Emerging Drugs of AbuseKavita Babu, MD, Edward W. Boyer, MD, PhD, Christina Hernon, MD, D. Eric Brush, MD

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doi:10.1016/j.cpem.2

Division of Medical

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Medical Toxicolo

of Massachusetts

Patterns of recreational drug use undergo constant change. Health care providers mustremain vigilant and informed regarding emerging drugs of abuse to care better for theirpatients. There is also a role for improved surveillance and characterization of novel drugs.This report reviews the clinical manifestations and toxicity of several new drugs of abuse,including dextromethorphan, hallucinogenic tryptamines (including bFoxy Methoxy Q),hallucinogenic amphetamines (including 2C-B and 2C-T-7), as well as the herbalhallucinogen, Salvia divinorum.Clin Ped Emerg Med 6:81-84 ª 2005 Elsevier Inc. All rights reserved.

KEYWORDS drugs of abuse, dextromethorphan, tryptamines, hallucinogenic amphetamines,Salvia divinorum

The decreased availability of lysergic acid diethyla-

mide (LSD) in recent years has created a niche for

novel hallucinogens that are rapidly gaining popularity

among adolescents and young adults [1]. Their increased

use reflects the intensity of neuropsychiatric effects, ease

of procurement, decreased cost, presumed safety, and in

some instances, perceived legality. Unfortunately, the

emergence of these drugs, which include tryptamines,phenethylamines, and Salvia divinorum, has not been well

recognized by the medical community [1].

Clinical identification of these new drugs of abuse can

be difficult, if not impossible. Routine diagnostic testing

may not identify these compounds or differentiate them

from more common drugs of abuse. Thus, the medical

literature contains few case reports of toxicity from these

substances. Essentially, the only method of determiningexposure to these hallucinogens may come from infor-

mation provided by the patient. Increasing awareness of

clinicians regarding these emerging drugs of abuse will

enable better surveillance and further characterization of

both the drugs and their users. All cases of toxicity from

nt matter ª 2005 Elsevier Inc. All rights reserved.

005.04.002

Toxicology, Department of Emergency Medicine,

assachusetts Medical School, Worcester, MA

correspondence: Kavita Babu, MD, Division of

gy, Department of Emergency Medicine, University

Medical School, Worcester, MA 01655.

recreational drug abuse should be managed in conjunc-

tion with a poison control center or toxicologist to

facilitate management and improve national surveillance.

DextromethorphanDextromethorphan (also called bDXMQ or bRoboQ) is one

of a class of compounds known as dissociative agents that

include phencyclidine (PCP, bangel dust Q) and ketamine

(bSpecial K,Q bVitamin K Q). Striking increases in dextro-

methorphan abuse have been observed recently. Toxic

Exposure Surveillance System data suggest that abuse or

misuse of the drug by adolescents between the ages of 13

and 19 years has increased more than 300% over a 3-yearperiod [2]. Interestingly, dextromethorphan abuse

appears to follow a seasonal variation, with the peak

exposures occurring between September and May. The

abuse of dextromethorphan may be slightly more prev-

alent in women [3-5].

Younger adolescents may be at greater risk for dextro-

methorphan abuse [3,4,6,7]. In reports to poison control

centers, the most common ages of children abusing thedrug were ages 14 (23.1%), 16 (21.8%), 15 (15.4%), and

13 (10.3%) [7]. Dextromethorphan abuse has been

reported in children as young as 11 years [5]. Despite

the large number of over-the-counter products that

contain dextromethorphan, 1 product line appears to be

preferred for abuse; up to 87% of dextromethorphan

abuse cases reported to poison control centers involved

81

K. Babu et al.82

Coricidin HBP (67%) or another Coricidin product

(21%) [3-5,8].

Dextromethorphan is well absorbed after ingestion,

with maximum serum concentrations occurring at

2.5 hours [9]. The major metabolite of dextromethor-

phan, dextrorphan, is the agent responsible for all

biologic activity. Dextrorphan reaches peak plasmaconcentrations at 1.6 to 1.7 hours after ingestion [10].

Dextromethorphan and its metabolites undergo renal

elimination, with less than 0.1% of the drug being

eliminated in the feces [11]. The half-life of the parent

compound is approximately 2 to 4 hours in individuals

with normal metabolism, but clinical effects from over-

dose may persist for a longer duration.

The clinical presentation of dextromethorphan intox-ication depends on the ingested dose. Minimally intoxi-

cated persons may develop tachycardia, hypertension,

vomiting, mydriasis, diaphoresis, nystagmus, euphoria,

loss of motor coordination, and giggling or laughing [12].

In addition to the above findings, persons with moderate

intoxication may demonstrate hallucinations and a dis-

tinctive plodding ataxic gait that has been compared with

bzombielikeQ walking [13]. Severely intoxicated individ-uals in a dissociated state may be agitated or somnolent

[3,4,12,14]. Extremely agitated patients may need to be

physically restrained by prehospital personnel or police,

actions that place patients at risk for hyperthermia,

metabolic acidosis, and death.

Experienced dextromethorphan users describe a rap-

idly developing and persistent tolerance to the drug [12].

Dependence on dextromethorphan is rarely described[15-17]. Although dextromethorphan is not thought to

have addictive properties, susceptible individuals may

develop cravings for and habitual use of the drug [4,18].

An abstinence syndrome, characterized by dysphoria and

intense cravings, may be associated with cessation of

dextromethorphan abuse [15,17,19,20]. Toxic psychosis

and cognitive deterioration may arise from chronic use of

the drug [15,19,20].Toxicity in the setting of dextromethorphan abuse can

arise from coingestants. In addition to dextromethor-

phan, over-the-counter cough formulations frequently

contain other pharmaceutical agents such as chlorphenir-

amine, acetaminophen, or pseudoephedrine [21]. Chlor-

pheniramine is an H1-receptor antagonist. Consequently,

individuals who have abused chlorpheniramine-contain-

ing dextromethorphan formulations may also exhibitanticholinergic signs and symptoms of tachycardia, dry

mucosa, mydriasis, agitated delirium, urinary retention,

gastrointestinal dysmotility, and warm flushed skin.

Severe chlorpheniramine intoxication has also been

associated with seizure activity, rhabdomyolysis, and

hyperthermia [3]. Pseudoephedrine intoxication may

mimic that of chlorpheniramine except that patients

may exhibit diaphoresis. It is essential for clinicians torecognize that acetaminophen is a component of more

than 100 cough and cold preparations. Accidental over-

dose may produce delayed hepatic injury and, poten-

tially, death.

Treatment of acute dextromethorphan intoxication is

mainly supportive [3,14,22]. Basic life support measures,

with rapid assessment of the airway and identification of

abnormal vital signs, should be immediately performed.Patients with clinical evidence of dehydration or rhabdo-

myolysis should receive intravenous saline solution.

Physical restraints may be required for severely agitated

patients but should be replaced as rapidly as possible by

chemical restraint. Agitation is best controlled with

benzodiazepines. Hypertension and tachycardia may also

respond well to sedating agents such as diazepam.

Hyperthermia should be managed aggressively; if benzo-diazepines and cooling blankets fail to produce an

adequate response, paralysis and orotracheal intubation

may be required to reduce muscular thermogenesis.

Activated charcoal is indicated in cases of recent

ingestion (eg, b1 hour after ingestion) but is of unclear

benefit. Respiratory depression is rarely described in

severe dextromethorphan intoxication but may respond

to high-dose intravenous naloxone [17].

TryptaminesTryptamines are a class of natural and synthetic halluci-

nogenic chemicals [23]. Naturally occurring tryptamines

include psilocin and psilocybin, the psychoactive com-

ponents of Psilocybe mushrooms. Bufotenine is an indole

alkaloid produced by Bufo and Rana species toads andhas been used in the production of hallucinogenic snuff

in South America. N,N-dimethyltryptamine (DMT) is an

ingredient of a hallucinogenic mixture known as

bayahuascaQ that is used in indigenous Amazonian

religious ceremonies [24].

Many of the tryptamines currently used for recreational

purposes were first synthesized in the laboratory of

chemist Alexander Shulgin, PhD [23]. The syntheticmethodology, dose, and clinical effects of many trypt-

amines were initially described in Dr Shulgin’s book,

TIHKAL (bTryptamines I Have Known and LovedQ). The

most noteworthy of the synthetic tryptamines are 5-Meo-

DiPT (bFoxy Methoxy Q), alpha-methyltryptamine (AMT,

IT-290), and 5-MeO-DMT (5-methoxy-N,N-dimethyl-

tryptamine) [24].

The pharmacology of tryptamines is poorly described.The route of administration, bioavailability, and duration

of effect depends upon the chemical modification of the

base structure, tryptamine. For example, 5-MeO-DiPT

(Foxy Methoxy) may be administered by oral, intranasal,

or intrapulmonary routes, but DMT must be smoked (due

to extensive first-pass metabolism of the pure chemi-

cal). Clinical effects last for as little as 5 minutes with

DMT or persist as long as 12 hours with 5-MeO-AMT.Each tryptamine appears to follow a dose-dependent

Emerging drugs of abuse 83

response in producing a variety of hallucinogenic expe-

riences [23].

Patients who use tryptamines exhibit many findings

seen in the serotonin syndrome. Vital sign abnormalities

observed in tryptamine users include hypertension,

tachycardia, tachypnea, and in severe intoxication, hyper-

thermia. Clinical effects of tryptamines include diapho-resis, mydriasis, sialorrhea, nausea, vomiting, diarrhea,

and trismus. The neurological examination may be

notable for tremor, hyperreflexia, clonus, and increased

muscle tone. Neuropsychiatric effects include agitated

delirium, confusion, and auditory and visual hallucina-

tions. Patients using Foxy Methoxy experience disinhi-

bition that may promote high-risk sexual activity [23].

The prevalence of tryptamine use is unknown; what iscertain, however, is that adolescents and young adults

are increasingly abusing tryptamines. Several factors

have contributed to the increase in tryptamine popular-

ity. First, excerpts from TIKHAL became widely avail-

able on the internet, leading to increased interest in this

class of drug. Second, drug users recognized that the US

Drug Enforcement Administration (DEA) has not yet

scheduled many tryptamines as controlled substances.Third, the DEA has successfully disrupted the supply of

LSD in recent months; drug users desiring a hallucino-

genic experience have been forced to use other sub-

stances, many of which can be purchased via the

internet [23].

Treatment of tryptamine intoxication may be similar

to other sympathomimetic agonists. Patients should have

vital signs aggressively corrected with a combination ofsupportive care and sedation. Activated charcoal may be

useful after oral exposure but has limited utility for

drugs that are insufflated or smoked. Benzodiazepines

are the mainstay of treatment for agitation, hypertension,

and hallucinations. Severely deranged vital signs may

require treatment with b-adrenergic antagonists or nitro-

prusside [23].

Hallucinogenic AmphetaminesHallucinogenic amphetamines are congeners of methyl-

enedioxymethamphetamine (MDMA, bEcstasyQ).

Alexander Shulgin initially described many members of

this chemical class in his book, bPhenethylamines I Have

Known and LovedQ (PIKHAL). As with tryptamines, many

drug users have transitioned to hallucinogenic amphet-amine use because of the declining availability of LSD. The

manufacture of more than 300 amphetamines is described

in PIKHAL. Of these, the most commonly used hallucino-

genic amphetamines are 2C-B (bNexus,Q bBromo,Q bEros,QSpectrum), and 2-CT7 (bBlue mysticQ) [25].

2C-B gained popularity during the late 1980s as a legal

substitute for Ecstasy, but it was permanently classified by

the DEA as a Schedule I substance in 1995. When 2C-Bwas scheduled, 2-CT7 emerged as the next blegalQ Ecstasy

product. Anecdotal reports of deaths after 2-CT7 use did

not limit the drug’s popularity, and in March 2004, 2-CT7

was classified as a Schedule I controlled substance [26].

Pharmacological data for hallucinogenic amphetamines

are lacking. Although 2C-B and 2-CT7 may be adminis-

tered via oral, intranasal, and intrarectal routes, the

bioavailability, metabolism, and excretion of these drugsare poorly described. Both 2C-B and 2-CT7 exert their

effects within 1 hour of use, and physiological and

neuropsychiatric effects may persist for 6 to 10 hours.

Low doses produce hypertension and tachycardia,

whereas elevated doses are associated with shifts in color

perception, enhanced auditory and visual stimulation,

and even morbid hallucinations. Vomiting is a commonly

described side effect of 2-CT7. It is uncertain if any of the3 deaths after 2-CT7 use was associated with aspiration or

seizure activity [25,26].

Management of toxicity from hallucinogenic amphet-

amines is similar to that for MDMA poisoning. Provision

of supportive care, correction of vital signs, sedation with

benzodiazepines, and evaluation for electrolyte abnor-

malities remain the hallmark of care. Clinicians should

remain wary for signs of aspiration or seizure activity andtreat these findings aggressively.

Salvia Divinorum(Salvia, Diviner’s Sage)S divinorum is a perennial herb classified as a member of

the mint family. While more than 500 species of Salviaexist, S divinorum is most recognized for its hallucino-

genic properties. The active ingredient of S divinorum is

Salvinorin A, a psychotropic diterpene that stimulates the

opiate j receptor to produce hallucinations that mimic

those of psilocybin [27]. Plants may be purchased from a

variety of sources, including bheadQ shops, record stores,

and online sources. Similarly, seeds may be purchased

from internet vendors along with suggestions for suc-cessful cultivation [28].

The internet may have figured prominently in the

expansion of this substance’s use. Because the DEA has

not scheduled S divinorum and its active ingredients,

many Web sites tout Salvinorin A as a blegalQ halluci-

nogen. Furthermore, online drug encyclopedias report

that Salvia does not trigger any positive results on

qualitative urine drug screens (btoxic screensQ). Salvia’scurrent popularity may be attributable to its marketing as

a legal undetectable drug that can be safely purchased. So

prevalent is the use of S divinorum among suburban

adolescents that some Midwestern towns have adopted

local legislation to render Salvinorin A illegal.

The pharmacology of Salvia is poorly described, but

Salvia may be chewed, smoked, or ingested as a

decoction, an extract derived through boiling the leaves[29]. Interestingly, Salvinorin A is deactivated in the

K. Babu et al.84

gastrointestinal tract by an unknown mechanism, so

pharmacological effect depends upon the amount of drug

absorbed through the oral mucosa [29]. Hallucinations

occur rapidly after exposure to the drug and are typically

quite vivid [29]. One of the characteristic psychotropic

effects is that of synesthesia, where users may report a

confusion of the senses, such as hearing colors orsmelling sounds [29]. Hallucinogenic effects are typically

brief, lasting only 1 to 2 hours. Side effects are not

described, but individuals may be susceptible to trauma,

such as falls, through lack of insight [30].

In comparison to other hallucinogens, the physiolog-

ical and neuropsychiatric effects produced by Salvia are

relatively mild [30]. Symptoms severe enough to require

treatment in the emergency department are uncommonbut may include agitation and confusion. Gastrointestinal

decontamination with activated charcoal may be consid-

ered if presentation is early after ingestion or if

coingestants are suspected. Agitation may be managed

through administration of benzodiazepines. To date, no

significant cases of Salvia toxicity or deaths from over-

dose have been reported [30].

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