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Long-Term Effects of See page 5.

from the director: Research Report Series

Hallucinogens and — which have street names like , angel dust, and 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 cause to swing wildly and HALLUCINOGENS AND real-world sensations to appear unreal, sometimes frightening. Dissociative drugs like PCP, , DXM, and DISSOCIATIVE DRUGS divinorum may make a user feel out of control and disconnected from their body Including LSD, PCP, Ketamine, Psilocybin, and environment. Salvia, , and

In addition to their short-term effects on and mood, hallucinogenic What Are drugs are associated with psychotic- Hallucinogens and like episodes that can occur long after a person has taken the , and Dissociative Drugs? dissociative drugs can cause respiratory , abnormalities, and allucinogens are a class of drugs that cause —profound a withdrawal syndrome. The good news is distortions in a person’s of reality. Hallucinogens can be found in that use of hallucinogenic and dissociative Hsome and (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 While the exact mechanisms by which hallucinogens and dissociative drugs cause their fact, salvia is currently the most widely effects are not yet clearly understood, research suggests that they work at least partially used drug in this class. by temporarily disrupting communication between systems throughout the and that regulate mood, sensory perception, , hunger, body NIDA research is developing a clearer picture of the dangers of hallucinogenic temperature, sexual behavior, and muscle control. and dissociative drugs. We have compiled the scientific information in this report to inform readers and hopefully prevent the use of these drugs.

Nora D. Volkow, M.D. Director Psilocybin mushrooms, LSD, and are commonly used hallucinogenic and dissociative compounds National Institute on Drug Abuse continued inside

U.S. Department of Health and Human Services | National Institutes of Health Common Hallucinogens and Research Report Series Dissociative Drugs

Classic Hallucinogens* cultures from and Central or compressed into pills for illicit use. America. Psilocybin can either be Because ketamine is odorless and LSD (d-lysergic acid dried or fresh and eaten raw, mixed tasteless and has -inducing diethylamide)—also with , or brewed into a , and , it is sometimes added to known as acid, produces similar effects to LSD. drinks to facilitate sexual assault. blotter, doses, hits, microdots, sugar Dissociative Drugs DXM cubes, trips, tabs, (Dextromethorphan)— or window panes—is one of the PCP also known as most potent mood- and perception- ()— robo—is a altering hallucinogenic drugs. It is a also known as suppressant and clear or white, odorless, -soluble ozone, rocket fuel, expectorant ingredient material synthesized from lysergic love boat, hog, in some over-the-counter (OTC) cold acid, a compound derived from a rye embalming fluid, or and cough that are often . LSD is initially produced in superweed—was originally developed abused by adolescents and young crystalline form, which can then be in the 1950s as a general . The most common sources of used to produce tablets known as for . While it can be found abused DXM are “extra-strength” “microdots” or thin squares of gelatin in a variety of forms, including cough , which typically contains called “window panes.” It can also tablets or capsules, it is usually sold around 15 milligrams of DXM per be diluted with water or and as a liquid or powder. PCP can teaspoon, and pills and gel capsules, sold in liquid form. The most common be snorted, smoked, injected, or which typically contain 15 milligrams form, however, is LSD-soaked paper swallowed. It is sometimes smoked of DXM per pill. OTC medications punched into small individual squares, after being sprinkled on marijuana, that contain DXM often also contain known as “blotters.” , or . and .

Psilocybin Ketamine—also Salvia divinorum— (4-phosphoryloxy- known as K, also known as N,N-dimethy- Special K, or diviner’s sage, Maria ltryptamine)—also cat Valium—is Pastora, Sally-D, known as magic a dissociative or magic mint—is a mushrooms, shrooms, currently used as psychoactive boomers, or little smoke—is extracted an anesthetic for humans as well as common to Southern Mexico and animals. Much of the ketamine sold from certain types of mushrooms Central and South America. Salvia on the street has been diverted from found in tropical and subtropical divinorum (salvia) is typically ingested regions of South America, Mexico, veterinary offices. Although it is by chewing fresh or by drinking and the . In the past, manufactured as an injectable liquid, their extracted juices. The dried leaves psilocybin was ingested during ketamine is generally evaporated of salvia can also be smoked or religious ceremonies by indigenous to form a powder that is snorted vaporized and inhaled.

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

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Street Names for Select Hallucinogenic and Dissociative Drugs LSD Ketamine PCP • acid • vitamin K • angel/angel dust • blotter • bump • boat/love boat • dots • green • peace • sugar • K/Special K • killer weed • trips • purple • super grass • window pane • super acid • ozone

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.1 New hallucinogenic/dissociative drugs have also emerged on the scene in recent years. Salvia, historically used by indigenous tribes of Southern Mexico during religious , 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 While regular use of hallucinogenic and dissociative drugs in general has more than 1.5 times that of LSD (3.4 remained relatively low in recent years, a recent study reported that the United percent versus 2.2 percent) and almost States ranks first among 36 nations in the proportion of high school students 5 times that of PCP (3.4 percent ever using LSD or other hallucinogens in their lifetime (6 percent versus 2 versus 0.7 percent).2 percent in ).3

Why Do People Take Hallucinogenic or Dissociative Drugs? Hallucinogenic and dissociative drugs have been used for a variety of reasons.4,5 Historically, hallucinogenic plants have been used for religious rituals to induce states of detachment from reality and precipitate “visions” 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 of thinking or being. Hallucinogens have also been investigated as therapeutic agents to treat associated with perceptual distortions, such as , obsessive- compulsive disorder, , and .

NIDA Research Report Series 3 How Do Hallucinogens (LSD and Psilocybin) Affect the Brain and Body? How Do Hallucinogens Work? Classic hallucinogens are thought to produce their perception-altering effects by acting on neural circuits in the brain that use the neurotransmitter .6-9 Specifically, some of their most prominent effects occur in the prefrontal cortex—an area involved in mood, , and perception—as well as other regions important in regulating arousal and physiological responses to stress and panic.

What are the Short- trips, however, include terrifying Term Effects of and nightmarish feelings of Hallucinogens? and despair that include fears of losing control, insanity, or . Ingesting hallucinogenic drugs Specific short-term effects of LSD and can cause users to see images, hear psilocybin include: sounds, and feel sensations that seem real but do not exist. Their LSD effects typically begin within 20 to • Increased pressure, heart rate, 90 minutes of and can last and body temperature as long as 12 hours. are • and sleeplessness often unpredictable and may vary with the amount ingested and the • Loss of appetite, dry mouth, user’s personality, mood, expectations, and sweating Short-Term and surroundings. The effects of • Numbness, weakness, and tremors General Effects of hallucinogens like LSD can be Hallucinogens • Impulsiveness and rapid emotional described as drug-induced — shifts that can range from fear to Sensory Effects distortion or disorganization of a , with transitions so rapid • Hallucinations, including person’s capacity to recognize reality, that the user may seem to seeing, hearing, touching, or think rationally, or communicate with several emotions simultaneously smelling things in a distorted way or perceiving things that others. Users refer to LSD and other Psilocybin† do not exist hallucinogenic experiences as “trips” • Feelings of relaxation (similar to • Intensified feelings and and to acute adverse or unpleasant effects of low doses of marijuana) sensory experiences (brighter experiences as “bad trips.” On some colors, sharper sounds) trips, users experience sensations • Nervousness, , and panic • Mixed (“seeing” reactions that are enjoyable and mentally sounds or “hearing” colors) stimulating and that produce a sense • Introspective/spiritual experiences • Changes in sense or perception of time (time goes of heightened understanding. Bad by slowly)

Physical Effects • Increased energy and Ingesting hallucinogenic drugs can cause users heart rate to see images, hear sounds, and feel sensations • that seem real but do not exist.

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

4 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- often referred to as “flashbacks”)— Term Effects of have been associated with use of Hallucinogens? classic hallucinogens (see sidebar). Although occurrence of either is LSD users quickly develop a high rare, it is also unpredictable and may degree of tolerance to the drug’s happen more often than previously effects, such that repeated use requires thought, and sometimes both increasingly larger doses to produce conditions occur together. While similar effects. Use of hallucinogenic the exact causes are not known, drugs also produces tolerance to both conditions are more often other drugs in this class, including seen in individuals with a history psilocybin and .‡ Use Long-Term Effects of psychological problems but can of classic hallucinogens does not, of Hallucinogens happen to anyone, even after a single however, produce tolerance to drugs exposure. There is no established Persistent psychosis that do not act directly on the same treatment for HPPD, in which • Visual disturbances brain cell receptors (in other words, flashbacks may occur spontaneously • Disorganized thinking there is no cross-tolerance to drugs that and repeatedly although less intensely • Paranoia act on other neurotransmitter systems, than their initial occurrence. Some • Mood disturbances such as marijuana, , or and PCP, among others). Furthermore, Hallucinogen Persisting drugs can be prescribed to help tolerance for hallucinogenic drugs is Perception Disorder (HPPD) improve mood and treat psychoses, short-lived—it is lost if the user stops • Hallucinations however. may also taking the drugs for several days—and • Other visual disturbances help patients cope with fear or physical withdrawal symptoms are (such as seeing halos or trails associated with visual typically not experienced by users when attached to moving objects) disturbances or other consequences chronic use is stopped. • Symptoms sometimes of long-term LSD use. More research mistaken for neurological Two long-term effects—persistent on the causes, incidence, and long- disorders (such as stroke or psychosis and hallucinogen persisting term effects of both disorders is being brain tumor) perception disorder (HPPD; also conducted.

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.10,11 Glutamate plays a major role in cognition (including learning and memory), , and the perception of (the latter via activation of pain-regulating cells outside of the brain). PCP also alters the actions of , a neurotransmitter responsible for the euphoria and “” 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 (the kappa ) on nerve cells.12,13 These receptors differ from those activated by the more commonly known such as and .

‡ Mescaline is not described in this report.

NIDA Research Report Series 5 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 for several hours (although some users report feeling the drug’s effects for days). See text box for general effects of dissociative drugs.

General Common Effects of Dissociative Drugs

Low to Moderate Doses High Doses

Numbness Hallucinations

Loss of coordination, disorientation, and confusion Memory loss

Dizziness, nausea, Physical distress, including dangerous changes in blood pressure, heart rate, respiration, and body temperature Changes in sensory perceptions (such as sight, sound, shapes, time, and body image) Marked psychological distress, including feelings of extreme panic, fear, anxiety, paranoia, invulnerability, exaggerated Hallucinations strength, and aggression

Feelings of detachment from self and environment Use with high doses of alcohol or other central can lead to respiratory distress or Increase in blood pressure, heart rate, respiration, arrest, resulting in death and body temperature

In addition to these general doses, ketamine users also report recommended doses (typically 15–30 effects, different dissociative experiencing terrifying feelings of milligrams), can lead to serious side drugs can produce a variety of almost complete sensory detachment effects when abused. For example, distinct and dangerous effects. likened to a near-death experience use of DXM at doses from 200 For example, at moderate to high (called a “K-hole,” similar to a to 1,500 milligrams can produce doses, PCP can cause a user to bad LSD trip). Salvia users report dissociative effects similar to PCP have or severe muscle intense but short-lived (up to 30 and ketamine and increase the risk contractions, become aggressive minutes) effects, including emotional of serious or violent, or even experience mood swings (ranging from sadness and cardiovascular effects such as psychotic symptoms similar to to uncontrolled ). respiratory distress, seizures, and schizophrenia. At moderate to high DXM, which is safe and (increased heart rate) doses, ketamine can cause , effective as a cough suppressant from the antihistamines found in immobility, and amnesia. At high and expectorant when used at cough .

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 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.

6 NIDA Research Report Series Glossary

Central Nervous System: The brain and spinal cord. Kappa opioid receptor: A receptor on nerve cells that is activated by certain opioid-like compounds : The region of the brain responsible produced in the body. These receptors differ from for cognitive functions including reasoning, mood, those activated by the more commonly known and perception of stimuli. opioids, such as heroin and morphine.

Dissociative: a type of compound, such as Neurotransmitter: A chemical compound that acts as phencyclidine or ketamine, that produces an a messenger to carry signals from one nerve cell to anesthetic effect characterized by a feeling of being another. detached from the physical self. NMDA receptors: N-methyl-D-aspartate receptors, DXM: A common street name for dextromethorphan. a type of that is important for learning and memory; it is the target of drugs such : A sudden but temporary recurrence as PCP and ketamine. of aspects of a drug experience (including sights, sounds, and feelings) that may occur days, weeks, or Persistent psychosis: Unpredictable and long-lasting even more than a year after hallucinogenic drug use. visual disturbances, dramatic mood swings, and hallucinations experienced by some LSD users after Glutamate: An excitatory neurotransmitter found they have discontinued use of the drug. throughout the brain that influences the and is involved in learning and memory, Serotonin: A neurotransmitter involved in a broad among other functions. range of effects on perception, movement, and emotions. Serotonin and its receptors are the targets Hallucinogen: A drug that produces hallucinations— of most hallucinogens. 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. and Mental Health 4. 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 from the 2012 National Survey on hallucinogens in the treatment of revealed. Proc Natl Acad Sci U S A Drug Use and Health: Summary of : From indirect evidence to 109(6): 1820–1821, 2012. National Findings, NSDUH Series H-44, testable hypotheses. 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 5. Bonson, K.R. Hallucinogenic Drugs. In on Drugs. Ketamine use: A review. Abuse and Mental Health Services Encyclopedia of Life , Nature 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, P.M.; 6. Passie, T.; Halpern, J.H.; Stichtenoth, J.A. PCP: From to Bachman, J.G.; and Schulenberg, J.E. D.O.; Emrich, H.M.; and Hintzen, A. modelling schizophrenia. Curr Opin 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.W.; Rothman, for Social Research, the University of R.B.; and Prisinzano, T.E. Michigan, 2014. 7. Nichols, D.E. Hallucinogens. Pharmacol of the naturally Ther 101(2): 131–181, 2004. occurring kappa-opioid hallucinogen 3. Hibell, B.; Guttormsson, U.; Ahlström, . Pharmacol Rev 63(2): S.; Balakireva, O.; Bjarnason, T.; 8. Schindler, E.A.; Dave, K.D.; Smolock, 316–347, 2011. Kokkevi, A.; and Kraus, L. The 2011 E.M.; Aloyo, V.J.; and Harvey, J.A. ESPAD Report: Substance Use Among and 13. MacLean, K.A.; Johnson, M.W; Students in 36 European Countries. distinctions in the behavioral Reissig, C.J.; Prisinzano, T.E.; and Stockholm, Sweden: The Swedish pharmacology of (+/-)-1-(2,5-dimethoxy- Griffiths, R.R. -related effects of Council for Information on Alcohol and 4-iodophenyl)-2-aminopropane (DOI) salvinorin A in humans: Dissociative, Other Drugs (CAN), 2012. and lysergic acid diethylamide (LSD). hallucinogenic, and memory effects. Pharmacol Biochem Behav 101(1): (Berl). 226(2): 69–76, 2012. 381–392, 2013.

NIDA Research Report Series 7 Where Can I Get More Scientific Information on Hallucinogen Abuse?

To learn more about hallucinogens What’s on the NIDA Web Site Other Web Sites Information on hallucinogen and and other drugs of abuse, or • Information on drugs of abuse and dissociative drugs is also available to order materials on these related health consequences topics free of charge in English through these other Web sites: • NIDA publications, news, and or Spanish, visit the NIDA events • Substance Abuse and Mental Web site at www.drugabuse. Health Services Administration • Resources for health care gov or contact the DrugPubs Health Information Network: professionals Research Dissemination Center at www.samhsa.gov 877-NIDA-NIH (877-643-2644; • Funding information (including TTY/TDD: 240-645-0228). program announcements and • Drug Enforcement Administration: deadlines) http://www.deadiversion.usdoj.gov • International activities • Monitoring the Future: • Links to related Web sites (access http://www.monitoringthefuture.org/ to Web sites of many other • The Partnership at Drug Free.org: organizations in the field) http://www.drugfree.org/drug-guide NIDA Web Sites www.drugabuse.gov www.teens.drugabuse.gov www.drugabuse.gov/publications/ term/160/DrugFacts http://easyread.drugabuse.gov

For Information

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NIH Publication Number 14-4209 • Revised January 2014 Feel free to reprint this publication.

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