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Home , Euphoria, Ketamine, MDMA, Mescaline

Club : MDMA, Gamma-Hydroxybutyrate (GHB), Rohypnol, and PAUL M. GAHLINGER, M.D., PH.D., M.P.H., University of Utah Health Sciences Center, Salt Lake City, Utah

Club drugs are substances commonly used at , music festivals, , and dance to enhance social intimacy and sensory . The most widely used club drugs are 3,4-methylene- O A patient infor- dioxymethamphetamine (MDMA), also known as ; gamma-hydroxybutyrate (GHB); mation handout on (Rohypnol); and ketamine (Ketalar). These drugs are popular because of their low cost and convenient club drugs, written by the author of this distribution as small pills, powders, or liquids. Club drugs usually are taken orally and may be taken in article, is provided combination with each other, with , or with other drugs. Club drugs often are adulterated or on page 2627. misrepresented. Any club overdose should therefore be suspected as polydrug use with the actual substance and dose unknown. Persons who have adverse reactions to these club drugs are likely to consult a family physician. Toxicologic screening generally is not available for club drugs. The primary management is supportive care, with symptomatic control of excess stimulation or . There are no specific except for flunitrazepam, a that responds to flumazenil. Special care must be taken for immediate control of , , rhab- domyolysis, and syndrome. Severe drug reactions can occur even with a small dose and may require critical care. overdose usually resolves with full recovery within seven hours. Education of the patient and family is essential. (Am Fam Physician 2004;69:2619-26,2627. Copyright© 2004 Ameri- can Academy of Family Physicians)

lthough alcohol remains the TABLE 1 primary “social lubricant,” it has Street Names for “Club Drugs” been joined by many newer psy- choactive drugs that are used MDMA Ecstasy, X, M, E, XTC, rolls, beans, to intensify social exeriences. Clarity, Adam, lover’s speed, hug ABecause of the prevalence of these drugs drug at dance parties, raves, and nightclubs, they GHB G, liquid ecstasy, Grievous Bodily Harm, gib, soap, scoop, nitro often are referred to as “club drugs.” The most prominent club drugs are MDMA (3,4-methy- GBL* Blue Nitro, GH Revitalizer, Gamma G lenedioxymethamphetamine), also known as BD* Weight Belt Cleaner, Serenity, ecstasy; gamma-hydroxybutyrate (GHB); fluni- Thunder Nectar, Revitalize Plus trazepam (Rohypnol); and ketamine (Ketalar). Flunitrazepam Mexican valium, circles, roofies, Table 11 lists the various street names for these (Rohypnol) la rocha, roche, rophies, R2, rope, forget-me pill agents. Ketamine K, special K, super K, vitamin K, Club drugs are favored over other recre- (Ketalar) kit-kat, keets, super acid, jet, cat ational drugs, such as marijuana, lysergic acid valiums diethylamide (LSD), , and opi- ates, because they are believed to enhance social MDMA = 3,4-methylenedioxymethamphetamine; GHB interaction. They often are described as “entac- = gamma-hydroxybutyrate; GBL = gamma butyrolac- togens,” giving a of physical closeness, tone; BD = 1,4-butanediol. , and . MDMA is structurally *—Chemical precursors of GHB. similar to and , which is Information from Gahlinger PM. Illegal drugs: a com- a . However, it is not as stimulat- plete guide to their history, chemistry, use and abuse. ing or addictive as amphetamine, and is consid- New York: Plume, 2004:169-72. ered much less likely to cause than LSD and other potent .2 GHB

Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2004 American Academy of Family Physicians. For the pri- vate, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or MDMA The most troublesome potential outcome of MDMA ingestion MDMA was developed in 1914 as an is hyperthermia and the associated “.” suppressant, but animal tests were unimpressive, and it was never tested in . In 1965, psy- chiatrists prescribed the drug to through psychologic defenses as an “empathy agent.” By and Rohypnol are powerful / 1985, illegal laboratories were producing the agents. Ketamine is a that drug for recreational use, and it was classified produces a dreamy tranquility and as a schedule I . in small doses. Unlike , these MDMA has become the most common stimu- encourage sociability and seldom cause nausea. lant found in dance clubs and is available at 70 The popularity of these club drugs is due percent of raves.8 MDMA usually is sold as small to their low cost and convenient distribution tablets of variable colors imprinted with popular as small pills, powders, or liquids that can be icons or words. A high proportion of MDMA taken orally. Consequently, these drugs are pills are adulterated with substances such as caf- popular among young persons who have been feine, ,9 ,10 or educated about the hazards of drug potent hallucinogens such as LSD, paramethoxy- and the dangers of , , and meth- amphetamine (PMA),methylenedioxyamphetamine amphetamine. However, most users are unaware (MDA), N-ethyl-3,4-methylenedioxyamphetamine that MDMA is a type of methamphetamine, and (MDEA), and 4-bromo-2,5-dimethoxyamphet- incorrectly assume that substances that appear amine (2-CB).11 Many of these substances are as pharmaceuticals are safe to use. “designer drugs” that are illicitly manufactured Club drugs often are taken together, with variants of pharmaceuticals and have intentional alcohol, or with other drugs to enhance their and unintentional effects. For example, MDEA effect. Often, they are misrepresented, adul- (“Eve”), 2-CB, and PMA (“death”) are substituted terated, or entirely substituted for another but have primarily hallucinogenic, substance without the users’ knowledge. These and often unpleasant, effects.1 actions result in an extraordinarily high risk of MDMA ingestion increases the release of unanticipated effects and overdose.3 serotonin, , and from In the past 10 years, there has been a general- presynaptic and prevents their metabo- ized decrease in the use of marijuana, cocaine, lism by inhibiting . Effects and heroin in the , according to of an oral dose appear within 30 to 60 minutes statistics from the Drug Enforcement Admin- and last up to eight hours.12 A quicker onset of istration, the Monitor- action can be achieved by snorting the powder ing the Future Study, the Columbia Univer- of a crushed tablet. Users of MDMA describe sity National Survey of American Attitudes initial of agitation, a distorted sense of on , the Community Epidemiol- time, and diminished hunger and thirst, followed ogy Working Group, and the Partnership for a by euphoria with a sense of profound insight, Drug-Free America.4 However, during this same intimacy, and well-being.13 To further enhance period, the use of club drugs has dramatically the sensory effects, users often wear fluores- increased.5 A 2001-2002 Chicago household cent necklaces, bracelets, and other accessories, survey6 of 18- to 40-year-old persons showed and apply mentholated ointment on their lips that 38 percent had attended a , and 49 or spray on a surgical mask. percent of these had a taken a club drug. One Unpleasant side effects of MDMA include tris- Australian study7 showed that only 8 percent mus and , which can be reduced by suck- of club-goers had not consumed any psychoac- ing on a pacifier or lollipop.14 tive substance. Adverse effects of MDMA ingestion result

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from sympathetic overload and include tachy- naturally in the central nervous system, where cardia, , diaphoresis, tremor, hyperten- it is believed to mediate cycles, body tem- sion,15 arrhythmias,16 ,17 esophoria perature, cerebral glucose , and (tendency for eyes to turn inward), and uri- memory.31 nary retention.18 However, the most trouble- GHB was first synthesized in France in 1960 some potential outcome of MDMA ingestion is as an anesthetic. It later achieved popularity as a hyperthermia19 and the associated “serotonin recreational drug and a nutritional supplement syndrome.” Serotonin syndrome is manifested by marketed to bodybuilders.32 Nonprescription grossly elevated core body temperature, rigid- sales in the United States were banned in 1990 ity, myoclonus, and autonomic instability;20 it because of adverse effects, including uncon- results in end-organ damage, trolled movements and depression of the respi- and acute renal failure, hepatic failure, adult ratory and central nervous systems (CNS).33,34 respiratory distress syndrome, and coagulopa- In 2000, with 60 deaths reported from overdose thy.21 and concern over its use as a “date rape” drug, MDMA ingestion directly causes a rise in GHB was reclassified as a schedule I controlled antidiuretic hormone.22 Heat from the exertion substance.35 In 2002, oxybate, a formu- of dancing in a crowded room coupled with the lation of GHB, was approved for the treatment MDMA-induced hyperthermia can lead easily of narcolepsy and classified as schedule III. to excessive water intake and severe hyponatre- Recently, has been studied as a mia.23 Neurologic effects include , treatment for alcohol withdrawal.36,37 delirium, , headache, , depres- GHB is easily manufactured from industrial sion, , , and , all of chemicals. Internet Web sites offer instructions which may continue for several weeks. for home production and sell kits with the Two days after ingestion of MDMA, users requisite materials. GHB is chemically related typically experience depression consistent with to gamma butyrolactone and 1,4-butanediol, serotonin depletion,24 which may be severe.25 which are metabolized in the body to GHB.38 One study26 showed that, compared with alco- The salty powder usually is dissolved in water hol withdrawal, persons who are withdraw- and sold at $5 to $10 per dose. Overdose is ing from MDMA were more depressed, irritable, common because the strength of the solution is and unsociable. Repeated use of MDMA has often unknown. The unpleasant salty or soapy been associated with cognitive deficits in animals taste may be masked in flavored or alcoholic and humans, with potentially permanent memory beverages.39 Effects of GHB appear within 15 to impairment.27,28 30 minutes of oral ingestion and peak at 20 to A number of products are sold legally as 60 minutes, depending on whether it is mixed with “herbal ecstasy.” These products, available in food. is increased if taken with alcohol health food stores or on the Internet, con- or other CNS .40 tain such as , , and GHB produces euphoria, progressing with guarana, with variable additions of common higher doses to dizziness, , hypo- herbs or vitamins.29 Users of these products tonia, and .41 Overdose may result in may believe they are safe alternatives to MDMA, Cheyne-Stokes respiration, seizures, coma, and but several cases of toxic overdose have been death. Coma may be interrupted by agitation, reported from the intense stimulation of ephed- with flailing activity described similar to a rine or excessive caffeine.30 drowning swimmer fighting for air.42 Bradycar- dia and hypothermia are reported in about one GHB third of patients admitted to a hospital for using GHB is a derivative of the inhibitory neu- GHB and appear to be correlated with the level rotransmitter -aminobutyric acid and occurs of .43 Chronic use of GHB may

JUNE 1, 2004 / VOLUME 69, NUMBER 11 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN-2621 norepinephrine, dopamine, serotonin, and glu- Gamma-hydroxybutyrate (GHB) produces euphoria, progress- tamate activation in the N-methyl-D-aspartate 49 ing with higher doses to dizziness, hypersalivation, hypotonia, channel. This agent can cause bizarre ideations and —side effects that and amnesia. limited its medical use but appealed to recre- ational drug users. Ketamine is difficult to manufacture; there- produce dependence and a withdrawal syndrome fore, most of the illicit supply is diverted from that includes , insomnia, tremor, and in and veterinary products. As severe cases, treatment-resistant psychoses.44 a pharmaceutical, ketamine is distributed in a liquid form that can be ingested or injected. In Rohypnol clubs, it usually has been dried to a powder and Flunitrazepam, marketed as Rohypnol, is a is smoked in a mixture of marijuana or , potent benzodiazepine with a rapid onset. Manu- or is taken intranasally. A typical method uses factured by Roche Laboratories, it is available a nasal inhaler, called a “bullet” or “bumper”; in more than 60 countries in Europe and Latin an is called a “bump”. Ketamine often America for preoperative anesthesia, , is taken in “trail mixes” of methamphetamine, and treatment of insomnia. In the United States, cocaine, citrate (Viagra), or heroin.50 imported Rohypnol came to prominence in the Effects of ketamine ingestion appear rapidly 1990s as an inexpensive recreational sedative and last about 30 to 45 minutes, with sensations and a “date rape” drug.45 The tablets are sold on of floating outside the body, visual hallucina- the street for $0.50 to $5 a piece. tions, and a dream-like state.51 Along with these In a single 1- or 2-mg dose, Rohypnol reduces “desired” effects, users also commonly experience anxiety, inhibition, and muscular tension with confusion, , and delirium. a that is approximately 10 times that They also may experience , palpita- of (Valium). Higher doses produce tions, hypertension, and respiratory depression anterograde amnesia, lack of muscular control, with apnea. “Flashbacks” or visual disturbances and loss of consciousness. Effects occur about can be experienced days or weeks after inges- 30 minutes after ingestion, peak at two hours, tion.32 Some chronic users become addicted and and may last up to eight to 12 hours. The effects exhibit severe withdrawal symptoms that require are much greater with the concurrent inges- detoxification. tion of alcohol or other sedating drugs. Some users experience , dizziness, confu- Treatment sion, visual disturbances, , or Because club drugs are illicitly obtained and aggressive behavior.46 often are adulterated or substituted, they must Like other , chronic use of be considered as unknown substances. In the Rohypnol can produce dependence. The with- ever-changing world of illegal drug distribu- drawal syndrome includes headache, tension, tion, Internet Web sites can be helpful in identi- anxiety, restlessness, muscle , photosensitiv- fying the rapidly changing appearances of these ity, numbness and tingling of the extremities, and substances (Table 2). increased seizure potential.47 The immediate concern with the use of club drugs is cardiorespiratory maintenance. Users Ketamine often present with multiple drug ingestions, Ketamine was derived from which may include and (PCP) in the 1960s for use as a dissociative anes- drugs (e.g., MDMA combined with GHB or thetic.48 It causes anesthesia without respiratory alcohol). When the predominant symptoms are depression by inhibiting the neuronal uptake of controlled, the symptoms of a second under-

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Club Drug Treatment Pathway

What drug was taken?

TABLE 2 Internet Resources on “Club Drugs” Not sure Positive identification of drug http://www.clubdrugs.org Yes http://www.drugabuse.com Ask for sample, description, Consider adulteration, http://www.drugabuse.gov/drugpages/clubdrugs.html or visual identification. or drug substitution. http://www.drugdigest.org http://www.drugid.org No http://www.erowid.org http://www.streetdrugs.org

Cardiac monitoring Pulse oximetry Urinalysis lying drug may surface. Most hallucinogens Chemistry panel are CNS stimulants; in overdose, patients may Toxicology screen Seizure precautions exhibit hyperthermia, hypertension, tachycardia, Consider escape and self-injury risk. anxiety, and agitation. The risk of escape or self- injury also should be considered. No standard treatment regimen has been iden- If less than 60 minutes since ingestion, tified for club . Basic management consider gastric lavage. should include cardiac monitoring, pulse oxim- etry, urinalysis, and performance of a compre- hensive chemistry panel to check for Stimulants: Depressants: imbalance, renal toxicity, and possible underly- MDMA Flunitrazepam Flumazenil ing disorders (Figure 1). Precautions should be Amphetamines (Rohypnol) 19 Hallucinogens (e.g., LSD, 2-CB) GHB taken to prevent seizures. Ketamine (Ketalar) Gastrointestinal decontamination with acti- vated charcoal and a cathartic may be use- ful in acute exposures if the drug was taken Anxiety or agitation: diazepam (Valium), lorazepam (Ativan), or (Versed) orally within the previous 60 minutes. Other- Severe hypertension: labetalol (Normodyne), wise, unless a massive dose was taken, inducing phentolamine (Regitine), or nitroprusside emesis is seldom effective and may increase psy- (Nipride) Hyperthermia: rapid cooling chologic distress. Hypertension and tachycardia Serotonin syndrome: generally will resolve with the management of (Periactin) or (Thorazine) anxiety or agitation. Severe hypertension can be Rhabdomyolysis: alkaline IV fluids (D5W with sodium bicarbonate) treated with labetalol (Normodyne), phentol- amine (Regitine), nitroprusside (Nipride), or simi- lar agents. For agitation, benzodiazepines such as diazepam, lorazepam (Ativan), or midazolam Provide supportive care. (Versed) may be used.52 Consider flight risk. Hyperthermia should be treated immedi- Consider psychiatric consult. Provide education to patient and family. ately with tepid water bathing and fanning. One study53 reported that a single tablet of FIGURE 1. Algorithm for the management and treatment of ingestion of a ”club MDMA resulted in fatal hyperthermia. The use drug.” (MDMA = 3,4-methylenedioxymethamphetamine; LSD = lysergic acid of dantrolene (Dantrium) is questionable and diethylamide; 2-CB = 4-bromo-2,5-; GHB = gamma- no longer recommended.54 Alkalinization of the hydroxybutyrate; IV = intravenous) , which usually is recommended for rhab-

JUNE 1, 2004 / VOLUME 69, NUMBER 11 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN-2623 Rohypnol and its active 7-amino- There are no specific antidotes for ingestion of club drugs, flunitrazepam may be detected by gas chroma- except for Rohypnol, which has the flumazenil. tography/mass spectrometry testing up to 72 hours after ingestion. For assistance with assay in cases of suspected rape, contact Roche Labo- ratories (800-608-6540) for a free screening domyolysis, should be used cautiously because it for Rohypnol. Tests for ingestion of ketamine reduces the renal clearance of amphetamine. The are seldom available, but ketamine may be sus- serotonin antagonists chlorpromazine (Thora- pected if a toxicologic test is positive for PCP.58 zine) and cyproheptadine (Periactin) appear to be Providing the patient and family with educa- effective in mild to moderate cases of serotonin tional materials about specific substances may syndrome.55 be helpful. These materials are available on many There are no specific antidotes for ingestion Web sites. of club drugs, except for Rohypnol, which has the antidote flumazenil. With supportive care, The author indicates that he does not have any con- patients usually will recover completely within flicts of . Sources of funding: none reported. seven hours. REFERENCES GHB has a rapid elimination, and the drug is cleared within four to six hours after ingestion, 1. Gahlinger PM. Illegal drugs: a complete guide to their history, chemistry, use and abuse. New York: regardless of the dose. Intubation should be Plume, 2004. avoided unless it is absolutely necessary, because 2. Cami J, Farre M, Mas M, Roset PN, Poudevida S, Mas patients may become unexpectedly combative or A, et al. Human of 3,4-methylene- 56 dioxymethamphetamine (“ecstasy”): psychomotor have protracted periods of emesis. The presence performance and subjective effects. J Clin Psycho- of suggests ingestion of stimulants and pharmacol 2000;20:455-66. makes intubation more difficult. A benzodiaz- 3. Drug Abuse Warning Network. Club drugs. Rockville, Md: Office of Applied Studies, Substance Abuse and epine may be given for withdrawal symptoms. Mental Health Services Administration (SAMHSA), Urine or blood tests for amphetamine or meth- 2000. amphetamine may detect MDMA; these tests also 4. Partnership Attitude Tracking Study Spring 2000. Teens in grades 7 through 12. Accessed March 17 will detect MDMA-related compounds such as 2004 at: http://www.drugfreeamerica.org/acrobat/ 2-CB, but with decreased sensitivity.57 A 50-mg pats2000full.pdf. dose of MDMA can be detected as unchanged 5. Koesters SC, Rogers PD, Rajasingham CR. MDMA (‘ecstasy’) and other ‘club drugs.’ The new epidemic. drug in the urine up to 72 hours after ingestion. Pediatr Clin North Am 2002;49:415-33. Standard toxicologic tests cannot detect GHB, 6. Fendrich M, Wislar JS, Johnson TP, Hubbell A. A but the National Forensic Laboratory (National contextual profile of club drug use among adults in Chicago. 2003;98:1693-1703. Medical Services, 800-522-6671) will perform 7. Lenton S, Boys A, Norcross K. Raves, drugs and expe- urinalysis for detection of GHB for a fee. rience: drug use by a sample of people who attend raves in Western . Addiction 1997;92:1327- 37. The Author 8. National Institute on Drug Abuse. The Monitoring the Future national results on adolescent drug use: PAUL M. GAHLINGER, M.D., Ph.D., M.P.H., is an adjunct professor in the Department of overview of key findings, 2001. Ann Arbor, Mich: Family and Preventive at the University of Utah Health Sciences Center, Salt University of Michigan Institute for Social Research, Lake City, where he completed an occupational and environmental medicine residency. 2002. He received his medical degree from the University of California-Davis School of Medi- 9. Graeme KA. New drugs of abuse. Emerg Med Clin cine. Dr. Gahlinger also is in private practice at the Kaysville Clinic, Layton, Utah, and is a North Am 2000;18:625-36. medical review officer for the Bioastronautics Research Division, NASA. 10. Baggott M, Heifets B, Jones RT, Mendelson J, Sferios E, Zehnder J. Chemical analysis of ecstasy pills. JAMA Address correspondence to Paul M. Gahlinger, M.D., Ph.D., M.P.H., 225 10th Ave., Salt Lake 2000;284:2190. City, UT 84103 (e-mail: [email protected]). Reprints are not available from the author. 11. National Institute on Drug Abuse. Epidemiologic trends in drug abuse: proceedings. Rockville, Md.: National Institute on Drug Abuse, Division of Epide-

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