| disease | Mental Disorders Due to Psychoactive Substances |
Drug dependence, also known as drug addiction, refers to an intense craving for drugs. Patients compulsively take drugs chronically or periodically to seek the mental effects after ingestion and to avoid the suffering caused by withdrawal. Tolerance refers to the gradual reduction in the effectiveness of a drug with repeated use, requiring an increased dose to achieve the same effect as during the initial stage. Cross-tolerance occurs when tolerance developed to one drug results in tolerance to another drug upon initial use. This phenomenon can be observed between morphine and other sedatives, alcohol, and many analgesic hypnotics. Drug dependence is categorized into psychological dependence and physical dependence. Psychological dependence refers to the patient's craving for the drug to obtain the specific pleasure it provides. Its development is related to the type of drug and individual characteristics. Drugs that easily induce psychological dependence include morphine, heroin, codeine, pethidine, barbiturates, alcohol, amphetamines, and cannabis. Contributing factors include genetic predisposition, past educational environment, and current circumstances. It is generally believed that personality or specific mental states significantly influence susceptibility to drugs. Physical dependence refers to the physiological or biochemical changes in the central nervous system caused by repeated drug use, necessitating the continuous presence of the drug in the body to avoid withdrawal syndrome symptoms. Mild cases involve general discomfort, while severe cases may lead to life-threatening spasms. Typical drugs that induce physical dependence include opioids, barbiturates, and alcohol. Some drugs, such as nicotine, cause only psychological dependence without physical dependence. Many drugs can lead to dependence. ICD-10 classifies them into ten major categories: alcohol, opioids, cannabis, sedatives and hypnotics, cocaine, other stimulants (including caffeine), hallucinogens, tobacco, volatile solvents, and other psychoactive substances.
bubble_chart EpidemiologySince World War II, the number of addicts to narcotic drugs such as heroin and opium has rapidly increased in many countries across Europe, America, and Asia, becoming a major public health and social issue in numerous nations. The primary trend in drug dependence abroad is that the majority of heroin addicts are adolescents, driven by the pursuit of pleasure and recreation. This type of addiction has the characteristic of rapid spread or epidemic-like proliferation. Due to the high toxicity of heroin, addicts suffer from severe self-poisoning and a sharp rise in suicides, resulting in an extremely high mortality rate among this group. Data from the UK indicates that the mortality rate in this population is more than 20 times higher than that of the general population.
In China, the prevalence of opium and drug abuse was largely controlled after the founding of the People's Republic. However, since the 1980s (late stage [third stage]), there has been a resurgence, with a rapid spreading trend. Clinically, the common types of drug dependence in the 1970s were primarily sedatives and hypnotics. Since the 1980s, cases of addiction to anti-anxiety medications have gradually increased, while morphine-type drug addiction mainly involved pethidine, often due to medical misuse. Since the 1990s, heroin addiction has become the most prevalent clinical form.
The factors leading to drug addiction are not singular but are related to the availability of drugs, genetic predisposition, personality susceptibility, and sociocultural influences.
Some drug addicts, particularly young people, exhibit certain degrees of personality or moral disorders before drug use, such as poor academic performance, truancy, or disciplinary violations. Some come from families with a history of mental illness or personality disorders, or have experienced unhappy childhoods.
Healthcare and pharmacy professionals who have easy access to drugs may become a high-risk group.
Mechanisms of drug dependence formation: ① Metabolic tolerance and cellular tolerance. Metabolic tolerance refers to the accelerated drug metabolism process, leading to decreased concentration in tissues, weakened effects, and shortened effective duration. Cellular tolerance occurs due to certain adaptive changes in nerve cells, causing them to function normally only when high concentrations of the drug are present in the blood. The mechanism of this cellular adaptation remains unclear. ② Receptor theory. Morphine receptors with a special affinity for morphine-like drugs and endogenous morphine receptor agonists have been discovered in the brain. It is thus hypothesized that the rapid formation of drug dependence may be related to the special affinity between exogenous morphine and morphine receptors. When these receptors are blocked, tolerance increases sharply. ③ The disuse supersensitivity hypothesis of withdrawal syndrome. Long-term blockade of morphine receptors by morphine not only leads to increased tolerance but may also cause disuse supersensitivity due to receptor blockade by addictive drugs, resulting in withdrawal syndrome during discontinuation. ④ The biogenic amine theory. Research data indicate that monoamine neurotransmitters are involved in the mechanisms of analgesia and addiction. After morphine injection, the turnover rate of 5-HT in the brain increases with the development of tolerance.
Clinical Types of Drug Dependence
1. Morphine-Type Dependence
Opioid substances include opium, alkaloids extracted from opium (such as morphine), its derivatives like heroin, and synthetic compounds such as pethidine, methadone, and pentazocine. In addition to their analgesic effects, these drugs can induce euphoria and are highly addictive. Continuous use at common doses for just two weeks can lead to addiction, characterized by strong psychological dependence, physical dependence, and tolerance. The maximum prescribed dose of morphine for medical use is 0.03g per administration and 0.1g per day. However, literature reports indicate that morphine addicts may consume doses as high as 0.5–1.0g per use.
**Clinical Manifestations** Since the 1990s, heroin addiction has become a common issue in China's healthcare system. Since 1992, Peking University Sixth Hospital alone has treated over 20 cases. The majority of patients are male, aged 19–38, with self-employed individuals accounting for 70% of cases. Initial heroin use is often encouraged by friends and driven by curiosity. About 90% of patients report experiencing dizziness, nausea, or even vomiting after their first use. After intermittent use for 3–6 days, all cases reported experiencing a "high." The initial method of consumption is typically smoking ("chasing the dragon"), where heroin powder is added to a cigarette. Later, most users switch to heating the powder on foil and inhaling the vapors. The time to addiction depends on the frequency, dosage, and method of use, with addiction typically developing after about one month of use. For these individuals, life revolves around one goal: obtaining drugs by any means necessary.
**Psychiatric Symptoms** Patients exhibit low mood, depression, and irritability, which temporarily improve after drug use. Severe personality changes include selfishness, lying, sophistry, lack of concern for others, and loss of social responsibility. Memory declines, concentration falters, and creativity and initiative diminish. Insomnia and poor sleep quality are common, often with reversed circadian rhythms. Intellectual impairment is not prominent.
**Physical Symptoms** General health deteriorates, with loss of appetite, profuse sweating, constipation, weight loss, dry skin, and reduced libido. Male patients may experience erectile dysfunction and loss of sexual desire, while females may suffer from menstrual irregularities or amenorrhea. Vasomotor symptoms include facial flushing, dizziness, cold sweats, fluctuations in body temperature, palpitations, and tachycardia. Laboratory findings may show elevated white blood cell counts and reduced blood sugar levels.
**Neurological Examination** Tremors, unsteady movements and gait, slurred speech, a positive Romberg sign, constricted pupils, and hyperactive reflexes may be observed. Some patients exhibit sucking reflexes, palmomental reflexes, a positive Hoffmann sign, or hyperesthesia. Electroencephalography (EEG) may show Grade I abnormalities, with increased beta or theta activity.
**Withdrawal Syndrome** Opioid withdrawal is extremely distressing. Symptoms emerge 6–8 hours after discontinuation and include anxiety, yawning, rhinorrhea, shivering, pain in various body parts, and insomnia unresponsive to sedatives. Patients may moan in agony, beg for drugs, or resort to threats and lies. Transient disturbances of consciousness, ranging from drowsiness to delirium, are common within 24–36 hours of withdrawal, lasting 1–3 days. During this period, psychomotor agitation and vivid hallucinations may occur.
**Autonomic Symptoms** Prominent features include nausea, vomiting, generalized hyperalgesia, dilated pupils, fever, and sweating. Muscle spasms are frequent. These symptoms typically subside after 72 hours, but psychiatric symptoms like anxiety and insomnia may persist for 1–2 weeks or longer.
Even after physical withdrawal symptoms diminish, psychological cravings ("drug hunger") may remain intense. Medical staff must remain vigilant to prevent relapse.
2. Barbiturate and Other Sedative-Hypnotic Dependence
With the widespread clinical use of sleeping pills and sedatives, addiction cases are not uncommon, particularly involving secobarbital and methaqualone. Barbiturates can relieve tension but are prone to causing psychological dependence. Due to the development of tolerance, doses tend to increase over time, and prolonged repeated use can lead to physical dependence. According to literature reports, a daily dose of secobarbital below 0.4g is unlikely to cause physical dependence, whereas a daily dose of 0.6g taken for one month can result in physical dependence and withdrawal symptoms.
Clinical Manifestations Patients who take sleeping pills in large quantities over a long period may exhibit varying degrees of chronic poisoning symptoms. A single large dose of barbiturates can cause impaired consciousness and a hypomanic state, lasting from several hours to several days, accompanied by neurological signs such as tremors, slurred speech, and unsteady gait. Long-term, heavy use can lead to cognitive impairment: significant declines in memory, calculation ability, and comprehension, difficulty in thinking, and reduced work and learning capacity. After drug addiction, personality changes become evident: resorting to stealing or deceiving to obtain drugs, neglecting family responsibilities, denying addiction, lying outright, and only pleading desperately with family or doctors for drugs when withdrawal symptoms become unbearable. Patients lose their motivation and sense of responsibility toward family and society.
Physical Symptoms: These may include emaciation, weakness, loss of appetite, and gastrointestinal dysfunction; a sallow or grayish complexion, excessive sweating, positive skin scratch test, and significantly reduced or absent sexual function. Drug-induced hepatitis is often present. Neurological Signs: Tremors of the tongue and hands, hyperactive tendon reflexes, ankle clonus, as well as positive pyramidal tract signs, palm-chin reflex, and pouting reflex may be observed.
Withdrawal Syndrome: Generally appears 1–3 days after discontinuation. The higher the addictive dose and the stronger the sedative effect of the drug, the more severe the withdrawal symptoms. Mild cases may experience general discomfort, malaise, restlessness, dizziness, and other neurosis-like symptoms. Severe cases may exhibit systemic muscle spasms, grand mal seizures, hallucinations, schizophrenia-like symptoms, and impaired consciousness: agitation, impulsivity, incoherent speech, paranoia, and hallucinations.
III. Addiction to Anti-Anxiety Drugs
The earliest anti-anxiety drug prone to addiction was meprobamate. Over the past 10–20 years, with the widespread clinical use of benzodiazepine derivatives, cases of addiction to drugs such as chlordiazepoxide, diazepam, and alprazolam have emerged due to improper use, excessive doses, or prolonged duration. Among these, meprobamate has the highest tolerance and addictive potential and has been banned as an addiction-prone drug in many countries. The author observed two cases of meprobamate addiction, with patients taking 20–40 tablets daily. There are also reports of addiction occurring even at standard therapeutic doses, possibly related to the patient’s predisposition.
Clinical Manifestations Long-term, heavy use of anti-anxiety drugs can lead to emaciation, weakness, pallor, dull skin, and reduced sexual function. Cognitive impairment is generally not prominent. Neurological symptoms include: decreased muscle tone, diminished or absent tendon reflexes, and unsteady gait. After addiction, some degree of personality change occurs. Mild cases may exhibit irritability and weak willpower. Severe cases involve lying, concealing symptoms, and resorting to deception or theft to obtain drugs from emergency rooms.
Withdrawal Syndrome: Addicted patients often feel discomfort if they miss even a single dose during the day. Pronounced psychiatric symptoms typically emerge 1–3 days after discontinuation: transient hallucinations, excitement, euphoria, and total insomnia. The clinical presentation resembles barbiturate withdrawal symptoms. Grand mal seizures may occur.
IV. Other Addiction-Prone Drugs
These include amphetamines, cannabis indica, and cocaine.
Amphetamines are central nervous system stimulants that reduce drowsiness and fatigue. A small oral dose of 5–10mg can alleviate fatigue and enhance mental alertness and excitability. The effects typically last for 4 hours, followed by fatigue and drowsiness. Daily use of small doses quickly leads to tolerance.
Withdrawal Syndrome: Depression is the most common symptom, peaking 48–72 hours after discontinuation and gradually subsiding thereafter. In severe cases, psychiatric symptoms may persist for weeks. Tricyclic antidepressants are effective in treatment.
Long-term, heavy use of amphetamines can lead to amphetamine-induced psychosis. The clinical symptoms are very similar to paranoid schizophrenia: delusions of persecution and referential ideas occur while consciousness remains clear. However, the duration is short, and symptoms disappear within a few days to a few weeks after stopping the drug. Antipsychotic medications such as phenothiazines and butyrophenones are effective in treatment.
Cannabis is an ancient addictive substance second only to opium, widely prevalent in the Near East and Central Asia. Methods of use include oral ingestion, smoking, and chewing. Over the past decade, marijuana (marihuana) has also become widely popular in North America, the United States, and Western Europe. Cannabis produces moderate psychological dependence and has minimal medicinal properties. Inhaling 7mg can induce euphoria, while 14–20mg can cause pronounced psychiatric symptoms.
After cannabis intoxication, individuals experience intense pleasure, heightened energy, euphoria, and overwhelming confidence. Illusions and perceptual disturbances may occur, along with excitement and fear. This is followed by depression, restlessness, ataxia, and ultimately sleep.
Cocaine is an alkaloid extracted from the leaves of the South American coca shrub. It has local anesthetic properties and acts as a central nervous system stimulant and euphoriant. Indigenous people chew these leaves to relieve fatigue and elevate mood. Common methods of use include subcutaneous injection and inhalation. Its clinical manifestations closely resemble those of amphetamines, and it induces strong psychological dependence.
Diagnostic Criteria for Substance Dependence
1. A history of prolonged or repeated use of psychoactive substances.
2. Strong craving and tolerance for psychoactive substances, with at least two of the following: ① Inability to resist the desire to use the substance; ② Markedly increased determination to obtain the substance; ③ Frequent abandonment of other activities or hobbies due to substance use; ④ Continued use despite awareness of its harm, or self-justification, or unsuccessful attempts to reduce or stop use; ⑤ Experience of pleasure during use; ⑥ Increased tolerance to the substance; ⑦ Withdrawal syndrome upon discontinuation.
Diagnostic Criteria for Withdrawal Syndrome
1. A history of dependence on psychoactive substances.
2. After stopping or reducing the use of the dependent psychoactive substance, at least three of the following psychological symptoms appear: ① Mood changes, such as anxiety, depression, dysphoria, irritability, etc.; ② Impaired consciousness; ③ Insomnia; ④ Fatigue or drowsiness; ⑤ Psychomotor agitation or retardation; ⑥ Difficulty concentrating; ⑦ Memory impairment; ⑧ Impaired judgment; ⑨ Hallucinations or illusions; ⑩ Delusions; ⑪ Personality changes.
3. Accompanied by at least two of the following physical symptoms or signs: ① Nausea or vomiting; ② Muscle or body pain; ③ Pupillary changes; ④ Runny nose, tearing, or yawning; ⑤ Abdominal pain or diarrhea; ⑥ Dryness-heat sensation or elevated body temperature; ⑦ Severe discomfort; ⑧ Spasms.
4. The nature and severity of symptoms depend on the type and dose of the psychoactive substance. Resuming sufficient use can rapidly alleviate the withdrawal syndrome.
bubble_chart Treatment Measures
Once a patient becomes addicted to drugs or the craving for addictive substances is so intense, it is generally difficult to quit automatically. Therefore, hospitalization for treatment is necessary. Even if voluntarily admitted, patients often resort to lying, stealing, or other means to obtain drugs. Thus, a thorough inspection of the patient's clothing, belongings, and books is essential upon admission, and all opportunities to acquire addictive drugs must be eliminated. This is the key to ensuring effective treatment. Early treatment yields noticeable results.
Treatment principles: Gradually withdraw the addictive drugs. For most adults, the drugs can be completely withdrawn within a week. For those who are physically weak, have a long history of addiction, take large doses, or are elderly, the withdrawal process should be slower to avoid cardiovascular emergencies or collapse, typically over 10 days to 2 weeks.
Various physical support therapies can improve the patient's nutrition and alleviate the discomfort and acute withdrawal symptoms. High doses of B vitamins, vitamin C, and niacin can be administered. Under suitable conditions, brain metabolic therapy can be provided: an energy mixture, high doses of vitamin C, niacin, and sodium glutamate can be added to 200–500 ml of a 5–10% glucose solution for intravenous drip, once daily for 20 sessions. This has a good effect in alleviating withdrawal symptoms and reducing autonomic nervous system reactions.
During withdrawal, patients often experience insomnia, anxiety, and other emotional reactions. Non-addictive sedatives such as hydroxyzine, small doses of perphenazine, chlorpromazine, or thioridazine can be used. For significant anxiety, anti-anxiety medications like estazolam or diazepam may be appropriate. Nitrazepam also has anti-epileptic effects and can prevent major seizures during withdrawal.
Some countries use substitution therapy, replacing highly addictive drugs with less addictive ones, particularly in heroin addiction treatment—for example, using methadone to replace morphine or heroin. Some domestic institutions are also trialing this approach.
During heroin withdrawal, patients may experience agitation or even impaired consciousness, which is most severe in the first few days. It is crucial to promptly control agitation and ensure patient safety. Generally, chlorpromazine and promethazine (25–50 mg each) can be administered intramuscularly or orally three times daily. For severe agitation, in adult patients with stable cardiovascular function, a chlorpromazine-promethazine mixture diluted in saline can be slowly injected intravenously. Additionally, intramuscular haloperidol (5–10 mg, 2–3 times daily) can help control agitation. After physical dependence is managed, psychological cravings may persist for a long time. Based on clinical symptoms, antipsychotics or anti-anxiety medications should be continued for at least 2–3 months to consolidate treatment.
Supportive psychotherapy is crucial. Most patients lack willpower and confidence in treatment, so they must be consistently encouraged and supported to persist. Encouraging participation in recreational and sports activities can divert attention from drug cravings. Family and social support are key to consolidating post-discharge recovery. During rehabilitation, support and supervision from family and workplace are essential to cut off access to drugs and contact with suppliers. Otherwise, even if withdrawal is successful in a hospital setting, relapse is likely after discharge. Outpatient follow-up for two years is recommended to prevent recurrence.
Preventing drug addiction requires comprehensive measures and collaboration among multiple sectors (such as health, public security, judiciary, and commerce) to control the production, distribution, and clinical use of addictive substances. Medical professionals should be educated on relevant knowledge to enhance vigilance and early recognition of addiction to sleeping pills, anti-anxiety medications, and morphine-like drugs, thereby reducing the incidence of addiction. In areas where drug addiction has already become prevalent, widespread public awareness campaigns should be conducted to highlight the dangers of drug dependence, mobilizing social forces to assist relevant authorities in implementing necessary measures.
