Loosening the Grip: a handbook of Alcohol Information 9th

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Understanding and managing prescription opioid abuse is one of the major challenges in pain management worldwide. The relationships between prescriptive usage of opioids and reported morbidity at the national level, using data front the Drug Abuse Warning Network (DAWN), were examined. When the major prescription opioids were evaluated, the association between prescriptive medical use in kilograms and reported morbidity, as measured by a ratio between the two, was similar for the intermediate-potency opioids (hydrocodone, methadone, oxycodone, and morphine). This rate was much lower for low-potency opioids (codeine, meperidine, pentazocine, and propoxyphene) and much greater for high-potency opioids (hydromorphone and fentanyl). When the drugs were adjusted by potency (relative to morphine), the rates of reported morbidity per kilogram of morphine equivalent opioid in prescriptive usage were similar among the opioids. Using the potency-adjusted total kilograms of opioid in prescriptive use for all the opioids evaluated, there was a statistically significant association (r(2) = 0.9791) with the reported morbidity for prescription analgesics as a class, as measured in the DAWN system. These data suggest that non-medical use of opioids is predictable based on potency and extent of prescriptive use. Copyright 2006, Elsevier Science

Davids E, Gastpar M. Buprenorphine in the treatment of opioid dependence (review). European Neuropsychopharmacology 14(3): 209–216, 2004. (101 refs.)

Buprenorphine has become of increasing interest to be an alternative to methadone in the treatment of heroin addicts. The aim of the paper is to review, from a clinical perspective, the current status of what is known about the pharmacology of buprenorphine, with a particular emphasis on the issues of maintenance therapy in heroin addiction. A systematic review of published follow-up data, from observational and experimental studies was done. Electronic databases Medline and PSYNDEXplus were searched from their earliest entries. Buprenorphine appears to be a well-tolerated drug, with a benign overall side effect. Buprenorphine is an additional treatment option for heroin dependent patients, especially for those who do not wish to start or continue with methadone or for those who do not seem to benefit from adequate dosages of methadone. Copyright 2004, Elsevier Science BV

Degenhardt L, Hall W. Is cannabis use a contributory cause of psychosis? (review). Canadian Journal of Psychiatry 51(9): 556–565, 2006. (86 refs.)

Objective: To assess whether cannabis use in adolescence and young adulthood is a contributory cause of schizophreniform psychosis in that it may precipitate psychosis in vulnerable individuals. Method: We reviewed longitudinal studies of adolescents and young adults that examined the relations between self-reported cannabis use and the risk of diagnosis with a psychosis or of reporting psychotic symptoms. We also reviewed studies that controlled for potential confounders, such as other forms of drug use and personal characteristics that predict an increased risk of psychosis. We assessed evidence for the biological plausibility of a contributory causal relation. Results: Evidence from 6 longitudinal studies in 5 countries shows that regular cannabis use predicts an increased risk of a schizophrenia diagnosis or of reporting symptoms of psychosis. These relations persisted after controlling for confounding variables, such as personal characteristics and other drug use. The relation did not seem to be a result of cannabis use to self-medicate symptoms of psychosis. A contributory causal relation is biologically plausible because psychotic disorders involve disturbances in the dopamine neurotransmitter systems with which the cannabinoid system interacts, as demonstrated by animal studies and one human provocation study. Conclusion: It is most plausible that cannabis use precipitates schizophrenia in individuals who are vulnerable because of a personal or family history of schizophrenia. Copyright 2006, Canadian Psychiatric Association

Dietze P, Miller S, Clemens S, Matthews S, Gilmour S, Collins L. The Course and Consequences of the Heroin Shortage in Victoria. NDARC Technical Report No. 206. Sydney, Australia: National Drug and Alcohol Research Centre, 2004. (56 refs.)

Executive Summary. Heroin and related harms increased dramatically in Victoria in the late 1990s. In late 2000/early 2001, reports suggested a dramatic decline in the supply of heroin, a phenomenon commonly termed the "heroin drought." This was accompanied by media reports of changes in heroin use and associated harms such as overdose. This prompted research efforts by the National Drug Law Enforcement Research Fund. Among the key findings were that indeed there was a dramatic decrease in December 2000-January 2001. In terms of the characteristics and immediate effects of the shortage -- there were decreases in the purity of heroin; reported declines in ease of access and an accompanying increase in price; there was a 61% decline in opioid hospitalizations in Victoria; a decline in the treatment occasions provided for specialized drug services; and an increase in robbery incidents reported to police. Nonetheless, the overall extent of intravenous drug use was little changed, although amphetamine, benzodiazepine, prescribed opioid and cannabis use increased among intravenous drug uses. An accompanying result was that the general health of intravenous drug users declined; there was an increase in mental health problems, especially associated with stimulant use; and an increase in the prevalence of injection-related problems among intravenous users as well as increase in injection practices associated with infection. There was also an impact upon police with a decline in resources devoted to heroin policing, an improvement in linkages between health and law enforcement agencies. Following an Executive Summary and Introduction this report has ten major sections. They outline the history of the heroin market, changes in drug use among injecting drug users; description of the heroin shortage; changes in health effects of drug use; resulting changes in drug treatment patterns; changes in drug related crime; changes that resulted for health and law enforcement officials; and the impression of key informants. Copyright 2004, National Drug and Alcohol Research Centre (Australia)

Dorsey TL, Zawitz MW, Middleton P. Drugs and Crime Facts. Washington DC: U.S. Department of Justice, 2007. NCJ 165148. www.ojp.usdoj.gov/bjs/pub/pdf/dcf.pdf

ElSohly MA, National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Quarterly Report, Potency Monitoring Project, Report #87, Aug. 9, 2004–Nov. 8, 2004

Fedala PJ, Bridge TP, eds. Buprenorphine and buprenorphine/ naltrexone: A Guide for Clinicians. Drug and Alcohol Dependence 70(2, Supplement 1): 559–577, 2003.

This is a special consisting of nine article, with the collection entitled "Buprenorphine and Buprenorphine/Naloxone, A Guide for Clinicians." The articles are especially directed toward physicians, pharmacists, nurses, therapists, and other clinical-care staff providing treatment services to opioid-addicted individuals in the United States. Buprenorphine is a mu-opioid partial agonist that has been used as an analgesic for approximately the last 25 years. As a mu-opioid partial-agonist, buprenorphine fills the treatment gap between the full agonists, methadone and levomethadyl acetate, and the antagonist naltrexone. More recently, a combination product containing both buprenorphine and naloxone for sublingual administration has been developed to reduce the potential for abuse of buprenorphine itself. Both buprenorphine and the buprenorphine/naloxone combination have recently been approved for the treatment of opioid addiction.

Fergusson DM, Boden JM, Horwood LJ. Cannabis use and other illicit drug use: Testing the cannabis gateway hypothesis. Addiction 101(4): 556–569, 2006. (67 refs.)

Aim: To examine the associations between the frequency of cannabis use and the use of other illicit drugs. Design: A 25-year longitudinal study of the health, development and adjustment of a birth cohort of 1265 New Zealand children. Measurements: Annual assessments of the frequency of cannabis use were obtained for the period 14-25 years, together with measures of the use of other illicit drugs from the same time period. Findings: The frequency of cannabis use was associated significantly with the use of other illicit drugs, other illicit drug abuse/dependence and the use of a diversity of other drugs. This association was found to be particularly strong during adolescence but declined rapidly as age increased. Statistical control for confounding by both fixed and time dynamic factors using random- and fixed-effects regression models reduced the strength of association between frequency of cannabis use and other illicit drug use, but a strong association between frequency of cannabis use and other illicit drug use remained even after control for non-observed and time-dynamic sources of confounding. Conclusions: Regular or heavy cannabis use was associated with an increased risk of using other illicit drugs, abusing or becoming dependent upon other illicit drugs, and using a wider variety of other illicit drugs. The risks of use, abuse/dependence, and use of a diversity of other drugs declined with increasing age. The findings may support a general causal model such as the cannabis gateway hypothesis, but the actual causal mechanisms underlying such a gateway, and the extent to which these causal mechanisms are direct or indirect, remain unclear. Copyright 2006, Society for the Study of Addiction to Alcohol and Other Drugs

Fergusson DM, Poulton R, Smith PF, Boden JM. Drugs: Cannabis and psychosis. British Medical Journal 332(7534): 172–175, 2006. (23 refs.)

The United Kingdom is considering reclassifying cannabis because of concerns about links with mental health problems. This column deals with what the evidence does and does not show. It considers two areas of extensive research which have not been integrated. One is the link between cannabis and psychosis and the other is how cannabis affects neurochemical functioning. Among the evidence noted are (1) all studies have found that the use of cannabis is associated with increased risks of psychosis or psychotic symptoms and there is a dose-response relationship; and this relationship has been found with different measures for outcome and when confounded variables are controlled, as well as reverse causality. (2) The neurological pathways that link cannabis use and increased psychotic symptoms are not wholly clear. the most likely involve the effects of dealt-9-terthydocannabiono on the regulation of dopamine and serotonin, both of which are known to have a role in maintaining the psychotic state. It is noted that the use of cannabis accounts for about 10% of the cases of psychosis. At a policy level this leads to the confronting "a choice of evils: in which the rights of the majoring who use cannabis without problem, are balanced against the risk for a minority who may incur serious health consequences. Copyright 2006, BMJ Publishing Group

Ferri M, Davoli M, Perucci CA. Heroin maintenance treatment for chronic heroin-dependent individuals: A Cochrane systematic review of effectiveness (review). Journal of Substance Abuse Treatment 30(1): 63–72, 2006. (42 refs.)

Background: Many medications have been used for stabilizing heroin users: Methadone, Buprenorphine and LAAM. The present review focus on the prescription of heroin to heroin dependents. Objectives To assess the efficacy and acceptability of heroin maintenance versus methadone or other substitution treatments for opioid dependence, in retaining patients in treatment; reducing the use of illicit substances and improving health and social functioning. Search strategy The Cochrane Central Register of Trials (CENTRAL) issue 1, 2005; MEDLINE 1966-2005, EMBASE 1980-2005 and CINAHL till 2005 (on OVID) were searched. There was no language or publication year restrictions. Many researchers were contacted for information. Selection criteria Randomised controlled trials of heroin (alone or combined with methadone) maintenance treatment compared with any other pharmacological treatments for heroin dependents. Data collection and analysis The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. Studies were not pooled together because of heterogeneity. Main results 2400 references were obtained and 20 studies were eligible, 4 met the inclusion criteria for a total of 577 patients. The studies could not be analysed cumulatively because of heterogeneity of interventions and outcomes. Retention in treatment: no groups difference was found in two studies; one study (N= 96) found RR= 2.82 (95% CI 1.70- 4.68) favouring heroin; one study (N= 235) found RR 0.79 (95% CI 0.68- 0.90) favouring methadone. Relapse to illegal heroin use (self-reported): in one study people using heroin in treatment was 64% (heroin group) and 59% ( methadone group); in the other study the RR of heroin use was 0.33 (95% CI 0.15- 0.72) favouring heroin. Criminal offence: one study showed the potential of heroin prescription in reducing the risk of being charged RR 0.32 (95% CI 0.14- 0.78). Social functioning: two studies did not show statistical difference between intervention groups, and two studies considered criminal offence and social functioning as part of a multidomain outcome measure showing improvements among those treated with heroin plus methadone over those on methadone only. Authors' conclusions No definitive conclusions about the overall effectiveness of heroin prescription is possible. Results favouring heroin treatment come from studies conducted in countries where easily accessible Methadone Maintenance Treatment at effective dosages is available. In those studies heroin prescription was addressed to patients who had failed previous methadone treatments. The present review contains information about ongoing trials which results will be integrated as soon as avilable. Copyright 2005, Wiley-Liss

Fiellin DA, Pantalon MV, Chawarski MC, Moore BA, Sullivan LE, O’Connor PG, et al. Counseling plus buprenorphine-naloxone maintenance therapy for opioid dependence. New England Journal of Medicine 355(4): 365–374, 2006. (30 refs.)

Background: The optimal level of counseling and frequency of attendance for medication distribution has not been established for the primary care, office-based buprenorphine-naloxone treatment of opioid dependence. Methods: We conducted a 24-week randomized, controlled clinical trial with 166 patients assigned to one of three treatments: standard medical management and either once-weekly or thrice-weekly medication dispensing or enhanced medical management and thrice-weekly medication dispensing. Standard medical management was brief, manual-guided, medically focused counseling; enhanced management was similar, but each session was extended. The primary outcomes were the self-reported frequency of illicit opioid use, the percentage of opioid-negative urine specimens, and the maximum number of consecutive weeks of abstinence from illicit opioids. Results: The three treatments had similar efficacies with respect to the mean percentage of opioid-negative urine specimens (standard medical management and once-weekly medication dispensing, 44 percent; standard medical management and thrice-weekly medication dispensing, 40 percent; and enhanced medical management and thrice-weekly medication dispensing, 40 percent; P=0.82) and the maximum number of consecutive weeks during which patients were abstinent from illicit opioids. All three treatments were associated with significant reductions from baseline in the frequency of illicit opioid use, but there were no significant differences among the treatments. The proportion of patients remaining in the study at 24 weeks did not differ significantly among the patients receiving standard medical management and once-weekly medication dispensing (48 percent) or thrice-weekly medication dispensing (43 percent) or enhanced medical management and thrice-weekly medication dispensing (39 percent) (P=0.64). Adherence to buprenorphine-naloxone treatment varied; increased adherence was associated with improved treatment outcomes. Conclusions: Among patients receiving buprenorphine-naloxone in primary care for opioid dependence, the efficacy of brief weekly counseling and once-weekly medication dispensing did not differ significantly from that of extended weekly counseling and thrice-weekly dispensing. Strategies to improve buprenorphine-naloxone adherence are needed. (ClinicalTrials.gov number, NCT00023283.) Copyright 2006, Massachusetts Medical Society

Fuller BE, Guydish J, Tsoh J, Reld MS, Resnick M, Zammarelli L, et al. Attitudes toward the integration of smoking cessation treatment into drug abuse clinics. Journal of Substance Abuse Treatment 32(1): 53–60, 2007. (44 refs.)

This article examines the variables associated with the presence of smoking cessation interventions in drug abuse treatment units, as well as staff attitudes toward the integration of smoking cessation services as a component of care. Surveys were administered to 106 organizations, 348 treatment clinics, and 3,786 employees in agencies that participated in the National Drug Abuse Treatment Clinical Trials Network. Organizational factors, attributes of the treatment setting, and staff attitudes toward smoking cessation treatment were assessed. Use of smoking cessation interventions was associated with the number of additional services offered at clinics, residential detoxification services, and attitudes of the staff toward smoking cessation treatment. Staff attitudes toward integrating smoking cessation services in drug treatment were influenced by the number of pregnant women admitted, the number of ancillary services provided, the attitudes of staff toward evidence-based practices, and whether smoking cessation treatment was offered as a component of care. Copyright 2007, Elsevier Science

Gable RS. Comparison of acute lethal toxicity of commonly abused psychoactive substances (review). Addiction 99(6): 686–696, 2004. (103 refs.)

Aims: To determine the acute lethal toxicity of a range of psychoactive substances in terms of the dose customarily used as a single substance for non-medical purposes. Design and method: A structured English-language literature search was conducted to identify experimental studies and clinical reports that documented human and non-human lethal doses of 20 abused substances that are distributed widely in Europe and North America. Four inclusion criteria were specified for the reports, and approximately 3000 relevant records were retrieved from search engines at Biosis, Science Citation Index, Google and the National Library of Medicine's Gateway. In order to account for different drug potencies, a 'safety ratio' was computed for each substance by comparing its reported acute lethal dose with the dose most commonly used for non-medical purposes. Findings: The majority of published reports of acute lethal toxicity indicate that the decedent used a co-intoxicant (most often alcohol). The calculated safety ratios varied between substances by more than a factor of 100. Intravenous heroin appeared to have the greatest direct physiological toxicity; several hallucinogens appeared to have the least direct physiological toxicity. Conclusions: Despite residual uncertainties, the substantial difference in safety ratios suggests that abused substances can be rank-ordered on the basis of their potential acute lethality. Copyright 2004, Society for the Study of Addiction to Alcohol and Other Drugs

Gettman J. Marijuana production in the United States (2006). Bulletin of Cannabis Reform. December 2006. (26 refs)

Executive Summary. 1) Marijuana is the largest cash crop in the United States, more valuable than corn and wheat combined. Using conservative price estimates domestic marijuana production has a value of $35.8 billion. The domestic marijuana crop consists of 56.4 million marijuana plants cultivated outdoors worth $31.7 billion and 11.7 million plants cultivated indoors worth $4.1 billion. 2) The top ten marijuana producing states are California, Tennessee, Kentucky, Hawaii, Washington, North Carolina, Florida, Alabama., West Virginia, and Oregon. Five states (California, Tennessee, Kentucky, Hawaii and Washington) had marijuana crops worth over $1 billion.) 3) Despite intensive eradication efforts domestic marijuana production has increased ten fold over the last 25 years from 1,000 metric tons (2.2 million pounds) in 1981 to 10,000 metric tons (22 million pounds) in 2006, according to federal government estimates. 4) Marijuana is the top cash crop in 12 states, one of the top 3 cash crops in 30 states, and one of the top 5 cash crops in 39 states. The domestic marijuana crop is larger than Cotton in Alabama, larger than Grapes, Vegetables and Hay combined in California, larger than Peanuts in Georgia, and larger than Tobacco in both South Carolina and North Carolina. 5) From 2001 to 2005 federal and state eradication programs eradicated an average of 33,033 outdoor cultivation sites per year and an average of 2,701 indoor marijuana grow-rooms per year. From 1982 to 2005 the Drug Enforcement Administration's Domestic Cannabis Eradication/Suppression Program (DCESP) eradicated over 103 million cultivated marijuana plants, an average of 4.3 million cultivated plants a year over this 24 year period. 6) The ten-fold growth of production over the last 25 years and its proliferation to every part of the country demonstrate that marijuana has become a pervasive and ineradicable part of the national economy. The failure of intensive eradication programs suggests that it is finally time togive serious consideration to marijuana's legalization in the United States. Data is provided in 9 tables. Copyright 2007, Project Cork [available online. www.drugscience.org/Archive/bcr2/bcr2_index.html]

Green AR, Mechan AO, Elliott JM, O’Shea E, Colado MI. The pharmacology and clinical pharmacology of 3, 4-methylenedioxymethamphetamine (MDMA, “ecstasy”) (review). Pharmacological Reviews 55(3): 463–508, 2003. (414 refs.)

The amphetamine derivative (+/-)- 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug among young people, particularly those involved in the dance culture. MDMA produces an acute, rapid enhancement in the release of both serotonin (5-HT) and dopamine from nerve endings in the brains of experimental animals. It produces increased locomotor activity and the serotonin behavioral syndrome in rats. Crucially, it produces dose-dependent hyperthermia that is potentially fatal in rodents, primates, and humans. Some recovery of 5-HT stores can be seen within 24 h of MDMA administration. However, cerebral 5-HT concentrations then decline due to specific neurotoxic damage to 5-HT nerve endings in the forebrain. This neurodegeneration, which has been demonstrated both biochemically and histologically, lasts for months in rats and years in primates. In general, other neurotransmitters appear unaffected. In contrast, MDMA produces a selective long-term loss of dopamine nerve endings in mice. Studies on the mechanisms involved in the neurotoxicity in both rats and mice implicate the formation of tissue-damaging free radicals. Increased free radical formation may result from the further breakdown of MDMA metabolic products. Evidence for the occurrence of MDMA-induced neurotoxic damage in human users remains equivocal, although some biochemical and functional data suggest that damage may occur in the brains of heavy users. There is also some evidence for long-term physiological and psychological changes occurring in human recreational users. However, such evidence is complicated by the lack of knowledge of doses ingested and the fact that many subjects studied are or have been poly-drug users. Copyright 2003, The American Society for Pharmacology & Experimental Therapeutics

Griffiths RR, Mumford GK. Caffeine: A drug of abuse? Psychopharamcology. The Fourth Generation of Progress. American College of Neuropsychopharmacology, 2003. The widespread use of culturally sanctioned caffeine-containing foods presents an intriguing paradox. On one hand, it is the experience of most regular caffeine users that caffeine produces only rather subtle effects that are generally so well-woven into the fabric of daily experience that they are not clearly differentiated from the changes in mood and behavior associated with normal experience. On the other hand, however, caffeine is arguably the most robust form of drug self-administration known. The article covers the reinforcing effects of caffeine, in animals and humans, subjective effects tolerance, physical dependence and as a drug of abuse.

available online

Gupta PC, Ray CS. Epidemiology of betel quid usage. Annals of Academy of Medicine (Singapore) 33(4, Supplement S): 31–36, 2004. (41 refs.)

Betel quid chewing is an ancient practice common in many countries of Asia and among migrated communities in Africa, Europe and North America. It enjoys complete social acceptance in many societies and is also popular among women. In its most basic form, betel quid consists of betel leaf (Piper betel), areca nut, the main psychoactive ingredient, and slaked lime (calcium hydroxide). Areca nut is said to be the fourth most commonly used psychoactive substance in the world, after caffeine, nicotine and alcohol. There are a great variety of ingredients and ways of preparing betel quid in different countries. In some, particularly in India, tobacco is added to the quid. In recent years, commercially-manufactured non-perishable forms of betel quid (pan masala or betel quid mixtures and gutka), not containing betel leaf, have been marketed. Within a short period of about 2 decades, this industry has risen in value to several hundred US million dollars. Use of areca nut in any form is not safe for oral health; the use of commercially manufactured forms seems even riskier. Copyright 2004, Academy of Medicine of Singapore

Hall AP, Henry JA. Acute toxic effects of ‘Ecstasy’ (MDMA) and related compounds: Overview of pathophysiology and clinical management (review). British Journal of Anaesthesia 96(6): 678–685, 2006. (75 refs)

Since the late 1980s 'Ecstasy' (3,4-methylenedioxymethamphetamine, MDMA) has become established as a popular recreational drug in western Europe. The UK National Criminal Intelligence Service estimates that 0.5-2 million tablets are consumed weekly in Britain. It has been reported that 4.5% of young adults (15-34 yr) in the UK have used MDMA in the previous 12 months. Clinically important toxic effects have been reported, including fatalities. While the phenomenon of hyperpyrexia and multi-organ failure is now relatively well known, other serious effects have become apparent more recently. Patients with acute MDMA toxicity may present to doctors working in Anaesthesia, Intensive Care and Emergency Medicine. A broad knowledge of these pathologies and their treatment is necessary for anyone working in an acute medical speciality. An overview of MDMA pharmacology and acute toxicity will be given followed by a plan for clinical management. Copyright 2006, Oxford University Press

Hall WD, Lynskey M. Is cannabis a gateway drug? Testing hypotheses about the relationship between cannabis use and the use of other illicit drugs (review). Drug and Alcohol Review 24(1): 39–48, 2005. (66 refs.)

We outline and evaluate competing explanations of three relationships that have consistently been found between cannabis use and the use of other illicit drugs, namely, (1) that cannabis use typically precedes the use of other illicit drugs; and that (2) the earlier cannabis is used, and (3) the more regularly it is used, the more likely a young person is to use other illicit drugs. We consider three major competing explanations of these patterns: (1) that the relationship is due to the fact that there is a shared illicit market for cannabis and other drugs which makes it more likely that other illicit drugs will be used if cannabis is used; (2) that they are explained by the characteristics of those who use cannabis; and (3) that they reflect a causal relationship in which the pharmacological effects of cannabis on brain function increase the likelihood of using other illicit drugs. These explanations are evaluated in the light of evidence from longitudinal epidemiological studies, simulation studies, discordant twin studies and animal studies. The available evidence indicates that the association reflects in part but is not wholly explained by: (1) the selective recruitment to heavy cannabis use of persons with pre-existing traits (that may be in part genetic) that predispose to the use of a variety of different drugs; (2) the affiliation of cannabis users with drug using peers in settings that provide more opportunities to use other illicit drugs at an earlier age; (3) supported by socialisation into an illicit drug subculture with favourable attitudes towards the use of other illicit drugs. Animal studies have raised the possibility that regular cannabis use may have pharmacological effects on brain function that increase the likelihood of using other drugs. We conclude with suggestions for the type of research studies that will enable a decision to be made about the relative contributions that social context, individual characteristics, and drug effects make to the relationship between cannabis use and the use of other drugs. Copyright 2005, Australian Medical and Professional Society on Alcohol and Other Drugs

Higdon JV, Frei B. Coffee and health: A review of recent human research (review). Critical Reviews in Food Science and Nutrition 46(2): 101–123, 2006. (290 refs.)

Coffee is a complex mixture of chemicals that provides significant amounts of chlorogenic acid and caffeine. Unfiltered coffee is a significant source of cafestol and kahweol, which are diterpenes that have been implicated in the cholesterol-raising effects of coffee. The results of epidemiological research suggest that coffee consumption may help prevent several chronic diseases, including type 2 diabetes mellitus, Parkinson's disease and liver disease (cirrhosis and hepatocellular carcinoma). Most prospective cohort studies have not found coffee consumption to be associated with significantly increased cardiovascular disease risk. However, coffee consumption is associated with increases in several cardiovascular disease risk factors, including blood pressure and plasma homocysteine. At present, there is little evidence that coffee consumption increases the risk of cancer. For adults consuming moderate amounts of coffee (3-4 cups/d providing 300-400 mg/d of caffeine), there is little evidence of health risks and some evidence of health benefits. However, some groups, including people with hypertension, children, adolescents, and the elderly, may be more vulnerable to the adverse effects of caffeine. In addition, currently available evidence suggests that it may be prudent for pregnant women to limit coffee consumption to 3 cups/d providing no more than 300 mg/d of caffeine to exclude any increased probability of spontaneous abortion or impaired fetal growth. Copyright 2006, Taylor & Francis, Inc.

Hser Y, Hoffman V, Grella CE, Anglin MD. A 33-year follow-up of narcotics addicts. Archives of General Psychiatry 58(5): 503–508, 2001. (17 refs.)

Background: This study examined longitudinal patterns of heroin use, other substance use, health, mental health, employment, criminal involvement, and mortality among heroin addicts. Methods: The sample was composed of 581 male heroin addicts admitted to the California Civil Addict Program (CAP) during the years 1962 through 1964; CAP was a compulsory drug treatment program for heroin-dependent criminal offenders. This 33-year follow-up study updates information previously obtained from admission records and 2 face-to- face interviews conducted in 1974-1975 and 1985-1986; in 1996-1997, at the latest follow-up, 284 were dead and 242 were interviewed. Results: In 1996-1997, the mean age of the 242 interviewed subjects was 57.4 years. Age, disability, years since first heroin use, and heavy alcohol use were significant correlates of mortality. Of the 242 interviewed subjects, 20.7% tested positive for heroin (with additional 9.5%;, urine refusal and 14.0% incarceration, for whom urinalyses were unavailable), 66.9% reported tobacco use, 22.1% were daily alcohol drinkers, and many reported illicit drug use (eg, past- year heroin use was 40.5%; marijuana, 35.5%; cocaine, 19.4%, crack, 10.3%; amphetamine, 11.6%). The group also reported high rates of health problems, mental health problems, and criminal justice system involvement. Long-term heroin abstinence was associated with less criminality, morbidity, psychological distress, and higher employment. Conclusions: While the number of deaths increased steadily over time, heroin use patterns were remarkably stable for the group as a whole. For some, heroin addiction has been a lifelong condition associated with severe health and social consequences. Copyright 2001, American Medical Association

Huang BJ, Dawson DA, Stinson FS, Hasin DS, Ruan WJ, Saha TD, et al. Prevalence, correlates, and comorbidity of nonmedical prescription drug use and drug use disorders in the United States: Results of the National Epidemiology Survey on Alcohol and Related Conditions. Journal of Clinical Psychiatry 67(7): 1062–1073, 2006. (58 refs.)

Objective: To present national data on the prevalence, correlates, and comorbidity of nonmedical prescription drug use and drug use disorders for sedatives, tranquilizers, opioids, and amphetamines. Method: Data were derived from the National Epidemiologyogic Survey on Alcohol and Related Conditions (NESARC), a face-to-face nationally representative survey of 43,093 adults conducted during 2001 and 2002. Results: Lifetime prevalences of nonmedical use of sedatives, tranquilizers, opioids, and amphetamines were 4.1%, 3.4%, 4.7%, and 4.7%, respectively. Corresponding rates of abuse and/or dependence on these substances were 1.1%, 1.0%, 1.4%, and 2.0%. The odds of nonmedical prescription drug use and drug use disorders were generally greater among men, Native Americans, young and middle-aged, those who were widowed/separated/divorced or never married, and those residing in the West. Abuse/dependence liability was greatest for amphetamines, and nonmedical prescription drug use disorders were highly comorbid with other Axis I and II disorders. The majority of individuals with nonmedical prescription drug use disorders never received treatment. Conclusions: Nonmedical prescription drug use and disorders are pervasive in the U.S. population and highly comorbid with other psychiatric disorders. Native Americans had significantly greater rates of nonmedical prescription drug use and drug use disorders, highlighting the need for culturally-sensitive prevention and intervention programs. Unprecedented comorbidity between nonmedical prescription drug use disorders and between nonmedical prescription drug use disorders and illicit drug use disorders suggests that the typical individual abusing or dependent on these drugs obtained them illegally, rather than through a physician. Amphetamines had the greatest abuse/dependence liability, and recent increases in the potency of illegally manufactured amphetamines may portend an epidemic in the youngest NESARC cohort. Copyright 2006, Physicians Postgraduate Press

Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: Empirical validation of symptoms and signs, incidence, severity, and associated features (review). Psychopharmacology 176(1): 1–29, 2004. (139 refs.)

Rationale: Although reports of caffeine withdrawal in the medical literature date back more than 170 years, the most rigorous experimental investigations of the phenomenon have been conducted only recently. Objectives: The purpose of this paper is to provide a comprehensive review and analysis of the literature regarding human caffeine withdrawal to empirically validate specific symptoms and signs, and to appraise important features of the syndrome. Methods: A literature search identified 57 experimental and 9 survey studies on caffeine withdrawal that met inclusion criteria. The methodological features of each study were examined to assess the validity of the effects. Results: Of 49 symptom categories identified, the following 10 fulfilled validity criteria: headache, fatigue, decreased energy/activeness, decreased alertness, drowsiness, decreased contentedness, depressed mood, difficulty concentrating, irritability, and foggy/not clearheaded. In addition, flu-like symptoms, nausea/vomiting, and muscle pain/stiffness were judged likely to represent valid symptom categories. In experimental studies, the incidence of headache was 50% and the incidence of clinically significant distress or functional impairment was 13%. Typically, onset of symptoms occurred 12-24 h after abstinence, with peak intensity at 20-51 h, and for a duration of 2-9 days. In general, the incidence or severity of symptoms increased with increases in daily dose; abstinence from doses as low as 100 mg/day produced symptoms. Research is reviewed indicating that expectancies are not a prime determinant of caffeine withdrawal and that avoidance of withdrawal symptoms plays a central role in habitual caffeine consumption. Conclusions: The caffeine-withdrawal syndrome has been well characterized and there is sufficient empirical evidence to warrant inclusion of caffeine withdrawal as a disorder in the DSM and revision of diagnostic criteria in the ICD. Copyright 2004, Springer

King R, Mauer M. The war on marijuana: The transformation of the war on drugs in the 1990s. Harm Reduction Journal 3 (article 6), 2006. (71 refs.)

Background: As the "war on drugs" enters the latter half of its third decade since being forged into the American lexicon by President Ronald Reagan, the public has grown more skeptical of the current strategy and has proven to be receptive to a broader consideration of alternatives to incarceration. This has been the case most notably with marijuana offenses, where the policy discussion has shifted in some localities to one of decriminalization or de-prioritizing law enforcement resources dedicated to pursuing possession offenses. Despite the increased profile surrounding marijuana policy in recent years, there remains a significant degree of misunderstanding regarding the current strategy, both in terms of how resources are being allocated and to what eventual gain. Methods: Previous studies have analyzed drug offenses as a general category, but there has yet to be a single study that has focused specifically on marijuana offenders at all stages of the system. This report analyzes multiple sources of data for the period 1990-2002 from each of the critical points in the criminal justice system, from arrest through court processing and into the correctional system, to create an overall portrait of this country's strategy in dealing with marijuana use. Results: The study found that since 1990, the primary focus of the war on drugs has shifted to low level marijuana offenses. During the study period, 82% of the increase in drug arrests nationally (450,000) was for marijuana offenses, and virtually all of that increase was in possession offenses. Of the nearly 700,000 arrests in 2002, 88% were for possession. Only 1 in 18 of these arrests results in a felony conviction, with the rest either being dismissed or adjudicated as a misdemeanor, meaning that a substantial amount of resources, roughly $4 billion per year for marijuana alone, is being dedicated to minor offenses. Conclusion: The results of this study suggest that law enforcement resources are not being effectively allocated to offenses which are most costly to society. The financial and personnel investment in marijuana offenses, at all points in the criminal justice system, diverts funds away from other crime types, thereby representing a questionable policy choice. Copyright 2006, BioMed Central

Knight CA, Knight I, Mitchell DC, Zepp JE. Beverage caffeine intake in US consumers and subpopulations of interest: Estimate from the Share of Intake Panel Survey. Food and Chemical Toxicology 42:1923–1930, 2004. (15 refs)

Purpose: Throughout childhood there is a shift from predominantly milk-based beverage consumption to other types of beverages, including those containing caffeine. Although a variety of health effects in children and adults have been attributed to caffeine, few data exist on caffeine intake in children aged one to five years. Methods: Because beverages provide about 80% of total caffeine consumed in children of this age group, beverage consumption patterns and caffeine intakes were evaluated from two beverage marketing surveys: the 2001 Canadian Facts study and the 1999 United States Share of Intake Panel study. Results: Considerably fewer Canadian children than American children consume caffeinated beverages (36% versus 56%); Canadian children consume approximately half the amount of caffeine (7 versus 14 mg/day in American children). Differences were largely because of higher intakes of carbonated soft drinks in the US. Conclusions: Caffeine intakes from caffeinated beverages remain well wthin safe levels for consumption by young children. Copyright 2006, Dietitians of Canada

Lai SH, Lai H, Page JB, McCoy CB. The association between cigarette smoking and drug abuse in the United States. Journal of Addictive Diseases 19(4): 11–14, 2000. (22 refs.)

Cigarette smoking has been identified as an independent risk factor for many human diseases. However, the association between cigarette smoking and illegal drug use has not been thoroughly investigated. We have analyzed the 1994 National Household Survey on Drug Abuse to clarify whether cigarette smoking has any effect on the initiation of illegal drug use. Data from 17,809 respondents completing the 1994 "new" (1994-B) questionnaire were analyzed — logistic regression analyses were performed with the use of statistical package SUDAAN, taking into consideration the multistage sampling design. The results show that those who had smoked cigarettes were far more likely to use cocaine (OR = 7.5; 95% CI: 5.7-9.9), heroin (OR = 16.0; 95% CI: 6.8-37.9), crack (OR = 13.9; 95% CI: 7.9-24.5) and marijuana (OR 7.3; 95% CI:6.2-8.7). The associations are consistent across age-strata and remain after adjusting for race and gender. This study suggests that cigarette smoking may be a gateway drug to illegal drug use. Copyright 2000, Haworth Press

Lundqvist T. Cognitive consequences of cannabis use: Comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions. Pharmacology, Biochemistry and Behavior 81(2): 319–330, 2005. (91 refs.)

This review aims to compare cognitive consequence between cannabis, and stimulants and heroin with regards to attention, memory and executive functions. The available studies using brain imaging techniques and neuropsychological tests show that acutely, all drugs create a disharmony in the neuropsychological network, causing a decrease of activity in areas responsible for short-term memory and attention, with the possible exception of heroin. Cannabis induces loss of internal control and cognitive impairment, especially of attention and memory, for the duration of intoxication. Heavy cannabis use is associated with reduced function of the attentional/executive system, as exhibited by decreased mental flexibility, increased perserveration, and reduced learning, to shift and/or sustain attention. Recent investigations on amphetamine/methamphetamine have documented deficits in learning, delayed recall, processing speed, and working memory. MDMA users exhibit difficulties in coding information into long-term memory, display impaired verbal learning, are more easily distracted, and are less efficient at focusing attention on complex tasks. The degree of executive impairment increases with the severity of use, and the impairments are relatively lasting over time. Chronic cocaine users display impaired attention, learning, memory, reaction time and cognitive flexibility. Heroin addiction may have a negative effect on impulse control, and selective processing. Copyright 2005, Elsevier Science

Maurer HH, Sauer C, Theobald DS. Toxicokinetics of drugs of abuse: Current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine (review). Therapeutic Drug Monitoring 28(3): 447–453, 2006. (72 refs.)

This review summarizes the major metabolic pathways of the drugs of abuse, tetrahydrocannabinol, cocaine, heroin, morphine, and codeine, in humans including the involvement of isoenzymes. This knowledge may be important for predicting their possible interactions with other xenobiotics, understanding pharmaco-/toxicokinetic and pharmacogenetic variations, toxicological risk assessment, developing suitable toxicological analysis procedures, and finally for understanding certain pitfalls in drug testing. The detection times of these drugs and/or their metabolites in biological samples are summarized and the implications of the presented data on the possible interactions of drugs of abuse with other xenobiotics, ie, inhibition or induction of individual polymorphic and nonpolymorphic isoenzymes, discussed. Copyright 2006, Lippincott, Williams & Wilkins

Maxwell JC. Party drugs: Properties, prevalence, patterns, and problems (review). Substance Use & Misuse 40(9–10): 1203–1240, 2005. (172 refs.)

This review summarizes the latest literature on "party" or "club" drugs, defined as MDMA, GHB, ketamine, and Rohypnol, as published from 2002 to early 2005. Club drugs have been categorized as being used at raves and dance parties. The literature shows that each drug has different properties, users, and settings. Each drug has different adverse effects and requires different acute care protocols. Although these drugs were identified early, scientific information about them, including the toxicological tests to identify them, is still evolving. Increasing numbers of studies on the short- and long-term effects of these drugs on humans are being published, but because of limitations on research using human subjects, they may not always be as rigorous as desired and can be cited by drug users to discredit findings of harm. The lack of research-based information on these drugs has led to the emergence of web sites that may or may not provide accurate data. Evaluated chemical dependency treatment protocols using the latest research for each of these different drugs are needed. Copyright 2005, Marcel Dekker, Inc

McDonough M, Kennedy N, Glasper A, Bearn J. Clinical features and management of gamma-hydroxybutyrate (GHB) withdrawal: A review. Drug and Alcohol Dependence 75(1): 3–9, 2004. (25 refs.)

Aim: To examine the clinical course of gamma-hydroxybutyrate (GHB) withdrawal and generate management guidelines. Design: Review and analysis of all published reports of GHB or GHB precursor withdrawal identified from electronic searches. Findings: In total, 38 cases of GHB (n=28) or GHB precursor (n=10) withdrawal were identified, 36 of which were from the US. A rapidly deteriorating course into delirium (53% of cases) was typical for heavily dependent users. Symptoms were broadly similar to alcohol withdrawal but often occurred earlier in usage with delirium being associated with severe dependence as determined by more frequent ingestion. High dose benzodiazepines were effective in pharmacological management of GHB withdrawal. In benzodiazepine refractory cases withdrawal responded to other sedative agents, mainly pentobarbital or chloral hydrate. No withdrawal seizures but one death was recorded. Conclusions: GHB withdrawal is potentially life threatening and requires vigorous clinical management, preferably as an inpatient for severe cases. A management algorithm is proposed. Copyright 2004, Elsevier Science

McRae AL, Budney AJ, Brady KT. Treatment of marijuana dependence: A review of the literature (review). Journal of Substance Abuse Treatment 24(4): 369–376, 2003. (47 refs.)

Until recently, relatively little research has focused on the treatment of marijuana abuse or dependence; however, marijuana use disorders are now receiving increased attention. This paper reviews the initial clinical trials evaluating the efficacy of outpatient treatments for adult marijuana dependence. Findings from five controlled trials of psychotherapeutic interventions suggest that this disorder appears responsive to the same types of treatment as other substance dependencies. Moreover, these initial studies suggest that many patients do not show a positive treatment response, indicating that marijuana dependence is not easily treated. Strengths and weaknesses of the data are presented. Preliminary data from less controlled studies relevant to the treatment of marijuana dependence are discussed to suggest future research areas. Although very few studies on treatment for marijuana abuse and dependence have been completed, the initial reports identify promising treatment approaches and demonstrate a need for more research on the development of effective interventions. Copyright 2003, Elsevier Science

Mullins ME. Laboratory confirmation of flunitrazepam in alleged cases of date rape. Academic Emergency Medicine 6(9): 966–968, 1999. (10 refs.)

This brief report summarizes the outcome of more than 1,000 consecutive tests performed through May 1998, in cases suspected of involving flunitrazepam (Rohypnol). [Flunitrazepam has never been marketed in the US., but has been marketed in Europe and Latin America for treatment of insomnia and as a pre-operative sedative.] This is being used illicitly in the US and has become identified as the "date rape" drug. Hoffman-La Roche has assisted "date rape" victims by providing free, comprehensive testing for flunitrazepam to EDs, law enforcement agencies, and sexual assault crisis clinics. The testing is conducted on urine samples. Of the 1,077 tests conducted, funitrazepam was present in only six assays. A total of 41% of all assays were negative for all drugs tested. The remaining 59% had one or more detectable drugs including alcohol. A total of 400 assays (36%) detected alcohol, and 200 (18%) detected marijuana. All other benzodiazepines, excluding Flunitrazepam, were found in 131 positive test (12%). Gamma-hydroxy-butyrate was identified in 46 samples (4%), (the limit of detection was 2 ng/mL). Thus while widely reported, the actual documented occurrence of flunitrazepam in "date rape" appears to be relatively rare. Copyright 2000, Project Cork

Nicholson KL, Balster RL. GHB: a new and novel drug of abuse. Drug and Alcohol Dependence 63(1): 1–22, 2001. (218 refs.)

There has been increasing attention in the United States to problems of abuse of gamma-hydroxybutyrate (GHB), with some evidence for problems in other parts of the world as well. In vitro and animal research show that. while GHB shares some properties with abused central nervous system depressant drugs, it has unique aspects of its pharmacology as well, including actions at a specific neural receptor which probably mediates many of its effects. Abuse potential assessment of GHB using standard animal models has not yielded a picture of a highly abusable substance, but little human testing has yet been done. Very little systematic data exist on tolerance and dependence with GHB, but both have been seen in human users. Quantitative data on the prevalence of GHB abuse is incomplete, but various qualitative measures indicate that a mini-epidemic of abuse began in the late 1980s and continues to the present. GHB is often included with the group of 'club drugs', and can be used as an intoxicant. It also has been used as a growth promoter and sleep aid and has been implicated in cases of 'date rape', usually in combination with alcohol. Undoubtedly the easy availability of GHB and some of its precursors has contributed to its popularity. Recent changes in the control status of GHB in the US may reduce its availability with as yet unknown consequences for the scope of the public health problem. Drug abuse experts need to familiarize themselves with GHB as possibly representing a new type of drug abuse problem with some unique properties. Copyright 2001, Elsevier Science

Patton GC, Coffey C, Carlin JB, Sawyer SM, Wakefield M. Teen smokers reach their mid-twenties. Journal of Adolescent Health 39(2): 214–220, 2006. (40 refs.)

Purpose: Most outcome studies of adolescent smokers have focused on tobacco use in the short term. Few have reported on the health of adolescent smokers as they reach young adulthood. Methods: The design was a 10-year, eight-wave cohort study of a state-wide community sample of 1943 participants in Victoria, Australia. Participants were initially aged 14 to 15 years. Tobacco use was assessed with self-reported frequency of use and a seven-day retrospective diary. The Fagerstrom Test for Nicotine Dependence was used to define nicotine dependence in young adulthood. A computerized interview assessment was used during the teens and in young adulthood. Results: Former daily smokers in adolescence accounted for most cases of nicotine dependence and high-dose (10+ cigarettes per day) smoking in young adulthood. Other substance abuse and psychiatric morbidity in young adulthood were also markedly elevated in this group. This was most clearly evident for cannabis dependence, where close to two-thirds of all cases were formerly daily tobacco smokers. Male smokers were more likely to continue as young adults. Persistent symptoms of depression and anxiety during the teens predicted progression to nicotine dependence, as did having a parent smoking daily. Conclusions: The poor health outcomes of daily adolescent smokers as they reach young adulthood provide a rationale for greater tobacco control initiatives directed at early users. Clinical interventions might usefully consider factors such as psychiatric morbidity and parental smoking. Copyright 2006, Society for Adolescent Medicine

Pepling RS. Kava. Chemical & Engineering News. 83(46): 53, 2005. (2 refs.)

This column, prompted by the author's trip to Hawaii and a visit to an outdoor cafe serving kava describes the beverage, its origins and use in the south Pacific, and more recent use in the west. Kava is touted as a natural relaxant. As a beverage it is described as "a turpentine-smelling, bitter-tasting, muddy-water" drink. The active ingredients, termed kavalactones, affect the regions of the brain that regulates fear and anxiety, via a variety of mechanisms, such as by blocking sodium or calcium channels and by activating -aminobutyric acid receptors. Kava has gained popularity in the west, not as a beverage .but as a food supplement, sold in capsules. However in 2001, these kava products were linked to liver failure. That led to a ban on kava sales in some European countries. Subsequent research suggested that harm was generated not by the kavalactones, but through contaminants, the inclusion of an over-ground portion of the plant, containing the alkaloid pipermethystine. Only the root which does not contain pipermethystine is traditionally used in the beverage. Copyright 2005, Project Cork

Richter KP, Choi WS, Alford DP. Smoking policies in US outpatient drug treatment facilities. Nicotine & Tobacco Research 7(3): 475–480, 2005. (32 refs.)

Most drug treatment patients smoke cigarettes, and some facilities are beginning to help patients quit. Facility smoking policies can help or hinder this effort. The present study describes smoking policies in outpatient drug treatment. It is a secondary analysis of a survey on smoking cessation treatment in outpatient methadone maintenance facilities in the United States. One clinic leader (a medical director, head nurse, or clinic director) from each of the 697 U.S. facilities was invited to participate in the study. Main outcome measures included whether clinics had a written smoking policy as well as the types of indoor and outdoor policies in place for patients and staff. A total of 408 (59%) of U.S. clinics responded. Most clinics (73%) had a written smoking policy for patients, and more (82%) had written policies for staff. Over 90% banned indoor smoking by staff and patients., Few totally banned outdoor smoking. Approximately half in some way restricted where patients (48%) and staff (55%) smoke outdoors. Compared with clinics that did not treat nicotine dependence, significantly more clinics that treated nicotine dependence had written policies on smoking and restricted outdoor smoking for patients and staff. Likewise, many public clinics and those affiliated with hospitals had outdoor smoking restrictions for patients and staff. Drug treatment facilities routinely ban alcohol use and drug dealing on their grounds. Only I in 10 ban smoking. Outpatient facilities should restrict or ban outdoor tobacco use in order to remain consistent with their mission and avoid sabotaging clinic efforts to treat, and patient and staff efforts to stop, smoking. Copyright 2005, Taylor & Francis, Ltd.

Riley SCE, Hayward E. Patterns, trends, and meanings of drug use by dance-drug users in Edinburgh, Scotland. Drugs: Education, Prevention and Policy 11(3): 243–262, 2004. (21 refs.)

A survey of drug use in the past year was completed by 124 clubbers (50% male, 50% female, age range 14-44, mean 24 years). Participants were self selecting and recruited in clubs and pre-club bars. Prevalence rates for alcohol, cannabis, and ecstasy were over 80%; 63% reported cocaine and 53% amphetamine use, 15%-43% used ketamine, psilocybin, LSD and nitrites. A pattern of polydrug and co-drug use was identified. Most participants (70%) bought their drugs through friendship/family networks. Main reasons given for drug use were relaxing, socializing and dancing. Risk behaviours identified were drug driving (19%), unprotected sex (39%); and 'taking too many drugs' (44%). At least 40% reported anxiety, nausea and paranoia. Three focus groups aided the interpretation of data, for example describing the strategic use of drugs and alcohol throughout a night and explaining how negative experiences may change, but not necessarily stop, drug use. The study provides further evidence that there is a characteristic pattern of dance-drug use, while identifying an increase in cocaine and alcohol use. Older participants' greater experience with cocaine and fewer negative drug-related experiences are discussed in relation to health promotion. Copyright 2004, Carfax Publishing

Robinson SE. Buprenorphine-containing treatments: Place in the management of opioid addiction (review). CNS Drugs 20(9): 697–712, 2006. (154 refs)

Although the synthetic opioid buprenorphine has been available clinically for almost 30 years, its use has only recently become much more widespread for the treatment of opioid addiction. The pharmacodynamic and pharmacokinetic profiles of buprenorphine make it unique in the armamentarium of drugs for the treatment of opioid addiction. Buprenorphine has partial g-opioid receptor agonist activity and is a kappa-opioid receptor antagonist; hence, it can substitute for other mu-opioid receptor agonists, yet is less apt to produce overdose reactions or dysphoria. On the other hand, buprenorphine can block the effects of opioids such as heroin (diamorphine) and morphine, and can even precipitate withdrawal in individuals physically dependent upon these drugs. Buprenorphine has significant sublingual bioavailability and a long half-life, making administration on a less than daily basis possible. Furthermore, its discontinuation is associated with only a mild withdrawal syndrome. Clinical trials have demonstrated that sublingual buprenorphine is effective in both maintenance therapy and detoxification of individuals addicted to opioids. The introduction of a sublingual formulation combining naloxone with buprenorphine further reduces the risk of diversion to illicit intravenous use. Because of its relative safety and lower risk of illegal diversion, buprenorphine has been made available in several countries for treating opioid addiction in the private office setting, greatly enhancing treatment options for this condition. Copyright 2006, Adis International

Shiner M. Out of harm’s way? Illicit drug use, medicalization and the law. British Journal of Criminology, 43:772–796, 2003. (61 refs.)

Although British drugs policy has become increasingly contested, debate in this area has continued along well-established lines. Recent reviews, including those conducted by the independent inquiry into the Misuse of Drugs Act and the Select Committee on Home Affairs, have called for reform largely on the basis of the established medicalized philosophy. While the related notions of dangerousness and harmfulness have produced a strong emphasis on control and law enforcement, little attention has been given to the extent to which they provide an appropriate basis for policy. In this article a social classification of illicit drug use is developed and comparisons are made with existing medico-legal classifications. Considerable congruence is evident between these approaches and it is argued that social dimensions of drug use reinforce recent calls for a shift away from enforcement-led approaches, including downgrading the legal classification of cannabis, ecstasy and LSD. However, while social dimensions broadly support the conclusions of the independent inquiry they also highlight the need for more wide-ranging reform. In particular, they suggest that the process of reclassification should be extended to include magic mushrooms and more controversially, perhaps, cocaine. Copyright 2003, Institute for the Study and Treatment of Delinquency

Simmons MM, Cupp MJ. Use and abuse of flunitrazepam. Annals of Pharmacotherapy 32(1): 117–119, 1998. (17 refs.)

This brief article is a response to the question, "What should health care professionals know about flunitrazepam?" It is a fast-acting benzodiazepine, 10 times more potent than diazepam, that is not available in the United States and is illegal to import. It covers, pharmacokinetics, therapeutic uses, comparison with other benzodiazepines, regulation, illicit use, tablet appearance, and detection. Copyright 1998, Project Cork

Sinha J. History and Development of the Leading International Drug Control Conventions. Special report prepared for the Senate Special Committee on Illegal Drugs. Law and Government Division, Canadian Parliament: Ottawa Canada, 2001. (21 refs.)

This report was prepared for the Canadian Parliament as it considered a system of laws for drug control policy.
Available online.

Topp L, Day C, Degenhardt L. Changes in patterns of drug injection concurrent with a sustained reduction in the availability of heroin in Australia. Drug and Alcohol Dependence 70(3): 275–286, 2003. (88 refs.)

Between 1996 and 2000, heroin was the drug most frequently injected in Australia, and viable heroin markets existed in six of Australia's eight jurisdictions. In 2001, there was a dramatic and sustained reduction in the availability of heroin that was accompanied by a substantial increase in its price, and a 14% decline in the average purity of seizures analysed by forensic laboratories. The shortage of heroin constitutes a unique natural experiment within which to examine the impact of supply reduction. This paper reviews one important correlate of the shortage, namely changes in patterns of illicit drug injection. A number of studies have consistently suggested that between 2000 and 2001, there was a sizeable decrease in both prevalence and frequency of heroin injection among injecting drug users. These changes were accompanied by increased prevalence and frequency of stimulant injection. Cocaine was favoured in NSW, the sole jurisdiction in which a cocaine market was established prior to the heroin shortage; whereas methamphetamine predominated in other jurisdictions. Some data suggest that, at least in the short-term, some drug injectors left the market altogether subsequent to the reduced heroin availability. However, the findings that (1) some former heroin users switched their drug preference to a stimulant; and (2) subsequently attributed this change to the reduced availability of heroin, suggests that reducing the supply of one drug may serve to increase the use of others. Given the differential harms associated with the use of stimulants and opiates, this possibility has grave implications for Australia, where the intervention and treatment system is designed primarily to accommodate opiate use and dependence. Copyright 2003, Elsevier Scientific

Uchtenhagen A. Substitution management in opioid dependence. Journal of Neural Transmission 88 (supplement): 33–60, 2003. (64 refs.)

Substitution treatment (replacement therapy) is the most widespread and the most frequently researched therapeutic approach to heroin dependence. At present, the "gold standard" is methadone maintenance, but the use of other agonists and of combined compounds with antagonists are increasingly used, especially buprenorphine. This paper reviews the main findings from research and their consequences for best practice rules. The evolution and organisation of substitution treatment in Europe is described, indicating a major discrepancy in administrative regulations. Emerging trends are also mentioned, as well as the merits and limitations that mark the place of substitution treatment in a comprehensive therapeutic network for opioid dependence. Copyright 2003, Springer-Verlag

Valdez A, Cepeda A, Kaplan CD, Yin ZN. The legal importation of prescription drugs into the United States from Mexico: A study of customs declaration forms. Substance Use and Misuse 33(12): 2485–2497, 1998. (14 refs.)

The nature and magnitude of the problem of the diversion of prescription drugs from legal to illegal markets have been identified as a high priority by the federal government. This study was based on a random sample (2,005) of declaration forms of persons declaring Mexican prescription drugs at the US Customs office in Laredo, Texas. Of the 75 different types of drugs, the most frequently declared drugs were Valium (71%), Rohypnol (46%), and Tafil (25%), drugs highly associated with nonmedicinal use among United States teenagers and young adults. These data reinforce a documented need for more transnational cooperative efforts between the United States and Mexico. Copyright 1998, Marcel Dekker, Inc.

van den Brink W, van Ree JM. Pharmacological treatments for heroin and cocaine addiction (review). European Neuropsychopharmacology 13(6): 476–487, 2003. (133 refs.)

Aims: To provide an overview of the pharmacological options for the treatment of heroin- and cocaine-dependent patients based on known biochemical pathways to addiction and the chronic disease model as a starting point for treatment planning. Results: Recent pre-clinical and clinical studies indicate that different brain structures and different neurotransmitters are involved in different stages of the addiction process. In addition, clinical experience shows that heroin and cocaine addiction can best be conceptualised and treated as a chronic, relapsing disorder with the following treatment goals: crisis intervention, cure or recovery (detoxification, relapse prevention) and care or partial remission (stabilization and harm reduction). The various high-quality studies, systematic literature reviews and formal meta-analyses clearly demonstrate that today many proven effective interventions are available for crisis intervention, detoxification, stabilization and harm reduction for hero in-dependent patients. Interventions directed at relapse prevention are still problematic and only effective in a minority of motivated patients in stable living conditions and adequate social support. In contrast, no proven effective pharmacological interventions are available for the treatment of cocaine-dependent patients, maybe with the exception of some patient groups that seem to benefit from treatment with disulfiram or amantadine. Treatment innovations are primarily based on experimental animal studies. Newly developed cannabinoid receptor antagonists and cortisol synthesis inhibitors show great promise. Conclusion: Heroin addiction is a chronic relapsing disease that is difficult to cure, but stabilization and harm reduction can greatly increase the life time expectancy and the quality of life of the patient, his direct environment and society as a whole. Currently, no proven effective pharmacological interventions are available for cocaine addiction, and treatment has to rely on existing cognitive behaviour therapies combined with contingency management strategies. Copyright 2003, Elsevier Science

van den Brink W, Goppel M, van Ree JM. Management of opioid dependence (review). Current Opinion in Psychiatry 16(3): 297–304, 2003. (83 refs.)

Purpose of the review: The present review provides an overview of the most recent developments in the treatment of opioid-dependent patients, using a chronic disease model as a starting point, and taking crisis intervention, cure (detoxification, relapse prevention), care (stabilization and harm reduction) and palliation as the major treatment goals. Recent findings: The various high-quality studies, systematic literature reviews and formal meta-analyses clearly demonstrate that, currently, many proven effective interventions are available for crisis intervention, detoxification, stabilization and harm reduction. Interventions directed at relapse prevention are still problematic and only effective in motivated patients in stable living conditions and with adequate social support. Treatment innovations are primarily based on experimental animal studies. Newly developed cannabinoid receptor antagonists and cortisol synthesis inhibitors show great promise. Summary: Opioid dependence is a chronic relapsing disease that is difficult to cure, but stabilization and harm reduction can greatly increase the life expectancy and quality of life of patients, their direct environment and society as a whole. Copyright 2003, Rapid Science Publishers

Van Etten ML, Anthony JC. Comparative epidemiology of initial drug opportunities and transitions to first use: Marijuana, cocaine, hallucinogens and heroin. Drug and Alcohol Dependence 54(2): 117–125, 1999. (31 refs.)

The earliest stages of involvement with illicit drugs have been understudied. In a recent report, we examined initial opportunities to try marijuana and transitions from first opportunity to first use of that drug. This report extends that work by investigating early involvement with cocaine, heroin, and hallucinogens as well. We examine sex and race-ethnicity differences in estimates of having a drug opportunity, and in the probability of progressing from having an opportunity to try a drug to actually using the drug. Self-report interview data collected for the National Household Surveys on Drug Abuse (NHSDA) from 1979 to 1994 were analyzed. Results showed that an estimated 51% of US residents have had an opportunity to try marijuana; comparative estimates for cocaine, hallucinogens, and heroin are 23, 14, and 5%, respectively. Among those who eventually used each drug, the vast majority made the transition from first opportunity to first use within 1 year. Males were more likely than females to have opportunities to try these drugs, but were not more likely than females to progress to actual use once an opportunity occurred. Time trends indicate recent increases from 1990 to 1994 in the estimated probability of using an illicit drug once an opportunity occurs, particularly for hallucinogens. Exploratory analyses on race-ethnicity yielded some interesting leads for future research. This study sheds light on the epidemiology of the earliest stages of drug involvement in the USA. Implications for prevention efforts and for our understanding of sex differences in drug involvement are discussed. Copyright 1999, Elsevier Scientific Ltd.

Zaghloul A, Abdalla A, El Gammal H, Moselhy H. The consequences of khat use: A review of literature (review). European Journal of Psychiatry 17(2): 77–86, 2003. (42 refs.)

Khat is an evergreen tree, which grows in certain areas of East Africa and the Arabian Peninsula. The leaves of the khat have stimulating effect, and therefore chewed habitually by many people living in the area where it grows. Due to the availability of air transport, this drug has made its appearance in Western Europe and in the USA. In this article we will review all the issues related to khat consequences and its use and abuse in different areas of the world. Copyright 2003, European Journal of Psychiatry, Inc

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