Psychedelics

By Julia Yu, Connie Gong, and Michelle Dearolf

• Subclass of hallucinogens, generally non-addictive

• These interfere with perceptions, emotions, and memory

• The time they take to metabolize can be gauged from the complexity of the molecule

• effects include:hallucinationSynesthesiaaltered sense of time and spacechanges in perception of reality/self

• Drugs include: LSD, mescaline, psilocybin, amanita, ayahuasca, bufotenine

Psychedelic Drugs

• 5-HT(2A) agonists

• ergolines (LSD)

• tryptamine-based (psilocybin, psilocin, DMT) imitate serotonin

• phenethylamine-based (mescaline) imitate catecholemines

• tryptamine-based highs more empathetic, emotional, sensual; phenethylamine-based highs more hallucinogenic

• low dose: surface and shape warping, color variations

Serotonergic Psychedelics

Serotonin releasers- MDMA (Ecstasy), a derivative of mescaline- cause a feeling of empathy and openness

• Dissociatives (NMDA antagonists)- Ketamine- out-of-body experiences

• Cannabinoids- Marijuana- general feeling of wellbeing and euphoria

• Other - Salvia – generally causes bad trips

Other (pseudo-)Psychedelics

Salvia Divinorum

psilocin

DMT

psilocybin

harmine

bufotenine

lysergic-acid diethylamide

Similarities to Serotonin LSD, psilocin, psilocybin, and DMT are similar to serotonin, all share indole rings and are derived from tryptamine

Indoleamines: 6-membered benzene ring and 5-membered ring with nitrogen

Serotonergic neurons extend from the raphei nucleus

Many hallucinogens share similarities with the neurotransmitter serotonin

Some Psychedelics are thought to be serotonin receptor antagonists, shown to bind to 5HT-2A serotonin receptors

Effects on Serotonergic Neurons

Some psychedelics can be impeded by drugs that stimulate serotonin production, suggesting that psychedelics lower serotonin concentration in the brain

Strength of a tryptamine-based psychedelic can be deduced from its affinity to 5HT-2A receptors

The exact mode of action remains unknown

Serotonin

The locus coeruleus is responsible for integrating sensory input. It responds to any sensory input

direct stimulation results in panic, hyper responsiveness, sensitivity

People under the influence of psychedelics have the same symptoms

Psychedelics increase firing rate of locus coeruleus; nonpsychedelics, even with structural similarities to LSD and other similar drugs do not have this effect

This suggests that the locus coeruleus is responsible for alteration of mind state

Effects on Norepinephrinergic Neurons[Simpsons]

Magic Mushrooms Psilocybin mushrooms, also called

Magic Mushrooms or Shrooms, are fungi that contain the psychoactive compounds Psilocin and psilocybin

There are about 180 species of psilocybin mushrooms.

Have been used for thousands of years Native Central and South Americans. In the mid-1960s, psilocybin was isolated and mushrooms were being studied and used recreationally.

In 1968 psilocybin mushrooms became illegal in the US (Schedule 1)

Psilocybe semilanceata mushrooms

[Alice in Wonderland]

Magic Mushrooms: Psilocin psychedelic mushroom alkeloid

Psilocybin is rapidly dephosphorylated in the body to psilocin which acts as a 5HT2A, 5HT2C and 5HT1A agonist.

Psilocin is structurally similar to serotonin (5-HT), differing only by the hydroxyl group being on the 4-position rather than the 5 and the dimethyl groups on the nitrogen. Psilocin has no significant effect on dopamine receptors (unlike LSD) and only affects the noradrenergic system at very high dosages.

no lethality, no withdrawal

cross tolerance between psilocin, mescaline, DMT

psilocin

Magic Mushrooms: psilocybin

precursor to psychedelic psilocin

member of indole, and tryptamine class

can be converted into psilocin through dephosphorylation in highly acidic conditions used to relieve cluster headaches

is broken down in the liver into psilocin, then degraded by MAO

use of MAO inhibitors can extend duration of high

The high causes distortion in time and a oneness with the universe, and can be accompanied by bad trips (general feeling of fear associated with a session)

some long-term effects similar to that of schizophrenia

psilocybin

PsilocybinHofmann, who synthesized LSD, willingly ingested

extracts himself for testing

Psilocybin and LSD are “essentially the same molecules except that: (1) the phosphoryl or hydroxy group at the top of the indole ring was moved around to other ring positions, and (2) different numbers of methyl groups (CH3) and other carbon chains were added to the side chains and to the nitrogen on the indole ring to see how these changes would affect psychoactivity.” – Hoffman

Psilocybin was tested widely at Harvard in the 60s

Timothy Leary, and Richard Alpert ran Harvard Psilocybin Project for the treatment of psychiatric and psychological disorders

Work at University of Arizona showed administration to OCD patients would induce a reduction of OCD-characteristic symptoms

Panaeolus Mushroom

[CNN Video]

Peyote Peyote (Lophophora williamsii) is a spineless

cactus.

Also know as Buttons, Cactus, mesc, orMescalito

Native to southwest Texas and Mexico

Active ingredient is mescaline

Prepared from aboveground plant (button); can be eaten fresh, dried, or stewed into power teas

Peyote

History of Peyote

Historically it was used by indigenousAmericans. It is dried and eaten to inducevisions.

Specimens date back to 3780 – 3660 BCE

Tribal groups including the Huichol, Tonkawa, Comanche, and Kiowa have used it historically for spiritual rituals.

Played a part in the Ghost Dance

Banned during a blanket ban on Native American rituals in late 1880s – early 1900s

Peyote Today

Classified as a Schedule I (illegal)hallucinogen and has been prohibited from use since the 1970s

Part of the Comprehensive Drug Abuse Prevention and Control Act (1970)

Because it was used for religious purposesfor centuries, there was some legal controversy when the Supreme Court tried to outlaw use. Now it is legal for certified members of Native American Church, especially in Texas, but is otherwise illegal.

Use described by Aldous Huxley, Picasso, Hunter S. Thompson

Peyote

Mescaline 3,4,5-trimethoxyphenethylamine

primary active chemical in peyote

psychoactive alkaloid structurally similarto dopamine, NE, ephinephrine

not addictive, but does result in tolerance-building

causes cross-tolerance in LSD and other psychedelics

not well-metabolized; up to 60% is excreted in the urine; the rest is excreted in its carboxylic acid form after being degraded by MAO

synthesized derivatives include MDMA (Ecstasy, E, X, ADAM)

Mescaline

Mescaline Although labeled a hallucinogen, it does not produce true hallucinations (like LSD does). Instead it enhances true perception rather than creating false perception

Activates the serotonin 5-HT(2A) and (2C) receptors as a partial agonist

Mescaline

The method from here is unknown and we do not know how psychedelia is activated

Though to involve excitation of neurons in the prefrontal cortex (implicated in sentience, human intelligence, and personality)

Ayahuasca Ayahuasca, also known as Huasca, Vine, or

Tea, is a powerful psychedelic

traditional South American brewed mixture prepared by trained Shaman, used spiritually and for healing purposes

name means “spirit vine” or “vine of the souls”, made from B. caapi vine and any combination of other traditional plants, containing DMT ayahuasca tourism: foreigners wanting a taste of an exotic ritual travel to Peru, take part in traditional ceremony

causes dizziness, nausea, vomiting, psychedelic visions

not addictive

While none of the standard plant constituents of ayahausca are specifically controlled federally in the United States, DMT is Schedule I in the U.S. and in most countries

Ayahuasca brew

Ayahuasca

Bansteriopis caapi - ayahuasca vine, contains harmine compounds

contains MAO inhibiting alkaloids, which has a sedative, effect. The vine can be used to treat depression but has no psychedelic effects

the primary visions associated with Ayahuasca come when DMT-containing plants are added to the brew

accompanies DMT containing plants:Chacruna (Psychotria viridis), Sameruca (Pychotria carthaginensis), and Chalipanga (Diplopterys cabrerana)

Bansteriopis caapi

without MAO inhibitors in the vine, the DMT would be broken down in digestive tract and not have any effect,

- harmines allow DMT to diffuse through lining of the intestine, past the blood brain barrier, and into the brain to bind with receptors

Chalipanga (Diplopterys cabrerana)

Ayahuasca art: Pablo Amaringo

[Ayahuasca video]

Bufotenine (toad-licking)

Bufotenine

• 5-hydroxy-dimethyltryptamine

• Found in many species of plant and Buffo toad venom

• toads shoot venom at enemies: also it is a digoxin-like cardiac glycosides, which causes death.

• toads secrete bufotoxins from parotoid glands on their skin.

first isolated from toad skin by Austrian chemist Handovsky at the University of Prague during World War I

Bufotenine is illegal in the US without a Drug Enforcement Administration license (schedule 1 hallucinogen). It cannot be prescribed

Bufotenine It is found in the Amazon, Atlantic rainforests, and in the deserts of southwest US and Mexico

Bufotenine is used in Chinese medicine and aphrodisiac marketed as a street drug, called ch’an su

in 1955, Fabing & Hawkins administered the drug at up to 16 mg to prisoners, reported LSD-like effects in a much shorter period

constricts blood vessels and raises blood pressure

endogenous bufotenine found in the urine of autistic-spectrum people, schizophrenic, or paranoid adults

[Simpsons Toad Licking]

LSD, also known as Acid, Blotter, Doses, and Trips, is synthesized from ergot

ergot is a fungus that grows on rye (Claviceps purpurea)

the fruiting structure is ergot sclerotium. It contains alkaloid ergotamine (2% by weight)

LSD (Lysergic Acid Diethylamide): Ergot

Ergot

eating ergot is called ergotism;  “St. Anthony’s fire”

causes uterine contractions (ergometrine), nausea, seizures, unconsciousness

used in Middle Ages to induce abortions and stop maternal bleeding

[Illusion]

LSD comes in many forms including: Blotters (paper soaked in LSD solution), pills, liquid, powder, etc.

It is illegal (Schedule 1) in the US

LSD acts as a psychological amplifier: enhanced colors, user feels connected to others and the universe, users may feel paranoid

LSD

LSD

LSD Blotters

Use of LSD can lead to a “bad trip”: bizarre, frightening images, strong emotions, paranoia, disorientation

known to destabilize those at risk for schizophrenia

can cause Hallucinogen-Persisting Perception Disorder, constant hallucination even when not on LSD

-no treatment; sometimes it goes away after months or years, but it can result in permanent brain changes

LSD LSD is the most widely known and produced psychedelic Albert Hofmann experimented widely with ergot derivatives for viable medical use; 5 years later, he experienced a psychedelic trip after “accidentally” ingesting LSD He redid his trip by intentionally ingesting 250 micrograms, finding very strong effects 1950s, CIA Project MKULTRA: give LSD to random people (CIA employees, military personnel, doctors, other government agents, prostitutes, mentally ill patients, and members of the general public) to observe the effects

Albert Hofmman

counterculture of the 60s: condoned and encouraged by several figures: Mr.  Aldous Huxley, Timothy Leary, and Al Hubbard On October 24, 1968, possession of LSD was made illegal in the United States.

LSD is still approved in some places for psychiatric study/use

[Across the Universe]

Amanita Amanita is the most toxic mushroom genus

worldwide; it accounts for 95% of deaths caused by mushroom poisoning

symptoms: nausea, vomiting, diarrhea, headache and bronchospasm; with larger doses: acrimation, hypotension and shock.

Mushrooms which contain the psychoactive chemicals ibotenic acid and muscimol.

These chemicals are related to each other in structure and with the neurotransmitters GABA and glutamic acid

Muscimol

ibotenic acid

muscimol is a GABA(A) agonist

ibotenic acid is an agonist of NMDA glutamic receptors

these reactions are thought to cause the psychoactive effects

muscimol is mainly responsible for these effects

[Amanita video]

Amanita

Other names for Amanita include Fly-agaric and Panther Mushroom

Effects include:nausea and twitching to drowsiness, cholinergic crisis-like effects (low blood pressure, sweating and salivation), auditory and visual distortions, mood changes, euphoria, relaxation, ataxia, and loss of equilibrium

It was rarely consumed as a drug until psilocybin was banned in the UK. Now legal amanita has been more in use

It is used as an Entheogen, a psychoactive substance used in a psychotherapeutic, religious, shamanic, or spiritual context, by Siberians.

It is thought to be the main ingredient of Soma, and is written about in the Indian religious text, Rig Veda

Clinical Implications

New research shows that Psychedelic drugs such as LSD, ketamine, and psilocybin may help treat patients with depression, compulsive disorders, or chronic pain when combined with psychotherapy.

Many suffers of severe psychiatric problems do not respond to selective serotonin reuptake inhibitors (such as Prozac)

These mind-altering drugs, in low doses, may help patients lower their perception of pain

Yale researchers found Ketamine helps regeneration of synaptic connections in sufferers of depression

Bibliography

http://psychedelic-information-theory.com/Psychedelic-Pharmacology

http://www.erowid.org/

http://www.psychedelic-library.org/

http://peyote.org/

http://www.neurosoup.com/schedule1/bufotenine.htm

http://www.drugabuse.gov/infofacts/lsd.html

http://www.nationalgeographic.com/

Amanita (4:13/5/6:15) http://www.youtube.com/watch?v=QUnxobP1yds&feature=related

Illusions: http://www.youtube.com/watch?v=9CxM7a6CbyIhttp://www.ritsumei.ac.jp/~akitaoka/rotsnake.gifhttp://gethighnow.com/face-off/http://gethighnow.com/syd-barrett-dedicated-fractal-acid-words/http://gethighnow.com/binaural-beats-self-hypnosis/http://gethighnow.com/cambiata-illusion/http://gethighnow.com/theta-wave-brain-synchronization/