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Home , Anesthetic, Dextromethorphan, Dissociative, Drug, Hallucinogen, Ibogaine

N A TIONAL INSTITUTE ON ABUSE ResearchReport S E R I E S with street names like acid, angel dust, and K distort the way a user perce i v e s time, motion, colors, sounds, and self. These drugs can disrupt a person’s ability to think and communicate rationally, or even AND to recognize reality, sometimes resulting in bizarre or dangerou s be h a v i o r . Hallucinogens such Including LSD, PCP, as LSD cause to swing DRUGS , Dextrom e t h o r p h a n wildly and real-world sensations to assume unreal, sometimes Hallucinogens cause their frightening aspects. Dissociative What are ef fects by disrupting the inter- drugs like PCP and ketamine may hallucinogens? action of nerve cells and the make a user feel disconnected ne u r otransmitter serot o n i n . and out of control. allucinogens are drugs Distributed throughout the In addition to their short-term that cause — and , the serot o n i n ef fects on and mood, pr ofound distortions in a system is involved in the control LSD is associated with psychotic-like H person’s of rea l i t y . episodes that can occur long after of behavioral, perceptual, and Under the influence of hallucino- a person has taken the drug, and regulatory systems, including PCP and ketamine can cause gens, people see images, hear mood, hunger, body tempera- respiratory , heart sounds, and feel sensations that tu r e, sexual behavior, muscle rate abnormalities, and a with- seem real but do not exist. Some co n t r ol, and sensory perce p t i o n . drawal syndrome. Use of LSD and hallucinogens also prod u c e LSD (an abbreviation of the other hallucinogens by secondary rapid, intense emotional swings. Ge r man words for “lysergic school students has declined since 1998, but ketamine and LSD are becoming more widely used at dance clubs and all-night by older teens and young . NIDA res e a r ch is developing a clearer picture of the dangers of these -altering drugs. We have compiled the scientific in f o r mation in this report to in f o r m readers and to stren g t h e n pr evention and treatment effo r t s . and ar e that people have used to Alan I. Leshner, Ph.D. pr oduce “visions.” Di re c t o r National Institute on Drug Abuse

U . S . D e p a r t m e n t o f H e a l t h a n d H u m a n S e r v i c e s • N a t i o n a l I n s t i t u t e s o f H e a l t h 2NIDA RESEARCH REPORT SERIES

acid diethylamide”) is the drug dissociat i o n — f r om the environ - most commonly identified with ment and self. But these mind- Why do the term “” and the altering effects are not people take most widely used in this class of hallucinations. PCP and ketamine hallucinogens? drugs. It is considered the typical ar e theref o r e more prop e r l y hallucinogen, and the character- known as “dissociative anesthet- allucinogenic drugs have istics of its action and effe c t s ics.” , a widely played a role in human described in this Research Report available suppres s a n t , Hlife for thousands of years. apply to the other hallucinogens, when taken in high doses can Cu l t u r es from the tropics to the including , psilocybin, pr oduce effects similar to those ar ctic have used plants to induce and . of PCP and ketamine. states of detachment from rea l i t y The dissociative drugs act by and to precipitate “visions” What are altering distribution of the neuro- to provide mystical transmitter glutamate throu g h o u t insight. These plants contain dissociative the brain. Glutamate is involved chemical compounds, such as drugs? in perception of , res p o n s e s mescaline, psilocybin, and ibo- to the environment, and memory. gaine, that are structurally similar rugs such as PCP (phen- PCP is considered the typical to , and they prod u c e cyclidine) and ketamine, dissociative drug, and the their effects by disrupting norma l Dwhich were initially description of PCP’s actions and functioning of the serotonin sys- developed as general ef fects in this Research Report tem. Historically, hallucinogenic for surgery, distort perceptions la r gely applies to ketamine and plants were used largely for of sight and sound and produce de x t r omethorphan as well. social and religious , and feelings of detachment— their availability was limited by

Prevalence of Students Who Have Ever Used Hallucinogens and PCP

14% 14% 14% ■ 12th-graders ■ ■ ▲ 10th-graders 12 ■ 12 12 ● ■ 8th-graders 10 ▲ 10 10 ■ ▲ ▲ 8 ▲ 8 ■ 8 ■ ■ (Data not available for 6 ▲ 6 6 8th- and 10th-graders) ● ■ ▲ ▲ ▲ ● 4 ● ● 4 ▲ 4 ■ ■ ● ■ ● ■ ▲ ● ● ■ ■ 2 2 ● ● 2 0 0 0 1992 1994 1996 1998 2000 1992 1994 1996 1998 2000 1992 1994 1996 1998 2000 LSD Other Hallucinogens PCP

Source: the Future Survey, 2000 NIDA RESEARCH REPORT SERIES 3 the climate and soil conditions they req u i r e. After the develop- ment of LSD, a synthetic com- hemist , working at the Sandoz pound that can be manufactured CCorporation pharmaceutical laboratory in Switzerland, an y w h e r e, abuse of hallucino- first synthesized LSD in 1938. He was conducting res e a r ch gens became more widesprea d , on possible medical applications of various lysergic acid and from the 1960s it increa s e d compounds derived from , a that develops dramatically. All LSD manufac- on rye grass. Searching for compounds with therapeutic tu r ed in this country is intended value, Hofmann created more than two dozen ergo t - d e r i v e d for illegal use, since LSD has synthetic molecules. The 25th was called, in German, no accepted medical use in the Lys e rg - S ä u r e-Diäthylamid 25, or LSD-25. Five years after . he first created the drug, Hofmann accidentally ingested Physical a small amount and experienced a series of frightening characteristics of LSD se n s o r y effe c t s : LSD is a clear or white, odorless, “My surroundings . . . transformed themselves in more wa t e r -soluble material synthe- sized from lysergic acid, a te r rifying ways. Everything in the room spun arou n d , compound derived from a rye and the familiar objects and pieces of furni t u r e assumed fungus. LSD is the most potent gr otesque, threatening forms. They were in continuous mood- and perce p t i o n - a l t e r i n g motion, animated, as if driven by an inner res t l e s s n e s s drug known: oral doses as small . . . . Even worse than these demonic transforma t i o n s as 30 micrograms can prod u c e of the outer world were the alterations that I perce i v e d ef fects that last 6 to 12 hours. in myself, in my inner being. Every exertion of my will, LSD is initially produced in ev e r y attempt to put an end to the disintegration of the crystalline form. The pure crystal outer world and the dissolution of my ego, seemed to can be crushed to powder and be wasted effo r t. A demon had invaded me, had taken mixed with binding agents to possession of my body, mind, and .” pr oduce tablets known as “m i c r odots” or thin squares of gelatin called “window panes”; mo r e commonly, it is dissolved, discolor soon after it is manufac- receptors, and that its effects are diluted, and applied to paper tu r ed, and drug distributors often most prominent in two brain or other materials. The most apply LSD to colored paper, regions: One is the cerebral cor- common form of LSD is called making it difficult for a buyer to tex, an area involved in mood, “blotter acid”—sheets of paper de t e r mine the drug’s purity or age. , and perception; the soaked in LSD and perfo r a t e d other is the locus ceruleus, into 1/4-inch square, individual LS D ’ s effects which receives sensory signals dosage units. Variations in manu- The precise mechanism by which fr om all areas of the body and facturing and the presence of LSD alters perceptions is still has been described as the brain’s contaminants can produce LSD un c l e a r . Evidence from laborato- “novelty detector” for important in colors ranging from clear or ry studies suggests that LSD, like ex t e r nal stimuli. white, in its purest form, to tan hallucinogenic plants, acts on LSD’s effects typically begin or even black. Even uncontami- certain groups of serot o n i n within 30 to 90 minutes of inges- nated LSD begins to degrade and receptors designated the 5-HT2 tion and may last as long as 4NIDA RESEARCH REPORT SERIES

Structure of Serotonin and Selected Hallucinogens

SEROTONIN LYSERGIC ACID DIETHYLAMIDE - LSD

PSILOCYBIN MESCALINE

Hallucinogenic drugs are much like the serotonin in their molecular structure as well as where and how they act in the brain.

12 hours. Users refer to LSD ality, mood, expectations, and user’s emotions may shift rapidly and other hallucinogenic experi- su r ro u n d i n g s . th r ough a range from fear to ences as “trips” and to the acute Users of LSD may , with transitions so adverse as “bad some physiological effects, such rapid that the user may seem to trips.” Although most LSD trips as increased pres s u r e and experience several emotions include both pleasant and , , loss of si m u l t a n e o u s l y . unpleasant aspects, the drug’s appetite, dry mouth, sweating, LSD also has dramatic effe c t s ef fects are unpredictable and , numbness, and trem o r s ; on the . Colors, smells, may vary with the amount but the drug’s major effects are sounds, and other sensations ingested and the user’s person- emotional and sensory. The seem highly intensified. In some NIDA RESEARCH REPORT SERIES 5 cases, sensory perceptions may of LSD. The causes of these Because HPPD symptoms may blend in a phenomenon known ef fects, which in some users be mistaken for those of other as , in which a person occur after a single experience ne u r ological disorders such as seems to hear or feel colors and with the drug, are not known. st r oke or brain tumors, suffe re r s see sounds. Ps y c h o s i s . The effects of may consult a variety of clinicians Hallucinations distort or trans- LSD can be described as drug- be f o r e the disorder is accurately fo r m shapes and movements, induced —distortion diagnosed. There is no estab- and they may give rise to a per- or disorganization of a person’s lished treatment for HPPD, ception that time is moving very capacity to recognize rea l i t y , although some antidepres s a n t slowly or that the user’s body is think rationally, or communicate drugs may reduce the symptoms. changing shape. On some trips, with others. Some LSD users may help patients users experience sensations that experience devastating psycho- adjust to the associated ar e enjoyable and mentally stim- logical effects that persist after with visual distraction and to ulating and that produce a the trip has ended, producing a minimize the fear, expressed of heightened understanding. long-lasting psychotic-like state. by some, that they are suffe r i n g Bad trips, however, include terri- LSD-induced persistent psychosis brain damage or psychiatric fying and nightmarish may include dramatic mood di s o r d e r . feelings of and despair swings from to prof o u n d that include fears of insanity, de p r ession, vivid visual disturb- What are the facts , or losing control . ances, and hallucinations. These LSD users quickly develop a ef fects may last for years and about dissociative can affect people who have no high degree of tolerance for the history or other symptoms of drugs? drug’s effects: After repeated use, psychological disorder. they need increasingly large r PC P ’ s forms and effe c t s Hallucinogen Persisting doses to produce similar effe c t s . CP , developed in the 1950s Pe r ception Disorde r . Some LSD use also produces tolerance as an intravenous surgi c a l fo r mer LSD users report experi- for other hallucinogenic drugs ences known colloquially as Panesthetic, is classified as a such as psilocybin and mescaline, “flashbacks” and called “HPPD” dissociative : Its seda- but not to drugs such as mari- by . These episodes tive and anesthetic effects are juana, , and PCP, are spontaneous, repeated, -like, and patients experi- which do not act directly on the sometimes continuous recur- ence a feeling of being “out of se r otonin receptors affected by rences of some of the sensory body” and detached from their LSD. Tolerance for LSD is short- distortions originally produced en v i r onment. PCP was used in lived—it is lost if the user stops by LSD. The experience may veterinary but was taking the drug for several days. include hallucinations, but it never approved for human use Th e r e is no evidence that LSD most commonly consists of visual because of problems that aros e pr oduces physical withdrawal disturbances such as seeing false during clinical studies, including symptoms when chronic use is motion on the edges of the field and extreme agitation stopped. of vision, bright or colored flash- experienced by patients emergi n g Two long-term effe c t s — es, and halos or trails attached to fr om . persistent psychosis and hallu- moving objects. This condition is During the 1960s, PCP in pill cinogen persisting perce p t i o n typically persistent and in some fo r m became widely abused, but disorder (HPPD), more common- cases remains unchanged for the surge in illicit use rec e d e d ly ref e r r ed to as “flashbacks”— years after individuals have rapidly as users became dissatis- have been associated with use stopped using the drug. fied with the long delay between 6NIDA RESEARCH REPORT SERIES

taking the drug and feeling its Po w d e r ed PCP—known as can result in fracture or in e ffects, and with the unpre- “ozone,” “rocket fuel,” “love damage or failure as a dictable and often violent boat,” “hog,” “embalming fluid,” consequence of muscle cells behavior associated with its use. or “superweed”—ap p e a r ed in br eaking down. Very high doses the 1970s. In powdered form, the of PCP can cause convulsions, drug is sprinkled on marijuana, coma, , and death. Street Names for , or parsley, then smoked, PCP’s effects are unpred i c t a b l e . Hallucinogens and and the onset of effects is rapid. Typically, they are felt within Dissociative Drugs Users sometimes ingest PCP by minutes of and last for snorting the powder or by swal- several hours. Some users rep o r t lowing it in form. Norma l l y feeling the drug’s effects for LS D a white crystalline powder, PCP days. One drug-taking episode ■ acid may produce feelings of detach- ■ is sometimes colored with - blotter ment from reality, including ■ blotter acid soluble or -soluble dyes. distortions of space, time, and ■ dots When snorted or smoked, ■ microdot PCP rapidly passes to the body image; another may pro- ■ pane brain to disrupt the functioning duce hallucinations, panic, and ■ paper acid of sites known as NMDA fe a r . Some users report feelings ■ sugar (N-methyl-D-aspartate) of invulnerability and exagger- ■ sugar cubes complexes, which are receptors ated strength. PCP users may ■ trip for the neurotransmitter gluta- become severely disoriented, ■ window glass mate. Glutamate receptors play violent, or suicidal. ■ window pane a major role in the perc e p t i o n Repeated use of PCP can ■ Zen of pain, in cognition—in c l u d i n g result in , and re c e n t Ke t a m i n e le a r ning and memory— and in res e a r ch suggests that rep e a t e d ■ bump . In the brain, PCP also or prolonged use of PCP can ■ cat Valium alters the actions of , cause withdrawal syndrom e ■ green a neurotransmitter res p o n s i b l e when drug use is stopped. ■ oil for the euphoria and “rush” Symptoms such as memory ■ jet associated with many abused ■ loss and depression may persist K dr u g s . ■ purple for as long as a year after a At low PCP doses (5 mg or ■ Special K ch r onic user stops taking PCP. ■ special la coke less), physical effects include ■ super acid shallow, rapid brea t h i n g , Na t u r e and effects ■ super C in c r eased blood pres s u r e and of ketamine ■ vitamin K heart rate, and elevated tempera- Ketamine (“K,” “Special K,” tu r e. Doses of 10 mg or more “cat Valium”) is a dissociative PC P cause dangerous changes in anesthetic developed in 1963 ■ angel blood pres s u r e, heart rate, and to replace PCP and curren t l y ■ angel dust respiration, often accompanied used in human anesthesia and ■ boat by nausea, blurred vision, dizzi- veterinary medicine. Much of the ■ dummy dust ■ love boat ness, and decreased awaren e s s ketamine sold on the street has ■ peace of pain. Muscle contractions may been diverted from veterinarians’ ■ supergrass cause uncoordinated movements of fices. Although it is manufac- ■ zombie and bizarre postures. When tu r ed as an injectable liquid, in se v e r e, the muscle contractions illicit use ketamine is generally NIDA RESEARCH REPORT SERIES 7

The effects vary with , and de x t r omethorphan users describe a set of distinct dose-dependent “plateaus” ranging from a mild effect with distorted visual perceptions at low (a p p r oximately 2-ounce) doses to a sense of complete dissocia- tion from one’s body at doses of 10 ounces or more. The effe c t s typically last for 6 hours. Over- the-counter that contain dextromethorphan often contain and decon- gestant ingredients as well, and high doses of these mixtures can seriously increase risks of Ex t r a - s t r ength cough is the most common source of abused dextrom e t h o r p h a n . de x t r omethorphan abuse. evaporated to form a powder sion of sexual assaults ref e r r ed to that is snorted or compres s e d as “drug rape.” Where can I get into pills. more scientific Ketamine’s chemical structure Na t u r e and effects and are of dextrom e t h o r p h a n information on similar to those of PCP, and its De x t r omethorphan (sometimes hallucinogens ef fects are similar, but ketamine called “DXM” or “robo”) is a is much less potent than PCP co u g h - s u p p r essing ingredient in and dissociative with effects of much shorter a variety of over-the-counter cold drugs? duration. Users report sensations and cough medications. Like PCP ranging from a pleasant feeling and ketamine, dextrom e t h o r p h a n act sheets on LSD, PCP, other of floating to being separated acts as an NMDA receptor antag- illicit drugs, and related topics fr om their bodies. Some keta- onist. The most common source Far e available free, in English mine experiences involve a of abused dextromethorphan is and Spanish, with a call to NIDA terrifying feeling of almost com- “e x t r a - s t r ength” cough syrup, Infofax at 1-888-NIH-NIDA plete sensory detachment that is which typically contains 3 mil- (1-888-644-6432) or, for the deaf, likened to a near-death experi- ligrams of the drug per milliliter 1- 8 8 8 - T T Y -NIDA (1-888-889-6432). ence. These experiences, similar of syrup. At the doses rec o m - Further information on to a “” on LSD, are called mended for treating hallucinogens and dissociative the “K-hole.” (1/6 to 1/3 ounce of , drugs can be obtained also Ketamine is odorless and taste- containing 15 mg to 30 mg th r ough NIDA’s home page less, so it can be added to bever- de x t r omethorphan), the drug is (www.drugabuse.gov) and from ages without being detected, and safe and effective. At much the National Clearinghouse for it induces . Because of higher doses (4 or more ounces), Alcohol and Drug Informa t i o n these , the drug is de x t r omethorphan produces (NCADI) at 1-800-729-6686. sometimes given to unsuspecting dissociative effects similar to NCADI’s Web site is www.health.org. victims and used in the commis- those of PCP and ketamine. 8NIDA RESEARCH REPORT SERIES

Gl o s s a r y Ac i d : Common street name for LSD. Ha l l u c i n o g e n : A drug that produces NM D A : N-m e t h y l - D - a s p a r tate, a chemical ha l l u c i n a t i o n s — d i s t o r tion in perception of compound that reacts with glutamate rec e p t o r s Angel dust: Common street name for PCP. sights and sounds—and disturbances in on nerve cells. emotion, judgment, and memory. Ce r ebral corte x : Region of the brain res p o n s i - PC P : , a dissociative anesthetic ble for cognitive functions including rea s o n i n g , HP P D : Hallucinogen persisting perception abused for its mind-altering effe c t s . mood, and perception of stimuli. di s o r der; the spontaneous and sometimes con- Persistent psychosis: Un p r edictable tinuous rec u r rence of perceptual effects of LSD and long-lasting visual disturbances, dramatic Dissociative anesthetic: Compound, such as long after an individual has ingested the drug . phencyclidine or ketamine, that produces an mood swings, and hallucinations experienced anesthetic effect characterized by a feeling of Ke t a m i n e : Dissociative anesthetic abused for by some LSD users after they have discontinued being detached from the physical self. its mind-altering effects and sometimes used to use of the drug. facilitate sexual assault. Ro b o : Common street name for DX M : Common street name for dextrom e t h o r - de x t ro m e t h o r p h a n . ph a n . Locus cerul e u s : Region of the brain that receives and processes sensory signals from all Se ro t o n i n : A neurotransmitter that causes Fl a s h b a c k : Slang term for HPPD (see below). ar eas of the body. a very broad range of effects on perce p t i o n , movement, and the emotions by modulating Gl u t a m a t e : A neurotransmitter associated with Ne u ro t r a n s m i t t e r : Chemical compound that the actions of other in pain, memory, and response to changes in the acts as a messenger to carry signals or stimuli most parts of the brain. en v i ro n m e n t . fr om one nerve cell to another.

Re f e re n c e s Access information Abraham, H.D.; Aldridge, A.M.; and Gogia, P. Javitt, D.C., and Zukin, S.R. Recent advances in the on the Interne t The of hallucinogens. phencyclidine model of . Am e r i c a n • Wh a t ’ s new on the NIDA Web site Ne u ro p s y c h o p h a rm a c o l o g y 14: 285-298, 1996. Jo u r nal of 148:1301-1308, 1991. • In f o r mation on drugs of abuse Aghajanian, G.K., and Marek, G.J. Serotonin and Sanders-Bush, E. Neurochemical Evidence That • Publications and communications hallucinogens. Ne u ro p s y c h o p h a rm a c o l o g y Hallucinogenic Drugs are 5-HT2c Re c e p t o r (including NIDA NO T E S ) 21: 16S-23S, 1999. : What Next? In: Lin, G.C., and Glennon, • Calendar of events Ba c k s t r om, J.R.; Chang, M.S.; Chu, H.; Niswender, R.A., eds. Hallucinogens: An Update. National C.M.; and Sanders-Bush, E. -directed sig- Institute on Drug Abuse Research Monograph • Links to NIDA organizational units naling of serotonin 5-HT2c receptors: diffe re n c e s No. 146. NIH . No. 94-3872. Was h i n g t o n , • Funding information between serotonin and lysergic acid diethylamide D.C.: U.S. Government Printing Office, 1994. (including program announcements (LSD). Ne u ro p s y c h o p h a rm a c o l o g y 21: 77S-81S, and deadlines) 19 9 9 . Un g e r l e i d e r , J.T., and Pechnick, R.N. Hallucinogens. • In t e r national activities In: Lowenstein, J.H.; Ruiz, P.; and Millman, R.B., Ca r roll, M.E. PCP and hallucinogens. Advances in eds. : A Compreh e n s i v e • Links to related Web sites Alcohol and Substance Abuse 9(1-2): 167-190, Textbook, Second Edition. Ba l t i m o r e: Williams & (access to Web sites of many other or ganizations in the field) 19 9 0 . Wilkins, 1992. Christophersen, A.S. s : an overview and epidemiology. Tox i c o l o g y Le t t e r s 112-113: 127-131, 2000. NIDA Web Sites www.drugabuse.gov Frankenheim, J. , and Lin, G.C. Hallucinogenic Dr ugs. In: Craighead, W.E., and Nemerof f, C., www.steroidabuse.org eds. Encyclopedia of and www.clubdrugs.org Ne u ro s c i e n c e . New York: John Wiley & Sons, in pres s . NIH Publication Number 01-4209 Printed March 2001 NCADI Hofmann, A. LSD: My Problem Child. New Yor k : Feel free to reprint this publication. Web Site: www.health.org McGraw-Hill, 1980. Phone No.: 1-800-729-6686