Psychedelics

By Julia Yu, Connie Gong,

and Michelle Dearolf
 Psychedelic Drugs
• 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:
hallucination
Synesthesia
altered sense of time and space
changes in perception of reality/self

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

bufotenine
 Serotonergic Psychedelics
• 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

 Other (pseudo-)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 Salvia Divinorum

• Other
- Salvia – generally causes bad trips
 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

harmine

psilocin

lysergic-acid diethylamide

bufotenine

psilocybin

DMT
 Effects on Serotonergic Neurons
 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 Serotonin

 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

 [Simpsons]

Effects on Norepinephrinergic Neurons

 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
 [Alice in Wonderland]

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

Psilocybe semilanceata mushrooms
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)

 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), psilocin

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

 Magic Mushrooms: psilocybin
 precursor to psychedelic psilocin

 member of indole, and tryptamine class

 can be converted into psilocin through

dephosphorylation in highly acidic conditions
psilocybin
 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

 [CNN Video]

Psilocybin
Hofmann, 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
Panaeolus Mushroom
Work at University of Arizona showed administration to OCD
patients would induce a reduction of OCD-characteristic
symptoms
 Peyote
 Peyote (Lophophora williamsii) is a spineless
cactus.

 Also know as Buttons, Cactus, mesc, or

Mescalito
Peyote

 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
 History of Peyote

 Historically it was used by indigenous

Americans. It is dried and eaten to induce
visions.

 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) Peyote

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 purposes

for 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

 Mescaline
 3,4,5-trimethoxyphenethylamine

 primary active chemical in peyote

 psychoactive alkaloid structurally similar

to dopamine, NE, ephinephrine
Mescaline

 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
 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 brew

 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
 Bansteriopis caapi - ayahuasca vine, contains harmine
compounds

 contains MAO inhibiting alkaloids, which has a

sedative, effect. The vine can be used to treat depression Bansteriopis caapi
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)
Chalipanga (Diplopterys cabrerana)

 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
 [Ayahuasca video]
Ayahuasca art: Pablo Amaringo
 Bufotenine (toad-
licking)
• 5-hydroxy-dimethyltryptamine
• Found in many species of plant and Buffo toad
venom Bufotenine

• 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
 [Simpsons Toad Licking]

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
 [Illusion]

LSD (Lysergic Acid Diethylamide): Ergot

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)
Ergot

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

 causesuterine contractions (ergometrine), nausea, seizures,
unconsciousness
 used in Middle Ages to induce abortions and stop maternal bleeding
 LSD
 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 LSD
and the universe, users may feel paranoid

 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 Blotters
 [Across the Universe]

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

 [Amanita video]

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.
Muscimol

 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 is a GABA(A) agonist

 ibotenic acid is an agonist of NMDA glutamic receptors

 these reactions are thought to cause the psychoactive effects ibotenic acid

 muscimol is mainly responsible for these effects

 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=9CxM7a6CbyI
http://www.ritsumei.ac.jp/~akitaoka/rotsnake.gif
http://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/