Drug Abuse and Addiction

Drug Abuse

• Drug abuse includes the misuse of illegal, prescription, or over-the-counter drugs in amounts or for purposes other than intended
• Drug abuse can cause social, physical, emotional, and job-related problems
• Drug addiction is a non-medical term describing a drug abuser's intense focus on obtaining and using drugs
• Drugs of abuse typically impact the central nervous system (CNS) to alter the user's mental state; some enhance physical performance
• Long-term drug use can lead to tolerance, psychological, and/or physical dependence
• Parenteral drug administration under unsterile conditions commonly leads to complications

Classes of Commonly Abused Drugs

• CNS Depressants: Ethanol and Barbiturates
• CNS Stimulants: Cocaine and Amphetamines
• Marijuana

Neurotransmitters and Drug Action

• Drugs acting as CNS stimulants or depressants increase the release of corresponding neurotransmitters
• Neurotransmitters are chemical mediators that facilitate cell communication
• Neurotransmitters can be excitatory or inhibitory
• Excitatory neurotransmitters include glutamate, norepinephrine, dopamine, and serotonin (5HT); norepinephrine and dopamine are catecholamines
• Inhibitory neurotransmitters include GABA and glycine

Cocaine

• Cocaine inhibits CNS transporters of dopamine, norepinephrine, and serotonin
• Cocaine users can have up to 5-fold increases in circulating catecholamine concentrations
• Cocaine is available as "crack" and can be smoked

Cocaine Mechanism of Action

• Cocaine blocks the dopamine transporter (also norepinephrine and serotonin transporters at higher doses) in the CNS to inhibit dopamine uptake in the mesolimbic pathway, which includes the "brain reward" center
• Cocaine use leads to elevated mood (euphoria), agitation, increased heart rate and blood pressure, higher self-confidence, and mental alertness

Cocaine Overdose

• Cocaine overdose commonly results in fatalities due to arrhythmias, seizures, or respiratory depression
• Cardiac toxicity can result from the blockade of norepinephrine reuptake by cocaine and its local anesthetic action contributes to seizures
• Cocaine's vasoconstrictive action may cause severe hypertensive episodes, leading to myocardial infarcts and strokes

Cocaine Withdrawal

• Cocaine withdrawal can cause severe depression which reinforces the compulsion to use the drug
• Other withdrawal symptoms include apathy, irritability, increased sleep duration, disorientation, and depression

Cocaine Pharmacological Properties

• Cocaine can be inhaled (snorted) or smoked (free-base form, "crack cocaine")
• Short-term, repeated IV administration or smoking is referred to as a "spree" or "run"
• Cocaine use leads to intense euphoria ("rush"), increased wakefulness, alertness, self-confidence, ability to concentrate, increased motor activity, increased sexual urge, and decreased appetite

Marijuana

• Marijuana ("cannabis", "grass") refers to the psychoactive components of the Cannabis sativa plant
• Active constituents of marijuana include delta-9-tetrahydrocannabinol, cannabinol, and cannabidiol

Marijuana Active Constituents

• Delta-9-tetrahydrocannabinol acts as an agonist to inhibit adenylyl cyclase through G-protein-linked cannabinoid receptors; normal CNS function is unknown
• Cannabinol accounts for most CNS effects and localizes in cognitive and motor areas of the brain; cannabinoid CB2-receptors can be found in the immune system
• Cannabidiol has no reported psychoactive effects

Marijuana Use and Effects

• Marijuana is typically smoked, but can be ingested; it is highly lipid soluble
• The effects of smoking marijuana are immediate and can last 2–3 hours
• CNS effects include a feeling of being "high," euphoria, disinhibition, uncontrollable laughter, changes in perception, and a dreamlike state
• Mental concentration may be difficult

Marijuana Phases of Use

• The initial phase of marijuana use ("high") is characterized by euphoria, uncontrolled laughter, loss of sense of time, and increased introspection
• The second phase includes relaxation, a dreamlike state, sleepiness, and difficulty in concentration
• At extremely high doses, acute psychosis with depersonalization has been observed

Marijuana Physiological Effects and Therapeutic Uses

• Physiological effects of marijuana include increased pulse rate and conjunctival reddening
• Marijuana, and its analogue dronabinol, is used therapeutically to decrease intraocular pressure for glaucoma treatment, as an antiemetic in cancer chemotherapy, and to stimulate appetite in AIDS patients

Marijuana Adverse Effects

• Long-term effects can be similar to cigarette smoking, including periodontal disease.
• Can cause exacerbation of preexisting paranoia or psychosis
• "Amotivational syndrome" may be related to the user's personality type
• Short-term memory impairment and disturbances of the immune, reproductive, and thermoregulatory systems