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.

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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.

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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

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