At Home Drug Withdrawal

Sobriety Success

The dependence on sobriety is defined as the state of sobriety. When a person is sober, they can live on a daily basis without their thoughts and behaviors being controlled by substance dependence. They do not feel obliged to use it because they manage to live without it. They see and appreciate so much the benefits of living without substance that they do not feel they have to use drugs or alcohol. Therefore, they refrain from using it to continue enjoying this new, healthier lifestyle. The success product of sobriety is a step-by-step manual for everyone. The product has been said to be beneficial for many people around the world. The reason why the product is gaining so much popularity among individuals. They see and appreciate so much the benefits of life without substance that they do not feel they have to use drugs or alcohol. Therefore, they refrain from using it to continue enjoying this new, healthier lifestyle. This strategy encourages you to maintain the long-term vision of recovery. Recognize that this is not a one-off thing, something you try for a few weeks to several months, then return to your previous life. You will be in recovery if you decide it's the life you want to live for the rest of your life. As such, there is no immediate timeline to which you must adhere, nor should you strive to achieve goals that you are clearly not ready to face. Read more here...

Sobriety Success Summary

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Cocaine Induced Disorders

292.89 Cocaine Intoxication Specify if. With Perceptual Disturbances 292.0 Cocaine Withdrawal 292.81 Cocaine Intoxication Delirium 292.xx Cocaine-Induced Psychotic Disorder 292.84 Cocaine-Induced Mood DisorderIW 292.89 Cocaine-Induced Anxiety DisorderI,W 292.89 Cocaine-Induced Sexual Dysfunction1 292.85 Cocaine-Induced Sleep DisorderI,W 292.9 Cocaine-Related Disorder NOS

Intravenous Drug Abuse

A syndrome of diffuse osteosclerosis was first reported with intravenous drug abuse in St. Louis (61). The syndrome is considered rare and its cause is unknown. Patients have presented with aching limbs and a generalized increase in density throughout the skeleton. One such subject, a 38-year-old Caucasian man underwent BMD measurements with DXA (QDR-2000) of the spine and proximal femur and of the spine using QCT (General Electric HiSpeed Advantage) (62). The BMD in all regions was dramatically increased compared to age- and sex-adjusted normal values. Spine values by DXA were 160 of predicted and by QCT, 185 of predicted. Values in the proximal femur ranged

Selfadministration Of Cocaine Rationale

Intravenous self-administration of a drug is considered a good measure of the rewarding properties of that drug. There are several indications that the 5-HT1b receptor might be able to modulate cocaine self-administration. The 5-HT1b agonists are able to decrease the rate of self-administration of DA-releasing drugs on a fixed ratio schedule, indicating an increase in the rewarding efficacy of the DA-releasing drug (19). Similarly, on a progressive ratio schedule of reinforcement, administration of a 5-HT1B agonist raised the break point for self-administration of cocaine (18). To further investigate the role of the 5-HT1B receptor in cocaine self-administration, we assessed the behavior of 5-HT1B knockout mice under several different intravenous self-administration paradigms. We first measured how quickly they acquired stable self-administration behavior on a fixed- ratio reinforcement schedule. Then, we compared the dose-response curve for self-administration on this schedule...

Pharmacological Treatment of Chronic Cocaine Addiction

Clinical researchers have tried to identify drugs to reduce cocaine craving and prevent relapse. Numerous drugs looked promising in initial open-label trials but did not prove efficacious in subsequent placebo-controlled studies. These pharmacological treatments have included dopaminergic agonists (e.g., monamine oxidase inhibitors, amantadine, mazindol, methylphenidate, pemoline, bromocriptine, L-dopa, and pergolide), neurotransmitter precursors (L-tyrosine, L-tryptophan, and multivitamins with B complex), carbamazepine, and antide-pressants, including desipramine and fluoxetine. In a meta-analysis examining 45 clinical trials examining mostly antidepressants, carbamazepine, and dopa-mine agonists, no significant impact of drug treatment was found, regardless of the type of drug or dose used (Lima, Soares, Reisser, & Farrell, 2002). Clinical trials with bupropion, olanzapine, naltrexone, buprenorphine, and other drugs are ongoing. As our understanding of the neurobiological basis of...

Locomotor Effects Of Cocaine Rationale

Psychostimulants such as cocaine have been shown to increase locomotion and, at high doses, to induce stereotyped movements (25,26). The ability of these substances to stimulate locomotion has been suggested to parallel their addictive potential (27). Because 5-HT1B KO mice appear to be more vulnerable to the reinforcing effects of cocaine, they may also be more sensitive to the stimulating effects of the drug. On the other hand, based on the role of the 5-HT1B receptor in neural circuitry, we might expect KO mice to be less sensitive to the locomotor effects of cocaine. Specifically, 5-HT1b receptor stimulation may enhance DA release by reducing GABA-ergic inhibition (5,14,15). Therefore, a knockout of the 5-HT1B receptor might be expected to remove this modulation of GABA release and thereby indirectly reduce DA neurotransmission. If increased DA release is essential to the locomotor activating effects of cocaine, we might expect 5-HT1B receptor knockout mice to have an attenuated...

Behavioral Sensitization To Cocaine Rationale

Behavioral sensitization, or reverse tolerance, to the motor effects of cocaine has been shown to develop following repeated intermittent exposure to cocaine. This phenomenon has been suggested to reflect the addictive properties of cocaine (28). It is possible that WT and KO mice sensitize differently to cocaine. It is also possible that the initial difference in locomotor response to cocaine reflects a difference in the neurochemical substrates underlying sensitization. We therefore studied the effects of repeated administration of cocaine on the locomotor behavior of KO and WT mice. In order to compare the effect of a genetic knockout of the 5-HT1B receptor with the effect of acute blockade of this behavior, we assessed sensitization in WT mice pretreated with GR127935, as well.

Drug Dependence Versus Physical Dependence

A patient who seeks to continue using a medicine because it is helpful is no more demonstrating drug-seeking behavior than is a patient who finds eyeglasses helpful in the treatment of myopia demonstrating glasses-seeking behavior if deprived of a corrective lens. Drug abuse and drug dependence are characterized by use despite problems caused by that use (loss of control) and by denial (and dishonesty) neither of which is seen in appropriate medical treatment (DuPont & Gold, 1995).

Regulation And Relationship To Cocaine

The mechanisms by which DAT phosphorylation is translated into functional upregulation or downregulation of DAT activities are not understood. Alteration of transporter activity can be hypothesized to occur by an increase or decrease in the number of transporters at the cell surface or by a change in DAT binding or transport efficiency. Evidence is accumulating that kinase-induced changes in activity of DAT (45,48), as well as that of SERTs, norepinephrine transporters (NETs), and GATs (55,62,63), are accompanied by redistribution of transporters between the plasma membrane and intracellular compartments. The evidence for direct change in DAT catalytic properties is less compelling, but the possibility still remains that transport may be controlled by multiple coincident processes in a manner similar to the complex events leading to desensitization and downregulation of G-protein-coupled receptors (64). The molecular mechanisms underlying regulation of DAT functions have clear...

Pain And Opioid Addictiona Continuum Approach

While pain and addiction can and sometimes do exist as comorbid conditions, they may also present as part of a dynamic continuum with pain at one end of the spectrum and addiction at the other extreme. In cases when the identified substance of misuse is one in which there can be no doubt about the medical inappropriateness of ongoing use, such as with alcohol or cocaine use, a comorbid pain and substance-use disorder should be considered. When the drug in question can arguably be both the problem and the solution, depending on clinician training and perspective, a continuum model may better apply. This can be the

Withdrawal In Rodent Models Of Cocaine Abuse

Chronic cocaine treatments do not appear to have the marked neurotoxic effects like those produced by amphetamine on DA and serotonin neurons (for a review, see ref. 32). In fact, most preclinical studies have shown no reduction in radioligand binding to the DAT following chronic treatment of rats with cocaine, suggesting that DA terminals remain intact. Daily passive administration of cocaine for 10 d had no effect on binding to DA (33), norepinephrine, or serotonin (34) uptake sites. Continuous infusion of cocaine for 7 d also had no effect on the number of DAT binding sites (35). However, withdrawal from repeated administration of cocaine produces an decrease in transporter binding in the rat nucleus accumbens (36). Because this decrease only occurs after withdrawal from the drug, it is likely to be a compensatory mechanism related to some other, earlier drug effect. Many experimental cocaine treatment paradigms have been developed as animal models of human cocaine abuse and it has...

In Autopsy Studies Of Chronic Cocaine Users

Although it is unclear exactly how the DAT protein regulates to alter the intensity and duration of DAergic neurotransmission, transcriptional regulation of transporter expression, increased membrane trafficking, and altered phosphorylation states of the DAT protein are possible mechanisms (51). Cocaine congeners bind to two sites on the DAT, one of which mediates high-affinity DA uptake (6). High-affinity cocaine binding sites on the DAT protein are increased in cocaine overdose victims (52-54), although it is not known if this increase is correlated with a change in transporter function or gene product expression. In contrast to these findings, the apparent density of high-affinity cocaine binding sites in victims of agitated cocaine delirium were unchanged from control values, suggesting a defect in the ability of the transporter to regulate synaptic DA levels with a cocaine challenge (14,55). Our group has used semiquantitative reverse transcriptase-polymerase chain reaction...

Cocaine and Other Stimulants

Cocaine is an alkaloid extracted from the leaf of the Erythroxylon coca bush. The hydrochloride salt is water soluble and can be administered orally, intravenously, or intranasally. The intravenous route of administration has an onset of action of 10-60 seconds, with a peak effect achieved in minutes and duration of effect that lasts up to 1 hour. Administration of the drug by the intranasal route has an onset of action of up to 5 minutes, with a peak effect achieved in approximately 20 minutes. The total duration of action by the intranasal route is 1 hour. The free-base form, known as crack cocaine, can be heated and smoked. This form has the quickest onset of action of 3-5 seconds, reaching its peak effect in 1 minute. (Lange and Hillis, 2001) The quick and intense effects of crack cocaine may potentially make it the most addictive form of the drug. The effects of cocaine are mediated by blocking the synaptic reuptake of norepinephrine and dopa-mine, resulting in an excess of these...

Opioid Peptides Cannabinoids and Cocaine and Amphetamine Regulated Transcript

The appetite-stimulating effect of marijuana in humans has been well known for centuries 38 . Endogenous cannabinoids, in particular anan-damide, increase appetite and food intake via the activation of specific receptors known as CB1 39 , which are expressed in hypothalamic and central areas involved in the control of feeding behaviour 40, 41 . In fact, CB1 receptor mRNA is co-expressed with CRH, cocaine- and amphetamine-regulated transcript (CART), melanin-concentrating hormone (MCH) and prepro-orexin 42 . Cocaine- and amphetamine-regulated transcript is co-expressed in ARC in POMC neurons 3,44 , and is directly modulated by leptin 44 . It is also expressed in PVN, NTS, lateral and dorso-medial hypothalamus and nucleus accumbens 45 . At the peripheral level, CART is expressed in the myenteric gut plexus, vagus nerve, pancreatic somatostatin cells, and antral gastrin cells 45 . Until now, no specific receptors for CART have been identified 45 , thus a full description of the...

Medical Complications Direct Results of Cocaine

Medical consequences of acute and chronic cocaine abuse may be categorized as those caused directly by cocaine, those due to adulterants, and those related to route of administration. The most common direct medical consequences of cocaine use include cardiovascular and CNS difficulties. Cocaine use may account for up to 25 of cases of acute myocardial infarction among patients 18-45 years of age (Weber, Hollander, Murphy, Braunwald, & Gibson, 2003). Upon acute administration, cocaine increases blood pressure and heart rate, primarily through an action on the sympathetic nervous system. Through its pharmacological effect at alpha- and beta-adrenergic receptors, cocaine may increase oxygen demand of the myocardium by increasing blood pressure and heart rate. Cocaine also suppresses the baroreflex response and vagal tone, further contributing to its effects on heart rate. At the same time that cocaine is increasing the workload on the heart, it induces coronary artery vasoconstriction...

Cocaine and Methamphetamine

Although the argument often goes unchallenged in court, all drugs do not, by definition, produce impairment. Even though some US states define being under the influence as synonymous with the presence of any drug, some drugs do improve performance. In fact, low to moderate acute doses of cocaine and amphetamine can be expected to increase positive mood, energy, and alertness, especially in nontolerant individuals (74). It has been known since World War II that use of D-amphetamine can increase the ability to sustain attention for prolonged periods when performing monotonous tasks. For that reason, radar operators and pilots of both Allied and Japanese armies were issued supplies of amphetamine. Many of the performance tasks related to driving can be improved, at least in the laboratory, by treatment with stimulants (75). Although the results of one retrospective autopsy study suggest that methamphetamine users seem more likely to be involved in traffic accidents (76), a driving...

Cocaine and Crack

Cocaine occurs naturally in the leaves of the coca plant Erythroxylum coca, which grows predominantly in South America. Cocaine hydrochloride is a white powder that is usually snorted but can be taken orally. Crack is prepared by mixing cocaine hydrochloride with sodium bicarbonate and water and heating it. The cocaine base precipitates out and forms small rocks as it cools. Crack may be smoked in a pipe or heated on foil with the vapor inhaled. Both crack and cocaine may be injected. The onset-of-action and plasma half-life varies depending on the route of use, rapidly if taken intravenously or smoked compared with when it is snorted. The duration of effects will also vary with administration route (70). Ingestion of stimulant drugs, such as cocaine or amphetamine, result in activation of the sympathetic nervous system with resulting euphoria followed by irritability, depression, insomnia, and paranoia (Table 12). Effects of Cocaine and Amphetamine Intoxication Cocaine produces a...

Methamphetamine

According to the NHSDA (Substance Abuse and Mental Health Services Administration, 2001b), approximately 4 of the population (8.8 million people) have tried methamphetamine in their lifetime. Emergency department (ED) mentions of methamphetamine in 2001 (15,000 mentions) were not significantly different from mentions in 1994, 1999, or 2000. However, there was an increase and subsequent decline of ED mentions in 1997 (Substance Abuse and Mental Health Services Administration, 2001a). The highest rates of use are seen in patients 26-29 years of age, followed by patients ages 18-25 39 of methamphetamine admissions were patients 20-29 years old. In addition, TEDS data reveal that 80 of ED mentions were white (Substance Abuse and Mental Health Services Administration, 2002). Rates of use are highest in Hawaii, San Francisco, San Diego, Phoenix, Seattle, Denver, Los Angeles, and, Minneapolis (Substance Abuse and Mental Health Services Adimnistration, 2001b). D-Methamphetamine hydrochloride...

Cocaine

Metabolites in humans benzoylecgonine and ecgonine methyl ester are major metabolites. Norcocaine is a minor metabolite. Cocaine's plasma half-life is very short that of benzoylecgonine is much longer. Benzoylecgonine can be detected for days after use. Urine concentrations of benzoylecgonine can be extremely high (100,000s of ng mL). Preferred routes of administration smoking, snorting and injection. Oral route reported to be ineffective but Therapeutic uses Ear-Nose-Throat (ENT) surgical procedures and Tetracaine-Cocaine-Adrenalin (TAC) solution for open wound instillation and topical anesthesia for suture repair of lacerations.

Drug Abuse Dependence

A common comorbidity associated with alcohol use disorders is co-occurring drug use disorders. In 2001, the National Household Survey on Drug Abuse found that among teenagers who binge drink, two-thirds were also abusing drugs. In contrast, one in 20 teenagers who did not drink abused drugs. Drawing upon the ECA and NCS data, it has been determined that one in five individuals with an alcohol use disorder will also have a drug use disorder. A breakdown of the NCS data indicates that those with either alcohol abuse or alcohol dependence in 40 of cases have either drug abuse or drug dependence. The more serious the drug use disorder, the more likely it is that alcohol abuse-dependence will be found. For example, the ECA data indicate that if no drug problem exists, the rate of alcohol abuse-dependence is 11 (compared to 13 for the total population). When tetrahydrocannabinol abuse-dependence is present, the prevalence of alcohol abuse-dependence rises to 36 . The rates of alcohol...

The Dopamine DA Hypothesis

Until recently, the modal hypothesis on the pathophysiology of schizophrenia was that excessive dopaminergic transmission in the forebrain is a key causative factor. This DA hyperfunction hypothesis was primarily based on the observation that all clinically effective antipsychotic drugs have potent antagonist or inverse agonist activity at DA D2 receptors, and that the therapeutic efficacy of these compounds was highly correlated with their affinity for striatal D2 receptors. In addition, the psychotomimetic properties of indirect DA agonists like amphetamine and cocaine, and observed alterations in striatal DA release in schizophrenic patients, further supported the involvement of DA in the pathophysiology of schizophrenia.

Head Computerized Tomographic CT Scan

Intracranial hemorrhage Suspect intraparen-chymal cerebrovascular accident or subarach-noid hemorrhage amphetamines, cocaine, ephedrine and pseudoephedrine, phenylpro-panolamine, phencyclidine (PCP) or subdural head trauma (alcohol, sedative-hypnotics, seizures). Lucencies Suspect basal ganglia necrosis carbon monoxide, cyanide, hydrogen sulfide (H2S), methanol suspect vasospasm cocaine, ergots septic emboli intravenous drug users (IVDUs). FIGURE 3.12 Subarachnoid hemorrhage intravenous cocaine abuse. Cranial computerized axial tomogram (CT) at the level of the pons that demonstrates acute blood hyperdensities in the suprachiasmatic cistern extending into the left Sylvian fissure, consistent with acute subarachnoid hemorrhage following intravenous cocaine overdose. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

Sympathomimetic toxidrome

Features Fight or flight hypertension, tachycardia, sweating, fever, excitation-psychomotor agitation, tremor, seizures, dilated pupils. Causes Amphetamines diet drugs, cocaine, theophylline, caffeine, methylphenidate, mono-amine oxidase inhibitors over-the-counter cold medications, especially those containing phenylpropanolamine (PPA), ephedrine, and pseudoephedrine. Mechanisms Increased release of catecholamines (amphetamines), blockade of catecholamine re-uptake (cocaine), inhibition of catecholamine metabolism (monoamine oxidase inhibitors), indirect adrenergic receptor stimulation (ephedrine). Antidote Beta-blockers.

Transition To Addiction

As we have seen, the pleasure derived from various drugs' activation of the brain's natural reward system promotes continued drug use during the initial stages of opioid addiction. Subsequently, repeated exposure to these drugs induces the brain mechanism of dependence, which leads to daily drug use to avert the unpleasant symptoms of drug withdrawal for many substances, although for some drugs, withdrawal symptoms are minimal and may contribute minimally to dependence features and relapse after discontinuation. Further prolonged use of drugs that produce dependence lead to more long-lasting changes in the brain that may underlie the compulsive drug-seeking behavior and related adverse consequences that are the hallmarks of addiction. Recent research has generated several models to explain how habitual drug use produces changes in the brain that may lead to drug addiction. In reality, the process of addiction probably involves components from each of these models, as well as other...

The Important Role Of Stress

That drug abuse patients are more vulnerable to stress than the general population is a clinical truism. Numerous preclinical studies have documented that physical stressors (e.g., foot shock or restraint stress) and psychological stressors can cause animals to reinstate drug use (e.g., Shaham, Erb, & Stewart, 2000). Furthermore, stressors can trigger drug craving in addicted humans (Sinha, Catapano, & O'Malley, 1999). One potential explanation for these observations is that abused drugs, including opiates and stimulants, raise levels of cortisol, a hormone that plays a primary role in stress responses cortisol, in turn, raises the level of activity in the mesolimbic reward system (Kreek & Koob, 1998). By these mechanisms, stress may contribute to the abuser's desire to take drugs in the first place, as well as to his or her subsequent compulsion to keep taking them.

Inborn Errors of Metabolism

MEKC has been applied to therapeutic drug monitoring. Using MEKC theophylline and its analogues have been separated in plasma. In addition, it has been used to detect and quantitate serum levels of digoxin (44,45). MEKC can also efficiently separate and quantitate antiepileptic drugs that are used in combination, especially ethosuxamide, phenobarbitol, pheny-toin, and carbamazepine (46). (See Chapter 17 for a detailed discussion of the use of CE in therapeutic drug monitoring.) CE has also been used in the clinical and forensic arena (see Chapter 19). In these cases, the use of urine to identify intoxication and or drug abuse of opiates, barbiturates, benzodi-azepines, stimulants, and doping screening is possible within a few minutes (47-51). It is also possible to use CE to screen post mortem fluids for illicit drugs or elevated levels of legal drugs (see Chapter 20). CE has also been applied to determine the tissue concentration of 5-Fluorouracil (5-Fl) in tumor and subcutaneous...

Imaging The Dopaminergic System

Direct measurements of dopamine transporter binding sites are possible with 11C cocaine (77), or the cocaine analogs 20-carbomethoxy-30- 4-iodophenyl tropane (0-CIT) and tropane (FP-CIT), labeled with either 18F or 11C for PET or 123I for SPECT (78-80). Other dopamine transporter ligands include tropane ( 123I IPT) (81), its 4-fluorophenyl analog 123I altropane

Dopamine transporter polymorphisms

DAT terminates dopaminergic neurotransmission by reuptake of dopamine (DA) in presynaptic neurons and plays a key role in DA recycling. DAT can also provide reverse transport of DA under certain circumstances. Psychostimulants such as cocaine and amphetamines and drugs used for attention deficit hyperactivity disorder (ADHD) such as methylphenidate exert their actions via DAT. Altered DAT function or density has been implicated in various types of psychopathology, including depression, BPAD, suicide, anxiety, aggression, and schizophrenia. Altered transport properties associated with some of the coding variants of DAT suggest that individuals with these DAT variants could display an altered DA system.17'20 Multiple human dopamine transporter (hDAT, SLC6A3) coding variants have been described, though to date they have been incompletely characterized. The antidepressant, bupropion (6) dose-dependently increases vesicular DA uptake an effect also associated with VMAT-2 protein...

Multiplicity and ligand selectivity

CESs are largely microsomal in origin, with molecular weights of 55-60 kDa. At least four families (CES1-CES4, EC 3.1.1.1) exist, based on sequence similarity, and in humans, the liver (CES1A1, hCE1) and intestinal forms (CES2, hCE2) appear to play the most important roles in detoxication bioactivation of xenobiotics.95 hCE1 metabolizes heroin and cocaine and is relatively selective for several of the angiotensin-converting enzyme inhibitors, such as delapril and imidapril, whereas hCE2 is more selective for irinotecan and oxybutynin. Therefore, hCE1 often appears to be associated with the removal of small (methyl, ethyl) groups, whereas hCE2 seems to prefer larger moieties, although this is far from a strict rule.92

How Psychiatrists Can Contribute To Containment Of The Most Challenging Public Health Problem The World Has Faced On A

The range of mental health issues encountered by HIV AIDS care providers is broad (e.g., abuse of alcohol, cocaine, crystal methamphetamine personality disorders agitation psychosis) and population-specific (e.g., adolescents, Latinas, people who are homeless or incarcerated). Because service delivery systems (medical care, mental health care, substance abuse treatment) are structured to work separately (historically due to different funding streams), efforts to navigate multiple systems often fail. Integrated HIV mental health care remains rare (Satriano et al., 2007), and comprehensive listings of regional HIV mental health service agencies do not exist. Patients may not themselves recognize the role that mental health problems are playing in their health (Messeri et al., 2002). As a result, HIV AIDS medical service providers may be unable to integrate adequately HIV AIDS, mental health, and substance abuse treatment services, even through existing referral networks, let alone to...

Dopamine transporter DAT knockout mouse

Psychostimulants such as methylphenidate, amphetamine, and cocaine (all at relatively high doses) paradoxically robustly attenuated hyperactivity in DAT knockout animals in a novel environment.43 Interestingly, these 'calming-like' effects of the stimulants were delayed, but long-lasting, particularly for methylphenidate (up to 4h). Further, the effects of methylphenidate were dose-dependent in the DAT knockouts, but methylphenidate dosing over the same range in wild-type controls produced the more usual enhancement of activity, following an inverted U-shaped dose response. While these data were exciting, subsequent work described in the same article provided some puzzling information extracellular dopamine concentrations in the striatum of DAT knockouts, measured by in vivo microdialysis in freely moving mice after the administration of methylphenidate, did not change, in contrast to wildtype controls, which were significantly elevated. The most likely reason for this is that...

Presynaptic Da Function

Imaging of dopamine transporter (DAT) is another way for probing the impaired nigrostriatal dopaminergic system in PD. DAT is expressed on dopaminergic nigral terminals, and quantification of striatal DAT appears to be directly related to the extent of nigral cell degeneration (24). This has received more attention in recent years as radiotracers that bind to the striatal DAT have been successfully developed for both PET and SPECT imaging. The most common agents are the cocaine analogs, such as (123I)P carbomethoxy-iodophenyl tropane (CIT) and (18F)FP-PCIT (25, 26), as well as -carbomethoxy-3 P -(4-fluorophenyl) tropane (CFT) labeled with (18F) and (11C) (27-29). DAT binding is estimated by an uptake ratio or distribution volume ratio between the striatum and a reference tissue such as cerebellum.

Postsynaptic Da Function

Because RAC has a low affinity to D2 receptors, PET imaging with this tracer has been widely used to measure DA release under interventions that modulate dopaminergic systems. The amount of release is estimated by the percentage reduction in RAC binding as a result of the competition between external stimulation and endogenous DA. It has been reported that stri-atal RAC binding relative to baseline is reduced in PD after acute levodopa administration, most notably in the posterior putamen (18 ), followed by the anterior putamen (12 ), and the caudate nucleus (6 ) (38). The magnitude of reduction is correlated with the drug-free disability of motor function. This gradient of DA release is consistent with the topographic pattern of DA lesions portrayed by presynaptic PET imaging markers. Another study has recently demonstrated that pharmacological challenge with methamphetamine produces significantly reduced DA release in striatum, but normal levels of prefrontal DA release in advanced...

Experimental Models of Addiction

In order to identify potential medications for the treatment of drug addiction, animal models have been created that allow the elucidation of the underlying mechanisms of drug-induced behaviors. By its definition, addiction is a unique and complicated human behavior and a single animal model simply cannot predict medication efficacy in humans. Thus most investigators use an arsenal of in vitro and in vivo tests to study neurochemical mechanisms underlying the pharmacological actions and abuse liability of various drugs of abuse, as well as for discovering potential medications. In vitro binding and functional assays are generally used to determine mechanisms of action of test compounds (new compound entities, NCEs) and then those with the desired in vitro profile are further investigated in animal models. Biochemical assessment using in vivo microdialysis is often employed to further delineate NCE effects on neurotransmitter levels in various brain regions. Ultimately, behavioral...

Current and Targeted Medications

A current list of medications approved for the treatment of drug addiction is shown in Table 4. A brief description of these medications for treatment of specific drugs of abuse is described below. In all cases, new medications are under clinical and preclinical investigation. Examples of potential medications currently under clinical investigation are listed in Table 5 with their chemical structures being shown in Figure 8. As the mechanisms of actions of these agents are widely varied, no attempt to describe structure-activity relationships (SARs) within these classes of molecules has been made. However, the interested reader is referred to relevant review articles throughout the text that describe in more detail the drug design and synthesis of these agents.

Unmet Medical Needs

Cocaine methamphetamine substantial burden of medical illness compared to age- and gender-matched US population controls.70 Drug-related complications occur not only in public sector patients, but also in a community sample of patients enrolled in a health maintenance organization.71 Some of the widely accepted medical complications are summarized in Table 7. Drug abuse is a leading contributor to the spread of AIDS, HIV, and hepatitis C, and drug abuse treatment can reduce the spread of these illnesses.8 Not unexpectedly, intravenous drug use causes various surgical complications.72 The medical and psychiatric needs of patients with substance dependence are far from met. There are a variety of reasons for this, as described in detail in the 1999 report of the US Surgeon General.73 Unfortunately, the various infrastructure and financial factors that affect the delivery of mental health and drug abuse treatments adversely impact the ability to develop new medications for substance...

New Research Areas

Intensive investigation toward novel clinical candidates for treatment of drug addiction has ensued and many candidates with a diversity of mechanisms of action have been identified and are in various stages of preclinical and clinical development. A list of these potential medications is given in Table 6 with their chemical structures shown in Figure 8. These compounds have been identified based on their current clinical use and or their mechanism of action which has been deemed pertinent to drug addiction, as discussed in Section 6.07.2. Their efficacy in treating drug addiction remains to be established but in all cases, a proof of concept in animal models has been provided.8'51'54'75'76

Preclinical Targets for Stimulant Addiction

Since there are no FDA-approved medications for the treatment of cocaine and amphetamine addiction, intensive efforts have been directed toward discovering medication candidates. In this regard, over the past decade, a focus on elucidating mechanisms underlying the reinforcing effects and addictive liability of cocaine, as well as those underlying relapse, has prompted the identification of receptor transporter candidates for drug discovery. Although many targets have been proposed, the following receptors transporters and examples of promising drug candidates that have high affinity and selectivity for these targets have been widely studied and currently hold the most potential for medication development. The monoamine neurotransmitter transporters are the principle sites of action of the psychostimulants cocaine and methamphetamine. These psychostimulants bind to the monoamine transporters and inhibit the reuptake of their respective neurotransmitters. Methamphetamine is further...

Clinical Trial Issues

For PD, two different clinical study designs (drug wash-out and randomized delayed starts) have been used in attempts to distinguish this difference for NCEs.69 The first uses a drug wash-out period at the end of the treatment course. Patients are followed for different time periods following drug withdrawal to determine if a benefit persists in the absence of continued drug use. While this is a logical design, there are inherent problems. One issue is that the pharmacodynamic effects of treatment may outlast the duration of the physical presence of the drug. Another is that patients with more severe symptoms cannot tolerate discontinuation of a symptomatic treatment thus patients with less severe symptoms may be preferentially retained in a study. The second design is a randomized delayed-start trial in which patients are randomized to treatment groups following receipt of placebo for various durations. This study design also has challenges (1) treatment earlier in the course of...

Guidelines for Client Selection

ACT can be used with a variety of clients and clinical presentations, with no specific limitations to its use. However, it is most useful when applied with clients who are assessed to be emotionally avoidant and or cognitively fused, have chronic conditions, or who have multiple treatment failures. ACT has been demonstrated to be effective when used in the treatment of PTSD (Follette et al., 1993 Walser, Loew, Westrup, Gregg, & Rogers, 2003a Walser, Westrup, Rogers, Gregg, & Loew, 2003b Batten & Hayes, 2005), anxiety and stress (Bond & Bunce, 2000 Twohig & Woods, 2004 Zettle, 2003), substance abuse dependence (Gifford etal., 2004 Hayes etal., 2002), coping with positive psychotic symptoms (Bach & Hayes, 2002), chronic pain (Dahl, Wilson, & Nilsson, 2004 McCracken, Vowles, & Eccleston, 2004), stigma and prejudice in drug abuse counselors (Hayes et al., 2004a), depression (Folke & Parling, 2004 Zettle & Hayes, 1986 Zettle & Raines, 1989), self-management of diabetes (Gregg, 2004), and a...

Cardiovascular Toxicity

Confirm cocaine packs by abdominal x-ray. Institute ECG monitoring. Activated charcoal (AC) and cathartic, then multi-dose activated charcoal (MDAC) to reduce absorption and enhance elimination. Whole-bowel irrigation (WBI) with polyethylene glycol electrolyte solution (PEG-ELS) to reduce gastrointestinal mucosal contact time, speed transit, and increase elimination. Surgical removal for symptomatic patients with packet rupture or intestinal obstruction. Follow-up imaging with abdominal x-rays consider barium enema. Figure 9.12 Management Cocaine v. Heroin Body Packers. A flow chart outlining the clinical practice management strategies for body packers of cocaine or heroin. Figure 9.12 Management Cocaine v. Heroin Body Packers. A flow chart outlining the clinical practice management strategies for body packers of cocaine or heroin.

Prescription vs Designer

Dextroamphetamine, methamphetamine, methylphenidate (Ritalin most popular prescribed drug for preteens with ADHD), pemoline. Weight reduction Amphetamine, dexto-amphetamine, methamphetamine, dexfen-fluramine, phentermine and fenfluramine (phen-fen combination withdrawn by the FDA due to increased risks of pulmonary hypertension and valvular heart disease). Pure methamphetamine ice or speed, methamphetamine. Designer amphetamines

Ghrelin as a New Factor in the Control of Energy Balance Appetite and Food Intake

AgRP causes only a modest effect on the orexi-genic effect of ghrelin, simultaneous genetic ablation completely abolishes ghrelin's modulatory action on food intake 55 . However, other agents are likely to be involved in mediating the impact of ghrelin on appetite, food intake and energy balance these include orexins, pro-opiomelanocortin (POMC), cocaine- and amphetamine-related transcript (CART), MCH, ciliary neurotropic factor (CNTF), gamma amino butyric acid (GABA), galanin, corticotropin-releasing hormone (CRH) and somatostatin 46, 50,56 . Besides the increase of appetite and food intake, reduced cellular fat oxidation and promotion of adipogenesis reportedly contributes to increased fat mass induced by ghrelin 10,50 .

General Appearance Manner and Attitude

And neatness of attire, responsiveness, cooperation, and ability to maintain eye contact. Observation for psychomotor retardation (slowing) or agitation can be helpful. The psychiatrist can listen carefully for rate, quality, tone, audibility, modulation, and form of speech, including evidence ofprosody, aphasias, or dysphasias. Additionally, observation of skin for icterus, pallor, cyanosis, edema, rashes, or other lesions can be helpful. The psychiatrist should also evaluate whether the patient appears healthy or ill, robust or cachectic, with signs of wasting and protein energy undernutri-tion. Obvious signs ofspecific medical illness or organ impairment include seizures, involuntary movements, tremors, paresis, paralysis, facial droop or asymmetry, exophthalmos, neck fullness, spider angiomata, asci-tes, anascarca, dyspnea, clubbing, and pedal edema. The psychiatrist can look for signs of delirium such as fluctuating levels of consciousness, mood, and behavior and falling asleep...

Desacyl Ghrelin as an Anorexigenic Peptide

Peripheral administration of des-acyl ghrelin showed an increase in c-Fos expression in the hypothalamic arcuate nucleus and in the paraven-tricular nucleus. The anorexigenic cocaine- and amphetamine-regulated transcript (CART) and urocortin 25 , as well as corticotropin-releasing factor type 2 receptor, but not type 1, are involved in this action 26 . Peripheral des-acyl ghrelin may directly activate the brain receptor by crossing the blood-brain barrier 27 but not by the activation of vagal afferent pathways 2, 25 . According to these results, the intracisternal administration of des-acyl ghrelin decreased food intake in food-deprived rats and inhibited gastric emptying without altering small intestine transit 11 .

Cytokine Peptide Interactions

Other endogenous cytokine-peptide interactions relevant to wasting, cachexia and the cachexia-anorexia syndrome include reciprocal cytokine-leptin (a member of the long-chain helical cytokine family)-neuropeptide Y-corti-cotropin-releasing hormone-glucocorticoid interactions, and perhaps also among cytokines and other CNS neuropeptide regulators involved in the control of energy balance including cocaine- and amphetamine-regulated transcript, melanin-concentrating hormone, agouti-related protein, a-melanocyte-stimulating hormone, and hypocre-tins orexins 8,10,12, 22,27 . Various of these can affect metabolic processes directly (e.g. gluconeo-genesis, glycogenolysis). The hypothalamus plays a critical role with multiple neuronal groups involved, including the arcuate nucleus, the paraventricular nucleus, the ventromedial nucleus, and the lateral hypothalamus. The arcuate nucleus has leptin-responsive neurons with different functions, e.g. the pro-opiomelanocortin-producing neurons that...

The Cigarette Century

It was not until 1988 that the addictive nature of cigarette smoking was formally recognized. Major conclusions from the 1988 Surgeon General's report (U.S. Department of Health and Human Services, 1988) were as follows (1) Cigarettes and other forms of tobacco are addicting (2) nicotine is the drug in tobacco that causes addiction and (3) the pharmacological and behavioral processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine.

Future Considerations

Thomas E Prisinzano was born in New York City, and studied at the University of Delaware, where he obtained a BS in 1995, and Virginia Commonwealth University, where he completed his PhD in 2000 under the direction of Professor RA Glennon. He was then awarded an Intramural Research Training Award Fellowship to study in the laboratory of Dr Kenner C Rice at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). While at NIDDK, he worked on drugs of abuse and treatment agents. Subsequently, he took up his present position as an Assistant Professor in Division of Medicinal and Natural Products Chemistry at the University of Iowa in May 2003. His scientific interests include the development of novel analgesics, in particular, the development of novel compounds to study the neurochemical mechanisms of drug dependence and tolerance.

In Search of a Mechanisms of Action

At least in narcoleptic dogs, via a mechanism independent of the hypocretin receptor.36 Additionally, in DAT knockout mice, modafinil-like methamphetamine and the selective DAT blocker, GBR 12909, lacked wake-promoting effects.36 Increases in dopamine release in the rat nucleus accumbens were observed following modafinil administration but this was secondary to a reduction in GABAergic transmission that led to a reduction of GABAA receptor signaling in dopamine terminals.37 Modafinil dose-dependently reduced g-amino-butyric acid (GABA) outflow from the cortex of awake guinea-pig,38 and from the striatum, pallidum, and substantia nigra,39 and, more importantly, from the medial preoptic area and posterior hypothalamus of the awake rat.40 The latter are hypothalamic fields where functional inhibition of GABA release by modafinil may be relevant for its vigilance-promoting effects. Modafinil also increased glutamate release in the ventrolateral and ventromedial thalamic areas,...

Treatment And Management Of Substance Use Disorders

Methadone detoxification is the preferred method of managing opioid withdrawal. Schedules using bu-prenorphine and or clonidine for opioid detoxification are also available (NIH Consensus Development Conference, 1998). Detoxification from cocaine and stimulants is not done pharmacologically. Network therapy is an office-based treatment of SUD advocated by Galanter and colleagues (Galanter and Brook, 2001) that employs both psychodynamic and cognitive-behavioral approaches. The treatment includes a therapeutic network of non-abusing family members, significant others, and peers who actively participate with the therapist to provide cohesiveness and support, undermine denial, and promote compliance with treatment. Studies have demonstrated significantly less illicit substance use among patients receiving this treatment for cocaine and opiate abuse. (Galanter et al., 1997, 2004)

Applications in Substance Abuse Research

Perhaps the greatest advantage of PET and SPECT lies in their tremendous flexibility for studying a variety of brain functions, an attribute based on the virtually unlimited number of biologically relevant compounds that lend themselves to radiola-beling. To date, studies in substance abuse disorders have taken advantage of these techniques to study the in vivo pharmacology of drugs of abuse as well as the effects of abused drugs and or drug addiction on neuronal activity metabolism and brain chemistry. A majority of substance abuse studies have focused on cocaine addiction, and this disorder will be emphasized to illustrate the types of applications. Since all drugs of abuse are fundamentally organic (i.e., carbon containing) molecules, 11C radiochemistry makes PET uniquely suited to the study of their pharmacokinetics (i.e., since insertion of the radiolabel does not alter the native pharmacology of the parent drug). In fact, PET radiotracers currently exist for 11C cocaine, 11C...

What Is Not Part Of The Treatment

Thus far, only a few studies of clients with PTSD and substance abuse have used exploration of past trauma as a key intervention. in one study (Brady et al., 2001) results indicated that the 39 of their sample who was able to complete at least 10 of the 16 sessions showed positive outcomes in PTSD symptoms and cocaine use (as well as other symptoms), which were maintained at the 6-month follow-up. However, most clients were noncompleters and the researchers excluded clients with suicidal ideation, and thus likely selected a less impaired sample. in a study that combined Seeking Safety plus Exposure Therapy-Revised (Najavits et al., in press-a), positive outcomes were found in various domains, including psychiatric and substance abuse symptoms. However, a large number of modifications to standard exposure therapy was created, the treatment was conducted individually, and various safety parameters were put in place to maximize clients' ability to safely tolerate the work. For a...

Substance Misuse and Fitness for Interview

Withdrawal states can pose a bigger problem for the doctor assessing fitness for interview. Although most confessions made in these circumstances are reliable (74), it should be recognized that the person suffering from drug withdrawal may be particularly vulnerable to providing a false confession. Such persons may believe that compliance will result in early release and that the risks entailed in providing a false confession may seem worthwhile in the presence of an overwhelming desire to re-establish access to their supply of drugs (75). Although symptoms of mild withdrawal from opiates, for example, is considered unlikely to be a barrier to interview (62,73), the physical and mental distress occasioned by established withdrawal may seriously impair a suspect's fitness to undergo the somewhat threatening and difficult experience of police interrogation.

Behavioral Sensitization In Adult Animals

Antelman et al. (64,65), Robinson et al. (66,67), and Kalivas and Stewart (68) have shown the potential bidirectional cross-sensitization between sensitization induced by psychomotor stimulants and some types of environmental stressors. This is of considerable interest in relation to the high comorbidity of substance abuse and the affective disorders (28,69,70), both of which have been linked to stressful life experiences in their initiation, progression, and in the precipitation of relapse. Thus, cocaine sensitization can be used both as a model for psychomotor stimulant abuse with long-term effects on gene expression and as a potential model of the effects of recurrent stressors on these and related neural systems. We have been particularly interested in the observation that cocaine-induced behavioral sensitization has an important conditioned component (71-73). Repeated administration of the psychomotor stimulant in the same environment comes to evoke increasing behavioral...

Conditioned Components of Sensitization

Cocaine (96-98), as well as many stressors (49,99-101) has been demonstrated to increase CRF release, and the conditioned component of cocaine sensitization appears to also involve a conditioned corticosterone response (102). Adrenalectomy can block sensitization in amphetamine and cocaine Co-morbidity with drug abuse may work in both directions affective illlness o drug abuse paradigms (103,104) and intracerebroventricular (icv) administration of the CRF antagonist alpha-helical CRH has also been reported to block amphetamine sensitization (105) but not cocaine sensitization conditioned (Weiss et al., unpublished data). The studies of Brown et al. (106) on conditioned effects of stimulants indicate that it is not the striatal or accumbens systems that are direct targets of cocaine that show a conditioned increase in c-fos expression. Rather, it is the limbic and cortical structures that appear to be affected by exposure to an environment previously paired with drug. CRF itself,...

Woman with Guilt and Shame about Not Disclosing Childhood Sexual Abuse

Mary, who was in her mid-30s, had a longstanding history of drug abuse and had been in two relationships with boyfriends who were abusive. She had had almost 2 years of sobriety when she volunteered to receive cognitive trauma therapy (CTT). To correct hindsight-biased thinking, it is critical to identify negative outcomes that were unforeseeable. Recalling unforeseeable outcomes as foreseeable reflects hindsight-biased thinking, and if outcomes were not foreseeable, they were not preventable. Mary's therapist established that many important outcomes were not foreseeable when Mary chose to keep the molestation a secret after it first happened. Mary did not know that her uncle was going to molest her again, that the abuse was going to continue for 5 years, and that it was going to result in her dropping out of school and engaging in years of drug addiction. In addition, she did not know that, when she was molested on subsequent occasions, it was going to make her appear more implicated...

Management in Custody

Necrotizing fasciitis and septic thrombophlebitis are rare but life-threatening complications of intravenous drug use. Any detainee suspected of either of these needs hospital treatment. Advice about harm reduction should also be given. This includes encouraging drug users to smoke rather than inject or at least to advise them to avoid injecting into muscle or skin. Although most IDUs are aware of the risk of sharing needles, they may not realize that sharing any drug paraphernalia could be hazardous. Advice should be given to use the minimum amount of citric acid to dissolve the heroin because the acid can damage the tissue under the skin, allowing bacteria to flourish. Drugs should be injected at different sites using fresh works for each injection. This is particularly important when speedballing because crack cocaine creates an anerobic environment. Medical help should be requested if any injection site become painful and swollen or shows signs of pus collecting under the skin....

Synopsis Of The Novel

In part 2 it is mid-April, and Rabbit and Janice return to springtime Brewer. While Janice looks for a job, Rabbit reflects on his dismal past, visiting his ill lover, Thelma, whose disease, systemic lupus erythema-tosus, has depleted her family's income and spirit. Rabbit learns from her that Nelson is a cocaine addict, causing Rabbit additional worry about AIDS. He visits Springer Motors, discovering Nelson has taken down his old basketball star photos, has hired a woman, and that the homosexual AIDS-inflicted bookkeeper refuses to show him the books. Janice takes Penn State extension real estate courses, while Rabbit frets about Nelson. They talk about Nelson's drug addiction and bleeding the company then receive threatening calls from his unpaid drug dealers. They are guilt-ridden for raising Nelson to be so troubled. Rabbit asks his friend Charlie Stavros for advice, and they discuss Brewer's drug problem at large. Late one evening after the drugged-up Nelson attacks Pru, she...

Neurotransmitters And Behavioral Pharmacology

Cocaine is both a stimulant of the central nervous system (CNS) and a local anesthetic, with large abuse liability due to its reinforcing properties. It is widely believed that the cocaine reward system is the mesocorticolimbic pathway, which originates in the ventral tegmental area (VTA) and projects to numerous areas of the forebrain, including the frontal cortex, hippocampus, amygdala, and the striatum (including the nucleus accumbens and the caudate putamen) (Koob, 1992). Recent work examining neurochemical turnover rates suggests that discrete subpopulations of dopamine, serotonin, glutamate, and gamma-aminobutyric acid (GABA)-releasing neurons are responsible for cocaine reward. Data suggest that dopamine in the nucleus accumbens, VTA, septum, lateral hypothalamus, and brainstem glutamate in the nucleus accumbens and VTA and serotonin in the medial hypothalamus are implicated in cocaine reward. In addition, surprising findings in the cerebral cortex have included noradrenergic...

Neurotransmitter Involved In Opioid Dependence

Changes in various neurotransmitters, different from the opioids, have been reported during chronic opioid administration and at the time of spontaneous or naloxone-precipitated morphine abstinence, which underlie a heterologous regulation of the opioid-dependence processes (for a review, see refs. 38 and 53). One of the heterologous neurotransmitters closely related to the neurochemistry substrate of opioid addiction is the dopamine. Indeed, converging evidence suggests that many drugs of abuse act through mechanisms involving the brain neurotransmitter dopamine and the neural systems that it regulates (83). The binding of opioids to their specific receptors increases the activity of mesolimbic dopaminergic neurons in the mid-brain. The cell bodies of the dopamine neurons are located in the ventral tegmental area and project to the forebrain, nucleus accumbens, olfactory tubercle, frontal cortex, amygdala, and septal area. Rats will self-administer morphine directly into the...

Other Magnetic Resonance Methods

The 3DTOF technique acquires multiple thin slice ( 1.5 mm thick) images of brain which are used to reconstruct composite images of the brain vascular system. The composite images are known as maximum intensity projections (MlPs) and include only the brightest pixels from each source image which presumably are from flowing blood. It is possible to produce maximum intensity projection images in many different orientations using 3DTOF data. Angiographic techniques may be particularly useful in characterizing the blood flow abnormalities associated with acute and chronic drug abuse.

Pepper Black and White

Cretans used opium medicinally as early as 3400 b.p., and it was in use by early Egyptians and Sumerians, apparently. By the time of Mohammed (a.d. 570-632), its medicinal and narcotic properties were appreciated by the Arabians. Its narcotic usage moved to India, thence China. Antagonistic roles of British smugglers, and Chinese officials, trying to curb the scourge of millions, ended up in the Opium Wars of 1840 and 1855. Then morphine and heroin reciprocated within a century, causing addiction in thousands of Caucasians, to be supplanted, at least in part, in the 1980s by cocaine.

Longterm Dose And Abuse

Other common nonmedical patterns are to use benzodiazepines (often alprazolam or lorazepam) concomitantly with stimulants (often cocaine or methamphetamine) to reduce the unpleasant experiences of the stimulant use, and or to use benzodiazepines (often triazolam Halcion ) to treat the insomnia that accompanies stimulant abuse.

Population Based Studies

When considered in community samples, the presence of an SUD diagnosis elevates lifetime risks of additional SUD diagnoses (Regier et al., 1990). This is true with most classes of abused drugs. For example, the risk for a nonalcohol SUD is elevated among both males and females with alcohol dependence. In the National Comorbidity Survey (NCS), more than 40 of individuals with a DSM-III-R alcohol dependence had, excluding nicotine dependence, co-occurring drug abuse or dependence (Kessler et al., 1997). Between 13 and 18 of those with alcohol abuse will also have a co-occurring lifetime drug use disorder (NCS Kessler et al., 1997). Lifetime drug use disorder was also present in 21.5 of subjects (odds ratio OR 7.1) with an alcohol use disorder identified in the Epidemiologic Catchment Area survey (ECA Regier et al., 1990). In addition, among individuals with a nonalcohol substance use disorder in the ECA study, 47.3 also had a lifetime alcohol use disorder. Excluding nicotine dependence,...

Personality Correlates

In community samples, 28.6 of individuals with a current alcohol use disorder have at least one personality disorder, and 47.7 of those with a current drug use disorder have at least one personality disorder (Grant et al., 2004). Furthermore, of individuals with at least one personality disorder, 16.4 had a current alcohol use disorder and 6.5 had a current drug use disorder. Personality disorders are associated with poorer treatment outcome for patients with alcohol dependence and those with drug dependence (Helzer & Pryzbeck, 1988 Rounsaville, Dolinsky, Babor, & Meyer, 1987). In various treatment settings, patients with SUDs screened with standard instruments meet criteria for personality disorders, with 57-73 having at least one personality disorder diagnosis, and 35-50 having at least two personality disorder diagnoses (Kleinman et al., 1990 Kranzler, Satel, & Apter, 1994 Marlowe et al., 1995 Rounsaville et al., 1998 Skinstad & Swain, 2001). Personality disorder diagnoses are...

Categorical Personality Disorders

The risk of ASPD among drug-dependent individuals in community samples is 29 times that of the general population, and rates of ASPD among IDUs range between 35 and 71 (Darke et al., 2004 Dinwiddie et al., 1996 Regier et al., 1990). ASPD appears to be a risk factor for multiple substance dependence. For example, patients who meet dependence criteria for both cocaine and alcohol have higher psychiatric severity and are more likely to have ASPD than patients with cocaine dependence only (Cunningham, Corrigan, Malow, & Smason, 1993). Among clinical populations, sociopathy among substance abusers is associated with high treatment dropout and poorer treatment outcome (Leal, Ziedonis, & Kosten, 1994 Woody, McLellan, Luborsky, & O'Brien, 1985). T masson and Vaglum (2000) followed 100 treatment-seeking alcoholics with ASPD for 28 months in a European study Forty-seven percent of the cohort had multiple SUDs and more prior admissions, and they were more frequently involved in fights. The route...

Medication Induced Delirium

Principles to remember in cases of drug-induced delirium include the facts that (1) blood levels of possibly offending agents are helpful and should be obtained, but many persons can become delirious at therapeutic levels of the drug, (2) drug-induced delirium may be the result of drug interactions and polypharmacy and not the result of a single agent, (3) over-the-counter medications and preparations (e.g., agents containing caffeine or phenylpropanolamine) should also be considered, and (4) delirium can be caused by the combination of drugs of abuse and prescribed medications (e.g., cocaine and dopaminergic antidepressants).

Neuropsychological Impact Of Multiple Substance Use Disorders

As compared with non-polysubstance-using drug abusers, those with multiple SUDs demonstrate the greatest degree of chronic neuropsychological impairment and recover the least function with long-term abstinence (Beatty et al., 1997 Medina, Shear, Schafer, Armstrong, & Dyer, 2003). This may be due in part to the increased cumulative exposure of the brain to drugs and alcohol Multiple substance users tend to use as much of a particular substance (e.g., alcohol or cocaine) as those who use only alcohol or cocaine (Selby & Azrin, 1998). Selby and Azrin (1998) conducted a comprehensive neuropsychological battery with 355 prison inmates classified by DSM-IV criteria into four groups those with alcohol use disorders, cocaine use disorders, multiple SUDs, and no history of SUD. The multiple SUDs and the alcohol groups demonstrated significant impairment on most measures compared to the cocaine or no-drug groups, but the multiple SUDs group performed worse than the cocaine alone, alcohol alone...

Rapid Unexplained Deaths During Restraint

The individuals who die during restraint are not infrequently under the influence of drugs (particularly cocaine) or alcohol they may be suffering from some underlying natural disease (particularly of the cardiovascular system), or they may have suffered some trauma. These additional factors are sometimes seized by pathologists and courts to explain the death, sometimes even in the face of expert opinion that excludes the additional factor from playing a major part in the death. It would seem that there is a subgroup of the population that is either permanently or temporarily susceptible to the effects of restraint, whether those effects be mediated entirely or partially through decreased respiratory effort or some other factor.

Opioid Dependence and Opioid Maintenance Treatment

Polydrug use is the norm among heroin users. In a study of 329 primary heroin users by Darke and Hall (1995), the most prevalent drugs used during the preceding 6 months were tobacco (94 ), cannabis (84 ), alcohol (78 ), benzodiazepines (64 ), amphetamines (42 ), cocaine (24 ), and hallucinogens (22 ) the mean number of drug classes used was 5.2. However, it appears that as they grow older, illicit drug users reduce their range of drugs Age is inversely correlated in IDUs with the number of current dependence diagnoses, and young males who are not in treatment, and who inject amphetamines, are at higher risk for polysubstance use (Darke & Hall, 1995 Darke & Ross, 1997). Cocaine Use The use of cocaine by patients in methadone or buprenorphine maintenance treatment programs has been reported to be as high as 73 in a sample of 1038 newly admitted patients in 15 methadone clinics in New York City (Magura, Kang, Nwakeze, & Demsky, 1998). Contrary to popular belief, the simulta neous use of...

Electroencephalographs Studies of Chronic Substance Abusers

Before the evidence for EEG, EP, or ERP anomalies in patients with histories of alcohol or drug dependence is reviewed, it would be valuable to highlight some of the methodological and interpretive problems that are inherent in studying patients with drug use histories as well as several problems that are created by researchers themselves. These problems are not specific to EEG EP ERP research. Rather, they generalize across all of the neuroimaging modalities. In a 1997 study which excluded individuals with these complications (Fig. 1), we found no evidence of quantitative EEG abnormalities in a group of 19 heroin dependent patients, abstinent for 1-5 mo, compared to healthy controls (Costa and Bauer, 1997). Importantly, the patients in our study failed to exhibit the same enhancement of EEG beta power demonstrated in cocaine or alcohol dependent patients via the same

Chiral Ce Of Urinary Drugs And Metabolites Assays For Enantiomer Screening Of Misused Abused And Banned Substances

CE has proven to provide a simple, inexpensive, and effective approach for the separation of enantiomers after the addition of a chiral selector to the buffer. The separation by CE of the enantiomers of several drugs of interest in toxicology and doping control has been investigated. By using various cyclodextrins it was possible to effect the chiral differentiation of the optical isomers of racemethorphan and racemorphan (45), amphetamines, cathine, cathinone, cocaine, and others (68), as well as of urinary mephenytoin and phenytoin (69), urinary methadone (28,29), urinary MDMA (Ecstasy) (37), and various amphetamines in urine (35). the d-(+) and l-(-) isomers of 3-methoxy-N-methylmorphinan, respectively. Aumatell and Wells (45) demonstrated that these enantiomers could easily be distinguished using a chiral CZE assay that was developed for urinary analysis of the optical isomers of racemethorphan and racemorphan. Distinction of these compounds is not only of interest in forensic...

Basic Science Of Addiction

Drugs of misuse act at local cellular and membrane sites that are within a neurochemical system that is called the Reward and Withdrawal Pathway (11). This pathway is in the meso-limbic dopamine system, and it involves, among other structures, the ventral tegmental area, nucleus accumbens, amygdala, and prefrontal cortex of the primitive brain. Addiction is a neurobiological disease that causes disruption of this pathway. This disruption is mediated via receptor sites and neurotransmitters. Central to this reward and withdrawal pathway is the neurotransmitter dopamine, which has been shown to be relevant not only to drug reward, but also to food, drink, sex, and social reward (12,13). Disruption of this neurochemical pathway by drugs of abuse may lead to addiction. Drug withdrawal can intensify with repeated drug use and can persist during prolonged periods of drug abstinence, a symptom complex known as the protracted abstinence syndrome (14). This sensitization of a neural process...

Alteration of Affinity

Regulation of DA transport by membrane trafficking does not preclude the possibility of concomitant regulation by other mechanisms such as changes in transporter catalytic efficiency. Although most second-messenger treatments have not been found to alter the affinity of DAT for DA or antagonists (Table 1), such changes have been found in some instances, including increased Kd for 3H CFT binding after PMA treatment (44), and changes in the Km for DA in esponse to PMA (46), AA (47), and SNP (39). In addition, chromatographically resolved DAT charge isoforms, which may represent differentially phosphorylated DAT populations (see Evidence for Endogenous DAT Phosphorylation), display modest differences in cocaine and dopamine binding parameters (10). Because these altered binding properties were detected in detergent-solubilized DAT samples (10), membrane trafficking mechanisms presumably did not contribute to the results, and these findings may be consistent with direct alterations of...

Diagnostic and Statistical Manual of Mental DisordersIV

(7) Continued substance use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance (e.g., continued cocaine use despite recognition of cocaine-induced depression, or continued drinking despite recognition that an ulcer is made worse by alcohol consumption)

The Medical Review Interview Is

Use Standard Form One size fits all Review of COC fatal flaws correctable flaws noncritical flaws Identify self and affiliation Confirm identity of the donor (have donor confirm last 4 digits of SS ) Inquire about collection procedures Present medical Miranda Inquire re illicit drug use Offer split sample or re-test (required by RSPA, USCG)

The Association Between Dual Diagnosis And Treatment Outcome

In both SUD and psychiatric treatment-seeking populations, dually diagnosed patients typically experience worse outcomes than their singly diagnosed peers (Ritsher et al., 2002 Schaar & Oejehagen, 2001). However, there are specific populations in which the evidence regarding this is mixed, such as the severely and persistently mentally ill (SPMI) (Farris et al., 2003 Gonzalez & Rosenheck, 2002) and ASPD populations (Cacciola, Alterman, Rutherford, & Snider, 1995 Kranzler, Del Boca, & Rounsaville, 1996). The effect of other psychiatric disorders on SUD outcomes may vary by SUD type. For example, co-occurring major depression appears to predict worse alcohol outcomes (Brown et al., 1998 Greenfield et al., 1998), while there is less evidence for its predicting worse cocaine outcomes (McKay et al., 2002 Rohsenow, Monti, Martin, Michalec, & Abrams, 2002).

Endogenous DAT Phosphorylation and Regulation

We currently have little information regarding the types of physiological stimuli that provide the endogenous control for DAT phosphorylation and or functional regulation. This issue is of utmost importance to our understanding of the relevance of these phenomena to normal neurophysiology, dopaminergic neurodegeneration, and mechanisms of drug abuse. Potential candidates for physiological control are receptors that couple to PKC and possibly to other effectors such adenylate cyclase, keeping in mind that, as yet, there is no direct evidence linking pathways other than PKC to phos-phorylation of DAT. At present, there is no clear biochemical explanation for dopaminergic regulation of DAT function, and further experiments will be required to clarify the relationships between DA receptors, PKA, PKC, and DAT phosphorylation. However, a DA receptor-DAT phosphorylation link would also present a potential mechanism for cocaine involvement in control of DAT activity via the drug's ability to...

The Self Medication Hypothesis

A major criticism of the self-medication hypothesis has been its heavy reliance on anecdotal data from patients in psychotherapy and the relative paucity of empirical studies testing it (Aharonovich, Nguyen, & Nunes, 2001). Additionally, intoxicants may produce very different effects acutely compared to the effects of chronic administration. Studies of individuals with heroin (Meyer & Mirin, 1979), cocaine (Post, Kotin, & Goodwin, 1974), and alcohol (Mendelson & Mello, 1966) use disorders have observed a dichotomy between the acute effects of these drugs in producing euphoria or tension relief and the chronic or high-dose effects in producing dysphoria. Several researchers have sought to test empirically the self-medication hypothesis in larger samples. The results have tended not to support the specificity of using a particular addictive substance to alleviate specific psychopathology or mood states (Aharonovich et al., 2001 Weiss, 1992a). However, while not necessarily a validation...

Universal Precautions In Pain Medicine

Surprisingly, some clinicians struggle with the idea of taking a drug and alcohol history in all patients. Even asking about drug and alcohol misuse is seen as minimizing or dismissing the patients' complaints of pain. In no other area of medicine would such an attitude exist. The fact is that alcohol and drug addiction is present in virtually all areas of medicine, without particular respect for socioeconomic status, race, age, or sex. While the nature and distribution of these problems vary, it is unwise to limit one's inquiry into substance use based on classical societal stereotypes.

Sequential Parallel and Integrated Treatment Models

In sequential treatment, the more acute condition is treated first, followed by the less acute co-occurring disorder. The same staff may treat both disorders, or the less acute disorder may be treated after transfer to a different program or facility. For example, a manic patient with a cocaine use disorder needs mood stabilization before initiating substance abuse treatment. Conversely, a patient with major depression and alcohol withdrawal delirium is not in a position to discuss treatment adherence to antidepressant medication. Instead, this issue is best addressed when the patient is more stable. Although sequential treatment has the advantage of providing an increased level of attention to the more acute disorder, a typical disadvantage of this model is that patients are often

Of Age On The Human Dat mRNA

Reductions in DA and DA-related synaptic markers in the striatum are known to contribute to the cognitive and motor deficits associated with normal aging. Although cocaine, unlike methamphetamine, does not appear to be neurotoxic in experimental animals (20), this question has not been resolved fully in the human. In the postmortem human striatum, a progressive decrease in DAT density with age has been demonstrated using 3H GBR 12935 (13,21-23). Decreases in DAT density of75 and 65 were reported for subjects ranging from 19 to 100 yr (21) and from 18 to 88 yr (13), respectively. In vivo imaging of the DAT with cocaine and cocaine congeners ( 11C cocaine 24 and 123I p-CIT 25 ), and classical DAT inhibitors ( 11C nomifensine 26 ) also demonstrated a decline ofDAT with increasing age. Using 11C cocaine, a gradual decline in the density of cocaine recognition sites was detected over an age range of 21-63 yr (24). Using 123I p-CIT, a 51 decline in DAT density was observed over an age range...

Shortcomings of current therapy

By the ASDA) had higher frequency of psychosis, paranoia or disordered thinking, alcohol or poly-drug abuse, and psychiatric hospitalizations compared to patients using standard doses 112 . The presence of rebound hypersomnia is more frequent with higher dosages of amphetamines. Dextroamphetamine is a category D drug methamphetamine, modafinil, and mazindol are category C drugs and methylphenidate has no adequate animal studies and manufacturer suggests use if benefits outweigh risks. Pemoline is the only category B stimulant, and it carries a small, although significant, risk of hepatotoxicity. When the potential for teratogenicity is unknown, the benefits to the patient have to be weighed against the potential risks to the fetus for many patients, it is suggested that stimulant use be discontinued or reduced during attempts at conception and for the duration of the pregnancy 115 . For the treatment of cataplexy, GHB is a pregnancy category B drug, while the antidepressants, such as...

Attention DeficitHyperactivity Disorder

Although stimulants have been the most extensively studied treatment for adult attention-deficit hyperactivity disorder (ADHD) (Levin, Evans, & Kleber, 1999), there are concerns that they may worsen the course of the SUDs or be subject to abuse themselves in dually diagnosed populations (Gawin, Riordan, & Kleber, 1985). At the same time, it has also been observed that a childhood history of ADHD worsens outcomes for cocaine dependence (Carroll & Rounsaville, 1993). Therefore, improving a patient's difficulties with inattention and hyperactivity may have beneficial effects on substance abuse as well (Levin et al., 1999). Consistent with this, prospective studies of children who received stimulant treatment for ADHD indicate that stimulants have a protective effect against future development of SUDs as an adult (Wilens, 2001). Although not as well-studied as stimulants, nonstimulant medications that lack abuse potential are possible alternatives in the treatment of ADHD. In adult...

Baseline Maximum Taper High DowM M

Comparison of representative brain SPECT images of heroin- and cocaine-abusing men enrolled in a placebo-controlled trial of the partial opiate agonist buprenorphine for the treatment of polydrug dependence. Images are from three subjects, receiving high or low dose buprenorphine (12 or 6 mg, respectively) or placebo, and studied at three separate time points (at baseline, at maximum dose during buprenorphine treatment, and following a taper off treatment). A comparable midcortical slice includes the basal ganglia, thalamus, and frontal, temporal, parietal, and occipital cortex. Arrows indicate perfusion defects. The subject receiving high dose buprenorphine shows marked improvement in perfusion, seen as dark (purple) areas becoming light (orange or yellow), whereas the patient receiving the low dose shows more mild improvement. The patient receiving placebo shows no improvement in perfusion. Following drug taper, buprenorphine treatment groups show reduced perfusion. These...

Substance Induced Persisting Dementia Diagnosis

The presence of dementia makes the treatment of alcoholism or other drug dependence more difficult. Most treatment programs depend on education about substance abuse, working the 12 steps, some degree of sociability, and such relatively abstract concepts as secondary gratification and a higher power. Such treatment programs are often reluctant to engage in the painstaking repetition that individuals with substance-induced persisting dementia often require. These individuals may become frustrated in peer support groups such as Alcoholics Anonymous. Despite these obstacles, individuals with alcoholism who complete a treatment

Pathological Gambling and Other Behavioral Addictions

Several disorders, particularly those formally categorized in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) as impulse control disorders (ICDs) not elsewhere classified, have been described as behavioral addictions (American Psychiatric Association, 2000). The ICDs include pathological gambling (PG), kleptomania, intermittent explosive disorder, trichotillomania, and pyromania, and diagnostic criteria for compulsive computer use, compulsive sexual behavior, and compulsive buying (CB) have been proposed. Although there exists some controversy regarding the most precise categorization of these disorders, mounting evidence supports phe-nomenological, clinical, epidemiological, and biological links between behavioral and drug addictions. As such, it seems increasingly important that individuals involved in the prevention and treatment of substance use disorders (SUDs) have a current understanding of ICDs and the potential for future research...

Personality Disorder In Hiv Atrisk And Hivpositive Individuals

Personality disorder is a risk factor for HIV infection (Brooner et al., 1993). Prevalence rates of personality disorders among HIV-positive (19 -36 ) and HIV at-risk (15 -20 ) individuals (Perkins et al., 1993 Jacobsbergetal., 1995 Johnson etal., 1995) arehighand significantly exceed rates found in the general population (10 ) (Weissman, 1993). Antisocial (ASPD) and borderline (BPD) personality disorders are the most common (Golding and Perkins, 1996). Individuals with personality disorder, particularly ASPD, have high rates of substance abuse and are more likely to inject drugs and share needles compared to those without an Axis II diagnosis (Kleinman et al., 1994 Hudgins et al., 1995 Dinwiddie et al., 1996). Approximately, half of drug abusers meet criteria for a diagnosis of ASPD (Hudgins et al. 1995 Dinwiddie et al., 1996). Individuals with ASPD are also more likely to have higher numbers of lifetime sexual partners, engage in unprotected anal sex, and contract STDs, compared to...

Integration Of Psychotherapy And Pharmacotherapy For Dually Diagnosed Patients

This work was supported by Grant Nos. K02 DA00326 (Dr. Weiss), R01 DA015968 (Drs. Busch and Weiss), U10 DA015831 (Drs. Busch, Weiss, and Najavits), and K02 DA00400 (Dr. Najavits) from the National Institute on Drug Abuse. Adinoff, B. (1992). Long-term therapy with benzodiazepines despite alcohol dependence disorder. Am J Addict, J (4), 288-293. Aharonovich, E., Nguyen, H. T., & Nunes, E. V. (2001). Anger and depressive states among treatment-seeking drug abusers Testing the psychopharmacological specificity hypothesis. Am J Addict, J0(4), 327-334. Albanese, M. J., Bartel, R. L., Bruno, R. F., Morgenbesser, M. W., & Schatzberg, A. F. (1994). Comparison of measures used to determine substance abuse in an inpatient psychiatric population. Am J Psychiatry, J5J (7), 1077-1078. Alcoholics Anonymous. (1984). The AA member Medications and other drugs Brochure . New York Alcoholics Anonymous World Services. American Psychiatric Association. (1987). Diagnostic and statistical manual of mental...

Recreational Drugs and the Nervous System

Used legally to treat obesity, asthma, and narcolepsy. Herbal products containing ephedra, a drug originally procured from the Mah huang plant and also synthesized in laboratories, have been marketed as treatments for weight loss and for performance enhancement. Methamphetamine is an illegal amphetamine. A crystalline form of methamphetamine called ice is smoked to produce effects similar to crack cocaine.

Drug Tolerance Dependence And Withdrawal

From a clinical standpoint, withdrawal can be one of the most powerful factors driving dependence and addictive behaviors. This seems particularly true for opioids, alcohol, benzodiazepines, nicotine, and to a lesser extent stimulants such as cocaine. For hallucinogens, cannabinoids, or inhalants, withdrawal Repeated exposure to escalating dosages of most drugs alters the brain, so that it functions more or less normally when the drugs are present and abnormally when they are not. Two clinically important results of this alteration are drug tolerance (the need to take higher and higher dosages of drugs to achieve the same effect) and drug dependence (susceptibility to withdrawal symptoms). Withdrawal symptoms occur only in patients who have developed tolerance. Tolerance occurs because the brain cells that have receptors or transporters on them gradually become less responsive to the stimulation by the exogenous substances. For example, more opioid is needed to inhibit the cyclic AMP...

The Scientific Evidence

Complex social questions are posed by nearly all of the reported or imagined possible discoveries in behavioral genetics. Issues such as drug dependence, violence, and personality traits all may be viewed through a genetic lens. Some scholars are even studying whether economic behavior (Wheeler 1996) and legal doctrines (Berkman 1997) are biologically based.

Treatment Considerations

At its simplest, treatment of patients with chronic multiple SUDs requires a focus upon each disorder separately, in addition to providing patients with a coherent overall rationale and approach to addiction treatment. Although multiple SUDs have a net negative impact on treatment outcome, Abellanas and McLellan (1993) have shown that patients with multiple SUDs report generally similar motivation for change across drugs of abuse, meaning that their desire to modify their substance use remains consistent across substances. An additional issue is the specific impact of other substance use upon recovery for a particular SUD. Treatment is thus best constructed with a bottom-up approach, using evidence-based approaches where available (Rosenthal, 2004), rather than assuming that optimal treatment should be largely psychotherapeutic or pharmacotherapeutic. For example, there is a clear evidence base for the use of methadone as an agonist therapy for stabilization of opioid dependence...

Psychiatric Disturbance

Substance abuse can occur conjointly with virtually any Axis I or Axis II psychiatric disorder. This has important treatment implications, the most obvious of which is that for some individuals, alcohol or drug consumption may constitute an attempt at self-medication. Hence, treatment of the primary disorder may in some circumstances be sufficient to ameliorate the substance use disorder. Alternatively, prolonged drug abuse may precipitate a psychiatric disturbance, either directly by inducing neurochemical changes or indirectly through stress or maladjustment concomitant to a substance abusing lifestyle. A major task is therefore to delineate the type and severity of psychiatric morbidity that may be present and to determine whether it preceded or developed after the substance use disorder.

Preparation And Routes Of Administration

Cocaine is the most potent stimulant of natural origin. It is a benzoyl-methylecgonine, an ester of benzoic acid and a nitrogen-containing base. Cocaine occurs naturally in the leaves of Erythroxylon coca and other species of Erythroxylon indigenous to Peru, Bolivia, Java, and Columbia. There are several basic routes to cocaine administration chewing the leaves, cocaine sulfate (paste), cocaine hydrochloride, freebase cocaine, and crack cocaine. South American natives who chew coca leaves experience diminished hunger and fatigue, and an improved sense of well-being without evidence of chronic toxic-ity and dependence. However, other preparations and routes of administration of cocaine have a more rapid onset of action and are more problematic. Cocaine sulfate (paste) is the intermediate form between the coca leaf and the finished cocaine hydrochloride crystal. The smoking of coca paste, popularly known as pasta or bazooka, is prevalent in South America and also occurs in some parts of...

Discontinuation of Benzodiazepine

Discontinuation of sedatives and hypnotics, including the benzodiazepines, can be divided into three categories (1) long-term low-dose benzodiazepine use, (2) high-dose benzodiazepine abuse and multiple drug abuse, and (3) high-dose abuse of nonbenzodiazepine sedatives and hypnotics (especially intermediate-acting barbiturates). The first group of patients can usually be discontinued on an outpatient basis. Some of the second and even the third group can be treated as outpatients, but most will require inpatient care. Inpatient discontinuation today with managed care is generally reserved for patients who fail at outpatient discontinuation and for those who demonstrate acutely life-threatening loss of control over their drug use. The pharmacological management of inpatient benzodiazepine withdrawal from nontherapeutically high doses of these medicines is covered in standard texts dealing with inpatient detoxification (Wesson et al., 2003).

Comprehensive Hiv Services Lead To Improved Outcomes For Patients And Providers

Alterman AI, Erdlen FR, and LaPorte DJ (1982). Effects of illicit drug use in an inpatient psychiatric population. Addict Behav 7 231-242. Bleuler, E (1911). Dementia praecox oder Gruppe der Schizophrenien', In G. Aschaffenburg (ed.), Handbuch der Psychiatrie. Spezieller Teil. 4. Abteilung, I. H lfte. Leipzig und Wien Franz Deuticke. Carey MP, Carey KB, Weinhardt LS, and Gordon CM (1997). Behavioral risk for HIV infection among adults with a severe and persistent mental illness patterns and psychological antecedents. Community Dixon L, Hass G, Weiden PJ, Sweeny J, and Frances AJ (1991). Drug abuse in schizophrenic patients clinical correlates and reasons for use. Am J Psychiatry 148 224-230. Miller FT, and Tanenbaum JH (1989). Drug abuse in schizophrenia. Hosp Community Psychiatry 40 847-849. Regier DA, Farmer ME, Rae DS, Locke BJ, Keith SJ, Judd LL, and Goodwin FK (1990). Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area...

As Sources Of Distress

Similarly, respiratory events and illnesses such as opportunistic infections, tuberculosis, malignancies, adult respiratory distress syndrome, and pulmonary fibrosis (Rosen et al., 1997) remain common in HIVseropositive populations, especially among those with CD4 counts

Pharmacological Interventions And Treatment Implications

In summary, the various biological models of drug addiction are complementary and broadly applicable to chemical addictions. We next illustrate how long-term pharmacotherapies for opioid dependence, such as methadone, nal-trexone, and buprenorphine, can counteract or reverse the abnormalities underlying dependence and addiction. These agents are particularly informative, because they are an agonist, antagonist, and partial agonist, respectively. We do not review short-term treatments for relieving withdrawal symptoms and increasing abstinence but refer readers elsewhere for detailed neurobiologi-cal explanations for various abstinence initiation approaches (see Kosten & O'Connor, 2003).

Substance Withdrawal Delirium

Some varieties of drug withdrawal, although uncomfortable, are not life threatening (e.g., opioid withdrawal). Others such as alcohol withdrawal delirium are potentially fatal. Withdrawal delirium is much more common among individuals who are hospitalized than among individuals living in the community. The incidence of delirium tremens, for example, is found in 1 of all alcoholics, but in 5 of hospitalized alcohol abusers. Improvement of the delirium occurs when the offending agent is reintroduced or a cross-sensitive drug (e.g., a benzodiazepine for alcohol withdrawal) is employed.

Cognitive Behavioral and Nonpharmacological Treatments

Cocaine disorders have proven to be refractory to both psychological and pharmacological treatment. Consequently, considerable energy has been directed toward developing and testing the efficacy of new psychotherapeutic approaches in the treatment of cocaine use disorders. Many of these therapies have been adapted from ones originally developed to treat alcoholism. One approach that has received attention is cognitive-behavioral relapse prevention (Marlatt & Gordon, 1985). Relapse prevention strives to teach the addict how to recognize high-risk situations and deal with these using cognitive strategies that have been well rehearsed. Relapse prevention recognizes that with a chronic disorder such as addiction, relapses and remissions are expected. When a relapse occurs, more intense treatment and cognitive restructuring are necessary to help prevent a slip from escalating. Reminding patients of their prior progress, focusing on making the slip an isolated event, and maximizing the...

Drug Free Life

Drug Free Life

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