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Methylphenidate is a stimulant medication widely used for treating ADHD. Despite its wide margin of safety, MPH is thought to have high abuse potential (1). Cases of oral (2,3), intranasal (4,5), and intravenous (6,7) MPH abuse have been documented. However, consistent information is lacking regarding the prevalence of MPH abuse through the various routes of administration or regarding its use in a polysubstance context. Although rates of MPH abuse are thought to be lower than rates for other stimulants, it has been suggested that MPH misuse may be underreported (1). In a college student sample, rates of reported recreational MPH use among traditional-age students were comparable to rates of cocaine and amphetamine use, but any overlap in the rates of MPH and other stimulant use was not specified (8). A study of child and adolescent MPH abuse reported to poison centres found that polysubstance use was involved in 30% of the cases overall; however, it was more common in adolescents aged 15 to 19 years than in children aged 10 to 14 years, and it was more likely to be associated with clinical toxicity (9). Although the most common route of administration was oral in both age groups, the older group was also more likely to report intranasal use (9). However, because this sample consisted exclusively of cases reported to poison centres, it may not represent general patterns of MPH misuse, and its relevance to adults who misuse MPH is unknown. In a recent study examining illicit MPH use in a university student sample, individuals who misused MPH reported using significantly more psychoactive substances during the preceding year than did peers with no history of MPH misuse (10). Although such findings suggest that individuals who inappropriately use MPH may be more prone to substance misuse in general, the context and patterns of MPH administration were not delineated, and little is currently known about how MPH is related to the use of other specific substances. The present study aimed to elucidate patterns of MPH misuse and characteristics of MPH misusers in a university student population, including information on routes of administration, reasons for use, methods of obtaining MPH, and related patterns of past and concurrent polysubstance use. MethodThe study involved 50 individuals who reported recreational and (or) nonprescribed use of MPH and 50 control subjects matched for age, sex, and ethnicity. Participants were recruited from the McGill University student population between July 1, 2003, and May 31, 2004, as part of an ongoing study examining polydrug use in different populations. Subjects who misused MPH were recruited through advertisements posted on a university-based, classified Internet site, and control participants were recruited from a pool of volunteers who had expressed interest in participating in research at McGill’s Department of Psychology. During confidential face-to-face interviews (which were standardized and structured), participants provided details about their recreational and (or) nonprescribed use of various licit and illicit substances. Participants answered questions about their lifetime use of several specific substances, including tobacco, alcohol, cannabis, LSD, psilocybin (magic mushrooms), cocaine, mescaline, methamphetamine, MPH, ketamine, GHB, MDMA (ecstasy), PCP, heroin, ephedrine, AdderallTM, d-amphetamine, and “any other drug not already mentioned (please specify).” For each substance, subjects provided information regarding routes of administration and other substances ever coadministered with the drug, as well as details of all substances used simultaneously during the most recent administration. Participants were asked why they used MPH; 36 of them also indicated how they obtained the MPH. All subjects provided informed consent before participating, and all were paid $15 after their interview. The study was conducted in accordance with the Declaration of Helsinki and was approved by a McGill University research ethics committee. Statistical Analyses We used SPSS Version 11.0 (11) to analyze all data. We used independent sample t tests to test for differences in the total number of drugs used between subjects who misused MPH and matched control subjects, as well as between recreational MPH users and those reporting using MPH exclusively for study purposes. Chi-square tests were used to examine differences in the prevalence of the use of specific substances among these groups. Because analyses were conducted for 18 different substances, we used familywise Bonferroni corrections; the alpha level used to determine statistical significance for these tests was 0.003. Chi-square tests were also used to determine whether there were differences in the proportion of recreational MPH users and “studiers” who reported different routes of MPH administration or reported polysubstance use involving MPH. ResultsIn each subject group, 46% of the participants were men and 54% were women, 86% were white (while several other ethnic backgrounds were represented, none exceeded 5% of the sample), and the mean age was 21.4 years, SD 2.6. Table 1 presents lifetime history of substance use for both subject groups. MPH misusers reported using a greater variety of substances recreationally throughout their lifetimes (mean 7.7, SD 3.0) relative to control subjects (mean 3.8, SD 3.1) (t = 5.98, df 98, P < 0.001). Chi-square tests revealed that MPH users were more likely to report recreational use of ecstasy, cocaine, ephedrine, d-amphetamine, and psilocybin (all Ps < 0.001) than were control subjects.
Seventy percent of those who used MPH reported using it for recreational purposes, while the remaining 30% reported using it exclusively as an aid for study. The proportion of recreational users also taking MPH as a study aid was not consistently recorded. Among the recreational users, 77.1% reported the simultaneous use of other psychoactive substances (excluding tobacco) with MPH, and 26.7% of those reporting MPH use exclusively for study purposes reported using other substances simultaneously. Chi-square analysis revealed that a greater proportion of recreational users reported using MPH in a polydrug context (P < 0.001). However, there were no differences between the 2 groups in lifetime number of drugs used (t = 1.67, df 48, P = 0.10) or in the proportion reporting lifetime use of any given substance (all Ps > 0.05). Table 2 presents the prevalence of using other substances concurrently with MPH, for both lifetime and most recent use, in recreational users and in those reporting use for study only, as well as in the total sample.
Overall, the most common routes of MPH administration reported were oral (88%) and intranasal (50%); other routes reported included smoking (4%) and injection (2%). When participants reported multiple administration routes, the relative frequency of each was not recorded. Among the recreational MPH users, 82.9% reported oral administration, and 62.9% reported intranasal use. In contrast, the rates of oral and intranasal use in those using MPH only for study were 100% and 20%, respectively. Chi-square analysis showed that those reporting MPH use exclusively for study were less likely to report intranasal use (P < 0.01); however, there were no differences in the relative proportions reporting oral administration (P > 0.05). Of the 36 MPH users who provided additional information about their source(s) of MPH, most (77.8%) reported obtaining it from a friend or acquaintance with a prescription. Other methods included black market purchases (16.7%), getting one’s own prescription (11.1%), and theft (4%). DiscussionIn this study, we sought to elucidate characteristics of a sample of university students who misused MPH and to identify their patterns of misuse and sources of the drug. Relative to matched control subjects, the MPH users reported the recreational use of more drugs throughout their lifetime, particularly other prescription and nonprescription stimulant drugs such as cocaine, ephedrine, AdderallTM, and d-amphetamine. This suggests that MPH misusers may possess a general vulnerability to stimulant misuse rather than a preference for MPH per se and that MPH may sometimes be used as substitution for more expensive or difficult-to-obtain substances, such as cocaine. It is also possible that in some cases the propensity to misuse MPH may represent an attempt to self- medicate undiagnosed ADHD symptoms (12). This may be especially true among subjects who reported nonprescribed MPH use for study purposes only. However, because these individuals reported high levels of other illicit substance use, it would be difficult to ascertain the degree to which ADHD symptoms were a cause or a consequence of their drug misuse without an adequate period of abstinence (12). The most common route of MPH misuse in this sample was oral, and the second most common was intranasal. Oral administration was the most frequent method reported by both recreational MPH users and those using it exclusively for study, whereas intranasal use was relatively more common among recreational users. Because we did not record all the potential reasons for MPH use in recreational users or the frequency of their different administration routes, we cannot determine the relative prevalence of oral and intranasal MPH use for recreational purposes in this study. Nevertheless, our findings of oral MPH misuse are consistent with some previous reports that MPH may frequently be misused orally (1,3). The MPH users in this study often used the drug in a polydrug context, especially with alcohol or cannabis (Table 2). Little is known about the effects of mixing MPH with other substances. Although we do not know whether the use of additional substances with MPH is associated with increased morbidity and mortality, a study of MPH overdoses in children and adolescents suggests that polysubstance use may be associated with increased toxicity (9). Alcohol–MPH coadministration is associated with the production of a novel metabolite, ethylphenidate (13), and toxic effects have been reported following the ingestion of high doses of both substances (14). There are also reports that combined alcohol–MPH administration results in enhanced euphoria and a diminished sense of drunkenness (3), which could lead to dose escalation. To our knowledge, the specific effects and consequences of the concurrent use of cannabis (or other illicit drugs) with MPH have yet to be systematically investigated. Given the high rates of drug mixing by MPH users in the present sample, further research in this area seems warranted. Because the primary source of MPH in this sample was prescription diversion, increased attention should be directed to ensuring prescription compliance as well as to identifying those individuals most likely to divert their medication. Previous research found that adolescents who misused their own prescription stimulant medication were more likely to give it or sell it to others (15). Although it is not known whether this is also the case for adults, practitioners may wish to exert particular caution in prescribing MPH to individuals with histories of substance abuse. Our results should be interpreted in light of several methodological limitations. First, because those who misused MPH were self-selected and the sample size was relatively modest, it is possible that the results do not represent MPH misuse in the university student population. In 2 previous studies of MPH misuse among college students, 2.5% and 16% of participants, respectively, reported inappropriate MPH use, and the respective response rates of those invited to participate were 64% and 20% (8,10). Thus obtaining a comparable number of MPH misusers by sampling an entire student population could be expected to require several thousand subjects, without any additional assurance of a representative sample. Nevertheless, only a true random sample of subjects who misuse MPH would ensure the generalizability of the findings. Second, our investigation did not distinguish between immediate-release MPH and the newer extended-release formulation that is believed to be less liable to be abused intranasally. Although the high levels of oral MPH abuse reported may be due in part to misuse of extended-release MPH, we cannot determine the respective misuse patterns of immediate- and extended-release MPH formulations with the present data, and this issue needs to be addressed in future investigations. Funding and SupportMr Barrett and Dr Pihl are supported by the Canadian Institutes for Health Research. Ms Darredeau is supported by the Natural Sciences and Engineering Research Council of Canada. AcknowledgementsWe thank Matthew Tichauer for his assistance with subject recruitment and data collection. References1. Kollins SH, MacDonald EK, Rush CR. Assessing the abuse potential of methylphenidate in nonhuman and human subjects: a review. Pharmacol Biochem Behav 2001;68:611–27. 2. Goyer PF, Davis GC, Rapoport JL. Abuse of prescribed stimulant medication by a 13-year-old hyperactive boy. J Am Acad Child Psychiatry 1979;18:170–5. 3. Barrett SP, Pihl RO. Oral methylphenidate–alcohol co-abuse. J Clin Psychopharmacol 2002;22:633–4. 4. Garland JE. Intranasal abuse of prescribed methylphenidate. J Am Acad Child Adolesc Psychiatry 1998;37:573–4. 5. Jaffe SL. Intranasal abuse of prescribed methylphenidate by an alcohol and drug abusing adolescent with ADHD. J Am Acad Child Adolesc Psychiatry 1991;30:773–5. 6. Parran TV, Jasinski DR. Intravenous methylphenidate abuse: prototype for prescription drug abuse. Arch Intern Med 1991;151:781–3. 7. Stecyk O, Loludice TA, Demeter S, Jacobs J. Multiple organ failure resulting from intravenous abuse of methylphenidate hydrochloride. Ann Emerg Med 1985;14:597–9. 8. Babcock Q, Byrne T. Student perceptions of methylphenidate abuse at a public liberal arts college. J Am Coll Health 2000;49:143–5. 9. Klein-Schwartz W, McGrath J. Poison centers’ experience with MPH abuse in pre-teens and adolescents. J Am Acad Child Adolesc Psychiatry 2003;42:288–94. 10. Teter CJ, McCabe SE, Boyd CJ, Gutherie SK. Illicit methylphenidate use in an undergraduate student sample: prevalence and risk factors. Pharmacotherapy 2003;23:609–17. 11. SPSS Inc. SPSS. Version 11.0. Chicago (IL): SPSS Inc; 2002. 12. Wilens TE. Impact of ADHD and its treatment on substance abuse in adults. J Clin Psychiatry 2004;65(Suppl 3):38–45. 13. Markowitz JS, Devane L, Boulton DW, Nahas Z, Risch SC, Diamond F, and others. Ethylphenidate formation in human subjects after the administration of a single dose of MPH and ethanol. Drug Metab Dispos 2000;28:620–4. 14. Markowitz J, Logan BK, Diamond F, Patrick KS. Detection of the novel metabolite ethylphenidate after methylphenidate overdose with alcohol coingestion. J Clin Psychopharmacol 1999;19:362–6. 15. Poulin C. Medical and nonmedical stimulant use among adolescents: from sanctioned to unsanctioned use. CMAJ 2001;165:1039–44. Author(s)Manuscript received June 2004, revised, and accepted October 2004 1. Doctoral Candidate, Department of Psychology, McGill University, Montreal, Quebec. 2. Honours Student, Department of Psychology, McGill University, Montreal, Quebec. 3. Professor, Department of Psychology, McGill University, Montreal, Quebec. Address for correspondence: Mr SP Barrett, Department of Psychology, McGill University, 1205 Dr Penfield Avenue, Montreal, QC H3A 1B1 e-mail: barrett@ego.psych.mcgill.ca
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