Signs and Symptoms of Drug Abuse (by Drug)

General Concepts

• ALL addictive drugs act on the dopamine mesolimbic-reward pathway
• Withdrawal symptoms are often the opposite of intoxication
  • e.g. miosis in opioid intoxication and mydriasis in withdrawal 
• Depressant withdrawal is generally more life-threatening than stimulant withdrawal
• Injection drug users at risk for
  • right-sided endocarditis
  • hepatitis and abscesses
  • overdose
  • hemorrhoids
• AIDS

Depressants

• Opioids (e.g. morphine, heroin, methadone)
  • intoxication 
    • nausea and vomiting with constipation
    • respiratory depression 
    • pupillary constriction (pinpoint pupils = miosis)
    • seizures (overdose is life-threatening)
    • for heroin use look for track marks (needle injections)
  • treatment for intoxication 
    • naloxone/naltrexone
      • opioid receptor antagonist
    • symptomatic treatment
  • withdrawal 
    • anxiety, insomnia, anorexia, sweating, dilated pupils, piloerection (“cold turkey”), fever, rhinorrhea, nausea, stomach cramps, diarrhea (“flulike” symptoms), muscle jerks, yawning
    • unpleasant but not life-threatening
  • treatment for withdrawal (examples mainly for heroin)
    • methadone
      • long-acting IV opiate
      • used for heroin detoxification or long-term maintenance
      • safe and used in pregnancy
    • suboxone
      • long acting oral administration with fewer withdrawal symptoms than methadone
      • naloxone + buprenorphine (partial opioid agonist)
      • naloxone is not active when taken orally, so withdrawal symptoms occur only if injected
        • intended to prevent overdose/enjoyment when suboxone is injected
• Barbiturates
  • intoxication
    • respiratory/CNS depression
    • does not have a depression “ceiling”
  • treatment of intoxication
    • must treat withdrawal with barbiturates not benzodiazepines
    • symptom management
      • assist respiration
      • ↑ BP
  • withdrawal 
    • anxiety, seizures, delirium
      • similar to alcohol
    • life-threatening cardiovascular collapse
    • additive affects with alcohol
• Benzodiazepines
  • intoxication
    • amnesia, ataxia, stupor/somnolence, minor respiratory depression
    • has a depression “ceiling”
    • additive affects with alcohol
    • treat with flumazenil (competitive GABA antagonist)
  • treatment for intoxication
    • flumazenil (competitive GABA antagonist)
  • withdrawal
    • rebound anxiety
    • seizures (life-threatening), tremor
    • insomnia
  • treatment for withdrawal 
    • long acting benzodiazepine (e.g. diazepam) to taper off dose
    • symptomatic treatment
• Alcohol
• see Alcohol topic 

Stimulants

• Amphetamines 
  • mechanism
    • simulates biogenic amine (DA, NE, 5HT) release 
  • intoxication
    • mental status changes
      • euphoria, impaired judgment, delusions, hallucinations, prolonged wakefulness/attention
    • sympathetic activation,
      • psychomotor agitation, pupillary dilation, hypertension, tachycardia, fever, cardiac arrhythmias
  • withdrawal
    • depression, lethargy, headache, stomach cramps, hunger, hypersomnolence
• MDMA (“ecstacy”) 
  • mechanism
    • similar to amphetamines
    • effects 5-HT more than dopamine
      • may damage serotonergic neurons
  • intoxication
    • hyperthermia and social closeness
      • club drug
  • withdrawal
    • mood offset for several weeks
• Cocaine 
  • mechanism
    • block biogenic amine (DA, NE, 5HT) reuptake 
  • intoxication
    • mental status changes
      • euphoria, psychomotor agitation, grandiosity, hallucinations (including tactile), paranoid ideations
    • sympathetic activation
      • ↓ appetite, tachycardia, pupillary dilation, hypertension, angina, sudden cardiac death, stroke (intense vasoconstriction)
    • stereotyped behavior
      • repetitive motions (e.g. digging through trash)
  • treatment for intoxication
    • benzodiazepines
    • neuroleptics
    • reduce blood pressure and body temperature
  • withdrawal
    • severe depression and suicidality, hyperphagia, hypersomnolence, fatigue, malaise, severe psychological craving
• Caffeine
  • intoxication
    • restlessness and insomnia
    • ↑ diuresis
    • muscle twitching
    • cardiac arrhythmias
  • withdrawal
    • headache, lethargy, depression, weight gain
• Nicotine
  • intoxication
    • restlessness, insomnia, anxiety, arrhythmias
  • withdrawal
    • irritability, headache, anxiety, weight gain, craving
  • treatment for cessation
    • bupropion (NE and dopamine reuptake inhibitor)
    • varenicline (partial nicotinic receptor agonist) 
• nicotine administration via other routes (patch, gum, lozenges)

Hallucinogens

• PCP 
  • intoxication
    • belligerence, impulsiveness, fear, homicidality, psychosis, delirium, seizures, psychomotor agitation, vertical and horizontal nystagmus, tachycardia, ataxia 
  • withdrawal
    • depression, anxiety, irritability, restlessness, anergia, disturbances of thought and sleep
  • note: ketamine is a similar drug; both are NMDA antagonists 
• LSD 
  • mechanism
    • action at 5-HT receptor
  • intoxication
    • visual hallucinations and synesthesias (e.g. seeing sound as color)
    • marked anxiety or depression, delusions, pupillary dilation
    • bad trip panic
  • withdrawal
    • largely no withdrawal because it does not effect dopamine
    • flashbacks years later
• Marijuana 
  • mechanism
    • binds to CB1/CB2 cannabinoid receptors
  • intoxication 
    • euphoria, anxiety, disinhibition, paranoid delusions, perception of slowed time, impaired judgment, social withdrawal, ↑ appetite, dry mouth, hallucinations
      • largely psychological effects
    • amotivational syndrome
  • withdrawal
    • mild symptoms
      • irritability, depression, insomnia, nausea, anorexia
    • most symptoms peak in 48 hours and last for 5-7 days
    • can be detected in urine up to 1 month after last use
  • note: dronabinol is a cannabinoid used as an antiemetic