Addiction Management

Addiction Management: Key Concepts

• Dependence vs. Addiction: Dependence involves withdrawal symptoms when the substance is removed, while addiction is compulsive use despite negative consequences, often triggered by cravings. Dependence is primarily physical; addiction is psychological, characterized by compulsive drug-seeking and relapse. Dependence often arises from chronic use, but only a small percentage of users become addicted.

Mechanisms of Addiction

• Dopamine System: All addictive drugs activate the mesolimbic dopamine system, highlighting the crucial role of dopamine mechanisms.

• Tolerance: Chronic exposure to addictive drugs leads to brain adaptations (down-regulation/up-regulation).

• Withdrawal: Withdrawal symptoms arise after drug exposure ends, exhibiting the adaptive changes.

Drug Classes and Mechanisms

• G-protein Coupled Receptors: Opioids, cannabinoids, GHB, LSD, mescaline, psilocybin.

• Ionotropic Receptors/Ion Channels: Nicotine, alcohol, benzodiazepines, phencyclidine, ketamine.

• Biogenic Amine Transporters: Cocaine, amphetamine, ecstasy.

Specific Drug Examples

Cocaine

• Mechanism of Action (MoA): Inhibits sodium channels, blocks dopamine, serotonin, and norepinephrine reuptake. The effect on dopamine is primarily responsible for its addictive qualities.
• Targets: Sodium channels, dopamine, serotonin, and norepinephrine transporters.
• Intoxication: Euphoria, hyperactivity, suppression of appetite, local anesthesia, pupil dilation, aggressiveness, psychosis, possible sudden death.
• Toxicity: Agitation, convulsions, hypertension, coronary insufficiency, hyperthermia, rhabdomyolysis, renal impairment.
• Withdrawal: Restlessness, headache, hunger, depression, irritability, insomnia/hypersomnia, strong craving.
• Treatment: Diazepam, Phentolamine (cardiovascular), Hyperthermia (immersion), potentially Nitroglycerine and beta-blockers (but with caution).

Amphetamines

• Structure: Similar to catecholamine neurotransmitters.
• MoA: Enters nerve terminals, displaces neurotransmitters, inhibiting reuptake, and stimulating release.
• Targets: Synaptic vesicular amine transporters, monoamine oxidase, dopamine, norepinephrine, and serotonin transporters.
• Effects: Elevated catecholamines leading to arousal and reduced sleep; effects on dopamine leading to euphoria and psychosis; serotonin-related effects such as hallucinations and anorexia.
• Toxicity: Hyperthermia, respiratory depression, seizures, metabolic acidosis, renal failure, hepatic injury, coma.

LSD

• MoA: Activates serotonin 5-HT2A receptors, increasing glutamatergic transmission. Repeated use rapidly induces downregulation.
• Target: Serotonin 5-HT2A receptor.
• Effects: Mood alteration, hallucinations, altered perception, possible panic ("bad trips").

Marijuana

• Components: THC and CBD are cannabinoids.
• MoA: THC acts on CB1 and CB2 receptors, while CBD negatively modulates CB1 receptors.
• Effects: Increased appetite, pain reduction, emotional/cognitive changes, anxiety, paranoia, altered time perception, social withdrawal, dry mouth.

Nicotine

• MoA: Binds to nicotinic cholinergic receptors in the brain and autonomic ganglia, stimulating neurons.
• Targets: Nicotinic cholinergic receptors (various subtypes).
• Intoxication: Restlessness, insomnia, anxiety, anorexia, arrhythmias, loss of appetite, sweating, diarrhea, nausea.
• Withdrawal: irritability, headaches, anxiety, weight gain, cravings, bradycardia, difficulty concentrating, and insomnia.

Ethanol

• MoA: Alters cell membranes, ion channels, enzymes, and receptors. Binds to GABA and glycine receptors, inhibiting NMDA receptors.
• Intoxication: Disinhibition, emotional liability, slurred speech, ataxia, aggression, blackouts, hallucinations, memory impairment.
• Withdrawal: Tremor, tachycardia, hypertension, malaise, nausea, seizures, delirium tremens.
• Treatment: Disulfiram, naltrexone, acamprosate.

Barbiturates

• Toxicity: Respiratory depression, and anxiety, seizures, and delirium during withdrawal.
• Treatment: sodium bicarbonate.

Opioids

• Effects: CNS depression, nausea, vomiting, sedation, decreased pain perception, respiratory depression and pupil constrictions
• Withdrawal: Increased sympathetic activity, nausea/vomiting, diarrhea, diaphoresis, rhinorrhea, piloerection, yawning, stomach cramps, myalgias, arthralgias, restlessness, anxiety, anorexia.
• Treatment: Naloxone, methadone, or buprenorphine.

PCP

• Effects: Belligerence, impulsiveness, psychomotor agitation, nystagmus, hyperthermia, tachycardia, psychosis, homicidality.
• Withdrawal: Recurrence of symptoms due to reabsorption in GI tract.
• Treatment: antipsychotics and benzodiazepines.

Synthetic Opioids, Bath Salts

• Synthetic opioids: Associated with MPTP-induced Parkinson's-like disorders. No withdrawal.
• Bath salts: Agitation, combativeness, delirium, psychosis (lasting weeks); No withdrawal.