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PubMed1994

Time course of effects of brief inhalations of nitrous oxide in normal volunteers.

Nitrous oxide is commonly used (abused) recreationally by inhaling it in a bolus form (i.e. single or several breaths). The time course of the psychoactive effects of nitrous oxide, via this mode of inhalation, has not been adequately characterized and thus formed the basis for this study. Twelve healthy volunteers participated in four sessions, using a randomized, cross-over, placebo-controlled design. In each session one of the following four measures were assessed: self-reported strength of drug effects, mood, memory and psychomotor performance. Within sessions, subjects were exposed to four different concentrations of nitrous oxide in a randomized fashion: 0% (oxygen-placebo), 40%, 60% and 80%. At each concentration, or "trial", subjects took four deep breaths of the gas. Peak drug effects, as reported by our subjects, occurred within 30 seconds after the last inhalation of nitrous oxide, persisted for about a minute, and then gradually subsided to near-baseline levels by 5 minutes post-inhalation. Certain aspects of mood were briefly affected by nitrous oxide, generally in a dose-related fashion with increases in visual analog scale ratings of "anxious", "stimulated", "coasting (spaced out)", "lightheaded", "confused", and "high". Free recall of wards that had been presented between 30 and 60 seconds post-inhalation was significantly reduced after 80% nitrous oxide, relative to oxygen-placebo. There was a trend towards psychomotor impairment (Concentration x time: p = 0.08), as measured by the Digit Symbol Substitution Test, with peak decrements in performance (about a minute after inhalation) being greater after 80% nitrous oxide than after 0% nitrous oxide. Our results suggest that there arc acute, albeit brief, adverse effects of inhaling bolus concentrations of nitrous oxide.

Administration, Inhalation↗
PubMed1985

Methylene chloride inhalation: an unusual form of drug abuse.

Methylene chloride is a chlorinated hydrocarbon used widely in home and industry. Its intentional abuse has not been reported previously. We describe the case of a 14-year-old boy who presented with lethargy, nausea, and chills six hours after the intentional inhalation of a household product containing methylene chloride. The patient's elevated carboxyhemoglobin level responded well to 100% oxygen therapy. The pathophysiology and treatment of methylene chloride are discussed.

Absorption↗
PubMed1989

Adolescent cocaine abuse. Addictive potential, behavioral and psychiatric effects.

Four hundred seventy-nine drug abusing adolescent patients enrolled in seven Straight, Inc. Adolescent Drug-Abuse Treatment Programs in five geographic regions across the United States were studied to determine the severity and patterns of cocaine abuse. Of these, 341 admitted to cocaine use and became part of this survey. Cocaine use was categorized as heavy, intermediate, or light. Areas examined were the addictive spectrum, psychosocial dysfunction, and psychiatric symptoms. Intermediate and heavy users of cocaine abused significantly less marijuana and inhalants than light cocaine abusers. Heavy and intermediate users were more likely to use cocaine intravenously and to use crack. They developed tachyphylaxis more frequently, progressed to weekly use in less than 3 months more frequently, and became preoccupied with obtaining and using cocaine significantly more frequently. They used more sedative hypnotics to calm themselves and engaged in more criminal behavior, such as stealing from parents and stores and passing bad checks. They had more arrests for possession of drugs, stole more cars, sold more drugs, and were more likely to trade sexual favors to obtain the drug. Heavy and intermediate users were significantly more psychiatrically disturbed than light users, becoming more suspicious, nervous, aggressive, and demonstrating increased symptoms of fatigue, sleeplessness, decreased appetite, and increasing cocaine dysphoria. All of these symptoms could be mistaken for psychiatric disorders. This study suggests that cocaine is as addictive in adolescents as in adults; possibly more so. It also causes psychosocial dysfunction and psychiatric symptoms. Further research into cocaine addiction among adolescents is indicated.

Adolescent↗
PubMed1998

Death during deliberate propane inhalation.

Propane gas is used as a fuel and very rarely it is abused by young people in Greece. In this paper, we report a case of abuse of propane inhalation that resulted in accidental death. The determination of propane in autopsy samples was done by headspace gas chromatography and semiquantitation in liver, blood and the contents of the plastic bag through which the gas was diffused, which proved to be lethal.

Administration, Inhalation↗
PubMed2005

Bone mass toxicity associated with inhalation exposure to toluene.

The inhalation of a wide range of organic solvents has become popular among young adults. Toluene is one of the most commonly used solvents in industry; it is easily available and convenient to use. Many toxicologic effects on biological systems secondary to deliberate inhalation of toluene have been reported, but investigations on adverse effects associated with bone morbidity is limited. The purpose of this study is to determine bone mineralization and investigate the adverse effects of toluene on bone. The bone mineral density and content of the femoral neck of mice exposed to toluene at 300 ppm for 8 wk were measured by dual X-ray absorptiometry and found significantly reduced compared to the control group. Chronic exposure to toluene was found to affect bone metabolism, and toluene-induced changes could contribute to bone resorption and inhibition of bone formation. Toluene seems to be the responsible component for the demineralizating effects of commonly abused substances, and medical doctors must promote their education about the health hazards in those who abuse solvents especially in areas where inhalant abuse is endemic.

Absorptiometry, Photon↗
PubMed1993

Inhaled isobutyl nitrite compromises T-dependent, but not T-independent, antibody induction.

Habitual abuse of nitrite inhalants has been linked in epidemiological studies with seropositivity to human immunodeficiency virus and, separately, with Kaposi's sarcoma among AIDS patients. Mice exposed to isobutyl nitrite in an inhalation chamber for 45 min/day for 14 days had depressed IgM and IgG antibody responses. The inhibition was dose-dependent at 750-900 ppm, but antibody responses were increased at an intermediate (600 ppm) dose. Gender differences in immunotoxicity were not observed. Antibody responses to a T-independent antigen (DNP-ficoll) were not affected by the immunotoxic exposure, suggesting that B-cells were refractory to the toxic exposure. Toxic exposure to isobutyl nitrite did not selectively deplete a particular spleen cell population, but caused equivalent reductions of T-cells and B-cells. Finally, exposed mice remained immunocompromised for 3-5 days after terminating exposures. Normal immune responses returned by 5-7 days, suggesting that inhibition of cellular function was reversible.

Administration, Inhalation↗
PubMed1991

Exposure to inhaled isobutyl nitrite reduces T cell blastogenesis and antibody responsiveness.

Isobutyl nitrite is a drug of abuse popular among male homosexuals and among adolescents. In order to approximate the nitrite exposures of inhalant abusers, mice were treated with 900 ppm isobutyl nitrite in an inhalation chamber for 45 min per day for 14 days. After 14 consecutive days of exposure to isobutyl nitrite, mice weighed an average of 4% less than mice exposed to air. The spleens of nitrite-exposed mice weighed 15% less and had 24% fewer cells per spleen than those of controls. Adjusted for equal cell numbers, T cell mitogenic and allogeneic proliferative responses were significantly reduced by 33 and 47%, respectively. The frequency of T-dependent plaque-forming cells (PFC) was inhibited by 63% and the total number of PFC per spleen was reduced by 72% in nitrite-exposed mice. In contrast, B cell proliferative responses to LPS were unaltered, suggesting that the toxicity of isobutyl nitrite did not affect all lymphoid cells equally. The data suggest that habitual inhalation of isobutyl nitrite could impair immune competence and that toxicity appeared to be directed toward T cell functions.

Administration, Inhalation↗
PubMed2003

Facilitation of electrical brain self-stimulation behavior by abused solvents.

Animal models are needed to study the abuse-related behavioral and pharmacological effects of inhaled solvents. Previous studies have suggested that intracranial self-stimulation techniques may be successfully adapted for testing the effects of solvent exposure. The present study aimed to assess the effects of toluene, cyclohexane, acetone, and petroleum benzine (a widely used mixture of hexanes and heptanes) in rats trained to lever press or nose-poke for electrical stimulation delivered through electrodes implanted into the medial forebrain bundle. It was found that toluene, cyclohexane, and benzine but not acetone, increased rates of responding, particularly at the lower stimulation intensities. In another set of experiments utilizing an auto-titration procedure, all tested solvents significantly reduced self-stimulation thresholds. However, only for toluene and benzine were these effects observed at the exposure levels that did not impair rates of operant performance. There may not be such a clear separation of effects for acetone and cyclohexane. Thus, toluene and benzine appear to selectively affect brain reward systems in a manner similar to that for most other abused drugs. Data from intracranial self-stimulation studies of solvents may be useful in abuse potential assessment of individual compounds and for examining neural and behavioral processes involved in inhalant abuse.

Animals↗
PubMed1985

Abuse liability and pharmacodynamic characteristics of intravenous and inhaled nicotine.

The potential role of nicotine in tobacco dependence was investigated using the strategies of abuse liability assessment. Eight male volunteer cigarette smokers with histories of drug abuse resided on a research ward for the duration of the study. Each subject was tested with three doses of i.v. nicotine (0.75, 1.5 and 3.0 mg/10-sec infusion) and placebo each test day, and with three doses of inhaled nicotine, in the form of research cigarette smoke (0.4, 1.4 and 2.9 mg estimated yield) and placebo (sham-smoking), given on alternate test days. Each subject was tested on 4 days with both routes of administration, according to identical experimental protocols. Physiologic, subjective and observer data were collected at intervals ranging from 15 sec to 10 min beginning 10 min before drug administration and continuing for 30 min after administration. Both i.v. and inhaled nicotine produced dose-related increases in heart rate and blood pressure, and i.v. nicotine produced a transient bradycardia in four subjects during the first 30 sec after drug administration. Skin temperature was decreased by nicotine and pupil diameter was not consistently changed. Ratings of drug dose "strength" and drug "liking" were directly related to dose level whereas "desire to smoke cigarettes" was inversely related. Scores on the Morphine-Benzedrine Group (or Euphoria) scale of the Addiction Research Center Inventory were elevated by nicotine, and i.v. doses were identified frequently as cocaine. Signs and symptoms were similar for nicotine across the two routes of administration and included coughing, dizziness, nausea and relaxed feelings. Nicotine shared the pharmacologic profile of prototypic drugs of abuse. The study supports the hypothesis that the role of nicotine in tobacco dependence is equivalent to the role of other psychoactive drugs in substance abuse, e.g., to the role of cocaine in coca leaf use.

Adult↗
PubMed1996

Inhalation exposure to volatilized opioids produces antinociception in mice.

The goal of this study was to determine whether opioids of varying potencies are pharmacologically active via the inhalation route of administration in mice. The opioids evaluated included heroin, morphine, codeine, fentanyl and meperidine; each of these drugs has the potential for abuse in humans. Inhalation exposure to each of these compounds produced antinociception in a dose-dependent manner as assessed in the tall-flick test. No pyrolysis products were detected after heating either morphine or codeine at 250 degrees C for 5 min. Although 6-acetylmorphine was found after heating heroin, it accounted for less than 5% of the recovered sample. Heroin was somewhat less potent by inhalation administration than i.v. injection, with ED50 values of 1.6 and 0.69 mumol/kg, respectively. In contrast, the relative potency of morphine was substantially greater when inhaled than when injected, with respective ED50 values of 0.77 and 3.9 mumol/kg. Whereas the body to brain ratios of [3H]morphine were approximately 8 and 20 for inhalation exposure and i.v. injection, respectively, the ratio for heroin was approximately 5 regardless of administration route. This pattern of results suggests that the increase in morphine potency upon inhalation may have resulted from an increased accessibility to the brain compared with i.v. injection. Finally, naloxone reversed the antinociceptive effects of volatilized heroin, but neither the kappa selective antagonist nor-binaltorphimine nor the delta selective antagonist naltrindole blocked this antinociception, which suggests the involvement of mu opioid receptors. These findings taken together suggest the potential for the abuse of a variety of opioids, in addition to heroin, through the inhalation route of administration by humans.

Administration, Inhalation↗
PubMed1998

Inhalation of volatile substances: an emerging threat to readiness?

Volatile substance abuse is the deliberate inhalation of volatile substances to achieve intoxication. We discuss the history and pathophysiological effects of commonly abused volatile substances. We explore three deaths and one serious accident in active duty military settings. The causes for abuse in the military environment are numerous and include remote duty, peer influence, low cost, rapid onset, limitation of ethanol use, difficult detection/screening for use, and lack of knowledge among users and authorities. The lethality of these substances and their casual use can constitute a threat to military readiness. Our experience suggests an increase in the use of these substances in the military paralleling their increasing use in the general population. Education and awareness training could limit fatalities and decrease the threat in military and civilian populations.

Adult↗
PubMed1993

Minor structural brain changes in young drug abusers. A magnetic resonance study.

Twenty-three drug abusers and seventeen controls underwent clinical neurological examinations and magnetic resonance imaging (MRI) of the brain. The drug abuse encompassed cannabis, inhalants, opiates, psychedelics, amphetamines, and cocaine but not necessarily all drugs in all persons. The drug abuse was always combined with heavy alcohol consumption. One drug abuser had abnormal neurological findings which consisted of lower limb ataxia and 3 others had mild imbalance. MRI examinations did not show differences in width of the third, fourth or lateral ventricles nor the diameter of the cerebral aqueduct but the drug abusers had significantly smaller vermes cerebelli compared to controls. White matter changes also occurred more often in the drug abuser group. These findings are not consistent with known side-effects of the narcotic drugs but more probably a result of very high alcohol consumptions in parallel with drug abuse. Alcohol is clearly a much more potent brain toxic agent than are the most commonly abused narcotic drugs.

Adult↗
PubMed1994

Nitrite inhalants: history, epidemiology, and possible links to AIDS.

Nitrite inhalants have been commonly abused substances in the United States. Nitrite inhalants and AIDS was a popular topic in the early 1980s, when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use in the USA waned. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in a few laboratory studies, and it remains a candidate cofactor in the pathogenesis of AIDS-related Kaposi's sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Deliberate metallic paint inhalation and cultural marginality: paint sniffing among acculturating central California youth.

Deliberate metallic paint inhalation, paint sniffing, has recently become the focus of community concern in central California, as numbers of recalcitrant young abusers have entered the overloaded Mental Health and Juvenile Justice systems. This study, based on an extension of psychological, sociological and anthropological explanations of inhalant abuse, describes the adolescent paint sniffer and proposes that a combination of interacting factors both differentiates him/her from other-drug abusing youth, and predisposes him/her to inhalant use. The experimental hypothesis was tested by a stepwise discriminant analysis performed on 50 subjects, equally divided into two groups, paint and other-drug. Six variables, in combination, were found to significantly differentiate the groups, and the derived function accounted for 56% of the between group differences. The following conclusions can be drawn from this investigation. Firstly, the adolescent paint sniffer is demonstrably and meaningfully different as discriminated by a combination of personal, familial and sociocultural variables. Secondly, these identified factors have predisposed the sniffer to abuse, and cannot be considered simply the consequence of said abuse. Finally, it can be concluded that the paint sniffer is a youth disengaged from the symbols and traditions of his/her culture of origin and concomitantly rejected by the majority culture. Inhalant intoxication provides a "cheap" and effective escape from his/her isolation. Recommendations for prevention, early intervention and treatment are addressed.

Acculturation↗
PubMed1999

Analysis of isobutyl nitrite inhalant in rat and human blood: application for pharmacokinetic investigations.

Organic nitrites have been used therapeutically for the treatment of angina pectoris and as diagnostic agents for the evaluation of cardiac heart murmurs. In addition, these highly volatile vasodilators are being used as inhalant drugs of abuse. We developed a gas chromatographic assay using electron capture detection for the analysis of a representative nitrite inhalant, isobutyl nitrite (ISBN), in rat and human whole blood. Unconventional sampling and processing techniques were required because of the high volatility and chemical instability of nitrites in biological fluids. Our method produced a mean recovery of ISBN from rat blood of about 86% over a concentration range of 1.0 to 400 ng/ml. The inter-day coefficient of variation was below 15% at the lowest quantifiable concentration of 1 ng/ml ISBN in rat blood. In this report, we applied the analytical method to obtain new pharmacokinetic information about ISBN. Results show that rats inhaling 900 ppm ISBN for 45 min produced steady-state blood concentrations of about 290 ng/ml, and a rapid elimination half-life of 1.4 min.

Administration, Inhalation↗
PubMed1988

Aerosol treatment abuse.

A 4 year old boy with excellent inhaler technique was found to be abusing his salbutamol and beclomethasone dipropionate inhalers. This resulted in aggressive behaviour and probable hallucinations.

Aerosols↗
PubMed1990

Development of a System for Registry of Information on Drug use in Mexico.

Mexico's need for uniform information about drug abuse led to creation of an information collection system in 1986. This system, known as the System for Registry of Information on Drugs (SRID), currently covers the Mexico City metropolitan area. Plans call for it to be expanded in two phases--so as to provide coverage first of the states near the U.S. border and those with substantial tourism, and then to cover the nation as a whole. This article describes the data collection procedures used and the results of the four SRID assessments conducted in the Mexico City area from mid-1986 through mid-1988. These results indicate there were about nine male drug abusers in this period for every female; that drug use typically began young; that the drugs most commonly abused were marijuana, inhalants, alcohol, tobacco, and tranquilizers; that cocaine use was limited but apparently increasing; and that most of the drug abusers interviewed had not completed secondary school, were not in school at the time interviewed, and had relatively low socioeconomic status.

Adolescent↗