CHAPTER 12

Psychedelics

Psychedelic/Hallucinogens

Called by many different names Psychotogens Psychotomimetics Psychedelics

Primary effect is to produce perceptual changes & hallucinations

Can influence several sensory systems, perception of time, space & events

Different Types of Psychedelics

Serotonergic LSD Psilocybin/Psilocin DMT - Ayahuaca Bufotenine Ololiuqui

Catecholamine-like Mescaline MDMA (ecstasy)

MDA MDE

DOM Myristin and Elemicin

Cholinergic Muscarine Scopolamine

Glutamatergic PCP Ketamine Dextromethorphan

Opioid Salvinorin A

SerotonergicPsychdelics

LYSERGIC ACID DIETHYLAMIDE (LSD)

Lysergic acid – Derived from ergot alkaloidsErgot is a poisonous fungus that infects rye &

other grains & grassesAlbert Hoffman: 1938 - synthesized #25 in

series of new molecules doing ergot alkaloid chemistry

1943 - returned to #25 making new batch & absorbed some through skin

LSD in the USA

Came to U.S. in 1950s in two ways:• Clinical usage: Supplied to psychologists and

psychiatrists encouraged their taking drug

• Military Usage: U.S. military and CIA as incapacitating agent and truth drug

• U.S. government gave LSD to unsuspecting individuals to study effects

LSD in the USA

1960s - popular use advocates East Coast: Timothy Leary (clinical psychologist at Harvard) West Coast: Ken Kesey (noted author)

graduate student in California got dose in psychology study shortly after this goes to work in psychiatry year later, writes One Flew Over The Cuckoo's Nest

LSD in the USA

Spread through country with huge publicity until peak 1968 to 1972

Schedule I in 1968Stuffy politicians didn’t know what to do because

LSD was used by white, middle to upper class, college students

Early 1990s - LSD came back

LSD & Neurotransmission

Binds to 5-HT2A receptors agonist effect

Increases amount of sensory information getting to cortex through overriding filter mechanisms

This is how the drug influences perception, especially for vision

Pharmacology of LSD

Pharmacological Effects Effects heavily dependent

on dose taken not just intensity of effects,

but type of effectsLow doses = mild

perceptual alterations comparable to effects of

marijuana use, but greater clarity

 

Effects of LSD

High Doses progression through mental and

emotional experiences 6-12 hrs duration Each trip unique, highly

dependent upon setting and personal expectations

Can alter subjects’ emotional feelings during trip by experimenter’s previous behavior warm and supportive or

suspicious and nonsupportive

Effects of LSD

Effects of drug come on in about 30 minfirst signs are autonomic activationfollowed by overt behavioral signs - loosening of

emotional inhibitions giddiness, laughter for no reason mood euphoric and expansive, but labile mood swings

notableabnormal color sensations, luminescencecolors reported as more brilliant

Effects of LSD

space and time disordersadded depth with loss of perspective - up/down

alteredclose in space influenced more than distantgeneral slowing of time reported

LSD Hallucinationsgratings, latticework,

honeycomb, chessboard, tunnels, funnels, alleys, cones,

vessels, and spirals can be present with eyes open or

closed involve bright light in center

with figures moving in from periphery

forms appear to move in depth and take on color shades, red common

Sounds can take on visual forms music may take on enhanced

meaning or intensity

LSD & Bad Trips

Psychological impact - traumatizing, imagery dark, insights appalling

Usually occur in novice users, feel out of controlGenerally negative set and setting are key

contributing factorsCan lead to suicide or prolonged psychotic

reactionCan usually be talked down from a bad trip

LSD & Flashbacks

Spontaneous recurrence of trip after period of normalcy

can occur after long periods of abstinencemore common after multiple high dose useprolonged afterimages for days and weeks after

tripping mechanism unknown can be brought on by other drugs or setting most commonly reported in low light situationsnot intrinsically dangerous and usually go away

Psilocybin/Psilocin

Magic Mushrooms, Liberty Caps Central America and

northwestern U.S. Last about 6-10 hours Need a lot to get same effect

as LSD 5-HT2A agonist Same basic effects as LSD Mushrooms occasionally

toxic

DMT

Dimethyltriptamine 5-HT2A agonist Alkaloid Often smoked Main ingredient in Ayahuasca Same effects as LSD

Bufotenine

Dimethyl-serotonin A product of

abnormal serotonin breakdown

Like LSD and others Can occur in urine of

people with psychiatric disorders Psychosis Paranoia Depression

Ololiuqui

Substance found in morning glory seedsSimilar to LSDSignificant nausea, vomiting and cramping

Tolerance/Dependence

Not significant producers of tolerance or dependence

No withdrawal eitherPeople and animals do not self-administerProblems related to the things people do

while under the influence Accidents Suicide Aggression/violence Toxic reactions

Catecholamine-likePsychedelics

Mescaline

Active drug in peyoteStructurally similar to

NEHowever, most of the

effect is mediated by our friend, the 5-HT2A

agonist actionLegal for members of

the Native American Church

Ecstasy

MDMA (methylene-dioxy-methamphetamine)

Synthesized in 1912Structurally related to amphetamines

Sympathomimetic Weak in altering perceptual functions But strong effects on emotions - empathogen Used in combo with psychotherapy

MDMA

CH2 NHCH CH3

CH3O

O

PharmacodynamicsPharmacodynamics

Monoamine neurotransmission increase synaptic DA and 5-HT blocks 5-HT transporter enters neuron and causes release of 5-HT

Ecstasy Effects

Stimulant effects typically noted shortly after ingestion increased heart rate increased blood pressure dry mouth decreased appetite increased alertness elevated mood jaw clenching

Ecstasy Effects

Subjective Effects

euphoria increased

physical and emotional energy

heightened sensual awareness

subjective feeling of increased closeness or enhanced communication

Cognitive Effects

memory loss

X Tox

Malignant hyperthermia and dehydrationIdiopathic toxic response (not common but

nasty) Renal failure Rhabdomyolysis – disintegration of muscle tissue

Street X is even more of a problem because it’s not always X or may have other drugs

X Tox

Potent neurotoxin 1-2 times street dose depletes forebrain 5-HT (not DA) Kills the transporter receptor (SSRI) Degeneration of 5-HT terminals

Fine axons from dorsal raphe Can get 30% loss with single injection Up to 80% with repeated injections

Can induce psychiatric disturbance in vulnerable individuals. Treatment refractory depression

MDMA & MDA neurotoxicityMDMA & MDA neurotoxicity

9.9

Normal MDAPCA

5-HT immunoreactive fibers in rat parietal cortex

McCann et al.(1997)

Control

MDMA

Squirrelmonkeys 18 mo post-trtmt

Neocortex Hippocampus Caudate5-HT immuno-reactivity

What is PMA?

Paramethoxy-amphetamine"Death" "Mitsubishi Double Stack"

"Killer" "Red Mitsubishi"Substitute for MDMACheaper to makeSlower, longer effectsMore hallucinogenicIncidence of toxic side effects much higher

than MDMA (narrow safety margin)

Designer Psychedelics

DOM, MDA, DMA, MDE, TMA, AMT, 5MeO-DIPT

All structurally related to mescaline and methamphetamine; therefore MDMA.

MDA is a metabolite of MDMA. May be responsible for much of the MDMA effect.

Myristin and Elemicin

Found in nutmeg and maceStructurally similar to mescalineSignificant nausea and vomitingThe sick usually limit use

DISSOCIATIVE ANESTHETICS

GlutamatergicPsychedelics

PhencyclidinePCPPCPNMDA receptor antagonistNMDA receptor antagonist

Blocks the function of glutamateBlocks the function of glutamate

Used as an analgesic and anestheticUsed as an analgesic and anestheticCan be administered by any routeCan be administered by any routeOddly enough, animals self-administer Oddly enough, animals self-administer

(euphoria) (euphoria)Induces amnesia and true psychosisInduces amnesia and true psychosis

Hallucinations, paranoia, agitation, dissociation Hallucinations, paranoia, agitation, dissociation

Higher doses lead to stupor, coma Higher doses lead to stupor, coma seizures, death seizures, death

A perfect example of a Schedule I drugA perfect example of a Schedule I drug

Ketamine

Special KVery similar to PCP,

not as powerfulLiquid, but can be

powdered for snorting or smoking

But just as dumb, stupid, useless and unsafe

Another perfect example of a Schedule I drug

Subjective Effects of PCP/Ketamine

Sensations of light coming through the body and/or colorful visions

Complete loss of time senseBizarre distortions of body shape or sizeAltered perception of body consistencySensations of floating or hovering in spaceFeelings of leaving one’s bodyVisions of spiritual or supernatural beingsEmotions ranging from euphoria to hositlity

Dalgarno & Shewan (1996)

Dextromethorphan

Active ingredient in most OTC cough medicine

NMDA receptor blockade at high dosesMostly teenage males abuse itLike PCP and K at 20-30 X OTC doseCoricidin –Bad news

CholinergicHallucinogens

Muscarine/Muscimol

Found in mushrooms (Amanita Muscaria)

Muscimol is a GABAA agonist Trance-like, dreamy state

with dreamlike illusions Like Ambien

Muscarine is an Acetylcholine agonist (muscarinic receptors) Not psychotropic Peripheral effects: sweating,

limb twitching, seizure activity

Atropine & Scopolamine

Found in – Atropa belladonna, Datura Stramonium, Henbane

Acetylcholine receptor (muscarinic) antagonistsDissociatives that induces delirium , hallucinations, and amnesiaClassic anti-cholinergic symptoms

Hot as hell Dry as a bone Mad as a hatter Blind as a bat Red as a beet

Used in the treatment of motion sickness & to dilate pupils during eye-exams.

Opioid Hallucinogen - Salvinorin A

Comes from a plant in the mint family Salvia Divinorum

Affinity for kappa opioid receptors Agonist action

Like LSD and psilocybin

Fresh leaves are chewed and left in mouth

Dried leaves smoked Not effective if taken

orally

Most potent, but not most powerful, of all naturally occurring hallucinogens

It’s still legal, but not likely for long