Substance-related and addictive disorders

Substance-related disorders are a class of psychiatric disorders characterized by a craving for, the development of tolerance to, and difficulties in controlling the use of a particular substance or set of substances. There are two groups of substance-related disorders: substance-induced disorders and substance use disorders (SUDs). Substance-induced disorders include intoxication, withdrawal, and substance-induced mental disorders. SUDs (e.g., opioid use disorder and alcohol use disorder) have unique features but are all characterized by cognitive and behavioral changes and physical symptoms related to the continued use of one or more substances despite negative consequences. The addictive potential of these substances results from how they act on the brain's reward system and affect emotion, mood, and perception, often inducing a euphoric state colloquially referred to as a “high.” Individuals with SUD may participate in high-risk or illegal behaviors (e.g., exchanging sex for drugs, unsafe needle practice, erratic or aggressive behavior, theft), either as a result of substance use or in pursuit of substances, which can lead to social isolation, housing instability, and worsening of mental illness (e.g., comorbid bipolar disorder, major depressive disorder, or anxiety disorder). Treatment for SUD involves counseling (e.g., motivational interviewing), psychotherapy, and/or pharmacotherapy.

• DSM-5 classifies substance-related disorders according to the underlying substance ^[1]
  • Alcohol, caffeine, cannabis, hallucinogens (phencyclidine, other hallucinogens), inhalants, opioids, sedatives, hypnotics, or anxiolytics, stimulants (amphetamines or amphetamine-type substances, cocaine, other stimulants), tobacco, other/unknown substances
• Substance-related disorders are divided into:
  • Substance use disorders
  • Substance-induced disorders (intoxication, withdrawal, and substance-induced mental disorders)
• DSM-5 classifies gambling disorder as a non-substance-related addictive disorder

Substance use disorder ^[1][2][3]

• Description: a chronic condition in which an uncontrolled pattern of substance use leads to significant physical, psychological, and social impairment or distress, with continued use despite substance-related problems.
• Epidemiology
  • Sex: ♂ > ♀
  • Alcohol and nicotine use are most common.
• Characteristics: features that are typical for all substance use disorders (≥ 2 features must occur within 1 year to fulfill the DSM-V criteria)
  • Impaired control
    • Using a substance in larger amounts and/or for a longer time than originally intended
    • Repeated failed attempts to cut down on use
    • A great deal of time spent on substance-related activities (e.g., seeking out, buying, using, recovering from use)
    • Intense desire to obtain and use substance (craving)
  • Social impairment
    • Problems fulfilling work, school, family, or social obligations (e.g., not attending work or school, neglecting children or partner)
    • Problems with interpersonal relationships directly related to substance use (withdrawal from relationships, marital issues)
    • Reduced social, occupational, and recreational activities (e.g., less time socializing with friends, neglecting hobbies)
  • Risky use
    • Use in physically hazardous situations; (e.g., driving a car under the influence, unprotected sex, operating heavy machinery)
    • Continued use despite awareness of problems related to or exacerbated by substance use (e.g., continued alcohol use despite having cirrhosis)
  • Pharmacologic indicators
    • Drug tolerance: the need to continuously increase the dose of a substance to achieve the same desired effect
    • Drug withdrawal: a substance-dependent collection of symptoms that appear after cessation of prolonged heavy drug use accompanied by a strong urge to readminister the substance
      • Often, withdrawal symptoms are the opposite of intoxication effects, e.g., heroin intoxication causes sedation and constipation, whereas heroin withdrawal causes anxiety, insomnia, and diarrhea.
      • Hallucinogens and inhalants do not cause withdrawal.
• Exception: patients undergoing supervised treatment with certain psychoactive substances (e.g., stimulants, cocaine, opioids, nitrous oxide, sedative-hypnotic drugs, anxiolytic drugs, cannabis) ^[4]
  • Tolerance and withdrawal can be normal physiological adaptations.
  • In the absence of other DSM-V criteria, tolerance and withdrawal do not necessarily indicate substance use disorder.

Withdrawal from some substances, such as alcohol, benzodiazepines, and barbiturates, can be fatal!

Substance-induced disorders

• Intoxication: a temporary condition caused by recent ingestion of a substance that alters a person's consciousness, cognition, perception, judgment, affect, and/or behavior; commonly occurs in substance use disorders but also in one-off use
• Withdrawal: a condition characterized by behavioral, physiological, and cognitive changes caused by a sudden reduction or cessation of substance intake after a prolonged period of heavy intake; usually occurs in association with substance use disorders
• Substance/medication-induced mental disorders: a psychiatric disorder that develops within 1 month of intoxication or withdrawal of a substance and is not attributable to an independent mental disorder (e.g., substance/medication-induced anxiety disorder)

Related definitions

• Abuse
  • In the context of substance use, the term “abuse” should generally be avoided due to its impreciseness and the historical burden of stigma.
  • “Substance use” is generally the preferred term in this context, with “substance misuse” being appropriate in the context of prescription drugs.
• Drug-seeking behavior
  • A maladaptive behavioral response to substance addiction that involves manipulative and/or demanding behaviors to obtain the desired substance
  • Often indicative of an underlying substance use disorder
  • Examples of drug-seeking behavior
    • Faking/aggravating symptoms
    • Bribes, threats, theft (e.g., prescription pads)
    • Forging prescriptions or using those of others (e.g., under the names of family members)
    • Pretending to lose prescriptions and asking for new ones
    • Insisting that a treatment that does not involve one or more certain (addictive) drugs is ineffective or not tolerated (e.g., due to an alleged allergy)
    • Demanding a stronger medication or higher dose due to an allegedly high drug tolerance
    • Claiming that another, an ostensibly more experienced or more caring, physician would prescribe the desired drug or threatening to see another physician if the desired drug is not prescribed.
• Medication-assisted treatment (MAT): treatment for substance use disorder that combines counseling with pharmacological and behavioral therapy, tailored to each patient's needs. ^[5]

SUD screening ^[8]

Indications

• Tobacco use: all adults and pregnant individuals ^[9]
• Unhealthy alcohol use: adults in primary care settings ^[10]
• Unhealthy drug use: adults, if treatment can be offered ^[11]

Validated screening tools

• Alcohol use disorders identification test-concise (AUDIT-C) ^[10]
• Single alcohol screening question (SASQ) ^[10]
• Tobacco, alcohol, prescription medication, and other substance use tool (TAPS) ^[11]
• National Institute on Drug Abuse (NIDA) quick screen ^[11]

The harms of screening for unhealthy drug use outweigh the benefits when treatment cannot be provided or when findings may result in punitive actions (e.g., some US state laws penalize pregnant individuals who use substances or seek addiction treatment). ^[11]

SUD assessment ^[5]

• Indications
  • Positive SUD screening
  • History of SUD
  • Classic toxidrome or findings that suggest drug intoxication or withdrawal, e.g.:
    • Altered mental status, acute agitation
    • Acute cardiopulmonary symptoms
    • Needle or track marks
  • Prior to initiating a long-term opioid or benzodiazepine prescription
• Components
  • Cravings and withdrawal symptoms
  • Reasons, amount, frequency, route, and duration of substance use
  • Impact on overall well-being
  • Prior experiences with treatment, including:
    • Facilitators (e.g., coping skills, recovery supports)
    • Barriers (e.g., triggers, mobility impairment, health literacy)
  • Current level of interest in treatment
• Further evaluation
  • Screen all patients for coexisting disorders (e.g., intimate partner violence, mood disorders, anxiety).
  • Consider drug testing if results will impact management.

The screening, brief intervention, and referral to treatment (SBIRT) model may be used to identify and assess SUD in any care setting. ^[5]

Drug testing ^[12][13]

• Definition: the testing of biological samples for the presence of drugs and drug metabolites

Urine drug test

• Overview
  • Immunoassay testing is the most frequently used method for urine drug testing.
  • Mass spectrometry/gas chromatography is used to confirm immunoassay results.
  • Example situations for the use of a urine drug test include workup of altered mental status and monitoring during SUD treatment or chronic opioid therapy.
• Detectable substances (immunoassay)
  • Phencyclidine (PCP)
  • Opioids
  • THC (marijuana)
  • Cocaine
  • Amphetamine
• Undetectable substances (immunoassay)
  • GHB
  • MDMA
  • Semisynthetic and synthetic opioids
  • Ketamine
  • Psilocybin (hallucinogenic mushrooms), DMT (ayahuasca), mescaline (peyote)
  • Synthetic drugs
• Substances that can cause cross-reactivity and yield false positive results ^[14]
  • Marijuana: food containing hemp
  • PCP: doxylamine, dextromethorphan, tramadol
  • Opioids: poppy seeds, rifampin
  • Benzodiazepines: sertraline
  • Amphetamines: pseudoephedrine, ephedrine, phenylephrine, metformin

Urine drug test immunoassays can generate false-positive and false-negative results because of cross-reactivity with other medications (e.g., rifampin with opioid assays, sertraline with benzodiazepines, metformin with amphetamines). ^[12]

Blood/serum drug test

• Usage: assess intoxication or impairment in emergency situations
• Examples: drug overdosage, after motor vehicle crash

Laboratory methods

• Immunoassays
  • Rapid presumptive results for many substances (e.g., point-of-care urine drug tests)
  • Provide quantitative results
  • Can generate false-positive and/or false-negative results
• Mass spectrometry
  • Often obtained based on a presumptive positive result
  • Definitive results
  • Can provide quantitative drug levels

Always confirm qualitative point-of-care drug test results (i.e., with mass spectrometry) when the results might have legal, financial, or employment implications.

Management

• Treatment options depend on the respective substance being used (e.g., “Management of alcohol withdrawal” and “Opioid withdrawal”) and patient preferences.
• Utilize person-centered language, motivational interviewing, and strategies for harm reduction in OUD. ^[15]
• Manage withdrawal, if present.
• Medication-assisted treatment (MAT): treatment for substance use disorder that combines counseling with pharmacological and behavioral therapy, tailored to each patient's needs. ^[5]

Disposition ^[16][17]

The most appropriate treatment setting may change over time and is influenced by: ^[18]

• The presence and severity of withdrawal symptoms and/or comorbid conditions
• Patient preference and social history
  • Current circumstances
  • Social support
• Need for medication oversight (e.g., methadone)

Withdrawal management settings ^[16][17]

Forced treatment is not recommended as it is often followed by relapse and a loss of trust in treatment services and providers.

See the article “Overview of alcohol use,” “Alcohol intoxication,” “Alcohol use disorder,” and “Alcohol withdrawal.”

• Substance: caffeine (usually ingested with coffee, tea, soda, or energy drinks) ^[6][19]
• Mechanism of action: adenosine antagonist → increased cAMP → neurological excitation and facilitated catecholamine release ^[19]
• Epidemiology:
  • Caffeine is the most widely consumed psychoactive substance in the world. ^[20]
  • ∼ 7% of the US population expericence symptoms consistent with caffeine intoxication. ^[1]
• Clinical features of intoxication
  • To meet the DSM-V criteria for caffeine intoxication, individuals must exhibit at least five of the following symptoms shortly after caffeine intake. ^[1]
    • Psychomotor agitation
    • Excitement
    • Insomnia
    • Incoherent speech and/or chaotic flow of thoughts
    • Muscle twitching
    • Flushed face
    • Cardiac arrhythmias or tachycardia
    • Severe restlessness
    • Anxiety, nervousness
    • Inexhaustibility
    • Diuresis
    • Gastrointestinal disturbance
  • The following features may be also present: ^[1][19][20]
    • Tremor
    • Light flashes
    • Tinnitus
    • Seizures
    • Headache
  • Doses of about 10 g of caffeine can be lethal. ^[19]
• Clinical features of withdrawal: The DSM-V requires at least three of the following symptoms to be present within 24 hours after abrupt reduction of caffeine intake to account for caffeine withdrawal ^[1]
  • Caffeine withdrawal headache
  • Depressed mood, irritability
  • Drowsiness, fatigue
  • Difficulty concentrating
  • Flu-like symptoms, muscle pain
• Related disorders
  • Caffeine-induced anxiety disorder (see “Anxiety disorders”)
  • Caffeine-induced sleep disorders (see “Delayed sleep phase disorder”)
• Treatment ^[21][22]
  • Overdose: supportive therapy (e.g., beta-blockers for tachyarrhythmia)
  • Withdrawal: Symptoms typically manifest within 24 hours after the last intake and resolve spontaneously within 10 days.

• Cannabis use disorder: DSM-V requires ≥ 2 of the following features to occur within a 1-year period of cannabis use, accompanied by agitation and severe impairment of functioning
  • Using cannabis in larger amounts or over a longer period than intended
  • Persistent desire to cut down the amount of cannabis used or repeated unsuccessful efforts to stop using it
  • A large amount of time is spent using cannabis, trying to acquire it, or recovering from its effects
  • Strong craving to consume cannabis
  • Cannabis use has a negative impact on social and professional function (e.g., at work, school, or home)
  • Continued cannabis use despite social or interpersonal problems that are directly caused or exacerbated by its use
  • Loss of interest in activities that were important to user prior to regular cannabis use
  • Recurrent use of cannabis in situations in which its use is associated with the risk of physical harm (e.g., driving a car)
  • Continued cannabis use despite persistent or recurrent psychological or physical problems that can most likely be attributed directly to the use of cannabis
  • Tolerance, which can manifest as:
    • The need to markedly increase the amount of cannabis to achieve the desired effect/intoxication
      and/or
    • A reduced effect over time when the same amount of cannabis is used
  • Withdrawal, which can manifest in the form of:
    • Clinical features of cannabis withdrawal
      and/or
    • Substance use to alleviate or avoid withdrawal symptoms
• Other cannabis-induced disorders
  • Cannabis intoxication
  • Cannabis withdrawal
  • Cannabinoid hyperemesis syndrome
  • Cannabis-related psychiatric disorders
  • Medical disorders, e.g., pulmonary problems or reduced fertility
  • See “Cannabis-induced disorders” for details.

Hallucinogens are a heterogeneous group of substances that can trigger hallucinations following exposure. These substances have varying mechanisms of action and associated physiological and neuropsychiatric effects.

Substances with hallucinogenic properties ^[23][24]

Commonly used substances include:

• Classic hallucinogens (psychedelics)
  • Lysergic acid diethylamide (LSD)
  • Psilocybin
  • Dimethyltryptamine (DMT)
• Dissociative drugs
  • Phencyclidine (PCP)
  • Ketamine
  • Dextromethorphan (at high doses) ^[25]
• Serotonergic stimulants
  • MDMA
  • Mescaline
• Botanicals
  • Ayahuasca
  • Cannabis
  • Salvia divinorum

LSD, DMT, psilocybin, and MDMA are controlled substances in the United States. ^[23]

Classic hallucinogens may be beneficial for the treatment of depression and anxiety. ^[26]

Hallucinogen intoxication

• Clinical features: The DSM-V requires the following features to be present during or shortly after the use of hallucinogens (other than phencyclidine) for the diagnosis of intoxication. ^[1]
  • Behavioral/mental (paranoid ideation, anxiety, depression, fear of “going crazy”, impaired judgment)
  • Perceptual (synesthesia, derealization, depersonalization, illusions)
  • At least 2 of the following somatic symptoms:
    • Tachycardia
    • Palpitations
    • Mydriasis
    • Diaphoresis
    • Tremor
    • Incoordination
    • Blurred vision
• Treatment ^[6]
  • Most hallucinogen intoxications are treated with supportive care, e.g.:
    • Antipsychotics for substance-induced psychosis
    • Benzodiazepines for agitation
    • External cooling for hyperthermia
  • Some substances require specific management.
    • See “PCP.”
    • See “MDMA.”
    • See “Cannabis intoxication.”

Hallucinogen withdrawal

• Hallucinogens are not typically associated with symptoms of withdrawal.
• Withdrawal symptoms (e.g., cravings) may occur in chronic MDMA users; see “Stimulant withdrawal.” ^[27]

Hallucinogen persisting perception disorder (HPPD; flashbacks) ^[28]

• Episodic or continuous symptoms (optical hallucinations, depression, and panic) that occur weeks after the initial intoxication
• Spontaneous recurrence of acute hallucinogen intoxication due to reabsorption of the intoxicating substance from bodily stores

• Substance: phencyclidine (PCP); the liquid form is often sprayed on tobacco or cannabis and smoked.
• Street names: angel dust, peace pill, elephant tranquilizer, hog ^[29]
• Mechanism of action ^[29]
  • Inhibits dopamine, serotonin, and norepinephrine reuptake
  • Antagonizes NMDA receptors → stimulant or depressive neurological effects (dose dependent)
  • Binds to the sigma receptor complex
• Clinical features
  • Phencyclidine use disorder
    • Signs of injury, e.g., due to fights, accidents
    • Memory and speech deficits
    • Cognitive impairment
  • PCP intoxication: The DSM-V requires the following features to be present to account for phencyclidine (or pharmacologically similar substance) intoxication ^[1][30]
    • Behavioral changes (violence, belligerence, psychomotor agitation, impulsiveness, impaired judgment) must develop during or shortly after the use of phencyclidine or similar substance
    • At least 2 of the following signs should be present within an hour after the use of phencyclidine or similar substance
      • Hypertension, tachycardia, dysrhythmias
      • Horizontal or vertical nystagmus
      • Ataxia
      • Dysarthria
      • Muscle rigidity
      • Hyperacusis
      • Seizures or coma
      • Decreased sensation to pinprick (increased pain tolerance)
    • The following features may be also present ^[1][31]
      • Miosis
      • Hyperthermia
      • Synesthesia
      • Confusion, disorientation
      • Delirium
      • Amnesia
• Phencyclidine-induced mental disorders: psychosis; (e.g., hallucinations), mania
• Treatment of PCP intoxication ^[29][30]
  • Reduction of environmental stimuli
  • Gastrointestinal decontamination
  • Supportive care
  • Sedation with benzodiazepines (for severe agitation) or haloperidol (if psychotic symptoms are present)
• Complications
  • Trauma (commonly accompanied by intracranial hemorrhage)
  • Seizures
  • Rhabdomyolysis
  • Reabsorption of the drug in the gastrointestinal tract may lead recurrence of symptoms.

LSD ^[6]

• Substance: lysergic acid diethylamide
• Street names: acid
• Mechanism of action: 5HT_2A-serotonin-receptor agonist (increased serotonin concentrations in the synaptic cleft → hallucinations)
• Specific clinical features of intoxication
  • Mental changes: marked anxiety and paranoia, psychosis
  • Perceptual changes: Depersonalization, visual and/or auditory perceptual distortion, and synesthesia are particularly noticeable.
  • Flashbacks (rarely unsettling)
  • Mydriasis
• Treatment of intoxication
  • Supportive care, reassurance
  • Psychotic symptoms: first-generation antipsychotics
  • Anxiety: benzodiazepines
• Hallucinogen use disorder: Substance use disorders due to LSD are rare. ^[32]

Phenethylamine derivatives

A class of substances with serotonergic and sympathomimetic effects

• MDMA
  • Intoxication is associated with serotonin syndrome and hyponatremia; see “Stimulant intoxication” for details. ^[33]
  • Substance use disorders related to MDMA are poorly defined. ^[27]
    • Misuse and dependence can occur, but are less likely and usually less severe than other stimulants.
    • Standard management of substance use disorders is recommended. ^[27]
• Mescaline
  • A hallucinogen found in the peyote cactus
  • Street names: mesc, cactus, buttons
  • Management of intoxication is similar to that of MDMA (see “Stimulant intoxication” and “Serotonin syndrome”).
  • Mescaline is rarely involved in substance use disorders. ^[34][35]

• Substances: hydrocarbon-based inhalants (e.g., glue, paint thinners, fuel, nitrous oxide, alkyl nitrites) ^[1][36]
• Street names: poppers (alkyl nitrite); whippits (nitrous oxide)
• Epidemiology: most prevalent in high-school-aged individuals ^[36]
• Mechanism of action: : Inhalants generally work by depressing the CNS. ^[36]
• Inhalant use disorder
  • The features of substance use disorders listed in the “Overview” section are applicable to inhalant use disorder
  • Glue sniffer's rash: characteristic eczematous rash between the nose and upper lip after prolonged use of inhalants
• Clinical features of inhalant intoxication ^[1][36]
  • Short duration of symptoms (rapid onset and resolution)
  • Lingering odor of inhalant substance
  • Slurred speech, headache, diplopia, agitation, hallucinations, gait disturbance, somnolence
  • Euphoria, disinhibition, dizziness, confusion, lethargy, disorientation, drowsiness
  • Nausea and vomiting
  • Nystagmus, muscle weakness, tremor, hyporeflexia, ataxia
  • Overdose: asphyxia, suffocation, seizure, coma, death (due to respiratory depression)
• Clinical features of withdrawal: usually no withdrawal symptoms, but regular users may develop symptoms of CNS excitation (e.g., tachycardia, irritability, hallucinations, dysphoria, insomnia, headache)
• Treatment ^[36]
  • Supportive treatment, reassurance
  • Intubation may be necessary
  • Psychotherapy
• Complications ^[36]
  • Impaired cognition
  • Peripheral neuropathy
  • Malignancy
  • Aplastic anemia
  • Myocarditis and myocardial infarction
  • Urinary calculi
  • Glomerulonephritis

See “Opioid use disorder“ for details.

• Substance: opiates (fentanyl, oxycodone, hydrocodone; heroin)
• Street names
  • Smack and dope (heroin)
  • The blues, fenty powder (fentanyl)
• Forms of preparation: illegal or prescription drugs for oral ingestion, injection, smoking, snorting
• Mechanism of action
  • κ-, δ-, and μ-receptor agonists (morphine, heroin, codeine, fentanyl)
  • Mixed agonist/antagonist action (buprenorphine)

See benzodiazepine overdose, benzodiazepine dependence, and barbiturate intoxication in the article on sedative-hypnotic drug overdose.

See “Stimulant intoxication and withdrawal” for evaluation and management of acute intoxication and withdrawal of stimulant drugs.

• Definition: Stimulant-related disorders encompass conditions caused by cocaine, amphetamines, amphetamine-substituted substances, and synthetic cathinones.
• Examples
  • Cocaine use disorder
  • Amphetamine use disorder
• Diagnostic criteria: Use the DSM-V criteria for general substance use disorders.
• Treatment
  • Cocaine use disorder: psychotherapy, group programs ^[37]
  • Amphetamine and methamphetamine use disorder: psychotherapy and support programs ^[38]
  • Synthetic cathinone dependence: psychotherapy and support programs

See “Tobacco product use and smoking cessation.”

• Definition: Gambling disorder is a disorder in which the affected individual feels the compulsion to gamble despite negative consequences and/or multiple attempts to stop. Also, the gambling behavior cannot be better explained by a manic episode. ^[1]
• Epidemiology ^[1][39]
  • Sex: ♂ > ♀
  • No specific age group
• Etiology: combination of factors (genetic, environmental, neurochemical abnormalities) ^[1][39]
• Diagnosis: ≥ 4 of the following in a 12 month period ^[1]
  • Using increasing amounts of money to gamble
  • Relying on others for financial support to maintain habit
  • Restlessness or irritability when attempting to stop gambling
  • Constant preoccupation with gambling
  • Continuous gambling in an attempt to undo losses (“chasing one's losses”)
  • Jeopardizing relationships or careers as a result of gambling
  • Numerous failed attempts to quit gambling
  • Lying to others to conceal the extent of gambling
  • Gambling when feeling helpless, guilty, anxious or depressed
• Treatment ^[39][40]
  • Group therapy (Gamblers Anonymous)
  • Cognitive behavioral therapy
  • Treatment of underlying psychiatric conditions (e.g., bipolar disorder, substance use disorder, etc.)
  • Approx. ⅓ patients recover without treatment.
  • Pharmacotherapy (e.g., with serotonin reuptake inhibitors, opioid antagonists, topiramate) is still being researched.
• Complications ^[1][39]
  • Often occurs in conjunction with other psychiatric disorders (antisocial personality disorder, depressive disorder, bipolar disorder, and substance use disorders)
  • Associated with poor general health, including tachycardia and angina

Pharmacology

• Substances (street names: G, Georgia home boy, liquid ecstasy, liquid X) ^[41][42]
  • GHB: recreational drug used to induce euphoria, disinhibition, enhanced empathy, and/or increased libido ^[42]
  • GHB is also used as a performance-enhancing drug by athletes. ^[43]
• Mechanism of action: direct agonist of GABA receptors (similar to benzodiazepines) ^[44]
• Pharmacokinetics ^[41][42]
  • Onset: 15–20 minutes
  • Peak effect: 30–60 minutes
  • Half-life: 20–50 minutes (dose-dependent)

GHB is sometimes used in drug-facilitated sexual assault because of its rapid onset, amnesic effect, and difficult detection. ^[41][42]

Risky substance use

• Acute intoxication: See “GHB intoxication and overdose.”
• Chronic GHB use and dependence ^[45]
  • Most common in young men
  • Tolerance can cause dose escalation, which increases the risk of GHB overdose.
  • Withdrawal symptoms can lead to frequent reuse (e.g., every few hours).

GHB withdrawal ^[41][46]

Abrupt cessation of chronic GHB use can precipitate a potentially fatal withdrawal syndrome.

Clinical features ^[41][46]

The clinical features of GHB withdrawal are similar to those of alcohol withdrawal and benzodiazepine withdrawal. ^[41]

• CNS stimulation: tremor, increased muscle tone, seizures, coma
• Neuropsychiatric changes
  • Insomnia, irritability, anxiety, agitation, psychosis
  • Confusion, delirium, hallucinations
• Autonomic stimulation: tachycardia, hypertension, diaphoresis
• GI: nausea, vomiting, abdominal cramping, diarrhea

Features of GHB withdrawal may appear as early as 1–6 hours after the last ingestion and persist for over 14 days. ^[41]

Management ^[41][46]

• Begin high-dose benzodiazepine therapy (e.g., diazepam, lorazepam).
• Urgently consult psychiatry or addiction medicine to guide pharmacotherapy. ^[41][47]
• Consider admission to the ICU for severe symptoms or if high doses of sedatives are required.
• Monitor for complications including seizures, rhabdomyolysis, and hyperthermia.

Acute GHB withdrawal is a medical emergency and may result in death if not appropriately diagnosed and managed. ^[41][46]