Psychopharmacology

Psychopharmacology (from Greek ; ; and ) is the scientific study of the effects drugs have on mood, sensation, thinking, behavior, judgment and evaluation, and memory. It is distinguished from neuropsychopharmacology, which emphasizes the correlation between drug-induced changes in the functioning of cells in the nervous system and changes in consciousness and behavior.

The field of psychopharmacology studies a wide range of substances with various types of psychoactive properties, focusing primarily on the chemical interactions with the brain. The term "psychopharmacology" was likely first coined by David Macht in 1920. Psychoactive drugs interact with particular target sites or receptors found in the nervous system to induce widespread changes in physiological or psychological functions. The specific interaction between drugs and their receptors is referred to as " drug action", and the widespread changes in physiological or psychological function is referred to as " drug effect". These drugs may originate from natural sources such as plants and animals, or from artificial sources such as chemical synthesis in the laboratory.

Historical overview

Early psychopharmacology

Not often mentioned or included in the field of psychopharmacology today are psychoactive substances not identified as useful in modern mental health settings or references. These substances are naturally occurring, but nonetheless psychoactive, and are compounds identified through the work of ethnobotanists and ethnomycologists (and others who study the native use of naturally occurring psychoactive drugs). However, although these substances have been used throughout history by various cultures, and have a profound effect on mentality and brain function, they have not always attained the degree of scrutinous evaluation that lab-made compounds have. Nevertheless, some, such as psilocybin and mescaline, have provided a basis of study for the compounds that are used and examined in the field today. Hunter-gatherer societies tended to favor hallucinogens, and today their use can still be observed in many surviving tribal cultures. The exact drug used depends on what the particular ecosystem a given tribe lives in can support, and are typically found growing wild. Such drugs include various psychoactive mushrooms containing psilocybin or muscimol and cacti containing mescaline and other chemicals, along with myriad other plants containing psychoactive chemicals. These societies generally attach spiritual significance to such drug use, and often incorporate it into their religious practices.
With the dawn of the Neolithic and the proliferation of agriculture, new psychoactives came into use as a natural by-product of farming. Among them were opium, cannabis, and alcohol derived from the fermentation of cereals and fruits. Most societies began developing herblores, lists of herbs which were good for treating various physical and mental ailments. For example, St. John's wort was traditionally prescribed in parts of Europe for depression (in addition to use as a general-purpose tea), and Chinese medicine developed elaborate lists of herbs and preparations. These and various other substances that have an effect on the brain are still used as remedies in many cultures.

Modern psychopharmacology

The dawn of contemporary psychopharmacology marked the beginning of the use of psychiatric drugs to treat psychological illnesses. It brought with it the use of opiates and barbiturates for the management of acute behavioral issues in patients. In the early stages, psychopharmacology was primarily used for sedation. With the 1950s came the establishment of lithium for mania, chlorpromazine for psychoses, and then in rapid succession, the development of tricyclic antidepressants, monoamine oxidase inhibitors, and benzodiazepines, among other antipsychotics and antidepressants. A defining feature of this era includes an evolution of research methods, with the establishment of placebo-controlled, double-blind studies, and the development of methods for analyzing blood levels with respect to clinical outcome and increased sophistication in clinical trials. The early 1960s revealed a revolutionary model by Julius Axelrod describing nerve signals and synaptic transmission, which was followed by a drastic increase of biochemical brain research into the effects of psychotropic agents on brain chemistry. After the 1960s, the field of psychiatry shifted to incorporate the indications for and efficacy of pharmacological treatments, and began to focus on the use and toxicities of these medications. The 1970s and 1980s were further marked by a better understanding of the synaptic aspects of the action mechanisms of drugs. However, the model has its critics, too – notably Joanna Moncrieff and the Critical Psychiatry Network.

Chemical signaling

Neurotransmitters

Psychoactive drugs exert their sensory and behavioral effects almost entirely by acting on neurotransmitters and by modifying one or more aspects of synaptic transmission. Neurotransmitters can be viewed as chemicals through which neurons primarily communicate; psychoactive drugs affect the mind by altering this communication. Drugs may act by 1) serving as a precursor to a neurotransmitter; 2) inhibiting neurotransmitter synthesis; 3) preventing storage of neurotransmitters in the presynaptic vesicle; 4) stimulating or inhibiting neurotransmitter release; 5) stimulating or blocking post-synaptic receptors; 6) stimulating autoreceptors, inhibiting neurotransmitter release; 7) blocking autoreceptors, increasing neurotransmitter release; 8) inhibiting neurotransmission breakdown; or 9) blocking neurotransmitter reuptake by the presynaptic neuron.

Hormones

The other central method through which drugs act is by affecting communications between cells through hormones. Neurotransmitters can usually only travel a microscopic distance before reaching their target at the other side of the synaptic cleft, while hormones can travel long distances before reaching target cells anywhere in the body. Thus, the endocrine system is a critical focus of psychopharmacology because 1) drugs can alter the secretion of many hormones; 2) hormones may alter the behavioral responses to drugs; 3) hormones themselves sometimes have psychoactive properties; and 4) the secretion of some hormones, especially those dependent on the pituitary gland, is controlled by neurotransmitter systems in the brain.

Psychopharmacological substances

Alcohol

Alcohol is a depressant, the effects of which may vary according to dosage amount, frequency, and chronicity. As a member of the sedative-hypnotic class, at the lowest doses, the individual feels relaxed and less anxious. In quiet settings, the user may feel drowsy, but in settings with increased sensory stimulation, individuals may feel uninhibited and more confident. High doses of alcohol rapidly consumed may produce amnesia for the events that occur during intoxication. Other effects include reduced coordination, which leads to slurred speech, impaired fine-motor skills, and delayed reaction time. The effects of alcohol on the body's neurochemistry are more difficult to examine than some other drugs. This is because the chemical nature of the substance makes it easy to penetrate into the brain, and it also influences the phospholipid bilayer of neurons. This allows alcohol to have a widespread impact on many normal cell functions and modifies the actions of several neurotransmitter systems. Alcohol inhibits glutamate (a major excitatory neurotransmitter in the nervous system) neurotransmission by reducing the effectiveness at the NMDA receptor, which is related to memory loss associated with intoxication. It also modulates the function of GABA, a major inhibitory amino acid neurotransmitter. Abuse of alcohol has also been correlated with thiamine deficiencies within the brain, leading to lasting neurological conditions that affect primarily the ability of the brain to effectively store memories. One such neurological condition is called Korsakoff's syndrome, for which very few effective treatment modalities have been found. The reinforcing qualities of alcohol leading to repeated use – and thus also the mechanisms of withdrawal from chronic alcohol use – are partially due to the substance's action on the dopamine system. This is also due to alcohol's effect on the opioid systems, or endorphins, that have opiate-like effects, such as modulating pain, mood, feeding, reinforcement, and response to stress.

Antidepressants

Antidepressants reduce symptoms of mood disorders primarily through the regulation of norepinephrine and serotonin (particularly the 5-HT receptors). After chronic use, neurons adapt to the change in biochemistry, resulting in a change in pre- and postsynaptic receptor density and second messenger function. The Monoamine Theory of Depression and Anxiety, which states that the disruption of the activity of nitrogen containing neurotransmitters (i.e. serotonin, norepinephrine, and dopamine) is strongly correlated with the presence of depressive symptoms. Despite its longstanding prominence in pharmaceutical advertising, the myth that low serotonin levels cause depression is not supported by scientific evidence.

Monoamine oxidase inhibitors (MAOIs) are the oldest class of antidepressants. They inhibit monoamine oxidase, the enzyme that metabolizes the monoamine neurotransmitters in the presynaptic terminals that are not contained in protective synaptic vesicles. The inhibition of the enzyme increases the amount of neurotransmitter available for release. It increases norepinephrine, dopamine, and 5-HT, thus increasing the action of the transmitters at their receptors. MAOIs have been somewhat disfavored because of their reputation for more serious side effects.

Tricyclic antidepressants (TCAs) work through binding to the presynaptic transporter proteins and blocking the reuptake of norepinephrine or 5-HT into the presynaptic terminal, prolonging the duration of transmitter action at the synapse.

Selective serotonin reuptake inhibitors (SSRIs) selectively block the reuptake of serotonin (5-HT) through their inhibiting effects on the sodium/potassium ATP-dependent serotonin transporter in presynaptic neurons. This increases the availability of 5-HT in the synaptic cleft. The main parameters to consider in choosing an antidepressant are side effects and safety. Most SSRIs are available generically and are relatively inexpensive. Older antidepressants such as TCAs and MAOIs usually require more visits and monitoring, which may offset the low expense of the drugs. SSRIs are relatively safe in overdoses and better tolerated than TCAs and MAOIs for most patients.

Antipsychotics

All proven antipsychotics are postsynaptic dopamine receptor blockers (dopamine antagonist

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