- Clinical science
Substance-related disorders are a class of psychiatric disorders characterized by a craving for, the development of a tolerance to, and difficulties in controlling the use of a particular substance or a set of substances, as well as withdrawal syndromes upon abrupt cessation of substance use. While these substances may have different mechanisms of action, their addictive potential typically lies in the way they act on the brain's reward system and affect emotion, mood, and perception – producing what is colloquially referred to as a “high.” Individuals with a substance use disorder will frequently harm themselves and/or others as a result of substance use. Patients with substance use disorders often present with other psychiatric conditions that also require treatment, such as bipolar disorder, major depressive disorder, or anxiety disorder. Generally, treatment for substance use disorders includes long-term psychotherapy or group therapy in addition to medical supervision of withdrawal symptoms.
In gambling disorder, individuals feel a compulsion to gamble despite negative consequences and/or multiple attempts to stop. Gambling disorder is thought to involve many of the same neurobiological mechanisms as substance-related addictions and shares some of the same psychosocial risk factors.
Substance use disorder
- Definition: pathologic collection of cognitive, behavioral, and physiological symptoms related to the use of a substance
- Sex: ♂ > ♀
- Alcohol and nicotine use is most common
- Using substance inlarger amounts and/or for a longer time than originally intended
- Repeated failed attempts to cut down on use
- Spending a great deal of time on substance-related activities (e.g., buying, using, recovering from use, etc.)
- Intense desire to obtain and use substance (craving)
- Problems fulfilling work, school, family, or social obligations (e.g., not attending work or school, neglecting children or partner, etc.)
- Problems with interpersonal relationships directly related to substance use
- Reduced social and recreational activities (e.g., less time socializing with friends, spending less time with family)
- Use in physically hazardous situations (e.g., operating heavy machinery, driving a car)
- Use despite awareness of physical problems (e.g., continued alcohol use despite having cirrhosis)
- Definition: the need for individuals to continuously increase the dose of a substance to achieve the same desired effect
- Corollary: individuals experience less of an effect despite taking the same amount of a substance
- The degree of tolerance can vary greatly depending on factors such as route of administration, duration of use, and genetic factors!
- Definition: Substance-dependent collection of symptoms that appear after cessation of prolonged heavy drug use
- Often, the withdrawal symptoms are the opposite of intoxication effects (e.g., heroin intoxication causes sedation and constipation, whereas heroin withdrawal causes anxiety, insomnia, and diarrhea)
- Drug tolerance
- Impaired control
|Differential diagnosis of drug intoxication|
|Pupils||Blood pressure||Pulse||Other symptoms|
- Substance: caffeine (usually ingested with coffee or tea)
- Action: adenosine antagonist → increased cAMP → neurological excitation
Epidemiology: most prevalent psychoactive substance in the US
- Withdrawal: headache, irritability, drowsiness, muscle pain, depression
- Overdose: supportive
- Withdrawal: resolves spontaneously within ∼ 10 days
- Substance: cannabis
- Street names: , grass,
Forms of preparation(most commonly smoked; vaporized; ingested orally via pill, capsules, oil, food)
- : dried leaves and buds of the plant
- Hashish (hash): resin of the cannabis plant
- Medical marijuana (e.g., dronabinol)
- Mechanism of action: tetrahydrocannabinol ( main active component) interacts with cannabinoid receptors CB1 and CB2 → inhibition of
Clinical features of intoxication 
- Euphoria or dysphoria
- Joviality, anxiety, panic
- , hallucinations
- Increased or decreased blood pressure
- Perceptual disturbances (e.g., distorted sense of time)
- Social detachment
- Impaired judgment
- Impaired reaction time, concentration, and coordination (e.g., increased risk of motor vehicle accidents)
- (red eyes),
- Increased appetite (also called “the munchies”)
- Dry mouth
- Clinical features of withdrawal 
- Treatment: psychosocial support and interventions
Cannabis-induced with , thoughts, and/or
- Possible association between regular use and the development of schizophrenic psychoses
- Higher rates of other psychiatric disorders (including , , etc.)
- Cannabis-induced anxiety disorder
- Cannabis-induced sleep disorder
- Higher lifetime probability of other
- Cannabinoid hyperemesis syndrome 
- Long-term effects include pulmonary problems (e.g., wheezing, shortness of breath), immunosuppression, and sex hormone imbalance.
- Cannabis-induced with , thoughts, and/or
Medical pain in cancer patients, and reduce in patients with . can be used to increase appetite and treat nausea/vomiting in terminally ill patients, relieve
DroNABINOl is a pharmaceutical canNABINOid.
- Substance: phencyclidine; (PCP); liquid form is often sprayed on tobacco or cannabis and smoked.
- Action: activates dopaminergic neurons and antagonizes NMDA receptors → stimulant or depressive neurological effects (depends on dose)
- Street names: angel dust, peace pill, elephant tranquilizer
- Decreased sensation to pinprick (↑ pain tolerance)
- Violent, and/or abnormal behavior; , confusion; , amnesia; , disorientation, psychosis (e.g., hallucinations; ), miosis; , seizures, synesthesia; (one sensory stimulation → another sensory perception), ataxia; , dysarthria
- Hypertension, tachycardia, dysrhythmias
- Hyperthermia, muscle rigidity
- Overdose: vertical nystagmus (most common symptom in overdose), delirium, seizures
- There are rarely acute symptoms of withdrawal or dependence.
- Flashbacks may occur.
- Substances: lysergic acid diethylamide (LSD), mescaline
- Action: 5HT2A-serotonin-receptor andD2-receptor-agonist. The increase of serotonin and dopamine in the synaptic cleft is responsible for hallucinations.
- Intoxication: optical hallucinations, illusions, depersonalization, flight of ideas, confusion
- There are rarely acute symptoms of withdrawal or dependence.
- “Flashbacks” (hallucinogen persisting perception disorder, HPPD): caused by reabsorption of substance from bodily stores. Depression and panic are typical features.
- Substances: glue, paint thinners, fuel, nitrous oxide, alkyl nitrites
- Action: : Varies by specific inhalant, but generally work by depressing the CNS
- Street names: poppers, whippits
- Epidemiology: most prevalent in high-school aged individuals
- Withdrawal: : usually no withdrawal symptoms, but regular users may develop symptoms of CNS excitation (e.g. tachycardia, irritability, or hallucinations)
- Action: : κ-, δ-, and μ-receptor agonists (, , , ), mixed agonist/antagonist action ()
- Street names: smack, dope
- Epidemiology: Opioids are involved in about 75% of deaths from pharmaceutical overdose.
- See in the article on .
- See in the article on .
- Opioid maintenance therapy: long-term pharmacotherapy that involves substituting addictive opioids, e.g., heroin, with a less euphoric, but longer-acting opioid; (e.g., methadone; , buprenorphine).
- Pharmacological treatment should be accompanied by psychosocial treatment (e.g., ).
- Treat associated comorbidities of IV opioid addiction (e.g., HIV, hepatitis C, endocarditis).
Overdose with opioid analgesics is the most common cause of death among adults < 50 years.
See sections on sedative-hypnotic drugs article. and in the
- Substances: cocaine, crack (free base form of cocaine)
- Street names: coke, blow
- Snorting can cause damage to the nasal vessels and result in nosebleeds
- Marked psychological dependence even after first exposure; characterized by a strong desire to use cocaine
- Physiologic “crash”: lack of energy, depression, constricted pupils, psychomotor agitation, vivid dreams, increased appetite
- ↓ Reuptake of norepinephrine → ↑ α- and β1‑stimulation → vasoconstriction and vasospasm → myocardial infarction, cerebrovascular accident, or ischemic colitis
- Rhabdomyolysis: : seen in 20% of cocaine overdoses , likely due to alterations in skeletal muscle in chronic cocaine users → acute renal tubular necrosis due to myoglobinuria
- Cocaine-induced vasospasm
- Substances: amphetamines
- Action: increased release and inhibited reuptake of adrenaline, norepinephrine, serotonin, and dopamine → sympathetic stimulation and hallucinogenic effects
- Street names: speed, uppers, molly, crystal meth
- Resemble those of cocaine
- ↑ libido; , constipation, tachycardia with arrhythmias; , mydriasis; , ↑ body temperature; , ↑ perspiration; , ↓ appetite, weight loss, grinding teeth
- Neuropsychiatric symptoms; : sleep disorders, megalomania, seizures, delusional parasitosis (delusion that body is infested with parasites or bugs)
- Hyponatremia (MDMA): dry mouth and diaphoresis; → extreme thirst → ↑ water intake without electrolyte repletion → hyponatremia → seizures and life-threatening cerebral and pulmonary edema
- Overdose →
- Similar to that of cocaine
- Physiologic “crash” after use due to receptor downregulation characterized by lack of energy, depression, increased appetite
Substances: methylenedioxypyrovalerone (MDPV), mephedrone, methylone 
- A synthetic analog of naturally-occurring cathinones (a monoamine alkaloid derived from the khat plant)
- Chemically similar to amphetamines
- Action: increased release and decreased reuptake of monoamines (norepinephrine, dopamine, serotonin) → sympathetic stimulation and hallucinogenic effects 
- Street names: bath salts, psychoactive bath salts (PABS), bloom, vanilla sky 
- Clinical features 
- Diagnosis: : based on history and clinical features; synthetic cathinones cannot be detected with routine urine toxicology screening
- Treatment 
- Substance: nicotine from the tobacco plant → cigarettes
- Action: stimulates autonomic → and stimulation in 
- Epidemiology: most prevalent cause of preventable morbidity and mortality in the United States 
- , mild , weight loss
- Restlessness, anxiety
- Increased gastrointestinal motility
- Irritability, frustration, anger, restlessness, anxiety
- Dysphoria, depressed mood
- Impaired concentration
- ↑ appetite, weight gain,
- Intoxication 
- Assessment: Smoking history is measured in pack years
- Treatment 
- Cardiovascular disease
- Cancer (e.g., lung cancer)
- Also see during
- Definition: : addictive disorder in which individuals feel a compulsion to gamble despite negative consequences and/or multiple attempts to stop.
- Sex: ♂ > ♀
- No specific age group
- Etiology: combination of factors (genetic, environmental, neurochemical abnormalities)
Diagnosis: ≥ 4 of the following in a 12 month period
- Relying on others for financial support to support habit
- Restlessness 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
- Belief that gambling helps relieve dysphoria
- Substance: gamma-hydroxybutyric acid (GHB)
- Action: Direct agonist of GABA receptors (similar to benzodiazepines)
- Street names: liquid ecstasy (unrelated to MDMA)
- Clinical features: intoxication
- Treatment: Supportive
Gamma-hydroxybutyric acid is sometimes used as a “date rape” drug because of its quick onset, amnestic effects, and complicated detection!