Cocaine: Forms, Usage, and Effects

• In 2018, roughly 5.5 million people in the United States used cocaine.
• Cocaine use appears to have increased since 2018.

Cocaine Forms

• Powder cocaine is extracted from coca leaves.
• Crack cocaine consists of crystals of cocaine hydrochloride.

Cocaine Methods of Use

• Snorting cocaine allows absorption through the nasal mucosa.
• Smoking cocaine allows rapid absorption into the bloodstream via alveoli.
• Injecting cocaine subcutaneously or intravenously allows immediate bloodstream entry, but carries the highest risk of overdose.
• Crack cocaine produces a faster, more intense high compared to snorted powder cocaine, leading to stronger addiction potential.

Cocaine Mechanism of Action

• Cocaine is a sympathomimetic agent that acts on both the central nervous system (CNS) and adrenergic nerve endings.

CNS Effects

• Cocaine blocks dopamine reuptake which leads to dopamine accumulation in the synaptic cleft.
• Blocks dopamine reuptake results in hyperstimulation, causing euphoria, paranoia, and hyperthermia.
• Euphoria is the intense pleasure caused by excessive dopamine.
• Paranoia results from overstimulation of the amygdala and fear-processing circuits.
• Hyperthermia (high body temperature) is caused by dysregulation of hypothalamic thermoregulatory pathways.

Adrenergic Nerve Ending Effects

• Cocaine blocks the reuptake of epinephrine and norepinephrine, enhancing sympathetic activity.
• Cocaine stimulates presynaptic release of norepinephrine, leading to hypertension, tachycardia (rapid heart rate), and peripheral vasoconstriction.
• Hypertension is the increased blood pressure due to vasoconstriction.
• Tachycardia is the exaggerated sympathetic stimulation of a rapid heart rate.
• Peripheral vasoconstriction results in decreased blood flow to extremities and organs.

Cocaine Acute Toxicity: Cardiovascular Effects

• The most dangerous acute effect of cocaine is on the cardiovascular system, leading to:
  • Hypertension and tachycardia, which increase strain on the heart.
  • Peripheral vasoconstriction, potentially leading to limb ischemia.
  • Coronary artery vasoconstriction, which reduces oxygen supply to the heart.
  • Promotion of thrombus formation by facilitating platelet aggregation, increasing clot risk.
• The net effect is myocardial ischemia or infarction (heart attack)
• This is due to increased cardiac workload (tachycardia) and decreased coronary blood flow (vasoconstriction).
• Fatal arrhythmias may occur, even in first-time users.
• Cocaine disrupts cardiac ion transporters, triggering dangerous arrhythmias independently of its vascular effects.

Cocaine Acute Toxicity: Neurological Effects

• Seizures can result from extreme CNS hyperstimulation.
• Hyperthermia is the uncontrolled elevation in body temperature due to hypothalamic dysregulation.

Cocaine Acute Toxicity: Pregnancy-Related Effects

• Cocaine reduces placental blood flow, leading to fetal hypoxia and spontaneous abortion.
• It also causes neurologic development impairment in fetuses of chronic users.

Cocaine Chronic Toxicity

• Chronic effects of cocaine use:
  • Nasal septum perforation due to chronic snorting and mucosal ischemia.
  • Decreased lung diffusing capacity in users who inhale cocaine smoke.
  • Dilated cardiomyopathy is a progressive weakening of heart muscle due to toxic effects.
• Decreased lung diffusing capacity refers to a reduction in the ability of the lungs to transfer oxygen (O₂) from the air into the bloodstream, and carbon dioxide (CO₂) from the blood into the air
• Cocaine and its metabolites can directly damage the lungs when they are inhaled, either through snorting or smoking.
• Inhalation of cocaine causes irritation and inflammation of the airways and alveoli, which can damage the alveolar-capillary membrane (the barrier through which gases like oxygen and carbon dioxide diffuse).
• Inflammation and injury to the alveolar walls can lead to thickening of the alveolar-capillary membrane, reducing the efficiency of gas exchange and resulting in a decreased lung diffusing capacity.
• Cocaine can also cause bleeding in the lungs, especially when smoked, which can further impair gas exchange by filling the alveoli with blood or fluid and reduces the surface area available for diffusion.

Cocaine Withdrawal

• Cocaine is a stimulant that affects neurotransmitter systems, particularly dopamine, serotonin, and norepinephrine, which play major roles in mood regulation, reward pathways, and overall energy levels.
• Over time, the brain adapts to the presence of cocaine, and the sudden absence of the drug leads to a cascade of physiological and psychological changes.
• Cocaine is a stimulant that increases dopamine levels in the brain, primarily by blocking the reuptake of dopamine.
• Prolonged use causes the brain to decrease natural dopamine production in response to the constant influx of the neurotransmitter.
• When cocaine is no longer available, the brain experiences a dopamine deficit, leading to depression as a result of the diminished reward system.
• Cocaine stimulates the central nervous system and increases energy and alertness by raising levels of norepinephrine and dopamine.
• When the drug is suddenly stopped, the body's energy levels crash due to neurotransmitter depletion.
• Cocaine use disrupts the normal sleep-wake cycle by increasing levels of norepinephrine and dopamine, which keep the user awake and alert.
• After withdrawal, the rebound effect can cause extreme fatigue but also lead to sleep disturbances, such as insomnia or hypersomnia (excessive sleep), as the brain tries to regulate itself without the stimulant influence.
• Cocaine boosts dopamine levels in areas of the brain involved in reward, motivation, and focus.
• After cessation, the brain struggles to function normally without the usual dopamine rush, leading to difficulty concentrating and anhedonia (the inability to feel pleasure).
• The brain's reward system has been downregulated, so everyday activities no longer feel rewarding.
• Cocaine acts as an appetite suppressant by increasing norepinephrine levels, which reduces hunger.
• When the drug is withdrawn, the body compensates by increasing appetite, often leading to overeating or craving high-calorie foods, as the body tries to stabilize its energy levels.
• Cocaine withdrawal often leads to REM sleep rebound.

Cocaine Withdrawal Symptoms

• Psychological symptoms:
  • Depression, fatigue, lethargy, and sleep disturbances.
  • Difficulty concentrating and anhedonia (lack of pleasure).
  • Increased appetite and vivid dreams.
• Physiologic symptoms:
  • Severe depression with suicidal ideation, constricted pupils, and psychomotor agitation

Cocaine Withdrawal Treatment

• Supportive care can help symptoms resolve within 72 hours, but may last up to two weeks in heavy users.
• Cocaine use disorder is best addressed using psychotherapy and group programs.

Marijuana Prevalence

• Marijuana is the most widely used illegal drug in the United States.
• Roughly 44 million people used marijuana in 2017.
• Marijuana is made from the leaves of Cannabis sativa, Cannabis indica, or hybrids.
• Delta-9-tetrahydrocannabinol (THC) is the psychoactive substance in marijuana.

Marijuana Beneficial Effects

• Medical uses of marijuana:
  • Decreasing intraocular pressure in glaucoma.
  • Combating intractable nausea secondary to cancer chemotherapy.

Marijuana Acute Effects

• Distorted Sensory Perception:
  • Distorts perception of time, speed, and distance.
  • Impaired motor coordination, lasting 4-5 hours.
• Cardiovascular effects:
  • Increased heart rate and sometimes blood pressure, which may lead to angina in individuals with coronary artery disease.

Marijuana Chronic Effects

• Respiratory effects from chronic marijuana smoking:
  • Laryngitis, bronchitis, and cough.
  • Asthma-like symptoms and mild airway obstruction.
  • Associations with severe complications (e.g., COPD or lung cancer) are not yet established.

Marijuana Legalization

• Legislation regarding marijuana varies by state.
• Some states have legalized recreational use.
• Legalization may influence patterns of use and public health outcomes.