Clinical Aspects of Inhalant Addiction

Types of Inhalants Being Abused

Inhalants encompass a wide range of pharmacologically diverse substances that readily vaporize. Unlike most other substances of abuse, which are classified into groups that share a specific central nervous system (CNS) action or perceived psychoactive effect, inhalants are grouped by their common route of administration. Inhalants are classified into three groups on the basis of their currently known pharmacologic actions ( Table 28.1 ). Group I includes volatile solvents, fuels, and anesthetics that contain aliphatic, aromatic, or halogenated hydrocarbons. All of these ingredients are found in thousands of commonly used and readily available consumer products. Group II includes nitrous oxide. Group III includes volatile alkyl nitrites. The most commonly abused inhalants are found in Group I. Virtually any hydrocarbon can have mind-altering effects when inhaled in large enough doses. Nitrous oxide, or “laughing gas,” is diverted from medical or dental anesthesia use and sold in balloons for inhalation or is simply inhaled from whipped cream aerosol cans. Alkyl nitrites, or “poppers,” are also abused; typically, amyl nitrite ampoules intended to treat angina are “popped” open and inhaled. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) excludes Group II and III inhalants from the inhalant-related disorders, which are classified as other (or unknown) substance-related disorder.

Epidemiology

Inhalants are easily available, legal, and inexpensive, which contribute to the high use of inhalants among poor and young persons. According to the 2018 National Institute on Drug Abuse (NIDA) survey of the United States, the past year use of inhalants is at its lowest levels in the history of the survey among 10th and 12th graders (2.4% and 1.6%, respectively). Rates of inhalant use are traditionally highest among 8th graders. Past year use among this age group is at 4.6%, down from 12.8% at its peak rate in 1995. In another 2017 survey by the National Survey on Drug Use and Health (NSDUH), past year inhalant use among individuals 12 to 17, 18 to 25, and 26 years of age or older are 2.3, 1.6, and 0.3 percent, respectively.

According to the NIDA and NSDUH surveys, most inhalant users are male; however, 8th grade girls are more likely to try inhalants than are 8th grade boys. In terms of ethnicity, Hispanics have the highest rates of past year use among 8th and 10th graders, compared to both African Americans and Caucasians. Urban and rural settings see comparable rates of inhalant abuse. Inhalant abusers may be related to certain occupations where abusable solvents, propellants, or anesthetics are readily available. Inhalants are sometimes referred to as gateway drugs, which means they are among the first drugs people try before moving on to other substances, such as alcohol, marijuana, and cocaine. Inhalant use accounts for 1% of all substance-related death and around 0.5% of all substance-related emergency room visits. Twenty-two percent of inhalant users who die of sudden sniffing death syndrome (SSDS) have no history of previous inhalant abuse–they are first-time users.

Mechanisms of Action

The immediate effects of group I and II inhalants are similar to the early classic stages of anesthesia. The abuser is initially stimulated and then disinhibited and prone to impulsive behaviors. Speech becomes slurred and gait is uneven. Euphoria, frequently with hallucinations, is followed by drowsiness and sleep, particularly after repeated inhalations. Coma is unusual because, as the user becomes drowsy, exposure to the inhalant is terminated before large enough doses are absorbed. The mechanisms of action of these inhalants have not been well defined. It is likely that inhalants act as a mix of N -methyl- d -aspartic acid (NMDA) antagonist and γ-aminobutyric acid (GABA) agonist to produce CNS depressant effects.

Nitrites have pharmacologic effects that are significantly different from those of other inhalants. Instead of direct CNS effects, they primarily cause vasodilation and smooth muscle relaxation. The sensations of floating and increased skin tactility as well as warmth and throbbing occur within 10s of inhalation and then diminish within 5 min. Abuse of nitrites may result in tachycardia, flushing, blurred vision, headache, lightheadedness, significant hypotension, syncope, and high enough levels of methemoglobinemia to cause cyanosis and lethargy. Other inhalants are used to alter mood, but nitrites are inhaled to enhance sexual feelings, penile engorgement, and anal sphincter relaxation to intensify sexual experience.

Morbidity and Mortality

Inhalant abuse causes psychosocial as well as organic morbidity. Ongoing inhalant abuse is associated with failure in school, delinquency, and an inability to adjust to societal norms. The chief organic morbidity is CNS damage, resulting in dementia and cerebellar dysfunction. Typically, there is a loss of cognitive and other higher functions, gait disturbances, and loss of coordination. Imaging studies demonstrate a loss of brain mass and white matter degeneration. Other organic effects are related to specific chemicals found in some but not all products. The strength of the association ranges from definite to likely to speculative. Definite associations include peripheral neuropathy, deafness, and metabolic acidosis. Likely morbidities include embryopathy, neonatal withdrawal, and lung damage. Speculative morbidities include cardiomyopathy, toxic hepatitis, decreased visual acuity, aplastic anemia, and leukemia.

Death due to inhalant abuse can occur by several mechanisms, including asphyxia, suffocation, risky behaviors, aspiration, and SSDS. Asphyxia is probably of only theoretical concern because it requires the partial pressure of the inhalant to be so high that oxygen is displaced. Suffocation occurs when the mode of use involves inhalation through the nose and mouth from a plastic bag, which may occlude the airway if the user loses consciousness. Disinhibition while under the influence of inhalants may cause dangerous behaviors such as drowning, jumps or falls from heights, hypothermia, and fire-associated deaths (due to the flammability of most inhalants). The risk of death from aspiration is similar to that for alcohol or other depressants and is related to the combination of decreased level of consciousness and loss of protective airway reflexes. SSDS is usually associated with cardiac arrest. The inhalant causes the heart to beat rapidly and erratically, resulting in cardiac arrest.

Chronic nitrous oxide abuse causes short-term memory loss and peripheral neuropathy. The peripheral neuropathy results when nitrous oxide inactivates vitamin B ₁₂ and mediates a pernicious anemia–type syndrome, which includes anemia, leukopenia, sensorimotor neuropathy, and posterior/lateral column spinal cord disease. Nitrites are abused mainly for their sensory and sexual effects, and use may promote higher-risk sexual practices, facilitate transmission of sexually transmitted infections, and result in pharmacologic interactions, such as with sildenafil (Viagra). Chronic abuse of volatile alkyl nitrites has documented hematologic and immune system effects without associated cognitive deficits.