Serving Substance Abuse Professionals Since 1993

Last Update: 08.09.11

C O R K O N L I N E

powerpoint presentations
CORK database search
resource materials
bibliographies
clinical tools
user services
newsletters
about cork
home

CORK Bibliography: Abuse Potential

55 citations. January 2009 to present

Prepared: September 2011

Ahijevych K; Garrett BE. The role of menthol in cigarettes as a reinforcer of smoking behavior. (review). Nicotine & Tobacco Research 12(Supplement 2): S110-S116, 2010. (34 refs.)

The World Health Organization has identified several additives such as menthol in the manufacturing of cigarettes to specifically reduce smoke harshness. These additives may have important implications for reinforcing smoking behavior and motivation to quit smoking. The purpose of this paper is to synthesize research related to the role of menthol's sensory characteristics in strengthening the reinforcing effects of nicotine in cigarettes and the impact on nicotine addiction and smoking behavior. Research reports from 2002 to 2010 on the addictive potential of menthol cigarettes were reviewed that included qualitative focus groups, self-reports and biomarkers of nicotine dependence, human laboratory, and epidemiological studies. Positive sensory effects of menthol cigarette use were identified via reports of early smoking experiences and as a potential starter product for smoking uptake in youth. Menthol cigarettes may serve as a conditioned stimulus that reinforces the rewarding effects of smoking. Nicotine dependence measured by shorter time-to-first cigarette upon waking was increased with menthol cigarette use in most of the studies reviewed. Smoking quit rates provide additional indicators of nicotine dependence, and the majority of the studies reviewed provided evidence of lower quit rates or higher relapse rates among menthol cigarette smokers. The effects of menthol cigarette use in increasing the reinforcing effects of nicotine on smoking behavior were evidenced in both qualitative and quantitative empirical studies. These findings have implications for enhanced prevention and cessation efforts in menthol smokers.

Allen B; Cruz TB; Leonard E; Unger JB. Development and validation of a scale to assess attitudes and beliefs about menthol cigarettes among African American smokers. Evaluation & the Health Professions 33(4): 414-436, 2010. (28 refs.)

To develop more effective smoking cessation interventions for the 70% of African American smokers who smoke menthol cigarettes, it is important to understand smokers' reasons for choosing menthols verses nonmenthols. This study conducted a focus group of African American smokers about their attitudes and beliefs about menthol cigarettes. These attitudes and beliefs, along with others from the literature, were included in a survey of 720 African American smokers in Los Angeles County, California. Five common factors emerged-Medicinal Effects, Image, Less Harmful, Tradition, and Taste/Sensation. Menthol smokers had significantly higher scores on the Taste/Sensation, Medicinal Effects, and Less Harmful scales than nonmenthol smokers did. Men were significantly more likely than women to endorse Medicinal Effects, Image, and Tradition, whereas women were significantly more likely to endorse Taste/Sensation. Education was inversely associated with endorsement of Medicinal Effects, Image, Less Harmful, and Tradition. Respondents aged 40 years or older had significantly higher scores on Medicinal Effects, Image, and Less Harmful, compared with younger respondents. Smoking cessation interventions for African American menthol smokers should address commonly held myths that menthols have medicinal effects and are less harmful than nonmenthols, especially among smokers who are older, male, and/or have low levels of education. The new measures presented in this article could be useful for tailoring cessation interventions to individual smokers' attitudes and beliefs about menthol cigarettes.

Babalonis S; Lile JA; Martin CA; Kelly TH. Physiological doses of progesterone potentiate the effects of triazolam in healthy, premenopausal women. Psychopharmacology 215(3): 429- 439, 2011. (50 refs.)

Gender plays a critical role in the effects of drugs and drug abuse liability. Biological factors, including ovarian hormones, may contribute to gender differences in drug abuse. Preclinical and some clinical research suggests that progesterone and its metabolites have activity at the GABA(A) receptor and may enhance the effect of GABAergic compounds (e.g., benzodiazepines). Because women are exposed to varying levels of progesterone from puberty until menopause, and appear more sensitive to the negative consequences of benzodiazepine use, it is important to understand the impact of progesterone on GABAergic drug effects. The purpose of this experiment was to characterize the behavioral effects of progesterone, alone and in combination with the short-acting benzodiazepine, triazolam, to determine if progesterone potentiates the behavioral effects of triazolam. Oral micronized progesterone (0, 100, and 200 mg) and oral triazolam (0.00, 0.12, and 0.25 mg/70 kg) were administered to healthy, premenopausal women (n = 11) under conditions of low circulating sex hormones. The subjective, performance and physiological effects of progesterone, alone and in combination with triazolam, were assessed. Triazolam alone produced prototypical sedative-like effects. Progesterone alone also engendered some sedative effects, although the time course of the effects was more limited than that of triazolam. Progesterone increased and extended the duration of triazolam effects and delayed the onset of triazolam peak effects, most notably at the 0.12 mg/70 kg dose. Progesterone potentiates the behavioral effects of benzodiazepines and may contribute to benzodiazepine use and abuse among women.

Benowitz NL; Dains KM; Dempsey D; Havel C; Wilson M; Jacob P. Urine menthol as a biomarker of mentholated cigarette smoking. Cancer Epidemiology, Biomarkers & Prevention 19(12): 3013-3019, 2010. (26 refs.)

Objectives: Menthol cigarettes are smoked by 27% of U. S. smokers, and there are concerns that menthol might enhance toxicity of cigarette smoking by increasing systemic absorption of smoke toxins. We measured urine menthol concentrations in relation to biomarkers of exposure to nicotine and tobacco carcinogens. Methods: Concentrations of menthol glucuronide (using a novel analytical method), nicotine plus metabolites (nicotine equivalents, NE), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and polycyclic aromatic hydrocarbon (PAH) metabolites were measured in the urine of 60 menthol and 67 regular cigarette smokers. Results: Urine menthol was measurable in 82% of menthol and 54% in regular cigarette smokers. Among menthol smokers, urine menthol was highly correlated with NE, NNAL, and PAHs. In a multiple regression model NE but not menthol was significantly associated with NNAL and PAHs. Conclusions: Urine menthol concentration is a novel biomarker of exposure in menthol cigarette smokers, and is highly correlated with exposure to nicotine and carcinogens. Menthol is not independently associated with carcinogen exposure when nicotine intake is considered.

Butler SF; Black R; Serrano JMG; Folensbee L; Chang A; Katz N. Estimating attractiveness for abuse of a not-yet-marketed "abuse-deterrent" prescription opioid formulation. Pain Medicine 11(1): 81-91, 2010. (29 refs.)

Objective. The present study builds on research to model abusers' perceptions of particular analgesics' attractiveness for abuse and extends these methods to derive an estimate of attractiveness for abuse of a not-yet-marketed abuse-deterrent formulation (ADF) of a prescription opioid (Remoxy (R), Pain Therapeutics, Inc., San Mateo, CA, and King Pharmaceuticals, Inc., Bristol, TN). In a previous study, the Opioid Attractiveness Technology Scaling (OATS) method identified, from a drug abuser's point of view, the particular features of a prescription opioid relevant to its attractiveness for recreational use. A second online sample rated the extent to which these features applied to particular products they had actually used/abused. These data were used to model the abusers' overall preference for prescription opioids they had used/abused. Design. In the present study, this method was applied to a not-yet-marketed ADF using substance abuse counselors as proxies for prescription opioid abusers. Thirty-eight counselors were given materials describing the new ADF along with four known products. Results. Thirty-two counselors demonstrated sufficient agreement with abusers' ratings of the overall attractiveness of these drugs. The overall model yielded a significant pseudo R-2 of 0.15 (P < 0.001), with increasing model fit based on preferred route of administration, from swallowing whole (pseudo R-2 = 0.06; P < 0.001) and best for those who preferred to inject (pseudo R-2 = 0.40; P < 0.001). Data from a cross-validation group of 16 counselors/proxies were used to calculate the OATS scores for the five rated drugs and revealed significant differences between the ADF and OxyContin (R) (Purdue Pharma LP, Stamford, CT), Percocet (R) (Endo Pharmaceuticals, Chadds Ford, PA), and Vicodin (R) (Abbott Laboratories, Abbott Park, IL), but not Talwin (R) NX (Sanofi-aventis, Bridgewater, NJ), which was identified in the prior study as a highly unattractive drug for recreational purposes. Conclusions. The OATS method shows promise for providing pre-marketing estimates of attractiveness for abuse of not-yet-marketed ADFs.

Chien CC; Huanga HT; Lung FW; Lin CH. Zolpidem withdrawal delirium, seizure, and acute psychosis: Case reports and literature review. (review). Journal of Substance Use 16(4): 330-338, 2011. (39 refs.)

Zolpidem, a non-benzodiazepine hypnotic drug, shows a high affinity for the BZ1 (omega 1) subtypes of the modulatory sites within the GABAA receptor complex, but classical benzodiazepines (diazepam, lorazepam) have a non-specific affinity profile at omega 1 and omega 2 subtypes of the GABAA receptor. Therefore, zolpidem is thought to be safer than benzodiazepines. We present five cases with withdrawal delirium, seizure, acute psychosis and orofacial dyskinesia that developed following cessation of zolpidem. Adverse effects such as withdrawal seizure and withdrawal delirium have been rarely reported in relation to zolpidem. Chemically unrelated to benzodiazepines, zolpidem is thought to have fewer adverse effects, but shares a pharmacokinetic profile with the benzodiazepines. It is advised that the normal criteria for the prescription of benzodiazepines also be used when prescribing non-benzodiazepine sedatives and hypnotics, as they act upon the same receptor, namely, the benzodiazepine-GABA-chloride complex. However, at higher than recommended doses for extended periods of time, the addictive potential of zolpidem may be similar to that of the benzodiazepines. It is possible that zolpidem abandons its selectivity for the BZ1 receptors and demonstrates all the actions of classic benzodiazepines.

Cicero TJ; Ellis MS; Paradis A; Ortbal Z. Determinants of fentanyl and other potent mu opioid agonist misuse in opioid-dependent individuals. Pharmacoepidemiology and Drug Safety 19(10): 1057-1063, 2010. (29 refs.)

Purpose: Based on preclinical and clinical abuse liability assessments, fentanyl and other potent mu opioid agonists (e.g., hydromorphone and morphine) should be the most misused opioids if accessibility in the real world were not an issue. Since the latter is seldom true, we postulated that there would be a significant mismatch between actual and predicted rates of misuse. Methods: We recruited 1818 prescription-opioid dependent patients entering drug treatment programs to complete an anonymous survey, covering drug use and health related issues. Results: Hydrocodone and oxycodone products were the drugs of choice in 75% of patients, whereas potent pc opioid agonists (fentanyl, hydromorphone, and morphine), with the greatest predicted abuse potential, were very rarely chosen (<5% each). Most unexpectedly, the rank order of the actual drug of choice and the preferred drug in an ideal world were highly correlated. The reason most commonly given for the failure to endorse fentanyl, for example, as an actual or preferred drug, was fear of toxicity and overdose. We found few differences in drug use patterns between a subset of high-risk, impaired health care professionals (N = 196), and all other patients other than source of drug (forged prescriptions and doctors more common and dealers much less common in the HC sample). Conclusions: These results indicate that it should not be assumed - particularly for new drug formulations that a high potential for abuse will result in actual abuse; and, most importantly, that the hesitancy to use potent opioids because of fears of abuse may be misguided.

Comer SD; Sullivan MA; Vosburg SK; Manubay J; Amass L; Cooper ZD et al. Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers. Addiction 105(4): 709-718, 2010. (40 refs.)

Background: Sublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, cross-over study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs). Methods: Intravenous heroin users (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the three buprenorphine maintenance dose conditions. Results: Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of 'drug liking' and 'desire to take the drug again' were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient. Conclusions: These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, that potential is lower than it is for buprenorphine alone, particularly when participants received higher maintenance doses and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment.

Connolly GN; Behm I; Osaki Y; Wayne GF. The impact of menthol cigarettes on smoking initiation among non-smoking young females in Japan. International Journal of Environmental Research and Public Health 8(1): 1-14, 2011. (53 refs.)

Japan presents an excellent case-study of a nation with low female smoking rates and a negligible menthol market which changed after the cigarette market was opened to foreign competition. Internal tobacco industry documents demonstrate the intent of tobacco manufacturers to increase initiation among young females through development and marketing of menthol brands. Japanese menthol market share rose rapidly from less than 1% in 1980 to 20% in 2008. Menthol brand use was dominated by younger and female smokers, in contrast with non-menthol brands which were used primarily by male smokers. Nationally representative surveys confirm industry surveys of brand use and provide further evidence of the end results of the tobacco industry's actions-increased female smoking in Japan. These findings suggest that female populations may be encouraged to initiate into smoking, particularly in developing nations or where female smoking rates remain low, if the tobacco industry can successfully tailor brands to them. The Japanese experience provides a warning to public health officials who wish to prevent smoking initiation among young females.

Cubbin C; Soobader MJ; LeClere FB. The intersection of gender and race/ethnicity in smoking behaviors among menthol and non-menthol smokers in the United States. Addiction 105(Supplement 1): 32-38, 2010. (31 refs.)

Aims: To determine whether menthol is related to initiation, quantity or quitting, we examined differences in smoking behaviors among menthol and non-menthol smokers, stratified by gender and race/ethnicity, and adjusting for age, income and educational attainment. Design: Cross-sectional, using data from the 2005 National Health Interview Survey and Cancer Control Supplement. Setting United States. Participants: Black, Hispanic and white women and men aged 25-64 years. Measurements: For each group, we examined (i) proportion of menthol smokers (comparing current and former smokers); (ii) age of initiation, cigarettes smoked per day and quit attempt in the past year (comparing menthol and non-menthol current smokers); and (iii) time since quitting (comparing menthol and non-menthol former smokers). We calculated predicted values for each demographic group, adjusting for age, income and educational attainment. Findings: After adjusting for age, income and education, black (compared with Hispanic and white) and female (compared with male) smokers were more likely to choose menthol cigarettes. There was only one statistically significant difference in age of initiation, cigarettes smoked per day, quit attempts or time since quitting between menthol and non-menthol smokers: white women who smoked menthol cigarettes reported longer cessation compared with those who smoked non-menthol cigarettes. Conclusions: The results do not support the hypothesis that menthol smokers initiate earlier, smoke more or have a harder time quitting compared with non-menthol smokers. A menthol additive and the marketing of it, given the clear demographic preferences demonstrated here, however, may be responsible for enticing the groups least likely to smoke into this addictive behavior.

Davis SP; McClave-Regan AK; Rock VJ; Kruger J; Garrett BE. Perceptions of menthol cigarette use among U.S. adults and adult smokers: Findings from the 2009 HealthStyles Survey. Nicotine & Tobacco Research 12(Supplement 2): S125-S135, 2010. (48 refs.)

Perceptions of menthol cigarette use may have implications for smoking initiation and cessation. This study explores harm and health perceptions of menthol cigarette use among a national sample of U.S. adults and current smokers. We examined data from the 2009 HealthStyles survey (n = 4,556), an annual mail survey of adults >= 18 years of age that collects information on attitudes and behaviors, including smoking. Frequencies and weighted percentages were calculated by sex, race/ethnicity, age, education level, household income, and smoking status. Unadjusted odds ratios (OR) were used to compare perceptions of menthol cigarette use between demographic groups. Close to half of adults (45.8%) believed that menthol cigarettes are just as harmful as nonmenthol cigarettes, and 40.9% of adults did not know whether menthol cigarettes are more or less harmful than nonmenthol cigarettes. Few adults (0.6%), including smokers, perceived menthol cigarettes to be less harmful than nonmenthol cigarettes. Blacks (OR = 3.22, 95% CI = 1.80-5.76) were more likely to believe that menthol cigarettes have health benefits when compared with Whites. Almost half of current smokers believed menthol cigarettes are equally addictive as nonmenthol cigarettes and 74.9% believed menthol and nonmenthol cigarettes are equally hard to quit. Findings suggest directions for targeted public health messages for menthol cigarette use. Future research is needed among a nationally representative sample to capture more subtle differences in perceptions among menthol and nonmenthol smokers.

Donoghue J; Lader M. Usage of benzodiazepines: A review. (review). International Journal of Psychiatry in Clinical Practice 14(2): 78-87, 2010. (58 refs.)

Purpose. The use of benzodiazepines remains a source of controversy. Some prescribers believe that they are beneficial and espouse their use; others regard their risk: benefit ratio as too adverse for any but occasional use. This review considers these viewpoints based on the appropriate literature. Survey. The recent English-language literature relating to this topic was surveyed. The publications proved too heterogeneous for a formal meta-analysis, so a descriptive review is provided. Overview. Surveys of benzodiazepine use provide data mainly from the UK, Europe and North America. Prescribing patterns varied widely but long-term usage is common and sometimes the norm. Conclusions. Long-term prescription of benzodiazepines still takes place despite general warnings from the medical and other professions and drug regulatory bodies that long-term use is unjustified both from the lack of a systemic database establishing such efficacy and a large literature documenting the risks of long-term usage, such as dependence. The young and the old are particularly at risk. Continued monitoring is essential, but the regulatory authorities may need to take a more active role in curbing such undesirable practice.

Duke AN; Correia CJ; Walsh SL; Bigelow GE; Strain EC. Acute effects of intramuscular and sublingual buprenorphine and buprenorphine/naloxone in non-dependent opioid abusers. Psychopharmacology 211(3): 303-312, 2010. (37 refs.)

Buprenorphine is a partial mu opioid receptor agonist with clinical efficacy as a pharmacotherapy for opioid dependence. A sublingual combination formulation was developed containing buprenorphine and naloxone with the intent of decreasing abuse liability in opioid-dependent individuals. However, the addition of naloxone may not limit abuse potential of this medication when taken by individuals without opioid physical dependence. The present study investigated the effects of buprenorphine alone and in combination with naloxone administered intramuscularly and sublingually to non-dependent opioid abusers. In a within-subject crossover design, non-dependent opioid-experienced volunteers (N = 8) were administered acute doses of buprenorphine (4, 8, and 16 mg) and buprenorphine/naloxone (4/1, 8/2, and 16/4 mg) via both intramuscular and sublingual routes, intramuscular hydromorphone (2 and 4 mg as an opioid agonist control), and placebo, for a total of 15 drug conditions. Laboratory sessions were conducted twice per week using a double-blind, double-dummy design. Buprenorphine and buprenorphine/naloxone engendered effects similar to hydromorphone. Intramuscular administration produced a greater magnitude of effects compared to the sublingual route at the intermediate dose of buprenorphine and at both the low and high doses of the buprenorphine/naloxone combination. The addition of naloxone did not significantly alter the effects of buprenorphine. These results suggest that buprenorphine and buprenorphine/naloxone have similar abuse potential in non-dependent opioid abusers, and that the addition of naloxone at these doses and in this dose ratio confers no evident advantage for decreasing the abuse potential of intramuscular or sublingual buprenorphine in this population.

Fagan P; Moolchan ET; Hart A; Rose A; Lawrence D; Shavers VL et al. Nicotine dependence and quitting behaviors among menthol and non-menthol smokers with similar consumptive patterns. Addiction 105(Supplement 1): 55-74, 2010. (95 refs.)

Aims: This study examines the associations between usual cigarette brand (i.e. menthol, non-menthol) and markers for nicotine dependence and quitting behaviors. Design: The 2003 and 2006/07 Tobacco Use Supplements to the Current Population Surveys were pooled to conduct secondary data analysis. Setting National data were collected using in-person and telephone computer-assisted interviews by the United States Census Bureau among civilian, non-institutionalized people aged 15 years and older. Participants: Data were analyzed among daily current smokers aged 18+ (n = 46 273). Measurements The associations between usual cigarette brand and time to first cigarette within 5 and 30 minutes after waking, quit attempts in the past 12 months and length of smoking abstinence in the past 12 months were examined. Bivariate and multivariate logistic regression models were stratified by smoking intensity: <= 5, 6-10, 11-19 and 20+ cigarettes per day. Findings Menthol smokers reported a mean of 13.05 compared with 15.01 cigarettes per day among non-menthol smokers (P < 0.001). Multivariate results showed that among smokers consuming 6-10 cigarettes per day, menthol smokers were significantly more likely than non-menthol smokers to consume their first cigarette within 5 minutes after waking (odds ratio = 1.22, 95% confidence interval = 1.05,1.43). The multivariate models did not show significant associations between usual cigarette brand and quit attempts in past 12 months or duration of smoking abstinence >2 weeks in the past 12 months. Conclusions: Findings from this national survey of daily smokers demonstrate that menthol smokers in the United States who report consuming 6-10 cigarettes per day show greater signs of nicotine dependence than comparable non-menthol smokers.

Fass JA. Carisoprodol legal status and patterns of abuse. Annals of Pharmacotherapy 44(12): 1962-1967, 2010. (21 refs.)

OBJECTIVE: To review the current legal status and patterns of abuse of carisoprodol. DATA SOURCES: A literature search was conducted through MEDLINE (1950-August 2010), PubMed (1966-August 2010), EMBASE (1966-August 2010), and International Pharmaceutical Abstracts (1970-August 2010) using the search terms carisoprodol and abuse. In addition, reference citations from publications identified were reviewed. State laws and regulations were accessed through NABPLAW Online (2010) using the search term carisoprodol. Federal proposed rules were accessed through the Federal Register (1995 Volume 59-2010 Volume 75) using the search term carisoprodol. STUDY SELECTION AND DATA EXTRACTION: State laws and federal proposed rules regarding carisoprodol were examined. Case reports and studies involving carisoprodol abuse were evaluated. DATA SYNTHESIS: Carisoprodol is not federally scheduled under the Controlled Substances Act (CSA). However, carisoprodol is scheduled in 36% (n = 18) of states of the US. The Drug Enforcement Administration issued a Notice of Proposed Rulemaking in the Federal Register on November 17, 2009, to place carisoprodol into schedule IV of the CSA, with a deadline to submit written comments by December 17, 2009. Case reports, retrospective studies, and national reports, including reports from the American Association of Poison Control Centers and results from the Monitoring the Future national survey on drug use, have identified carisoprodol's abuse potential. CONCLUSIONS: Carisoprodol should be placed in schedule IV of the CSA based on its abuse potential and current state laws and regulations. Federally scheduling carisoprodol would lead to uniformity among the states and hopefully assist in preventing prescription drug abuse. Larger, well-designed studies evaluating carisoprodol abuse should be performed.

Fenton MC; Keyes KM; Martins SS; Hasin DS. The role of a prescription in anxiety medication use, abuse, and dependence. American Journal of Psychiatry 167(10): 1247-1253, 2010. (34 refs.)

Objective: Prescriptions for anxiety medications have increased substantially in recent years. Individuals with anxiety disorders are at risk of nonmedical use of these medications, but information about whether this risk is elevated among patients with a prescription for such medications is lacking. The authors compared risk of nonmedical use in individuals in a national sample with and without a prescription for anxiety medication and identified characteristics associated with nonmedical use. Method: Data were drawn from face-to-face surveys of 34,653 adult participants in the National Epidemiologyogic Survey on Alcohol and Related Conditions. The risk of nonmedical use of prescription anxiety medication and associated drug use disorders was computed for individuals who had or had not ever received a prescription for anxiety medication; among those who had received a prescription, characteristics associated with nonmedical use were analyzed. Results: Prescription of anxiety medication was associated with lifetime and past-year nonmedical use (odds ratios, 1.6 and 1.9, respectively) and lifetime DSM-IV abuse or dependence (odds ratio, 2.6). Among respondents who received a prescription (N = 4,294), nonmedical use was associated with male sex, younger age, white race, history of use of illicit drugs, history of other drug use disorders, and history of illegal behaviors. Conclusions: These results indicate that prescription for anxiety medications is associated with nonmedical use of these medications, although the direction of causality cannot be determined in this study. Although anxiety medications have clinical utility, greater clinical attention should be given to the potential for their abuse among patients at particular risk.

Fernander A; Rayens MK; Zhang M; Adkins S. Are age of smoking initiation and purchasing patterns associated with menthol smoking? Addiction 105(Supplement 1): 39-45, 2010. (34 refs.)

Aims The purpose of this study was to examine the relationship between age of cigarette smoking initiation and cigarette purchasing patterns on menthol smoking among current smokers. Design Secondary analyses were conducted using logistic regression with balanced replicated weights. Setting Data from the 2003 and 2006/07 Tobacco Use Supplement (TUS) to the Current Population Survey (CPS), collected by the National Cancer Institute, the Centers for Disease Control and Prevention and the Census Bureau, formed the basis for this investigation. Participants A total of 66 145 current smokers who participated in the TUS CPS administration in 2003 and 2006/07 were examined. Measurements: Demographic characteristics (gender, race/ethnicity, age, education and income), smoking frequency, purchase type (pack, carton, or both), age of initiation and menthol cigarette use were assessed. Findings: One-quarter of the sample smoked menthol cigarettes; most purchased their cigarettes by the pack when rather than by the carton; average age of cigarette smoking initiation was 18 years; and females, ethnic/racial minorities and younger participants were more likely to smoke menthol cigarettes compared with males, whites or older respondents. Other demographic factors associated with menthol cigarette use among current smokers included a high school education (the prevalence of menthol use among this cohort was greater than either those with less education or those with more). The multivariate logistic model only marginally revealed that age of smoking initiation predicted menthol smoking: findings are suggestive that the longer the delay of initiation the more likely that an individual smoked menthol cigarettes [odds ratio (OR) = 1.01; 95% confidence interval (CI): 1.00-1.01]. In addition, relative to those who purchased cigarettes by the pack, smokers who purchased cigarettes by the carton were less (OR = 0.86; 95% CI: 0.81-0.91) likely to be menthol smokers. Conclusions: Menthol smokers in the United States are more likely to be female, younger, from ethnic minority groups, and to have a high school education. The findings that menthol smokers in the U.S. tend to start smoking later than smokers of other types of cigarettes are suggestive only and require further study.

Flaherty BP. Latent class and mixture models' potential contributions to understanding connections between menthol and other cigarette smoking characteristics. (editorial). Addiction 105(Supplement 1): 11-12, 2010. (15 refs.)

Foulds J; Hooper MW; Pletcher MJ; Okuyemi KS. Do smokers of menthol cigarettes find it harder to quit smoking? (review). Nicotine & Tobacco Research 12(Supplement 2): S102-S109, 2010. (31 refs.)

Menthol cigarette smokers may find it harder to quit smoking than smokers of nonmenthol cigarettes. We conducted a systematic review of published studies examining the association between menthol cigarette smoking and cessation. Electronic databases and reference lists were searched to identify studies published through May 2010, and results were tabulated. Ten studies were located that reported cessation outcomes for menthol and nonmenthol smokers. Half of the studies found evidence that menthol smoking is associated with lower odds of cessation, while the other half found no such effects. The pattern of results in these studies suggest that the association between smoking menthol cigarettes and difficulty quitting is stronger in (a) racial/ethnic minority populations, (b) younger smokers, and (c) studies carried out after1999. This pattern is consistent with an effect that relies on menthol to facilitate increased nicotine intake from fewer cigarettes where economic pressure restricts the number of cigarettes smokers can afford to purchase. There is growing evidence that certain subgroups of smokers find it harder to quit menthol versus nonmenthol cigarettes. There is a need for additional research, and particularly for studies including adequately powered and diverse samples of menthol and nonmenthol smokers, with reliable measurement of cigarette brands, socioeconomic status, and biomarkers of nicotine intake.

Gardiner P; Clark PI. Menthol cigarettes: Moving toward a broader definition of harm. (editorial). Nicotine & Tobacco Research 12(Suppl. 2): S85-S93, 2010. (56 refs.)

The current practice of the tobacco industry of primarily focusing on the extent that menthol cigarettes contribute or do not contribute to excess morbidity and mortality in various diseases does not, in and of itself, fully illuminate the harm caused by these products. In fact, this practice actually masks and obscures the public health harm associated with menthol cigarettes. Given this, this commentary develops and presents a broader definition of harm in which to view menthol cigarettes and as the necessary and underlying rationale of why this candy-flavored ingredient should be removed from all tobacco products. This paper relies on the scientific presentations of the 2nd Conference on Menthol Cigarettes, and the peer-reviewed literature on menthol cigarettes. A broader definition of harm from menthol cigarettes must be analyzed from a broad public health perspective and take into account youth uptake and initiation, menthol's ability to augment addiction through unique sensory properties, spurious health messages associated with these products, menthol's role in cessation inhibition and relapse promotion, and the blatant predatory marketing of these products to the most vulnerable sectors of society. The Food and Drug Administration (FDA) should apply the same logic that outlawed other candy flavorings and apply it to menthol cigarettes; in the end, all candy flavorings, including menthol, only serve to make the poisons inherent in tobacco smoke go down easier. Additionally, the mobilization of communities most affected by the menthol cigarettes, the FDA, and candy flavorings and the tobacco industry's machinations will be discussed.

Gjerden P; Bramness JG; Slordal L. The use and potential abuse of anticholinergic antiparkinson drugs in Norway: a pharmacoepidemiological study. British Journal of Clinical Pharmacology 67(2): 228-233, 2009. (26 refs.)

What is already known about this subject. Anticholinergic antiparkinson drugs are used to ameliorate extrapyramidal symptoms caused by either Parkinson's disease or antipsychotic drugs, but their use in the treatment of Parkinson's disease is assumed to be in decline. center dot Patients with psychotic conditions have a high prevalence of abuse of drugs, including anticholinergic antiparkinson drugs. What this study adds. Anticholinergic antiparkinson drugs in Norway were primarily prescribed to patients using antipsychotic medication. center dot The risk of abuse of this group of drugs was small, even among patients who probably abused other drugs. The use of anticholinergic antiparkinson drugs is assumed to have shifted from the therapy of Parkinson's disease to the amelioration of extrapyramidal adverse effects induced by antipsychotic drugs. There is a considerable body of data suggesting that anticholinergic antiparkinson drugs have a potential for abuse. The aim was to investigate the use and potential abuse of this class of drugs in Norway. Data were drawn from the Norwegian Prescription Database on sales to a total of 73 964 patients in 2004 of biperiden and orphenadrine, and use in patients with Parkinson's disease or in patients who were also prescribed antipsychotic agents. Possible abuse of these drugs was assessed by the level of use, skewedness of use, indications of drug-seeking behaviour and concomitant use of benzodiazepine tranquillizers, a group of prescription drugs with a recognized potential for abuse. Anticholinergic antiparkinson drugs were prescribed to 4.5% of all outpatients who used antipsychotic drugs. This outnumbered sales to patients with Parkinson's disease by > 20 to 1. We found indications of abuse of benzodiazepine tranquillizers among patients using antipsychotics, but there were no clear indications of abuse of anticholinergics, even among patients who were strongly suspected of abuse of benzodiazepines. Anticholinergic antiparkinson drugs were used primarily by patients with psychotic illnesses. These patients have a very high prevalence of legal and illegal drug abuse, but the risk of abuse of anticholinergic antiparkinson drugs seemed small.

Greene WM; Sylvester M; Abraham J. Addiction liability of pharmacotherapeutic interventions in obesity. (review). Current Pharmaceutical Design 17(12): 1188- 1192, 2011. (42 refs.)

Obesity and substance use disorders are rapidly growing problems throughout the world. Of the current mainstay therapies of diet, exercise, behavioral modification, surgery, and medications, drugs have the greatest risk for abuse and dependence. As each of these disorders share similar underpinnings mediated by the dopaminergic brain reward pathways, clinicians must seriously consider the safety of both the patient's physical and mental health when prescribing treatments. Specifically, balance and awareness of the factors involved in the variable abuse potentials of these prescribed medications is paramount. A cursory review of weight loss medications commonly used is performed with attention to FDA status, mechanism of action, and abuse potential. Concurrent strategies to minimize risk such as drug screening, ruling out doctor shopping, temporal considerations, monitoring for signs and symptoms of abuse and/or dependency, and a safety-tiered prescribing approach is also discussed in order to optimize best treatment practice. As the understanding of these disorders progresses along with the evolution of agreed nomenclature and awareness of compulsive behavioral disorders in general, greater safety and more appropriate interventions may be achieved. Further areas of research will help to elucidate nuances of the coocurrance and treatment of these disorders and perhaps guide drug research and development in the area of drug treatments of obesity.

Hammons G. What is the biological fate of mentholated cigarette smoking? (editorial. Addiction 105(Supplement 1): 8-10, 2010. (19 refs.)

Healton CG; Beck SE; Cartwright J; Vallone DM. Prohibiting menthol in tobacco products: A policy whose time has come. (editorial). Addiction 105(Supplement 1): 5-7, 2010. (17 refs.)

Hendricks EJ; Greenway FL. A study of abrupt phentermine cessation in patients in a weight management program. American Journal of Therapeutics 18(4): 292-299, 2011. (31 refs.)

Phentermine is the most widely used antiobesity drug in the United States. Although no evidence of phentermine addiction has been published, fear that phentermine has addiction potential has contributed to curtailment of its worldwide use in clinical practice. The aim of this study was to evaluate the abuse and addiction potential of long-term phentermine pharmacotherapy in patients in a weight management program. Thirty-five patients in a weight management program who abruptly stopped taking prescribed phentermine on their own initiative were examined using the 18-item Kampman Cocaine Selective Severity Assessment scale modified for phentermine. The Kampman Cocaine Selective Severity Assessment scale has also been modified by McGregor for amphetamines to assess withdrawal from amphetamine in amphetamine-addicted subjects. For comparison, 35 new patients were examined with the same scale before any treatment was initiated. Data from the treated and untreated groups were compared by t test with each other and with published data from amphetamine-addicted subjects. There were no significant differences in individual items or total scores between the patients who stopped phentermine abruptly and the patients who had never taken phentermine. There was a striking and significant difference in individual and total scores between the phentermine-treated subjects and the amphetamine-dependent subjects. Cravings for the substance abused, the hallmark characteristic of substance dependence and withdrawal, were entirely absent in the phentermine-treated subjects. Abrupt cessation of long-term phentermine therapy does not induce amphetamine-like withdrawal. Long-term phentermine therapy does not induce phentermine cravings. Symptoms observed after abrupt phentermine cessation represent loss of therapeutic effect and are not withdrawal.

Henningfield JE; Hatsukami DK; Zeller M; Peters E. Conference on abuse liability and appeal of tobacco products: Conclusions. and recommendations. (editorial). Drug and Alcohol Dependence 116(1-3): 1-7, 2011. (54 refs.)

The rate of initiation and progression to dependence and premature mortality are higher for tobacco products than for any other dependence producing substance. This is not explained simply by the addictiveness ("abuse liability") or by enticing product designs ("product appeal") alone, but rather by both of these factors in combination with marketing and social influences that also influence "product appeal". A working meeting of leading experts in abuse liability (AL) and product appeal was convened to examine how these disciplines could be more effectively applied to the evaluation of tobacco products for the purposes of regulation that would include setting standards for designs and contents intended to reduce the risk of initiation and dependence. It was concluded that abuse liability assessment (ALA) is a validated approach to testing pharmaceutical products but has not been extensively applied to tobacco products: such application has demonstrated feasibility, but special challenges include the diverse range of products, product complexity, and the absence of satisfactory placebo products. Consumer testing for product appeal is widely used by consumer product marketers as well as by researchers in their efforts to understand consumer product preferences and use but has not been extensively applied to tobacco products except by the tobacco industry. Recommendations for testing, methods development, and research were developed. A major recommendation was that tobacco products should be tested for AL and product appeal, and the results integrated and evaluated so as to more accurately predict risk of initiation, dependence, and persistence of use.

Hersey JC; Nonnemaker JM; Homsi G. Menthol cigarettes contribute to the appeal and addiction potential of smoking for youth. Nicotine & Tobacco Research 12(Supplement 2): S136-S146, 2010. (63 refs.)

Menthol cigarettes are a common choice of cigarettes among young smokers that contribute to the addictive potential of cigarette smoking. We reviewed prior research and analyzed the 2006 National Youth Tobacco Survey (NYTS), using logistic regression to assess the relationship between menthol cigarette use and needing a cigarette within 1 hr after smoking. In the 2006 NYTS, 51.7% (95% CI: 45.8-57.5) of middle school smokers and 43.1% (95% C.I.: 37.0, 49.1) of high school smokers reported that they usually smoked a menthol brand of cigarettes, using a menthol smoking status definition based on consistency between smokers' report of the brand and the menthol status of the cigarettes they usually smoked. A logistic regression model of dependence, controlling for background (i.e., school level, gender, and race/ethnicity) and smoking level (i.e., years, frequency, and level of smoking) found that smoking menthol cigarettes was significantly associated with reduced time to needing a cigarette among smokers with a regular brand (odds ratio [OR]: 1.86, p = .003) and among established smokers (OR: 2.06, p = .001). This is consistent with other studies that found that youth who smoked menthol cigarettes were significantly more likely than those who smoked nonmenthol cigarettes to report signs of nicotine dependency. Menthol cigarettes contribute to the appeal of youth smoking and to the addictive potential of smoking cigarettes among youth. It is important to control the use of menthol cigarettes and to implement cessation strategies that are effective with youth smokers.

Hoffmann F; Hies M; Glaeske G. Regional variations of private prescriptions for the non-benzodiazepine hypnotics zolpidem and zopiclone in Germany. Pharmacoepidemiology and Drug Safety 19(10): 1071-1077, 2010. (28 refs.)

Purpose: Although evidence is lacking, there is general perception that zolpidem and zopiclone ('Z-drugs') are more effective and safer than benzodiazepines leading to an increased prescribing of Z-drugs. In Germany, 85% of the inhabitants are covered by statutory health insurance (SHI), the rest is privately insured. Z-drugs are covered by SHIs but physicians can also provide private prescriptions for SHI insured persons, who then have to pay for these out of pocket. Since private prescriptions are not documented in SHI claims data, physicians might prescribe drugs associated with abuse as private prescriptions. We aim to quantify SHE versus private prescriptions of Z-drugs and analyze regional variations. Methods We studied a sample of 2500 community pharmacies located across Germany from 2006 to 2008. We analyzed the amount of private prescriptions in numbers of packages. Drug utilization was expressed in defined daily doses (DDDs) per 1000 inhabitants per day (DID). Results: The proportions of private prescriptions ranged between 36.7% and 36.9% per annum for zopiclone, this was significantly higher for zolpidem (49.4-49.6% per annum). There are substantial regional variations for zolpidem (28.8-82.6%) and zopiclone (22.5-68.6%). In all federal states the proportion of zolpidem not reimbursed by SHIs is higher than that of zopiclone (6.3-15.4%). The nation-wide outpatient consumption was 2.5 DID for zolpidem and 2.7 DID for zopiclone with large regional variations. Conclusions In addition to large regional variations, zolpidem is more often prescribed as a private prescription than zopiclone. This might be a signal for a higher abuse potential of zolpidem.

Jasinski DR; Krishnan S. Abuse liability and safety of oral lisdexamfetamine dimesylate in individuals with a history of stimulant abuse. Journal of Psychopharmacology 23(4): 419-427, 2009

Lisdexamfetamine dimesylate (LDX) is the first prodrug stimulant and is indicated for the treatment of attention-deficit/hyperactivity disorder. A single-centre, double-blind, randomised, placebo-controlled, 6-period crossover study evaluated the abuse potential of single oral doses of 50, 100 (equivalent to 40 mg d-amphetamine), and 150 mg LDX, 40 mg d-amphetamine and 200 mg diethylpropion in 36 individuals with a history of stimulant abuse. On the primary abuse liability measure, maximum change of the Drug Rating Questionnaire-Subject Liking Scale compared with placebo, d-amphetamine and diethylpropion showed significant differences of 4.5 and 4.0 units, respectively (P < 0.001 for both vs placebo). LDX, administered at 50, 100 and 150 mg, showed nonsignificant differences of 2.0 and 2.1 units, respectively, at the two lower doses but a significant (P < 0.001 vs placebo) difference of 6.1 units at the highest dose. Subjects significantly favoured d-amphetamine 40 mg versus LDX 100 mg (2.4 units difference; P < 0.05). There was no significant difference in liking scores between d-amphetamine 40 mg and LDX 150 mg. Drug Rating Questionnaire-Subject Feel-Drug-Effect score was significantly lower for 100 mg LDX than for 40 mg d-amphetamine. There were no statistically significant differences between LDX and diethylpropion hydrochloride, a Schedule IV amphetamine-like stimulant, on abuse-related liking scores. Cardiovascular responses of LDX and d-amphetamine were similar at equivalent doses. In conclusion, at an equivalent amount of amphetamine base taken orally, LDX 100 mg had attenuated responses on measures of abuse liability compared with immediate-release d-amphetamine 40 mg. Abuse-related liking scores of LDX at a dose corresponding to a 50% higher amphetamine base (LDX 150 mg) were similar to d-amphetamine 40 mg.

Jasinski DR; Krishnan S. Human pharmacology of intravenous lisdexamfetamine dimesylate: Abuse liability in adult stimulant abusers. Journal of Psychopharmacology 23(4): 410-418, 2009

The objective of this study is to determine the safety, tolerability and abuse liability of single intravenous (i.v.) doses of lisdexamfetamine dimesylate (LDX) and immediate-release d-amphetamine sulphate in adult stimulant abusers compared with placebo. Adult substance abusers were enrolled in this phase I, randomized, single-centre, double-blind study. An initial cohort of three subjects was enrolled to assess safety followed by a primary cohort that consisted of nine subjects. Single i.v. doses of LDX (25 or 50 mg), immediate-release d-amphetamine sulphate (10 or 20 mg) or placebo were administered at a minimum of 48-h intervals in a single-dose, three-way crossover design. 20 mg of d-amphetamine showed significantly increased abuse-related liking scores compared with placebo (P < 0.05), whereas the liking effects of 50 mg LDX did not significantly differ from placebo. The mean C-max of d-amphetamine was 38.9 +/- 8.1 and 105 +/- 91.4 ng/ml after the administration of 50 mg LDX and 20 mg d-amphetamine respectively. The mean T-max of d-amphetamine was 2.51 h after the administration of 50 mg LDX and 0.82 h after the administration of 20 mg d-amphetamine. LDX was well tolerated in this population. In contrast to d-amphetamine, LDX administered intravenously did not produce significant subjective abuse-related liking scores at assessed doses.

Kann IC; Biorn E; Luras H. Competition in general practice: Prescriptions to the elderly in a list patient system. Journal of Health Economics 29(5): 751-764, 2010. (43 refs.)

Income motivation among general practitioners (GPs) is frequently discussed in the health economics literature. The question addressed in the present study on reimbursement drugs and addictive drugs is whether increased competition among GPs, which is part of a declared health policy to improve efficiency, contributes to more prescriptions for the elderly. The dataset comprises registered data of all prescribed drugs dispensed at pharmacies from the Norwegian Prescription Database merged with data on GPs. In choosing a method, particular attention is given to the fact that patients tend to be attracted to GPs who fit their preferences. Hence, we treat the composition of the patient list as endogenous. The results indicate that the stronger competition a GP faces, the more drugs are prescribed, which implies that GPs' prescription style may conflict with their role as gatekeepers, and even worse, it may be a hazard to patients' health.

Kim D; Steinhart B. Seizures induced by recreational abuse of bupropion tablets via nasal insufflation. Canadian Journal of Emergency Medicine 12(2): 158-161, 2010. (25 refs.)

Bupropion is a newer generation antidepressant that is commonly used for treatment of depression and for smoking cessation. Seizures are a frequently reported adverse effect of bupropion in therapeutic oral doses; however, there are limited data about the consequences of nasal insufflation of bupropion. We report the case of a patient who presented to the emergency department (ED) with a recent history of generalized tonic-clonic seizures whose etiology was initially a diagnostic mystery. After an initial visit to another ED, the patient presented to our ED later that day with a recurrence of the seizures after crushing and nasally insufflating oral bupropion tablets. We review important implications of this case to emergency medicine, including the potential for abuse of bupropion, the difference between intranasal and oral administration, the changing trends in the etiology of drug-related seizures and the importance of examining the nares in patients with unexplained seizure and delirium.

King B; Yong HH; Borland R; Omar M; Ahmad AA; Sirirassamee B et al. Malaysian and Thai smokers' beliefs about the harmfulness of 'light' and menthol cigarettes. Tobacco Control 19(6): 444-450, 2010. (22 refs.)

Objective: This study explored the extent to which Malaysian and Thai smokers believe "light" and menthol cigarettes are less harmful than "regular" cigarettes and the correlates of these beliefs. Methods The study used data from wave 1 of the International Tobacco Control Southeast Asia Survey. 2006 adult smokers (95.3% male) from Malaysia and 2000 adult smokers (94.5% male) from Thailand were interviewed face to face in 2005. Results 29% of Malaysian respondents reported currently smoking light cigarettes and 14% menthols, with 19% agreeing that lights are less harmful and 16% agreeing that menthols are less harmful. 38% of Thai respondents reported currently smoking light cigarettes and 19% menthols, with 46% agreeing that lights are less harmful and 35% agreeing that menthols are less harmful. Malaysian smokers reporting current use of light or menthol cigarettes were more likely to believe that they are less harmful. Reported use of lights did not relate to beliefs for Thai respondents. The belief that light and/or menthol cigarettes are less harmful was strongly related to the belief that they have smoother smoke. Conclusions: The experience of smoother smoke is likely to produce some level of belief in reduced harm, regardless of how brands are labelled and whether or not Federal Trade Commission FTC/International Organisation for Standardisation tar, nicotine and carbon monoxide yield figures are used.

Kirkpatrick MG; Haney M; Vosburg SK; Comer SD; Foltin RW; Hart CL. Zolpidem does not serve as reinforcer in humans subjected to simulated shift work. Drug and Alcohol Dependence 112(1-2): 168-171, 2010. (25 refs.)

Zolpidem attenuates shift-change-related sleep and performance disruptions. It is unknown whether these benefits alter the reinforcing effects of the drug during shift work. This study examined zolpidem-related reinforcing effects during simulated shift work. Eleven volunteers (3F, 8M) completed this 16-day within-participant, residential laboratory study.. Each day participants were given an opportunity to self-administer oral zolpidem (10 mg) or receive a $1 voucher immediately following a 9-h work period and immediately before going to bed. Participants worked under two shift conditions: (1) during the night shift, participants completed computerized task batteries from 00:30 to 09:30 h and went to bed at 16:00 h and (2) during the day shift, participants completed task batteries from 08:30 to 17:30 h and went to bed at 24:00 h. Shift conditions alternated three times during the study. Despite the fact that sleep, psychomotor performance, and some ratings of mood were disrupted during night-shift work, there was no significant effect of shift on choice to take zolpidem. Overall, participants selected markedly fewer zolpidem doses than monetary vouchers (17% versus 83%). Thus, zolpidem did not serve as a reinforcer even when sleep was disrupted. These data are consistent with previous reports indicating that sedatives produce limited reinforcing effects in individuals without a history of drug abuse.

Kreslake JM; Yerger VB. Tobacco industry knowledge of the role of menthol in chemosensory perception of tobacco smoke. (editorial). Nicotine & Tobacco Research 12(Supplement 2): S98-S101, 2010. (34 refs.)

Sensory perception is a key determinant of smoking behavior and, therefore, reinforcement and addiction. The tobacco industry has conducted extensive research on the chemosensory and physiological effects of menthol in tobacco smoke and has actively promoted menthol's sensory characteristics. Based upon previously published examinations of internal tobacco industry documents, this commentary summarizes what is currently known about the tobacco industry's use of menthol to modify sensory characteristics in cigarettes and the implications of these activities for smoking behavior. The industry considers menthol to be an important tool for modulating the sensory effects of nicotine in different product variations, particularly those designed to be acceptable to "starters" or people interested in quitting. Regulatory efforts should consider that menthol enables the tobacco industry to customize a highly addictive product in a manner that contributes to initiation and deters cessation due to its chemosensory effects.

Larance B; Degenhardt L; Lintzeris N; Winstock A; Mattick R. Definitions related to the use of pharmaceutical opioids: Extramedical use, diversion, non-adherence and aberrant medication-related behaviours. (review). Drug and Alcohol Review 30(3): 236- 245, 2011. (106 refs.)

This paper (i) reviews the language used to describe and manage those patient practices that fall outside standard medical models of opioid treatment (for pain and opioid dependence), and (ii) proposes a consistent terminology that can be applied across multiple healthcare settings. Method. Peer-reviewed and grey literature documenting empirical studies of (non-)adherence with opioid treatment, proposed definitions or other potentially important aspects of terminology were included in this review. Results. There are international inconsistencies in the terminology used to describe the unintended consequences of opioid treatment, and the terms used often lack specificity. The terms 'hazardous use', 'extramedical use', 'opioid dependence', 'diversion', 'non-adherence' and 'aberrant behaviours' are defined. We advocate for consistent application of these terms in the context of opioid treatment, and propose that care is taken to describe individual practices and intentions. Conclusions. The increasing global attention on the use and diversion of pharmaceutical opioids warrants a discussion of current terms and definitions. Exaggerated concerns regarding 'addiction potential' may result in restrictions in the supply of opioids and the under-treatment of legitimate medical conditions. Researchers, clinicians, policy-makers and patients need to ensure greater care is given to terminology, including detailed descriptions of patient practices, the context in which they occur and severity of associated harm.

Lawrence D; Rose A; Fagan P; Moolchan ET; Gibson JT; Backinger CL. National patterns and correlates of mentholated cigarette use in the United States. Addiction 105(Supplement 1): 13-31, 2010. (74 refs.)

Aim: To examine the patterns and correlates of mentholated cigarette smoking among adult smokers in the United States. Design: Cross-sectional data on adult current smokers (n = 63 193) were pooled from the 2003 and 2006/07 Tobacco Use Supplements to the Current Population Survey. Measurements The associations between socio-demographic and smoking variables were examined with gender-and race/ethnicity-stratified multivariate logistic regression models predicting current use of mentholated cigarettes. Findings Multivariate logistic regression analyses demonstrated that black smokers were 10-11 times more likely to smoke mentholated cigarettes than white smokers men: odds ratio (OR): 11.59, 99% confidence interval (CI): 9.79-13.72; women: OR: 10.12, 99% CI: 8.45-12.11). With the exception of American Indian/Aleut/Eskimo smokers, non-white smokers were significantly more likely to smoke mentholated cigarettes than were white smokers. Additional significant factors associated with mentholated cigarette smoking included being unmarried (never married: OR: 1.21, 99% CI: 1.09-1.34; divorced/separated: OR: 1.13, 99% CI: 1.03-1.23), being born in a US territory (OR: 2.01, 99% CI: 1.35-3.01), living in a non-metropolitan area (OR: 0.87, 99% CI: 0.80-0.96), being unemployed (OR: 1.24, 99% CI: 1.06-1.44) and lower levels of education. Race/ethnicity-stratified analyses showed that women were more likely than men to smoke mentholated cigarettes. Among black smokers, young adults (aged 18-24 years) were four times more likely to smoke mentholated cigarettes compared with individuals aged 65+. Conclusions: Race/ethnicity, gender and age are significant correlates of mentholated cigarette smoking among current smokers. Given the importance of menthol in the cigarette market and the potential untoward health effects of this additive, continued surveillance of the prevalence and correlates of mentholated cigarette use among diverse socio-demographic groups is warranted to inform appropriate interventions.

Licata SC; Mashhoon Y; MacLean RR; Lukas SE. Modest abuse-related subjective effects of zolpidem in drug-naive volunteers. Behavioural Pharmacology 22(2): 160-166, 2011. (47 refs.)

Recent case reports suggest that the short-acting benzodiazepine-like hypnotic, zolpidem, may have abuse potential among individuals who have no personal history of abusing drugs or alcohol, particularly at doses higher than those recommended for treating insomnia. This study recruited drug-naive volunteers to assess the subjective effects of multiple doses of zolpidem (0, 5, 10, or 20 mg) administered in a within-subject double-blind design. Participants (n = 11) answered computerized questionnaires (Addiction Research Center Inventory, visual analog scales, and a hypothetical Drug versus Money Choice) to address the hypothesis that a supratherapeutic dose (20 mg) would increase ratings of abuse-related subjective effects, while lower therapeutic doses (5 and 10 mg) would not. Although participants rated some effects as negative at 10 and 20 mg, the highest dose engendered predominantly positive abuse-like effects such as 'High', 'Like', and 'Good Effects'. However, no dose of zolpidem was chosen over money ($0.35-$10) when participants made hypothetical choices between them. Results suggest that although individuals without a drug abuse history are not inclined to choose zolpidem when presented with an alternative reinforcer such as money, it may possess moderate abuse potential that limits its clinical utility.

Mello NK. Hormones, nicotine, and cocaine: Clinical studies. (review). Hormones and Behavior 58(1): 57-71, 2010. (163 refs.)

Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (2 min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine's sustained positive effects (<20 min), ratings of "high" and "rush" began to decrease within one or two puffs of a high-nicotine cigarette while nicotine levels were increasing. Peak nicotine levels increased progressively after each of three successive cigarettes smoked at 60 min intervals, but the magnitude of the subjective effects ratings and peak ACTH and cortisol levels diminished. Only DHEA increased consistently after successive cigarettes. The possible influence of neuroactive hormones on nicotine dependence and cocaine abuse and the implications for treatment of these addictive disorders are discussed.

Okuyemi KS; Lawrence D; Hammons G; Alexander LA. Use of mentholated cigarettes: What can we learn from national data sets? (editorial). Addiction 105(Supplement 1): 1-4, 2010. (7 refs.)

Palmer RHC; Young SE; Hopfer CJ; Corley RP; Stallings MC; Crowley TJ et al. Developmental epidemiology of drug use and abuse in adolescence and young adulthood: Evidence of generalized risk. Drug and Alcohol Dependence 102(1/3): 78-87, 2009. (63 refs.)

Past studies highlight a narrowing gender gap and the existence of a shared etiology across substances of abuse; however, few have tested developmental models using longitudinal data. We present data on developmental trends of alcohol, tobacco, and marijuana use, abuse and dependence assessed during adolescence and young adulthood in a community-based Colorado twin sample of 1733 respondents through self-report questionnaires and structured psychiatric interviews. Additionally, we report on the rates of multiple substance use and disorders at each developmental stage, and the likelihood of a substance use disorder (SUD: i.e., abuse or dependence) diagnosis in Young adulthood based on adolescent drug involvement. Most notably, we evaluate whether the pattern of multiple substance use and disorders and likelihood ratios across substances support a model of generalized risk. Lastly, we evaluate whether the ranked magnitudes of substance-specific risk match the addiction liability ranking. Substance use and SUDs are developmental phenomena, which increase from adolescence to Young adulthood with few and inconsistent gender differences. Adolescents and young adults are not specialized users, but rather tend to use or abuse multiple substances increasingly with age. Risk analyses indicated that progression toward a SUD for any substance was increased with prior involvement with any of the three substances during adolescence. Despite the high prevalence of alcohol use, tobacco posed the greatest substance-specific risk for developing subsequent problems. Our data also confirm either a generalized risk or correlated risk factors for early onset substance use and subsequent development of SUDs.

Rock VJ; Davis SP; Thorne SL; Asman KJ; Caraballo RS. Menthol cigarette use among racial and ethnic groups in the United States, 2004-2008. Nicotine & Tobacco Research 12(Supplement 2): S117-S124, 2010. (40 refs.)

Understanding the patterns of menthol cigarette use can be useful in developing and justifying polices designed to prevent and reduce cigarette use and exposure to tobacco smoke. This report provides an update and summary of the demographic distribution and trends of menthol cigarette use in the United States. Data from the 2004-2008 National Survey on Drug Use and Health were analyzed to estimate menthol cigarette use among current smokers by race/ethnicity, sex, and age (12 years and older). A t-test was used to compare estimates for menthol and nonmenthol use by demographic group. Trend analyses were conducted to examine differences in menthol cigarette use by race/ethnicity and age from 2004 to 2008. Over half of menthol cigarette smokers were female (52.2%), and approximately 29.4% of all menthol smokers were Black, which was almost 10 times the percentage of nonmenthol smokers who were Black (3.0%, p < .01). Prevalence of past month menthol cigarette use was highest among current smokers aged 12-17 years (44.7%) and decreased as age group increased. From 2004 to 2008, menthol cigarette use increased significantly among White smokers aged 12-17 years (from 40.3% in 2004 to 46.0% in 2008, p < .01). Menthol cigarette use among young adult smokers aged 18-25 years increased for Hispanics (from 33.9% in 2004 to 42.4% in 2008, p < .01) and Whites (from 26.7% to 32.5%, p < .01). Demographic disparities in menthol cigarette use persist in the United States. Continued monitoring and improvement of existing surveillance systems to identify patterns and trends in menthol cigarette use are needed.

Schneider JP; Matthews M; Jamison RN. Abuse-deterrent and tamper-resistant opioid formulations: What is their role in addressing prescription opioid abuse? CNS Drugs 24(10): 805-810, 2010. (43 refs.)

About one in every three individuals will experience chronic pain in their lifetime, and opioids are known to be an effective means to treat this condition. Much attention, however, has been given to the fact that prescription opioid analgesics are some of the most frequently abused drugs, and misuse is prominent in patients with chronic pain. Several new opioid formulations that are designed to prevent or deter the abuse of opioids are currently in development, and two have been approved for marketing (morphine sulphate co-formulated with naltrexone hydrochloride [Embeda (R)] and a new formulation of the extended-release oxycodone [OxyContin (R)]). In this article, we review the various types of abuse-deterrent and tamper-resistant formulations in clinical development. We believe that continued advances in opioid formulations can help mitigate risk for those with legitimate need for pain control, but only if used rationally in the context of good clinical practice.

Schoedel KA; Chen N; Hilliard A; White L; Stott C; Russo E et al. A randomized, double-blind, placebo-controlled, crossover study to evaluate the subjective abuse potential and cognitive effects of nabiximols oromucosal spray in subjects with a history of recreational cannabis use. Human Psychopharmacology: Clinical and Experimental 26(3): 224-236, 2011. (35 refs.)

Objective. This study aimed to evaluate the abuse potential and cognitive effects of nabiximols (Sativex (R), GW Pharma Ltd. Salisbury, UK), an oromucosal spray primarily containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Methods. This was a single-dose, randomized, double-blind, crossover study comparing nabiximols (4, 8, and 16 consecutive sprays: 10.8, 21.6, and 43.2 mg THC, respectively) with dronabinol 20 and 40 mg (synthetic THC: Marinol (R), Solvay Pharmaceuticals, Brussels, Belgium) and matching placebos in 23 recreational cannabis users. Subjective and cognitive/psychomotor measures were administered over 24 h post-dose. Results. Dronabinol was significantly different from placebo on abuse potential measures, thereby confirming study validity. Nabiximols 10.8 mg was not significantly different from placebo on primary measures but was different on some secondary measures. Nabiximols 21.6 mg was significantly greater than placebo on some primary/secondary measures, whereas nabiximols 43.2 mg showed significant effects on most measures. Nabiximols 10.8 mg was significantly lower than dronabinol doses on most measures (p < 0.05). Dronabinol 20 mg effects were numerically higher than nabiximols 21.6 mg but were statistically significant only for some measures. Dronabinol 40 mg and nabiximols 43.2 mg were generally not statistically different. Conclusions. Both dronabinol and nabiximols had significant abuse potential compared with placebo at higher doses. Nabiximols showed similar or slightly less abuse potential compared with dronabinol. Therefore, the abuse potential of nabiximols should be no higher than that of dronabinol.

Shram MJ; Sellers EM; Romach MK. Oral ketamine as a positive control in human abuse potential studies. Drug and Alcohol Dependence 114(2-3): 185- 193, 2011. (46 refs.)

The selection of a relevant and appropriate positive control is of key importance in the design of a clinical abuse potential study. Ketamine is a N-methyl-n-aspartate receptor antagonist used clinically as an anaesthetic, yet also abused for its euphoric and perceptual properties. The current study sought to identify 2 doses of oral ketamine that are safe and produce subjective effects that would make them suitable for use as positive controls in abuse potential studies. A single-center, partially double-blind, placebo-controlled, ascending dose (65,100 and 150 mg)study was carried out in 11 healthy recreational polydrug users who first passed a pharmacologic qualification session to ensure they could distinguish and like the effects of a psychoactive drug (20 mg n-amphetamine) compared to placebo. Subjective data were collected through questionnaires (e.g., Addiction Research Center Inventory [ARCI] scales) and visual analog scales (VAS). Generally, oral ketamine was well tolerated and could be used safely at 65 mg and 100 mg. Peak responses to ketamine were significantly different (p < 0.05) from placebo on measures of positive (e.g., drug liking VAS), perceptual (e.g., VAS of floating, detached, hallucinating) and sedative (e.g., ARCI phenobarbital-chlorpromazine-alcohol group scale) effects. Effects were generally not dose-dependent, though significant differences for some subjective effects measures were observed between 65 mg and 100 mg ketamine. The current study indicates that oral ketamine doses of 65 mg and 100 mg are useful positive controls for future abuse potential studies of compounds with a similar mechanism of action, or with possible perception-altering and euphoric effects.

Shriner RL. Food as a bariatric drug. (review). Current Pharmaceutical Design 17(12): 1198- 1208, 2011. (81 refs.)

As obesity, type 2 diabetes (T2DM) and the metabolic syndrome sweep across the research and the clinical landscape of medical care, effective pharmacologic remedies for the treatment of obesity have become imperative. The complexities of nutrient impact on neurotransmitter and endocrine modulating chemistry have become increasingly better characterized as have the basic neurochemical pathways that mediate their effects. Food addiction has emerged as an important phenomenon that may help to explain and improve our capabilities of rendering bench lab research into impactful clinical intervention. Against this challenging backdrop of current research and study we introduce the notion that food may, itself, represent a type of drug. In this review of food as a drug, we outline some of the emerging science that argues how proteins, carbohydrates and fats operating on three basic levels of organismic functioning may constitute the most powerful drugs we have available to effectuate weight loss or weight gain over time. In addition, certain foods may not only be more addictive than others, but may actually have a direct effect on pro-inflammatory mediators that determine both metabolic dysfunction as well as overall neuropsychiatric function and well-being.

Tauras JA; Levy D; Chaloupka FJ; Villanti A; Niaura RS; Vallone D et al. Menthol and non-menthol smoking: The impact of prices and smoke-free air laws. Addiction 105(Supplement 1): 115-123, 2010. (23 refs.)

Aims: To examine the relationship between menthol and non-menthol prices and smoke-free air laws and the choice between menthol and non-menthol cigarettes among current smokers. Design, setting and participants: Data were extracted from the nationally representative (USA) 2003 and 2006/07 Tobacco Use Supplements to the Current Population Survey. A total of 57,383 adult smokers (aged 18+) were examined. Measurements: A regression model was used to estimate the probability of being a menthol smoker conditional on being a current smoker who had a distinct preference for either non-menthol or menthol cigarettes. Cigarette prices, smoke-free air laws and socioeconomic and demographic characteristics were examined as covariates. Findings The prices of menthol and non-menthol cigarettes were associated with the choice between menthol and non-menthol cigarettes. However, smokers did not find menthol and non-menthol cigarettes to be close substitutes for one another. Non-menthol cigarettes were found to be less of a substitute for menthol cigarettes than vice versa. Young adults and African Americans were less responsive to prices with respect to switching between menthol and non-menthol cigarettes than were older adults and non-African Americans, respectively. Conclusions: The US Food and Drug Administration (FDA) is grappling with the issue of whether or not to ban menthol cigarettes. The findings from this study suggest that smokers do not find menthol and non-menthol cigarettes to be close substitutes. The strong preference for mentholated cigarettes may serve as a lever to reduce smoking prevalence when combined with increased access to effective cessation treatments.

Tjaderborn M; Jonsson AK; Ahlner J; Hagg S. Tramadol dependence: A survey of spontaneously reported cases in Sweden. Pharmacoepidemiology and Drug Safety 18(12): 1192-1198, 2009. (38 refs.)

Background: Tramadol is a weak opioid analgesic, which is generally considered to be safe. However, conflicting data exist on the dependence potential of tramadol. Objective The aim of this study was to investigate occurrence of tramadol dependence and associated risk factors using spontaneously reported adverse drug reactions. Methods The Swedish database for spontaneously reported adverse drug reactions, Swedish Drug Information System (SweDIS), was searched for reports on tramadol dependence from I January 1995 until 31 December 2006. Selection was conducted based on the DSM-IV definition of dependence. Available information was scrutinised and registered and then presented descriptively. Results: A total of 104 reports of tramadol dependence were identified, of which 60 (58%) concerned women. The median age (range) was 45 (15-84) years. Information on a history of substance abuse was present in 31 patients (30%) and 41 patients (39%) had a documented past or current use of a drug of abuse. Prescribed doses of tramadol ranged between 50-800 mg/day, and ingested doses between 50-4000 mg/day. Time of onset ranged from some weeks up to 4 years. In 72 (69%) cases the reaction was classified as serious, mainly due to hospitalisations for detoxification or discontinuation of tramadol. Conclusions: There is an occurrence of tramadol dependence in association with analgesic treatment within the recommended dose range. In susceptible patients a severe and serious dependence syndrome may develop. A history of abuse or use of a drug of abuse seems to be an important risk factor.

Trinidad DR; Perez-Stable EJ; Messer K; White MM; Pierce JP. Menthol cigarettes and smoking cessation among racial/ethnic groups in the United States. Addiction 105(Supplement 1): 84-94, 2010. (44 refs.)

Aim: To examine the association between smoking mentholated cigarettes and smoking cessation, separately for different racial/ethnic groups. Design Secondary data analysis of the 2003 and 2006-07 Tobacco Use Supplements to the Current Population Survey. Setting: United States. Participants: African American, Asian American/Pacific Islander, Hispanic/Latino, Native American, non-Hispanic white adults. Measurements: Examined relations between the use of mentholated cigarettes and measures of smoking cessation. Findings: Among African Americans (ORadj = 1.62, 95% CI: 1.35-1.95) and Hispanics/Latinos (ORadj = 1.21, 95% CI: 1.00-1.47), those who currently smoked mentholated cigarettes were more likely be seriously considering quitting in the next six months than were non-menthol smokers, after adjusting for sociodemographic factors. African Americans (ORadj = 1.87, 95% CI: 1.60-2.19) and Hispanics/Latinos (ORadj = 1.34, 95% CI: 1.11-1.62) who smoked mentholated cigarettes were also significantly more likely to have a positive estimation of successfully quitting in the next six months compared to non-menthol smokers. These associations were not found among Asian Americans/Pacific Islanders, Native Americans/Alaska Natives and Non-Hispanic Whites. Among former smokers, across racial/ethnic groups, those who smoked mentholated cigarettes (vs. non-menthols) were significantly less likely to have successfully quit for at least six months: African Americans (ORadj = 0.23, 95% CI: 0.17-0.31), Asian Americans/Pacific Islanders (ORadj = 0.22, 95% CI: 0.11-0.45), Hispanics/Latinos (ORadj = 0.48, 95% CI: 0.34-0.69) and Non-Hispanic Whites (ORadj = 0.28, 95% CI: 0.25-0.33). Conclusion: Across race/ethnic groups, those who used to regularly smoke mentholated cigarettes were less likely to have experienced long-term quitting success. Cessation programs should consider the type of cigarette typically smoked by participants, particularly menthols.

Uhlmann C; Froscher W. Low risk of development of substance dependence for barbiturates and clobazam prescribed as antiepileptic drugs: Results from a Questionnaire Study. CNS Neuroscience & Therapeutics 15(1): 24-31, 2009. (29 refs.)

There is no systematical research about the topic of dependence on antiepileptic drugs (AED) for patients with epilepsy, despite the fact that barbiturates and benzodiazepines comprise a potential risk of dependence. We hypothesize that there is no psychological substance dependence for patients with epilepsy, possibly because of their outcome expectations. The aim of the study was to examine these patients in terms of substance dependence. One hundred inpatients at the Lake Constance Epilepsy Center were asked about their experiences with AED in terms of dependence in a structured interview. We registered general statements about dependence of AED, markers for substance dependence, and outcome expectations. About 50% of the patients reported withdrawal symptoms and the development of tolerance, but less than 10% noticed loss of control and craving. Withdrawal symptoms and development of tolerance were significantly lower in a group of patients without barbiturates or clobazam versus patients with barbiturates or/and clobazam. There was no significant difference between these two groups in psychological criteria of dependence, that is, loss of control and craving. Outcome expectations of AED were clearly related to the efficacy against seizures, and only to a small amount to psychotropic effects. The study demonstrates that physiological variables of dependence are present more in patients with epilepsy with a permanent intake of barbiturates or clobazam, but psychological variables of dependence are rarely present in epileptic patients, with or without an intake of barbiturates and clobazam. These results confirm our hypothesis that substance dependence is not a major problem in benzodiazepines and barbiturates in patients with epilepsy. Outcome expectations seem to be related mainly to the anticonvulsant and not the psychotropic effect. This might be the reason for the absence of dependence.

Wang YG; Swick TJ; Carter LP; Thorpy MJ; Benowitz NL. Safety overview of postmarketing and clinical experience of sodium oxybate (Xyrem): Abuse, misuse, dependence, and diversion. Journal of Clinical Sleep Medicine 5(4): 365-371, 2009. (40 refs.)

Study Objectives: This study reviewed the cumulative postmarketing and clinical safety experience with sodium oxybate (Xyrem (R)), a treatment approved for cataplexy and excessive daytime sleepiness in narcolepsy. Study objectives were to investigate the occurrence of abuse/misuse of sodium oxybate since first market introduction in 2002, classify cases using DSIM-IV criteria for substance abuse and dependence, and describe specific characteristics of these cases. Methods: We retrospectively reviewed postmarketing spontaneous adverse event (AE) reports from 15 countries for all cases containing reporting terminology related to abuse/misuse to determine its occurrence. All death cases independent of causality were reviewed to identify associated risk factors. Results: Approximately 26,000 patients worldwide received sodium oxybate from first market introduction in 2002 through March 2008. of those 26,000 patients, 0.2% reported >= 1 of the events studied. These included 10 cases (0.039%) meeting DSM-IV abuse criteria, 4 cases (0.016%) meeting DSIM-IV dependence criteria, 8 cases (0.031%, including 3 of the previous 4) with withdrawal symptoms reported after discontinuation of sodium oxybate, 2 confirmed cases (0.008%) of sodium oxybate-facilitated sexual assault, 8 cases (0.031%) of overdose with suicidal intent, 21 deaths (0.08%) in patients receiving sodium oxybate treatment with 1 death known to be related to sodium oxybate, and 3 cases (0.01%) of traffic accidents involving drivers taking sodium oxybate. During this period, approximately 600,000 bottles of sodium oxybate were distributed, and 5 incidents (0.0009%) of diversion were reported. Conclusion: Cumulative postmarketing and clinical experience indicates a very low risk of abuse/misuse of sodium oxybate.

Ware MA; St Arnaud-Trempe E. The abuse potential of the synthetic cannabinoid, nabilone. Addiction 105(3): 494-503, 2010. (49 refs.)

Aim: Nabilone is a synthetic cannabinoid prescription drug approved in Canada since 1981 to treat chemotherapy-induced nausea and vomiting. In recent years, off-label use of nabilone for chronic pain management has increased, and physicians have begun to express concerns about nabilone becoming a drug of abuse. This study evaluates the evidence for abuse of nabilone, which is currently ill-defined. Study design Scientific literature, popular press and internet databases were searched extensively for evidence of nabilone abuse. Focused interviews with medical professionals and law enforcement agencies across Canada were also conducted. Findings: The scientific literature and popular press reviews found very little reference to nabilone abuse. Nabilone is perceived to produce more undesirable side effects, to have a longer onset of action and to be more expensive than smoked cannabis. The internet review revealed rare and isolated instances of recreational use of nabilone. The database review yielded little evidence of nabilone abuse, although nabilone seizures and thefts have occurred in Canada in the past few years, especially in Ontario. Most law enforcement officers reported no instances of nabilone abuse or diversion, and the drug has no known street value. Medical professionals reported that nabilone is not perceived to be a matter of concern with respect to its abuse potential. Conclusions: Reports of nabilone abuse are extremely rare. However, follow-up of patients using nabilone for therapeutic purposes is prudent and should include assessment of tolerance and dependence. Prospective studies are also needed to definitively address the issue of nabilone abuse.

Yargic I; Ozdemiroglu FA. Pregabalin abuse: A case report. Bulletin of Clinical Psychopharmacology 21(1): 64- 66, 2011. (7 refs.)

Pregabalin is a gamma-amino butyric acid (GABA) analogue used in the treatment of epilepsy, neuropathic pain, and generalized anxiety disorder. Although pregabalin is not a controlled medication in Turkey, it has a potential risk of abuse. It has not been approved for the treatment of psychiatric disorders (such as generalized anxiety disorder) in Turkey, so it is not yet popular as a drug of abuse among psychiatric patients. We report the first case of pregabalin abuse in Turkey in a 37 year old male patient who has a history of bipolar disorder and benzodiazepine abuse. In spite of the fact that pregabalin can be used in the treatment of benzodiazepine dependence, and pregabalin augmentation could be beneficial in treatment of anxiety disorders unresponsive to other medications, clinicians should be cautious while using pregabalin in treating patients with a history of drug or alcohol dependence.

Yorgason JT; Jones SR; Espana RA. Low and high affinity dopamine transporter inhibitors block dopamine uptake within 5 sec of intravenous injection. Neuroscience 182: e125- 132, 2011. (68 refs.)

Extensive evidence suggests that the reinforcing effects of cocaine involve inhibition of dopamine transporters (DAT) and subsequent increases in dopamine (DA) levels in the striatum. We have previously reported that cocaine inhibits the DAT within 4-5 s of i.v. injection, matching the temporal profile of the behavioral and subjective effects of cocaine. Intravenous injection of GBR-12909, a high affinity, long-acting DAT inhibitor, also inhibits DA uptake within 5 s. Given that high affinity, long-acting drugs are considered to have relatively low abuse potential, we found it intriguing that GBR-12909 had an onset profile similar to that of cocaine. To further explore the onset kinetics of both low and high affinity DAT inhibitors, we examined the effects of i.v. cocaine (1.5 mg/kg), methylphenidate (1.5 mg/kg), nomifensine (1.5 mg/kg), GBR-12909 (1.5 mg/kg), PTT (0.5 mg/kg), and WF23 (0.5 mg/kg) on electrically-evoked DA release and uptake in the nucleus accumbens core. Results indicate that all of the DAT inhibitors significantly inhibited DA uptake within 5 s of injection. However, the timing of peak uptake inhibition varied greatly between the low and high affinity uptake inhibitors. Uptake inhibition following cocaine, methylphenidate, and nomifensine peaked 30 s following injection. In contrast, peak effects for GBR-12909, PTT, and WF23 occurred between 20 and 60 min following injection. These observations suggest that the initial onset for iv. DAT inhibitors is extremely rapid and does not appear to be dictated by a drug's affinity.

Younis AA; Moselhy HF. Benzhexol-dependence resulting from self-medication for intermittent explosive disorder. International Journal of Psychiatry in Clinical Practice 13(1): 11-15, 2009. (29 refs.)

Objective. Recent observations in Iraq during the period of sanction suggest the existence of benzhexol prescribing linked to its calming effects on explosive behaviours. This inspired our group to research the existence of this practice and the characteristics of those involved in it. Method. All patients from the psychiatric service in Merjan Hospitalital, Al Hilla City, Babylon Governate, Iraq, who had a prescription for benzhexol between January 1991 and December 2000, were identified. All participants received their diagnosis based on the clinical criteria of the DSM-IV, after taking a comprehensive medical and psychiatric history, mental state examination and collateral information from family members. The patients were evaluated by the same qualified consultant psychiatrist at the initial assessment and all through the period of follow-up. Results. In the 10-year period under study, 354 patients were prescribed benzhexol. A total of 190 patients diagnosed as intermittent explosive disorder (IED) and 164 suffering from severe mental disorders or personality disorders were excluded from the study. The average age of the IED group was 29.5 years. On direct questioning, the main reason patients gave most frequently for using benzhexol was to control the aggressive outbursts (N=92, 48.4), to get high (N=49, 25.8), to relax (N=26, 13.7), to get rid of boredom (N=23, 12.1). In total, the whole group were prescribed benzhexol, at an average dose of 12.5 mg/day (range 2-20 mg/day). At the time of final assessment the mean dose of prescribed benzhexol had fallen slightly to 12 mg/day (2-20 mg/day), with 10 patients being benzhexol free. Of the 190, three patients had a diagnosis of obsessive compulsive disorders, 36 patients had a diagnosis of benzodiazepines dependence, and a further five had a diagnosis of alcohol dependency syndrome. Eighty percent felt satisfied with the effect of the drug and 95 were not motivated to stop it. Conclusions. There are a significant number of patients who are routinely prescribed benzhexol as a replacement therapy. The main original reason for starting it is to control outbursts and improves their reaction to stress situations. This growing issue raises the need for awareness, by both public and medical practitioners, of the potential adverse effects of benzhexol and its untoward consequences.