1.2 Pharmacology of Major Drug Classes

Pharmacology Fundamentals

Before the drug classes, four concepts appear across nearly every pharmacology item on the ADC exam:

• Route of administration — IV and smoked routes produce the fastest peak (seconds to minutes) and the highest abuse liability; oral routes are slowest.
• Onset and peak — how quickly subjective effects start and reach maximum.
• Half-life (t½) — time for plasma concentration to fall by 50%. Short half-life predicts faster, sharper withdrawal; long half-life predicts delayed, protracted withdrawal.
• Mechanism — which neurotransmitter system the drug acts on (GABA, mu opioid, dopamine, serotonin, glutamate, cannabinoid).

Two additional terms recur: an agonist activates a receptor (heroin, methadone), a partial agonist activates it with a ceiling (buprenorphine), and an antagonist blocks it (naloxone, naltrexone). Knowing these labels lets you predict overdose reversal and medication-assisted treatment behavior.

CNS Depressants

Depressants slow central nervous system activity by enhancing GABA (the brain's main inhibitory transmitter) or, for opioids, by activating mu opioid receptors. The risk of fatal overdose comes from respiratory depression, especially when depressants are combined.

High-yield pairing: Benzodiazepines + opioids + alcohol is the most lethal combination because all three suppress respiratory drive. Most opioid overdose deaths in the United States now involve illicitly manufactured fentanyl, which is roughly 50–100 times more potent than morphine and frequently contaminates the street supply. Counselors should normalize take-home naloxone for every opioid client and family.

CNS Stimulants

Stimulants increase dopamine and norepinephrine activity in the brain.

Stimulant withdrawal — the crash — is dysphoric and exhausting but is not medically dangerous in most healthy adults; suicide risk during the crash, however, is real and must be assessed. Cocaine mixed with alcohol forms cocaethylene, a longer-acting and more cardiotoxic metabolite the exam may name.

Hallucinogens / Dissociatives

• Classic hallucinogens (LSD, psilocybin, mescaline, DMT) — partial agonists at 5-HT2A serotonin receptors. Long duration (LSD 8-12 hr). Low addiction liability but rapid tolerance; bad trips and hallucinogen persisting perception disorder (HPPD) are key risks.
• Dissociatives (ketamine, PCP, dextromethorphan) — NMDA glutamate receptor antagonists. Cause detachment from body or reality. PCP is linked to violent agitation; ketamine has therapeutic uses in depression at low doses but produces dependence with chronic recreational use.

Cannabis

• Delta-9-THC is a partial agonist at CB1 cannabinoid receptors densely expressed in the hippocampus, cerebellum, and prefrontal cortex.
• Cannabis Use Disorder is recognized in DSM-5-TR; daily use raises addiction risk substantially.
• Withdrawal: irritability, anxiety, sleep disturbance, decreased appetite, vivid dreams; begins within 24-72 hours and peaks in the first week.
• Synthetic cannabinoids (K2, Spice) are full agonists with unpredictable potency and serious psychiatric and cardiac toxicity.

Inhalants

Inhalants are a heterogeneous group of volatile solvents, aerosols, gases, and nitrites (glue, paint thinner, butane, nitrous oxide, amyl nitrite). They produce rapid intoxication through diffusion across pulmonary membranes. Risks include:

• Sudden Sniffing Death Syndrome — fatal cardiac arrhythmia, even on first use.
• Permanent leukoencephalopathy and peripheral neuropathy with chronic use.
• High prevalence among adolescents because the products are legal and accessible.

Route to Reinforcement Hierarchy

The faster a drug reaches the brain, the more reinforcing it is. From most to least addictive route:

1. Smoking / inhalation (seconds)
2. Intravenous injection (15-30 seconds)
3. Intranasal (snorting) (3-5 minutes)
4. Oral (15-60 minutes)

This is why crack cocaine is more addictive than powdered cocaine taken intranasally, and why heroin smoked or injected is more addictive than oral oxycodone taken as prescribed.