ACCEPTED MANUSCRIPT Frequency of energy drink use predicts illicit prescription stimulant use *Conrad L. Woolsey1, PhD, CHES, CC-AASP; Laura B. Barnes2; PhD; Bert H. Jacobson2 PhD, FACSM; Weston S. Kensinger3, PhD; CHES; Adam E. Barry4, PhD; Niels C. Beck5, PhD, MD; Andrew G. Resnik5, MD; Marion W. Evans, Jr.6, D.C., PhD, MCHES, CWP
1. United States Sports Academy 2. Oklahoma State University 3. Penn State University 4. University of Florida 5. University of Missouri Medical School 6. University of Western States
*Corresponding Author: Conrad L Woolsey 1 Academy Drive, Daphne, AL 36526 918-978-4221
[email protected]
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ACCEPTED MANUSCRIPT Author contributions
Conrad L. Woolsey designed the study, was the primary researcher and main author for the manuscript. Laura B. Barnes conducted statistical analyses, assisted with literature review, writing the results section and with revisions. Bert H. Jacobson served as a co-investigator, helped with statistical analyses, literature review, and reviewed the manuscript. Weston S. Kensinger served as a co-investigator, helped with data collection, and reviewed the manuscript. Adam E. Barry wrote additional main points to the intro, purpose, discussion, and conclusion sections. Niels C. Beck assisted in the design of the study, served as a co-investigator for a larger follow-up study, and reviewed the manuscript. Andrew G. Resnik contributed to the initial literature review and reviewed the manuscript. Marion W. Evans Jr. assisted with revisions and reviewed the manuscript.
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ACCEPTED MANUSCRIPT ABSTRACT Background: The purpose of this study was to examine energy drink (ED) usage patterns and to investigate the illicit use of prescription stimulants among college students. Methods: A sample of 267 undergraduate and graduate students (mean age of 22.48 among stimulant users) from a large Midwestern university and its branch campus locations voluntarily participated in the study. Results: Among prescription stimulant users without a valid medical prescription, MannWhitney U tests and logistic regression analysis revealed that the frequency of ED use was a significant predictor of the illicit use of prescription stimulants. Moreover, frequency of ED consumption was a significant predictor of the illicit use of prescription stimulant medications with the odds for using increasing by .06 with each additional day of ED use past zero days (odds for use = 1.06, p =.008). Conclusions: Results indicate that the frequency of ED use is a significant predictor of the illicit use of prescription stimulants. All prescription stimulant users with or without a valid script also used EDs. This finding is important to practitioners because of the harmful interactions (e.g., serotonin syndrome) that can occur when ED ingredients (e.g., ginseng, yohimbine, evodamine, etc.) are mixed with prescription stimulants.
Keywords: energy drinks (EDs), illicit prescription stimulant use, nonmedical prescription use
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ACCEPTED MANUSCRIPT INTRODUCTION
Between 1990 and 2000, the overall number of prescriptions for ADHD medications in the U.S. increased by an estimated 368% to a total of 23.4 million.1 During this time frame, an increase in amphetamine-dextroamphetamine mixed salts (e.g., Adderall) production followed with a reported production increase of 9,008,000% over 10 years.1 By 2005, there were 31.8 million prescriptions reported for stimulant medications with the most popular being Adderall.1,2 A 2005 nationwide survey, conducted among 119 colleges, found that up to 25% of student respondents on different campuses had illicitly used prescription stimulants in the past year. 2 Additionally, the rates of illicit use were the highest among academically competitive colleges. Recent reports continue to suggest illicit prescription stimulant use is increasing and poses a significant public health problem for college students.3-9 This study is unique because little is known about the relationship between ED consumption and prescription stimulant use. The emergence of prescription drug use/abuse among college students coincides with another relatively new college behavioral health issue, the consumption of energy drinks (EDs). Previous studies have reported that ED consumption is associated with the increased use of alcohol and other drugs.10-11 For example, Miller (2008)11 found that the frequency of ED consumption was associated with the increased use of alcohol, nicotine, marijuana, and non-stimulant prescription drugs such as opiates. However, according to a comprehensive research review on this topic by Varga (2012)8, “Prescription stimulant misuse has dramatically increased over the past 10 years, but the amount of research regarding college students and illicit prescription stimulant use is still very limited.” Of the research that is
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ACCEPTED MANUSCRIPT available, Arria and others (2010)7 reported that ED consumption was associated with the increased use of alcohol, nonmedical prescription stimulants, and other illegal drugs among a large (n=1060) undergraduate sample followed longitudinally. Moreover, college student ED users were significantly more likely to begin using prescription stimulants in the year following ED use. Among ED users who reported no previous prescription stimulant use during their second year of college, nearly one fifth (19%) subsequently started using prescription stimulants without a prescription the following year, compared to 8.2% among non-ED users.7 Additionally, ED use predicted the subsequent nonmedical use of prescription stimulants and analgesics even after controlling for confounding variables such as demographics, sensation seeking, caffeine use, and prior drug use. 7 Pharmacologic Similarities Between Adderall & ED In the United States, Adderall is regulated by the Controlled Substance Act as a Schedule II drug because of its high potential for abuse as well as severe psychological and physiological addiction.12 While differing in intensity and duration, the mechanisms of action of stimulant drugs such as cocaine and amphetamines are similar to prescription stimulants such as amphetamine/dextroamphetamine mixed salts. Prescription stimulants work by increasing the release of pleasure reward neurotransmitters (e.g., dopamine, serotonin, nor-epinephrine) and impact the mesolimbic reward pathways of the brain, resulting in high potential for abuse and addiction.13-15 Similar to prescription stimulants, many ED ingredients also effect motivation, concentration, mood, and behavior by impacting neurotransmitter functioning in the brain. Some ingredients that have been studied for their effects on neurotransmitters are: taurine, glucose, glucuronolactone (ie, synthesized metabolite of glucose), caffeine, guarana/yerba mate, inositol,
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ACCEPTED MANUSCRIPT ginseng, yohimbine hydrochloride (HCl), bitter orange, and evodamine.16 The stimulating ingredients in EDs work by facilitating an increase in the release of and/or prolonged action of pleasure-reward neurotransmitters and stress hormones (e.g., epinephrine) providing a burst of energy followed by a low or crash.17 Other vitamin and amino acid ingredients such as Bvitamins, N-Acetyl tyrosine, and L-carnitine play supportive roles in helping the brain produce more neurotransmitters after they are depleted by drugs such as caffeine.17 Caffeine has been mentioned previously, but the interactions and neurological effects of other ED ingredients also needs to be emphasized by researchers and health care providers. Several ED ingredients demonstrate particularly insidious neurological effects that may augment the effects of prescription drugs. These ingredients include, but are not limited to caffeine, taurine, inositol, ginseng, and yohimbine hydrochloride. Neurological Effects of ED Ingredients. Caffeine. Current evidence suggests caffeine interacts with the neuronal systems in the brain involved in reinforcing the use of alcohol and other drugs.18,19 It is important for consumers to understand that herbal forms of caffeine are generally not included in ED overall caffeine content calculations. Among the hundreds of ED brands now available, several contain 250 to 500 mg per container.16 Caffeine works in the brain by binding to adenosine receptors as a nonselective adenosine antagonist, and is molecularly similar to adenosine which allows it to occupy adenosine receptor sites.20 These adenosine receptors (A1 & A2A) have important roles including regulating the release of neurotransmitters such as dopamine and nor-epinephrine.21,22 As a result, researchers suggest that high doses of caffeine can increase tolerance and potentially cravings to other substances.18,19
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ACCEPTED MANUSCRIPT Inositol. The ingestion of caffeine is known for leaching vitamins such as inositol and other key nutrients in the body. Inositol facilitates neuron communication and has been shown to regulate serotonin activity. In clinical trials, inositol has been successfully used as an antidepressant medication in place of selective serotonin reuptake inhibitors (SSRIs).23,24 Taurine. Taurine readily crosses the blood-brain barrier and has several important roles in physiological processes including inhibitory neurotransmission.25 At higher doses, such as that found in EDs, taurine appears to act as an anti-anxiety agent because of its effects on gammaaminobutyric acid (GABA).25-27 Taurine is prescribed as a supplement and/or medication for people with neurological disorders (e.g., Parkinson’s disease) affecting the dopamine system including epileptics and muscle movement disorders such as facial twitches.28 Ginseng. Ginseng is widely used, but its mechanisms of action are not fully understood. Side-effects reported from ginseng include insomnia, nausea, diarrhea, headaches, nose bleeds, high blood pressure, low blood pressure, and breast pain. 29 Ginseng may also lead to mild serotonin syndrome (i.e., serotonin toxicity) and mania when mixed with anti-depressants; thus, exacerbating the extrapyramidal effects (i.e., inability to regulate movements) caused by neuroleptic drugs.30 Yohimbine Hydrochloride. Yohimbine HCl is a powerful herbal stimulant and aphrodisiac available in the U.S. as an herbal supplement and as a prescription medicine used to treat male erectile dysfunction.31 Yohimbine has also been used for the treatment of sexual side effects caused by anti-depressant medications.32 Side effects of yohimbine include anxiety, rapid heart rate, high blood pressure, overstimulation, insomnia/sleep disturbance, panic attacks, hallucinations, headaches, dizziness, and skin flushing.32 Yohimbine has also caused seizures,
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ACCEPTED MANUSCRIPT renal failure, and is contraindicated for those with liver, kidney or heart problems, and psychological disorders.31,32 As a result of the increasing rates of both (a) illicit prescription stimulant use, (b) ED consumption by college students, as well as (c) the limited research examining the co-occurrence of these behaviors, the current investigation examined whether college students who reported ED use also reported illicitly using prescription stimulants. We hypothesized that regular ED use would increase the odds of illicit use of prescription stimulants. To test our hypothesis, we surveyed college students regarding their energy drink use as well as their use of stimulant drugs. Students answered a series of questions regarding their use of EDs and then separately their use of stimulant drugs. Mann Whitney U tests and logistic regression analysis were used to identify specific aspects of ED use that predicted illicit prescription stimulant use.
METHODS Data Collection Procedures A web-based survey was administered over a 4-week period in April and May of 2009 at a large Midwestern University and two of its branch campuses. After Institutional Review Board (IRB) approval, students were recruited through the university’s student email announcement system. The email contained an IRB approved description of the study and the participant’s rights page with a weblink to the online survey. After completing the survey, participants were taken to a separate and secure website where they were able to print a certificate to be entered in a lottery drawling for 6 cash prizes of $100. Completion of the full survey took participants approximately 15-20 minutes. All responses were anonymous and stored on a secure server
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ACCEPTED MANUSCRIPT maintained by the University, behind several firewall protections. No class credit or bonus was offered for participation in the study. The project was funded by the primary researcher’s college through an internal faculty research grant. Instrument The previously used Quick Drink Screen (QDS) was used to measure the quantityfrequency of ED use.16,33,34 The QDS is a daily estimation measure that provides a retrospective estimate of a person’s average consumption. The QDS contains only four drinking variables, is highly reliable and consistent when compared to the 12-month Timeline Followback, only takes 3-5 minutes to administer (versus 20-30), and is an efficient choice when multiple measures are used.34 The ED quantity-frequency and stimulant specific questions were part of the larger survey which also examined the “combined-use of alcohol and EDs” and reasons for using EDs. Reliability of the instrument was assessed using the Wilcoxon test. The test-retest (~2-week interval) coefficient was r =.92 (p
