Copyedited by: Aleli L. Anacay
LETTER TO THE EDITORS
Dependence on Internet-Purchased Ethylphenidate To the Editors: ntil recently, ethylphenidate (EPH) was only known to be created by the metabolic transesterification of methylphenidate (MPH) and ethanol when they were consumed together.1,2 However, EPH can also be produced chemically from MPH mixed with both hydrochloric and ethanolic hydrochloric acids.3,4 Ethylphenidate has been previously described to exhibit psychostimulant properties2,5; however, to date, no cases of abuse or dependence have been reported by treatment-seeking patients. In this case study, we report on the case of a man who abused EPH he purchased from the Internet and developed dependence for the molecule.
U
CASE REPORT The patient, a 24-year-old white male, reported no medical history but substance abuse. He reported Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for tobacco dependence from the age of 13 years, for cannabis abuse from the age of 16 years, and for heroin and morphine dependence from the age of 19 to 20 years. He also occasionally used stimulants including cocaine, amphetamine, or ecstasy for recreational purposes. After he was prescribed methadone 120 mg/d, he stopped using morphine at the age of 20 years. This treatment was progressively tapered and stopped at the age of 22 years. Between the ages of 22 and 24 years, he did not use any opiates but still smoked tobacco and sporadically used stimulants (cocaine and amphetamine). A few months before he interacted with our addiction service, he ordered a small amount of EPH on an English website. He retrospectively said he was experiencing a busy time at work and was looking for a pharmacological boost. He found that the effects of EPH were closer to those of cocaine than of amphetamine, in that EPH not only suppressed his need to sleep and enhanced his creativity but also induced euphoria and well-being while enabling him to foster social relationships.6 Progressively, he ordered more EPH until he was taking 50 pills (20 mg/pill) each day. After continued use, he was unable to fall asleep and was driven
to use heroin daily to counterbalance the effects of EPH. At the initial consultation, the medical examination found a tachycardia at 120 beats per minute, and the patient was clearly agitated, albeit cooperative. Methadone was slowly reintroduced at a prescription of 90 mg/d after 1 week. We also prescribed propranolol (20 mg/d) for 2 two weeks to foster the regularization of his heart rate. His last EPH intake occurred 6 days after initiating this treatment. Thereafter, a 3-day period of mood lowering and fatigue was noted. The patient remained abstinent from heroin and stimulants over the next 2 months. He was lost to follow-up after that. However, he gave us his written informed consent for publishing his case 2 weeks after his initial consultation. The case was also declared to the Pharmacodependence/ Addictovigilance Center (CEIP) of Lille.
DISCUSSION Ethylphenidate abuse was detected for the first time during an autopsy, and a package containing EPH purchased on the Internet was found at the subject's home.4 This suggested that EPH is becoming a specific abusable drug. To our knowledge, this is the first report accounting EPH abuse and trafficking. Moreover, the patient fulfilled 6 of the 7 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for dependence. The assessment was performed independently by 2 addiction physicians (B.R. and A.M.). Interestingly, dependence was not a complication described previously in regard to this substance. The potential of abuse of MPH, from which EPH is produced, was already widely known.7,8 Neurobiologically, MPH inhibits the recapture of noradrenaline and dopamine in the synaptic cleft.4 Ethylphenidate was described to exhibit the same mechanism of action, although EPH's ability to inhibit noradrenaline recapture is approximately 10% of MPH's ability.2,9 Interestingly, cocaine is known to inhibit dopamine recapture.2 In this case report, the subject reported that EPH exerted similar subjective effects compared with cocaine. The aforementioned limited pharmacological effect of EPH on noradrenaline recapture could explain why the EPH subjective effects are more similar to cocaine than MPH. Amphetamine derivatives, such as MPH, are known to induce adrenergic cardiovascular adverse effects including tachycardia,
Journal of Clinical Psychopharmacology • Volume 35, Number 4, August 2015
arrhythmia, increased blood pressure, or vasospasms.10 In a recently published autopsy, EPH is suspected to have contributed to the death of an individual via both endocarditis and pneumonia.4 In this case report, EPH seemed to induce cardiovascular adverse effects. Additional investigations are warranted to better understand the pharmacological and clinical features of EPH, including comparisons with other psychostimulants such as amphetamine drugs or cocaine.
AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest.
Baptiste Pignon, MD Service d'Addictologie and Centre d'Evaluation et d'Information sur les Dépendances CHRU de Lille Lille, France
[email protected]
Arnaud Muyssen, MD Service d'Addictologie CHRU de Lille Lille, France
Sylvie Deheul, MD Centre d'Evaluation et d'Information sur les Dépendances and Laboratoire de Pharmacologie Médicale CHRU de Lille Lille, France
Olivier Cottencin, MD, PhD Service d'Addictologie CHRU de Lille and Université Lille Nord de France Lille, France
Benjamin Rolland, MD, PhD Service d'Addictologie and Laboratoire de Pharmacologie Médicale CHRU de Lille and Université Lille Nord de France Lille, France
REFERENCES 1. Markowitz JS, Logan BK, Diamond F, et al. Detection of the novel metabolite ethylphenidate after methylphenidate overdose with alcohol coingestion. J Clin Psychopharmacol. 1999;19:362–366.
www.psychopharmacology.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
1
Letter to the Editors 2. Markowitz J. Ethylphenidate: from biomarker to designer drug. Ment Health Clin. 2013;3:100. 3. Casale JF, Hays PA. Ethylphenidate: an analytical profile. Microgram J. 2011;8:58–61. 4. Krueger J, Sachs H, Musshoff F, et al. First detection of ethylphenidate in human fatalities after ethylphenidate intake. Forensic Sci Int. 2014;243C:126–129. 5. Patrick KS, Corbin TR, Murphy CE. Ethylphenidate as a selective dopaminergic agonist and methylphenidate–ethanol transesterification biomarker. J Pharm Sci. 2014;103:3834–3842.
2
www.psychopharmacology.com
Journal of Clinical Psychopharmacology • Volume 35, Number 4, August 2015 6. Newton TF, De La Garza R, Kalechstein AD, et al. Cocaine and methamphetamine produce different patterns of subjective and cardiovascular effects. Pharmacol Biochem Behav. 2005; 82:90–97. 7. Morton WA, Stockton GG. Methylphenidate abuse and psychiatric side effects. Prim Care Companion J Clin Psychiatry. 2000;2: 159–164. 8. Imbert B, Cohen J, Simon N. Intravenous abuse of methylphenidate. J Clin Psychopharmacol. 2013;33:720–721.
9. Williard RL, Middaugh LD, Zhu HJ, et al. Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity. Behav Pharmacol. 2007; 18:39–51. 10. Kaye S, McKetin R. Cardiotoxicity Associated With Methamphetamine Use and Signs of Cardiovascular Pathology Among Methamphetamine Users. University of New South Wales, Sydney, Australia: National Drug and Alcohol Research Centre (NDARC); 2005.
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
