Research Report Series (2014): Hallucinogens and Dissociative Drugs Including LSD, PCP, Ketamine, Psilocybin, Salvia, Peyote, and Dextromethorphan

from the director:

Hallucinogens and dissociative drugs—
which have street names like acid,
angel dust, and vitamin K—distort the
way a user perceives time, motion,
colors, sounds, and self. These drugs
can disrupt a person's ability to think
and communicate rationally, or even to
recognize reality, sometimes resulting
in bizarre or dangerous behavior.
Hallucinogens such as LSD and psilocybin
cause emotions to swing wildly and
real-world sensations to appear unreal,
sometimes frightening. Dissociative

HALLUCINOGENS/AND
jioeceeeme DISSOCIATIVEDRUGS

control and disconnected from their body Including LSD; PCP Ketamine; Esilocybin,
and environment, oa 1F) Peyoter: and Dextromethorphan

A
In addition to their short-term effects | “4 %
on perception and mood, hallucinogenic
drugs are associated with psychotic-
like episodes that can occur long after
a person has taken the drug, and
dissociative drugs can cause respiratory

depression, heart rate abnormalities, and allucinogens are a class of drugs that cause hallucinations—profound

a withdrawal syndrome. The good news is distortions in a person’s perceptions of reality. Hallucinogens can be found in
that use of hallucinogenic and dissociative some plants and mushrooms (or their extracts) or can be man-made, and they
drugs among U.S. high school students, are commonly divided into two broad categories: classic hallucinogens (such as LSD)

in general, has remained relatively low in and dissociative drugs (such as PCP). When under the influence of either type of drug,
recent years. However, the introduction people often report experiencing rapid, intense emotional swings and seeing images,

of new hallucinogenic/dissociative drugs, hearing sounds, and feeling sensations that seem real but are not.

such as Salvia, is of particular concern. In
fact, salvia is currently the most widely
used drug In this class.

While the exact mechanisms by which hallucinogens and dissociative drugs cause their
effects are not yet clearly understood, research suggests that they work at least partially
by temporarily disrupting communication between neurotransmitter systems throughout

NIDA research is developing a clearer the brain and spinal cord that regulate mood, sensory perception, sleep, hunger, body

picture of the dangers of hallucinogenic
and dissociative drugs. We have compiled
the scientific information in this report to
inform readers and hopefully prevent the
use of these drugs.

temperature, sexual behavior, and muscle control.

Nora D. Volkow, M.D.
Director Psilocybin mushrooms, LSD, and Salvia divinorum are commonly

| | used hallucinogenic and dissociative compounds
National Institute on Drug Abuse Se ee

Classic Hallucinogens*

_ + >

» LSD (d-lysergic acid
diethylamide)—also

; >’
—— known as acid,
in blotter, doses, hits,

microdots, sugar

cubes, trips, tabs,
or window panes—is one of the
most potent mood- and perception-
altering hallucinogenic drugs. It is a
clear or white, odorless, water-soluble
material synthesized from lysergic
acid, a compound derived from a rye
fungus. LSD is initially produced in
crystalline form, which can then be
used to produce tablets known as
“microdots” or thin squares of gelatin
called “window panes.” It can also
be diluted with water or alcohol and
sold in liquid form. The most common
form, however, is LSD-soaked paper
punched into small individual squares,
known as “blotters.”

Psilocybin
(4-phosphoryloxy-
N,N-dimethy-
Itryptamine)—also

known as magic
mushrooms, shrooms,
boomers, or little smoke—is extracted
from certain types of mushrooms
found in tropical and subtropical
regions of South America, Mexico,
and the United States. In the past,
psilocybin was ingested during
religious ceremonies by indigenous

cultures from Mexico and Central
America. Psilocybin can either be
dried or fresh and eaten raw, mixed
with food, or brewed into a tea, and
produces similar effects to LSD.

Dissociative Drugs

PCP
(Phencyclidine)—
also known as

ozone, rocket fuel,
love boat, hog,
embalming fluid, or
superweed—was originally developed
in the 1950s as a general anesthetic
for surgery. While it can be found

in a variety of forms, including
tablets or capsules, it is usually sold
as a liquid or powder. PCP can

be snorted, smoked, injected, or
swallowed. It is sometimes smoked
after being sprinkled on marijuana,
tobacco, or parsley.

Ketamine—also

tx ee
= Se =) knownasK,
—~seeaeees Special K, or
pe ee <= —cat ‘Valium—is

a dissociative
currently used as
an anesthetic for humans as well as
animals. Much of the ketamine sold
on the street has been diverted from
veterinary offices. Although it is
manufactured as an injectable liquid,
ketamine is generally evaporated

to form a powder that is snorted

Common
Hallucinogens and
Dissociative Drugs

or compressed into pills for illicit use.
Because ketamine 1s odorless and
tasteless and has amnesia-inducing
properties, it is sometimes added to
drinks to facilitate sexual assault.

DXM
(Dextromethorphan)—
also known as
robo—is a cough
suppressant and
expectorant ingredient
in some over-the-counter (OTC) cold
and cough medications that are often
abused by adolescents and young
adults. The most common sources of
abused DXM are “extra-strength”
cough syrup, which typically contains
around 15 milligrams of DXM per
teaspoon, and pills and gel capsules,
which typically contain 15 milligrams
of DXM per pill. OTC medications
that contain DXM often also contain
antihistamines and decongestants.

Salvia divinorum—
also known as
diviner’s sage, Maria
Pastora, Sally-D,

or magic mint—is a
psychoactive plant
common to Southern Mexico and
Central and South America. Salvia
divinorum (salvia) is typically ingested
by chewing fresh leaves or by drinking
their extracted juices. The dried leaves
of salvia can also be smoked or
vaporized and inhaled.

*In this report, the term “hallucinogen” will refer to the classic hallucinogenic drugs LSD and Psilocybin.

~ ih

Street Names for Select Hallucinogenic and Dissociative Drugs

LSD Ketamine

e acid e vitamin K

e blotter e bump

e dots e green

e sugar e K/Special K
e trips e purple

® window pane

How, Widespread

Is the Abuse of
Hallucinogens and
Dissociative Drugs?

According to the 2012 National
Survey on Drug Use and Health,
more than 180,000 Americans aged
12 and older reported current (past-
month) use of LSD and 32,000
reported current use of PCP.'! New
hallucinogenic/dissociative drugs
have also emerged on the scene in
recent years. Salvia, historically used
by indigenous tribes of Southern
Mexico during religious rituals, has
replaced LSD and PCP as the most
commonly used hallucinogenic drug.
In fact, past-year use of salvia among

the nation’s 12th-grade students is
more than 1.5 times that of LSD (3.4
percent versus 2.2 percent) and almost
5 times that of PCP (3.4 percent
versus 0.7 percent).”

e super acid

PCP

e angel/angel dust
e boat/love boat

® peace

e killer weed

e super grass

® ozone

Past-Year Use of Hallucinogenic and Dissociative
Drugs Among 12th-Grade Students

—O— Salvia
“@ (SD

—*—PCP

Use in the Past Month (%)

—__s_*
ee

2007 2008 2009 2010 2011 2012 2013

Source: Monitoring the Future National Survey Results on Drug Use, 2013 Overview

While regular use of hallucinogenic and dissociative drugs in general has
remained relatively low in recent years, a recent study reported that the United
States ranks first among 36 nations in the proportion of high school students
ever using LSD or other hallucinogens in their lifetime (6 percent versus 2
percent in Europe).°

Why Do People Take Hallucinogenic
or Dissociative Drugs?

Hallucinogenic and dissociative drugs have been used for a variety of reasons.*»
Historically, hallucinogenic plants have been used for religious rituals to induce
states of detachment from reality and precipitate “visions” thought to provide
mystical insight or enable contact with a spirit world or “higher power.” More
recently, people report using hallucinogenic drugs for more social or recreational
purposes, including to have fun, help them deal with stress, or enable them

to enter into what they perceive as a more enlightened sense of thinking or
being. Hallucinogens have also been investigated as therapeutic agents to treat
diseases associated with perceptual distortions, such as schizophrenia, obsessive-
compulsive disorder, bipolar disorder, and dementia.

NIDA Research Report Series 3

What are the Short-
Term Effects of
Hallucinogens?

Ingesting hallucinogenic drugs

can cause users to see images, hear
sounds, and feel sensations that

seem real but do not exist. Their
effects typically begin within 20 to

90 minutes of ingestion and can last
as long as 12 hours. Experiences are
often unpredictable and may vary
with the amount ingested and the
user’s personality, mood, expectations,
and surroundings. The effects of
hallucinogens like LSD can be
described as drug-induced psychosis—
distortion or disorganization of a
person’s capacity to recognize reality,
think rationally, or communicate with
others. Users refer to LSD and other
hallucinogenic experiences as “trips”
and to acute adverse or unpleasant
experiences as “bad trips.” On some
trips, users experience sensations

that are enjoyable and mentally
stimulating and that produce a sense
of heightened understanding. Bad

panic.

How Do Hallucinogens Work?

trips, however, include terrifying
thoughts and nightmarish feelings of
anxiety and despair that include fears
of losing control, insanity, or death.
Specific short-term effects of LSD and
psilocybin include:

LSD
¢ Increased blood pressure, heart rate,
and body temperature

¢ Dizziness and sleeplessness

¢ Loss of appetite, dry mouth,
and sweating

¢ Numbness, weakness, and tremors

¢ Impulsiveness and rapid emotional
shifts that can range from fear to
euphoria, with transitions so rapid
that the user may seem to experience

several emotions simultaneously
Psilocybin‘™

¢ Feelings of relaxation (similar to
effects of low doses of marijuana)

¢ Nervousness, paranoia, and panic
reactions

¢ Introspective/spiritual experiences

Ingesting hallucinogenic drugs can cause users

to see images, hear sounds, and feel sensations

that seem real but do not exist.

How Do Hallucinogens (LSD and
Psilocybin) Affect the Brain and Body?

Classic hallucinogens are thought to produce their perception-altering

effects by acting on neural circuits in the brain that use the neurotransmitter
serotonin.®’ Specifically, some of their most prominent effects occur in the prefrontal
cortex—an area involved in mood, cognition, and perception—as well as other
regions important in regulating arousal and physiological responses to stress and

Short-Term
General Effects of

Hallucinogens

Sensory Effects

e Hallucinations, including
seeing, hearing, touching, or
smelling things in a distorted
way or perceiving things that
do not exist

e Intensitied feelings and
sensory experiences (brighter
colors, sharper sounds)

e Mixed senses (“seeing”
sounds or “hearing” colors)

e Changes In sense or
perception of time (time goes
by slowly)

Physical Effects

e Increased energy and
heart rate

e Nausea

"Misidentification of poisonous mushrooms resembling psilocybin could lead to unintentional, potentially fatal poisoning

Ak NIDA Research Report Series

LSD users quickly develop a high degree of tolerance
to the drug’s effects, such that repeated use requires
increasingly larger doses to produce similar effects.

What are the Long-
Term Effects of
Hallucinogens?

LSD users quickly develop a high
degree of tolerance to the drug’s
effects, such that repeated use requires
increasingly larger doses to produce
similar effects. Use of hallucinogenic
drugs also produces tolerance to
other drugs in this class, including
psilocybin and mescaline.* Use
of classic hallucinogens does not,
however, produce tolerance to drugs
that do not act directly on the same
brain cell receptors (in other words,
there is no cross-tolerance to drugs that
act on other neurotransmitter systems,
such as marijuana, amphetamines, or
PCP, among others). Furthermore,
tolerance for hallucinogenic drugs is
short-lived—it 1s lost if the user stops
taking the drugs for several days—and
physical withdrawal symptoms are
typically not experienced by users when
chronic use 1s stopped.

Two long-term effects—persistent
psychosis and hallucinogen persisting
perception disorder (HPPD; also

often referred to as “flashbacks” )—
have been associated with use of
classic hallucinogens (see sidebar).
Although occurrence of either 1s

rare, it is also unpredictable and may
happen more often than previously
thought, and sometimes both
conditions occur together. While

the exact causes are not known,

both conditions are more often

seen in individuals with a history

of psychological problems but can
happen to anyone, even after a single
exposure. There 1s no established
treatment for HPPD, in which
flashbacks may occur spontaneously
and repeatedly although less intensely
than their initial occurrence. Some
antidepressant and antipsychotic
drugs can be prescribed to help
improve mood and treat psychoses,
however. Psychotherapy may also
help patients cope with fear or
confusion associated with visual
disturbances or other consequences
of long-term LSD use. More research
on the causes, incidence, and long-
term effects of both disorders is being
conducted.

Long-Term Effects
of Hallucinogens

Persistent psychosis

e Visual disturbances
e Disorganized thinking
e Paranoia

e Mood disturbances

Hallucinogen Persisting

Perception Disorder (HPPD)

e Hallucinations

e Other visual disturbances
(such as seeing halos or trails
attached to moving objects)

e Symptoms sometimes
mistaken tor neurological
disorders (Such as stroke or
brain tumor)

What are the Effects of Common Dissociative Drugs
on the Brain and Body?
How Do Dissociative Drugs Work ?

Laboratory studies suggest that dissociative drugs, including PCP, ketamine, and DXM,
cause their effects by disrupting the actions of the brain chemical glutamate at certain
types of receptors—called N-methyl-D-aspartate (NMDA) receptors—on nerve cells
throughout the brain.!"'' Glutamate plays a major role in cognition (including learning and
memory), emotion, and the perception of pain (the latter via activation of pain-regulating

cells outside of the brain). PCP also alters the actions of dopamine, a neurotransmitter
responsible for the euphoria and “rush” associated with many abused drugs.

Salvia divinorum works differently. While classified as a dissociative drug, salvia causes its effects by activating a specific
type of opioid receptor (the kappa opioid receptor) on nerve cells.'*!? These receptors differ from those activated by the more
commonly known opioids such as heroin and morphine.

* Mescaline is not described in this report.

NIDA Research Report Series Le.

What are the Short-Term Effects of Dissociative Drugs?

Dissociative drugs can produce visual and auditory distortions and a sense of floating and dissociation (feeling
detached from reality) in users. Use of dissociative drugs can also cause a user to experience anxiety, memory loss,
and impaired motor function, including body tremors and numbness. These effects, which depend on the amount of
the drug taken, are also unpredictable—typically beginning within minutes of ingestion and lasting tor several hours
(although some users report feeling the drug's effects for days). See text box for general effects of dissociative drugs.

‘CT=Jal-1e-]mOvolonlaalolaM =sni-.eun-meoy mm DIl-t-Lelert- na hV.-m Dig eler-

Low to Moderate Doses

Numbness

Loss of coordination, disorientation, and confusion
Dizziness, nausea, vomiting

Changes in sensory perceptions (Such as
sight, sound, shapes, time, and body image)

Hallucinations
Feelings of detachment trom self and environment

Increase in blood pressure, heart rate, respiration,

High Doses
Hallucinations
Memory loss

Physical distress, including dangerous changes In blood
pressure, heart rate, respiration, and body temperature

Marked psychological distress, including feelings of extreme
panic, fear, anxiety, paranoia, invulnerability, exaggerated
strength, and aggression

Use with high doses of alcohol or other central nervous
system depressants can lead to respiratory distress or
arrest, resulting in death

and body temperature

In addition to these general
effects, different dissociative
drugs can produce a variety of
distinct and dangerous effects.
For example, at moderate to high
doses, PCP can cause a user to
have seizures or severe muscle
contractions, become aggressive
or violent, or even experience
psychotic symptoms similar to
schizophrenia. At moderate to high
doses, ketamine can cause sedation,
immobility, and amnesia. At high

6 NIDA Research Report Series

doses, ketamine users also report
experiencing terrifying feelings of
almost complete sensory detachment
likened to a near-death experience
(called a “K-hole,” similar to a
bad LSD trip). Salvia users report
intense but short-lived (up to 30
minutes) effects, including emotional
mood swings (ranging from sadness
to uncontrolled laughter).

DXM, which is safe and
effective as a cough suppressant
and expectorant when used at

recommended doses (typically 15—30
milligrams), can lead to serious side
effects when abused. For example,
use of DXM at doses from 200

to 1,500 milligrams can produce
dissociative effects similar to PCP
and ketamine and increase the risk
of serious central nervous system
and cardiovascular effects such as
respiratory distress, seizures, and
tachycardia (increased heart rate)
from the antihistamines found in
cough medicines.

What are the Long-Term Effects of
Dissociative Drugs?

While the long-term use of most dissociative drugs has not been investigated
systematically, research shows that repeated use of PCP can lead to tolerance
and the development of a substance use disorder that includes a withdrawal
syndrome (including craving for the drug, headaches, and sweating) when drug
use is stopped. Other effects of long-term PCP use include persistent speech
difficulties, memory loss, depression, suicidal thoughts, anxiety, and social
withdrawal that may persist for a year or more after chronic use stops.

Glossary
Central Nervous System: The brain and spinal cord.

Cerebral cortex: The region of the brain responsible
for cognitive functions including reasoning, mood,
and perception of stimuli.

Dissociative: a type of compound, such as
phencyclidine or ketamine, that produces an
anesthetic effect characterized by a feeling of being
detached from the physical self.

DXM: A common street name for dextromethorphan.

Kappa opioid receptor: A receptor on nerve cells
that is activated by certain opioid-like compounds
produced in the body. These receptors differ from
those activated by the more commonly known
opioids, such as heroin and morphine.

Neurotransmitter: A chemical compound that acts as
a messenger to carry signals from one nerve cell to
another.

NMDA receptors: N-methyl-D-aspartate receptors,
a type of glutamate receptor that is important for

Flashback: A sudden but temporary recurrence

learning and memory; it is the target of drugs such

of aspects of a drug experience (including sights,

sounds, and feelings) that may occur days, weeks, or
even more than a year after hallucinogenic drug use.

Glutamate: An excitatory neurotransmitter found

as PCP and ketamine.

Persistent psychosis: Unpredictable and long-lasting
visual disturbances, dramatic mood swings, and

hallucinations experienced by some LSD users after

throughout the brain that influences the reward

system and is involved in learning and memory,

among other functions.

Hallucinogen: A drug that produces hallucinations —

they have discontinued use of the drug.

Serotonin: A neurotransmitter involved in a broad

range of effects on perception, movement, and
emotions. Serotonin and its receptors are the targets

distortions in perception of sights and sounds—and
disturbances in emotion, judgment, and memory.

HPPD: Hallucinogen persisting perception disorder;
the spontaneous and sometimes continuous

recurrence of perceptual effects of LSD long after an
individual has ingested the drug.

References
1. Substance Abuse and Mental Health Bogenschutz, M.P; and Pommy, J.M. 9. Lee, H.M.; and Roth, B.L.
Services Administration. Results Therapeutic mechanisms of classic Hallucinogen actions on human brain
from the 2012 National Survey on hallucinogens in the treatment of revealed. Proc Natl Acad Sci USA
Drug Use and Health: Summary of addictions: From indirect evidence to 109(6): 1820-1821, 2012.
National Findings, NSDUH Series H-44, testable hypotheses. Drug Test Anal
HHS Publication No. (SMA) 12-4713. 4(7-8): 543-555, 2012. 10. Morgan, C.J.; Curran, H.V.; and
Rockville, MD: U.S. Department of Independent Scientific Committee
Health and Human Services, Substance Bonson, K.R. Hallucinogenic Drugs. In on Drugs. Ketamine use: A review.
Abuse and Mental Health Services Encyclopedia of Life Sciences, Nature Addiction 107(1): 27-38, 2012.
Administration, 2012. Publishing Group, 2001.
11. Morris, B.J.; Cochran, S.M.; and Pratt,
2. Johnston, L.D.; O'Malley, PM.; Passie, I.; Halpern, J.H.; Stichtenoth, J.A. PCP: From pharmacology to
Bachman, J.G.; and Schulenberg, J.E. D.O.; Emrich, H.M.; and Hintzen, A. modelling schizophrenia. Curr Opin
Monitoring the Future national results The pharmacology of lysergic acid Pharmaco 5(1):101-106, 2005.
on adolescent drug use: Overview of diethylamide: A review. CNS Neurosci
key findings, 2013. Ann Arbor: Institute Ther 14(4): 295-314, 2008. 12. Cunningham, C.VW.; Rothman,
for Social Research, the University of R.B.; and Prisinzano, T-E.
Michigan, 2014. Nichols, D.E. Hallucinogens. Pharmacol Neuropharmacology of the naturally
Ther 101(2): 131-181, 2004. occurring kappa-opioid hallucinogen
3. Hibell, B.; Guttormsson, U.; Ahlstrom, salvinorin A. Pharmacol Rev 63(2):
S.; Balakireva, O.; Bjarnason, T.; Schindler, E.A.; Dave, K.D.; Smolock, 316-347, 2011.
Kokkevi, A.; and Kraus, L. The 20717 E.M.; Aloyo, V.J.; and Harvey, J.A.
ESPAD Report: Substance Use Among Serotonergic and dopaminergic 13. MacLean, K.A.; Johnson, M.W;

Students in 36 European Countries.
Stockholm, Sweden: The Swedish
Council for Information on Alcohol and
Other Drugs (CAN), 2012.

distinctions in the behavioral
pharmacology of (+/-)-1-(2,5-dimethoxy-
4-iodophenyl)-2-aminopropane (DO!)
and lysergic acid diethylamide (LSD).
Pharmacol Biochem Behav 101(1):
69-76, 2012.

of most hallucinogens.

Reissig, C.J.; Prisinzano, T-E.; and
Griffiths, R.R. Dose-related effects of
salvinorin A in humans: Dissociative,
hallucinogenic, and memory effects.
Psychopharmacology (Berl). 226(2):
381-392, 2013.

NIDA Research Report Series J

Where can | get further information about hallucinogens?

To learn more about hallucinogens
and other drugs of abuse,

visit the NIDA Web site at
www.drugabuse.gov or

contact the DrugPubs Research
Dissemination Center at
877-NIDA-NIH (877-643-2644;
TTY/TDD: 240-645-0228).

NATIONAL INSTITUTE ON DRUG ABUSE

NIDA
== DRUGPUBS

RESEARCH DISSEMINATION CENTER

What's on the NIDA Web Site

¢ Information on drugs of abuse and
related health consequences

¢ NIDA publications, news, and
events

Resources for health care
professionals

¢ Funding information (including
program announcements and
deadlines)

International activities

e Links to related Web sites (access
to Web sites of many other
organizations in the field)

NIDA Web Sites
www.drugabuse.gov
www.teens.drugabuse.gov
www.drugabuse.gov/publications/
term/160/DrugF acts
www.easyread.drugabuse.gov

For Physician Information

NIDAMED £3

www.drugabuse.gov/nidamed

on Drug Abuse

National Institute

Other Web Sites

Information on hallucinogens and
dissociative drugs is also available
through these other Web sites:

¢ Substance Abuse and Mental
Health Services Administration
Health Information Network:
www.samhsa.gov

¢ Drug Enforcement Administration:
www.deadiversion.usdoj.gov

¢ Monitoring the Future:
www. monitoringthefuture.org/

¢ The Partnership at Drug Free.org:
www. drugfree. org/drug-guide

NIH Publication Number 14-4209 ¢ Revised January 2014

S NIDA Research Report Series

Feel free to reprint this publication.