence". A mild degree of habitual intoxication may be accompanied by elevated mood and euphoria. However, merriment and a feeling of warmth toward interlocutors can easily give way to anger and aggression toward others. Motor activity is increased, but movements are chaotic and uncoordinated. Sexual desire and appetite may increase.

Moderate and severe sedative-hypnotic AI is characterized by gross somatic and neurological disorders. Hypersalivation and conjunctival hyperemia are frequently observed. A peculiar greasy appearance of the skin is often noted.

As the degree of intoxication increases, the subject falls into a deep sleep. Bradycardia and hypotension are noted. Pupils are dilated, their reaction to light is sluggish; nystagmus, diplopia, dysarthria, depression of superficial reflexes and muscle tone, and ataxia are observed. Involuntary defecation and urination may occur. In severe intoxication, the depression of consciousness progresses, and deep sleep passes into a coma. Blood pressure drops, the pulse becomes frequent and superficial. Respiration is shallow, and may acquire a pathological Kussmaul or Cheyne-Stokes pattern. The skin becomes pale, body temperature drops, and deep reflexes disappear [1,5].

Acute intoxication with non-pharmaceutical GABA-mimetics (GBL, BDO) used by dependent patients to alter their mental state is characterized by a short duration (3-4 hours). The main danger is respiratory depression, marked bradycardia, and the potential development of convulsive disorders and acute encephalopathy [1].

1.6.5 Clinical presentation of acute cocaine intoxication

Mild and moderate acute cocaine intoxication is characterized by the onset of psychopathological disorders very similar to a hypomanic state: an elevation of mood, mental, and physical activity is typical. Subjectively, there is a perceived enhancement of creative abilities, unprecedented quick-wittedness, and a special depth of one's own thoughts. An improvement in well-being, lightness throughout the body, and a sense of permissiveness are also noted. Sexual desire increases. Somatic disorders are limited to palpitations and elevated blood pressure. The skin is pale, with a characteristic eye shine and pupil dilation.

In severe acute cocaine intoxication, acute paranoid psychosis frequently develops, a characteristic feature of which is tactile hallucinosis. Patients experience a sensation of insects crawling over the body, sometimes feeling itching under the skin or in internal organs. Unexplained behavioral oddities may occur, such as a tendency to pile various objects into heaps. As the degree of intoxication increases, tachycardia and blood pressure rise; cardiac rhythm disturbances in the form of tachyarrhythmias, atrial fibrillation, and ventricular fibrillation may be observed. Myocardial infarction, stroke, transient ischemic attack, and convulsive seizures may develop [1].

1.6.6 Clinical presentation of acute intoxication with other psychostimulants, including caffeine

Mild and moderate stimulant intoxication is characterized by euphoria and increased self-esteem. The mood is elevated, cheerful, with a shade of agitation and heightened interest in everything happening. At the same time, rapid shifts in emotional experiences are possible, accompanied by irritability, wariness, conflict behavior, and in some cases, belligerence and aggressiveness. In some instances, there is a sensation of accelerated passage of time. Auditory and visual perception become sharpened. Enhanced attention is combined with increased distractibility. Increased sociability and motor excitation, most often unproductive, are characteristic. Sexual desire increases, and memory capacity improves. Stimulants suppress appetite and the need for sleep.

When consuming illicitly prepared ephedrone, a feeling of lightness and weightlessness often arises.

Stimulant intoxication is accompanied by somatovegetative disorders in the form of pale skin, dry mucous membranes, tachycardia, and elevated blood pressure. A neurological examination reveals wide pupils with a weakened reaction to light, muscle tremor, and stereotyped movements of the lips and tongue. As the severity of intoxication increases, tachycardia worsens, cardiac rhythm disturbances may occur, and blood pressure continues to rise. Nausea, vomiting, and headache may be observed. Convulsive seizures, transient ischemic attacks, stroke, myocardial infarction, and acute renal failure are possible.

In severe stimulant intoxication, acute paranoid psychoses, delirium, and oneiroid states may develop. After pervitin use, a delusion-like state may develop with ideas of possessing special abilities, such as the ability to predict events, read the thoughts of other people, and control them from a distance, often while retaining partial insight into the experienced phenomena [1].

Caffeine intoxication is most often observed after consuming so-called 'chifir'—a beverage prepared by prolonged boiling of a large amount of tea, and less frequently upon abusing so-called 'energy' drinks. Acute caffeine intoxication is clinically similar to a hypomanic state. There is an elevation of mood, perception becomes brighter and more vivid, the pace of thought accelerates, and sociability and speech activity increase. Sexual activity may intensify.

Somatoneurological disorders in severe caffeine intoxication are represented by dizziness, tachycardia, extrasystoles, a relatively minor increase in blood pressure, and increased diuresis. Complaints of headache may occur; examination reveals tremor, hyperreflexia, and increased pain sensitivity.

In severe caffeine intoxication, the development of delirium, twilight states of consciousness, and acute hallucinosis is possible [1].

1.6.7 Clinical presentation of acute hallucinogen intoxication

Acute intoxication with hallucinogens is characterized by the development of psychosis of the oneiroid or delirium type. Perception of time and body schema is disrupted. The emotional sphere is characterized by frequent shifts in opposing affects, ranging from euphoria to anxiety, suspiciousness, or dysphoria. Insight into one's condition disappears. The grossest disorders are observed in the sphere of perception. This primarily concerns visual disturbances. The world becomes brighter, objects are colored in unusual colors or a single color. The outlines of objects blur or, conversely, acquire clear boundaries; objects may be surrounded by a peculiar halo ('aura'). Visual hallucinations, both elementary and scenic, are characteristic. Deceptions of perception most often take the form of true hallucinations, but pseudohallucinations can also occur. Auditory hallucinations are much less common, and taste, tactile, and olfactory illusions and hallucinations are extremely rare. Metamorphopsias, as well as derealization and depersonalization, are very characteristic of intoxication with LSD and other psychodysleptics. The psychotic state is accompanied by nausea, sweating, facial flushing, and a feeling of heat or cold. Mydriasis and hyperactive tendon reflexes are characteristic. Acute intoxication with anticholinergic agents presents with headaches, ataxia, tremor, a feeling of numbness in the extremities, paresthesias, tachycardia, arterial hypertension, and dry mouth [1].

1.6.8 Clinical presentation of acute nicotine intoxication

Acute intoxications in smokers are extremely rare; most often they are associated with the abuse of tobacco preparations in the form of decoctions or infusions, and occasionally tinctures. In recent years, cases of acute nicotine intoxication from inhaling vapor from 'electronic cigarettes' using concentrated solutions ('liquids') have become more frequent. In mild and moderate nicotine intoxication, profuse salivation, nausea, tachycardia, dizziness, tinnitus, weakness, cold sweat, and spasms of the larynx, esophagus, and stomach are observed. As the degree of intoxication increases, vomiting and diarrhea may develop.

In severe nicotine intoxication, repetitive vomiting, visual and hearing impairments, and bradycardia occur. Hypersalivation and abdominal pain, intensifying during bouts of nausea and vomiting, are characteristic. Cardiac rhythm disturbances and cardiac arrest in diastole may be observed. The development of delusional disorders, convulsive seizures, and, in the most severe cases, a comatose state is possible [1].

1.6.9 Clinical presentation of acute volatile solvent intoxication

These substances are usually taken by inhalation of vapors, and less commonly by application through the skin. Individuals experiencing acute intoxication with these substances invariably exhibit a sharp chemical odor.

Acute intoxication with volatile solvents presents with acute hallucinosis, delirium, or oneiroid states. Alteration of consciousness begins with stupor, followed by visual and auditory hallucinations. Initially, insight into hallucinatory experiences may be preserved, but as the degree of intoxication deepens, hallucinations become vivid and scenic, insight is typically lost, and the subject is completely immersed in their own hallucinations. After the effects of psychoactive substances wear off, insight into the experience is rapidly restored. Within 10-30 minutes, consciousness clears completely, and hallucinations cease. The affect is generally labile, ranging from euphoria to anxiety, fear, and aggression. Somatoneurological disorders are represented by pale skin, tachycardia, dry mucous membranes, and possible nausea or vomiting. Gait instability, impaired motor coordination, slurred speech, nystagmus, muscle weakness, blurred vision, or diplopia are also characteristic. In severe cases, depression of consciousness reaching the level of coma is observed [1].

1.6.10 Clinical presentation of acute intoxication caused by the simultaneous use of multiple narcotic substances and other psychoactive substances

The clinical presentation of acute intoxication (AI) with multiple psychoactive substances (PAS) is usually determined by the effects of the predominant, most active substance. Thus, combined AI with cocaine and alcohol may clinically differ very little from cocaine AI, but the probability of developing severe complications from such combined intoxication (cardiac arrhythmias, ischemia) increases significantly.

A distinct staging in the development of AI symptoms from multiple PAS may also be observed. For example, with the simultaneous intake of cocaine and methadone, the effects of cocaine predominate initially, followed by those of methadone.

If PAS with similar effects are combined, synergism is observed, which is particularly dangerous when taking two or more hypnotics and sedatives. For example, the simultaneous intake of an opioid and benzodiazepine derivatives or alcohol and a GABA-mimetic frequently results in fatality [1].

2. Diagnostics, medical indications and contraindications for diagnostic methods

It is necessary to rely on the following diagnostic criteria:

- evidence of recent use of PAS (or substances) in doses high enough to cause AI;

- symptoms and signs of AI must correspond to the known action of the specific substance (or substances) as defined below (see subsection "Specific diagnostic signs of AI by various PAS") and must be of sufficient severity to lead to clinically significant disturbances in consciousness level, cognitive functions, perception, emotional state, or behavior;

- the presenting symptoms or signs cannot be explained by a non-substance-related medical condition or another mental or behavioral disorder [10].

2.1 Complaints and Anamnesis

Patient complaints in AI depend on the type and dose of PAS and are determined either by its primary pharmacological or side effects. Patient complaints may also be associated with complications of AI. In severe AI, complaints are generally absent because contact with the patient is difficult or impossible.

2.2 Physical Examination

- the patient's appearance and behavior are of significance;

- attention should be paid to recent injection marks;

- the odor emanating from the patient is significant, as it can help identify the PAS that caused the intoxication.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

Comments:

The clinical presentation of PAS AI can vary greatly both between different subjects and within the same subject depending on a multitude of factors. Thus, it may depend on the dynamics of PAS intake (the time over which the total amount was consumed), individual characteristics of the subject (age, ethnicity, sex, mental and physical condition), characteristics of the PAS (degree of purification, presence of toxic impurities), and ambient temperature. Finally, the degree of tolerance to PAS in dependent individuals is of great importance. Furthermore, when diagnosing PAS AI, it must be taken into account that its symptoms do not always reflect the primary action of the substance; for example, substances with sedative properties may cause agitation or hyperactivity symptoms, whereas stimulants may cause withdrawal into oneself and physical immobility [1,12].

2.3.1 AI caused by alcohol use (F10.0xx)

- alcohol odor;

- nausea and vomiting;

- skin hyperemia;

- mydriasis;

- nystagmus;

- accommodation disorder;

- facial flushing;

- scleral injection;

- tachycardia;

- arterial hypertension;

- speech, gait, and motor coordination impairment;

- rapid mood swings, frequently dysphoria;

- decreased pain sensitivity;

- psychomotor agitation or retardation.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

- alcohol odor;

- nausea and vomiting;

- skin pallor;

- involuntary urination;

- inability to stand and perform purposeful actions;

- impaired verbal contact (brief, often meaningless utterances or sounds);

- constricted pupils with sluggish reaction to light;

- depressed tendon reflexes and reduced corneal reflexes;

- spontaneous nystagmus;

- decreased pain sensitivity;

- altered heart rate (bradycardia or tachycardia), possible cardiac arrhythmias;

- arterial hypotension;

- obtundation, stupor, or coma.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

- sudden change in mental state after consuming a small amount of alcohol;

- psychomotor agitation;

- sharp shift in affect (anxiety, fear, rage);

- behavioral disorders (flight, aggression);

- twilight state of consciousness;

- complete, less frequently partial, amnesia of the events after prolonged sleep.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

Comments: When examining patients with alcohol AI, it is necessary to consider the high probability of complications requiring immediate medical care: traumatic brain injury (TBI), gastrointestinal bleeding (GIB), gastric content aspiration, acute pancreatitis, cardiac arrhythmias.

2.3.2 AI caused by opioid use (F11.0xx)

- miosis, lack of pupillary reaction to light;

- skin pallor;

- itching of the skin of the face, especially the tip of the nose, and the upper half of the trunk;

- sluggish facial expression;

- slowed speech with long pauses;

- bradypnea;

- bradycardia;

- arterial hypotension;

- decreased peristalsis;

- dysarthria;

- decreased pain sensitivity;

- complacency or euphoria;

- psychomotor retardation.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

- miosis or mydriasis, absence of pupillary light reflex;

- skin pallor;

- bradypnea;

- bradycardia;

- arterial hypotension;

- decreased or absent peristalsis;

- hyporeflexia;

- absence of pain sensitivity;

- dysarthria;

- obtundation, sopor, or coma;

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

Comments: A thorough physical examination of patients with suspected acute opioid intoxication must be performed in order to rule out skin and subcutaneous tissue infections.

2.3.3 Acute intoxication caused by cannabinoid use (F12.0xx)

- odor of cannabis, burnt leaves;

- mydriasis;

- scleral injection;

- dry mouth;

- increased appetite;

- changes in heart rate (bradycardia or tachycardia);

- changes in blood pressure (hypotension or hypertension);

- affective disorders (euphoria, fear, dysphoria);

- psychomotor agitation or retardation.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

- odor of cannabis, burnt leaves;

- nausea, vomiting;

- mydriasis;

- scleral injection;

- decreased pain sensitivity;

- altered heart rate (bradycardia or tachycardia), possible cardiac arrhythmias;

- changes in blood pressure (hypotension or hypertension);

- seizures;

- affective disorders (euphoria, fear, dysphoria);

- transient psychotic disorders (illusions and hallucinations, delusions, phenomena of derealization and depersonalization);

- psychomotor agitation or retardation.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

Comments: Acute intoxication with synthetic cannabinoids generally does not differ from acute intoxication with natural cannabis preparations. Due to the greater activity of synthetic cannabinoids regarding cannabinoid receptors, the state of acute intoxication develops earlier, its signs increase faster, and the intoxication is of shorter duration. As a rule, the state of intoxication is more severe, with frequent cases of poisoning and the development of severe complications.

2.3.4 Acute intoxication caused by the use of sedative and hypnotic drugs (F13.0xx)

- mydriasis or miosis;

- nystagmus;

- accommodation disorder;

- skin pallor;

- masked facial expressions;

- speech, gait, and motor coordination impairment;

- decreased tendon and corneal reflexes;

- decreased pain sensitivity;

- changes in heart rate (bradycardia or tachycardia);

- arterial hypotension;

- shallow, infrequent breathing;

- affective disorders (euphoria or dysphoria);

- lethargy;

- psychomotor agitation or retardation.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

- miosis or mydriasis, sluggish pupillary reaction to light;

- spontaneous nystagmus;

- accommodation disorder;

- pale or grayish skin tone, oily skin;

- lack of facial expression;

- inability to stand and perform purposeful actions;

- impaired verbal contact (muttering or isolated sounds);

- depression or absence of tendon and corneal reflexes;

- decreased pain sensitivity;

- changes in heart rate (bradycardia or tachycardia);

- arterial hypotension;

- involuntary urination is possible

- shallow, infrequent breathing;

- obtundation, stupor, or coma.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

Comments: AI with GABA-mimetics (butanediol, butyrolactone, etc.) generally does not differ from AI with other hypnotic and sedatives. At the peak of intoxication, seizures and bradyarrhythmia may develop.

2.3.5 AI caused by cocaine use (F14.0хх)

- mydriasis;

- skin pallor;

- arterial hypertension;

- tachycardia;

- hyperreflexia;

- affective disorders (euphoria or dysphoria);

- aggressiveness, grandiosity;

- insomnia;

- decreased appetite;

- psychomotor agitation.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

- mydriasis;

- skin pallor;

- nausea, vomiting;

- blood pressure changes (arterial hypertension, hypotension possible);

- pronounced tachycardia, tachyarrhythmia possible;

- hyperreflexia;

- transient psychotic disorders (illusions and hallucinations, delusions);

- seizures possible;

- psychomotor agitation, sometimes lethargy.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

2.3.6 AI caused by the use of other psychostimulants, including caffeine (F15.0хх)

- mydriasis;

- skin pallor;

- arterial hypertension;

- tachycardia;

- hyperreflexia;

- affective disorders (euphoria, hypomania, dysphoria);

- insomnia;

- decreased appetite;

- elevated body temperature;

- psychomotor agitation;

- delusion-like ideas of grandiosity.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

- mydriasis;

- skin pallor;

- hyperthermia;

- blood pressure changes (arterial hypertension, less commonly hypotension);

- tachycardia, tachyarrhythmia possible;

- hyperreflexia;

- transient psychotic disorders (illusions and hallucinations, delusions);

- muscle spasms, convulsions;

- psychomotor agitation, sometimes lethargy.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

Comments: Clinical manifestations of AI with new synthetic psychostimulants (synthetic amphetamines, methamphetamines, cathinones, and methcathinones) are quite diverse. These substances may vary in duration of action, onset of effect, and concomitant symptoms. In general, the clinical signs of AI with new psychoactive substances (PAS) of this group correspond to the signs of intoxication with known psychostimulants; however, their distinctive feature can be considered the presence of additional hallucinogenic and empathogenic effects.

2.3.7 AI Caused by Use of Hallucinogens (F16.0x)

Since the intoxication effects of hallucinogens are determined by psychotic disorders, the patient's condition must always be assessed as severe.

- mydriasis;

- nystagmus;

- coordination disorders;

- arterial hypertension;

- tachycardia;

- delirium-type impaired consciousness in AI with anticholinergic agents;

- oneiric-type impaired consciousness in AI with psychodysleptics;

- auditory, visual, or tactile illusions, or hallucinations;

- depersonalization;

- derealization;

- delusional ideas;

- psychomotor agitation or retardation.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

Comments: AI with new synthetic hallucinogens (phenethylamines and tryptamines) generally does not differ from that with "classic" psychotomimetics such as mescaline and psilocybin.

2.3.8 AI Caused by Nicotine Use (F17.0xx)

- nausea or vomiting;

- hypersalivation;

- abdominal pain;

- sweating;

- skin pallor;

- tachycardia, tachyarrhythmia possible;

- arterial hypertension;

- insomnia.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

- nausea or vomiting;

- nystagmus;

- marked pallor of the skin;

- speech, gait, and motor coordination impairment;

- bradycardia, bradiarrhythmia possible;

- arterial hypotension;

- bradypnea.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

2.3.9 AI Caused by Volatile Solvents (F18.0x)

Since the intoxication effects of volatile solvents are generally determined by psychotic disorders, and due to the high risk of severe complications (acute encephalopathy, acute renal or hepatic failure), the patient's condition must always be assessed as severe.

- "chemical" odor;

- mydriasis;

- nystagmus;

- accommodation disorder;

- pallor or cyanosis (with nitrite use);

- nausea, vomiting;

- hypersalivation;

- speech, gait, and motor coordination impairment;

- tachycardia;

- affective disorders (euphoria, fear, dysphoria);

- stupor or sopor possible;

- transient psychotic disorders (illusions and hallucinations, most commonly visual, less commonly auditory and tactile, metamorphopsias, depersonalization);

- psychomotor agitation or retardation.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

2.3.10 AI Caused by Multiple Drug Use and Use of Other Psychoactive Substances (F19.0xx)

2.3 Laboratory Diagnostics

Comments: Currently, qualitative determination of the following PAS by ICA is possible: amphetamine, marijuana, morphine**/heroin, cocaine, methamphetamine, barbiturates, benzodiazepines, phencyclidine, methadone, and ecstasy (MDMA). Rapid diagnostics is performed using test strips; mono-tests (one test per one PAS) and multi-tests (determination of up to 10 different PAS in a single test) can be used. ICA with photometric detection allows not only determining the presence of a PAS but also estimating its concentration. The disadvantages of ICA are the possibility of false-positive results and the inability to detect many PAS (e.g., synthetic cannabinoids and stimulants, hallucinogens, GABA mimetics, etc.). Therefore, when ambiguous ICA results are obtained, a chemical-toxicological study is required.

Comments: Professional breathalyzers allow a rapid and sufficiently accurate estimation of the concentration of ethanol vapors in exhaled air, which is directly dependent on the alcohol concentration in the patient's blood. The disadvantage of this method is the inability to determine the concentration of other alcohols and substances that are components of alcohol surrogates. Therefore, in case of a clear discrepancy between the breathalyzer results and the clinical picture, a chemical-toxicological study is required.

Comments: GC-MS is an accurate method for the qualitative and quantitative determination of PAS in biological media. The method allows, inter alia, non-targeted analysis, i.e., simultaneous determination of a large number of different PAS. The HPLC-MS method is less accessible due to its high cost, but has a significant advantage—it allows the detection of PAS that degrade upon heating.

Comments: In severe PAS-induced AI, water-electrolyte balance (WEB) and acid-base balance (ABB) disorders frequently develop. They manifest as thirst, edema, cardiac rhythm disturbances, blood pressure changes, weakness, and dry mucous membranes. Laboratory diagnostics is necessary to confirm or rule out these disorders (the minimum analysis includes determining potassium and sodium levels, blood gas composition, pH, BE) [1, 19].

2.4 Instrumental Diagnostics

Performing these diagnostic procedures does not establish the diagnosis of PAS-induced AI. Nevertheless, they are necessary for the early diagnosis of existing complications of chronic PAS use, which can significantly affect the outcome of AI.

Comments: Monitoring of vital functions should preferably be performed using hardware methods (with a resuscitation monitor). If a monitor is not available, vital signs should be checked periodically manually. The frequency of repeat measurements is determined by the attending physician depending on the severity of the patient's condition.

Comments: Diuresis monitoring in patients with severe PAS AI is necessary due to frequent renal dysfunction caused by the direct toxic effects of PAS and ballast substances contained in alcohol and drugs.

2.5 Other Procedures

Because PAS AI is characterized by high variability of clinical manifestations and a high probability of complications, it is often necessary to involve the following specialists for diagnosis and management [1]:

- General Practitioner (Physician);

- Neurologist;

- Anesthesiologist-Resuscitator.

Additional diagnostic methods are prescribed by specialists based on the specific clinical situation, in accordance with indications (radiography [X-ray],

ultrasound examination [ultrasound], computed tomography [CT], magnetic resonance imaging [MRI]).

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 General approaches to the treatment of acute psychoactive substance intoxication

Mild AI states do not require specific therapy. Moderate AI states may manifest with behavioral disorders that may require physical restraints and/or psychopharmacotherapy. Severe AI states require emergency medical care. The severity of AI does not always correlate with the concentration of PAS in the patient's blood. Immediate quantitative determination of PAS concentration in body fluids is technically not always feasible, so physicians often have to adhere to a symptomatic approach when choosing treatment tactics. For this reason, assessing the patient's level of agitation or sedation is extremely important. A very convenient diagnostic tool for this assessment is the Richmond Agitation-Sedation Scale (RASS) (Appendix G-1) [1, 19].

3.2 Treatment algorithm

3.2.1 Restraint of the patient in a functional bed

Comments: Restraints should be applied as delicately as possible, using soft, non-traumatic means (towels, sheets, fabric straps, etc.). Each limb and the shoulder girdle must be securely restrained; compression of nerve trunks and blood vessels must be avoided. The restrained patient must be constantly within the staff's field of vision. Restraint does not imply the removal of supervision, but rather requires constant monitoring of the patient's condition. The use of physical restraints requires a mandatory entry in the medical documentation indicating the time of application and removal of the restraints.

3.2.2 Treatment of psychomotor agitation and seizures (if they occur)

In cases of AI caused by stimulating PAS, psychotic states with agitation, and seizure disorders, it is very important to relieve agitation as quickly as possible with sedatives, because in these states the CNS oxygen and energy substrate requirements increase sharply. The capacity for their delivery in addiction patients is generally reduced, which can lead to oxygen deprivation, CNS dysfunction, and cerebral edema. Sedative therapy should be administered with caution, avoiding excessive sedation.

Comments: Diazepam** is the drug of choice, administered as a 0.5% solution, as a bolus of 5 mg as needed every 2-5 minutes, with a maximum daily dose of 0.25 mg/kg of body weight [17]. Other parenteral anxiolytics may also be used [16]. It should be taken into account that Diazepam** and other anxiolytics are contraindicated in AI caused by CNS depressants, and therefore they should not be used for short-term agitation in patients with acute alcohol intoxication. Only Diazepam** is recommended for the treatment of children and adolescents. For children older than 5 years, Diazepam** is administered intravenously and slowly at 1 mg every 2-5 minutes up to a maximum dose of 10 mg. If necessary, treatment is repeated in 2-4 hours.

Comments: Haloperidol** is the drug of choice, administered as a 0.5% solution in a single dose of no more than 10 mg [17, 18]. Other parenteral antipsychotics can also be used [16-20]. In children older than 3 years, haloperidol** is prescribed at 0.025-0.05 mg per day, with a maximum daily dose of 0.15 mg/kg. Other antipsychotics are contraindicated in patients under 18 years of age.

Comments: Diazepam** is prescribed at 0.15 mg/kg of the patient's weight (maximum single dose 10 mg) [18]. For children older than 5 years, Diazepam** is administered intravenously and slowly at 1 mg every 2-5 minutes up to a maximum dose of 10 mg.

Comments: Sodium thiopental** is prescribed at 2–7 mg/kg of the patient's body weight at a rate not exceeding 50 mg per minute. For children, Sodium thiopental** is prescribed as a 1% solution administered as a slow IV push over 3-5 minutes, as a single dose of 3-5 mg/kg of body weight. As an alternative to Sodium thiopental**, #Propofol** may be used at 20 mcg/kg of body weight per minute until a dose of 1–2 mg/kg is reached, followed by a continuous infusion of a maintenance dose of 30–200 mcg/kg/min [19]. Administration of #Propofol** is not recommended for children under 16 years of age. Sodium thiopental** and #Propofol** may only be used in the presence of an anesthesiologist-resuscitator, and with available equipment to support cardiac function, maintain airway patency, and provide respiratory support.

3.2.3 Gastric catheterization and lavage, administration of intestinal sorbents

Comments: Gastric lavage is performed via a gastric tube using clean water at room temperature until the washout is clear. If the patient has depressed consciousness, gastric lavage must be performed in the Fowler's position (head elevated) to prevent aspiration of gastric contents [16]. If the RASS sedation score is less than -3, the stomach is catheterized only after tracheal intubation. If specialists and equipment for intubation are unavailable, the patient must be transferred to a toxicology department.

3.2.4 Urinary bladder catheterization

Comments: Severe acute intoxication due to psychoactive substance use requires careful monitoring of diuresis, as urinary retention can lead to renal and heart failure, pulmonary edema, and cerebral edema. In case of unconsciousness, urinary catheterization is the only reliable method to monitor diuresis. An indication for urgent urinary catheterization is urinary retention for more than 6 hours.

3.2.5 Venous catheterization

Comments: A flexible intravenous catheter allows for infusion therapy and intravenous administration of drugs with a minimal risk of vascular wall injury and bleeding in patients with psychomotor agitation. The catheterization duration is 24–72 hours depending on the catheter material.

Comments: Central venous catheterization is performed by an anesthesiologist-resuscitologist.

3.2.6 Infusion therapy

Comments: Infusion therapy is the primary method for stimulating natural detoxification processes in narcology. Adult patients are administered infusion solutions at a rate of no more than 500 ml/hour, in volumes up to 3–4 l per day, up to 1 l per hour [26–27]. In children, infusion solutions are administered at a rate of 10 ml/kg per hour [25]. The infusion volume depends on the degree of intoxication and the severity of water-electrolyte balance and acid-base balance disorders. In the presence of pathological changes in the heart, lungs, liver, and kidneys, the infusion volume must be restricted. When administering large-volume infusion therapy for detoxification (forced diuresis method), careful monitoring of diuresis is necessary, which, if required, is stimulated by the administration of 20–40 mg of furosemide** per day [19]. If diuresis is inadequate to the prescribed infusion therapy, the dose of #furosemide** can be increased to 100–200 mg [26, 27]. The daily dose of furosemide** in children should not exceed 20 mg per day. Since infusion therapy can significantly affect blood electrolyte balance and acid-base balance, composition-balanced polyionic buffered solutions must be used. Infusion therapy is carried out until complete correction of water-electrolyte balance and normalization of acid-base balance is achieved.

3.2.7 Restoration of airway patency and/or mechanical ventilation

Comments: If there is no intensive care unit in the narcological hospital, the patient must be immediately transferred to a general intensive care unit.

3.2.8 Administration of specific antidotes

Comments: Naloxone** is administered intravenously as a bolus diluted in 0.9% sodium chloride solution**. The initial dose of naloxone** is 0.4 mg; if there is no effect, injections are repeated at intervals of 2–3 minutes, with a maximum total dose of 10 mg. If naloxone** is ineffective, the diagnosis of opioid acute intoxication is excluded. Children are recommended an initial dose of naloxone** of 0.01 mg per 1 kg of body weight intravenously. If the desired effect is not achieved, naloxone** is re-administered at a dosage of 0.1 mg per 1 kg of body weight. Depending on the patient's condition, intravenous infusion may be indicated. If intravenous administration is not feasible, the drug is administered slowly, intramuscularly or subcutaneously, at an initial dose of 0.01 mg per 1 kg of body weight. Repeated administration is possible if necessary.

Comments: Rapid awakening induced by the antidote in acute opioid poisoning leads to a significant increase in the oxygen and energy substrate demands of the central nervous system. In the presence of hypoxia, this can trigger decompensation of energy metabolism, increased cerebral edema, and a higher probability of a fatal outcome.

Comments: #Flumazenil is administered intravenously diluted in 5% dextrose** solution or sodium chloride** solution at an initial dose of 0.5 mg; if necessary, the injection is repeated every 60 seconds up to a total dose of 2 mg. If #Flumazenil is ineffective, acute poisoning with benzodiazepine derivatives (benzodiazepines) is unlikely. If a patient with acute benzodiazepine poisoning has been in a coma with respiratory depression for a prolonged period (more than half an hour), the administration of #Flumazenil is contraindicated. For children, the recommended initial dose is 0.01 mg/kg (up to 0.2 mg) IV over 15 seconds. If the desired level of consciousness recovery is not achieved after another 45 seconds, additional doses of 0.01 mg/kg (up to 0.2 mg) can be administered at 60-second intervals (no more than 4 times) up to a maximum total dose of 0.05 mg/kg, but not exceeding 1 mg. The dose is selected individually depending on the patient's response.

Comments: Metadoxine activates ethanol-metabolizing enzymes and accelerates the oxidation and elimination of ethanol and acetaldehyde. Metadoxine is prescribed at a dose of 300–600 mg (5–10 ml) intramuscularly or intravenously. For intravenous administration, the required dose of the drug is diluted in 500 ml of isotonic sodium chloride** solution or 5% dextrose** solution and administered as an intravenous drip over 1.5 hours. Metadoxine is not prescribed to patients under 18 years of age.

Comments: Galantamine** reversibly inhibits acetylcholinesterase, thereby increasing the level of endogenous acetylcholine, which in turn reduces the effect of psychoactive substances with anticholinergic action. The drug is prescribed at a dose of 10 mg intravenously. If signs of impaired consciousness persist, the injections are repeated; the maximum daily dose of the drug is 20 mg. In children over 3 years of age, galantamine** is prescribed at a dose of 0.03–0.28 mg/kg of body weight.

3.2.9 Administration of symptomatic treatment

Comments: Preparations containing succinic acid are prescribed: (Inosine + Nicotinamide + Riboflavin + Succinic acid)** or Ethylmethylhydroxypyridine succinate** or Meglumine sodium succinate** [19, 24, 25, 33, 34]. Of the listed drugs, only meglumine sodium succinate** is recommended for children and adolescents.

3.2.10 Psychotherapy in acute psychoactive substance intoxication

Comments: In acute psychoactive substance poisoning, psychotherapeutic treatment is sharply limited, as patients are not fully able to utilize the offered psychotherapeutic interventions. The main task of psychotherapeutic intervention during this period is engaging the patient and keeping them in a treatment program that is not limited to the management of acute poisoning. It is necessary to inform the patient's close relatives and family members about the need for further therapy for the dependence syndrome once the diagnosis is established.

During this period, family counseling must be conducted to involve family members and significant others in the therapeutic program. It is also necessary to talk with the patient, reassure them, explain the events that have occurred, prepare them for further treatment, and provide support. Psychotherapy is not performed in cases of impaired consciousness.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Specific rehabilitation measures within the framework of acute psychoactive substance intoxication are not carried out. Rehabilitation focuses on the restoration of somatovegetative and mental functions impaired as a result of intoxication.

5. Prevention and Dispensary Observation

In acute psychoactive substance intoxication, tertiary (modification) prevention is of the utmost importance; it is predominantly medical and individual in nature, and is aimed at preventing recurrent intoxications and reducing harmful effects on the mental and somatic spheres of a patient who has suffered severe intoxication. To determine the appropriate form of prevention and dispensary follow-up, it is crucial to establish whether the patient's acute intoxication is accidental or has occurred within the context of a substance use disorder. If a clinical examination reveals that a patient has been using psychoactive substances with harmful consequences, the patient should be offered preventive follow-up at a addiction treatment clinic for 1 year, and if a psychoactive substance dependence syndrome is identified, dispensary follow-up for 3 years [1].

6. Organization of Medical Care

- with moderate or severe acute psychoactive substance intoxication complicated by concomitant somatoneurological pathology that threatens the patient's life;

- with acute psychoactive substance intoxication complicated by delirium.

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

Comments: If the addiction hospital lacks an intensive care unit, such patients must be transferred immediately to a toxicology department or a general intensive care unit.

Comments: If immediate transfer of a patient with acute intoxication caused by methanol, ethylene glycol, isopropanol, and other psychoactive substances with lethal synthesis to a toxicology department is not feasible, and there is compelling evidence (anamnesis, pronounced acidosis, clinical signs) of surrogate poisoning, a 30% ethyl alcohol solution of 100 ml should be administered orally [12].

LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).

7. Additional Information

The outcome of acute intoxication resulting from psychoactive substance use is influenced by genetic factors (e.g., the activity of enzymes involved in psychoactive substance elimination), the presence of comorbid somatic diseases, and the speed at which emergency care is provided.

Criteria for Evaluating the Quality of Medical Care

Quality criteria for specialized medical care for adults with acute intoxication caused by the use of psychoactive substances (ICD-10 codes: F10.0; F11.0; F12.0; F13.0; F14.0; F15.0; F16.0; F18.0; F19.0).

References

Appendix A1. Working Group Composition

Co-Chairs:

Klimenko, Tatyana Valentinovna, MD, Prof.

Krupitsky, Evgeny Mikhailovich, MD, Prof.

Masyakin Anton Valerievich, MD, Associate Professor

Secretary:

Gubanov, Georgy Alexandrovich

Working Group Members:

Agibalova, Tatyana Vasilyevna, MD

Arkus, Maxim Leonidovich, PhD

Buzik Oleg Zhanovich, Doctor of Medical Sciences, Professor

Vinnikova Maria Alekseevna, Doctor of Medical Sciences, Professor

Kirzhanova Valentina Vasilyevna, MD, Prof.

Korchagina, Galina Alexandrovna, MD, Prof.

Ilyuk Ruslan Dmitrievich, D.Sc. in Medicine

Lobacheva Anna Stanislavovna, Ph.D. in Medicine

Nadezhdin Alexey Valentinovich, Ph.D. in Medicine

Nenastyeva Anna Yuryevna, Candidate of Medical Sciences

Poplevchenkov Konstantin Nikolaevich, Ph.D. in Medicine

Rybakova Ksenia Valeryevna, D.Sc. in Medicine

Authors:

1. Mikhailov Mikhail Albertovich, Doctor of Medical Sciences. Russian Society of Psychiatrists.

2. Utkin Sergey Ionovich, Candidate of Medical Sciences. Russian Society of Psychiatrists. Federation of Anesthesiologists and Reanimatologists.

Conflict of interest: none

All members of the working group have confirmed the absence of financial support / conflicts of interest that need to be disclosed.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of these clinical guidelines:

Psychiatrist-narcologist

District psychiatrist-narcologist

Adolescent psychiatrist

Psychiatrist

District psychiatrist

Psychotherapist

Medical psychologist

General Practitioner

Neurologist

The following information resources were used in the development of these clinical guidelines:

• "Requirements for the formatting of clinical guidelines for placement in the Rubricator." Letter of the First Deputy Minister of Health I.N. Kagramanyan dated September 01, 2016, No. 17-4/10/1-4939.

• Analysis of scientific literature sources and other data, as well as internet resources over the past 10 years:

domestic: guidelines for physicians, scientific publications in periodicals, e-library scientific electronic library, State Register of Medicines, Register of Medicines, Federal State Statistics Service of the Russian Federation;

international: Cochrane Library, Medline, MedScape, PubMed, National Institute on Alcohol Abuse and Alcoholism (NIAAA), Substance Abuse and Mental Health Services Administration (SAMHSA), European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)

Regulatory documents of the Government of the Russian Federation and the Ministry of Health of the Russian Federation.

Rating schemes for assessing the levels of evidence reliability (1, 2, 3, 4, 5) (Appendix 1, 2) and the levels of recommendation validity (A, B, C) (Appendix 3) were used in the development of these clinical guidelines.

Appendix 1. Level of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Appendix 2. Level of Evidence grading scale

(LoE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Appendix 3. Grade of Recommendation (GoR) scale

(GoR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Appendix A3. Reference Materials

The use of psychopharmacotherapy in children and adolescents in the treatment of acute psychoactive substance intoxication has the following features:

Diazepam** — in children older than 5 years, administered intravenously slowly at 1 mg every 2–5 minutes until reaching a maximum dose of 10 mg. If necessary, repeat the treatment after 2–4 hours.

Sodium thiopental** — administered to children as a 1% solution intravenously, slow bolus over 3–5 minutes, as a single dose at 3–5 mg/kg of body weight.

Haloperidol** — in children over 3 years of age, prescribed at 0.025–0.05 mg daily, maximum daily dose is 0.15 mg/kg.

Furosemide** — the daily dose in children should not exceed 20 mg per day.

Naloxone** — the recommended initial dose for children is 0.01 mg per 1 kg of body weight intravenously. If the desired effect is not achieved, naloxone** is re-administered at a dosage of 0.1 mg per 1 kg of body weight. Depending on the patient's condition, intravenous infusion may be indicated. If intravenous administration is not feasible, the drug is administered slowly, intramuscularly or subcutaneously at an initial dose of 0.01 mg per 1 kg of body weight. Repeat administration is possible if necessary.

#Flumazenil — the recommended initial dose is 0.01 mg/kg (up to 0.2 mg) i.v. over 15 seconds. If the desired level of consciousness recovery is not achieved after another 45 seconds, an additional 0.01 mg/kg (up to 0.2 mg) can be administered at 60-second intervals (no more than 4 times) up to a maximum total dose of 0.05 mg/kg, but not exceeding 1 mg. The dose is selected individually depending on the patient's response [25].

#Metadoxine — not recommended for use in children and adolescents under 18 years of age (safety and efficacy have not been established)

Galantamine** — in patients over 3 years of age, prescribed at a dose of 0.03–0.28 mg/kg, or:

from 3 to 5 years — 0.5–5.0 mg;

from 6 to 8 years — 0.75–7.5 mg;

from 9 to 11 years — 1.0–10.0 mg;

from 12 to 15 years — 1.25–12.5 mg;

over 15 years — 1.25–15.0 mg.

Ethylmethylhydroxypyridine succinate** — not recommended for use in children and adolescents under 18 years of age (safety and efficacy have not been established)

Inosine + Nicotinamide + Riboflavin + Succinic acid** — not recommended for use in children and adolescents under 18 years of age (safety and efficacy have not been established)

Meglumine sodium succinate** — recommended for children over 1 year of age

Order of the Ministry of Health of the Russian Federation No. 108 dated April 8, 1998, "On Emergency Psychiatric Care."

Letter of the Ministry of Health of the Russian Federation No. 2510/12967-02-32 dated December 26, 2002, "On Measures of Physical Restraint in the Provision of Psychiatric Care."

“Order of the Ministry of Health of the Russian Federation dated August 5, 2003,

No. 330 ‘On measures to improve therapeutic nutrition in healthcare institutions of the Russian Federation’.”

Order of the Ministry of Health of the Russian Federation No. 395n dated June 21, 2013, "On Approval of Medical Nutrition Standards."

Order of the Ministry of Health of the Russian Federation dated September 23, 2020, No. 1008n ‘On approval of the procedure for providing patients with therapeutic nutrition.’”

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Acute psychoactive substance (PAS) intoxication is a relatively short-term condition that occurs following the intake of PAS, characterized by diverse mental and behavioral disorders, posing a direct threat to the health and life of the patient and people around them, since behavior and reactions under the influence of psychoactive substances change drastically and may manifest as aggression directed at oneself and/or others. The intake of certain PAS can significantly disrupt the functioning of vital organs — heart, liver, kidneys, etc.

In a broad sense, PAS can refer to all chemical compounds of natural and artificial origin whose primary or secondary effect is an impact on the brain followed by an alteration in mental state. If the substance's ability to alter mood, physical condition, self-perception, perception of surroundings, behavior, and induce other psychophysical effects proves subjectively pleasant and desirable, then this substance has the potential to cause dependence.

According to their effect, all PAS can be conditionally divided into sedatives, stimulants, hallucinogens, and substances of mixed action (with certain reservations, since the effect often depends on the route of administration, dose, regularity and duration of intake, environment, initial mindset, and condition).

Sedative substances or depressants (opioids, hypnotics, sedatives, etc.), upon entering the body, exert a depressing effect on brain function, which leads to a disruption in the work of many organs and systems whose activity is regulated by the central nervous system. Accordingly, severe intoxication leads to depression of consciousness (up to coma), disruption of the respiratory and vasomotor center activity, heart rate is depressed, breathing becomes infrequent and shallow, blood pressure drops, and phenomena of cardiac and respiratory failure increase.

Stimulants (cocaine, amphetamines, methamphetamines ["salts", "crystals", "speed", etc.]) have a stimulating and excitatory effect on brain function and the body as a whole. Their effects manifest as increased activity, agitation, tachycardia with pronounced heart rhythm disturbances, elevated blood pressure, vasospasm, tremor, and as intoxication increases, ischemic attacks, seizures, severe psychosis, and the development of acute cardiovascular failure. At the same time, agitation may be replaced by stupor, respiratory depression, and coma.

Hallucinogens are a large group of psychoactive substances (PAS) that radically alter consciousness, distort perception and self-awareness, leading to hallucinations (the person "sees" or "hears" things that are not actually there) and severe behavioral disorders. In doing so, they may pose a threat to themselves and others. Inability to control one's actions and loss of contact with reality during intoxication often lead to tragic outcomes. Falls from heights, severe accidents, domestic injuries, suicides, and crimes committed under the influence of delusions and hallucinations are not uncommon.

The most widespread PAS globally are cannabinoids—hashish, hash oil, marijuana—and a large group of synthetic cannabinoids (SC), the so-called "spice", "mixes", and other smoking blends consisting of crushed plant matter that often lacks independent psychotropic effects. These are treated with chemical compositions containing SC. Smoking preparations containing cannabinoids is frequently followed by a transition from an agitated to a relaxed state, while high doses can induce hallucinations. Consequently, the clinical picture of cannabinoid intoxication is often unpredictable. Intoxication with cannabinoids is frequently accompanied by bouts of anxiety, panic, complete disorientation, and delusions. SC are significantly more toxic than natural cannabis preparations; intoxication with SC against a background of marked agitation can trigger severe psychotic schizophrenia-like disorders, seizures, cardiac dysfunction, acute respiratory and hepatorenal failure, and cerebral edema.

The severity of acute intoxication depends on the type of PAS, the dose administered, individual tolerance, and the patient's mental and physical health status. Mild PAS intoxication generally does not require active therapeutic interventions. However, continuous monitoring of the patient's condition is necessary due to the potential for deterioration as the degree of intoxication increases. This may be due, for example, to ongoing absorption of PAS from the stomach and intestines, the gradual dissolution of a PAS solution following intramuscular or subcutaneous injection, or a delayed or prolonged effect.

Severe PAS intoxication is immediately life-threatening and requires the immediate provision of intensive care.

When acute PAS intoxication is suspected, immunochromatographic rapid tests for the presence of such substances in urine or saliva can significantly facilitate diagnosis.

Upon the appearance of signs of acute PAS intoxication (disturbances in consciousness, behavior, cardiac activity, and respiration), an ambulance must be called immediately. In acute intoxication with excitatory and hallucinogenic PAS, one should try to calm the patient; in poisoning with sedatives, the patient should be kept awake. If the patient remains conscious and there is reliable information about oral ingestion of PAS, first aid at home may include gastric lavage. To do this, the patient should be given 2–3 liters of cold water to drink and vomiting induced by stimulating the pharynx (the so-called "restaurant" method). Subsequently, intestinal adsorbing agents (enterosorbents) may be used: colloidal silicon dioxide, polymethylsiloxane polyhydrate, and other silicon-based preparations. Drugs of this group effectively bind all PAS, including alcohol and its surrogates. Other intestinal adsorbing agents (activated charcoal, cellulose-based preparations, etc.) are ineffective for alcohol poisoning, but may be used to treat poisoning by other PAS.

Specialized medical care for severe acute PAS intoxication must be provided in a hospital setting and includes life support for respiration and cardiac activity, modern detoxification methods, including the administration of specific antidotes (drugs that block the effects of PAS), infusion therapy (intravenous administration of special solutions), and resuscitation measures when necessary.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Richmond Agitation-Sedation Scale (RASS)

Richmond Agitation-Sedation Scale (RASS)

The most reliable tool for assessing agitation and sedation in adult patients.

Sessler C.N., Gosnell M.S., Grap M.J., Brophy G.M., O’Neal P.V., Keane K.A., Tesoro E.P., Elswick R.K. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002; 166 (10): 1338– 1344.

Protsenko D.N. International guidelines for the management of agitation and delirium in adult patients in intensive care units. //Medical Alphabet. 2014. Vol. 2, No. 9. pp. 27-30.

RASS Assessment Procedure:

Patient observation:

- If awake, calm, and alert? — 0 points;

- If the patient shows signs of behavior characterized by anxiety or agitation — score from +1 to +4 points using the criteria listed above in the description.

If the patient is drowsy, ask them in a loud voice, calling them by name, to open their eyes and look at you. Repeat this several times if necessary. Ask the patient to maintain eye contact.

- If eye contact with the patient is possible and sustained for more than 10 seconds — score -1 point;

- If eye contact with the patient is possible, but not sustained for 10 seconds — score -2 points

- If the patient makes any movement in response to voice, excluding eye contact — score -3 points;

- If the patient does not respond to voice, perform physical stimulation by shaking the shoulder and rubbing the sternum;

- If the patient responds with any movement to physical stimulation — score -4 points;

- If the patient does not respond to voice or physical stimulation — score -5 points.