College students and use of K2 : an emerging drug of abuse in young persons

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College students and use of K2 : an emerging drug of abuse in young persons
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Hu, Xingdi
Primack, Brian A.
Barnett, Tracey E.
Cook, Robert L.
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Abstract:
Background K2 or “spice” has emerged as a popular legal alternative to marijuana among adolescents and young adults. However, no data has been published assessing prevalence of and associations with ever K2 use in any population. This study‟s aims were to examine prevalence of ever K2 use among a sample of college students, to determine characteristics of persons who use K2, and to access the association between K2 and other drug use. Findings Ever use of K2 was reported by 69 (8%) of the sample of 852 college students. Response rate was 36%. Bivariate and multivariate analyses assessed whether sociodemographic characteristics and other drug use were associated with ever use of K2. Ever use of K2 was reported by 69 (8%) of the sample. Among these 69 individuals, 61 (88%) had used a cigarette and 25 (36%) had used a hookah to smoke K2. In multivariate analyses, K2 use was more common in males (vs. females, adjusted Odds Ratio (aOR) = 2.0, 95% Confidence Interval (CI) = 1.2-3.5, p=0.01) and 1st or 2nd year college students (vs. 3rd year or above, aOR=2.4, 95% CI= 1.2-5.0, p=0.02). Conclusions Ever use of K2 in this sample was higher than ever use of many other drugs of abuse that are commonly monitored in adolescents and young adults. Although DEA had banned five synthetic cannabinoids recently, clinicians and public health officials concerned with substance abuse in youth should be aware of and monitor the use of this drug in college students over time.
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Published in journal Substance Abuse Treatment, Prevention and Policy.

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College students and use of K2: an emerging drug of abuse in young persons
IS 2 3 4 1 5
Xingdi Hu Brian A Primack Tracey E Barnett, Robert L Cook '
department of Epidemiology, University of Florida, Gainesville, Florida, USA Division of General Internal Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Division of Adolescent Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
4Department of Behavioral Science and Community Health, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA 5College of Medicine, University of Florida, Gainesville, Florida, USA
Corresponding author
Email address:
XH: qmshjwhx@phhp.ufi.edu BAP: primba@upmc.edu TEB: tebarnett@phhp.ufl.edu RLB: cookrl@phhp.ufi.edu


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ABSTRACT
Background
K2 or "spice" has emerged as a popular legal alternative to marijuana among adolescents and young adults. However, no data has been published assessing prevalence of and associations with ever K2 use in any population. This study's aims were to examine prevalence of ever K2 use among a sample of college students, to determine characteristics of persons who use K2, and to access the association between K2 and other drug use. Findings
Ever use of K2 was reported by 69 (8%) of the sample of 852 college students. Response rate was 36%. Bivariate and multivariate analyses assessed whether sociodemographic characteristics and other drug use were associated with ever use of K2. Ever use of K2 was reported by 69 (8%) of the sample. Among these 69 individuals, 61 (88%) had used a cigarette and 25 (36%) had used a hookah to smoke K2. In multivariate analyses, K2 use was more common in males (vs. females, adjusted Odds Ratio (aOR) = 2.0, 95% Confidence Interval (CI) = 1.2-3.5,/7=0.01) and 1st or 2nd year college students (vs. 3rd year or above, aOR=2.4, 95% CI= 1.2-5.0,/7=0.02). Conclusions
Ever use of K2 in this sample was higher than ever use of many other drugs of abuse that are commonly monitored in adolescents and young adults. Although DEA had banned five synthetic cannabinoids recently, clinicians and public health officials concerned with substance abuse in youth should be aware of and monitor the use of this drug in college students over time.


3
Findings
K2 or "spice" refers to a series of products that are advertised and sold legally as herbal blend incense. However, they are smoked by people to gain effects similar to marijuana, hashish, and other forms of cannabis. One or more synthetic cannabinoids, such as JWH-018, JWH-073 and CP 47, 497 C8 that mimic intoxication with marijuana with longer duration and poor detection on typical urine screens [1], are sprayed intentionally on dried herbs before they are packaged for sale as K2 [2]. These herbs have emerged as popular legal alternatives to marijuana among adolescents and young adults [3]. In response to the dangers of these products, on March 1, 2011, the Drug Enforcement Administration (DEA) issued the final order to temporarily ban five synthetic cannabinoids (JWH-018, JWH-073, JWH-200, CP 47,497 and CP 47,497 C8) following 18 states that had already implemented their own law or policy of controlling at one or more of these five synthetic cannabinoids [4].
According to the American Association of Poison Control Center (AAPCC), more than 2500 calls related to K2 were reported in 2010, compared with only 53 in 2009 [5]. Although no deaths have been reported, smoking K2 may produce several adverse health events, such as hallucinations, severe agitation, extremely elevated heart rate and blood pressure, coma, suicide attempts, and drug dependence, which is typically rare among classical cannabis users [6-8]. While some studies have detailed the adverse events and emergency department presentation associated with K2 use [8, 9], it is unclear if this product is being used by persons who typically do not smoke, or if it is only being used by other smokers.


The primary objectives of this study are (1) to describe the prevalence of ever K2 use among a sample of college students and characteristics of persons who use K2; and (2) to assess associations between K2 and other drug use, including tobacco, cigarettes and marijuana.
In September 2010, University of Florida students were asked about K2 use as part of a study focusing on hookah tobacco smoking. These data were collected electronically via electronic mail invitations. Of 2396 emails delivered, 852 (36%) of students responded; this response rate is in the moderate-good range for this type of survey [10]. The institutional review boards of the University of Florida and the University of Pittsburgh approved this study.
Participants responded to items assessing sociodemographic data and tobacco smoking knowledge, attitudes, and behavior. Marijuana use was assessed by asking "have you ever smoked marijuana, even a puff?" K2 smoking was assessed using two items which asked "Have you ever smoked 'spice' (also known as 'K2' or 'legal weed') from a hookah?" and "Have you ever smoked 'spice' (also known as 'K2' or 'legal weed') from something other than hookah, such as a cigarette?" Two-way chi-squared analysis was performed to assess if sociodemographic data, tobacco and marijuana smoking were associated with K2 use. All sociodemographic variables that were significantly associated with ever K2 use in these bivariate analysesand traditional risk factors for substance use, such as living arrangement and relationshipwere included in a multivariate logistic regression model to assess the adjusted associations while controlling for other covariates. In order to avoid the potential for co-linearity, the multivariate model did not include both age and year in school. Instead, year in school was


dichotomized to distinguish early college students (Is or 2n year) from more advanced students. All analyses were performed using SAS statistical software, version 9.2.
The average ( SD) age of this sample of 852 college students was 20.6 5.1 years. Nearly half (47%) of respondents were female. Racial/ethnic distributions were White (59%), Hispanic (17%), African American (8%), Asian/Pacific Islander (13%) and other (3%). Most students (70%>) were in their first or second year, and 64% of participants were single at the time of data collection. The majority (71%) of surveyed students were living off-campus (Table 1), and ever use of other substances was reported by 34% for cigarettes, 36% for marijuana, and 39% for hookah tobacco.
Ever use of K2 was reported by 69 (8%) of the sample. Among these 69 persons, K2 was used in a cigarette/joint by 61 (88%) and in a hookah by 25 (36%), respectively. Seventeen of the 69 individuals (25%) had used both hookahs and cigarettes to smoke K2. Among K2 users, ever use of other substances was reported by 61 (88%) for hookah tobacco, 63 (91%) for marijuana and 53 (77%>) for cigarettes.
Bivariate analyses showed that ever use of K2 was significantly associated with age, gender, year in school, and ever use of other substances (hookah tobacco, cigarettes and marijuana smoking) but not race, living arrangement, or relationship (Table 1). Multivariate logistic regression models included all appropriate covariates except for age, which was highly correlated with year in school (Pearson correlation coefficients.81). These analyses suggested that K2 use was more common among males compared with females and among 1st or 2nd year college students


6
rd
compared with 3 year or above college students (Table 1). Ever use of K2 was not significantly associated with living arrangement or relationship.
This study demonstrated that K2 or "spice", an emerging synthetic marijuana drug, had been used by 8% of a sample of college students from a large university; and that ever use of K2 was associated with male gender and younger age. To our knowledge, this is the first report of prevalence of ever K2 use and association of K2 use with sociodemographic characteristics and other substance use. Although 8% is below the prevalence of major substances, such as marijuana and tobacco, it is higher than the prevalence of many other drugs of abuse that are commonly monitored in college population, such as cocaine, LSD, heroin, sedatives, and anabolic steroids [11]. Considering the potential dangers of using K2 reported over the past several years, wider monitoring of this type of drug use would be warranted.
K2 could be a "gateway drug" related to other smoking substances. For example, students who smoked K2 might then advance to marijuana smoking. Although our data cannot show definitive temporal association, the data suggests that most users of K2 already smoked marijuana and therefore, it is not clear that K2 is a gateway drug to other smoking drugs. We found that K2 use was more common among 1st and 2nd year college students than 3rd year college students. This may indicate that K2 use begins in high school, which would be consistent with case studies that emphasize use in secondary school [3, 6, 8]. However, it is also possible that they started to use this substance very early in college but then reduced its usage due to emerging legal alcohol use and/or social maturation. Longitudinal cohort data may help illuminate these uptake patterns.


7
This study was limited by its cross-sectional design. We cannot infer whether K2 use preceded or followed hookah tobacco use, for example. Additionally, outcome variables were assessed with self-report, rather than biochemical validation, and the sample was drawn from only one large university. In this study, an overall 36% response rate was obtained; this rate was 41% for females versus with 31% for males. This response rate is expected for this type of survey; in fact, systematic reviews have demonstrated 36% average response rates for 31 studies using email survey over 14 years [10,12]. Additionally, it is possible that non-response in this survey resulted in a more conservative estimate of K2 use in this population, because responses obtained from these types of surveys are generally higher from female, higher-achieving, less risk-taking sociodemographic groups [13].
In conclusion, we found that K2 had been used by nearly one in ten college students and was particularly common among males and early college students. Ever use of K2 was also higher than ever use of many other drugs of abuse that are commonly monitored in adolescents and young adults. Prevention of use of K2 or other synthetic cannabinoids products should be focused on male students or those who just enter college. Additionally, clinicians and public health officials concerned with substance abuse in youth should be aware of this drug and monitor its use in college students over time. The latest national ban of five synthetic cannabinoids does not necessarily indicate the end of K2 or "spice". For example, K2 manufacturers have already started to produce and sell a new generation of K2 products that are claimed to be "completely legal everywhere" (using a similar product with another, not yet illegal, synthetic cannabinoid). Future study with longitudinal data may be useful to investigate the impact of this new policy.


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Competing interest
The authors declare that they have no competing interests.
Author's contributions
XH performed the data analysis and wrote the manuscript. BAP, TEB and RLC participated in the design of the study, collected the data and helped to draft the manuscript. All authors read and approved the final manuscript.
Acknowledgement
The study reported in this manuscript was funded by R01-CA140150 and a grant from the Steven D. Manners Memorial Fund. Publication of this article was funded in part by the University of Florida Open-Access Publishing Fund


9
Reference
1. Lindigkeit R, Boehme A, Eiserloh I, Luebbecke M, Wiggermann M, Ernst L, Beuerle T: Spice: a never ending story? Forensic Sci Int 2009, 191:58-63.
2. Brock T: "Spice" Wars.
[http://www.caymanchem.eom/app/template/Article.vm/article/2163/a/zl, accessed on May 2, 2011.
3. DeNoon DJ: FAQ: K2, Spice gold, and herbal 'incense'- legal herbal products laced with designer drugs: not your father's marijuana, [http://www.webmd.com/mental-health/news/k2-spice-gold-herbal-incense-faq1, accessed on April 26, 2011.
4. Drug Enforcement Adminstration : Schedules of Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into Schedule I, Federal Register, 76 (40). 2011.
5. American Association of Poison Control Centers: Fake Marijuana Spurs More than 2,500 Calls to U.S. Poison Centers this Year Alone, Alexandra, VA, 2010.
6. Missouri Department of Health and Senior Services: Health Advisory: K2 Synthetic Marijuana Use among Teenagers and Young Adults in Missouri, Missouri, 2010.
7. Muller H, Sperling W, Kohrmann M, Huttner HB, Kornhuber J, Maler JM: The synthetic cannabinoid spice as a trigger for an acute exacerbation of cannabis induced recurrent psychotic episodes. SchizophrRes 2010; 118:309-310.
8. Schneir AB, Cullen J, Ly BT: "Spice" girls: synthetic cannabinoid intoxication. J Emerg Med 2010; 40:296-299.
9. Zimmermann US, Winkelmann PR, Pilhatsch M, Nees JA, Spanagel R, Schulz K: Withdrawal phenomena and dependence syndrome after the consumption of "spice gold".
Dtsch Arztebl Int 2009; 106:464-467.
10. Keeter S, Miller C, Kohut A, Groves RM, Presser S: Consequences of reducing nonresponse in a national telephone survey. Public Opin Q 2000; 64:125-148.
11. Johnston LD, O'Malley PM, Bachman JG, Schulenberg JE: Monitoring the future national results on adolescent drug use: overview of key findings, 2010.
[http://www.monitoringthefuture.org/pubs/monographs/mtf-overview2010.pdfl, accessed on June 6,2011.


10
12. Sheehan KB: E-mail Survey Response Rates: A Review. Journal of Computer-Mediated Communication 2001; 6:0.
13. Hutchison J, Tollefson N, Wigington H: Response bias in college freshmen's responses to mail surveys. Research in Higher Education 1987; 26:99-106.


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Table
Table 1: Associations between characteristics of college students and K2 use (N=852).
Characteristic Sample n(%) K2 use n (row %) />-valuea (Wald x2, df) aORb (95% CI,/> value)
Age
18-19 572 (68) 55 (10) 0.02 (5.2, 1) -
20+ 265 (32) 13(5) -
Gender
Female 397 (47) 22 (6) <0.01 (6.9, 1) 1.0 (reference)
Male 452 (53) 47 (10) 2.0(1.2-3.5, 0.01)
Race
White 492 (59) 43 (9) 0.43 (3.8, 4) -
Hispanic 145(17) 15 (10) -
African American 66 (8) 2(3) -
Asian/Pacific Islander 107(13) 7(7) -
Otherc 25 (3) 2(8) -
Year in school
3rd year or above 252 (30) 11(4) <0.01 (6.9, 1) 1.0 (reference)
i st / ond 1 12 year 589 (70) 58 (10) 2.4(1.2-5.0, 0.02)
Relationship
Married/Engaged d 296 (36) 17(6) 0.06 (3.6, 1) 1.0 (reference)
Single 536 (64) 51 (10) 1.5 (0.8-2.6, 0.20)
Living arrangement
On-campus e 243(29) 22 (9) 0.32(1.0, 1) 1.0 (reference)
Off-campus 596 (71) 45 (8) 1.2(0.7-2.1, 0.49)
Cigarettes Ever
Yes 288 (34) 53 (18) <0.01 (61.1, 1) -
No 555 (66) 16(3) -
Marijuana Ever
Yes 294 (36) 63 (21) <0.01 (106.6, 1) -
No 535 (65) 5(1) -
Hookah Ever
Yes 331 (39) 61 (18) <0.01 (76.8, 1) -
No 511 (61) 8(2) -
df, degree of freedom; aOR, adjusted Odds Ratio; CI, Confidence Interval
a Chi-square analyses compare the proportion of those with and without K2 use for each
sociodemographic characteristic (Wald x and degree of freedom are presented)
b Multivariate logistic regression model includes gender, year in college, relationship, and living
arrangements.
0 Respondents in "other" race group are Native American/Alaskan Native and multiracial or biracial, including Asian/Black or White/Black.


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d Married/Engaged indicates students who were married, divorced or engaged.
e On-campus includes students living in campus residence hall, fraternity/sorority house and
other university/college housing.


Full Text

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1 College students and use of K2: an emerging drug of abuse in young persons Xingdi Hu 1 § Brian A Primack 2 3 Tracey E Barnett 4 Robert L Cook 1, 5 1 Department of Epidemiology Univer sity of Florida, Gainesville, Florida US A 2 Division of General Internal Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania US A 3 Division of Adolescent Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania US A 4 Department of Behavioral Science and Community Health College of Public Health and Health Professions, Univer sity of Florida, Gainesville, Florida US A 5 College of Medicine, University of Florida, Gainesville, Fl orida US A § Corresponding a uthor Email address : XH: qmshjwhx@phhp.ufl.edu BAP: primba@upmc.edu TEB: tebarnett@phhp.ufl.edu RLB: cookrl@ phhp.ufl.edu

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2 ABSTRACT Background K2 or s pice has emerged as a popular legal alternative to marijuana among adolescent s and young adults. However, no data ha s been published assessing prevalence of and associations with ever K2 use in any population T s were to examine prevalence of ever K2 use among a sample of college students, to determine characteristics of persons who use K2 and to access the association between K2 and other drug use Findings Ever use of K2 was reported by 69 (8%) of the sample of 852 college students Response rate was 36%. Bivariate and multivariate analyses assessed whether sociodemographic characteristics and other drug use were associated with ever use of K2 Ever use of K2 was reported by 69 (8%) of the sample Among these 69 individuals, 61 (88%) had used a cigarette and 25 (36%) had used a hookah to smoke K2. In m ultivariate analyses K2 use was more common in male s ( vs. females, adjusted Odds Ratio (aOR) = 2.0, 95% Confidence Interval (CI ) = 1.2 3.5 p =0.01 ) and 1 st or 2 nd year college students ( vs. 3 rd year or above, aOR=2.4, 95% CI= 1.2 5.0 p =0.02 ). Conclusions Ever use of K2 in this sample was higher than ever use of many other drugs of abuse that are commonly monitored in adolescents and young adults Al though D E A had banned five synthetic cannabinoids recently, c linicians and public health officials concerned with substance ab use in youth should be aware of and monitor the use of this drug in college students over time

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3 Findings K2 or s pice refer s to a series of products that are advertised and sold leg ally as herbal blend incense However, t hey are smoked by people to gain effects similar to marijuana, hashish, and other forms of cannabis. One or more synthetic cannabinoid s, such as JWH 018, JWH 073 a nd CP 47, 497 C8 that mimic intoxication with marijuana with longer duration and poor detection on typical urine screens [1] are sprayed intentionally on dried herbs before they are packaged for sale as K2 [2] The se herbs have emerged a s popular legal alternative s to marijuana among adolescent s and young adults [3] In response to the dangers of th ese product s on March 1, 2011, the Drug Enforcemen t Administration (DEA) issued the final order to temporarily ban five synthetic cannabinoids (JWH 018, JWH 073, JWH 200, CP 47,497 and CP 47,497 C8) follow ing 18 states that had already implemented their own law or policy of controlling at one or more of t hese five synthetic cannabinoids [4] According to the American Association of Poison Control Center (AAPCC), more than 2 500 c alls related to K2 were reported in 2010 compared with only 53 in 2009 [5] Although no deaths have been reported, smoking K2 may produce several adverse health events, such as hallucinations, severe agitation, extremely elevated heart rate and blood pressure, coma, suicide attempts and drug dependence whi ch is typically rare among classical cannabis users [6 8] While some studies have detailed the adverse events and emergency depart ment presentation associated with K2 use [8, 9] it is unclear if this product is being used by persons who typically do not smoke, or if it is only being used by other smokers.

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4 The primary objectives of this study are (1) to describe the prevalence of ever K2 use among a sample of college students and characteristics of persons who use K2; and (2) to assess associations between K2 and other drug use including tobacco, cigarettes and mariju ana In September 2010, University of Florida students were asked about K2 use a s part of a study focusing on hookah tobacco smoking. These data were collected electronically via e lectronic mail invitations. Of 2396 emails delivered, 852 (36%) of student s responded ; this response rate is in the moderate good range for this type of survey [10] The institutional review boards of the University of Florida and the University of Pittsburgh approved th is study. Participant s responded to items assessing soci o demographic data and tobacco smoking knowledge, attitudes, and behavior M arijuana use was assessed by asking K2 smoking was assessed using two items which H ave you ever smoked spice ) from a hookah ) from something other than hookah such as a cigarette ? T wo way chi squared analysis was performed to assess if socio demographic data tobacco and marijuana smoking were associated with K2 use. All sociodemographic variables that were significantly associated with ever K2 use in the se bivariate analyses and traditional risk factors for substance use, such as living arrangement and relationship were included in a multivariate logistic regression model to assess the adjusted association s while controlling for other covariates. In order to avoid the potential for co linearity, the multivariate mo del did not include both age and year in school. Instead, year in school was

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5 dichotomized to distinguish early college students ( 1 st or 2 nd year ) from more advanced students. All analyses w ere performed using SAS statistical software version 9.2. The av erage ( SD) age of this sample of 852 college students was 20.6 5.1 years Nearly half (47 %) of respondents were female. R acial /ethnic distributions were White (59 %), Hispanic (17 %), African American (8 %) Asian/ Pacific Islander (13 %) and other (3 %). M ost students (70 %) were in their first or second year and 64% of participants were single a t the time of data collection. The m ajority (71%) of surveyed students were living off campus ( T able 1 ) and e ver use of other substances was reported by 34% for cigarettes 36% for mari juana, and 39% for hookah tobacco Ever u se of K2 was reported by 69 (8 %) of the sample. Among these 69 persons, K2 was used in a cigarette/joint by 61 (88%) and in a hookah by 25 (36%) respectively Seventeen of the 69 individuals (25%) had used both h ookahs and cigarettes to smoke K2. Among K2 users ever use of other substances was reported by 61 ( 88 %) for hookah tobacco, 63 ( 91% ) for marijuana and 53 (77%) for cigarettes Bi variate analyses showed that ever use of K2 was significantly associated wi th age, gender, year in school, and ever use of other substances (hookah tobacco, cigarettes and marijuana smoking) but not race, living arrangement or relationship ( Table 1 ) Multivariate logistic regression models included all appropriate covariates exc ept for age which was highly correlated with year in school (Pearson correlation coefficient=0.81) These analyses suggested that K2 use was more common among males compared with females and among 1 st or 2 nd year college student s

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6 compared with 3 rd year or above college students ( T able 1 ). Ever use of K2 was not significantly associated with living arrangement or re lationship This study demonstrated that K2 or spice a n emerging synthetic marijuana drug had been used by 8% of a sample of college stud ents from a large university; and that ever use of K2 was associated with male gender and younger age. To our knowledge, this is the first report of prevalence of ever K 2 use and association o f K2 use with socio demographic characteristics and other substan ce use. Although 8% is below the prevalence of major substances such as marijuana and tobacco, it is higher than the prevalence of many other drugs of abuse that are commonly monitored in college population such as cocaine, LSD, heroin, sedatives, and an abolic steroids [11] Considering the potential dangers of using K2 reported over the past several years wider monitoring of this type of drug use would be warranted. r smoking substances. For example, students who smoked K2 might then advance to marijuana smoking. Although our data cannot show definitive temporal association, the data suggests that most users of K2 already smoked marijuana and therefore, it is not clea r that K2 is a gateway drug to other smoking drugs. We found that K2 use was more common among 1 st and 2 nd year college students than 3 rd year college students This may indicate that K2 use begins in high school which would be consistent with case studie s that emphasize use in secondary school [3, 6, 8] However, it is also possible that they started to use this substance very e arly in college but then reduced its usage due to emerging legal alcohol use and /or social maturation L ongitudinal cohort data may help illuminate these uptake patterns

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7 This study was limited by its cross sectional design. We cannot infer whether K2 us e preceded or followed hookah tobacco use, for example. Additionally, outcome variables were assessed with self report, rather than biochemical validation, and the sample was drawn from only one large university. In this study, a n overall 36% response rate was obtained ; this rate was 41% for females versus with 31% for males. This response rate is expected for this type of survey; in fact, systematic reviews have demonstrate d 36% average response rates for 31 studies usin g email survey over 14 years [10, 12] Additionally, it i s possible that non response in this survey resulted in a more conservative estimate of K2 use in this population because responses obtained from these types of surv eys are generally higher from female, higher achieving, less risk taking sociodemographic groups [13] In conclusion we found that K2 had been used by nearly one in ten college students an d was particularly common among males and early college students Ever use of K2 was also higher than ever use of many other drugs of abuse that are commonly monitored in adolescents and young adults. P revention of use of K2 or other synthetic cannabinoids products should be focused on male students or those who just enter college. Additionally, c linicians and public health officials concerned with substance abuse in youth should be aware of this drug and monitor its use in college students over time T he l atest national ban of five synthetic cannabinoids does not necessarily indicate the end of K2 or spice For example, K2 manufacturer s have already started to produce and sell a new generation of K2 products that are claimed to be completely legal everyw here (using a similar product with another, not yet illegal, synthetic cannabinoid). Future study with l ongitudinal data may be useful to investigate the impact of this new policy

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8 Competing interest The authors declare that they have no competing inter ests. XH performed the data analysis and wrote the manuscript. BAP, TEB and RLC participated in the design of the study, collected the data and helped to draft the manuscript. All authors read and approved the final manuscript. Ack nowledgement The study reported in this manuscript was funded by R01 CA140150 and a grant from the Steven D. Manners Memorial Fund. Publication of this article was funded in part by the University of Florida Open Access Publishing Fund

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9 R eference 1. Lindigkeit R, Boehme A, Eiserloh I, Luebbecke M Wiggermann M Ernst L Beuerle T : Sp ice: a never ending story? Forensic Sci Int 2009 191 :58 63. 2. Brock T: [ http://www.caymanchem.com/app/template/Article.vm/article/2163/a/z ] a ccessed on May 2, 2011. 3. DeNoon DJ: legal herbal products laced with arijuana. [ http://www.webmd.com/mental health/news/k2 spice gold herbal incense faq ] accessed on April 26 2011 4. Drug Enforcement Adminstration : Schedules of Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into Schedule I Fede ral Register, 76 (40). 2011. 5. American Association of Poison Control Cent ers: Fake Marijuana Spurs More than 2,500 Calls to U.S. Poison Centers this Year Alone Alexandra, VA, 2010. 6. Missouri Departmen t of Health and Senior Services: Health Advis ory: K2 Synthetic Marijuana Use among Teenagers and Young Adults in Missouri Missouri, 2010. 7. Muller H, Sperling W, Kohrmann M, Huttner HB Kornhuber J Maler JM : The synthetic cannabinoid s pice as a trigger for an acute exacerbation of cannabis induc ed recurrent psychotic episodes Schizophr Res 2010 ; 118 :309 310. 8. Schneir AB, Cullen J, Ly BT: "Spice" girls: synthetic cannabinoid i ntoxication. J Emerg Med 2010 ; 40 :296 299. 9. Zimmermann US, Winkelmann PR, Pilhatsch M, Nees JA Spanagel R Schulz K : Withdrawal phenomena and dependence syndrome after the consumption of "spice gold" Dtsch Arztebl Int 2009 ; 106 :464 467. 10. Keeter S, Miller C, Kohut A, Groves RM Presser S : Consequences of reducing nonresponse in a national telephone survey. Publi c Opin Q 2000 ; 64 :125 148. 11. Schulenberg JE : Monit oring the f uture national r esults on adolescent drug use: o verview of key findings, 2010 [ http://www.monitoringthefuture.org/pubs/monographs/mtf overview2010.pdf ] accessed on June 6 2011.

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10 12. Sheehan KB: E mail Survey Response Rates: A Review Journal of Computer Mediated Communication 2001 ; 6 :0 13. Hutchi son J, Tollefson N, Wigington H: Response bias in college freshmen's responses to mail surveys. Resear ch in Higher Education 1987 ; 26 :99 106.

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11 Table Table 1: Associations between characteristics of college students and K2 use (N=852). df, degree of freedom; aOR, adjusted Odds Ratio; CI, Confidence Interval a Chi square analyses compare the proportion of those with and without K2 use for each sociodemogra phic characteristic (Wald 2 and degree of freedom are presented ) b Multivariate lo gistic regression model include s gender, year in college, relationship, and living arrangements. c Respon are Native American/Alaskan Native and multiracial or biracial, including Asian/Black or White/Black. Characteristic Sample n (%) K2 use n ( row %) p value a ( 2 df) aOR b (95% CI, p value) Age 18 19 572 (68) 55 (10) 0.02 (5.2, 1) 20+ 265 ( 3 2 ) 1 3 ( 5 ) Gender Female 397 (47) 22 (6) <0.01 (6.9, 1) 1.0 (reference) Male 452 (53) 47 (10) 2.0 (1.2 3.5, 0.01 ) Race White 492 (59) 43 (9) 0.43 (3.8, 4) Hispanic 145 (17) 15 (10) African American 66 (8) 2 (3) Asian/Pacific Islander 107 (13) 7 (7) Other c 25 (3) 2 (8) Year in school 3 rd year or above 252 (30) 11 (4) <0.01 (6.9, 1) 1.0 (reference) 1 st / 2 nd year 589 (70) 58 (10) 2.4 (1.2 5.0, 0.02 ) Relationship Married/Engaged d 296 (36) 17 (6) 0.06 (3.6, 1) 1.0 (reference) Single 536 (64) 51 (10) 1.5 (0.8 2.6, 0.20) Living arrangement On campus e 243 (29) 22 (9) 0.32 (1.0, 1) 1.0 (reference) Off campus 596 (71) 45 (8) 1.2 (0.7 2.1, 0.49) Cigarettes Ever Yes 288 (34) 53 (18) <0.01 (61.1, 1) No 555 (66) 16 (3) Marijuana Ever Yes 294 (36) 63 (21) < 0.01 (106.6, 1) No 535 (65) 5 (1) Hookah Ever Yes 331 (39) 61 (18) <0.01 (76.8, 1) No 511 (61) 8 (2)

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12 d Married/En gaged indicates students who were married, divorced or engaged. e O n campus includes students living in campus residence hall, fraternity/sorority house and other university/colleg e housing.