Category:Phenethylamines: Difference between revisions

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This category groups ~~medicines belonging~~ to the [[~~Classes~~|~~Phenethylamines~~]] ~~class~~. ~~See~~ [[~~Classes~~]] for the ~~full taxonomy~~.

The phenethylamines are one of the largest and most varied families in all of

pharmacology, a family defined by a simple shared chemical skeleton, the

phenethylamine structure, from which an enormous range of substances is built.

The breadth is striking: the body's own signalling molecules: dopamine,

noradrenaline, and adrenaline are phenethylamines; so are the stimulants

[[Amphetamine|amphetamine]] and [[Methamphetamine|methamphetamine]]; so is the empathogen [[MDMA]]; so are the

[[:Category:Psychostimulants|psychostimulant]] cathinones; and so are a number

of ordinary medicines, among them some decongestants and bronchodilators. This

page concerns one particular branch of that family: the '''psychedelic

phenethylamines''', the serotonergic, vision-producing members, of which the

oldest and most famous is [[Mescaline|mescaline]].<ref name="mescaline-revival">Vamvakopoulou IA, Narine KAD. Mescaline: The forgotten psychedelic. ''Neuropharmacology''. 2023 Jan 1;222:109294. PMID: 36252614.</ref> Their history, like that of the

[[:Category:Tryptamines|tryptamine psychedelics]], is best told as a history of

people, and it begins with a cactus.

== Peyote and the first psychedelic ==

[[Mescaline]] is the active principle of '''[[Peyote|peyote]]''' (''Lophophora williamsii''),

a small, spineless cactus of the deserts of northern Mexico and the southern

United States, and of related cacti including the San Pedro. [[Peyote]] is among

the most anciently used psychoactive plants known: dried [[Peyote|peyote]] buttons

recovered from caves in Texas and Mexico have been dated to several thousand

years before the present, and it has been used ceremonially and medicinally by

the indigenous peoples of the region for a very long time.

{{PendellsCorner

| quote = This same site yielded two peyote plants reportedly radiocarbon dated to around 5000 BCE, making peyote the oldest hallucinogen known to have been used by human beings.

| volume = Gnosis

| page = 86

}}

That long tradition was met, after the Spanish conquest, with sustained

persecution. The Catholic Church treated the divinatory use of [[Peyote|peyote]] as

evidence of a pact with the devil, and the Inquisition condemned it; [[Peyote|peyote]]

ceremonies survived chiefly among peoples such as the Huichol, the Cora, and

the Tarahumara, who could retreat into terrain remote enough to escape the

authorities.

{{PendellsCorner

| quote = In a manual listing questions that priests should ask of Indian penitents, the question "Have you eaten peyote?" follows "Have you killed anyone?" and "Have you eaten the flesh of man?"

| volume = Gnosis

| page = 89

}}

Not every voice of the period was condemnatory. As early as 1591 the physician

Juan de Cárdenas argued that [[Peyote|peyote]]'s effects were a matter of its natural

properties, not of the supernatural, a strikingly early statement of what

would now be called a pharmacological view.

{{PendellsCorner

| quote = It is completely false to say that the herb out of its virtue makes the devil appear.

| volume = Gnosis

| page = 89

| source = Juan de Cárdenas, 1591

}}

Pendell, writing in our own time, draws the line from that history straight to

the present.

{{PendellsCorner

| quote = After four hundred years, the persecution of those who use psychedelic plants or substances or who smoke marijuana still has a religious fervor. (A man in Virginia was recently sentenced to four hundred years in prison for selling hallucinogens!) "Drug" users, to these religious fanatics, are worse than criminals, they are heretics for whom no punishment is too severe. Somewhere, nailed to a cross and wearing a crown of thorns on His head, a tear must fall from Jesus' eye.

| volume = Gnosis

| page = 90

}}

In the nineteenth century [[Peyote|peyote]] drew the attention of Western science. The

German toxicologist Louis Lewin examined the cactus in the 1880s, and in 1897

the chemist '''Arthur Heffter''', working in Leipzig, isolated its principal

active alkaloid and, by a series of self-experiments, identified it as the

substance responsible for [[Peyote|peyote]]'s visions. He named it '''[[Mescaline|mescaline]]'''. In

1919 the Viennese chemist '''Ernst Späth''' achieved the first complete

synthesis of [[Mescaline|mescaline]], making it the first psychedelic substance both

identified and made in the laboratory.<ref name="psychedelic-history">Nichols DE, Nichols CD. History of psychedelic drug science and molecular pharmacology. ''International Review of Neurobiology''. 2025. PMID: 40541313.</ref> [[Mescaline]] became, for the first half of

the twentieth century, the standard tool for the scientific study of

visionary states, and its literary fame was secured when Aldous Huxley

described his own [[Mescaline|mescaline]] experience in ''The Doors of Perception'' in 1954.<ref name="huxley1954">Huxley A. ''The Doors of Perception''. London: Chatto & Windus; 1954.</ref>

{{PendellsCorner

| quote = For there is in consciousness a Magic with which one can go beyond things. And Peyote tells us where this Magic is, and after what strange concretions, whose breath is atavistically compressed and obstructed, the Fantastic can emerge and can once again scatter in our consciousness its phosphorescence and its haze.

| volume = Gnosis

| page = 90

| source = Antonin Artaud, The Peyote Rite Among the Tarahumara

}}

== Shulgin and the synthetic phenethylamines ==

The modern history of the psychedelic phenethylamines is, to an unusual degree,

the work of one person: the chemist '''Dr. Alexander "Sasha" Shulgin'''.

Beginning in the 1960s, Shulgin took the [[Mescaline|mescaline]] molecule as a template and

systematically varied it, synthesizing and then personally evaluating, first

on himself, then with his wife Ann and a small circle of friends, a great

number of new substances. This work produced whole families of psychedelic

phenethylamines, among them the [[:Category:2C-x series|2C-x series]] and the

DOx series, and established much of what is understood about how small changes

in chemical structure change psychedelic effect.

In 1991 Alexander and Ann Shulgin published ''[[PiHKAL]]'', the title an

acronym for ''Phenethylamines i Have Known And Loved'', which combined an

autobiographical account with detailed descriptions of some two hundred

substances.<ref name="pihkal">Shulgin A, Shulgin A. ''PiHKAL: A Chemical Love Story''. Berkeley, CA: Transform Press; 1991.</ref> The book made the chemistry public in a way nothing before it had,

and several of the substances first described in it, [[2C-B]] among them,

went on to wide use. In 1994, two years after publication, Shulgin's

laboratory was raided by the United States Drug Enforcement Administration. The

2C-x series, the best known of these families, is covered in detail on its

own page; this page treats the psychedelic phenethylamines as a whole.

== Prohibition and revival ==

As with the other classical psychedelics, the psychedelic phenethylamines were

brought under strict legal control: [[Mescaline|mescaline]] was placed in the most

restrictive category of control in the United States by the early 1970s, with

a narrow exemption for the religious use of [[Peyote|peyote]] by the Native American

Church, and the later synthetic phenethylamines were controlled as they

appeared. Research nonetheless continued at a low level and has revived in

recent years, with renewed scientific and commercial interest in [[Mescaline|mescaline]] and

related substances as possible treatments in psychiatry;<ref name="mescaline-revival" /> as of the mid-2020s

this work is at an early stage and these remain investigational rather than

approved medicines.

== Members ==

The psychedelic phenethylamines fall into several groups. At the head of the

family stands '''[[Mescaline|mescaline]]''', the naturally occurring member. The largest

synthetic groups are the [[:Category:2C-x series|2C-x series]], covered as a

class on its own page, and the DOx series, the latter being the

[[Amphetamine|amphetamine]]-type relatives, longer-acting and more potent. A further group, the

'''NBOMe series''', consists of N-benzyl derivatives of the 2C compounds; these

are far more potent than their parents and, as noted below, considerably more

dangerous. The list is not exhaustive, and the boundaries of the family are

drawn differently by different authorities. The broader, non-psychedelic

phenethylamines, the [[Amphetamine|amphetamine]]-type stimulants, [[MDMA]] and the other

empathogens, the cathinones, are treated under their own categories.

== Mechanisms ==

The psychedelic phenethylamines are understood to produce their effects, like

the [[:Category:Tryptamines|tryptamine psychedelics]], chiefly by acting as

agonists at a particular serotonin receptor, the 5-HT2A receptor, that is, by

binding to that receptor and activating it. This shared action is thought to be

the common thread linking the psychedelic phenethylamines to the chemically

quite different tryptamine psychedelics, and it is why the two families are

grouped together as the "classical" or serotonergic psychedelics. That these

substances act at the 5-HT2A receptor is well established; how that receptor

activity gives rise to the actual psychedelic experience is far less well

understood and remains a subject of active research. The [[Amphetamine|amphetamine]]-type

members, such as the DOx compounds, also carry the structural features of a

stimulant, which contributes to their long duration and their effects on the

cardiovascular system.

== Safety ==

The psychedelic phenethylamines do not all carry the same risks, and the

differences between them matter a great deal. [[Mescaline]] itself, used in the

forms in which it has the longest record, has a low potential for the kind of

physical dependence associated with substances such as opioids; its

characteristic acute effects include nausea and vomiting, a marked rise in

heart rate and blood pressure, and the psychological risks common to all

psychedelics: acute fear or distress, and the possibility of precipitating or

worsening a psychotic illness in those who are predisposed to one.

The NBOMe series is a different and more serious matter, and the distinction is

important. These substances are extremely potent, active in amounts measured

in micrograms, and they have been associated with severe poisonings and with

deaths, through effects including seizures, dangerously high body temperature,

breakdown of muscle tissue, and kidney failure.<ref name="nbome">Zawilska JB, Kacela M. NBOMes, Highly Potent and Toxic Alternatives of LSD. ''Frontiers in Neuroscience''. 2020;14:78. PMID: 32174803.</ref> Because they can resemble other

psychedelics in their effects but are vastly more potent, NBOMe substances have

been sold deceptively as other drugs, sometimes as [[2C-B]], sometimes on

blotter resembling [[LSD]], with dangerous consequences for people who did not

know what they had taken. Figures for all these risks are population estimates

that vary between studies, and individual response varies considerably between

people.

== References ==

[[Category:MedCategory]]

[[Category:MedCategoryFull]]

[[Category:Pharmaceutical]]

[[Category:Plants]]

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