Psychoactive drug

An assortment of psychoactive drugs

A psychoactive drug, psychopharmaceutical, or psychotropic is a chemical substance that crosses the blood–brain barrier and acts primarily upon the central nervous system where it affects brain function, resulting in changes in perception, mood, consciousness, cognition, and behavior.^[1] These substances may be used recreationally, to purposefully alter one's consciousness, as entheogens, for ritual, spiritual, and/or shamanic purposes, as a tool for studying or augmenting the mind, or therapeutically as medication.

Because psychoactive substances bring about subjective changes in consciousness and mood that the user may find pleasant (e.g. euphoria) or advantageous (e.g. increased alertness), many psychoactive substances are abused, that is, used excessively, despite the health risks or negative consequences. With sustained use of some substances, psychological and physical dependence ("addiction") may develop, making the cycle of abuse even more difficult to interrupt. Drug rehabilitation aims to break this cycle of dependency, through a combination of psychotherapy, support groups and even other psychoactive substances such as acamprosate or naltrexone in the treatment of alcoholism, or methadone or buprenorphine maintenance therapy in the case of opioid dependency. However, the reverse is also true in some cases, that is certain experiences on drugs may be so unfriendly and uncomforting that the user may never want to try the substance again. This is especially true of the deliriants (e.g. datura) and powerful psychoactives (e.g. salvia divinorum). Most purely psychedelic drugs are considered to be non-addictive (LSD, psilocybin, mescaline etc.); "psychedelic amphetamines" (such as MDA, MDMA etc.) may produce an additional stimulant and/or euphoriant effect, and thus have an addiction potential.

In part because of this potential for abuse and dependency, the ethics of drug use are the subject of a continuing philosophical debate. Many governments worldwide have placed restrictions on drug production and sales in an attempt to decrease drug abuse. Ethical concerns have also been raised about over-use of these drugs clinically, and about their marketing by manufacturers.

History

Psychoactive drug use is a practice that dates to prehistoric times. There is archaeological evidence of the use of psychoactive substances (most likely plants) dating back at least 10,000 years, and historical evidence of cultural use over the past 5,000 years.^[2] The chewing of Coca leaves for example was found to date back over 8000 years ago in Peruvian society.^[3][4]

Medicinal use is one important facet of psychoactive drug usage, however some have postulated that the urge to alter one's consciousness is as primary as the drive to satiate thirst, hunger or sexual desire.^[5] The long history of drug use and even children's desire for spinning, swinging, or sliding indicates that the drive to alter one's state of mind is universal.^[6]

One of the first people to articulate this point of view, set aside from a medicinal context, was American author Fitz Hugh Ludlow (1836–1870) in his book The Hasheesh Eater (1857): "...drugs are able to bring humans into the neighborhood of divine experience and can thus carry us up from our personal fate and the everyday circumstances of our life into a higher form of reality. It is, however, necessary to understand precisely what is meant by the use of drugs. We do not mean the purely physical craving...That of which we speak is something much higher, namely the knowledge of the possibility of the soul to enter into a lighter being, and to catch a glimpse of deeper insights and more magnificent visions of the beauty, truth, and the divine than we are normally able to spy through the cracks in our prison cell. But there are not many drugs which have the power of stilling such craving. The entire catalog, at least to the extent that research has thus far written it, may include only opium, hashish, and in rarer cases alcohol, which has enlightening effects only upon very particular characters.^[7]

This relationship is not limited to humans. A number of animals consume different psychoactive plants, animals, berries and even fermented fruit, becoming intoxicated, such as cats after consuming catnip. Traditional legends of sacred plants often contain references to animals that introduced humankind to their use.^[8] Biology suggests an evolutionary connection between psychoactive plants and animals, as to why these chemicals and their receptors exist within the nervous system.^[9]

During the 20th century, many governments across the world initially responded to the use of recreational drugs by banning them and making their use, supply or trade a criminal offense. A notable example of this is the Prohibition era in the United States, where alcohol was made illegal for 13 years. However, many governments, government officials and persons in law enforcement have concluded that illicit drug use cannot be sufficiently stopped through criminalization. Organizations such as Law Enforcement Against Prohibition (LEAP) have come to such a conclusion believing "the existing drug policies have failed in their intended goals of addressing the problems of crime, drug abuse, addiction, juvenile drug use, stopping the flow of illegal drugs into this country and the internal sale and use of illegal drugs. By fighting a war on drugs the government has increased the problems of society and made them far worse. A system of regulation rather than prohibition is a less harmful, more ethical and a more effective public policy."^[10] In some countries, there has been a move toward harm reduction by health services, where the use of illicit drugs is neither condoned nor promoted, but services and support are provided to ensure users have adequate factual information readily available, and that the negative effects of their use be minimized. Such is the case of Portuguese drug policy of decriminalization, which achieved its primary goal of reducing the adverse health effects of drug abuse.^[11]

Uses

Psychoactive substances are used by humans for a number of different purposes to achieve a specific end. These uses vary widely between cultures. Some substances may have controlled or illegal uses while others may have shamanic purposes, and still others are used medicinally. Other examples would be social drinking or sleep aids. Caffeine is the world's most widely consumed psychoactive substance, but unlike many others, it is legal and unregulated in nearly all jurisdictions. In North America, 90% of adults consume caffeine daily.^[12]

Psychoactive drugs are divided into three groups according to their pharmacological effects:^[13]

• Stimulants ("uppers"). This category comprises substances that wake one up, stimulate the mind, and may even cause euphoria, but do not affect perception.

Examples: coffee, tobacco, amphetamine, tea, cacao, guarana, maté, ephedra, khat, and coca.

• Depressants ("downers"), including sedatives, hypnotics, and narcotics. This category includes all of the calmative, sleep-inducing, anxiety-reducing, anesthetizing substances, which sometimes induce perceptual changes, such as dream images, and also often evoke feelings of euphoria.

Examples: opioids, barbiturates, benzodiazepines, and alcohol.

• Hallucinogens, including psychedelics, dissociatives and deliriants. This category encompasses all those substances that produce distinct alterations in perception, sensation of space and time, and emotional states.

Examples: psilocybin, LSD, Salvia divinorum, marijuana and nitrous oxide.

Use in practice: The theory of dose, set, and setting

The theory of dosage, set, and setting is a useful model in dealing with the effects of psychoactive substances, especially in a controlled therapeutic setting as well as in recreational use. Dr. Timothy Leary, based on his own experiences and systematic observations on psychedelics, developed this theory along with his colleagues Ralph Metzner, and Richard Alpert (Ram Dass) in the 1960s.^[14]

Dosage

The first factor, dosage, has been a truism since ancient times, or at least since Paracelsus who said, "Dose makes the poison." Some compounds are beneficial or pleasurable when consumed in small amounts, but harmful or deadly in higher doses.

Set

The set is the internal attitudes and constitution of the person, including his expectations, his wishes, his fears. This is an important factor especially relative to the hallucinogens. These substances have the ability to activate, potentiate, and sometimes mercilessly expose everything that a person has in his or her consciousness or buried beneath it.

In traditional cultures set is shaped primarily by the worldview that all the individuals share.

Setting

The third aspect is setting, which pertains to the surroundings, the place, and the time-the space in which the experiences transpire.

This theory clearly states that the effects are equally the result of chemical, pharmacological, psychological, and physical influences. The model that Timothy Leary proposed applied to the psychedelics, although it also applies to other psychoactives.^[13]

Anesthesia

Main article: Anesthesia

General anesthetics are a class of psychoactive drug used on patients to block pain and other sensations. Most anesthetics induce unconsciousness, which allows patients to undergo medical procedures like surgery without physical pain or emotional trauma.^[15] To induce unconsciousness, anesthetics affect the GABA and NMDA systems. For example, halothane is a GABA agonist,^[16] and ketamine is an NMDA receptor antagonist.^[17]

Pain control

Main article: Analgesics

Psychoactive drugs are often prescribed to manage pain. As the subjective experience of pain is regulated by endogenous opioid peptides, pain can be managed using psychoactives that operate on this neurotransmitter system as opioid receptor agonists. This class of drugs can be highly addictive, and includes opiate narcotics, like morphine and codeine.^[18] NSAIDs, such as aspirin and ibuprofen, are a second class of analgesics. They reduce eicosanoid-mediated inflammation by inhibiting the enzyme cyclooxygenase.

Psychiatric medication

Main article: Psychiatric medications

Zoloft (sertraline) is an SSRI antidepressant.

Psychiatric medications are prescribed for the management of mental and emotional disorders. There are six major classes of psychiatric medications:

• Antidepressants, which are used to treat disparate disorders such as clinical depression, dysthymia, anxiety, eating disorders and borderline personality disorder.^[19]
• Stimulants, which are used to treat disorders such as attention deficit disorder and narcolepsy and to suppress the appetite.
• Antipsychotics, which are used to treat psychosis, schizophrenia and mania.
• Mood stabilizers, which are used to treat bipolar disorder and schizoaffective disorder.
• Anxiolytics, which are used to treat anxiety disorders.
• Depressants, which are used as hypnotics, sedatives, and anesthetics.

Recreational use

Main article: Recreational drug use

Many psychoactive substances are used for their mood and perception altering effects, including those with accepted uses in medicine and psychiatry. Examples include caffeine, alcohol, cocaine, LSD, and cannabis.^[20] Classes of drugs frequently used recreationally include:

• Stimulants, which activate the central nervous system. These are used recreationally for their euphoric effects.
• Hallucinogens (psychedelics, dissociatives and deliriants), which induce perceptual and cognitive distortions.
• Hypnotics, which depress the central nervous system. These are used recreationally because of their euphoric effects.
• Opioid analgesics, which also depress the central nervous system. These are used recreationally because of their euphoric effects.
• Inhalants, in the forms of gas aerosols, or solvents, which are inhaled as a vapor because of their stupefying effects. Many inhalants also fall into the above categories (such as nitrous oxide which is also an analgesic).

In some modern and ancient cultures, drug usage is seen as a status symbol. Recreational drugs are seen as status symbols in settings such as at nightclubs and parties.^[21] For example, in ancient Egypt, gods were commonly pictured holding hallucinogenic plants.^[22]

Because there is controversy about regulation of recreational drugs, there is an ongoing debate about drug prohibition. Critics of prohibition believe that regulation of recreational drug use is a violation of personal autonomy and freedom.^[23] In the United States, critics have noted that prohibition or regulation of recreational and spiritual drug use might be unconstitutional.^[24]

Ritual and spiritual use

Timothy Leary was a leading proponent of spiritual hallucinogen use.

Main article: Entheogens

Certain psychoactives, particularly hallucinogens, have been used for religious purposes since prehistoric times. Native Americans have used mescaline-containing peyote cacti for religious ceremonies for as long as 5700 years.^[25] The muscimol-containing Amanita muscaria mushroom was used for ritual purposes throughout prehistoric Europe.^[26] Various other hallucinogens, including jimsonweed, psilocybin mushrooms, and cannabis, have been used in religious ceremonies for millennia.^[27]

The use of entheogens for religious purposes resurfaced in the West during the counterculture movements of the 1960s and 70s. Under the leadership of Timothy Leary, new religious movements began to use LSD and other hallucinogens as sacraments.^[28] In the United States, the use of peyote for ritual purposes is protected only for members of the Native American Church, which is allowed to cultivate and distribute peyote. However, the genuine religious use of Peyote, regardless of one's personal ancestry, is protected in Colorado, Arizona, New Mexico, Nevada, and Oregon.^[29]

Military

Main article: Psychochemical weapons

Psychoactive drugs have been used in military applications as non-lethal weapons. In World War II, between 1939 and 1945, 60 million amphetamine pills were made for use by soldiers.^{[citation needed]} Brown-brown, a form of cocaine adulterated with gun powder, has been used in the Sierra Leone Civil War by child soldiers.^{[citation needed]}

Administration

For a substance to be psychoactive, it must cross the blood-brain barrier so it can affect neurochemical function. Psychoactive drugs are administered in several different ways. In medicine, most psychiatric drugs, such as fluoxetine, quetiapine, and lorazepam are ingested orally in tablet or capsule form. However, certain medical psychoactives are administered via inhalation, injection, or rectal suppository/enema. Recreational drugs can be administered in several additional ways that are not common in medicine. Certain drugs, such as alcohol and caffeine, are ingested in beverage form; nicotine and cannabis are often smoked; peyote and psilocybin mushrooms are ingested in botanical form or dried; and certain crystalline drugs such as cocaine and methamphetamines are often insufflated (inhaled or "snorted"). The efficiency of each method of administration varies from drug to drug.^[30]

Effects

Illustration of the major elements of neurotransmission. Depending on its method of action, a psychoactive substance may block the receptors on the post-synaptic neuron (dendrite), or block reuptake or affect neurotransmitter synthesis in the pre-synaptic neuron (axon).

Main article: Neuropsychopharmacology

Psychoactive drugs operate by temporarily affecting a person's neurochemistry, which in turn causes changes in a person's mood, cognition, perception and behavior. There are many ways in which psychoactive drugs can affect the brain. Each drug has a specific action on one or more neurotransmitter or neuroreceptor in the brain.

Drugs that increase activity in particular neurotransmitter systems are called agonists. They act by increasing the synthesis of one or more neurotransmitters or reducing its reuptake from the synapses. Drugs that reduce neurotransmitter activity are called antagonists, and operate by interfering with synthesis or blocking postsynaptic receptors so that neurotransmitters cannot bind to them.^[31]

Exposure to a psychoactive substance can cause changes in the structure and functioning of neurons, as the nervous system tries to re-establish the homeostasis disrupted by the presence of the drug. Exposure to antagonists for a particular neurotransmitter increases the number of receptors for that neurotransmitter, and the receptors themselves become more sensitive. This is called sensitization. Conversely, overstimulation of receptors for a particular neurotransmitter causes a decrease in both number and sensitivity of these receptors, a process called desensitization or tolerance. Sensitization and desensitization are more likely to occur with long-term exposure, although they may occur after only a single exposure. These processes are thought to underlie addiction.^[32]

Affected neurotransmitter systems

The following is a brief table of notable drugs and their primary neurotransmitter, receptor or method of action. It should be noted that many drugs act on more than one transmitter or receptor in the brain.^[33]

Neurotransmitter/receptor	Classification	Examples
Acetylcholine	Cholinergics (acetylcholine agonists)	arecoline, nicotine, piracetam
	Anticholinergics (acetylcholine antagonists)	scopolamine, dimenhydrinate, diphenhydramine, atropine, most tricyclics
Adenosine	Adenosine receptor antagonists[34]	caffeine, theobromine, theophylline
Dopamine	Dopamine reuptake inhibitors (DRIs)	cocaine, methylphenidate, amphetamine, bupropion
	Dopamine releasers	amphetamine, agomelatine
	Dopamine agonists	pramipexole, L-DOPA (prodrug)
	Dopamine receptor antagonists	haloperidol, droperidol, many antipsychotics
GABA	GABA reuptake inhibitors	tiagabine
	GABA receptor agonists	ethanol, barbiturates, diazepam and other benzodiazepines, zolpidem and other nonbenzodiazepines, muscimol, ibotenic acid
	GABA antagonists	thujone, bicuculline
Norepinephrine	Norepinephrine reuptake inhibitors	most non-SSRI antidepressants such as amoxapine, atomoxetine, bupropion, venlafaxine and the tricyclics
	Norepinephrine releasers	ephedrine, mianserin, mirtazapine, PPA, pseudoephedrine
	Norepinephrine antagonists	carvedilol, metoprolol, mianserin, prazosin, propanolol, trazodone, yohimbine
Serotonin	Serotonin receptor agonists	LSD, psilocybin, mescaline, DMT
	Serotonin reuptake inhibitors	most antidepressants including tricyclics such as imipramine, SSRIs such as fluoxetine and sertraline and SNRIs such as venlafaxine
	Serotonin releasers	fenfluramine, MDMA (ecstasy), mirtazapine, tramadol
	Serotonin receptor antagonists	ritanserin, mirtazapine, mianserin, trazodone, cyproheptadine, atypical antipsychotics
AMPA receptor	AMPA receptor positive allosteric modulators	aniracetam, CX717, piracetam
	AMPA receptor antagonists	kynurenic acid, NBQX, topiramate
Cannabinoid receptor	Cannabinoid receptor agonists	THC, cannabidiol, cannabinol
	Cannabinoid receptor inverse agonists	Rimonabant
Melanocortin receptor	Melanocortin receptor agonists	bremelanotide
NMDA receptor	NMDA receptor antagonists	ethanol, ketamine, PCP, DXM, Nitrous Oxide, memantine
GHB receptor	GHB receptor agonists	GHB, amisulpiride, T-HCA
Sigma receptor	Sigma-1 receptor agonists	cocaine, DMT, DXM, fluvoxamine, ibogaine, opipramol, PCP
Opioid receptor	μ-opioid receptor agonists	morphine, heroin, oxycodone, codeine
	μ-opioid receptor inverse agonists	naloxone, naltrexone
	κ-opioid receptor agonists	salvinorin A, butorphanol, nalbuphine
	κ-opioid receptor inverse agonists	buprenorphine
Histamine receptor	H1 histamine receptor antagonists	diphenhydramine, doxylamine, mirtazapine, mianserin, quetiapine, most tricyclics
Monoamine oxidase	Monoamine oxidase inhibitors (MAOIs)	phenelzine, iproniazid, tranylcypromine
	bind to MAO protein transporter	amphetamine, methamphetamine

Addiction

Main article: Substance use disorder

Comparison of physical harm and dependence of various drugs as estimated by The Lancet.^[35]

Psychoactive drugs are often associated with addiction. Addiction can be divided into two types: psychological addiction, by which a user feels compelled to use a drug despite negative physical or societal consequence, and physical dependence, by which a user must use a drug to avoid physically uncomfortable or even medically harmful withdrawal symptoms.^[36] Not all drugs are physically addictive, but any activity that stimulates the brain's dopaminergic reward system — typically, any pleasurable activity^[37] — can lead to psychological addiction.^[36] Drugs that are most likely to cause addiction are drugs that directly stimulate the dopaminergic system, like cocaine and amphetamines. Drugs that only indirectly stimulate the dopaminergic system, such as psychedelics, are not as likely to be addictive.^{[citation needed]}

Many professionals, self-help groups, and businesses specialize in drug rehabilitation, with varying degrees of success, and many parents attempt to influence the actions and choices of their children regarding psychoactives.^[38]

Common forms of rehabilitation include psychotherapy, support groups and pharmacotherapy, which uses psychoactive substances to reduce cravings and physiological withdrawal symptoms while a user is going through detox. Methadone, itself an opioid and a psychoactive substance, is a common treatment for heroin addiction. Recent research on addiction has shown some promise in using psychedelics such as ibogaine to treat and even cure addictions, although this has yet to become a widely accepted practice.^[39][40]

Legality

Historical image of legal heroin bottle

The legality of psychoactive drugs has been controversial through most of recent history; the Second Opium War and Prohibition are two historical examples of legal controversy surrounding psychoactive drugs. However, in recent years, the most influential document regarding the legality of psychoactive drugs is the Single Convention on Narcotic Drugs, an international treaty signed in 1961 as an Act of the United Nations. Signed by 73 nations including the United States, the USSR, India, and the United Kingdom, the Single Convention on Narcotic Drugs established Schedules for the legality of each drug and laid out an international agreement to fight addiction to recreational drugs by combatting the sale, trafficking, and use of scheduled drugs.^[41] All countries that signed the treaty passed laws to implement these rules within their borders. However, some countries that signed the Single Convention on Narcotic Drugs, such as the Netherlands, are more lenient with their enforcement of these laws.^[42]

In the United States, the Food and Drug Administration (FDA) has authority over all drugs, including psychoactive drugs. The FDA regulates which psychoactive drugs are over the counter and which are only available with a prescription.^[43] However, certain psychoactive drugs, like alcohol, tobacco, and drugs listed in the Single Convention on Narcotic Drugs are subject to criminal laws. The Controlled Substances Act of 1970 regulates the recreational drugs outlined in the Single Convention on Narcotic Drugs.^[44] Alcohol is regulated by state governments, but the federal National Minimum Drinking Age Act penalizes states for not following a national drinking age.^[45] Tobacco is also regulated by all fifty state governments.^[46] Most people accept such restrictions and prohibitions of certain drugs, especially the "hard" drugs, which are illegal in most countries.^[47][48][49]

At the beginning of the 21st century, legally prescribed illegal psychoactive drugs used for legitimate purposes have been targeted by the US Justice System.^[50]

In the medical context, psychoactive drugs as a treatment for illness is widespread and generally accepted. Little controversy exists concerning over the counter psychoactive medications in antiemetics and antitussives. Psychoactive drugs are commonly prescribed to patients with psychiatric disorders. However, certain critics believe that certain prescription psychoactives, such as antidepressants and stimulants, are overprescribed and threaten patients' judgement and autonomy.^[51][52]

See also

Pharmacy and Pharmacology portal

Contact high Demand reduction            Designer drug Drug Drug addiction

Drug rehabilitation Hard and soft drugs Neuropsychopharmacology            Poly drug use Project MKULTRA

Psychedelic plants Recreational drug use Responsible drug use Self-medication

References

Notes

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External links

• Neuroscience of Psychoactive Substance Use and Dependence by the WHO