Drug Dependence: Amphetamines and Cathinones

Drug Dependence: Amphetamines and Cathinones

• Addiction: Persistent drug use despite harm.
• Drug Dependence: Adaptive state causing withdrawal upon cessation of use. Receptor numbers decrease due to prolonged exposure.
• CNS Stimulants: Amphetamines, methamphetamines, MDMA (ecstasy/molly), and cathinones (khat). These drugs share similar effects and risks, but usage patterns and cultural significance vary.

Amphetamines

• Mechanism of Action (MoA): Increase neurotransmitter release (adrenaline, norepinephrine, serotonin, dopamine) and decrease reuptake, leading to CNS stimulation.
• Effects (central): Euphoria, increased energy, hallucinations, impaired judgment, agitation, confusion, sleep disturbances, psychosis.
• Effects (peripheral): Tachycardia, hypertension, arrhythmia, hyperthermia, mydriasis (pupil dilation), nausea, weight loss, muscle weakness. Amphetamines have opposite effects to opioids.
• Complications: Cardiac arrhythmias, cerebral hemorrhage, rhabdomyolysis, hyperthermia, memory impairment.
• Withdrawal Symptoms: Dysphoria, fatigue, depression, increased appetite, insomnia/hypersomnia, drug cravings, anxiety, aggression. Chronic use can lead to psychosis.
• Death: Usually from overdose, resulting in cardiovascular collapse or hyperthermia.
• Overdose Mechanisms: Hypertensive crisis, vasoconstriction + sympathetic nervous system stimulation → dangerously high blood pressure (stroke, myocardial infarction, aortic dissection), arrhythmia (tachycardia, irregular heartbeats → sudden cardiac arrest), severe hyperthermia (multiorgan failure, rhabdomyolysis, kidney failure), seizures (status epilepticus).
• Lethal Dose: 150-500 mg in non-tolerant users.
• Management: Symptom-based, such as benzodiazepines for seizures or agitation.

Khat (Cathinones)

• Description: Plant (leaves) chewed as a stimulant. Contains cathinones, a potent stimulant. Small doses might produce a coffee-like effect with increased blood flow to the brain and faster heart rate.
• Effects (positive): Euphoria, excitement, mild hyperactivity.
• Effects (negative): Agitation, hallucinations, paranoia, hypertension, tachycardia, mydriasis, constipation.
• Long-Term Complications: Liver damage, permanent tooth discoloration, ulcers, compromised self-control.
• Withdrawal: Mild depression, irritability (occasional use), lethargy, tremors (chronic use).
• Diagnosis: Blood, urine, or saliva testing.

Comparison

• Similarities: Euphoria, increased energy, agitation, psychosis, withdrawal symptoms (depression, irritability).
• Differences: Amphetamines have stronger, faster effects increasing severe complication risk (hypernatremia, cardiovascular events). Khat is more culturally embedded, and the intoxication is more gradual, but the risk of long-term dependence is similar.
• Death: Similar cardiovascular-related complications with khate in both cases
• Autopsy findings: Myocardial infarction, left ventricular hypertrophy and other cardio related effects found during autopsies for khate users. Also common findings of intracerebral hemorrhage, stroke, brain edema, and gastrointestinal ulcers