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

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...

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...

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...

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...

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

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...

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...

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...


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...


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...

Psychiatric Disorders 601411 Schizophrenia

Cocaine related disorders Cocaine induced disorders Dopamine (DA) and glutamate have been implicated in the molecular pathophysiology of schizophrenia. Thus stimulants that activate brain dopaminergic systems, e.g., cocaine or amphetamine, induce a paranoid psychosis similar to that seen with the positive symptom core of the disease suggesting that overactive DA transmission is a key facet of the disease. Similarly, based on the ability of the psychotomimetics phencyclidine and ketamine to block glutamate receptors (N-methyl-D-aspartate (NMDA)-subtype) the glutamate hypothesis suggests a hypoactivity of excitatory glutamatergic systems.7 Statistics compiled by the National Institute on Drug Abuse (NIDA) indicate that the prevalence of substance abuse and the cost of this disorder are considerable. In 1994, an estimated 9.4 of the US population was involved in substance abuse. Since most of the drugs of abuse are illegal, prevalence estimates often come from either treatment program...

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.

Historical Background

Although records of eye surgical techniques go back as far as 3000 years, modern eye surgery was largely developed thanks to the introduction of cocaine and then of general anaesthesia at the end of the nineteenth century. The use of eserine eye drops to reduce the intraocular pressure in glaucoma was introduced at the same time, this being the forerunner of a number of different medical treatments that are now available. Cataract surgery saw great advances at the beginning of the twentieth century, with the introduction of the intracapsular cataract extraction. In the 1920s, successful attempts were being made to replace the detached retina, which had previously been an irreversible cause of blindness. Such early surgical techniques have now been developed to produce some of the most dramatic means of restoring sight. As a spin-off from the last war came a revolutionary idea of spare-part surgery in the eye. The observation that crashed fighter pilots were able to tolerate small...

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.)

Origins Of Drug Liking

For example, opioids and cannabinoids can inhibit activity in N-Ac directly, whereas stimulants such as cocaine and amphetamine act indirectly by binding to various DA transporters and either inhibiting the reuptake of DA into the VTA neurons (cocaine) or actively pumping DA out of the VTA (amphetamine) at its synapse with the N-Ac neurons (Kosten, 2002 Stahl, 1998). Since stimulation of the DA D2 receptor inhibits the cyclic AMP system, this increase in DA in the synapse leads to relative inhibition of the N-Ac neuron. The mechanism is more complex than this, however, since the D1 receptor has the opposite effect on the cyclic AMP system (e.g., it increases the amount of cyclic AMP) and both D1 and D2 receptors are present on the N-Ac neurons. The presumption is that the D2 receptor effects predominate perhaps simply due to more D2 receptors, or due to a higher affinity of the D2 than the Dt receptors for DA. Other substances may be even more indirect in their stimulation. For...

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 Changed Set Point Model

The changed set point model of drug addiction has several variants based on the altered neurobiology of the DA neurons in the VTA and of the NA neurons of the LC during the early phases of withdrawal and abstinence. The basic idea is that drug abuse alters a biological or physiological setting or baseline. One variant, by Koob and LeMoal (2001), is based on the idea that neurons of the mesolimbic reward pathways are naturally set to release enough DA in the N-Ac to produce a normal level of pleasure. Koob and LeMoal suggest that abused drugs cause addiction by initiating a vicious cycle of changing this set point, such that the release of DA is reduced when normally pleasurable activities occur and these abused drugs are not present. Similarly, a change in set point occurs in the LC, but in the opposite direction, such that NA release is increased during withdrawal, as described earlier, thus accounting for both the positive (drug liking) and negative (drug withdrawal) aspects of drug...

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.

Neuronal Nicotinic Receptor Agonists

The incidence of smoking is high in patients with schizophrenia, a rate at least three times higher than the general population. In fact, nicotine appears to produce a modest transient improvement in cognitive and sensory deficits in these patients. It has been suggested that smoking in schizophrenia represents an attempt to self-medicate.39 However, these views must be interpreted with caution. Overall, schizophrenic patients have a high degree of comorbid abuse of a variety of substances including nicotine, alcohol, cannabis, cocaine, and amphetamine. Importantly, the rate of substance abuse is higher than in the general population for all of these substances in spite of the fact that such abuse is associated with poorer outcomes, exacerbation of positive symptoms, increased hospitalization, and increased frequency of homelessness. This increased propensity to abuse a variety of substances regardless of consequences suggests that there may be a disregulation of reward systems in...

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...

Cultural and Social Change

In recent centuries, political, commercial, and technical advances have influenced the types, supply, cost, and availability of psychoactive substances, along with modes of administration (Westermeyer, 1987). International commerce, built on cheaper and more efficient transportation, and increasing income have fostered drug production and distribution. Increasing disposable income has resulted in greater recreational intoxication (Caetano, Suzman, Rosen, & Voorhees-Rosen, 1983). Development of parenteral injection for medical purposes was readily adapted to recreational drug self-administration in the mid-1800s, within several years of its invention. Purification and modification of plant compounds (e.g., cocaine from the coca leaf, morphine and heroin from opium, and hashish oil from the cannabis plant) produced substances that were both more potent and more easily smuggled and sold illicitly. Laboratory synthesis has produced drugs that closely mimic naturally occurring...

History Of Substance Abuse Treatment

Historical and literary accounts have long documented individual attempts to draw back from the abyss of alcohol and drug abuse. At various times autobiographical, biographical, journalistic, and anecdotal, these descriptions list centuries-old recovery methods still employed today in lay and professional settings. Modalities include gradual decrease in dosage symptomatic use of nonad-dicting medications isolation from the substance relocation away from fellow users religious conversion group support asylum in a supportive and non-demanding environment and treatment with a variety of shamanistic, spiritual, dietary, herbal, and medicinal methods (Westermeyer, 1998). Beginning with Galenic medicine, a key strategy has been to identify certain syndromes as having their etiology in alcohol and drug abuse. Once the etiology is determined, the specific treatment (i.e., cessation of substance abuse) can be prescribed. Examples of such substance-associated disorders include delirium tremens...

Fields Of Expertise Within Toxicology

Many poisons can disturb mental and rational function leading to behavioral abnormalities. Psychototoxins include phencyclidine, LSD, and fungal toxins. Less commonly, stimulants such as cocaine and amphetamine can cause psychiatric problems. Psychiatric effects of high doses of corticosteroids have also been described. In addition to the developmental retardation, some investigators believe that cognitive impairment, hyperactivity, and perhaps even antisocial behavior may be caused by childhood lead exposure. Public discussion of these subtle toxic effects is highly politicized because childhood exposure to lead still occurs as a risk factor in slums and tenements. In addition to the necessity of continuous energy generation, the heart must maintain rhythmic function throughout its lifetime. Substances such as cocaine and cyclopropane that decrease the reuptake of norepinephrine after its release from noradrenergic neurons are prone to cause fatal arrhythmias. Additionally drugs that...

Preparation for Quitting

The physician should then provide the patient with some basic didactic information about quitting smoking. (1) Smoking represents an addiction to nicotine. Therefore smoking cessation must be undertaken as seriously as one would approach any other drug addiction. Willpower alone is insufficient. The patient must make quitting smoking his her top priority. (2) The goal should be total tobacco abstinence after the quit date. (3) The patient can expect to experience unpleasant nicotine withdrawal symptoms (e.g. mood disturbance, insomnia, irritability,

Radioligands Used In The Study Of Da Metabolism

Presynaptic markers directed to DAT are mostly tropane derivatives (cocaine analogs), such as 11C - or tropane (CFT, also known as 11C - or 18F -WIN 35,428), carbomethoxy-iodophenyl tropane (CIT), and 11C -RTI-32 (36). CIT can also be modified with either a fluoroethyl or fluoropropyl group. Because of the delayed time to equilibrium, the 18F-labeled FP-CIT is more suitable than its 11C analog, which has a much shorter half-life (37). nC -D-ihreo-methylphenidate (MP) may also be used to target the DAT, with a higher affinity and better pharmacokinetic properties than the majority of the tropanes (38). Although the DAT (but not all of its ligands) is fairly specific for DA, it has the disadvantage of being subject to up- or down-regulation by dopaminergic drugs and in response to extracellular levels of DA (39-41). Thus, findings may be attributable to disease or a consequence of its treatment. Numerous tropanes have been labeled with I-123 for SPECT imaging of the DAT, and there is to...

Hair Head and Pubic 51 Forensic Evidence

Hair is most commonly sampled to detect body fluids or retrieve foreign hairs or particles. It has been known for many decades that numerous ingested, prescribed, and illicit drugs (e.g., barbiturates, amphetamines, opiates, cocaine, benzodiazepines, y-hydroxy butyrate, and cannabis) are deposited in the hair (44). Although toxicology of hair was originally used to detect drugs that had been repeatedly ingested, recent advances in analytical techniques have meant that toxicology may be useful after single-dose ingestion as would occur in a substance-facilitated sexual assault (45,46). This is particularly pertinent because complainants of possible drug-facilitated sexual assaults frequently do not report the incident expeditiously because of amnesia and or doubt about what might have happened, and drugs may be accessible to analysis for longer periods in hair compared to blood or urine (47). In addition, it may be used as a reference sample for DNA analysis.

Multiplicity and ligand selectivity

CESs are largely microsomal in origin, with molecular weights of 55-60 kDa. At least four families (CES1-CES4, EC 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

Rates Of Psychiatric Disorders Among People Living With Hiv Infection

The landmark HIV Cost and Services Utilization Study (HCSUS) found that a large, nationally representative probability sample of adults receiving medical care for HIV in the United States in early 1996 (N 2,864 2,017 men, 847 women) reported major depression (36 ), anxiety disorder (16 ), and drug dependence (12 ) (Bing et al., 2001 Galvan et al., 2002), as well as heavy drinking at a rate (8 ) almost twice that found in the general population and high rates of drug use (50 ). The HCSUS study remains the most comprehensive view we have of the prevalence of psychiatric disorders among people living with HIV AIDS, though the study was not designed as a diagnostic assessment of psychiatric disorders among people with HIV AIDS and so rates of psychosis, bipolar disorder, alcohol abuse or dependence, and substance abuse, among others, were not obtained. Disorders of alcohol and other drug (AOD) abuse are differentiated from dependence in the Diagnostic and Statistical Manual of Mental...

Substance Induced Mood Disorder

Two broad categories of substances can be distinguished in this context. The first comprises substances with primarily psychoactive properties that are prone to abuse and can become addictive. This category includes alcohol opiates and related compounds such as ketamine barbiturates benzodiazepines and other central nervous system depressants stimulants, including amphetamines cocaine and related compounds such as methylenedioxymethamphet-amine (MDMA Ecstasy) phencyclidine (PCP) marijuana and hashish hallucinogens such as lysergic acid diethylamide (LSD) and mescaline inhalants and miscellaneous substances such as y-hydroxybutyrate (GHB). The second category comprises substances whose psychoactive properties are incidental to their main therapeutic effects. This category includes numerous medications used for acute and chronic nonpsychiatric conditions. With regard to psychoactive substance induced depression, Bakken and colleagues (2003) found that 48 of 241 substance abusers (age...

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...

Druginduced myocardial damage

Increases in cardiac troponin have been described in (1) patients treated with certain types of antineoplastic agents, (2) patients presenting to hospitals following alcohol and drug abuse, and (3) patients with therapeutic drug-induced cardiac toxicity. The release of cardiac troponin into the circulation following therapy with antineoplastic agents has been well documented (71-74). Both acute (within hours) and chronic (days to weeks) myocardial toxicity manifested by ischemia, arrhythmias, myocarditis, pericarditis, cardiomyopathy, and or MI after dosing with the anthracyclines 5-fluorouracil, doxorubicin, and daunorubicin have been associated with minimal and large increases in cTnl. Reports have documented that a medication dose-dependent pattern of myocyte injury is responsible for increases in troponin, even without electrocardiographic or echocardiographic abnormalities. Studies have shown that in patients undergoing high-dose chemotherapy, an increase in cardiac troponin...

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.

Epidemiology of Reproductive Toxicology

Antimicrobials, antiemetics, theophylline, caffeine, ethanol, and nicotine. From 15 to 25 of pregnant women report licit drug use (ethanol > nicotine), or illicit drug use (marijuana > cocaine > heroin), or have positive urine drug screens during pregnancy. Analgesics, vitamins, iron, antibiotics, theoph-ylline, and psychotropic medications account for 50 to 80 of all reported toxic ingestions by pregnant women.

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...

Testing Programs for Athletes

Despite the long history of drug abuse in sports and in the workplace, laboratory testing to detect drug use is a modern phenomenon. Only since 1967 has the International Olympic Committee Medical Commission banned certain drugs and tested for their use. Full-scale drug testing for doping by athletes began in the 1972 Munich Games. Since 1967, the number of banned substances has grown every year, and the sophistication of laboratory analysis and testing protocols has advanced.

Testing Programs in Occupational Settings

The five substances routinely tested for include marijuana, cocaine, amphetamines, opiates, and PCP. Other drugs, such as alcohol, may be added to the panel if suspected by the employer from objective evidence (i.e., slurred speech, alcohol on the breath). Keeping with the Rule of Fives, there are five situations in which drug testing is conducted (1) preemployment, (2) random, (3) postaccident, (4) probable cause, and (5) return to work follow-up. The employer may request testing for additional substances in the case of postaccident, reasonable suspicion, and return-to-work situations. In order to undergo this additional testing, the employee must be notified via an official Employee Drug Policy document. Recognizing the high prevalence of alcohol abuse, ethanol testing was mandated in a 1994 amendment. There are separate regulations for alcohol testing, including not requiring MRO participation.

Case Example Illustrating Common Obstacles

Sam was a 34-year-old unemployed European American male with a college education. He had a long history of alcohol and drug abuse, starting with his first drink at the age of 8. In addition, Sam had an extensive history of being physically and sexually assaulted. At the time he sought treatment, he had already been abstinent from alcohol and drugs for 6 months, due to a previous traumatic incident. Thus, at his initial assessment, Sam met criteria for PTSD, major depressive disorder, and polysubstance dependence in early full remission. The index event that brought him into treatment this time was a more recent assault, which included a sexual assault. The CPT treatment then began, and during the first session, the therapist explained the symptoms of PTSD, gave a rationale for treatment, described the course of the therapy, and explained the first homework assignment, which was to write an Impact Statement about the meaning of the index assault.

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.

Behavioral Environmental Modification

Although medication development for the treatment of drug addiction has been highlighted in this chapter, a brief discussion of the importance and role of behavioral therapy must be included for completeness. Indeed, drug addiction results from human behavior gone awry, and in most cases addicts who seek recovery from their addiction are more successful if they also engage in some form of behavioral environmental modification. The literature is vast on the topic of conditioned behavior and no attempt to further describe it will be made herein. However, as mentioned in the Introduction of this chapter, environmental factors and associations play a large role in relapse, and clinical intervention in the form of therapy and behavioral modification are proving successful.66 Recent investigations have shown that concepts of rewarding and aversive mechanisms can be applied to therapy, which, if available, can further be paired with pharmacotherapy.67 In contingency management,...

Imaging Of Postsynaptic Da Receptors

PET with RAC is capable of measuring synaptic DA release from embryonic nigral transplants. This was performed in a PD patient demonstrating the sustained and marked clinical improvement, as well as gradual increase of FDOPA uptake to normal during a period of 10 yr after grafting in the unilateral putamen (95). RAC binding to DA D2 receptors was measured with saline or methamphetamine infusion. Binding at baseline was normal in the grafted putamen but upregulated in the

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...

Substance Induced Mania

Substances known to induce mania include sympathomimetic agents (iproni-azid, procarbazine), psychostimulants (e.g., amphetamines, methylphenidate, cocaine, phencyclidine), tricyclic antidepressants, monoamine oxidase inhibitors, levodopa, yohimbine, bromide, alprazolam, corticosteroids, and many other substances (Table 3 11). In this regard, hypomania or mania that begins during or within 1 month of treatment with one or more of the medications listed here should be considered substance induced.

Differential Diagnosis of Sympathetic Toxidromes

Figure 9.4 Noncardiogenic Pulmonary Edema Crack Cocaine Injection. Frontal chest radiograph that demonstrates normal size and configuration of the cardio-mediastinal silhouette and bilateral diffuse pulmonary edema following the intravenous injection of crack cocaine. Noncardiogenic pulmonary edema may also follow opioid overdoses with the same radiographic patterns. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.) Figure 9.4 Noncardiogenic Pulmonary Edema Crack Cocaine Injection. Frontal chest radiograph that demonstrates normal size and configuration of the cardio-mediastinal silhouette and bilateral diffuse pulmonary edema following the intravenous injection of crack cocaine. Noncardiogenic pulmonary edema may also follow opioid overdoses with the same radiographic patterns. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.) Toxins Cocaine, phenycyclidine (PCP), amphetamines,...

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...

Clinical Findings CT Radiographic and MR

Crack cocaine inhalation intracranial and interventricular hemorrhage. Intravenous crack cocaine abuse septic cerebral emboli with multiple brain abscesses. Crack cocaine inhalation radiolucencies throughout the left lung interstitium. Intravenous crack cocaine abuse dissecting thoracic aneurysm. Intravenous cocaine abuse fatal mesenteric infarction with small bowel perforation. Figure 9.10 Dissecting Thoracic Aneurysm. Contrast-enhanced, Tl-weighted, sagittal-oblique, computerized axial tomogram (CT) of the chest that demonstrates an intimal flap dividing the descending thoracic aorta into true and false lumens consistent with dissecting thoracic aneurysm Type B in an intravenous cocaine abuser. (Courtesy of Carlos R. Gimenez, M.D., Professor of Radiology, LSU School of Medicine, New Orleans, LA.)

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...

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 .

Utility of Event Related Potentials in Substance Abuse Research

Herning et al., 1990), they can provide additional information on subtle cognitive impairments during acute intoxication that may not be severe enough to be identified by these other measures. Also, repeated ERP testing after drug administration can provide important information on the duration of the drug's effects on cognition. For instance, we have found that acute administration of cocaine (0.9 mg kg) results in a significant reduction in P300 amplitude as early as 10 min post-cocaine administration. These impairments persist for about 40 min and are still present when most of the subjects no longer report feeling intoxicated. This example illustrates the utility of ERPs when studying the acute effects of drugs of abuse and highlights the importance of combining electrophysiological measures with behavioral and subjective tests. Because ERPs are sensitive indices of the functional integrity of the brain (Hillyard et al., 1978 Donchin, 1979), they are also useful measures of...

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 .

Caveats in Interpreting Electrophysiologic Data in Substance Abuse Research

Perhaps the most important aspect regarding the usefulness of EEG and ERP measures in substance abuse research is the issue of specificity. Namely, whether the electrophysiological changes observed are unique to the specific drug or condition tested. Most of the data available to date suggests that EEG and ERP measures have limited diagnostic specificity. For instance, acute administration of either ethanol, cocaine or marihuana all result in significant increases in alpha activity (Lukas et al., 1986, 1990, 1991, 1995), these increases are not only indistinguishable from each other but are also similar to those observed during transcendental meditation (Lindsley, 1952 Brown, 1970 Wallace, 1970). Given the association between alpha activity and pleasurable states, these findings suggest that the drug-induced increases in alpha activity represent a neurophysiologic response associated with reinforcement in general. Even though electrophysiological measures are not always specific...

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.

Initial Evaluation Of The Patient With Substance Use Disorders

Team and be used to develop the safest possible treatment plan. The clinician should ask about specific illicit substances such as heroin, cocaine, marijuana, and the club drugs (see below). For taking a history of alcohol use, some clinicians have suggested the use of the CAGE questionnaire (Ewing, 1984) 1. Can you cut down on your drinking 2. Are you annoyed when asked to stop 3. Do you feel guilty about your drinking 4. Do you need an eye-opener when you wake up in the morning One should also ask about sedative or stimulant use, whether prescribed or nonprescribed, and any dietary supplements or herbs the patient may be taking. A substance abuse review of systems, focusing on renal, cardiac, gastrointestinal, and, for HIV patients especially, neurological symptoms, is essential. Other points of inquiry are the date the substance was first used patterns, amount, and frequency of use and routes of administration and reactions to the use. The time of last use is important to know to...

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,...

In Search and Discovery of Potential New Therapeutic Indications

Despite its stimulant activity, modafinil did not produce reinforcing or rewarding effects and did not modify the effects of cocaine in rats.97 Evaluation for cocaine-like discriminative stimulus effects in rats and for reinforcing effects in rhesus monkeys maintained on intravenous cocaine self-administration demonstrated that the reinforcing and discriminative stimulus effects of modafinil required very high doses.98 The low abuse potential was confirmed via an extensive data set in healthy human volunteers23,99 and in volunteers with a recent history of cocaine abuse where cocaine and methylphenidate, but not modafinil, produced cocaine-like discriminative stimulus, subject-rated, and cardiovascular effects.100 Based on the low potential of addiction and dependence, a preliminary study provided evidence that modafinil improved clinical outcome when combined with psychosocial treatment for cocaine dependence.101 An anecdotal story in a woman outpatient with social phobia and...

Stephen L Dilts Jr Stephen L Dilts

The history of opioid use goes back thousands of years in human history. The Ebers Papyri from approximately 7000 B.C. refer to the use of opium in children suffering from colic (Deneau & Mule, 1981). In the Victorian era, the use of laudanum was socially acceptable. In the present day, opioids use is stringently regulated, especially in the United States however, demand by addicts results in the existence of a black market characterized by crime, disease, poverty, and loss of personal and social productivity. The sexually promiscuous intravenous heroin user is at high risk to contract and effectively spread the deadly acquired immune deficiency syndrome (AIDS) virus, as well as venereal and other infectious diseases, such as hepatitis C. High overall death rates are associated with opioid abuse, approximately 10-15 per 1,000 in the United States (Jaffe, 1989). The Drug Abuse Warning Network (Substance Abuse and Mental Health Services Administration, 1995) indicates an alarming...

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...

Psychosocial Treatments

Although this chapter has presented only pharmacotherapies for opioid addiction, it is crucial that psychosocial interventions be used to help these patients change their lifestyles. It is generally accepted that escape from drug seeking and the accompanying antisocial impulses requires a change in deeply rooted behavioral patterns. Individual and group psychotherapy may be useful in approaching this goal. Contingency management may be very helpful (Robles, Stitzer, Strain, Bigelow, & Silverman, 2002). The various 12-step programs such as Narcotics Anonymous are also useful adjuncts to treatment and facilitate significant degrees of change. For those persons who continue to relapse in less restrictive treatment settings, a therapeutic community may be the appropriate next step (O'Brien & Biase, 1981) these nonhospital, community-based, 24-hour, live-in programs are geared to subject the addict to continuous treatment pressure for as long as 1 or 2 years. Personal freedom is...

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.

And Repeated Maternal Separations

The elegant studies of Liu et al. (42), Meany et al. (43), and Plotsky (44) have demonstrated permanent effects of repeated maternal separation on neuroendocrine regulation and behavior. Repeated separations of neonatal rats from their mothers for 180 min compared with non-separated controls or those separated for 15 min have revealed that these animals are hypercor-tisolemic as adults, at least partly based on increased corticotropin releasing factor (CRF) excretion. Most interestingly, these animals show anxiety in open-field situations and are also more prone to the acquisition of alcohol and cocaine self-administration compared with their littermate controls. The hypercortisolemia, anxious behaviors, and vulnerability for substance abuse are all reversible with chronic treatment with serotonin-selective antidepressants. However, when these treatments are discontinued, the hypercortisole-mia and proneness to substance abuse returns.

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,...

Major Depressive Disorder

Similarly, interpersonal therapy (IPT) has demonstrated efficacy in treating major depressive illness in HIV disease (Markowitz et al., 1992, 1995), and IPT may offer advantages to patients who have been recently diagnosed with HIV AIDS or have recently progressed in their disease severity. IPT is notable for its brevity and can successfully focus on the common problems encountered in HIV disease, including grief, changes of life after disease diagnosis, role identity during times of illness progression, interpersonal disputes related to family strife surrounding diagnosis, issues of homosexuality or drug abuse, and support of existing coping strategies.

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...

Psychiatric Comorbidity And Sequelae

More than one-half of all cocaine abusers meet criteria for a current psychiatric diagnosis and nearly three-fourths for a lifetime psychiatric diagnosis (Ziedonis, Rayford, Bryant, Kendall, & Rounsaville, 1994). The most common comor-bid psychiatric diagnoses among cocaine abusers include alcohol dependence, affective disorders, anxiety disorders, and antisocial personality disorder (Kleinman et al., 1990 Marlowe, Husband, Lamb, & Kirby, 1995 Mirin, Weiss, Griffin, & Michael, 1991 Rounsaville et al., 1991 Weiss, Mirin, Griffin, Gunderson, & Hufford, 1993). For most cocaine users, co-occurring psychiatric disorders (including agoraphobia, alcohol abuse, alcohol dependence, depression, posttraumatic stress disorder (PTSD), simple phobia, and social phobia) precede cocaine use (Abraham & Fava, 1999 Shaffer & Eber, 2002). The most frequent co-occurring substance use disorder is alcoholism 29 of cocaine abusers have a current alcoholism diagnosis, and 62 a lifetime...

Obstetric And Developmental Effects

In the United States, more than 100,000 babies are exposed prenatally to cocaine each year (Office of the Inspector General, 1990). Increasing evidence indicates that prenatal cocaine exposure is associated with negative perinatal outcomes, including premature delivery, low birthweight, microcephaly, newborn behavioral abnormalities, and possible long-term cognitive and developmental difficulties (Singer et al., 2002). However, the impact of cocaine on the developing fetus is difficult to ascertain, because no confined, homogeneous, syndromic pattern of malformations has been identified, and because the mechanisms by which cocaine impacts on the unborn child are complex maternal cocaine use may have both indirect and direct effects on a developing fetus (Vidaeff & Mastrobattista, 2003). Indirect effects of maternal cocaine use include negative health consequences for mothers, which then impact their pregnancies. Women using cocaine are more likely to suffer arrhythmias, cardiac...

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...

Distinguishing Medical And Nonmedical Use Of Benzodiazepines

Is the substance used to treat a diagnosed medical problem, such as anxiety or insomnia, or is it used to get high (or to treat the complications of nonmedical use of other drugs) Typical medical use of a benzodiazepine or other controlled substance occurs without the use of multiple nonmedical drugs, whereas nonmedical use of the benzodiazepines is usually polydrug abuse. Although alcoholics and drug addicts sometimes use the language of medicine to describe their reasons for using controlled substances nonmedically, self-administration or self-medication of an intoxicating substance outside the ordinary practice boundaries of medical care is a hallmark of drug abuse (DuPont, 1998). 5. Pattern. What is the pattern of the controlled substance use Typical medical use of controlled substances is similar to the use of penicillin or aspirin, in that it occurs in a medically reasonable pattern to treat an easily recognized health problem other than addiction. Typical use of...

Medical Use And Abuse

Workplace drug testing is usually limited to identification of marijuana, cocaine, morphine-codeine, amphetamine-methamphetamine, and phencycli-dine (PCP). However, benzodiazepines and barbiturates may be added to the test panel. Laboratory positive test results for patients with legitimate prescriptions for benzodiazepines and barbiturates are reported to employers by medical review officers (MROs) as negative, as are other laboratory results that reflect appropriate medical treatment with other controlled substances (MacDonald, DuPont, & Ferguson, 2003).

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.

Identification Of Problems Among Longterm Benzodiazepine Users

Medical and nonmedical substance use. Is the benzodiazepine dose the patient is taking reasonable Is the clinical response to the benzodiazepine favorable Is there any use of nonmedical drugs, such as cocaine or marijuana Is there any excessive use of alcohol (e.g., a total of more than four drinks a week, or more than two drinks a day) Are other medicines being used that can depress CNS functioning 2. Medical and nonmedical substance use. Is the dose of the benzodiazepine the patient is taking reasonable Is the clinical response to the benzodiazepine favorable Is there any use of nonmedical drugs, such as cocaine or marijuana Is there any excessive use of alcohol (e.g., a total of more than four drinks a week, or more than two drinks a day) Are there other medicines being used that can depress the functioning of the CNS

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.

Descriptive Approaches

Most broadly, the literature frequently describes polydrug use or poly-substance use. This nondiagnostic designation generally describes the use of multiple substances rather than framing the use and its effects in clinical terms, which is the intent of diagnosis. As such, polydrug use describes, at minimum, the use of multiple substances, whether licit or illicit. In the treatment research literature, polydrug use is often used to describe the lifetime number of drugs regularly used to a threshold SUD, in addition to the index substance (Ball, Carroll, Babor, & Rounsaville, 1995 Feingold, Ball, Kranzler, & Rounsaville, 1996). However, in other than addiction or mental health treatment settings, the expressions polysubstance use or polysubstance abuse are frequently meant to describe the use by subjects of as few as two substances, such as cocaine and alcohol, alcohol and cannabis, or opiates and cocaine (Ross, Kohler, Grimley, & Bellis, 2003). In a more differentiated...

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