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Measurement of adolescent drug use.

There is widespread agreement that estimates of adolescent drug use prevalence from the National Household Survey of Drug Abuse (NHSDA) and Monitoring the Future (MTF) are subject to considerable measurement error. Nevertheless, some have suggested that trends over time in these prevalence estimates probably reflect true trends in drug use, since underreporting may be assumed to be constant over time. A recent National Research Council report criticizes this assumption on logical grounds. The present study examines adolescent drug use responses on the NHSDA and MTF for evidence of "drug omission," "jargon confusion" and "conceptual confusion," three types of misreporting expected to vary in magnitude with changes in drug use practices and changes in survey items. Results demonstrate that adolescent drug users are significantly more likely than adults to report use of drugs not listed in the NHSDA. Among adolescents who wrote in the "other" drugs they used, 66% and 86% of hallucinogen and inhalant responses showed confusion over the meaning of the pharmacological terms used in the NHSDA. Almost 20% of MTF respondents who report lifetime use of Rohypnol or ecstasy, when specifically queried about these drugs, deny lifetime use of any substances in the drug classes intended to assess use of Rohypnol and ecstasy. MTF respondents reporting lifetime use of PCP underreport use of hallucinogens at rates that vary substantially over time, from a high of 45% (in 1986), to a low of just 8% (in 1998). The implications of these findings for adolescent drug use prevalence estimation and survey design are discussed.

Administration, Inhalation↗

Fatal "crack" cocaine ingestion in an infant.

This report describes a 10-month-old infant girl who died of cocaine poisoning. The infant was found apneic and in ventricular fibrillation after the parents summoned rescue personnel and claimed she had ingested rat poison. The parents later admitted that 2 hours before calling for assistance, the infant's 2-year-old brother was found eating "crack" cocaine and also feeding it to the infant. Investigators found "crack" cocaine throughout the house and in the infant's crib. At autopsy, the infant had two pieces of "crack" cocaine in the duodenum. The brain exhibited a markedly thinned corpus callosum. Toxicologic examination showed high concentrations of cocaine in the blood and in other specimens. The manner of death was classified as homicide because the infant was willfully placed in a hazardous environment with an easily accessible toxic substance, medical attention was deliberately delayed for 2 hours, and medical personnel were deceived when they were falsely told she had ingested rat poison. These features were thought to constitute neglect. The toxicologic characteristics of this case are unique. There are numerous reports of passive cocaine inhalation in infants and children less than 5 years of age, but ingestion of cocaine in this age group has rarely been documented. This age group also has no reported deaths due to cocaine ingestion and no cases of "crack" cocaine ingestion. The high concentrations of cocaine seen in this case, combined with the "crack" cocaine found in the duodenum, indicate ingestion as the route of exposure. The thinned corpus callosum in this case may be a consequence of intrauterine cocaine exposure.

Autopsy↗

Pulmonary effects of illicit drug use.

The lungs are at considerable risk from the use of injected or inhaled illicit drugs. The extent and clinical significance of illicit drug induced lung damage is not known completely. Drug use leads to an increase in infectious pulmonary disease, historically in relation to nonsterile injection techniques, and, more recently, in relation to HIV infection and its pulmonary manifestations. Barotrauma related to "smoking topography" or errant injections also represents a real risk of drug use. Although granulomatous disease that involves the pulmonary vasculature and interstitium is probably common in injection drug users, the clinical consequence of such is difficult to estimate. What effect smoked or injected illicit drugs have on short- and long-term pulmonary function also is hard to ascertain. The ubiquitous use of tobacco among users of illicit drugs certainly has confounding effects. Given that illicit drug use is common and that the "popular" drugs of abuse change from generation to generation, the pulmonary physician must remain informed about, and alert for, the effects of drugs of abuse.

Cocaine-Related Disorders↗

Parkinsonism induced by solvent abuse.

We report the first description of a patient with parkinsonism induced by solvent abuse. Our patient developed parkinsonism acutely, following heavy abuse of lacquer thinner. Her clinical deficits were indistinguishable from idiopathic parkinsonism (Parkinson's disease) and she responded to levodopa. Parkinsonism has persisted for more than 3 months. Brain computed tomography was normal. Positron emission tomographic studies showed normal fluorodopa uptake and reduced raclopride binding, indicating an unusual disturbance of striatal dopaminergic function. This patient suggests that organic solvents may cause parkinsonism in susceptible individuals.

Administration, Inhalation↗

Analysis of the reinforcing and subjective effects of different doses of nitrous oxide using a free-choice procedure.

The reinforcing and subjective effects of five doses of nitrous oxide (0, 10, 20, 30, 40% N(2)O in O(2)) were studied in 20 non-drug-abusers using a free-choice procedure. During each of five sessions, subjects sampled a dose of N(2)O and 100% O(2) (placebo) for 10 min each. Later they chose nine times, once every 5 min, among N(2)O (e.g. 'Agent A'), placebo (e.g. 'Agent B'), or a no-drug option. Mean preference ratios (N(2)O choices/[N(2)O choices+placebo choices]) and total N(2)O choice increased with increasing N(2)O dose. Individual preference ratios suggested that at least one active dose of N(2)O functioned as a reinforcer in 80% of subjects, and the doses that functioned as reinforcers varied across subjects. N(2)O choice was positively correlated with end-of-session and post-session ratings of N(2)O liking and of wanting to inhale N(2)O again, but not with ratings of those effects during sampling. Placebo was chosen significantly less than the no-drug option, even though both were 100% O(2). More robust reinforcing effects of N(2)O were observed in this subject population than in previous studies. Choice data emphasize the importance of examining a range of doses, and of examining those effects within-subject, when assessing reinforcing effects of drugs. Inclusion of the no-drug option eliminated the 'forced' choice of placebo, making preference ratios easier to interpret than in previous, forced-choice procedures. Reinforcing effects were more correlated with subjective effects assessed after the session than with subjective effects obtained while subjects were under the influence of the drug.

Adult↗

[Reversible posterior leukoencephalopathy, severe hypertension, and cocaine abuse].

Reversible posterior leukoencephalopathy syndrome is a brain disorder characterized by headache, nausea, vomiting, visual disturbance, depressed level of consciousness, convulsions and occasionally focal neurologic deficits. It is commonly associated with malignant hypertension, toxemia of pregnancy or the use of immunosuppressive agents. Early diagnosis and specific treatment is essential. We report a case of reversible posterior leukoencephalopathy in the context of a hypertensive crisis in an habitual cocaine sniffer. Reversible posterior leukoencephalopathy must be suspected in every patient with hypertensive crisis and compatible clinic manifestation. Neuroimaging studies show characteristic features which confirm the diagnosis.

Administration, Inhalation↗

Use of marijuana and other drugs by college students of São Paulo, Brazil.

Drug usage in a sample of 1,069 college students of São Paulo, Brazil, was investigated. The highest lifetime prevalence was reported for alcohol (82%) and tobacco (39%) followed by inhalants (28%), marijuana (26%), over-the-counter tranquilizers and stimulants (17%), and cocaine (10%). Current use is considerably smaller. Marijuana users were classified as having a "Stable," "Descending," and "Once" pattern of consumption frequency. These patterns were orderly related to sex, socioeconomic status, use of drugs, drug approval, and peer group. Drug usage appeared as predominantly social-recreational in this population, although the risk of misuse for "Stable" students should be evaluated.

Adolescent↗

Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity in rat brain.

RATIONALE: Ecstasy abuse commonly occurs in hot, overcrowded environments in combination with alcohol. Around 90% of ecstasy users take ethanol; over 70% of these users also often drink alcohol at hazardous levels. OBJECTIVES: We wished to examine whether binge ethanol administration enhanced the long-lasting 5-HT neurotoxicity induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats maintained at high ambient temperature and the role of acetaldehyde. MATERIALS AND METHODS: Rats were treated with a 4-day ethanol regimen leading to plasma ethanol levels of around 450 mg/dl. On day 5, rats were placed at 30 degrees C and administered MDMA (5 mg/kg). Rectal temperature and hydroxyl radical formation were measured immediately before and up to 6 h after MDMA. 5-HT concentration and 5-HT transporter density were determined 7 days later. A group of rats received cyanamide (50 mg/kg) on days 1 and 3 of the 4-day-ethanol inhalation. RESULTS: In ethanol treated rats, MDMA produced a hyperthermic response similar to that observed in controls but enhanced the loss of 5-HT concentration and 5-HT transporter density in the hippocampus. Cyanamide elevated the plasma acetaldehyde concentration fivefold to sevenfold, reduced the MDMA-induced hyperthermia and increased the neuronal damage with neurotoxicity also appearing in the cortex. MDMA increased hydroxyl radical production in the hippocampus, the effect being more marked in rats pre-exposed to ethanol. CONCLUSIONS: Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity by a mechanism not related to changes in acute hyperthermia but probably involving hydroxyl radical formation. The magnitude of this effect is more pronounced after increasing plasma acetaldehyde levels by aldehyde dehydrogenase inhibition.

Acetaldehyde↗

Prevalence of serologic markers of HBV, HDV, HCV and HIV in non-injection drug users compared to injection drug users in Gran Canaria, Spain.

Injection drug use (IDU) is one of the most significant risk factors for viral hepatitis (B, D and C) and human immunodeficiency virus (HIV) infection. However, there is little information about the risk of infection among non-injection drug users (non-IDUs). The present study was designed to perform several objectives: (a) to evaluate the prevalence of serological markers of hepatitis B, D, C virus and HIV in IDU and non-IDU patients; (b) to compare the prevalence of these markers between both groups; (c) to identify risk factors for HCV and HIV in this population; and (d) to correlate the presence of HCV and liver function. A total of 385 consecutive patients (122 IDUs and 263 non-IDUs), admitted to the Drug Dependency Treatment Unit at the Hospital Insular of Gran Canaria between 1993 to 1994, were included in the study. The serological markers of HBV, HDV, HCV and HIV were determined by ELISA and immunoblot methods. In all cases we also measured syphilis tests (RPR and FTAabs), serum aminotransferases and serum gammaglutamiltranspeptidase. Compared to the non-IDU, the IDU group presents a higher prevalence of antiHBc (55.0% vs. 20.7%, p < 0.0001), antiHCV (87.6% vs. 35.3%, p < 0.0001) and antiHIV (21.8% vs. 2.7%, p < 0.0001). There was no significant difference in RPR positivity (0.9% vs. 4.9%, p = 0.06). Delta infection was only detected in injection drug users, and the prevalence was low. Using logistic regression, the only risk factors associated with antiHCV positivity were injection drug addiction (OR: 9.2, 95% CI: 4.9-17.0) and antiHBc positivity (OR: 5.5, 95% CI: 3.0-9.9). Similarly, the associated risk factors for HIV were injection drug addiction (OR: 5.9, 95% CI: 2.3-15.0) and antiHBc positivity (OR: 3.8, 95% CI: 1.5-9.2). However, no correlation was found between antiHCV positive and antiHIV or between these markers and RPR positivity. Patients positive for antiHCV showed significant elevations in aspartate aminotransferase and alanine aminotransferase levels, when compared with patients negative for antiHCV: 65.0 vs. 39.2 U/l (p < 0.001) and 88.4 vs. 40.3 U/l (p < 0.001), respectively. We conclude that drug users have an elevated prevalence of HCV, HBV and HIV infection, even if drug use is only inhalated. On the other hand, the main risk factors associated with HCV and HIV are injection drug addiction and exposure to hepatitis B virus. Finally, in the study population, liver dysfunction is closely related to HCV infection.

Adolescent↗

[A study of high school students with alcoholic parents].

This is the first study in Japan which estimates the frequency of children with alcoholic parents in the general population and investigates the addictive substances abused by these children. In order to determine which children have alcoholic parents, a 10-item set of questions concerning the alcohol problems of parents known as CAST-J (Children of Alcoholics Screening Test-Japan) was prepared using CAST (Children of Alcoholics Screening Test) as a reference. In a preliminary survey, CAST-J and CAST were performed on 20 cases diagnosed as children of parents with alcohol-related problems by psychiatrists and 112 students of medically-related school. From these results, it was decided that those who had answered affirmatively to at least three of the 10 questions in CAST-J were children of alcoholic parents (parents with alcohol-related problems). The present survey was performed on 1,754 high school students who underwent the CAST-J and AAIS (Adolescent Alcohol Involvement Scale). The information on the experience of smoking and thinner inhalation was also obtained. Among these high school students, 11.6% of the total (8.4% of males and 15.2% of females) had alcoholic parents. Among the high school students with alcoholic parents, 21.7% were found to be alcohol misusers or alcoholic-like drinkers in the AAIS, which was significantly more than the 10.6% of students without alcoholic parents. This significant difference was seen for both males and females. It was also found that significantly more high school students with alcoholic parents had experienced smoking and thinner inhalation than those without such parents. In conclusion, it appeared that more than 10% of Japanese high school students have alcoholic parents, and they also often misuse addictive substances such as alcohol, tobacco and thinner.

Adolescent↗

Smoking, drinking and use of illicit drugs among adolescents in Ontario: prevalence, patterns of use and sociodemographic correlates.

Data from a cross-sectional survey of the health of Ontario children carried out in 1983 were used to provide estimates of the prevalence, patterns and sociodemographic correlates of the use of tobacco, alcohol and illicit drugs (substance use) among adolescents aged 12 to 16 years. Ninety-one percent of selected households participated. The prevalence rates of all categories of substance use, except use of inhalants, increased with increasing age. Among children aged 14 to 16 years the rates for girls were higher than those for boys for all categories of substance use except use of other, nondefined drugs. The prevalence rates of substance use tended to be higher in small urban areas except for use of marijuana (more prevalent in large urban areas) and use of inhalants (more prevalent in rural areas). The strongest evidence of clustering of substance use within families was found for smoking. Children who used less prevalent drugs (e.g., "hard" drugs) also tended to use the more prevalent ones (e.g., marijuana, tobacco and alcohol). Associations between substance use and low socioeconomic status suggested a positive relation with smoking and a negative relation with use of alcohol. The findings highlight the need for preventive programs aimed at specific subgroups in the adolescent population.

Adolescent↗

An epidemiological perspective of substance use among high school pupils in rural KwaZulu-Natal.

OBJECTIVES: To investigate prevalence and the factors influencing substance use among rural high school pupils in KwaZulu-Natal in order to develop and implement intervention programmes. DESIGN: Cross-sectional study. SETTING: Twenty-eight high schools in southern KwaZulu-Natal. SUBJECTS: One thousand three hundred and eighteen grade 10 pupils. OUTCOME MEASURES: An anonymous self-reporting questionnaire was used to investigate the use of alcohol, tobacco (cigarettes), cannabis and solvents. RESULTS: Of the male scholars, 52.9% (95% confidence interval (CI): 45.4-60.3) reported ever using alcohol, 16.9% (CI: 11.5-24.0) reported using cannabis, and 13.1% (CI: 7.2-22.5) had smoked more than one cigarette daily. Among male pupils 45.5% (CI: 38.6-52.6) had inhaled benzine and 34.6% (CI: 28.0-41.8), thinners; 7.4% (CI: 3.4-15.2) had used cocaine and 4.1% (CI: 1.0-10.6), crack. Female pupils reported significantly less use of alcohol (25.5%, CI: 17.6-35.3), cannabis (2.3%, CI: 1.3-4.1), cigarettes (more than one daily) (2.0%, CI: 1.0-4.1), and inhalation of benzine (18.8%, CI: 13.8-25.2) and thinners (10.8%, CI: 7.2-16). Logistical regression indicated that the odds of smoking cigarettes increased significantly (p < 0.0005) with use of the other substances. CONCLUSION: The results of this study confirm the prevalence of multi-substance use among pupils at the majority of rural high schools in this district and the need for targeted interventions to reduce/prevent this.

Adolescent↗

Regional cerebral blood flow in long-term heavy cannabis use.

Regional cerebral blood flow (rCBF) was measured by the 133Xenon inhalation method in nine male chronic cannabis users. The rCBF level in cannabis users was significantly (11%) lower than that of age- and sex-matched healthy controls. Four of the subjects were reexamined after 9-60 days of detoxification and showed a significant (12%) increase of the CBF level at followup. No significant regional flow abnormalities were noted. The global CBF reduction seen in the early phase of detoxification is most likely the consequence of the dysfunction of the central nervous system accompanying chronic cannabis use.

Adolescent↗

[Anesthesia for pneumonectomy in a patient with an amphetamine psychosis].

We report a 50 year old male patient with an amphetamine psychosis who had anesthesia for a pneumonectomy. The patient had been intoxicated with methylamphetamine since 1976. After drug abuse for 2 years, he suffered from hallucination and delusion. He was diagnosed to have amphetamine psychosis by psychiatrists and treated with major tranquilizers. During the treatment for the psychosis, a squamous cell carcinoma in the lung was found. Pneumonectomy was scheduled. Anesthesia was induced with thiopental 300 mg and maintained with isoflurane, nitrous oxide, oxygen and epidural lidocaine. In the recovery room, he was injected with a major tranquilizer. Epidural buprenorphine was used to lighten the pain stress. Psychotic state did not appear after the surgery. We also discuss amphetamine psychosis in Japan.

Amphetamine↗

Non-intentional doping in sports.

Compulsory drug testing was introduced in 1968 by the International Olympic Committee. Since then, several doping cases have been reported in sports competition world wide. Positive results are based on the detection of prohibited substances, their metabolites and markers in biological (mainly urine) samples supplied by athletes. In some cases, the evidences were not contested and athletes admitted the use of banned substances. However, in other cases, athletes denied the use of doping to enhance performance and claimed to have inadvertently or passively absorbed the drug. Unfortunately, no current accepted analytical method is capable of distinguishing between a sample from a cheater and one from an athlete who was passively exposed to a doping agent. Athletes' allegations have included the passive inhalation of drug smoke (e.g. marijuana) or the ingestion of food or products sold as nutritional supplements that contained prohibited substances. In the scientific literature, several studies have been performed to investigate the possibility of an accidental exposure being the reason for the appearance of detectable quantities of banned substances in urine samples. Based on these studies, this article discusses those cases where the athlete's claims could be possible in generating a positive result in doping control and in which circumstances it would be improbable to happen.

Brazil↗

A fatal overdose of cocaine associated with coingestion of marijuana, buprenorphine, and fluoxetine. Body fluid and tissue distribution of cocaine and its metabolites determined by hydrophilic interaction chromatography-mass spectrometry(HILIC-MS).

Chromatographic separation of highly polar basic drugs with ideal ionspray mass spectrometry volatile mobile phases is a difficult challenge. A new quantification procedure was developed using hydrophilic interaction chromatography-mass spectrometry with turbo-ionspray ionization in the positive mode. After addition of deuterated internal standards and simple clean-up liquid extraction, the dried extracts were reconstituted in 500 microL pure acetonitrile and 5 microL was directly injected onto a Waters Atlantis HILIC 150- x 2.1-mm, 3-microm column. Chromatographic separations of cocaine, seven metabolites, and anhydroecgonine were obtained by linear gradient-elution with decreasing high concentrations of acetonitrile (80-56% in 18 min). This high proportion of organic solvent makes it easier to be coupled with MS. The eluent was buffered with 2 mM ammonium acetate at pH 4.5. Except for m-hydroxy-benzoylecgonine, the within-day and between-day precisions at 20, 100, and 500 ng/mL were below 7 and 19.1%, respectively. Accuracy was also below +/- 13.5% at all tested concentrations. The limit of quantification was 5 ng/mL (%Diff < 16.1, %RSD < 4.3) and the limit of detection below 0.5 ng/mL. This method was successfully applied to a fatal overdose. In Switzerland, cocaine abuse has dramatically increased in the last few years. A 45-year-old man, a known HIV-positive drug user, was found dead at home. According to relatives, cocaine was self-injected about 10 times during the evening before death. A low amount of cocaine (0.45 mg) was detected in the bloody fluid taken from a syringe discovered near the corpse. Besides injection marks, no significant lesions were detected during the forensic autopsy. Toxicological investigations showed high cocaine concentrations in all body fluids and tissues. The peripheral blood concentrations of cocaine, benzoylecgonine, and methylecgonine were 5.0, 10.4, and 4.1 mg/L, respectively. The brain concentrations of cocaine, benzoylecgonine, and methylecgonine were 21.2, 3.8, and 3.3 mg/kg, respectively. The highest concentrations of norcocaine (about 1 mg/L) were measured in bile and urine. Very high levels of cocaine were determined in hair (160 ng/mg), indicating chronic cocaine use. A low concentration of anhydroecgonine methylester was also found in urine (0.65 mg/L) suggesting recent cocaine inhalation. Therapeutic blood concentrations of fluoxetine (0.15 mg/L) and buprenorphine (0.1 microg/L) were also discovered. A relatively high concentration of Delta(9)-THC was measured both in peripheral blood (8.2 microg/L) and brain cortex (13.5 microg/kg), suggesting that the victim was under the influence of cannabis at the time of death. In addition, fluoxetine might have enhanced the toxic effects of cocaine because of its weak pro-arrhythmogenic properties. Likewise, combination of cannabinoids and cocaine might have increase detrimental cardiovascular effects. Altogether, these results indicate a lethal cocaine overdose with a minor contribution of fluoxetine and cannabinoids.

Analgesics, Opioid↗

Anesthetic management of the cocaine abuse patient.

Cocaine is an extremely addictive local anesthetic which can produce stimulation of the sympathetic nervous system due to the inhibition of catecholamine reuptake at the synaptic junction. Because of the rapid metabolism of cocaine, the probability of a patient presenting to the operating room with acute intoxication is unlikely. However, the physiological effects of chronic cocaine abuse on various organ systems have an impact on anesthesia management. A preoperative review of major organ systems is essential. Selective beta 1 antagonists (i.e., esmolol) may need to be titrated with a direct vasodilator (i.e., nitroprusside) to manage hypertension and tachycardia. The nonselective beta antagonist effects of labetalol are much more potent than its alpha antagonist effects, which could result in unopposed alpha vasoconstriction. In addition, the equal affinity of the alpha adrenergic antagonist, phentolamine, for both alpha 1 and alpha 2 receptors may result in significant tachycardia. Nitroglycerin has also been used in management of hypertension associated with coronary vasoconstriction. There is controversy regarding management of ventricular dysrhythmias and asystole. Lidocaine is an amide local anesthetic that may have addictive effects, in the presence of cocaine, which may lower the seizure threshold. In addition, the use of epinephrine to treat asystole is controversial in the presence of a state of excess catecholamines induced by cocaine. General anesthesia may include barbiturates, nitrous oxide, and opioids. Inhalational agents may be used with caution due to their myocardial depressant effects. Regional anesthesia may be a good choice if coagulopathies and hypovolemia are corrected before the procedure.

Anesthesia↗

HIV/AIDS risk behaviors and correlates of injection drug use among drug users in Pakistan.

We studied prevalence and correlates of injection drug use, awareness of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and risky behaviors among drug users serviced by a nongovernmental organization catering to drug users in three Pakistani cities (Quetta, Peshawar, and Rawalpindi). Logistic regression analysis was used to identify correlates of injection drug use. Of 608 drug users, 99.8% were male; median age was 32 years, and 44% were married. Most (79.8%) were Pakistani; 15.3% were Afghani. The majority used heroin (98.7%), mostly by inhalation; 15.2% injected drugs. Only 41% had heard of HIV/AIDS, and 30% had been paid for donating blood. Injection drug use and needle sharing were highest in Quetta. Injecting drug users (IDUs) were nearly twice as likely to have donated blood and to have heard about HIV/AIDS compared to other drug users. Interventions to discourage transitions to injection, increase HIV testing, and safeguard the blood supply in Pakistan are urgently needed.

Adult↗