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Chapter 14

Hallucinogens

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Animism

Objects attain certain characteristics because of spirits

If a plant contains a spirit, then eating the plant transfers this spirit to the person who consumes it

Psychoactive plants that alter perceptions

May have been important in the development of spiritual and religious traditions and folklore in many societies

Animism and Religion

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Phantastica

Drugs that create a world of fantasy

Psychedelic

“Mind-viewing”

Implies a beneficial, visionary type of effect

Psychotomimetic

“Mimicking psychosis”

Produces hallucinations and altered reality, a state similar to psychosis

Terminology

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Entheogen

Substances that create spiritual or religious experiences

Entactogen

Substances that enhance feelings of empathy

Hallucinogens

A drug that produces profound alterations in perception, including unusual visual sensations and often changes in the perception of one’s own body

Terminology

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Hallucinogens can be classified by

Chemical structure

Known pharmacological properties

How much loss of awareness they cause

How dangerous they are

Two major groups

Phantastica

Alter perceptions while allowing the user to remain in communication with the present world

Deliriants

Produce more mental confusion, greater clouding of consciousness, and a loss of touch with reality

Classification

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Indole hallucinogens

Drugs that have the same basic indole structure of the neurotransmitter serotonin

Examples: LSD, psilocybin

Catechol hallucinogens

Drugs that have the same basic catechol structure of the neurotransmitters norepinephrine and dopamine

Examples: mescaline, MDMA (Ecstasy or molly)

Two Groups of Phantastica

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Indole Hallucinogens

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Figure 14.1 from text

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1938:

Synthesized by Dr. Albert Hofmann of Sandoz Laboratories in Switzerland

1943:

Dr. Hofmann took a large dose and described its hallucinogenic effects

Dose was 5–8 times the normal effective dose

Potency of the drug attracted attention

Comparable effects from mescaline would require 4,000 times the dose

LSD: Discovery

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1950s–1970s: a tremendous amount of LSD research

Attempting to develop a model of psychosis

Widely used as an adjunct to psychotherapy

1970s: Funding institutes stopped supporting human research

Most research since 1975 has been conducted with animals in an effort to understand the mechanism at the neural level

Secret Army/CIA Research

Poorly done and violated many ethical codes

U.S. required to pay reparations to research subjects

LSD: Early Research

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Timothy Leary

Conducted research on LSD and psilocybin at Harvard

Research was scientifically unsound and unethical

Started a religion (League of Spiritual Discovery) with LSD as a sacrament

Recreational use peaked in late 1960s

Use declined due to anecdotal reports of problems associated with:

“bad trips”

prolonged psychotic reactions

worries about possible chromosome damage

self-injurious behavior

“flashbacks”

Recreational Use

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One of the most potent psychoactive drugs

No known human overdose deaths

LD50 is about 400 times the behaviorally effective dose

LSD is usually taken orally

Absorbed rapidly through the gastrointestinal tract

Mechanism of action

Best evidence indicates that LSD acts by stimulating serotonin-2A receptors

LSD Pharmacology

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Image Source: Drug Enforcement Administration

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Metabolism

Metabolized by the liver

Half-life is about three hours

Tolerance develops rapidly

Within three to four days of daily doses

Recovery from tolerance is also rapid

Cross-tolerance occurs among LSD, mescaline, and psilocybin

Physical dependence to LSD or other hallucinogens has not been demonstrated

LSD Pharmacology

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Modification of perception

Visual images: Users see shapes and patterns, usually with intense colors and brightness

Users report an altered sense of time, changes in the perception of their own bodies, and alterations of auditory input

Synesthesia (“mixing of senses”)

Example: sounds may appear as visual images

Enhanced emotionality

Images may be perceived as beautiful and awe-inspiring or as intensely sad or frightening

Psychological and Behavioral Effects

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Typically last six to nine hours

First 20 min: Autonomic responses occur

Next 30–40 min: Alterations in mood, perception, and sensation begin

Within 1 hour: Full intoxication occurs

Loss of self-awareness and loss of control of behavior may occur

Time Course of Effects

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Impossible to determine true incidence of adverse reactions

For example, some bad reactions may be due to drug impurities

Flashbacks

DSM-5: Hallucinogen Persisting Perception Disorder

Recurrence of symptoms weeks or months after an individual has taken LSD

Relative rare in occurrence

Panic reactions

Relatively more common in occurrence

Adverse Reactions

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Several varieties of “magic mushrooms”

Psilocybe mexicana is the most well-known

Psilocybin is primary active ingredient

1958: Albert Hofmann isolated psilocybin

Dried mushrooms are 0.2–0.5 percent psilocybin

Psilocybin

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Image source: © IT Stock/age fotostock (Image Ch14_12Psilocybe2)

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Over the past decade, research has increased

Recent studies have investigated the drug’s effects on feelings of spirituality

Acute effects

Psilocybin dose-dependently induces intense changes in mood, perception, and thought

Most individuals describe the effects as pleasurable

At high doses, can cause anxiety

Chronic effects

Relatively little is known

One study indicated no long-term impairment

Acute and Long-Term Effects

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Image source: US Drug Enforcement Administration (Image Ch14_11Psilocybe1)

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Morning Glories

Hawaiian Baby Woodroses

Dimethyltryptamine (DMT)

Ayahuasca

Other Indole Hallucinogens

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Catechol Hallucinogens

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Peyote

A small, spineless, carrot-shaped cactus

Mescaline is primary active ingredient

Synthesized in 1918

More than 30 psychoactive compounds have been identified in peyote

Mescaline

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Image source: US Fish and Wildlife Service (Image Ch14_15Peyote)

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Native American Church uses peyote as a sacrament

Church is an amalgamation of Christianity and traditional beliefs and practices of Native Americans

Legal issues

1990: Supreme Court ruled that Oregon could prosecute its citizens for using peyote

1994: U.S. Congress passed an law stating that “no Indian shall be penalized” for peyote use for legitimate traditional uses

Mescaline: Cultural Use

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Rapidly absorbed after oral administration

Metabolism

Most mescaline is excreted unchanged

Half-life is about 6 hours

Psychological and behavioral effects

Low dose effects are primarily euphoric

Higher doses cause the full set of hallucinogenic effects

Tolerance develops more slowly to mescaline than to LSD

Cross-tolerance between LSD and mescaline

Mescaline: Pharmacology

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Large group of synthetic hallucinogens

Chemically related to amphetamines

Anecdotally, effects are similar to mescaline

But the chemical structure is close to the amphetamines

Examples

MDMA (“Ecstasy” or molly)

MDA

DOM

Amphetamine Derivatives

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Image Source: Drug Enforcement Administration

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Prior to 1985

Some psychiatrists used it as a therapeutic aid

After 1985: Schedule I

Effects

Increased heart rate and blood pressure

Increased euphoria and sociability

Heightened sense of “closeness” with others

MDMA research raises concerns

In animals, selective destruction of serotonin neurons

Limited evidence of neurotoxic effects in humans

MDMA: “Ecstasy” or “molly”

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Phantastica

Have similar effects

Act primarily through the serotonin 2A receptor

By comparison, deliriants

Have a greater tendency to produce mental confusion and a loss of touch with reality

Act through a number of different brain mechanisms

Deliriants

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Generic name: phencyclidine

By 1960, PCP had been characterized as

An excellent anesthetic for monkeys

A medically safe but psychologically troublesome anesthetic for humans

Psychological effects were unpredictable

Currently, PCP is licensed for use as an animal anesthetic

PCP

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1970s:

“Angel dust” = PCP sprinkled onto herbs and sold as marijuana

Relatively inexpensive and easy to manufacture

Most common cause of drug-induced visits to ER

Many legends about PCP effects but little data

Mechanism of action:

Binds selectively to the “sigma” receptor

Other deliriants bind to this receptor

PCP: Recreational use

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Examples:

Ketamine (“Special K”)

Dextromethorphan

Cause different degrees of depressant and dissociative effects

Other PCP-Like Drugs

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This group contains both naturally occurring and synthetic chemicals

Naturally occurring chemicals come from the potato family

Three pharmacologically active alkaloids are responsible for the effects of these plants

Atropine (dl-hyoscyamine)

Scopolamine (l-hyoscine)

l-hyoscyamine

All are potent central and peripheral cholinergic blockers

Anticholinergic Hallucinogens

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Physiological effects

Blocks production of mucus in the nose and throat

Prevents salivation

Mouth becomes dry and perspiration stops

Temperature can increase to fever levels

Heart rate increases

Eyes dilate, resulting in an inability to focus on nearby objects

Behavioral effects

At high doses, behavior pattern resembles toxic psychosis (delirium, mental confusion, loss of attention, drowsiness, loss of memory for recent events)

Anticholinergic Hallucinogens

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Naturally occuring anticholinergics

Belladonna (“deadly nightshade” plant)

Mandrake

Henbane

Datura

Synthetic Anticholinergics

widely used to treat pseudoparkinsonism produced by antipsychotic drugs

Anticholinergic Hallucinogens

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Salvia Divinorum

Can be smoked or eaten

Acts a kappa opioid agonist

Like psilocybin, may cause mystical-type effects in the laboratory

Other Deliriants

Amanita Muscaria

Effects are dissimilar to other hallucinogens

Acts as GABA agonist

Particularly dangerous

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