2.19.99

Bibliography for Inhalants 

Epidemiology
Edwards RW; Oetting ER. Inhalant use in the United States. NIDA Res Monogr 1995;148:8-28.
No abstract

This entire issue dedicated to the epidemiology of inhalant abuse in different parts of the world.
Neumark YD; Delva J; Anthony JC . The epidemiology of adolescent inhalant drug involvement. Arch Pediatr Adolesc Med 1998 Aug;152(8):781-6.
ABSTRACT:
OBJECTIVE: To fill some of the gaps in our knowledge of the epidemiology of inhalant drug use. We examine age, sex, and race or ethnicity variations in the occurrence of inhalant use as well as time trends and the purported transitory nature of inhalant use among adolescents in the United States.
DESIGN: The data analyzed in this report were collected as part of the National Household Survey on Drug Abuse from 1990 through 1995. This annual survey is designed to provide cross-sectional information about the patterns of drug use among nationally representative samples of US household residents aged 12 years and older.
PARTICIPANTS: The sample included 34826 adolescents aged 12 to 17 years who participated in the National Household Survey on Drug Abuse from 1990 through 1995 (N=2177-8005 per survey year). RESULTS: The use of inhalants, particularly aerosols and glue, increased during the first half of the current decade. Initiation of inhalant use is not limited to early adolescence and is not a transitory behavior among adolescents in the United States. The use of inhalants is equally common among members of both sexes, and non- Hispanic white youths are more likely to report use than are members of other race or ethnic groups.
CONCLUSIONS: The increasing use of inhalants, their widespread availability, and the risks involved with their use indicate a need for more focused attention on this public health problem.
 

Esmail A; Warburton B; Bland JM; Anderson HR; Ramsey J Regional variations in deaths from volatile solvent abuse in Great Britain. Addiction 1997 Dec;92(12):1765-71.
ABSTRACT:
AIMS: To assess geographical variations in mortality and the relationship of socio-economic correlates to deaths from volatile substance abuse (VSA) in Great Britain.
DESIGN: Analysis of the National Register of deaths from VSA by linking the addresses (postcode) of the deceased to census enumeration districts and hence wards and counties.
SETTING AND PARTICIPANTS: All 775 deaths in Great Britain listed in the national register between 1985-91. Population counts from the 1991 census were used as denominators.
MEASUREMENT: The Poisson heterogeneity test was used to test the null hypothesis that all standardized mortality ratios were from the same population. The t-test was used to compare differences in Townsend Deprivation scores between wards with and without VSA deaths. Multiple regression was used to assess the relationship between indices of deprivation and deaths from VSA. FINDINGS: One-third of all VSA deathsccurred in six regions of Great Britain which accounted for 17% of the at risk population. There was considerable variation in age standardized mortality ratios (ASMR) across regions. A ward level analysis indicated that wards with a VSA death had significantly higher levels of deprivation. The Townsend deprivation index showed mean deprivation scores of 2.8 and 0.2, respectively, for wards with and without a registered death (p < 0.0001). Multiple regression at county/region level found that 45% of the variation in ASMR was explained by the components of the Townsend deprivation index. CONCLUSIONS: Factors associated with deprivation are important in VSA deaths and this should be taken into account in planning public health measures to prevent mortality.

Overview

Sharp C, Rosenberg, N. Inhalants. In Substance Abuse: A Comprehensive Textbook. Eds. Lowinson J, Ruiz P, Langrod J, Millman R. Williams and Wilkins. Baltimore. 3rd edition. 1997, pp. 246-64.
No abstract.

An excellent summary of the subject. Note, though, that nitrous oxide is not discussed.
Dinwiddie SH. Abuse of inhalants: a review. Addiction 1994 Aug;89(8):925-939
ABSTRACT:
Inhalants, a chemically heterogeneous group of psychoactive substances found in adhesives, lighter fluids, spray paints, cleaning fluids and typewriter correction fluid, may be used by up to 10% of young people. This article reviews the health effects, epidemiology, risk of other substance use and addiction and psychiatric co-morbidity associated with the practice of inhalant use.

Gillman MA . Nitrous oxide abuse in perspective. Clin Neuropharmacol 1992 Aug;15(4):297-306.
ABSTRACT:
I present evidence that certain health professionals have a higher liability to drug abuse than does the general population. In view of this, data are presented in which the extremely limited contribution of nitrous oxide to this problem is assessed. I demonstrate on the basis of the limited published data now available that pure nitrous oxide addiction is very rare among health professionals, being the rarest drug of abuse among them. When used by the latter, it is most commonly part of a polydrug abuse pattern, not being a major component of the addiction in these cases. It is clear that nitrous oxide addiction is even less of a problem in the general population. Furthermore, after almost 200 years of use, its very minor addictive potential should by now have clarified itself. It would appear that it is unlikely to become, has never been, nor is it the moment of any real significance as a drug of abuse when compared with the many currently available addictive drugs, which clearly pose a much more serious prproblem.

This review also has section on the use of nitrous oxide in addiction medicine.
Newell GR; Spitz MR; Wilson MB. Nitrite inhalants: historical perspective. NIDA Res Monogr 1988;83:1-14.
ABSTRACT:
There are important reasons for considering nitrite inhalation as a factor in the development of AIDS-related KS in young male homosexuals. These are (1) the pharmacologic properties of amyl, butyl, and isobutyl nitrites, which are toxic; (2) the mutagenic, teratogenic, and carcinogenic products resulting from metabolism of N-nitroso compounds; (3) the potent carcinogenicity of N-nitroso compounds in 39 different animal species; and (4) the deleterious effects of volatile nitrites on human lymphocytes both in vitro and in vivo. Specifically related to this epidemic, there are additional reasons for pursuing the connection between nitrite inhalation and development of KS. These include: (1) the timing of the production and sales of volatile nitrites for use as recreational drugs and the subsequent outbreak of the AIDS epidemic (7 to 10 years); (2) the extensive use of nitrites among male homosexuals; (3) the virtual universal history of nitrite use by young male homosexuals in whom KS has developed during the past 3 years; and (4) the age group in which KS is developing is consistent with a cohort initially exposed 7 to 10 years ago.
 

Steffee CH; Davis GJ; Nicol KK A whiff of death: fatal volatile solvent inhalation abuse. South Med J 1996 Sep;89(9):879-84.
ABSTRACT:
Inhalation abuse of volatile solvents, previously known generically as "glue sniffing," is typically pursued by adolescents. A wide range of legal, easily obtained products containing volatile substances are available for abuse. We report two illustrative cases of fatal volatile substance abuse: gasoline sniffing in a 20-year-old man and aerosol propellant gas inhalation (aerosol air freshener) in a 16-year-old girl with underlying reactive airway disease. Although the ratio of deaths to nonfatal inhalation escapades is extremely low, volatile solvent abuse carries the risk of sudden death due to cardiac arrest after a dysrhythmia or vasovagal event, central nervous system respiratory depression, hypoxia and hypercapnia due to the techniques of inhalation, and other mechanisms. Investigation of the patient's substance abuse history, examination of the scene of death, and special toxicologic analyses are critical to identifying volatile substance inhalation abuse as the cause of death because anatomic autopsy findings will typically be nonspecific. Above all, physicians must suspect the diagnosis of volatile substance inhalation abuse, especially in any case of sudden death involving an otherwise healthy young person.

A good brief review to give to medical students.

Neurobiology

Evans EB; Balster RL CNS depressant effects of volatile organic solvents. Neurosci Biobehav Rev 1991 Summer;15(2):233-41.
ABSTRACT:
Volatile chemicals used widely as solvents can produce acute effects on the nervous system and behavior after inhalation exposure, and many are subject to abuse. This review considers the nature of the acute effects of volatile organic solvents by comparing their actions to those of classical CNS depressant drugs such as the barbiturates, benzodiazepines and ethanol. Like CNS depressant drugs, selected inhalants have been shown to have biphasic effects on motor activity, disrupt psychomotor performance, have anticonvulsant effects, produce biphasic drug-like effects on rates of schedule-controlled operant behavior, increase rates of punished responding, enhance the effects of depressant drugs, serve as reinforcers in self-administration studies and share discriminative stimulus effects with barbiturates and ethanol. Toluene and 1,1,1-trichloroethane, as well as subanesthetic concentrations of halothane, have been the most extensively studied; however, it is unclear whether important differences may exist among solvents in their ability to produce a depressant profile of acute effects. The possibility that selected solvents can have acute effects similar to those of depressant drugs may shed light on the nature of their acute behavioral toxicology and on their abuse.

Gyulai FE; Firestone LL; Mintun MA; Winter PM In vivo imaging of human limbic responses to nitrous oxide inhalation. Anesth Analg 1996 Aug;83(2):291-98.
ABSTRACT:
Human behavioral studies have shown that nitrous oxide, in subanesthetic concentrations, impairs psychomotor function, cognitive performance, and learning and memory processes. However, the cerebral mechanisms of such effects remain unknown. Positron emission tomography (PET) was used to map the brain areas associated with nitrous oxide effects. Regional cerebral blood flow (rCBF) was measured in eight volunteers, during room air (control) or 20% nitrous oxide (nitrous oxide) inhalation using 15(O)-water, to reflect regional neuronal activity. To control for the possibility that 20% nitrous oxide uncoupled cerebral blood flow and metabolism, in four of the subjects, regional cerebral metabolic rate (rCMR) was also measured using 18F- deoxyglucose during the two experimental conditions. Results of rCBF and rCMR scans were compared between conditions using the statistical parametric mapping method, and areas of nitrous oxide-related activation or deactivation were identified at a significance level of 0.005. Percent changes in rCBF scan pixels from these activated or deactivated areas were then compared with those of stereotactically corresponding rCMR scan pixels with t statistics (P < 0.05 was defined as a significant difference). It was found that cerebral blood flow and metabolism were not uncoupled by 20% nitrous oxide, since percent changes in rCBF and rCMR, detected during nitrous oxide inhalation, did not differ significantly from each other (P < 0.05). Nitrous oxide inhalation was associated with significant activation in the anterior cingulate cortex, a limbic area known to mediate psychomotor and cognitive processes.
Deactivation was found in the posterior cingulate, hippocampus, parahippocampal gyrus, and visual association cortices in both hemispheres; the former two regions are known to mediate learning and memory. These areas identified by PET in vivo may provide the neuroanatomical basis for the behavioral responses associated with subanesthetic nitrous oxide inhalation.

Gillman MA Nitrous oxide, an opioid addictive agent. Review of the evidence. Am J Med 1986 Jul;81(1):97-102
ABSTRACT:
Pharmacologic evidence that nitrous oxide is addictive through direct interaction with the endogenous opioid system includes the possibility that it is a partial agonist and acts at the mu, kappa, and sigma opioid receptors. The medical and psychiatric complications of its abuse are discussed with special reference to the 32 cases of myeloneuropathy so far reported; other dangers are also mentioned. Notwithstanding the extremely low incidence of reported cases of nitrous oxide addiction compared with all other addictive substances, greater controls should be placed on its commercial availability to at least maintain its low level of abuse.

Treatment

Westermeyer J . The psychiatrist and solvent-inhalant abuse: recognition, assessment, and treatment. Am J Psychiatry 1987 Jul;144(7):903-7.
ABSTRACT:
Solvent-inhalant abuse, existent for a century, has been gradually increasing in several sectors of our society over the last few decades. This form of substance abuse involves a variety of pharmacological agents as well as several target groups at risk. A key strategy for effective intervention is early recognition in clinical as well as other settings. Psychiatrists should appreciate the clinical manifestations of these substances because they often appear in psychiatric settings. Assessment and treatment of the solvent-inhalant abuser must take into account the special pharmacological, demographic, and ecological factors associated with this particular form of substance abuse.

Classic Contributions

Beauvais F; Oetting ER . Toward a clear definition of inhalant abuse. Int J Addict 1987 Aug;22(8):779-84
ABSTRACT:
The study of the nature and extent of the use of volatile, psychoactive substances has been hampered by a confusing terminology. Widely disparate substances such as glue, gasoline, anesthetic gases, and nitrites have all been discussed under the single rubric of "inhalant abuse." A classification scheme is proposed which differentiates users of substances such as volatile hydrocarbons (gasoline, glue, etc.) from users of the anesthetic gases and of the amyl and butyl nitrites. Since users of these three types of volatile chemicals differ on predisposing factors, level of dysfunction, and consequences of use, the former group should be classed generically as "inhalant" users, while the latter should be diagnosed as users of a specific drug.

Psychiatric Co-morbidity

Dinwiddie SH; Zorumski CF; Rubin EH Psychiatric correlates of chronic solvent abuse. J Clin Psychiatry 1987 Aug;48(8):334-7.
ABSTRACT:
Eleven chronic solvent abusers admitted for inpatient treatment were retrospectively identified and their records reviewed to determine associated medical and psychiatric illness and other substance abuse. Antisocial personality disorder and narcotics abuse were common in the group, as were symptoms suggesting neurological or gastrointestinal dysfunction. The patients' response to substance abuse treatment was poor. The findings indicate that persons who abuse solvents over a long period tend to have associated behavioral patterns that may contribute to poor social adjustment and to poor response to the treatment of their substance-abuse problems.

Ron MA Volatile substance abuse: a review of possible long-term neurological, intellectual and psychiatric sequelae. Br J Psychiatry 1986 Mar;148:235-46.
ABSTRACT:
The possibility that chronic abuse of volatile substances can cause permanent neurological, psychiatric, and intellectual sequelae is critically reviewed. Toluene, present in the commonly used adhesives, is most often implicated in 'glue sniffing'; this review focuses on its potential long-term effects. Many criticisms - particularly poor matching of control samples and inability to distinguish between acute and chronic effects - can be levelled at the available studies, while no adequate follow-up studies have been performed. In the light of present knowledge, the possibility that permanent structural brain damage, with accompanying psychiatric manifestations, results from solvent abuse remains inconclusive.

Yamanouchi N; Okada S; Kodama K; Sakamoto T; Sekine H; Hirai S; Murakami A; Komatsu N; Sato T. Effects of MRI abnormalities on WAIS-R performance in solvent abusers. Acta Neurol Scand 1997 Jul;96(1):34-9.
ABSTRACT:
OBJECTIVE: To clarify how chronic solvent abuse affects cognitive function using magnetic resonance imaging as an index of brain damage.
MATERIAL AND METHODS: A total of 25 chronic solvent abusers underwent magnetic resonance imaging with quantitative neurometry and Wechsler Adult Intelligence Scales revised. RESULTS: The abusers with white matter change (n=10) showed significantly (P<0.05) lower performance IQ, especially in Digit Symbol subtest (P<0.01). Also, the severity of pontine atrophy was significantly correlated with PIQ (r=0.60, P<0.01).
CONCLUSIONS: These data indicate that solvent abuse causes the decline in the test performance reflecting cognitive and fine motor dysfunction and that white matter changes and pontine atrophy may have some roles in this decline.

Public Policy and History

Balster RL . College on problems of drug dependence presidential address 1996: inhalant abuse, a forgotten drug abuse problem. NIDA Res Monogr. 1997;174:3-8.
No abstract.

Tenenbein M . Leaded gasoline abuse: the role of tetraethyl lead. Hum Exp Toxicol 1997 Apr;16(4):217-22.
ABSTRACT:
Volatile substance abuse is practised worldwide however reports of the abuse of leaded gasoline have been limited to northern Canada, southwestern USA and the Australian Outback. Chronic, heavy abuse of leaded gasoline results in an encephalopathy, cerebellar and corticospinal symptoms and signs, dementia, mental status alterations, and persistent organic psychosis. Much of this is due to the hydrocarbons of gasoline while the tetraethyl lead contributes to the altered mental status and is responsible for the persistent psychosis. Lead chelation therapy is not rational and has not been shown to benefit these patients.

Medical Complications

Meadows R; Verghese A .Medical complications of glue sniffing. South Med J 1996 May;89(5):455-62.
ABSTRACT:
Glue sniffing refers to the deliberate inhalation of volatile solvents, commonly found in adhesives, for the purpose of intoxication. The increasing prevalence of inhalant use suggests that many physicians will encounter a glue-sniffing patient at some time during their practice. Knowledge of the epidemiology, toxicology, and medical complications associated with glue sniffing is essential in obtaining an accurate history of substance abuse and in clinically managing these patients. This review of sources is intended to aid clinicians in the recognition of glue-sniffing patients and in the diagnosis of acute and chronic medical complications associated with the abuse of glues, solvents, and related substances. Glue sniffing has been linked to sudden death and chronic damage to the heart, lungs, kidneys, liver, peripheral nerves, and brain. Inhalant abuse in general is associated with mortality and morbidity, including social, educational, and economic deprivation in adolescents and young adults.

Lolin Y. Chronic neurological toxicity associated with exposure to volatile substances. Hum Toxicol 1989 Jul;8(4):293-300
ABSTRACT:
1. The main neurological disorders associated with chronic VSA are peripheral neuropathy, cerebellar disease, chronic encephalopathy and dementia. Apart from peripheral neuropathy, the clinical features are non-specific, evidence for solvent-related toxicity is in most cases circumstantial and there is no clear dose/response relationship.
2. Peripheral neuropathy is mainly associated with n-hexane and methyl n- butyl ketone.
3. Cerebellar disease is usually associated with toluene exposure; in the more severe cases there is often radiological evidence of irreversible cerebellar atrophy.
4. Chronic encephalopathy and dementia are the most serious consequence of solvent exposure, particularly to toluene in abusers and to mixed solvents in industrial workers. Postmortem studies in some abusers have shown generalized axonal degeneration, demyelination and brain atrophy.
5. Further studies on low level solvent exposure are needed as little is known about the neurological consequences of mild VSA, especially as regards individual susceptibility and possible interactions between solvents and other toxins such as ethanol.

Soderberg LS. Immunomodulation by nitrite inhalants may predispose abusers to AIDS and Kaposi's sarcoma. J Neuroimmunol 1998 Mar 15;83(1-2):157-61.
ABSTRACT:
Epidemiological studies indicating that nitrite inhalant abuse is a co- factor in HIV infection and in Kaposi's sarcoma are supported by recent experimental studies, described in this review. Inhalation exposure to the nitrites produce a nonspecific cytotoxicity, depleting many cells of the immune system. Apparently distinct from this cytotoxicity, inhalation of the nitrites impairs a variety of immune mechanisms, affecting both humoral and cell-mediated immunity. In addition, the inhalant-increased macrophage production of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), can directly stimulate HIV replication and can also stimulate the growth of Kaposi's sarcoma cells. Thus, nitrite inhalants may impair immune resistance to infection and actively promote viral replication and tumor growth.

Special Populations

Jones HE; Balster RL. Inhalant abuse in pregnancy. Obstet Gynecol Clin North Am 1998 Mar;25(1):153-67.
ABSTRACT:
Information from a variety of sources suggests the possibility of adverse effects of maternal inhalant abuse, although a well-controlled, prospective study in this area has not been conducted. One source of this concern is the data from occupational exposure to some of the abused solvents, specifically toluene and TCE, with numerous reports suggesting increased spontaneous abortion and fetal malformations. There are also data suggesting decreased fertility and an increased risk for spontaneous abortion in health care workers exposed to nitrous oxide. The relevance of these studies to problems of inhalant abuse is not clear. Although the chemicals involved are the same, there are many differences in the exposure parameters, the populations exposed, and the types of associated risk factors. Nonetheless, there are more than 100 cases reported in the literature of children born to solvent- abusing mothers. Many of these children were small at birth, and some have craniofacial abnormalities not unlike that seen in children with FAS. In the few studies reporting the findings of follow-up in these children, some evidence has been obtained for retardation in growth and development and for residual deficits in cognitive, speech, and motor skills. Clearly, more research is needed to rule out the concomitant risk factors and to identify specific chemicals and patterns of use associated with adverse effects. Animal studies provide more direct evidence that prenatal exposure to toluene or TCE can produce reduced birth weights, occasional skeletal abnormalities, and delayed neurobehavioral development, even under conditions designed to mimic inhalant abuse patterns. Additional research is needed to identify other chemicals with adverse effects, critical periods of exposure, effects of combinations of inhalants, or interactions with drugs of abuse. The research literature seems sufficient to alert clinicians to possible problems in patients who abuse inhalants while pregnant. Diagnosis and good prenatal care for these women are important. The evidence for neonatal withdrawal is limited at this time; however, infants born to women who have recently used inhalants should be observed carefully for an alcohol-like withdrawal syndrome. Although it is not possible to link a specific birth defect or developmental problem in the child of an inhalant abuser to prenatal exposure to a specific chemical, it is clear that inhalant abuse and its associated lifestyle place children at increased risk. A wider appreciation of this is needed among health care professionals and the general public.

An excellent, comprehensive review of the subject.
Henretig F . Inhalant abuse in children and adolescents. Pediatr Ann. 1996 Jan;25(1):47-52.
No abstract available.

 

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