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Home , Alkaloid, Ayahuasca, Dissociative, Drug, Hallucinogen, Ketamine

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, , , DMT, and cause HALLUCINOGENS AND to swing wildly and real-world sensations to appear unreal, sometimes frightening. Dissociative drugs like PCP, DISSOCIATIVE DRUGS , , and divinorum may make a user feel out of Including LSD, Psilocybin, Peyote, DMT, Ayahuasca, control and disconnected from their body PCP, Ketamine, Dextromethorphan, and Salvia and environment.

In addition to their short-term effects What Are on and mood, hallucinogenic Hallucinogens and drugs are associated with psychotic- like episodes that can occur long after Dissociative Drugs? a person has taken the , and dissociative drugs can cause respiratory allucinogens are a class of drugs that cause —profound distortions , abnormalities, and in a person’s of reality. Hallucinogens can be found in some and a withdrawal syndrome. The good news is (or their extracts) or can be man-made, and they are commonly divided that use of hallucinogenic and dissociative Hinto two broad categories: classic hallucinogens (such as LSD) and dissociative drugs (such drugs among U.S. high school students, as PCP). When under the influence of either type of drug, people often report rapid, intense in general, has remained relatively low in emotional swings and seeing images, hearing sounds, and feeling sensations that seem real recent years. However, the introduction but are not. of new hallucinogenic and dissociative While the exact mechanisms by which hallucinogens and dissociative drugs cause drugs is of particular concern. their effects are not yet clearly understood, research suggests that they work at least partially NIDA research is developing a clearer by temporarily disrupting communication between systems throughout picture of the dangers of hallucinogenic the brain and that regulate mood, sensory perception, sleep, hunger, body and dissociative drugs. We have compiled temperature, sexual behavior, and muscle control. the scientific information in this report to inform readers and hopefully prevent the use of these drugs.

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

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

Classic Hallucinogens*

LSD (d- Peyote ()— prevents the normal breakdown of diethylamide)—also also known as buttons, DMT in the digestive tract. Ayahuasca known as acid, blotter, , and mesc— has traditionally been used for doses, hits, microdots, is a small, spineless and religious purposes in indigenous sugar cubes, trips, tabs, or window cactus with mescaline as its main South American cultures, mainly in the panes—is one of the most potent mood- ingredient. It has been used by Amazon region. and perception-altering hallucinogenic natives in northern and the southwestern as a part drugs. It is a clear or white, odorless, Dissociative Drugs water-soluble material synthesized from of religious ceremonies. The top, or lysergic acid, a compound derived from “crown,” of the peyote cactus has PCP ()—also a rye . LSD is initially produced disc-shaped buttons that are cut out, known as ozone, rocket fuel, in crystalline form, which can then dried, and usually chewed or soaked love boat, hog, embalming be used to produce tablets known as in water to produce an intoxicating fluid, or superweed—was “microdots” or thin squares of gelatin liquid. Because the extract is so bitter, originally developed in the 1950s as a called “window panes.” It can also be some users prepare a tea by boiling general for surgery. While it can diluted with water or and sold the for several hours. Mescaline be found in a variety of forms, including in liquid form. The most common form, can also be produced through tablets or capsules, it is usually sold as however, is LSD-soaked paper punched chemical synthesis. a liquid or powder. PCP can be snorted, into small individual squares, known DMT (Dimeth- smoked, injected, or swallowed. It is as “blotters.” yltryptamine)—also sometimes smoked after being sprinkled on marijuana, , or parsley. Psilocybin known as Dimitri—is a (4-phosphoryloxy- powerful hallucinogenic Ketamine—also known N, N-dimethyl- chemical found naturally occurring in as K, Special K, or cat )—also some Amazonian plant species (see Valium—is a dissociative known as magic mushrooms, shrooms, “Ayahuasca”) and also synthesized in currently used as an boomers, or little smoke—is extracted the laboratory. Synthetic DMT usually anesthetic for humans as well as . from certain types of mushrooms found takes the form of a white crystalline Much of the ketamine sold on the street in tropical and subtropical regions of powder and is typically vaporized or has been diverted from veterinary , Mexico, and the United smoked in a pipe. offices. Although it is manufactured States. In the past, psilocybin was Ayahuasca—also as an injectable liquid, ketamine is ingested during religious ceremonies by known as hoasca, generally evaporated to form a powder indigenous cultures from Mexico and aya, and yagé—is a that is snorted or compressed into pills for Central America. Psilocybin can either hallucinogenic brew illicit use. Because ketamine is odorless be dried or fresh and eaten raw, mixed made from one of several Amazonian and tasteless and has -inducing with , or brewed into a tea, and plants containing DMT (the primary , it is sometimes added to drinks produces similar effects to LSD. psychoactive ingredient) along with a to facilitate sexual assault. vine containing a natural that

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

2 NIDA Research Report Series DXM (Dextromethorphan)— Past-Year Use of Hallucinogenic and Dissociative also known as robo—is Drugs Among 12th-Grade Students a cough suppressant and 8.0 expectorant ingredient in Salvia some over-the-counter (OTC) cold and LSD 6.0 cough that are often abused PCP by adolescents and young . The most common sources of abused DXM 4.0 are “extra-strength” cough syrup, which typically contains around 15 milligrams

of DXM per teaspoon, and pills and Use in the Past Month (%) 2.0 gel capsules, which typically contain 15 milligrams of DXM per pill. OTC 0.0 medications that contain DXM often also 2007 2008 2009 2010 2011 2012 2013 2014 contain and . Source: the Future National Survey Results on Drug Use, 2014 Overview

Salvia divinorum—also known as diviner’s sage, While regular use of hallucinogenic Maria Pastora, Sally-D, and dissociative drugs in general has Why Do or magic mint—is a remained relatively low in recent years, People Take common to southern one study reported that the United States Hallucinogenic Mexico and Central and South America. ranks first among 36 nations in the or Dissociative Salvia is typically ingested by chewing proportion of high school students ever fresh leaves or by drinking their extracted using LSD or other hallucinogens in Drugs? juices. The dried leaves of salvia can also their lifetime (6 percent versus 2 percent Hallucinogenic and dissociative drugs be smoked or vaporized and inhaled. in ) (Hibell, 2012). have been used for a variety of reasons Additionally, tourism to the Amazon (Bogenschutz, 2012; Bonson, 2001). for the purpose of using ayahuasca has Historically, hallucinogenic plants have How Widespread become increasingly popular among been used for religious to induce Is the Abuse of Americans and Europeans in recent states of detachment from reality and Hallucinogens and years, and ayahuasca use has also been precipitate “visions” to provide reported in major cities in and mystical insight or enable contact Dissociative Drugs? abroad (Barbosa, 2012; McKenna, with a spirit world or “higher power.” According to the 2013 National Survey on 2004). Although DMT is a schedule More recently, people report using Drug Use and Health, 229,000 Americans I drug, plants containing DMT are hallucinogenic drugs for more social or ages 12 and older reported current (past- not scheduled, and there is ambiguity recreational purposes, including to have month) use of LSD and 33,000 reported over ayahuasca’s legal status in the fun, help them deal with stress, or enable current use of PCP ( and United States (McKenna, 2004). Two them to enter into what they perceive Mental Health Services Administration, U.S. Brazilian churches have obtained as a more enlightened of thinking 2013). Among high school seniors, salvia permission to import and use these or being. Hallucinogens have also been was significantly more popular than plants in their ceremonies. investigated as therapeutic agents to LSD or PCP when it was added to the treat associated with perceptual Monitoring the Future survey in 2009. distortions, such as , Past-year use was reported to be 5.9 obsessive-compulsive disorder, bipolar percent for salvia, 2.7 percent for LSD, disorder, and . Anecdotal reports and 1.3 percent for PCP. Fortunately, rates and small studies have suggested that have dropped significantly for saliva—to ayahuasca may be a potential treatment 1.8 percent in 2014—with LSD and PCP for substance use disorders and other use dropping slightly (Johnston, 2014). mental health issues, but no large- scale research has verified its (Barbosa, 2012).

NIDA Research Report Series 3 are often unpredictable and may vary How Do with the amount ingested and the Hallucinogens user’s personality, mood, expectations, (LSD, Psilocybin, and surroundings. The effects of Peyote, DMT, and hallucinogens like LSD can be described as drug-induced —distortion Ayahuasca) Affect or disorganization of a person’s capacity the Brain and Body? to recognize reality, think rationally, or communicate with others. Users How Do Hallucinogens refer to LSD and other hallucinogenic Work? as “trips” and to acute adverse or unpleasant experiences as Classic hallucinogens are thought to Short-Term “bad trips.” On some trips, users produce their perception-altering effects General Effects sensations that are by acting on neural circuits in the brain of Hallucinogens that use the neurotransmitter enjoyable and mentally stimulating Sensory Effects (Passie, 2008; Nichols, 2004; Schindler, and that produce a sense of heightened understanding. Bad trips, however, • Hallucinations, including 2012; Lee, 2012). Specifically, some of seeing, hearing, touching, or include terrifying and their most prominent effects occur in smelling things in a distorted the prefrontal cortex—an area involved nightmarish feelings of and way or perceiving things that in mood, , and perception—as despair that include fears do not exist well as other regions important in of losing control, insanity, or . • Intensified feelings and Like LSD and psilocybin, DMT sensory experiences (brighter regulating arousal and physiological colors, sharper sounds) produces its effects through action at responses to stress and panic. • Mixed (“seeing” serotonin (5-HT) receptors in the brain What Are the Short- sounds or “hearing” colors) (Strassman, 1996). Some research has Term Effects of • Changes in sense or suggested that DMT occurs naturally perception of time (time Hallucinogens? in the in small quantities, goes by slowly) Ingesting hallucinogenic drugs can cause leading to the hypothesis that release of Physical Effects users to see images, hear sounds, and endogenous DMT may be involved in • Increased and feel sensations that seem real but do not reports of alien abductions, spontaneous heart rate exist. Their effects typically begin within mystical experiences, and near- • Nausea 20 to 90 minutes of and can death experiences, but this remains last as long as 12 hours. Experiences controversial (Barker, 2012).

Specific short-term effects of LSD, psilocybin, peyote, DMT, and ayahuasca include:

LSD Psilocybin DMT • Increased pressure, heart • Feelings of relaxation (similar to • Increased heart rate rate, and body temperature effects of low doses of marijuana) • Agitation • Dizziness and sleeplessness • Nervousness, paranoia, and • Hallucinations frequently involving • Loss of appetite, dry mouth, panic reactions radically altered environments as and sweating • Introspective/spiritual experiences well as body and spatial distortions • Numbness, weakness, and tremors • Misidentification of poisonous mushrooms Ayahuasca • Impulsiveness and rapid emotional resembling psilocybin could lead to • Increased blood pressure shifts that can range from fear to unintentional, potentially fatal poisoning • Severe (induced by the tea) , with transitions so rapid Peyote • Profoundly altered state of awareness that the user may seem to experience • Increased body temperature and and perceptions of otherworldly imagery several emotions simultaneously heart rate • Uncoordinated movements () • Profound sweating • Flushing

4 NIDA Research Report Series What Are the Long- especially among those using the brew Term Effects of for religious activities. Hallucinogens? Overall, two long-term effects— persistent psychosis and HPPD—have LSD users quickly develop a high degree been associated with use of classic of tolerance to the drug’s effects, such hallucinogens (see sidebar). Although that repeated use requires increasingly occurrence of either is rare, it is also larger doses to produce similar effects. unpredictable and may happen more Use of hallucinogenic drugs also often than previously thought, and produces tolerance to other drugs in this sometimes both conditions occur class, including psilocybin and peyote. together. While the exact causes are not Use of classic hallucinogens does not, known, both conditions are more often however, produce tolerance to drugs that Long-Term Effects seen in individuals with a history of do not act directly on the same brain psychological problems but can happen of Hallucinogens cell receptors. In other words, there is to anyone, even after a single exposure. Persistent psychosis no cross-tolerance to drugs that act on There is no established treatment for • Visual disturbances other neurotransmitter systems, such HPPD, in which flashbacks may occur • Disorganized thinking as marijuana, , or PCP, spontaneously and repeatedly although • Paranoia among others. Furthermore, tolerance for less intensely than their initial occurrence. hallucinogenic drugs is short-lived—it is • Mood disturbances Some and lost if the user stops taking the drugs for Hallucinogen Persisting drugs can be prescribed to help improve several days—and physical withdrawal Perception Disorder (HPPD) mood and treat psychoses, however. symptoms are not typically experienced • Hallucinations may also help patients when chronic use is stopped. • Other visual disturbances cope with fear or confusion associated The long-term residual (such as seeing halos or trails with visual disturbances or other psychological and cognitive effects attached to moving objects) consequences of long-term LSD use. of peyote remain poorly understood. • Symptoms sometimes More research on the causes, incidence, Although one study found no evidence mistaken for neurological and long-term effects of both disorders is disorders (such as stroke of psychological or cognitive deficits being conducted. or brain tumor) among Native Americans who use peyote regularly in a religious setting, those findings may not generalize to those who What Are the repeatedly abuse the drug for recreational Effects of Common purposes (Halpern, 2005). Peyote users Dissociative role in cognition (including learning and may also experience hallucinogen Drugs on the memory), , and the perception of (the latter via activation of pain- persisting perception disorder (HPPD)— Brain and Body? also often referred to as flashbacks. The regulating cells outside of the brain). active ingredient mescaline has also been How Do Dissociative PCP also alters the actions of , associated, in at least one report, to Drugs Work? a neurotransmitter responsible for the fetal abnormalities (Gilmore, 2001). euphoria and “rush” associated with Laboratory studies suggest that Long-term effects of DMT use many abused drugs. dissociative drugs, including PCP, and abuse and liability are Salvia divinorum works differently. ketamine, and DXM, cause their effects currently unknown. Unlike most other While classified as a dissociative drug, by disrupting the actions of the brain hallucinogens, DMT does not appear to salvia causes its effects by activating chemical glutamate at certain types of induce tolerance (Winstock, 2013). the kappa on nerve receptors—called N-methyl-D-aspartate As with some other hallucinogens, cells (Cunningham, 2011; MacLean, (NMDA) receptors—on nerve cells there is little information to suggest 2013). These receptors differ from those throughout the brain (Morgan, 2012; that ayahuasca use creates lasting activated by the more commonly known Morris, 2005). Glutamate plays a major physiological or neurological deficits, such as and .

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 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

Disorientation, confusion, and loss of coordination Memory loss

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

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 References : The brain Barbosa PC, Mizumoto S, Bogenschutz MacLean KA, Johnson MW, Reissig CJ, and spinal cord. MP, Strassman RJ. Health status of Prisinzano TE, Griffiths RR. -related ayahuasca users. . 2012; effects of in humans: : The region of the Anal 4(7-8):601-609. dissociative, hallucinogenic, and brain responsible for cognitive memory effects. functions including reasoning, mood, Barker SA, McIlhenny EH, 2013;226(2):381-392. and perception of stimuli. (Berl). Strassman R. A critical review of reportsof endogenous psychedelic McKenna, DJ. Clinical investigations of Dissociative: a type of compound, N, N-dimethyltryptamines in humans: the therapeutic potential of ayahuasca: such as phencyclidine or ketamine, 1955-2010. . 2012; rationale and regulatory challenges. that produces an anesthetic effect Drug Test Anal Jul-Aug;4(7-8):617-35. 2004;102(2):111-129. characterized by a feeling of being Pharmacol Ther. detached from the physical self. Bogenschutz MP, Pommy JM. Morgan CJ, Curran HV, Independent Therapeutic mechanisms of classic Scientific Committee on Drugs. DXM: A common street name for hallucinogens in the treatment of Ketamine use: a review. dextromethorphan. Addiction. : from indirect evidence to 2012;107(1):27-38. testable hypotheses. Flashback: A sudden but temporary Drug Test Anal. 2012;4(7-8):543-555. Morris BJ, Cochran SM, and Pratt JA. recurrence of aspects of a drug PCP: from to modelling experience (including sights, sounds, Bonson KR. Hallucinogenic drugs. schizophrenia. and feelings) that may occur days, Curr Opin Pharmacol. In: 2005;5(1):101-106. weeks, or even more than a year after Encyclopedia of Life . : Nature Publishing hallucinogenic drug use. Group; 2001. Nichols DE. Hallucinogens. Pharmacol 2004; 101(2):131-181. Glutamate: An excitatory Ther. Bouso JC, González D, Fondevila S, neurotransmitter found throughout et al. Personality, psychopathology, Passie T, Halpern JH, Stichtenoth the brain that influences the reward life attitudes and neuropsychological DO, Emrich HM, Hintzen A. The system and is involved in learning performance among users of pharmacology of lysergic acid and memory, among other functions. Ayahuasca: a longitudinal study. PLoS diethylamide: a review. CNS 2012;7(8). 2008;14(4):295-314. Hallucinogen: A drug that produces One. Neurosci Ther. hallucinations—distortions in Cunningham CW, Rothman RB, Schindler EA, Dave KD, Smolock EM, perception of sights and sounds—and Prisinzano TE. of Aloyo VJ, Harvey JA. disturbances in emotion, judgment, the naturally occurring kappa-opioid and distinctions in and memory. hallucinogen salvinorin A. Pharmacol the behavioral pharmacology of 2011;63(2):316-347. (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2- HPPD: Hallucinogen persisting Rev. aminopropane (DOI) and lysergic acid perception disorder; the spontaneous Gilmore HT. Peyote use diethylamide (LSD). and sometimes continuous recurrence Pharmacol Biochem during pregnancy. 2012;101(1): 69-76. of perceptual effects of LSD long after S D J Med. Behav. 2001;54(1):27-29. an individual has ingested the drug. Strassman RJ. Human Halpern JH, Sherwood AR, Hudson psychopharmacology of N,N- Kappa : A receptor on JI, Yurgelun-Todd D, Pope HG Jr. dimethyltryptamine. Behav Brain Res. nerve cells that is activated by certain Psychological and cognitive effects 1996;73(1-2):121-124. opioid-like compounds produced in of long-term peyote use among the body. These receptors differ from Native Americans. Biol . Substance Abuse and Mental Health those activated by the more commonly 2005;58(8):624-631. Services Administration. Results from known opioids, such as heroin and the 2013 National Survey on Drug morphine. Hibell B, Guttormsson U, Ahlström S, et Use and Health: Summary of National al. The 2011 ESPAD Report: Substance Findings. Rockville, MD: Substance Neurotransmitter: A chemical Use Among Students in 36 European Abuse and Mental Health Services compound that acts as a messenger Countries. Stockholm, Sweden: The Administration; 2014. HHS Publication to carry signals from one nerve cell Swedish Council for Information on No. (SMA) 14-4887. NSDUH Series to another. Alcohol and Other Drugs (CAN); 2012. H-49.

NMDA receptors: N-methyl-D-aspartate Johnston LD, O’Malley PM, Bachman Winstock AR, Kaar S, Borschmann receptors, a type of JG, Schulenberg JE. Monitoring the R. Dimethyltryptamine (DMT): that is important for learning and Future national results on drug use: prevalence, user characteristics and memory; it is the target of drugs such 1975-2014. Overview of key findings abuse liability in a large global sample. as PCP and ketamine. on Adolescent Drug Use. Ann Arbor, J Psychopharmacol. 2014;28(1):49-54. MI: Institute for Social Research, The Persistent psychosis: Unpredictable University of Michigan; 2014. and long-lasting visual disturbances, dramatic mood swings, and Lee HM, and Roth BL. Hallucinogen hallucinations experienced by some actions on human brain revealed. LSD users after they have discontinued Proc Natl Acad Sci U S A. 2012; use of the drug. 109(6):1820-1821. Serotonin: A neurotransmitter involved in a broad range of effects on perception, movement, and emotions. Serotonin and its receptors are the targets of most hallucinogens.

NIDA Research Report Series 7 Where can I get further information about hallucinogens?

To learn more about hallucinogens NIDA’s website includes: For Information and other drugs of abuse, • Information on drugs of abuse visit the NIDA website at and related health consequences www.drugabuse.gov or www.drugabuse.gov/nidamed contact the DrugPubs Research • NIDA publications, news, Dissemination Center at and events Other Websites 877-NIDA-NIH (877-643-2644; • Resources for Information on hallucingens TTY/TDD: 240-645-0228). professionals, educators, and dissociative drugs is and patients and families also available through: • Funding information (including • Substance Abuse and Mental program announcements and Health Services Administration: deadlines) www.samhsa.gov • International activities • Drug Enforcement Administration: • Links to related websites www.deadiversion.usdoj.gov (access to websites of many other organizations in the field) • Monitoring the Future: www.monitoringthefuture.org/ • Information in Spanish (en español) • The Partnership at Drug Free.org: NIDA Websites and Webpages www.drugfree.org/drug-guide www.drugabuse.gov www.teens.drugabuse.gov www.easyread.drugabuse.gov www.drugabuse.gov/drugs-abuse/ hallucinogens www.drugabuse.gov/publications/ term/160/DrugFacts www.hiv.drugabuse.gov/ www.researchstudies.drugabuse.gov/ www.irp.drugabuse.gov/

NIH Publication Number 15-4209 • Revised February 2015 This publication is in the public domain and may be used or reproduced in its entirety without permission from NIDA. Citation of the source is appreciated.

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