The Abused Substances

It is important to appreciate that these volatile substances vary in their physical as well as in their chemical properties. In particular, they vary greatly in their boiling points, some being gases and others being liquids at room temperature. Table 2 lists the compounds found in the products listed in Table 1 with their 

On inhalation, the substances pass rapidly into the blood from the alveoli. They are very lipophilic (ie, are preferentially absorbed into fatty organs such as fat stores and brain). They are subsequently slowly excreted either unchanged through the lungs or as metabolites in urine. Some, such as toluene, may be detected as long as 10 days after the last exposure. 

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The abused substances covered in this chapter include nicotine, alcohol, cocaine, amphetamines, cannabis, and opioids. While many more substances can be and have been abused, these drugs are among the most popular. 

Reward Therapy. A similar (yet nonspecific) approach is to use a medication that stimulates the brain s reward centers. Reward medications usually do not work in quite the same way as the substance of abuse however, the net effect in the final common pathway (i.e., the reward centers) may be the same. For the most part, these reward centers are activated by either dopamine or endogenous opioid agonists. One common feature of most abused drugs is that they stimulate these reward centers. This lies at the heart of their addictive potential. Some attempts have been made to use medications that activate these reward centers in place of the abused substance. The hypothesis is that the addict will have less intense craving for his/her preferred substance of abuse in the presence of these other agents. This is, of course, a relatively nonspecific approach that could theoretically be used to treat the abuse of many different substances. It has not yet, however, demonstrated any utility in the treatment of substance abuse. 

The findings of toxic leukoencephalopathy in this patient s brain-imaging studies were similar to those reported in patients who have inhaled impure heroin. However, he had used intravenous heroin and cocaine. This is therefore the first case report of leukoencephalopathy after intravenous use of these drugs. However, it should be noted that the authors did not indicate how the route of drug use was confirmed. They noted that lipophilic substances, such as hexachlorophene or triethylthin, were likely impurities in the abused substances. 

Detoxication of drugs of abuse has generally followed a traditional approach involving pharmacological intervention in the biochemical action of the abused substance. This intervention has usually taken the form of the development of inhibitors or antagonists of biological macromolecules such as central nervous system (CNS) receptors. 

Withdrawal of the abused substance results in a decrease in the large quantities of dopamine resulting from the drugs. The substance-dependent person experiences symptoms of depression, fatigue, and withdrawal. The only way to relieve these symptoms is to use increasing quantities of the abused substance of abuse, reinforcing dependence on the drug. 

The Controlled Substances Act of 1970 regulates die manufacture, distribution, and dispensing of drugs that have abuse potential (see information under Federal Drag Legislation and Enforcement in diis chapter). Drag under the Controlled Substances Act are divided into five schedules, based on their potential for abuse and physical and psychological dependence Display 1-2 describes the five schedules. 

Comparable findings for lifetime prevalence of psychiatric disorders were obtained in another study of 133 persons, which also found that 47% received a concurrent DSM-III diagnosis of substance abuse or dependence (Khantzian and Treece 1985). The most frequently abused substances were sedative-hypnotics (23%), alcohol (14%), and cannabis (13%). Similar rates of psychiatric disorders were found in other studies of drug abusers (Mirin et al. 1986 Woody et al. 1983). Although such diagnoses do not imply causality, and, in many cases, opioid dependence causes or exacerbates psychiatric problems, some causal link seems likely (Regier et al. 1990). 

Other anesthetics susceptible to abuse, such as ether and chloroform, have received far less attention, because they are considered to be less commonly abused substances. Nonetheless, when inhaled, ether and chloroform are also rapidly absorbed and distributed in the central nervous system (CNS), inducing a rapid euphoria. Ether and chloroform inhalation is facilitated by the fact that they have a low boiling point (i.e., approximately 34°C) (Delteil et al. 1974). 

Inhalation of other general anesthetics susceptible to abuse, such as ether and chloroform, appears to be limited to health professionals who have easy access to these compounds and who tend to use these dtugs in isolation. Recreational and social use of these substances has been somewhat limited by their high flammability and by frequent and intense undesirable adverse effects at moderate doses. It has been suggested that the abuse of ether or chloroform alone is a rare phenomenon (Delteil et al. 1974 Deniker et al. 1972), occurring usually in the context of dependence on othet substances, particularly alcohol (Krenz et al. 2003). 

Explain the commonalities of action of abused substances on the reward system in the brain. 

Virtually all abused substances appear to activate the same brain reward pathway. 

While activation of the reward pathways explains the pleasurable sensations associated with acute substance use, chronic use of abused substances resulting in both addiction and withdrawal may be related to neuroadaptive effects occurring within the brain. 

O Virtually all abused substances appear to activate the same brain reward pathway. Key components of the reward pathway are the dopamine (DA) mesocorticolimbic system that projects from the ventral tegmental area (VTA) and the nucleus accumbens (NA) to the prefrontal cortex, the amygdala, and the olfactory tubercle (Figs. 33-3 and 33-4).5 Animal studies... 

FIGURE 33-4. Where different abused substances interact with the reward system in the brain. Data from reference 5. (From h ttp //www.drugabuse.gov/pubs/Teaching/)... 

Unfortunately, unlike some medical diseases, substance dependence cannot be cured with medications alone. However, we can sometimes alleviate the effects of drug intoxication, attenuate the adverse effects of withdrawal, or use agents that may somewhat decrease craving for, and relapse to, abused substances. 

The intoxicating effects of opioids appear to be due to their action as agonists on mu (p) receptors of the opioid neurotransmitter system. Competitive p opioid antagonists such as naloxone and naltrexone acutely reverse many of the adverse effects of opioids. To date we do not have specific antagonists for most other abused substances, so rapid pharmacologic reversal of intoxication is usually not possible. 

Individuals with a pattern of chronic use of commonly abused substances should be assessed to determine if they meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for substance dependence (addiction).8 Criteria are not defined for each separate abused substance rather, a pattern of behavior common to the abuse or dependence of all drugs of abuse is established. 

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