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Book Title: Treating and Preventing Adolescent Mental Health Disorders
> pp. [370]-[374]
UNDEFINED: AUTHORS
Treating and Preventing Adolescent Mental Health Disorders
Print ISBN 9780195173642, 2005
pp. [370]-[374]
trolled drug, GHB precursors are readily available through Internet distributors. Because it is odorless and relatively tasteless, GHB has reportedly been added to the drink of unsuspecting victims. It can sedate or anesthetize an unwary recipient, leading to its use as a date rape drug (Schwartz, Milteer, & LeBeau, 2000).
Rohypnol: Flunitrazepam (Roofies, Rophie, Forget Me)
Rohypnol is a potent benzodiazepine sedative drug with similarities to Valium or Xanax, except for its increased potency (Simmons & Cupp, 1998). Although a prescribed medication in some countries, Rohypnol is not approved for prescription use in the United States. Taken by mouth in tablet form or when dissolved in beverages, Rohypnol rapidly produces profound sedation or loss of consciousness and marked amnesia for events occuring during the period of intoxication. With no odor, and almost tasteless, it can easily be administered to someone without their knowledge. Like GHB it has been associated with date rape and other sexual assaults (Schwartz et al., 2000; Slaughter, 2000).
Hallucinogens are a pharmacologically diverse group of drugs. They have in common the ability to produce profound distortions in sensory perception but accompanied by a relatively clear level of consciousness (Hollister, 1968). The perceptual distortions are typically termed hallucinations, though in fact true hallucinations are relatively uncommon. The sought-after alterations in visual images, perception of sounds, and bodily sensations are sometimes accompanied by intense mood swings and feelings of being out of control that can be disturbing to the uninitiated (Strassman, 1984). Some humans have valued hallucinogenic drugs for thousands of years. The older hallucinogenic plants, for example, mescaline, psilocybin, or ibogaine, contain chemicals structurally similar to brain neurotransmitters such as serotonin, dopamine, and norepinephrine. Historically, drug-induced hallucinogenic states were typically part of social and religious rituals rather
than entertainment. Plant-based hallucinogens are still available and are even sold over the Internet (for example, psilocybin mushrooms and peyote cacti), but since the 1960s the prototype hallucinogen has been LSD (lysergic acid diethylamide), an extremely potent, chemically synthesized drug, readily available through illicit sources and, compared to many drugs, relatively inexpensive (Hofmann, 1994). LSD's physiologic effects are relatively few and mild—dilated pupils, increased deep tendon reflexes, increased muscle tension, and mild motor incoordination. Heart rate increases as does blood pressure and respiration, but not greatly. Nausea, decreased appetite, and increased salivation are common. In nontolerant users, about 25 μg of LSD is a threshold dose. The psychological and perceptual state produced by LSD is in general similar to that produced by mescaline, psilocybin, and hallucinogenic amphetamine analogs. The major difference is potency. LSD is hundreds to thousands of times more potent. Acquired tolerance to LSD can be profound. After 3 days of successive daily doses, a 4-or 5-day drug-free period is necessary to again experience the full sensory effects. This limits, to some extent, frequency of use. In recent years, LSD has been distributed as “blotter acid”—that is, on sheets of paper perforated into postage stamp size squares with each square containing 30 to 75 μg of LSD, ingested as a chewed dose. The effects of a single dose last from 6 to 12 hr, diminishing gradually. LSD alters the function of brain serotonin receptors (Aghajanian & Marek, 1999). At higher doses LSD can produce a distressing drug-induced psychosis with similarities to naturally occurring psychotic states, such as acute schizophrenia. The user has difficulty in recognizing reality, thinking rationally, and communicating easily with others (Blaho, Merigan, Winbery, Geraci, & Smartt, 1997; Strassman, 1984). For reasons not well understood, an LSD-induced experience can be psychologically traumatic, particularly for poorly prepared novices. The symptoms persist long after the pharmacologic effects of LSD have worn off (Blaho et al., 1997). An LSD persistent psychosis with mood swings ranging from mania to depression, visual disturbances, and hallucinations is relatively un
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common. Individuals who are predisposed, for genetic or other unknown reasons, to developing schizophrenia may be more likely to experience this (Hollister, 1968). A disorder known as flashbacks, or more formally in DSM-IV, hallucinogen-persisting perception disorder, has been described (Halpern & Pope, 2003). Recurrent, primarily visual disturbances follow even a single exposure to LSD or other hallucinogen and recur over days or months. Flashback symptoms typically last only a few seconds. Only an occasional disorder following hallucinogen use, a flashback can be a substantial problem when it occurs. Considering the multiple hallucinogen doses taken by millions of people since the late 1950s, relatively few cases of flashback phenomena have been reported in the scientific literature (Halpern & Pope, 1999). Other hallucinogens such as mescaline, consumed in the form of peyote buttons from cacti, or tryptamine hallucinogens, for example, dimethyltryptamine (DMT), are less commonly used, probably because they are less available to adolescents. In recent years, however, trafficking over the Internet has enhanced availability (Halpern & Pope, 2001). Psilocybin is occasionally available to adolescents, usually ingested as psilocybin-containing mushrooms. Psilocybin sold illicitly as pills or capsules more likely contains phencyclidine or LSD rather than psilocybin. Newly rediscovered hallucinogens appear regularly. An example is Salvia divenorum, recently popularized through Internet resources (Halpern & Pope, 2001). Salvia illustrates the rapid awareness, increased interest, and progression of use of an old substance that, without the Internet, would likely have remained a relatively unknown plant hallucinogen. Salvia is a mint plant long used as a medicine and sacred sacrament in rural Mexico (Sheffler & Roth, 2003). A relatively mild hallucinogen at usually ingested doses, it is easily cultivated and now extensively discussed, advertised, and sold inexpensively via the Internet. Its active and potent component, salvinorin-A, is absorbed when the plant is chewed or the leaves are smoked. Salvia's pharmacologic effects and metabolite fate have not been adequately researched.
Phencyclidine (PCP, “Angel Dust”) and Ketamine (K, Special K, Vitamin K, Kat Valium)
Phencyclidine (PCP) and a shorter-acting analogue, ketamine, were developed as surgical anesthetics (Reich & Silvay, 1989). At lower doses both alter perception and produce feelings of detachment and of being disconnected or dissociated from the environment, leading to use of the term dissociative anesthetics to describe this class of drugs and distinguish them from hallucinogens. At anesthetic doses patients are quiet but with eyes open, fixed in a gaze, and in a seeming cataleptic state without experiencing pain during a surgical procedure. Both PCP and ketamine produce similar effects by altering the distribution of an important brain neurotransmitter, glutamate. Phencyclidine anesthesia produced a sometimes distressing delirium as the anesthetic was wearing off, so ketamine, which is shorter acting and slightly less potent but associated with briefer and less troublesome delirium, replaced it. Most abusers do not overdose to full anesthetic levels (Freese, Miotto, & Reback, 2002). However, depending on drug dose and tolerance, PCP or ketamine intoxication can progress from feelings of detachment and perceptual changes through confusion, delirium, and psychosis to coma and coma with seizures (Dillon, Copeland, & Jansen, 2003; Jansen & Darracot-Cankovic, 2001). After overdose, the progression to recovery follows the reverse pattern. Treatment of symptoms is primarily supportive. Ketamine produces a shorter period of intoxication; in a surgical setting a single anesthetic dose produces coma for only 10 minutes as compared to a much longer coma after a single large dose of phencyclidine. When abused, these drugs can be taken by mouth or, for more rapid effects, smoked or sniffed. When used medically they are injected. With frequent use, tolerance and dependence develop (Pal, Berry, Kumar, & Ray, 2002). Ketamine is odorless and tasteless and can be surreptitiously added to someone's drink to produce a period of impaired awareness and amnesia. Thus ketamine has been used during sexual assaults and date rape. Phencyclidine is inexpen
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sive to produce and distribute so it is often substituted for other illicit drugs—for example, it is misrepresented as MDMA or THC.
The term club drugs refers to a variety of drugs that have in common only that they are typically used at all-night parties or “rave” dances, clubs, and bars (Smith, Larive, & Romanelli, 2002; Weir, 2000). The drugs in this group are varied. Their pharmacology and patterns of use vary in different regions (Gross, Barrett, Shestowsky, & Pihl, 2002). Patterns of use, dose, and popular drug mixes change over time. The most common club drugs, particularly marijuana, cocaine, MDMA (ecstasy), and methamphetamine, are discussed elsewhere in this chapter. Club drugs that have come to the attention of adolescents include GHB, flunitrazepam (Rohypnol), and ketamine. Thus the list includes stimulants, depressants, and hallucinogens. MDMA, GHB, and Rohypnol have received the most recent attention as club drugs. The special appeal of club drugs to an adolescent includes their novelty and fad-like qualities. Unfortunately, among users there is a misperception about the relative safety of club drugs (Koesters, Rogers, & Rajasingham, 2002). Their use, particularly by novices, can lead to serious health problems (Tellier, 2002).
THE NEUROBIOLOGY OF ADDICTION
As discussed above, most adolescents who experiment with drugs do not progress to clinical problems. Some of them progress to the level of abuse and a smaller number progress to addiction (dependence). The latter has been the focus of much biological research because the chronic relapsing nature of addiction suggests that changes in the brain underlie its persistent course. Over the past several decades, neuroscientists have uncovered compelling evidence supporting the notion that addiction is a disease, primarily affecting specific brain regions that mediate motivation and natural reward. With the help of animal models and direct studies on addicted human subjects, scientists are rapidly unraveling neuronal mechanisms that underlie many of the clinical features of addiction, in
cluding drug euphoria, tolerance, withdrawal, craving, and hedonic dysregulation. It is now apparent that brain reward circuitry is stimulated by addictive agents during drug-induced euphoria and disrupted over the course of chronic exposure. The chronic dysregulation of these reward-related regions explains many of the clinical manifestations of addiction, and the restoration of normal hedonic function through medical interventions should ultimately improve the prognosis of this refractory disorder. Interestingly, addictive agents as diverse as heroin, alcohol, and cocaine (to name only a few) produce many similar neurochemical effects, supporting the established classification of different substance dependence disorders within the single category of addiction. The interaction between an addictive exogenous agent and endogenous reward-related circuitry produces two powerful forces, euphoria and craving, that initiate and drive addiction. Whether motivated by curiosity, boredom, peer pressure, or thrill seeking, the initial use of a euphoric drug indelibly embeds the experience into memory. Since we organisms are neurologically “wired” to repeat pleasurable experiences, drug euphoria positively reinforces subsequent use. When used excessively, addictive drugs produce unpleasant states (craving, withdrawal, impaired hedonic function) that negatively reinforce use and alternate with euphoria to produce a vicious cycle of addiction that becomes increasingly entrenched and uncontrollable, regardless of negative consequences. Although psychological, psychosocial, and environmental factors play critical roles in the initiation and perpetuation of addiction, brain involvement explains many of its paradoxes and provides important clues for the development of more effective and durable treatments.
Biological Research Based on Animal Models
Since the discovery of “pleasure centers” by Olds in the early 1950s, extensive research has been conducted using animal models that address the acute and chronic effects of addictive drugs on reward-related brain regions. These studies have contributed tremendously to our understanding
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of addiction by delineating relevant neuronal mechanisms and proposing hypotheses to define the disorder. Drug addiction, also known as substance dependence (American Psychiatric Association, 1994), is a chronically relapsing disorder that is characterized by (1) compulsion to seek and take the drug, (2) loss of control in limiting intake, and (3) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) when access to the drug is prevented (defined here as dependence; Koob and Le Moal, 1997). In experimental animals, the occasional but limited use of an addictive agent is very distinct from escalated drug use and the emergence of chronic drug dependence. Therefore, an important goal of current research is to understand the neuropharmacological and neuroadaptive mechanisms within reward-related neurocircuits that mediate the transition between occasional, controlled drug use and the loss of behavioral control over drug seeking and drug taking that defines chronic addiction (Koob and Le Moal, 1997). Historically, addiction was originally defined as the presence of an acquired abnormal state where a drug is needed to keep a normal state (Himmelsbach, 1943). Eventually, the definition
of addiction became tied to the emergence of intense physical disturbances when drug taking ceased (Eddy, Halbach, Isbell, & Seevers, 1965). However, this definition did not capture many aspects of addiction that are unrelated to physical withdrawal, necessitating a second definition of “psychic” dependence in which a drug produces “a feeling of satisfaction and a psychic drive that require periodic or continuous administration of the drug to produce pleasure or to avoid discomfort” (Eddy et al., 1965). Producing pleasure and avoiding discomfort, encountered clinically as euphoria and craving, are now accepted as the primary forces that drive addiction. From a modern perspective, drug addiction has aspects of both impulse control disorders and compulsive disorders (Fig. 17.5). Impulse control disorders are characterized by an increasing sense of tension or arousal before committing an impulsive act; pleasure, gratification, or relief is felt at the time of committing the act; and following the act there may or may not be regret, self-reproach, or guilt (American Psychiatric Association, 1994). In contrast, compulsive disorders are characterized by anxiety and stress before committing a compulsive repetitive be
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havior, and relief from the stress by performing the compulsive behavior. As an individual moves from an impulsive disorder to a compulsive disorder there is a shift from positive reinforcement (euphoria) driving the motivated behavior to negative reinforcement (craving, or discomfort) driving the motivated behavior. Drug addiction can be viewed as a disorder that progresses from impulsivity to compulsivity in a collapsed cycle of addiction comprised of three stages: preoccupation and anticipation, binge intoxication, and withdrawal and negative affect (Fig. 17.6). These stages have biological, social, and psychological aspects that feed into each other, intensify, and ultimately lead to the pathological state known as addiction (Koob & Le Moal, 1997). Given these considerations, the modern view of addiction has shifted from a focus of physical withdrawal symptoms to the motivational aspects of addiction. This shift in emphasis is supported by the clinical axiom that mere detoxification (the elimination of drug from the body with pharmacological suppression of physical withdrawal symptoms) is insufficient treatment for addiction. More central to the transition from drug use to addiction is the emergence of negative emotions, including craving, anxiety, and irritability, when access to the drug is prevented (Koob & Le Moal, 2001). Indeed, some have argued that the development of such a negative affective state should define addiction.
Animal Models of Drug Reward
Through extensive animal research, the neurotransmitters and brain circuits that mediate drug reward, have been largely delineated; the biological basis of drug reward is exemplified by the fact that laboratory animals will press levers to receive addictive substances. When provided unlimited access, animals will consistently self-administer cocaine and amphetamine to the point of death, and the power of drug reward should not be underestimated in the clinical setting. Diverse classes of addictive drugs affect different neurotransmitter systems and produce distinct activation patterns within reward circuits. Many addictive substances (including heroin, cocaine, amphetamine, alcohol, nicotine, and marijuana) acutely increase the neurotransmitter dopamine in elements of the ventral striatum, specifically the nucleus accumbens, but this increase is most robust for psychomotor stimulants and much more modest for sedative hypnotics. Other neurotransmitter systems are also involved, including opioid peptides, GABA, glutamate, and serotonin, and play more critical roles as one moves out of the domain of psychomotor stimulants. Dopamine levels in the nucleus accumbens are also elevated during activities that lead to natural rewards, providing compelling evidence that addictive drugs tap into natural motivational circuits.
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doi:10.1093/9780195173642.003.0018
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