In addition to alcohol, the major drugs of abuse are nicotine, marijuana (∆9-tetrahydrocannabinol), heroin, and the CNS stimulants, notably cocaine and amphetamine and its derivatives (Table Drugs of abuse).
Table: Drugs of abuse
| NICOTINE | MARIJUANA | COCAINE/AMPHETAMINE | |
| Route of administration | Smoking | Smoking | Smoking, oral IV |
| Mechanism of action | Mimics action of acetylcholine | Interacts with G-protein-coupled cannabinoid receptors among other actions | Cocaine binds the dopamine reuptake transporter. Amphetamine increases release of neuronal catecholamines, including dopamine |
| Pharmacologic effects | Stimulant and depressant actions on the CNS and cardiovascular system | Euphoria, uncontrollable laughter, introspection, loss of sense of time, sleepiness, loss of concentration | Euphoria, excitation, increased alertness, an orgasmic-like “rush” |
| Tolerance and dependence | Tolerance develops rapidly Strong psychologic dependence Withdrawal syndrome indicative of physical dependence | Arguably, some tolerance and very mild physical dependence | Rapid development of tolerance. Withdrawal syndrome characterized by increased appetite, depression, and exhaustion |
| Therapeutic uses | None | Nausea and vomiting of cancer. Appetite stimulation in AIDS (dronabinol) | Local anesthesia (cocaine). ADHD (methylphenidate). Narcolepsy (modafmil) |
| Adverse effects | Cancer, obstructive lung disease, cardiovascular disease | Bronchitis, increased pulse rate, reddening of conjunctiva | Paranoid schizophrenia. Amphetamine-specific necrotizing arteritis. Cocaine-related arrhythmias, seizures, respiratory depression, hypertension, stroke, increased fetal mortality, and abnormalities |
| Treatment of abuse | Nicotine gum and transdermal patch | Behavioral modification | Antipsychotic agents. Antidepressant agents |
Questions
[1] Alcohol is oxidized by which of the following enzymes?
A. Acetate oxidase
B. ADH
C. Aldehyde dehydrogenase
D. Monoamine oxidase
[2] Which of the following is the most common adverse effect resulting from chronic ethanol abuse?
A. Cirrhosis
B. Cutaneous vasodilation
C. Disinhibited j udgment
D. Respiratory depression
[3] Which of the following is a drug of abuse that blocks the dopamine uptake transporter?
A. Alcohol
B. Cocaine
C. Marijuana
D. Nicotine
Answers
[1] B. Alcohol is oxidized in the liver, stomach, and other organs to acetaldehyde by the cytosolic enzyme ADH and the hepatic microso-mal enzymes. Acetaldehyde is oxidized to acetate by mitochondrial hepatic aldehyde dehydrogenase.
[2] A. Liver cirrhosis is an effect of chronic alcohol use. Disinhibited judgment, respiratory depression, and cutaneous vasodilation are acute effects of alcohol.
[3] B. Cocaine is a drug of abuse that binds the dopamine reuptake transporter. Ethanol may nonspecifically disrupt cell membrane protein functions. Marijuana interacts with G-protein-coupled cannabinoid receptors. Nicotine mimics the action of acetylcholine.
Pharmacology pearls
Alcohol is the most widely used drug of abuse.
Delirium Tremens, a syndrome associated with the abrupt discontinuation of alcohol in a chronic abuser, carries a high mortality rate if not promptly identified and treated.
Withdrawal from other drugs of abuse may cause unpleasant symptoms for the patient, but is rarely life threatening.
In all hypotheses of addiction, increased concentrations of dopamine in the mesolimbic system is considered the neurochemical correlate of dependence and addiction.