Psychedelics, dissociatives and deliriants

The general group of pharmacological agents commonly known as hallucinogens can be divided into three broad categories: psychedelics, dissociatives, and deliriants. These classes of psychoactive drugs have in common that they can cause subjective changes in perception, thought, emotion and consciousness. Unlike other psychoactive drugs, such as stimulants and opioids, the hallucinogens do not merely amplify familiar states of mind, but rather induce experiences that are qualitatively different from those of ordinary consciousness. These experiences are often compared to non-ordinary forms of consciousness such as trance, meditation, conversion experiences, and dreams.

One thing that most of these drugs do not do, despite the ingrained usage of the term hallucinogen, is to cause hallucination. Hallucinations, strictly speaking, are perceptions that have no basis in reality, but that appear entirely realistic. A typical "hallucination" induced by a psychedelic drug is more accurately described as a modification of regular perception, and the subject is usually quite aware of the illusory and personal nature of their perceptions. Deleriants, such as diphenhydramine and atropine, may cause hallucinations in the proper sense.

Psychedelics, dissociatives, and deliriants have a long history of use within medicinal and religious traditions around the world. They are used in shamanic forms of ritual healing and divination, in initiation rites, and in the religious rituals of syncretistic movements such as União do Vegetal, Santo Daime, and the Native American Church. When used in religious practice, psychedelic drugs, as well as other substances like tobacco, are referred to as entheogens.



Starting in the mid-20th century, psychedelic drugs have been the object of extensive attention in the Western world. They have been and are being explored as potential therapeutic agents in treating depression, Post-traumatic Stress Disorder, Obsessive-compulsive Disorder, alcoholism, opioid addiction, cluster headaches, and other ailments. Early military research focused on their use as incapacitating agents. Intelligence agencies tested these drugs in the hope that they would provide an effective means of interrogation, with little success.

Yet the most popular, and at the same time most stigmatized, use of psychedelics in Western culture has been associated with the search for direct religious experience, enhanced creativity, personal development, and "mind expansion". The use of psychedelic drugs was a major element of the 1960s counterculture, where it became associated with various social movements and a general atmosphere of rebellion and strife between generations.

Despite prohibition, the recreational, spiritual, and medical use of psychedelics continues today. Organizations, such as Multidisciplinary Association for Psychedelic Studies and the Heffter Research Institute, have arisen to foster research into their safety and efficacy, while advocacy groups such as the Center for Cognitive Liberty and Ethics push for their legalization. In addition to this activity by proponents, hallucinogens are also widely used in basic science research to understand the mind and brain. In some cases, this includes research in humans, like that conducted by Roland Griffiths and colleagues.

Psychedelics
The word psychedelic (From Ancient Greek ψυχή (psychê) mind, soul + δηλος (dêlos) manifest, visible + -ic) was coined to express the idea of a drug that makes manifest a hidden but real aspect of the mind. It is commonly applied to any drug with perception-altering effects such as LSD, psilocybin, DMT, 2C-B, mescaline, and DOM as well as a panoply of other tryptamines, phenethylamines and yet more exotic chemicals, all of which appear to act mainly on the 5-HT2A receptor. Common herbal sources of psychedelics include psilocybe mushrooms, various ayahuasca preparations, peyote, San Pedro cactus, and the seeds of morning glory, and Hawaiian baby woodrose.

Much debate exists not only about the nature and causes, but even about the very description of the effects of psychedelic drugs. One prominent tradition involves the "reducing valve" concept, first articulated in Aldous Huxley's book The Doors of Perception. In this view, the drugs disable the brain's "filtering" ability to selectively prevent certain perceptions, emotions, memories and thoughts from ever reaching the conscious mind. This effect has been described as mind expanding, or consciousness expanding, for the drug "expands" the realm of experience available to conscious awareness. A large number of drugs, such as cannabis and Ecstasy, produce effects that could be classified as psychedelic (especially at higher doses) but are not considered to be strictly psychedelic drugs due to other effects that may be more (or equally) prevalent, such as sedation or disinhibition. In addition, drugs such as cannabis do not affect serotonin receptors like "true" psychedelics.

Psychedelic effects can vary depending on the precise drug, dosage, set, and setting. "Trips" range between the short but intense effects of intravenous DMT to the protracted ibogaine experience, which can last for days. Appropriate dosage ranges from extremely low (LSD) to rather high (mescaline). Some drugs, like the auditory hallucinogen DIPT, act specifically to distort a single sense, and others have more diffuse effects on cognition generally. Some are more conducive to solitary experiences, while others are positively empathogenic.

Many psychedelics (LSD, psilocybin, mescaline and numerous others) are non-toxic, making it difficult to overdose on these compounds.

Dissociatives
Dissociatives are drugs that reduce (or block) signals to the conscious mind from other parts of the brain, typically (but not necessarily, or limited to) the physical senses. Such a state of sensory deprivation can facilitate self exploration, hallucinations, and dreamlike states of mind which may resemble some psychedelic mindstates. Essentially similar states of mind can be reached via contrasting paths—psychedelic or dissociative. That said, the entire experience, risks and benefits are markedly different.

The primary dissociatives are similar in action to PCP (angel dust) and include ketamine (an anaesthetic), and dextromethorphan (an active ingredient in many cough syrups). Also included are nitrous oxide, and muscimol from the Amanita muscaria (fly agaric) mushroom.

Many dissociatives also have CNS depressant effects, thereby carrying similar risks as opioids to slowing breathing or heart rate to levels resulting in death (when using very high doses). This does not appear to be true in other cases; and the principal risk of nitrous oxide seems to be due to oxygen deprivation. Injury from falling is also a danger, as nitrous oxide may cause sudden loss of consciousness, an effect of oxygen deprivation. Long term use of dissociative anaesthetics such as PCP and ketamine (and possibly dextromethorphan) have been suspected to cause Olney's lesions (N-methyl-d-aspartate antagonist neurotoxicity), though these lesions have never been demonstrated in primates to date.

Deliriants
The deliriants (or anticholinergics) are a special class of dissociative which are antagonists for the acetylcholine receptors (unlike muscarine and nicotine which are agonists of these receptors). Deliriants are sometimes called true hallucinogens, because they do cause hallucinations in the proper sense: a user may have conversations with people who aren't there, or become angry at a 'person' mimicking their actions, not realizing it is their own reflection in a mirror. They are called deliriants because their effects are similar to the experiences of people with delirious fevers. While dissociatives can produce effects similar to lucid dreaming (during which one is consciously aware of dreaming while doing such), the deliriants have effects akin to sleepwalking (whereby one doesn't remember what happened during the experience).

Included in this group are such plants as deadly nightshade, mandrake, henbane and datura, as well as a number of pharmaceutical drugs, when taken in very high doses, such as the first-generation antihistamines diphenhydramine (Benadryl), its close relative dimenhydrinate (Dramamine or Gravol) and hydroxyzine, to name a few. Native Americans also consumed massive amounts of tobacco during religious ceremonies in order to experience the deliriant effects.

In addition to the dangers of being far more "out of it" than with other drugs and retaining a truly fragmented dissociation from regular consciousness without being immobilized, the anticholinergics are toxic, carry the risk of death by overdose, and also include a number of uncomfortable side effects. These side effects typically include dehydration and mydriasis (dilation of the pupils). 

Most modern-day psychonauts who use deliriants report similar or identical hallucinations and challenges. For example, diphenhydramine, as well as Dimenhydrinate, when taken in a high enough dosage, often are reported to evoke vivid, dark, and entity-like hallucinations, peripheral disturbances, feelings of being alone but simultaneously of being watched, and hallucinations of real things ceasing to exist. Deliriants also may cause confusion or even rage, and thus have been used by ancient peoples as a stimulant before going into battle.

History of use
Hallucinogenic substances are among the oldest drugs used by humankind, as hallucinogens naturally occur in mushrooms, cacti and a variety of other plants. Numerous cultures worldwide have endorsed the use of hallucinogens in medicine, religion and recreation, to varying extents, and some cultures have regulated or outright prohibited their use. In most developed countries today, the possession of many hallucinogens, even those found commonly in nature, is considered a crime punishable by fines, imprisonment or even death. In some countries, such as the United States and the Netherlands, partial deference may be granted to traditional religious use by members of indigenous ethnic minorities such as the Native American Church and the Santo Daime Church. Recently the União do Vegetal, a Christian-based religious sect whose composition is not primarily ethnicity-based, won a United States Supreme Court decision authorizing its use of ayahuasca.

Traditional religious and shamanic use
Historically, hallucinogens have been most commonly used in religious or shamanic rituals. In this context they are often referred to as entheogens, and they are used to facilitate healing, divination, communication with spirits, and coming-of-age ceremonies. Evidence exists for the use of entheogens in prehistoric times, as well as in numerous ancient cultures, including the Ancient Egyptian, Mycenaean, Ancient Greek, Vedic, Maya, Inca the and Aztec cultures. The Upper Amazon is home to the strongest extant entheogenic tradition; the Urarina of Peruvian Amazonia, for instance, continue to practice an elaborate system of ayahuasca shamanism, coupled with an animistic belief system.

The rise of the Abrahamic religions (Judaism and Christianity, and Islam) caused a decline of entheogenic use of hallucinogens use in its wake, as the authority of scripture and the priesthood gradually reduced the role granted to direct spiritual experience, especially by the laity. Examples of this development include the destruction of the Eleusinian Mysteries, which are now widely assumed to have involved entheogenic rituals, and the Great Witch Hunt of the Early Modern Age, in which practitioners of entheogenic rites in Western Europe were accused of associating with the devil. The Spanish conquistadores associated local entheogenic traditions of South America with heresy and satanism, and uprooted many of them, but nevertheless, some cultures there and elsewhere have kept their traditions alive to this day.

Early scientific investigations
Although natural hallucinogenic drugs have been known to mankind for millennia, it was not until the early 20th century that they received extensive attention from Western science. Earlier beginnings include scientific studies of nitrous oxide in the late 18th century, and initial studies of the constituents of the peyote cactus in the late 19th century. Starting in 1927 with Kurt Beringer's Der Meskalinrausch (The Mescaline Intoxication), more intensive effort began to be focused on studies of psychoactive plants. Around the same time, Louis Lewin published his extensive survey of psychoactive plants, Phantastica (1928). Important developments in the years that followed included the re-discovery of Mexican magic mushrooms (in 1936 by Robert J. Weitlaner) and ololiuhqui (in 1939 by Richard Evans Schultes). Arguably the most important pre-World War II development was by Albert Hofmann's 1938 invention of the semi-synthetic drug LSD, which was later discovered to produce hallucinogenic effects in 1943.

Hallucinogens after World War II
After World War II there was an explosion of interest in hallucinogenic drugs in psychiatry, owing mainly to the invention of LSD. Interest in the drugs tended to focus on either the potential for psychotherapeutic applications of the drugs (see psychedelic psychotherapy), or on the use of hallucinogens to produce a "controlled psychosis", in order to understand psychotic disorders such as schizophrenia. By 1951, more than 100 articles on LSD appeared in medical journals, and by 1961, the number increased to more than 1000 articles. Hallucinogens were also researched in several countries for their potential as agents of chemical warfare. Most famously, several tragic incidents associated with the CIA's MK-ULTRA mind control research project have been the topic of media attention and lawsuits.

At the beginning of the 1950s, the existence of hallucinogenic drugs was virtually unknown among the general public of the West. However this soon changed as several influential figures were introduced to the hallucinogenic experience. Aldous Huxley's 1953 essay The Doors of Perception, describing his experiences with mescaline, and R. Gordon Wasson's 1957 Life magazine article  (Seeking the Magic Mushroom) brought the topic into the public limelight. In the early 1960s, counterculture icons such as Jerry Garcia, Timothy Leary, Allen Ginsberg and Ken Kesey advocated the drugs for their psychedelic effects, and a large subculture of psychedelic drug users was spawned. Psychedelic drugs played a major role in catalyzing the vast social changes initiated in the 1960s. As a result of the growing popularity of LSD and disdain for the hippies with whom it was heavily associated, LSD was banned in the United States in 1967. This greatly reduced the clinical research about LSD, although limited experiments continued to take place, such as by Reese Jones in San Francisco.

Legal status and attitudes
As of 2008, most well known hallucinogens (aside from dextromethorphan, diphenhydramine and dimenhydrinate) are illegal in most Western countries. One notable exception to the current criminalization trend is in parts of Western Europe, especially in the Netherlands, where cannabis is considered to be a "soft drug". Previously included were hallucinogenic mushrooms, but as of October 2007 the Netherlands officials have moved to ban their sale following several widely publicized incidents involving tourists. While the possession of soft drugs is technically illegal, the Dutch government has decided that using law enforcement to combat their use is largely a waste of resources. As a result, public "coffeeshops" in the Netherlands openly sell cannabis for personal use, and "smart shops" sell drugs like ayahuasca, Salvia Divinorum and until the ban of magic mushrooms takes effect(expected to take effect spring, 2008), they are still available for purchase in smartshops as well. (See Drug policy of the Netherlands).

Since the latter part of the twentieth century, this attitude has spread throughout Europe; many European countries no longer actively pursue anti-drug policies, and rarely enforce extant legal penalties for personal-use quantities of hallucinogenic drugs. This is especially true with mild hallucinogens such as cannabis, which is rapidly gaining acceptance in western Europe as a harmless and socially acceptable intoxicant, much as alcohol is considered throughout the West. Despite being scheduled as a controlled substance in the mid 1980s, ecstasy's popularity has been growing since that time in western Europe and in the United States.

Attitudes towards hallucinogens other than cannabis have been slower to change. Several attempts to change the law on the grounds of freedom of religion have been made. Some of these have been successful, for example the Native American Church in the United States, and Santo Daime in Brazil. Some people argue that a religious setting should not be necessary for the legitimacy of hallucinogenic drug use, and for this reason also criticize the euphemistic use of the term "entheogen". Non-religious reasons for the use of hallucinogens including spiritual, introspective, psychotherapeutic, recreational and even hedonistic motives, each subject to some degree of social disapproval, have all been defended as the legitimate exercising of civil liberties, including freedom of thought and freedom of self-harm.

Many connect the idea of being "high" or going through a psychedelic state, as having brain damage or going crazy. This is due to the effect of the drug which, in some cases, can be overwhelming. Effects of these drugs can mimic psychological conditions such as psychosis, schizophrenia, and thought disorder. However, this is largely a misconception of the psychedelic state. After many studies investigating its possible use as a "psychotomimetic" and decades of personal/spiritual use it has become apparent that the psychedelic state is wholly different from a psychotic state and thus is ill-compared to schizophrenia and other mental disorders.

Several medical and scientific people, including the late Albert Hofmann, advocate the drugs should not be banned, but should be strongly regulated and warn they can be dangerous without proper psychological supervision. 

Taking a hallucinogenic drug without knowledge can result in psychological trauma, and has occurred many times because many psychedelic drugs such as LSD have low dose and can easily be added to food or drink, similar to "date rape drugs" or Mickey Finns, and those who deliberately do that can be charged with assault. (These occurrences have created some urban myths such as the blue star tattoo myth).

Psychedelics and mental illnesses in long-term users
Most psychedelics are not known to have long-term physical toxicity. However, amphetamine-like psychedelics, such as MDMA, that release neurotransmitters may stimulate increased formation of free radicals possibly formed from neurotransmitters released from the synaptic vesicle. Free radicals are associated with cell damage in other contexts, and have been suggested to be involved in many types of mental conditions including Parkinson's disease, senility, schizophrenia, and Alzheimer's. Research on this question has not reached a firm conclusion. The same concerns do not apply to psychedelics that do not release neurotransmitters, such as LSD, nor to dissociatives and deliriants.

No clear connection has been made between psychedelic drugs and organic brain damage; however, high doses over time of some dissociatives and deliriants have been shown to cause Olney's lesions in other animals, and have been suspected to occur in humans. Additionally, hallucinogen persisting perception disorder (HPPD) is a diagnosed condition where visual effects of drugs persist for a long time--although science and medicine have yet to determine what causes the condition.

Introduction to the psychedelic name zoo
The class of drugs described in this article has been described by a profusion of names, most of which are associated with a particular theory of their nature.

Louis Lewin started out in 1928 by using the word phantastica as the title of his ground-breaking monograph about plants that, in his words, "bring about evident cerebral excitation in the form of hallucinations, illusions and visions [...] followed by unconsciousness or other symptoms of altered cerebral functioning". But no sooner had the term been invented, or Lewin complained that the word "does not cover all that I should wish it to convey", and indeed with the proliferation of research following the discovery of LSD came numerous attempts to improve on it, such as hallucinogen, phanerothyme, psychedelic, psychotomimetic, psycholytic, schizophrenogenic, cataleptogenic, mysticomimetic, psychodysleptic, and entheogenic.

The word psychotomimetic, meaning "mimicking psychosis", reflects the hypothesis of early researchers that the effects of psychedelic drugs are similar to naturally occurring symptoms of schizophrenia, which has since been discredited. It remained for a long time somewhat of a shibboleth to be used in the titles of papers as a signal that the researcher disapproved of the casual use of a drug, but has now been displaced in the medical literature by hallucinogen. The latter term is not entirely accurate, since hallucinations, strictly speaking, must be entirely realistic but have no basis in reality, while psychedelic effects are often better described as distortions of the ordinary senses.

While the word psychotomimetic is now outmoded, the theory it implies is still clearly visible in the World Health Organization's definition of a hallucinogen as "a chemical agent that induces alterations in perception, thinking, and feeling which resemble those of the functional psychoses without producing the gross impairment of memory and orientation characteristic of the organic syndromes".

The word psychedelic was coined by Humphrey Osmond and has the rather mysterious but at least somewhat value-neutral meaning of "mind manifesting". The word entheogen, on the other hand, which is often used to describe the religious and ritual use of psychedelic drugs in anthropological studies, is associated with the idea that it could be relevant to religion. The words entactogen, empathogen, dissociative and deliriant, at last, have all been coined to refer to classes of drugs similar to the classical psychedelics that seemed deserving of a name of their own.

Taxonomy
Hallucinogens can be classified by their subjective effects, mechanisms of action, and chemical structure. These classifications often correlate to some extent. In this article, they are classified as psychedelics, dissociatives, and deliriants, preferably entirely to the exclusion of the inaccurate word hallucinogen, but the reader is well advised to consider that this particular classification is not universally accepted. The taxonomy used here attempts to blend these three approaches in order to provide as clear and accessible an overview as possible.

Almost all hallucinogens contain nitrogen and are therefore classified as alkaloids. THC and Salvinorin A are exceptions. Many hallucinogens have chemical structures similar to those of human neurotransmitters, such as serotonin, and temporarily modify the action of neurotransmitters and/or receptor sites.

Lewin's classes
A classical classification, mainly of historical interest, is that of Lewin (Phantastica, 1928):


 * Class I Phantastica roughly correspond to the psychedelics, which is a more modern term usually used as synonym to "hallucinogen" by people with positive attitudes towards them. Here the term is used a bit differently to discriminate one particular class of hallucinogens which it seems to describe best. They typically have no sedative effects (sometimes the opposite) and there is usually a clearcut memory to their effects. These drugs have also been referred to as the "classical" hallucinogens.


 * Class II Phantastica correspond to the other classes in our scheme. They tend to sedate in addition to their hallucinogenic properties and there often is an impaired memory trace after the effects wear off.

Pharmacological classes of hallucinogens
One possible way of classifying the hallucinogens is by their chemical structure and that of the receptors they act on. In this vein, the following categories are often used:


 * Psychedelics (serotonin 5-HT2A receptor agonists)
 * Tryptamines
 * Lysergamides
 * Phenethylamines
 * Substituted phenethylamines
 * Substituted amphetamines
 * Empathogens and/or Entactogens (serotonin releasers)


 * Cannabinoids (CB-1 cannabinoid receptor agonists)


 * Dissociatives
 * NMDA receptor antagonists and sigma1 ligands
 * Inhalants
 * Cholinergics


 * Deliriants (anticholinergics)
 * Tropanes
 * Antihistamines

Problems with structure based frameworks is that the same structural motif can include a wide variety of drugs which have substantially different effects. Another problem is that structural classes are not mutually exclusive. Examples: - LSD is both a tryptamine and a phenethylamine (it is simply a highly substituted phenethylamine) - Heroin and DXM are both also phenethylamines, though heroin is an opiate and DXM is a dissociative hallucinogen - Methamphetamine is a simple phenethylamine but is a psychostimulant, not a hallucinogen

Hallucinogenic organisms
The following is a list of some organisms known to contain hallucinogens


 * Plants
 * Psychedelics
 * Ayahuasca (contains DMT and an MAOI, commonly Banisteriopsis caapi with Psychotria viridis)
 * Epená (Virola sp.) (contains 5-MeO-DMT and DMT)
 * Hawaiian baby woodrose (Argyreia nervosa) (contains ergine)
 * Ololiuhqui/Coaxihuitl (Turbina/Rivea corymbosa) (contains ergine)
 * Tlitliltzin/Badoh Negro (Ipomoea violacea) (contains ergine)
 * Iboga (Tabernanthe iboga) (contains ibogaine)
 * Salvia divinorum (contains Salvinorin A)
 * Cacti psychedelics
 * Peruvian Torch cactus (Trichocereus peruvianus) (contains mescaline)
 * Peyote cactus (Lophophora williamsii) (contains mescaline)
 * San Pedro cactus (Trichocereus pachanoi) (contains mescaline)
 * Quasi-psychedelics
 * Cannabis (contains THC)
 * Sinicuichi (Heimia salicifolia) (questioned hallucinogenic activity)
 * Nutmeg (Myristica fragrans) (contains Myristicin)
 * Dissociatives
 * there are no known "true" (NMDA antagonists) plant dissociatives
 * Deliriants
 * Deadly nightshade (Atropa belladonna) (contains tropane alkaloids)
 * Floripondio (Brugmansia sp.) (contains tropane alkaloids)
 * Henbane (Hyoscyamus niger) (contains tropane alkaloids)
 * Mandrake (Mandragora sp.) (contains tropane alkaloids)
 * Thorn Apple/Jimson Weed (Datura sp.) (contains tropane alkaloids)
 * Fungi
 * Psychedelics
 * Psilocybe mushrooms (Psilocybe sp. and some Conocybe, Panaeolus and Stropharia) (contain psilocybin and psilocin)
 * Ergot fungus (Claviceps purpurea) (not hallucinogenic in itself, but contains ergotamine)
 * Dissociatives
 * Fly Agaric mushroom (Amanita muscaria) (contains muscimol)
 * Animals
 * Psychedelics
 * Psychoactive toads (Bufo alvarius) (contain 5-MeO-DMT and bufotenine)

Literature
The literature about psychedelics, dissociatives and deliriants is vast. The following books provide accessible and up-to-date introductions to this literature:
 * Ann & Alexander Shulgin: PIHKAL (Phenethylamines I Have Known And Loved), a Chemical Love Story
 * Ann & Alexander Shulgin: TIHKAL (Tryptamines I Have Known And Loved), the Continuation
 * Charles S. Grob, ed.: Hallucinogens, a reader

Winkelman, Michael J., and Thomas B. Roberts (editors) (2007).Psychedelic Medicine: New Evidence for Hallucinogens as Treatments 2 Volumes. Westport, CT: Praeger/Greenwood.

The following review paper is the definitive source of technical scientific information about hallucinogens:
 * David Nichols: Hallucinogens

A scholarly bibliography on the use of these substances in the history of psychology has also been developed for specific use by bloggers and Wikipedians. (Abstracts included for ease of updating.) Find it here.