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Recreational use of dextromethorphan,


"Robotripping"-A brief review

Article in American Journal on Addictions · June 2016


DOI: 10.1111/ajad.12389

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The American Journal on Addictions, 25: 374–377, 2016
Copyright © 2016 American Academy of Addiction Psychiatry
ISSN: 1055-0496 print / 1521-0391 online
DOI: 10.1111/ajad.12389

Brief Report: Recreational Use of Dextromethorphan,


“Robotripping”—A Brief Review

Cornel N. Stanciu, MD, Thomas M. Penders, MS, MD, Eden M. Rouse, MD


Department of Psychiatric Medicine, Brody School of Medicine, East Carolina University, Greenville, North Carolina

Background: Dextromethorphan (DXM) in combination with Preparations, commonly containing 10–30 mg DXM and
antihistamines and/or pseudoephedrine is widely available as an 4 mg Chlorpheniramine, are sold as syrups, pills, or inhalers.
over-the counter remedy commonly used for relief of colds and
cough. In supra-therapeutic amounts, DXM has psychoactive effects.
There are no restrictions on their sale. Their modest price
These cough preparations have been adopted by many young users of makes them readily accessible to anyone who has the means.
recreational drugs for these effects. When used as recommended, adverse psychoactive effects are
Objectives: This paper aims to highlight the increasingly prevalent generally minimal.3 When used recreationally, however, doses
practice of Robotripping, review pharmacokinetic and dynamic data commonly exceed label recommendations. Recreational users
and discuss potential tolerance and withdrawal from the substance as
well as treatment modalities. of DXM products refer to them by street labels such as “Red
Methods: A Medline search (1985–2015) for literature concerning Devils,” “Tripple C’s,” or “Skittles.” The practice of using
the DXM was conducted. This was supplemented by references large amounts to obtain psychoactive effects is known as
gleaned from recent epidemiological surveys and credible online “Robotripping.” Psychoactive symptoms are dose related and
sources to ensure most up to date information is gathered. range from impairment of motor, cognitive, and perceptual
Conclusion and Scientific Significance: Use in amounts exceeding
those recommended, a practice known as “Robotripping”, may result
functioning to hallucinations and dream-like experiences or
in a toxidrome of psychomotor agitation, hallucinations and paranoia delirium with visual hallucinations and dissociative states
best characterized as Intoxication Delirium. Increasing misuse places that may predispose users to aggressive behaviors.4
greater numbers at risk. Providers should be alert to such
presentations and be aware of methods for managing the symptoms.
With chronic use, tolerance and withdrawal has been noted along with
prolonging psychiatric sequelae. (Am J Addict 2016;25:374–377)
METHODOLOGY

A Medline literature search (1985–2015) was conducted


with keywords: “Robotripping,” “Dextromethorphan AND
Intoxication,” “Dextromethorphan AND Delirium,” “Dextro-
methorphan AND Psychosis,” “Dextromethorphan AND
INTRODUCTION
Mania,” “Dextromethorphan AND Altered Mental Status.”
Results were supplemented by references gleaned from recent
Recreational use of over-the-counter drugs is is an
epidemiological surveys and credible online sources (Fig. 1).
increasing public health problem. The Substance Abuse and
Following review of the initial returns, three of the authors
Mental Health Services Administration reports that over
judged each trial applying the set inclusion and exclusion
1 million individuals use preparations containing Dextrome-
criteria. As part of the inclusion criteria, primary focus was on
thorphan (DXM) annually.1 According to the Monitoring the
English literature, 1985 and recent, pertaining to humans only.
Future survey, the prevalence of misuse of cough preparation
No animal studies were included. Literature focusing strictly
among 12th graders in 2013 was 5%.2 DXM is the common
on pharmacological aspects was also not included. A total of
prescription agent found in cough and cold remedies.
30 papers met such criteria for use in the review.

Received October 28, 2015; revised May 4, 2016; accepted May


14, 2016. EPIDEMIOLOGY
Address correspondence to Penders, Department of Psychiatric
Medicine, Brody School of Medicine, East Carolina University, 600 Recreational misuse of nonprescription drugs is most
Moye Boulevard, Suite 400E, Greenville, NC 27834. commonly seen in young adults 18–25 year olds. It has been
E-mail: penderst@ecu.edu estimated that there has been a 17% increase in such use

374
Lower transformation has been seen to blunt positive euphoric
effects and enhance negative effects decreasing risk of abuse.9
Four progressive plateaus, based on dosage, have been
documented. The first is achieved at 1.5–2.5 mg/kg and involves
stimulating effects with MDMA-like perceptual alterations.
A second stage is reached at 2.5–7.5 mg/kg and is associated
with effects similar to alcohol and marijuana but with a more
pronounced impairment of motor, cognitive, and perceptual
functioning. Hallucinations may be seen. A third level
resembles ketamine with strong hallucinations and dissociative
symptoms. This is achieved between 7.5 and 15 mg/kg. Greater
amounts may lead to out-of-the-body, dreamy trance-like states
with visual hallucinations. At this level, delirious misperceptions
are common leading to violent and aggressive behaviors.4
Patients may present with severe agitation and limited
FIGURE 1. Flow diagram describing choice of papers.
perception of pain. Management of aggressive behavior in
this circumstance may lead to use of physical restraints.11
Visual hallucinations experienced are unique as Schwartz notes
different from LSD or psilocybin mushrooms; closed eye visual
between 2002 and 2005. The most commonly misused hallucinations consisting of “sheets, swirls, and blobs of color
products include anti-cholinergics, caffeine, and DXM.5 that move about” and never formed figures.12
Recently, there has been an abundance of reported cases of Intoxicated excited delirium describes the most serious and
DXM abuse worldwide. In a recent survey of students grades potentially deadly DXM-induced medical condition involving
7th–12th, King found 7.7% males and 6.3% females reported psychotic behavior, elevated temperature, and an extreme
ever abusing OTC drugs with the intent of getting high. Males psychomotor agitation fight-or-flight response by the nervous
were more likely to use for social or recreational purposes system. Due to extreme violence frequently encountered such
while females have a tendency to use to cope with personal presentations, typically encountered in the emergency room
stress. Both populations are vulnerable to similar adverse setting with law enforcement involvement, have result in
effects with overuse. There is wide variation in use with sudden death secondary to cardiac or respiratory arrest, an
ethnicity. Hispanics are most likely to abuse OTC drugs and outcome associated with the use of physical restraints.13 Men
this is concerning given they are the most rapidly growing present majority of such cases especially if mental illness or
population group in the US.6 The most common OTC drugs stimulant drug use compound the picture.10
abused are Nyquil (30.5%), Coricidin (18.1%), and
Robitussin(17.8%). As also reported, 81.9% of youth who
have abused OTC drugs also have used marijuana and 44% METABOLISM
have used hallucinogens and ecstasy.1
DXM undergoes extensive first pass metabolism through
cytochrome CYP2D6 and its main metabolite dextrorphan is
BEHAVIORAL PHARMACOLOGY metabolized by CYP3A4 and A5. A large proportion of the
population with varying CYP2D polymorphisms can include
At therapeutic doses of DXM, untoward effects are poor metabolizers and consequent enhanced duration of
generally mild, such as fever, diaphoresis, dizziness, nausea/ action.14 DXM and antihistamines (ie, chlorpheniramine) are
vomiting, and mydriasis.3 There are several abuse liability rarely abused in isolation. However, the frequently used
studies examining high doses of DXM.7–9 These support the combination may cause alteration in metabolism of each
notion that DXM has a relatively wide therapeutic window resulting in enhancement and prolongation of side effects.9,15
when appropriately used; however, supra-therapeutic doses Chlorpheniramine, an antihistamine with anticholinergic
result in acute impairments on several cognitive domains.8 properties, may cause dry flushed skin, mydriasis, tachycardia,
Symptoms observed following use of supra-therapeutic delirium. Its half-life exceeds 24 hours. Along with DXM,
dosages include paranoia, disorientation, aggression, halluci- they are both metabolized by CYP2D6 and when used in
nations, delusions of supra-natural abilities such as flight or excess effects are potentiated.
telepathy and insensitivity to pain. Physiological symptoms
diaphoresis, hyperthermia, tachycardia may also occur.4,7,10
Mania has also been reported.10 Psychoactive drug effects and MECHANISM OF ACTION
abuse potential is related to drug metabolism with variances in
CYP2D6 alleles regulating the metabolism of DXM to its The psychoactive effects of DXM are attributed to its
active metabolite with higher NMDA affinity, dextorphan. metabolite, dextrorphan. Both the parent compound and its

Stanciu, Penders, and Rouse August 2016 375


metabolite are NMDA receptor antagonists similar in action to SUMMARY AND CONCLUSION
ketamine and PCP. The NMDA-R is an ionotropic glutamate
receptor that functions both pre- and post-synaptically to Formulations of DXM marketed as cough preparations
regulate transmission, neuronal maturation, and plasticity.16 are being used increasingly as recreational substances. The
Hyperfunction of NMDA-R has been associated with seizure practice of ingesting doses above those recommended, known
activity, whereas inhibition has anticonvulsant effects. as “Robotripping,” may produce a toxidrome of delirium
Actions at the NMDA-R receptor have been associated with with agitation, paranoia, and hallucinations. Psychiatric and
psychosis, cognitive impairment and, in animals, a syndrome emergency providers should be alerted to these serious
resembling schizophrenia.17 This puts a twist on the complications of misuse. Treatment is supportive with a
“dopamine hypothesis” as glutamanergic pathways in the goal of controlling agitation and psychotic symptoms while
cortex exert both direct stimulatory and inhibitory (through awaiting remission of delirium. Benzodiazepines may assist
GABA interneurons) control over subcortical dopaminergic with limiting agitation. Low-dose and short-term antipsy-
pathways.18 Catatonia has also been linked to NMDA-R chotic agents have shown benefit in circumstances where
block and glutamate overexcitation. When blocking NMDA- hallucinations or paranoia are prominent.4 Tolerance and
Rs, GABA regulation is perturbed. Use of benzodiazepines withdrawal has been reported and clinicians should be mindful
may reverse these effects.3 As with ketamine, DXM also that with chronic use psychiatric sequelae may be prolonged.
has effects on serotonin transporters and other protein targets Efforts to educate youth populations about risks of “Robot-
such as sigma 1 receptors that might account for reported ripping” are advised.
antidepressant properties.19
Declaration of Interest
All authors of this paper declare that there are no personal
TREATMENT or financial interests/conflicts. This review is completely self-
funded. The authors alone are responsible for the content and
Management is symptomatic. The primary goal of acute writing of this paper.
management is control of agitation and psychotic symptoms
with supportive psychological treatment. Short-acting benzo-
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