6-1 Principles of Psychopharmacology

Psychoactive drugs—substances that alter mood, thought, or behavior—produce their effects by acting on neuronal receptors or on chemical processes in the nervous system, especially on neurotransmission at synapses. Drugs act either as agonists to stimulate neuronal activity or as antagonists to depress it. Psychopharmacology is the study of drug effects on the brain and behavior.

Drugs are administered by mouth, by inhalation, by absorption through the skin, rectally by suppository, and by injection. To reach a nervous system target, a psychoactive drug must pass through numerous barriers posed by digestion and dilution, the blood–brain barrier, and cell membranes. Drugs are diluted by body fluids as they pass through successive barriers, are metabolized in the body, and are excreted through sweat glands and in feces, urine, breath, and breast milk.

A common misperception about psychoactive drugs is that they act specifically and consistently, but learning also affects individual responses to drugs. The body and brain may rapidly become tolerant of (habituated to) many drugs, so the dose must increase to produce a constant effect. Alternatively, people may become sensitized to a drug: the same dose produces increasingly strong effects. These forms of unconscious learning also contribute to a person’s behavior under a drug’s influence.

6-2 Grouping Psychoactive Drugs

Psychoactive drugs can be organized according to their major behavioral effects into five groups: antianxiety agents and sedative-hypnotics, antipsychotic agents, antidepressants and mood stabilizers, opioid analgesics, and psychotropics. Each group, summarized in Table 6-1 on page 181, contains natural or synthetic drugs or both, and they may produce their actions in different ways.

6-3 Factors Influencing Individual Responses to Drugs

A drug does not have a uniform action on every person. Physical differences—in body weight, sex, age, or genetic background—influence a given drug’s effects on a given person, as do behaviors, such as learning, and cultural and environmental contexts.

The influence of drugs on behavior varies widely with the situation and as a person learns drug-related behaviors. Behavioral myopia, for example, can influence a person to focus primarily on prominent environmental cues. These cues may encourage the person to act in uncharacteristic ways.

Females are more sensitive to drugs than males are and may become addicted more quickly than males to lower doses of drugs. The incidence of female abuse of many kinds of drugs equals or exceeds male abuse of those drugs.

6-4 Explaining and Treating Drug Abuse

The neural mechanisms implicated in addiction are the same neural systems responsible for wanting and liking more generally. So anyone is likely to be a potential drug abuser. Addiction develops in a number of stages as a result of repeated drug taking.

Initially, drug taking produces pleasure (liking), but with repeated use the behavior becomes conditioned to associated objects, events, and places. Eventually, the conditioned cues motivate the drug user to seek them out (wanting), which leads to more drug taking. These subjective experiences become associated with prominent cues, and drug seeking promotes craving for the drug. As addiction proceeds, the subjective experience of liking decreases while wanting increases.

Treatment varies with the drug. Whatever the treatment approach, success likely depends on permanent lifestyle changes. Considering how many people use tobacco, drink alcohol, use recreational drugs, or abuse prescription drugs, to find someone who has not used a drug when it was available is probably rare. But because of either genetic or epigenetic influences, some people do seem particularly vulnerable to drug abuse and addiction.

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Excessive alcohol use can be associated with damage to the thalamus and hypothalamus, but the damage is caused by poor nutrition rather than the direct actions of alcohol. Cocaine can produce brain damage by reducing blood flow or by bleeding into neural tissue. MDMA (Ecstasy) use can result in the loss of fine axon collaterals of serotonergic neurons and associated impairments in cognitive function.

Psychedelic drugs, such as marijuana and LSD, can be associated with psychotic behavior. Whether this behavior is due to the drugs’ direct effects or to the aggravation of preexisting conditions is not clear.

6-5 Hormones

Steroid and peptide hormones produced by endocrine glands circulate in the bloodstream to affect a wide variety of targets. Interacting to regulate hormone levels is a hierarchy of sensory stimuli and cognitive activity in the brain that stimulates the pituitary gland through the hypothalamus. The pituitary stimulates or inhibits the endocrine glands, which send feedback to the brain via other hormones.

Homeostatic hormones regulate the balance of sugars, proteins, carbohydrates, salts, and other substances in the body. Gonadal hormones regulate the physical features and behaviors associated with sex characteristics and behaviors, reproduction, and parenting. Glucocorticoids are steroid hormones that regulate the body’s ability to cope with stress—with arousing and challenging situations.

The hippocampus plays an important role in ending the stress response. Failure to turn stress responses off after a stressor has passed can contribute to susceptibility to PTSD and other psychological and physical diseases. Stress may activate epigenetic changes that modify the expression of genes regulating hormonal responses to stress and may produce brain changes persisting long after the stress-provoking incident has passed.

Synthetic anabolic steroids, used by athletes and others alike, mimic the effects of testosterone and so increase muscle bulk, stamina, and aggression but can have deleterious side effects.