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...

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Neural Substrates Of Cocaine Abuse

A critical issue for the understanding of drug dependence is what neurochemical changes occur during the various phases of the course of addiction. Psychostimulant dependence has been a major focus of investigation, especially following the cocaine epidemic of the 1980s. Despite early misconceptions that considered cocaine as a recreational drug devoid of abuse and addictive potential, the recent cocaine epidemic has revealed the harmful consequences of cocaine use and its high abuse liability. Therefore, much experimental attention has been devoted over the past two decades to the search for the neural substrates responsible for cocaine abuse. With the use of experimental models of intravenous drug self-administration, it has become clear that cocaine and other psychostimulant drugs such as amphetamine are readily self-administered by various species of laboratory animals (1). The acute reinforcing properties of psychostimulant drugs appear to depend on dopamine neurotransmission...

The Role of mGluR5 in the Effects of Cocaine Implications for Medication Development

Investigations over the past several years have yielded insights into the contributions of metabotropic glutamate receptors (mGluRs) to the effects of psychostimulants. Recently, an important role was demonstrated for the mGluR subtype 5 in the locomotor stimulant and reinforcing effects of cocaine (1). The data obtained in that report will be summarized here, followed by a brief discussion of the implications of this evidence for the development of medications to treat cocaine dependence. Fig. 1. Locomotor response to cocaine administration in mGluR5 (+ +) (n 14) and (- -) (n 16) mice. Horizontal activity was measured during a 45-min period and was calculated as a percentage of baseline locomotor activity (vehicle treatment during the same period). Values represent mean activity counts SEM.*, P 0.05 versus saline vehicle **, p 0.01 versus vehicle. (Dunnett's test after two-way repeated measures analysis of variance) Reprinted with permission from Chiamulera et al. (1). Fig. 1....

Role Of Glutamate In The Conditioned Effects Of Cocaine

Although dopamine appears to be important for the formation of both the associative and nonasso-ciative components of sensitization, it has become apparent that other neurotransmitter systems are involved as well. Of particular importance is glutamate. Karler and colleagues (25,26) were the first to report that the development of sensitization to cocaine and amphetamine in mice was prevented by pretreatment with MK-801, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) type of It is likely that glutamate is also involved in the associative process underlying the development of cocaine-induced conditioned increases in locomotor activity that contribute to behavioral sensitization. Sensory information from conditioned stimuli, for example, needs to gain access to meso-accumbens DA neurons, which we, as well as others, have implicated in the acquisition and expression of conditioned psychomotor stimulant effects. Likewise, these neurons need to ultimately activate motor...

In Cocaine and Opioid Dependence

In the last 10 yr, a substantial amount of preclinical research has been dedicated to studying the role of excitatory amino acids, in particular, glutamate, in laboratory models of alcohol and drug dependence (1-4). As a result, we now have a wealth of information suggesting that glutamatergic neurotransmission is a major component of the neuroadaptive changes that mediate the development, maintenance, and expression of patterns of animal behavior that are believed to be a model of human alcohol and drug dependence. The data are sufficient to warrant further research that would apply this preclinical knowledge to the clinical field and advance the development of potential pharmacothera-peutics (cf. ref. 5). In this chapter, background information will be presented on the stages of clinical medication development and will review available human data relevant for the medication development for opioid and cocaine dependence. Opioid and cocaine dependences are complex behavioral disorders...

Glutamatedependent Synaptic Plasticity And Cocaine Addiction

An issue that deserves dedicated attention is the possibility that the relative contribution of excitatory amino acid neurotransmitters may become particularly significant during specific periods of exposure to cocaine. Excitatory amino acids are considered critical mediators of neural plasticity within the central nervous system, and this makes them ideal candidates as participating agents in the development of adaptive changes, which may represent integral parts of the addictive process In experiments where behavioral techniques were used in combination with electrophysiological analysis, evoked field responses measured in the nucleus accumens shell after stimulation of fimbria afferents were examined in rats exposed to the very first days of self-administration of cocaine. Significantly increased paired-pulse facilitaion of a specific component of the potential (a long-latency component termed P25) as well as a marked potentiation of the same potential after tetanic stimulation of...

Glutamate Neurotransmission And Cocaine Abuse

To investigate more closely the physiological significance of these observations, the reinforcing and locomotor-activating effects of psychostimulant drugs were tested after temporary reduction of nucleus accumbens excitatory amino acid neurotransmission obtained through local infusion of glutamate receptor antagonists. Microinfusion of both NMDA and non-NMDA receptor antagonists within the nucleus accumbens reduced the expression of the acute psychomotor-activating properties of cocaine and amphetamine administered systemically or amphetamine and dopamine infused into the nucleus accumbens (48-50) as well as novelty-induced locomotion in rats (51,52). These findings suggest that intact glutamate neurotransmission within the nucleus accumbens may be essential for the full expression of the acute locomotor-activating properties of psychostimulant drugs (53). Similarly, earlier studies pointed toward a tonic permissive role of excitatory amino acid in the expression of the acute...

Methamphetamine Manufacture

Either (-)-ephedrine or (+)-pseudoephedrine can be used to make meth-amphetamine by reductive dehalogenation using red phosphorus as a catalyst. If (-)-ephedrine is used as the starting material, the process will generate (+)-methamphetamine. If psuedoephedrine is used, the result will be dextromethamphetamine (136). As this synthetic route has become nearly universal, both state and federal governments have enacted laws limiting the amount of pure ephedrine or pseudoephedrine that can be purchased.

Cocaineinduced Convulsions

The incidence of convulsions in individuals who abuse cocaine is significant. Cocaine-induced convulsions can result from exposure to large doses of cocaine, typically in an overdose situation. In addition, convulsions can manifest as a result of kindling, in which increased sensitivity to cocaine is produced upon repeated exposure to the drug, eventually leading to seizures upon exposure to doses of cocaine that had previously been subconvulsive. These cocaine-kindled seizures have been associated with concomitant increases in NMDA receptor binding in the brain (47,48). In addition, NMDA receptor antagonists have been reported to significantly attenuate kindled seizures resulting from subchronic exposure to cocaine (47,49,50). V-methyl-d-aspartate receptor antagonists have also been reported to attenuate convulsions resulting from acute exposure to cocaine. The results from the acute studies are summarized in the subsections that follow. Most of the acute studies employ a similar...

Neurobiology Of Cocaineinduced Conditioned Increases In Locomotor Activity

We have employed a relatively simple design in some of our studies to evaluate the behavioral and neurobiological variables regulating the acquisition and expression of cocaine-induced conditioned effects. Basically, three groups of rats are employed in this paradigm. In its simplest form, on d 1 the first groups of rats (PAIRED) is injected with cocaine (30-40 mg kg ip) prior to placement in locomotor activity chambers (scented with peppermint) for 30 min. One hour following return to their home cages, these rats are injected with saline. The second group (UNPAIRED) is treated in a similar fashion, but receives saline prior to placement in the locomotor activity chamber and cocaine in the home cage. The third group (CONTROL) receives saline in both environments. On d 2, all rats are challenged with either saline or 10 mg kg of cocaine prior to placement in the locomotor activity chamber. In some of our studies, the training sessions were increased to 3, 5, or 7 d when it was...

Blockade Of Cocaineinduced Conditioned Effects With Mk801

Conditioned effects of cocaine were established and evaluated using the paradigm described above in which PAIRED, UNPAIRED, and CONTROL animals are employed. In the initial study, we used a 1-d conditioning procedure to evaluate the effects of MK-801 on the acquisition of cocaine-conditioned increases in locomotor activity. PAIRED rats were pretreated with either saline or various doses of MK-801 (0.25-1.0 mg kg ip) 30 min prior to injections of 40 mg kg of cocaine ip and then placed in activity chambers scented with peppermint for 30 min. One hour following return to their home cages, these rats received two saline injections separated by 30 min. UNPAIRED rats received two saline injections separated by 30 min prior to placement in the activity chamber and either saline or MK-801 injections 1 h after return to their home cages, followed by a second saline injection 30 min later. When tested with 10 mg kg of cocaine on d 2, PAIRED rats pretreated with saline expressed conditioned...

Cocaineinduced Lethality

Ideally, pharmacotherapies for the treatment of cocaine overdose should protect against the ultimate toxic endpoint, death. Since death from a cocaine overdose can occur suddenly or with short latency, a Fig. 5. Effect of NMDA glycine-site antagonists on cocaine-induced lethality. Pretreatment (white bars) of mice with NMDA glycine-site antagonists (ACEA1021, ACEA1031, and ACEA1328) significantly reduces the percentage of animals that die following a normally lethal dose of cocaine (saline bars). A comparably significant reduction in deaths from a cocaine overdose is observed even when mice are posttreated (dark bars) with NMDA glycine-site antagonists. Antagonist treatments resulting in reductions of 50 or greater are statistically significant. Includes data previously reported (51,52). Fig. 5. Effect of NMDA glycine-site antagonists on cocaine-induced lethality. Pretreatment (white bars) of mice with NMDA glycine-site antagonists (ACEA1021, ACEA1031, and ACEA1328) significantly...

Causes and symptoms

A second cause of anti-anxiety drug abuse is the use of these drugs, especially when combined with other drugs, such as cocaine. It is not uncommon for an addict to pair the use of a stimulant, such as cocaine or metham-phetamine, with a CNS depressant. This allows the user to feel alert for an extended period of time, and then be able to come down from the high, and even fall asleep.

Characteristics of HIV infection in childhood

More than 95 of children are infected by perinatal transmission of the virus from the mother to the child (vertical infection). Transmission by transfusion, sexual transmission and drug abuse are much less prevalent. In most cases (75-90 ) HIV is transmitted peri- or intrapartum. Only a small proportion of children are infected in utero (10-25 ). Transmission by breastfeeding is important in resource-poor settings, but plays a minor role in developed countries, where breastfeeding by known HIV-infected mothers is strongly discouraged. The increasing knowledge about how HIV is vertically transmitted has led to a highly effective transmission prophylaxis and significant reduction of the transmission rate to less than 2 . However, new infections in HIV-exposed children still occur

Activitydependent Synaptic Plasticity And The Induction Of Behavioral Sensitization In The Ventral Tegmental Area

LTP is expressed as a potentiation of AMPA receptor transmission (67,68). If the early phase of sensitization is associated with LTP at synapses onto midbrain DA neurons, the DA neurons should exhibit increased responsiveness to AMPA. To test this, single-unit recording studies examined the responsiveness of VTA DA neurons to glutamate agonists either 3 or 14 d after discontinuing repeated administration of cocaine or amphetamine (69,70). When glutamate or AMPA was applied directly to DA cell body regions by microiontophoresis, DA neurons recorded from amphetamine- or cocaine-treated rats showed enhanced excitatory responses compared to neurons recorded from saline controls. No difference was observed in responsiveness to NMDA. The enhanced responsiveness to glutamate and AMPA dissipated after 10-14 d of withdrawal, consistent with a role in induction mechanisms. augmented response to AMPA was transient, because it was present 3 d, but not 10-14 d, after the last injection. It was...

Integrating Diagnostic Levels

Any outstanding features that distinguish the diagnostic status of the patient can be added to the diagnostic statement. This addition enables the diagnostic summary to reflect more accurately the major factors of personality functioning for example, the addition of an indication of depressive features to any diagnostic formulation where this is appropriate. Information concerning a subject's alcohol abuse or drug addiction might also be appended in cases in which these involvements are known and have influenced the test results sufficiently to warrant reporting of associated findings.

Collisioninduced Dissociation

An interesting application of CID involves the use of on-line CF dialysis TSP coupled with MS MS for quantitative screening of drugs in plasma (107). The potential utility of the method was demonstrated by the quantitative analysis of the anticancer drug rogletimide in the plasma of patients after treatment. In-vivo microdialysis and TSP MS MS of the dopamine uptake blocker (GBR-12909) was conducted in the rat (108). The maximum concentration of GBR-12909 in the brain for a dose of 100 mg kg i.p. was determined to be 250 nmol L, with the maximal concentration occurring approximately 2 h post injection. This represents a 40-fold lower concentration of GBR-12909 in the brain as compared to cocaine concentrations obtained at a dose of 30 mg kg. The authors suggested that this could explain the discrepancy between relative in-vivo and in-vitro potencies of the two drugs. A combination of microdialysis and FAB MS MS was used to follow the pharmacokinetics of penicillin G directly in the...

Thiamin Deficiency Affects the Nervous System Heart

Thiamin deficiency can result in three distinct syndromes a chronic peripheral neuritis, beriberi, which may or may not be associated with heart failure and edema acute pernicious (fulminating) beriberi (shoshin beriberi), in which heart failure and metabolic abnormalities predominate, without peripheral neuritis and Wernicke's encephalopathy with Korsakoff's psychosis, which is associated especially with alcohol and drug abuse. The central role of thiamin diphosphate in

Ginseng And Morphine And Related Opioids

More recent work by Kim et al. (1995) confirmed the potential value of ginseng total saponins at 200 mg kg intraperitoneally in rodents in the prevention and therapy of the adverse reactions of morphine, ginseng total saponins being able to inhibit the development of sensitivity or reverse tolerance to the ambulatory-accelerating effect of morphine and to prevent the development of dopamine supersensitivity caused by chronic administration of morphine (10 mg kg per day for 7 days). Similarly, in mice, ginseng total saponins blocked the development of reverse tolerance to the ambulation-accelerating effect induced by the CNS stimulant methamphetamine (2 mg kg, subcutaneously) and also prevented the development of dopamine receptor supersensitivity induced by the chronic administration of methamphetamine. As ginseng saponins oppose the development of reverse tolerance to both morphine and methamphetamine as well as inhibiting dopamine supersensitivity, it was suggested that reverse...

Drugs Of Abuse Influence Synaptic Plasticity In The Nucleus Accumbens

One question is whether chronic drug exposure alters the likelihood of LTP or LTD in a manner that outlasts the presence of drug in the brain. Pulvirenti et al. (108) compared evoked field responses in the NAc after stimulation of fimbria afferents in rats exposed to either 1 or 5 d of cocaine self-administration and found that the acquisition of cocaine-seeking behavior is associated with enhancement of hippocam-pal-accumbens transmission. Thomas et al. (109) treated mice for 5 d with cocaine, challenged with cocaine after 10-14 d withdrawal to demonstrate behavioral sensitization, and prepared slices of NAc 1 d later. Although no changes in the size of field EPSPs were found, cocaine-treated mice showed a reduction in the amplitude of AMPA receptor-mediated quantal events, specifically at synapses activated by cortical afferents. This was found in the shell but not core. No changes in NMDA receptor-mediated synaptic responses or the probability of transmitter release were observed....

Typical vs Atypical Ischemia

Once we consider it more likely than not that this patient had ischemic disease, the question of whether it was typical or atypical is somewhat more difficult to ascertain. First, it is necessary to define these two terms. Typical ischemic heart disease is generally considered secondary to coronary atherosclerosis, with atherosclerotic plaque (s) narrowing the lumen and causing damage to the coronary artery wall. The presence of atherosclerosis may increase the possibility of superimposed coronary artery lesions including acute plaque hemorrhage or rupture, luminal thrombosis, and or coronary artery spasm. The presence of atherosclerosis does not provide information concerning the pathogenesis of the plaque, whether it is idiopathic but associated with cigarette smoking, hypercholesterolemia, hypertension, or diabetes mellitus (or combinations of all of these), or whether it may be secondary to less common risk factors such as hyperhomocysteinemia, cocaine use, or radiotherapy (chest...

Health Outcomes Of Stressful Life Events

Life Events Theory Health Psychology

The other major pathway is represented by health-compromising behaviors. People under stress might want to relieve their tension by consuming more tobacco, illicit drugs, alcohol, and so on. They feel too absorbed by their stress to monitor their diets and to maintain other preventive behaviors. Adherence to routine self-care might suffer during a stress episode. Among smokers, stress may increase the number of cigarettes consumed as well as the intensity of smoking by deep inhaling. When under stress, women seem to be more likely to engage in unhealthy eating behaviors, whereas men tend to turn to drinking and illicit drug use (Brannon & Feist, 1997).

Reward Deficiency Syndrome

Individuals tend to be at risk of multiple addictive, impulsive and compulsive behavioural problems, such as severe alcoholism, cocaine, heroin, marijuana and nicotine addiction, pathological gambling, sex addiction, chronic violence, posttraumatic stress disorder, risk taking behaviours and antisocial behaviour. As such, the use of tyrosine as a precursor to dopamine has a theoretical basis for use in this condition (Blum etal 2000). Drug withdrawal Tyrosine has been used to aid in the withdrawal of cocaine, caffeine and nicotine. Anecdotal reports suggest it is successful however, large controlled studies are not available to determine clinical significance. L-tyrosine supplementation has been considered because chronic cocaine use is believed to cause catecholamine depletion and cocaine withdrawal has been associated with major depression. To date, results from trials using tyrosine as a stand-alone treatment during cocaine withdrawal have produced disappointing results (Chadwick...

Special Populations Of Urban Lgbt People

In addition to race and immigration status, the age of urban LGBT people may impact the incidence of health problems as well as their access to health care. LGBT youth leave home more often than their heterosexual peers and make up a disproportionate percentage of the homeless youth population (Cochran, et al., 2002). Many of these young people are drawn to cities for the same reasons as LGBT adults. Regardless of where they live, LGBT youth face a number of challenges, including a host of elevated risk behaviors. Population-based studies of high school students have shown that LGB youth are more likely to report attempted suicide use tobacco, alcohol, and cocaine share syringes and have multiple sexual partners in the past three months (Goodenow, et al., 2002 Robin, et al., 2002). Despite their vulnerability to health problems, LGBT young people who are estranged from the families face legal barriers to receiving benefits and health care (Office of Gay and Lesbian Health, 1999). Not...

Polysubstance dependence

Polysubstance dependence is listed as a substance disorder in the Diagnostic and Statistical Manual of Mental Disorders published in 2000 (also known as the DSM-IV-TR). The DSM-V-TR is the latest revision of the manual that it is used by mental health professionals to diagnose mental disorders. When an individual meets criteria for dependence on a group of substances (at least three different types used in the same 12-month period) he or she is given the diagnosis of polysubstance dependence. For example, an individual may use cocaine, sedatives, and hallucinogens indiscriminately (i.e., no single drug predominated there was no drug of choice ) for a year or more. The individual may not meet criteria for cocaine dependence, sedative dependence, or hallucinogen dependence, but may meet criteria for substance dependence when all three drugs are considered as a group. Individuals who abuse alcohol and other drugs usually meet criteria for substance abuse and or dependence for each...

With Franco Tagliaro Zdeneck Deyl and Ivan Miksfk

These authors reported high efficiency separations of heroin, heroin impurities, degradation products, and adulterants (Fig. 8.1). Also discriminated were acidic and neutral impurities present in heroin seized by law enforcement agencies, as well as in illicit cocaine samples, with resolution of benzoylecgon-ine, cocaine, cis- and frans-cinnamoylcocaine. MEKC was also used with a broad spectrum of other compounds of forensic interest, including psilocybin, morphine, phenobarbital, psilocin, codeine, methaqualone, lysergic acid diethylamide (LSD), amphetamine, chlordiazepoxide, methamphetamine, lora-zepam, diazepam, fentanyl, phencyclidine hydrochloride (PCP), cannabidiol, and tetrahydrocannabinol (THC), which were all separated with baseline resolution.

A126 Electrospray ionization

In one application of ESI, ion-complexing agents such as cyclodextrins, oligosaccharides, bafilomycin, and a crown ether were made charged by the addition of sodium, potassium, rubidium, or cesium ions.20 Thanks to improved ionization-mass spectrometer interfaces such as orthogonal injection, electrospray has also been coupled to time-of-flight mass spectroscopy to create a rugged instrument capable of analyzing mass ranges up to and beyond 10 kDa.21 One typical application of ESI-TOF in high-speed separations is the analysis of peptides, benzodiazepines, heroin, cocaine and paraquat.22 A peptide mixture of 2 fmol formed from the tryptic digests of either P-galactosidase or yeast glucose-6-phosphate dehydrogenase was analyzed by electrospray using a modified triple quadrupole spectrometer equipped with a source designed for nL min flows.23 Peptides from yeast glucose-6-phosphate dehydrogenase were sequenced by MS MS. Pronucle-otides in biological media were analyzed in an on-line...

Ethical Issues in the Quality of Care

Because of the role that behavior plays in the occurrence of many of today's health problems, it has been suggested that many of these so-called health problems be demedicalized (B. Jennings, 1986). For example, illicit drug use, alcoholism, domestic violence, motor-vehicle accidents, and homicide are ills arising from and impacting upon the whole of society and not just the health care system. Demedicalization is intended to foster a multifaceted and integrated strategy for solving the given problem by utilizing and incorporating other rel

Candidate Mechanisms For Stable Druginduced Changes In The Brain

One such mechanism is a change in the shape or the number of excitatory synapses. This mechanism contributes to long-lasting changes in synaptic strength as a result of LTP and other forms of learning (37). Recently, changes in dendritic spines have been found after chronic drug administration. Repeated treatment with either amphetamine or cocaine increased dendritic branching, spine density, and the number of branched spines in Golgi-stained medium spiny neurons in the NAc and pyramidal neurons in the prefrontal cortex, effects which persisted at least 1 mo (38,39). Very similar alterations were observed in rats allowed to self-administer cocaine for 1 mo (40). Interestingly, nicotine produced effects similar to those found with cocaine and amphetamine perhaps more robust (41) , whereas chronic morphine produced effects opposite to those observed after cocaine or amphetamine, i.e., decreases in spine density and dendritic branching (42). The most important point is that these changes...

Mental Illness and Substance Abuse

Homeless adolescents also have very high rates of mental health problems and substance abuse. In a study from Seattle, 83 of street youths had been physically and or sexually victimized after leaving home, and 18 met criteria for posttraumatic stress disorder (Stewart, et al., 2004). Across the U.S., 55 of street youth and 34 of shelter youth had used illicit drugs other than marijuana since leaving home, in comparison to 13 of youth who had never been runaway or homeless (Greene, et al., 1997). Street youth use a wide range of drugs, including hallucinogens, amphetamines, sedative tranquilizers, inhalants, cocaine, and opiates. Unfortunately, the initiation of injection drug use is quite common, with an incidence rate of 8.2 per 100 person-years among street youth in Montreal (Roy, et al., 2003).

Routine Sampling Of Toxicologic Material

In the author's office, it is usual practice in all autopsies to save 50 mL each of central blood, bile, urine, liver, and brain, plus available femoral vein blood up to 50 mL, and all retrievable vitreous. Approximately half the blood is placed in containers with sodium fluoride as a preservative. Sodium fluoride inhibits both bacterial growth and serum esterases which hydrolyze cocaine postmortem. If commercially available gray-top Vacutainer tubes are not used, 250 mg of NaF can be added to 30 mL containers. Urine Urine is aspirated with a syringe through the dome of the bladder after the peritoneal cavity has been opened. If the bladder is nearly empty, it can be secured by hemostats before incising the dome to facilitate aspiration of the bladder lumen under direct vision. Toxicologists often prefer urine as a specimen for enzyme-multiplied immunotechnique (EMIT) and enzyme-linked immunosorbent assay (ELISA) drug screening, because it can be analyzed without extraction. NaF as a...

Current Promoted Uses

Ephedra was also sold in combination with many other herbs in obscure combinations. Labels frequently listed 10 or 15 different herbs, but, analysis usually disclosed only the ephedra alkaloids and caffeine as present in sufficient quantities to be physiologically active. After several well-publicized accidental deaths, products clearly intended for abuse, such as herbal ecstasy, and other look-alike drugs (products usually containing ephedrine or phenyl-propanolamine designed to look like illicit methamphetamine, but in concentrations higher than recommended by industry or the FDA) were withdrawn from the market. Labels on these products were frequently misleading. For example, one might suppose that a product called Ephedrine 60 contained 60 mg of ephedrine when, in fact, the actual ephedrine content was 25 mg.

Clinical Trials With Sympathomimetic And Serotonergic Drugs That Reduce Food Intake

In 1976 Scoville (4) summarized studies submitted to the FDA to support new drug applications for appetite-suppressing drugs (Table 4). There were over 200 double-blind controlled studies in this database in which subjects were measured serially and in which the data had been submitted to the FDA. These studies involved a number of different anorectic drugs including amphetamine, methamphetamine, phenmetrazine, benzphetamine, phendimetrazine, phentermine, chlor-phentermine, chlortermine, mazindol, fenfluramine, and diethylpropion. There were 4542 subjects on active medication and 3182 subjects on placebo. More than 90 of these studies demonstrated more weight loss on active medication. The dropout rate was 24.3 at 4 weeks and 47.9 at the end of studies that lasted from 3 to 8 weeks or more. Subjects on active medication lost 0.23 kg wk (0.5 lb wk) more than placebo, were twice as

Drug Dependency Assessment

Drug dependency assessment should include information not only on illicit drug use, but also on personal habits and prescription medication use. A patient who takes two tablets of hydrocodone and acetaminophen three times daily will be quite different from a patient who takes six tablets of hydrocodone and acetaminophen once daily. The patient who daily takes everything at once will have a much higher opioid tolerance than a patient who takes the six tablets in divided doses.

Uncompetitive Antagonists

Uncompetitive NMDA-receptor antagonists exhibit evidence of predicted clinical efficacy in a host of models of neurological and psychiatric disorders. For example, a series of uncompetitive antagonists dose-dependently protect against the convulsant effects of cocaine that are not otherwise robustly sensitive to standard anticonvulsant agents (Fig. 2A). At comparable doses, these compounds also produce neurological impairment in the inverted-screen test (Fig. 2B). The potencies of these NMDA antagonists to block the convulsant effects of cocaine are positively associated with their affinities for the ion channel (Fig. 3A). There is also a correlation between binding affinity and propensity to induce ataxia (Fig. 3B). In addition, some of the antagonists produce diverse behavioral effects characterized as dissociative anestheticlike, including locomotor stimulation

Overall Summary And Clinical Implications

Of the various subtypes of glutamate receptor, the NMDA receptor appears the most promising target for the development of drugs to treat acute cocaine overdose. NMDA receptor antagonists significantly attenuate cocaine-induced convulsions and lethality in preclinical studies in rodents. In contrast, AMPA kainate and metabotropic glutamate receptor antagonists are limited in effectiveness on their own against cocaine overdose, but may provide modulatory influences that could be beneficial as part of a polytherapy. An overactivation of NMDA receptors under overdose conditions would be consistent with the appearance of convulsions, respiratory distress, and cardiovascular collapse as major symptoms of a cocaine overdose. All of these systems are regulated by NMDA receptors and are consistent with the established role of these receptors in epilepsy, the maintenance of respiratory rhythms, and cardiovascular function (1-4). Although it is logical that NMDA receptor antagonists would...

No Is Required For The Induction And Expression Of Behavioral Sensitization To Psychostimulants

Sensitization to Cocaine and Methamphetamine 2.2. Effect of 7-Nitroindazole on Cocaine- and Methamphetamine-Induced Sensitization To investigate the role of NO in the development of sensitization to cocaine and METH, we first examined the effect of the nNOS inhibitor 7-nitroindazole (7-NI) on the psychomotor-stimulating effect of these drugs. Swiss Webster mice were injected with (1) vehicle saline (control), (2) vehicle cocaine (15 mg kg) once a day, (3) 7-NI (25 mg kg) cocaine, and (4) 7-NI saline for 5 consecutive days. Injections were paired with the locomotor-activity cages (test cage) on the first day and the fifth day, whereas the other injections were delivered in the home cage. This regimen allowed the development of conditioned locomotion as determined by the administration of saline injection in the test cage (23). Animals treated with vehicle cocaine developed marked locomotor sensitization to a challenge cocaine (15 mg kg) (Fig. 1) and cross-sensitization to...

Nitric Oxide Synthase

Glutamate-gating of NMDA receptors permits Ca2+ entry that specifically activates neuronal nitric oxide synthase (nNOS), a Ca2+-dependent enzyme that catalyzes the synthesis of the free-radical nitric oxide (NO) from l-arginine (180) (Fig. 1). Because NO may act as an intercellular messenger mediating forms of neuronal plasticity, blockade of nNOS could potentially interfere with the long-term consequences of NMDA receptor activation and might thereby have an influence on the behavioral effects of drugs of abuse or on their addictive properties. In fact, the NOS inhibitors N(G)-nitro-l-arginine-methyl ester (l-NAME) and 7-nitroindazole have been shown to block some of the behavioral effects of drugs of abuse, such as stereotypy induced by methamphetamine (181), sensitization to the behavioral stimulant effects of cocaine (182), and maintenance of cocaine self-administration in rats (183). l-NAME also blocks sensitization to the convulsant effects of cocaine in mice, an effect that can...

Hiv1 Infection And Nmda Receptorrelated Neuronal Apoptosis

Addiction to drugs, such as heroin, cocaine, and methamphetamine, is considered to be a major risk factor for HIV infection (22). Furthermore, it has been proposed that abuse of substances that cause by themselves profound alterations in CNS function could also affect the development of HIV-associated dementia (23). An autopsy study detected evidence of HIV encephalitis, including multinucleated giant cells and HIV p24 antigen, more frequently in HIV-positive drug users than HIV-infected homosexual man (24), and cocaine has been implicated in facilitation of HIV entry into the brain (25,26). However, although an effect of substance abuse on HIV-associated dementia appears likely, direct links between drug addiction and HIV-induced brain injury remain to be elucidated (23).

Tuberculosis in the homeless

The reasons for the high incidence of tuberculosis in the homeless and their epidemiological effect in causing new cases are multiple. In spite of a high rate of completion of chemotherapy overall in San Francisco, the highest rates of loss were among the homeless. At least some of these cases continue to be infectious. Many of the persons in this environment are vulnerable to tuberculous infection because of HIV infection or other factors that are more difficult to quantify, such as drug abuse, alcoholism, poor nutrition or generally poor health (Zolopa et al 1994).

Anxiety Disorders and Other Mental Disorders

The rates of alcohol abuse and dependency are reportedly higher in older minorities than non-Hispanic whites, particularly among older males. Data from the ECA (Helzer, Burnam, & McEvay, 1991), for example, indicate lifetime rates of 17.8 among older African American males, in comparison to 10.8 among older Hispanics and 10.4 among non-Hispanic whites. Both older African American and Hispanic males, however, are reported to have higher current rates of alcoholism (2.9 and 6.6 , respectively) than non-Hispanic white males (2.8 ). The rates are highest, however, among older Native Americans, particularly older males. The rates of alcohol abuse and dependency, as well as alcoholism are generally much lower in all groups of older females. The rates of drug abuse and dependency are very low among virtually all older adults, although they constitute a serious problem (Gaw, 1993). Both alcohol and drug abuse, however, may be underecognized in older adults, due to symptoms that may be...

Legal status and availability

Injectable amphetamines are class A, and oral amphetamines class B drugs. They used to be widely prescribed for depression (in the 1950s and 1960s) and for obesity (until quite recently). They are stimulants, and are thus related to cocaine (see below). They are now only licensed for treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents as part of a comprehensive treatment programme, and for narcolepsy or obstructive sleep apnoea syndrome. Inappropriate private prescription by 'slimming clinics' still occurs occasionally, and patients sometimes get supplies over the Internet. Easy chemical synthesis also makes for continued widespread availability.

History of substance use

Ask about the use of alcohol, smoking and other drugs (e.g. marijuana, cocaine, opiates, sedative-hypnotic agents, stimulants, solvents, and hallucinogens). Ask when it was first used, the amounts consumed and the routes of administration. Is there any evidence of dependence (craving, tolerance, inability to stop or control use, physiological withdrawal state, drug-related harm, reduction of interests and activities unrelated to drug use) Ask about periods of abstinence and related offences.

The Effects Of The Law On Set And Setting

More recently, work has been carried out looking at the strategic nature of attribution among users of illicit drugs. The main difference here is that while smoking is an increasingly disapproved of activity in social terms, it remains legal. By contrast, illicit drug use is an illegal activity, and as a consequence no one engaged in this activity is keen to advertise the fact, especially where the 'harder' drugs (opiates, cocaine) are concerned. Studies have revealed that users of heroin and cocaine exist in the community, that such use may not necessarily involve behaviours that one would call 'addicted' (i.e. the use appears to be stable and controlled over considerable periods of time) but the samples are difficult to find as they do not advertise their presence (Shewan et al., 1998). In this study, 74 people were identified who had used opiates at least 20 times in the last two years, but 'who had never been in addiction treatment or served a custodial sentence'. A study by...

Domestic Violence Courts

One example of a specialized court is the Vancouver, Washington Misdemeanor Domestic Violence Court. At monthly meetings of the Clark County Domestic Violence Sexual Assault Task Force, which included a wide array of community members and professionals (including Judge Randal Fritzler), there was a consensus that domestic violence was as much a community problem as a victim issue. Judge Fritzler decided to create a specialized domestic violence court and forged a partnership with a collaborative team that included Washington State University, probation officers, city and county prosecutors, city and county law enforcement, Young Women's Christian Association (YWCA) victim advocates, and offender treatment providers (Fritzler and Simon, 2000a, 2000b). The court has centralized the services that victims and offenders need in the courthouse, with the judge coordinating provision of legal, social, and psychological services. For example, battered women are able to get civil protection...

Changing Ones State Of Consciousness A Motivated

In a similar way, data cited by Frenk and Dar (2000) compare 'lifetime use' of supposed addictive drugs with 'last month' use, and produce results which lead to the same type of general conclusion. For example, a prevalence figure of 7.7 for lifetime use of all opiates translates into a figure of 0.7 foruse lastmonth. For cocaine, the comparable figures are 6.9 and 0.7 . Continuation rates for samples of drug users show a similar picture. Of a sample (100 ) of lifetime opiate users, 8.6 reported using last month. For cocaine, the comparable figure was 10.8 . A recent Scottish Office-funded study also demonstrated stable controlled use of heroin in a Scottish sample of users, over a two year period of time (Shewan et al., 1998). Finally, a study by Leitner, Shapland and Wiles (1993) showed a clear effect of social class on problem drug use by young people. Rates of 'ever having tried' an illegal drug were roughly the same for all social classes but a higher rate of escalating, heavy...

Outbreak Characterization

To conduct a case-control study, an investigator develops a questionnaire that covers all of the suspected sources and routes of transmission. Epidemiologists know from experience and knowledge of epidemiological patterns when to include items (e.g., intravenous drug abuse, food and water

Peripartum Hemorrhage

Normally implanted placenta after 20 weeks of gestation incidence is 0.2-2.4 may present with painful vaginal bleeding, hemorrhagic shock, fetal distress, irritable uterus potential for massive blood loss (blood loss may be concealed), disseminated intravascular coagulation (DIC), acute renal failure risk factors hypertension, uterine abnormalities, history of cocaine abuse.

Cardiovascular Diseases

Ephedrine and pseudoephedrine share properties with cocaine and with the amphetamines because they (1) stimulate p-receptors directly, and (2) also cause the increased release of norepinephrine. Chronic exposure to abnormally high levels of circulating catecholamines can damage the heart. This is certainly the case with cocaine and methamphetamine (116,117), but ephe-drine-related cardiomyopathy is an extremely rare occurrence, occurring only in individuals who take massive amounts of drug for prolonged periods of time. Only two papers have ever been published on the subject (118,119). Similar considerations apply to the relationship (if any) between myocardial infarction and ephedrine use. The report by Cockings and Brown described a 25-year-old drug abuser who injected himself with an unknown amount of cocaine intravenously (120). The only other published reports involved a woman in labor who was receiving other vasoactive drugs (121) and two pseudoephedrine users, one of whom was...

Neuroprotective Effects Of Monoamine Oxidase Inhibitors

Neuroprotective effects of the MAO-B inhibitors, selegiline and rasagiline, are dependent on their propargyl moiety and independent of their MAO inhibitory properties. The selegiline metabolite, desmethylselegiline, is responsible for the potential neuroprotective effects of selegiline. The S-isomer of rasagiline, TVP 1022, is one thousand times less potent at inhibiting MAO-B, yet demonstrates similar potential neuroprotective effects (27). Both selegiline and rasagiline have demonstrated neuroprotection in multiple in vitro and animal models (27-41). Selegiline and rasagiline inhibit apoptosis, or programmed cell death, in cell lines (28,30,34,35,42). Although the selegiline metabolite L-methamphetamine inhibits the anti-apoptotic activities of selegiline, the rasagiline metabolite aminoindan does not (43).

Summary And Directions For The Future

Opiate and cocaine addictions are complex disorders with a variety of processes that contribute to the maintenance of pathological behavior and relapse in abstinent individuals. Current animal paradigms are simplistic models of particular aspects of the disease and may be insufficient to predict the clinical utility and justify initiation of efficacy trials. We argue for the development of human laboratory paradigms and improvement of the methodology of small N clinical trials, both of which may be useful in medication development for substance-use disorders. This strategy may be preferable to the traditional strategy of initiation of expensive efficacy trials based on preclinical research for cocaine (but not for opioid dependence). The vast majority of medications for cocaine Preclinical research brings overwhelming evidence documenting the role of glutamatergic neurotransmission in the neurobiology of opioid and cocaine dependence and suggests that glutamatergic agents, in...

Sensitization And The Selfadministration Of Psychomotor Stimulant Drugs

It is now well established that animals previously exposed to sensitizing injection regimens of morphine, amphetamine, cocaine, or treatments with environmental stressors are subsequently more sensitive to the rewarding or incentive-motivational effects of these drugs as measured by the conditioned place-preference procedure (107-109). In addition, these animals are more susceptible to self-administer amphetamine and cocaine (110-118). The long-term neurobiological changes associated with these effects have also been suggested to play an important role in the reinstatement of drug-taking in individuals that have been drug free for some time (109,119-124). By examining those neuronal events known to influence locomotor sensitization to such drugs, it may be possible to gain an understanding of those neuronal systems underlying predisposition to self-administer these very drugs and liability for reinstatement of this behavior even in drug-free individuals. The neurotransmitter system...

Metabotropic Receptors

Metabotropic glutamate receptors (mGluRs) are seven transmembrane domain G-protein-coupled receptors that are activated by glutamate and that regulate neuronal excitability by a multiplicity of postsynaptic and presynaptic mechanisms. Eight distinct mGluRs have been identified by molecular cloning, some of which exist in multiple alternatively spliced forms. The family of mGluRs can be divided into two major groups based on the second-messenger systems to which they are coupled those that increase phosphatidylinositol (PI) hydrolysis through activation of phospholipase C (mGluRl, mGluR5) and those that are negatively coupled to cyclic AMP formation via inhibition of adenyl cyclase (mGluR2-4, mGluR6-8). On the basis of sequence homology, the second-messenger mechanisms to which they are coupled, and pharmacological criteria, it has been useful to further divide mGluRs into three major groups. Group I corresponds to the mGluRs linked to PI turnover, whereas groups II (mGluR2, mGluR3)...

Glutamate Neurotransmission And The Limbic System

Finally, the increase of extracellular dopamine content in the nucleus accumbens produced by systemic administration of cocaine has been shown to be reduced by local infusion of both the NMDA receptors antagonist AP-5 and the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (40). However, the interaction between dopamine and excitatory amino acids appear to be complex because, in untreated animals, local infusion of NMDA antagonists has been shown to increase dopamine release (41). It is also noteworthy that increasing endogenous extracellular glutamate concentrations through local microinfusion of the selective glutamate reuptake inhibitor transpyrrolidine-2,4-dicarboxylic acid (PDC) produced an increase of dopamine release in the rat striatum (42) and an increase in locomotor activity has been reported after microinfusion of PDC within the core of the nucleus accumbens (43). Investigation using in vivo microdialysis has also shown that activation of dopamine...

Specific Multicultural Issues

This issue is even more critical in mental health services involving African American clients with HIV AIDS. Boyd-Franklin et al. (1995) noted that among many African Americans the cause of death of a family member who has died of AIDS is treated as a toxic family secret (p. 57). Family secrets involving homosexuality and drug abuse (two leading risks for HIV infection) might have to be revealed to family members when a diagnosis of HIV or AIDS is made. The family of an individual with HIV AIDS might not reveal these secrets to their church (e.g., the minister) because of the shame and stigma associated with this disease. In the case of the therapist, these secrets are not expected to be revealed during the first encounter with the client who is seeking help to deal with symptoms of depression after knowing that he or she has HIV infection. In general, among many Hispanics, spirits, a divine providence, or supernatural events govern the world and the individual cannot control...

Disorders of the Endocardium

Infective endocarditis a disorder affecting the endocardial surface of the heart as the result of infection. The characteristic lesion is the vegetation, which consists of thrombus containing microorganisms. In acute bacterial endocarditis large friable vegetations are found on the valves, which can cause erosion or perforation of the underlying tissue. Predisposing factors to endocarditis are valvular anatomical abnormalities (congenital or acquired, e.g., rheumatic heart disease), sepsis, immunosuppression or IV drug abuse.

Institutional Obstacles

Many health care services for drug users are high-threshold services (Appel, et al., 2004). This means they are programs that are based on abstinence and require individuals to stop using the drugs they are addicted to. These programs are problematic, however, and they symbolize a common misconception about drug addiction therapy. Many abstinence programs do not recognize the long-term, comprehensive process by which an injection drug user successfully gains control over their addiction. A large part of a successful treatment plan involves preparing the individual to quit (i.e., through education, motivation, raising self-esteem, etc.) and may be conducted while the individual is still using drugs. Unfortunately, the majority of drug users who enter abstinence programs do not have this background. They are not properly prepared to quit, and so they often drop out.

Drug Use And Urban Environments

Differences in drug use between urban and rural areas vary over time and by geographical area. Some studies have demonstrated higher rates of drug use among urban populations as compared to rural populations (Mueser, et al., 2001), while others have shown the opposite (Othieno, et al., 2000 Leukefeld, et al., 2002). Data from the Monitoring the Future Study suggest that lifetime and annual drug use rates among adolescents are relatively similar across communities (table 1), and that in some cases use in rural areas exceeds that in urban areas (e.g. lifetime methamphetamine prevalence) (Johnston, et al., 2004). Another analysis of the MTF data suggested temporal changes in urban versus rural differences between 1976 and 1992 (Cronk and Sarvela, 1997). During the late 1970s and 1980s, rates of marijuana and cocaine use were higher among urban than rural adolescents. However, by the early 1990s use of these drugs among rural adolescents matched or exceeded those of their urban...

Drug Use Epidemiology

According to the 2002 NSDUH, approximately 108 million persons over age 12 had used an illicit drug in their lifetime and in the U.S. 35.1 million had used an illicit drug in the past year (Substance Abuse and Mental Health Services Administration and Office of Applied Studies, 2003b). The most frequently reported illicit drug used was marijuana (40.4 reported lifetime use, 11.0 past year use). In terms of lifetime use, cocaine and hallucinogens were also quite prevalent (14.4 and 14.6 , respectively), while amphetamines (9.0 ) and heroin (1.6 ) were less so. Trends in incidence within the U.S. vary over time for different drugs. Cocaine hit a peak of 1.7 million new users in 1981 and slowly declined through the 1980s and early 1990s. In the mid-1990s, incidence again began to rise resulting in a recent estimate of almost 1.2 million new users in 2001. The number of new hallucinogen users was stable throughout the 1970s and 1980s, but increased throughout 1990s growing from...

Pharmacologicalinduced Models Of Parkinsons Disease

Pharmacological manipulation of the dopaminergic system can take on two basic forms either targeting dopamine biosynthesis or destruction of nigrostriatal dopaminergic neurons. Both reserpine and alpha-methyl-para-tyrosine (AMPT) interfere with dopamine production and result in a temporary dopamine depletion lasting hours to days, whereas neurotoxicants such as 6-hydroxydopamine (6-OHDA) and (MPTP) result in midbrain dopaminergic cell death. Methamphetamine (METH) is a class of compound that selectively destroys axonal terminals of nigrostriatal dopaminergic neurons usually without significant cell death. Recently, other compounds, particularly pesticides and proteasome inhibitors, have been utilized as selective toxins targeting the dopaminergic system since the mitochondria of these cells display enhanced vulnerability during chronic exposure. The utility of compounds to generate animal models of parkinsonism are discussed in the following sections.

Neurotransmitters mental disorders and medications

Drug addictions Cocaine and crack cocaine are psychostimulants that affect neurons containing dopamine in the areas of the brain known as the limbic and frontal cortex. When cocaine is used, it generates a feeling of confidence and power. However, when large amounts are taken, people crash and suffer from physical and emotional exhaustion as well as depression.

Effect Of Nmda Receptor Antagonists On The Acquisition Of Cpp Produced By Drugs Of Abuse

Dose-dependently decreased the CPP for 10 and 20 mg cocaine kg but increased the CPP for 2.5-5 mg kg of cocaine, suggesting a biphasic effect on cocaine-induced CPP (28). The development of cocaine-induced CPP was also attenuated by MK-801 (29,30) and ACPC (26) (which, in addition, blocked the development of CPP induced by amphetamine, nomifensine, nicotine, and diazepam). Furthermore, metamphetamine-induced (31) but not amphetamine-induced (32) CPP was blocked by MK-801. MK-801 and L-701,324 attenuated also the development of CPP induced by alcohol (33). The effects of NMDA receptor antagonists on the acquisition of drug-induced conditioned place preference appear to be extremely consistent across the literature and provide substantial insight to the mechanisms of the development of drug addiction. However, by definition, their outcome is not that significant to the clinical applications.

Caffeinerelated disorders

Caffeine is a white, bitter crystalline alkaloid derived from coffee or tea. It belongs to a class of compounds called xanthines, its chemical formula being 1,3,7-trimethylxanthine. Caffeine is classified together with cocaine and amphetamines as an analeptic, or central nervous system stimulant. Coffee is the most abundant source of caffeine, although caffeine is also found in tea, cocoa, and cola beverages as well as in over-the-counter and prescription medications for pain relief.

Determinism Versus Volition

It is probably worth pointing out at this stage that the mechanistic conception of addiction, which is the one universally favoured by politicians and the media, does not receive anything like unanimous support from many of those involved in the counselling and treatment of drug problems. The idea of drug use as a motivated and active choice on the part of the user is not the territory of madmen and maverick academics but receives support at the grass roots level among many agency workers and others involved at the sharp end. Books by Cohen (1989,1990), Cameron (1995), Schaler (2000), Coomber (1998), Frenk and Dar (2000) and others all express drug problems from a multi-causal perspective rather than a monolithic pharmacological viewpoint. All see individual motivation and choice as a dimension of the problem to a greater or lesser extent. They all put the pilot back in the aeroplane. If the choice of the best philosophical model of humankind within which to study drug problems is...

Poststabilization Patient Assessment

One test that is unlikely to be of benefit in evaluating potential victims of toxin-related disasters is the toxicology screen. Such screens typically test for drugs of abuse (cocaine, amphetamines, LSD, PCP, marijuana), which are unlikely to be used in terrorist attacks. Even a positive result would be unhelpful, as it would likely be an incidental finding. The toxicology screen, therefore, really has no role in the routine management of poisoned patients in the disaster setting.

Key Health Issues For Homeless People

The burden of illness and disease is extremely high among homeless people (Levy and O'Connell, 2004). However, any consideration of the common health problems of homeless people must first recognize the large degree of heterogeneity among people who are homeless. Among street youth, single men, single women, and mothers with children, the patterns of illness differ notably. Adolescents suffer from high rates of suicide attempts, sexually transmitted diseases, and pregnancy (Greene and Ringwalt, 1996 Greene and Ringwalt, 1998 Greene, et al., 1999 Feldmann and Middleman, 2003). Female heads of homeless families tend to have far fewer health problems than single homeless women, although their health is poorer than their counterparts in the housed general population (Robertson and Winkleby, 1996). Homeless single men have a higher prevalence of alcohol abuse and drug abuse, whereas single women have a higher prevalence of serious mental illness (Fischer and Breakey, 1991). Cross-national...

Patient Selection

Disease states that would preclude pump implantation should also be identified. Contraindications to implantation generally consist of aplastic anemia, systemic infections, allergies to the metal or plastics used in the pump or catheter, active intravenous drug abuse, and coagulopathies 11 . Psychological contraindications can be identified by commonly used tests, such as the McGill Pain Questionnaire, Minnesota Mutiphasic Personality Inventory (MMPI-2), and the Beck Depression Inventory. Formal psychiatric consultation should be considered.

Glutamate Mediation Of Dopamine And 5ht Toxicity

Glutamate overflow and subsequent activation of the NOS pathway may differentially mediate DA and 5-HT toxicity. Glutamate overflow is not correlated with the depletion of 5-HT content in different brain regions after MA. In fact, 3,4-methylenedioxy-methamphetamine (MDMA), a more selective 5-HT toxin structurally similar to MA, damages striatal 5-HT terminals but does not result in glutamate overflow in this region (33) Abekawa et al. (149) report that administration of the NOS inhibitor l-NAME protects against MA-induced DA loss in the striatum, but it does not attenuate 5-HT toxicity in the striatum, nucleus accumbens, and medial frontal cortex of the same animals (150). However, pretreatment with a different NOS inhibitor, N -nitro-l-arginine (l-NOARG), partially protects against long-term 5-HT depletion induced by MDMA in frontal cortex and parietal cortex, but not in other brain regions (152). The interaction between glutamate and lasting depletion of 5-HT may, therefore, be...

Substance abuse and related disorders

Substance-related disorders are disorders of intoxication, dependence, abuse, and substance withdrawal caused by various substances, both legal and illegal. These substances include alcohol, amphetamines, caffeine, inhalants, nicotine, prescription medications that may be abused (such as sedatives), opioids (morphine, heroin), marijuana (cannabis), cocaine, hallucinogens, and phencyclidine (PCP). cocaine-related disorders See also Addiction Alcohol and related disorders Amnestic disorders Amphetamines and related disorders Antianxiety drugs and abuse-related disorders Caffeine and related disorders Cannabis and related disorders Cocaine and related disorders Denial Disease concept of chemical dependency Hallucinogens and related disorders Inhalants and related disorders Nicotine and related disorders Opioids and related disorders Phencyclidine and related disorders Polysubstance dependence Sedatives and related disorders Substance Abuse Subtle

Building as Product and Process

The fifth characteristic is information and communication. Cities have always been centers for the development and exchange of ideas, information and inventions (Castells, 1991). It is well known that targeted information is crucial for effective preventive measures in public campaigns about risk behaviors including tobacco smoking, alcohol consumption, drug abuse and safe sexual intercourse. City authorities can play a crucial role in health prevention and promotion by communicating information in innovative ways. There is much to be learnt from successful marketing strategies by private enterprises if public health campaigns about risk behaviors are to become more successful than they have been. Health education is a key factor in increasing the responsible behavior of individuals, social groups and communities (Wallerstein, 1992).

Psychostimulantinduced Neuroadaptations In The Interactions Between Glutamate And Dopamine

Repeated psychostimulant consumption ultimately results in classic symptoms of addiction such as craving, compulsive drug use, and paranoia. Identifying the neuroadaptations mediating the emergence of these enduring behavioral alterations is key to the understanding of the neurobiology of psychostimulant addiction and developing rational therapies. In general, acute systemic administration of psychostimulants alters dopamine and glutamate neurotransmission throughout the motive circuit thus, it is not surprising that neuroadaptations elicited by repeated psychostimulant administration have been identified throughout this circuit. The following sections will examine some of the neuroadaptations occurring in the VTA, PFC, and accumbens following cocaine administration. For a more complete discussion of the effects of repeated psychomotor stimulants, the reader is referred to a number of recent reviews on psychostimulant induced neuroadaptations (15,16,93,94). The primary molecular...

The message

The nature and content of the message may be uncomfortable for the doctor or the patient or both (Table 4.3). This applies to emotionally charged, complex or subtle content such as sexual problems, malignant disease, drug abuse, bereavement, malingering and psychiatric disorders.

Communicable Disease

A number of studies indicate that substance use may be a particular problem among immigrant latinos residing in urban areas. A study conducted in northern California found that compared to non-latino white students, latino students were both more likely to use alcohol, tobacco, marijuana, and other substances and to engage in various forms of violence and drunken driving (Brindis, et al., 1995). Young Central American immigrants have been found to have higher alcohol and illegal substance use, particularly hallucinogens, marijuana, cocaine, and PCP, in comparison with other latinos (Tomasello, et al., 1993). Kurtines and Szapocznik (1995) found from their work with immigrants in the Miami area that drug use may be related to difficulties with assimilation and the effects of immigration on family cohesiveness. Their research indicates that young people in immigrant families acculturate more rapidly and completely than older family members, resulting in the exacerbation of struggles by...

AMPA Receptors

Competitive antagonists acting at the glutamate recognition site of AMPA receptors have shown promising neuroprotective, anticonvulsant, analgesic, and anxiolytic activities in animal models (92,93). Competitive antagonists also display beneficial effects upon certain stages of drug dependence (see subsequent chapters, this book). competitive AMPA-receptor antagonists include quinoxalinediones such as CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), NBQX 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F)quinoxaline , and YM90K as well as several structurally novel compounds including isatin oximes such as NS 257 and decahydroisoquinolines such as LY293558 decahydroisoquinoline-3-carboxylic acid . Most of these antagonists do not discriminate well between AMPA and kainate receptors (94). This is also the case for the water-soluble and systemically available isatin oxime NS 257, which not only blocks AMPA and kainate receptors but also interacts with NMDA receptors (95,96). NBQX, however, exhibits...

Brachial Plexus

Brachial plexus most commonly involves lesions caused by trauma (traction injury to the arm, knife or ice pick wounds, or bullet penetration), metastatic carcinoma from the breast or lung, or delayed radiation damage to the plexus from treatment of the latter. Other causes are birth injuries, supraclavicular pressure during anesthesia, intravenous drug abuse, serum and vaccination reactions, and paralytic brachial neuritis of unknown cause (possibly virus).

Piotr Popik MD PhD

Alcohol and other drugs of abuse produce dependence, a chronic and relapsing disorder that is an enormously destructive public health problem. In the United States, mortality that can be attributed to these disorders is greater than mortality attributable to all other factors combined (1). Currently, there are a limited number of available medications to treat alcohol, opioid, and nicotine dependence, and no medication to treat cocaine, other stimulants, or cannabis dependence. Success rate of available treatments is relatively low, only 30-50 of patients remain abstinent at 1 yr after completion of the most successful treatment programs (2,3). Despite recent advances in the understanding of the neurobiolog-ical basis for these disorders and the development of new psychotherapeutic approaches, there is a lack of viable pharmacological treatments. At the same time, societal and political pressures continue for the development of effective and inexpensive treatments. stimuli (internal...

Placemaking

The homeless participated in all community activities such as the street painting and as a result took pride and ownership in the neighborhood the homeless helped to clean up litter and waste and have donated materials that were incorporated into the structures. Burglary, assault, vehicle theft, robbery, etc have declined significantly (P

Emphysema

Smokers with HIV develop pulmonary emphysema more often than smokers without HIV. It is possible that a pathogenic synergy arises from smoking and the pulmonary infiltration with cytotoxic T cells due to HIV infection (Diaz 2000). Smoking crack increases the risk of pulmonary emphysema even more. Here, it seems that superficial epithelial and mucosal structures are destroyed (Fliegil 1997). Furthermore, cocaine can lead to unusual manifestations with pneumothorax or alveolar infiltrates.

Nonhodgkins Lymphoma

The current recommendation for treating all NHL, except cerebral lymphoma, is systemic chemotherapy. The current recommendation for treating cerebral lymphoma is whole brain radiotherapy adjunctive chemotherapy may increase response rates in young patients with high performance status (6). As of 2003, the optimal chemotherapy regimen for treating NHL has not been identified. Median survival with chemotherapy is 35 years, intravenous drug abuse, stage III or IV disease, CD4 lymphocyte count 0.1 x 109 L, history of Kaposi's sarcoma or an opportunistic infection, Karnofsky performance score

Punishment

When a person is arrested and convicted of a crime, depending on the nature and seriousness of the offense, he or she may be fined, placed on probation, or incarcerated. Teenagers and older adults are much less likely than young and middle-aged adults to be incarcerated for the same crime. However, the conservative political and social climate of recent years has prompted less forgiveness on the part of the courts, not only for violent crimes but also for drug abuse violations and victimless crimes.

Commercial Kits

Many RIA and EIA kits are readily available for drugs of abuse and for drugs whose plasma concentrations have been correlated with therapeutic and toxic effects. The individual components of the kit, such as control standards, labeled hapten, and antisera, are also available from many commercial sources. The ease of using such kits is apparent, but the buyer must be aware of the potential pitfalls as well. Often the kits are made for purposes other than drug quantitation in clinical studies, drug pharmacokinetics for bioavailability assessment, or pharma-codynamics of biochemical markers (183). Instead, their intended uses are for the detection of drug abuse (toxic concentrations), therapeutic doses, and diagnosis of diseases or certain physiological conditions. The lowest limit of the calibrator range is often greater than that of the desired limit of quantitation for a pharmaco-kinetic or pharmacodynamic study. To save reagent and labor costs, the number of standards in a calibrator...

Continuityof Care

Continuity-of-care is also a challenging problem (Chan, et al., 2002). For many, the hospital emergency room is their first and only point of contact with the medical system. It is also clear that many of the people who frequent emergency rooms also make frequent visits to primary care (Byrne, et al., 2003). The transition between acute hospital care and community follow-up is sub-optimal because primary care clinics are not readily accessible, and those that do exist are unable to provide the requisite level of diagnostic testing and treatment. This is not sufficient for chronic illnesses such as drug addiction and HIV infection, both of which require long-term, consistent care. The result is a pattern of crisis-based medical interventions without a focus on early-detection, prevention or follow-up.

Zaleplon

Because zaleplon is used to help people fall asleep, it should not be used with other drugs (over-the-counter or prescription) that also cause drowsiness. Zaleplon should be used only with close physician supervision in people with liver disease and in the elderly, because these individuals are especially sensitive to the sedative properties of zaleplon. Zaleplon should not be used before driving, operating machinery, or performing activities that require mental alertness. People with a history of drug abuse, psychiatric disorders, or depression should be carefully monitored when using zaleplon since zale-plon may worsen symptoms of some psychiatric disorders and can become a drug of abuse.

Zolpidem

Because zolpidem is used to help people fall asleep, it should not be used with other drugs (either over-the-counter, herbal, or prescription) that also cause drowsiness (for example, antihistamines or alcohol). Zolpidem should be used only with close physician supervision in people with liver disease and in the elderly, because these individuals are especially sensitive to the sedative properties of zolpidem. Zolpidem should not be used before driving, operating machinery, or performing activities that require mental alertness. People with a history of drug abuse, psychiatric disorders, or depression should be carefully monitored when using zolpidem since zolpidem may worsen symptoms of some psychiatric disorders.

Robert W Peoples PhD

Nmda Receptor Alcohol

Alcohol is arguably the oldest drug known to man, its use dating back at least 10,000 yr to the dawn of human civilization (1). Although illicit drug use often receives more attention in contemporary society, alcohol abuse exacts a devastating toll In the United States at present, over 7 of the population meet diagnostic criteria for alcohol abuse or alcoholism (2), over 28 of children under 18 yr of age are exposed to alcohol abuse or dependence in the home (3), and the overall economic cost to society of alcohol abuse has been estimated at 185 billion (4). Despite intensive research since the latter part of the previous century, it is clear that the biological actions that are responsible for the characteristic effects of ethyl alcohol, or ethanol, on human physiology and behavior are still incompletely understood. Because of the simple chemical structure of ethanol (it differs from water only by two methylene groups) and its low potency (it produces most of its biological effects...

Acupuncture

Acupuncture's record of success has been sufficiently impressive to stimulate a number of research projects investigating its mechanisms as well as its efficacy. Research has been funded not only by the National Center for Complementary and Alternative Medicine (NCCAM), but also by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Dental Research, the National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute on Drug Abuse. In 1997 a consensus

The masquerades

It is important to utilise a type of fail-safe mechanism to avoid missing the diagnosis of these disorders. Some practitioners refer to consultations that make their 'head spin' in confusion and bewilderment, with patients presenting with a 'shopping list' of problems. It is in these patients that a checklist is useful. Consider the apparently neurotic patient who presents with headache, lethargy, tiredness, constipation, anorexia, indigestion, shortness of breath on exertion, pruritus, flatulence, sore tongue and backache. In such a patient we must consider a diagnosis that links all these symptoms, especially if the physical examination is inconclusive this includes iron deficiency anaemia, depression, diabetes mellitus, hypothyroidism and drug abuse.

History

Potent central nervous system (CNS) stimulant (6). Injections of ephedrine, called philopon (which means love of work ) were given to Japanese kamikaze pilots during World War II. A major epidemic of ephedrine abuse occurred in postwar Japan, when stockpiles of ephedrine accumulated for use by the Army were dumped on the black market. Abusers in Tokyo, and other large Japanese cities, injected themselves with ephedrine (then referred to as hirapon), in much the same way that methamphetamine is injected today (7). In the Philippines, a mixture of ephedrine and caffeine called shabu was traditionally smoked for its stimulating effect. In the late 1980s, shabu smoking gave way to the practice of smoking methamphetamine ( ice ). In what is perhaps a tribute to the past, some ice is sold under the philopon name.

Trazodone

Trazodone is used to treat depression and to treat the combination of symptoms of anxiety and depression. Like most antidepressants, trazodone has also been used in limited numbers of patients to treat panic disorder, obsessive-compulsive disorder, attention-deficit hyperac-tivity disorder, enuresis (bed-wetting), eating disorders such as bulimia nervosa, cocaine dependency, and the depressive phase of bipolar (manic-depressive) disorder. It should be noted, however, that trazodone has not received official approval from the United States Food and Drug Administration (FDA) for these secondary uses.

Comedication

Drug interactions involving drugs of abuse are of particular concern due to an increased risk of life threatening side effects. However, not surprisingly, data in this area are sparse. Several fatal cases with regard to the simultaneous intake of RTV and ecstasy (MDMA) or gammahydroxybutyrate (GHB) have been reported in the literature (Hales 2000, Harrington 1999). Metabolic inhibition of amphetamines, MDMA and phencyclidine (PCP), can result in hypothermia, hypertension, arrhythmias, tachycardias and cramps. Reduced metabolism of ketamine can result in respiratory depression, hallucinations and unconsciousness. Increased LSD plasma concentrations are associated with hallucinations, psychosis, agitation and flashbacks, and GHB with cramps, bradycardia, unconsciousness or respiratory depression. Cocaine, in the presence of NNRTIs, is metabolized more rapidly so that the liver toxic metabolite norcocaine can accumulate (Antoniou 2002). Marijuana (tet-rahydrocannibinol, THC) probably has...

Disordersi

PCP became an illicit street drug in the mid-1960s. It was most commonly found in large cities such as New York and San Francisco, and even today, most users tend to live in urban areas. Into the 1970s, PCP appeared mainly as a contaminant of other illict drugs, especially marijuana and cocaine. This complicated diagnosis of PCP use, as many people did not know that they had ingested the drug. PCP is easy to manufacture and is inexpensive. By the late 1970s, in some urban areas its use equaled that of crack cocaine. Use of PCP peaked between 1973 and 1979. Since 1980, PCP use has declined, although as with most illicit drugs, its popularity increases and decreases in cycles. PCP is a Schedule II drug under the Controlled Substances Act. In its pure form, it is a white powder that dissolves easily in water. Once dissolved, the solution can be sprayed on tobacco or marijuana cigarettes. Less pure forms range from yellowish-tan to brown and can be a sticky mass. On the street PCP has...

Conclusions

Other potential applications of ginseng in anticancer treatment, as liver protective agents, in alcohol intoxication therapy, for morphine, cocaine and amphetamine withdrawal problems, in topical preparations for skin affections such as acne and eczema and in cosmetics still require careful clinical trials to demonstrate indisputably that standardised ginseng phytochemicals or formulations are really effective in human subjects.

Risk Assessment

A history of suicide attempts (136-142) or drug abuse (106,143-146) should also be considered as a risk factor prior to initiating pharmacological intervention for pain management. These patients should only be given limited amounts of opioid analgesics, and coupled with frequent office visits for follow-up evaluation may reduce the risk for overdose or abuse. Often, it is not wise to start the patient on any opioid analgesics immediately after the initial office evaluation. It will be better to have the patient see the provider a few times prior to initiating opioid analgesia. This will provide the clinician with a better assessment of the patient's physical and emotional standing.

Other Approaches

In the future, it may be possible to modulate brain glutamate systems by treatments that are designed to modify the expression of critical genes involved in glutamate signaling. Indeed, drugs of abuse produce prominent changes in gene transcription that may alter the expression of components of the glutamate-signaling pathways and these changes have been hypothesized to play a role in the development of drug dependence (193). Furthermore, drugs used to treat drug dependence may also operate through similar pathways. For example, antidepressants, widely used to treat drug dependence (3), appear to have the common effect of increasing the levels of growth factors such as brain-derived neurotrophic factor (BDNF), as pointed out by Skolnick (194). Depression is comorbid with drug-dependence syndromes (195) and NMDA-receptor antagonists are effective in animal models of depression (194), as they are in models of drug addiction. Therefore, novel approaches to the treatment of drug addiction...

Naaladase

Until recently, pharmacological tools for selectively inhibiting NAALADase were not available. However, this situation changed with the design and synthesis of 2-(phosphonomethyl) pentanedioic acid (2-PMPA) (189), which is a high-affinity (K 280 pM) and selective NAALADase inhibitor (190). In addition to its potential role in the therapy of conditions associated with excessive glutamate, recent reports suggest a role for NAALADase inhibition in modulating the behavioral and toxic effects of drugs of abuse. Thus, 2-PMPA blocks the development of behavioral sensitization resulting from repeated exposure to cocaine in rats without affecting acute stimulant effects of cocaine (191). 2-PMPA also attenuates both the expression and development of cocaine-kindled seizures in mice without producing the motor side effects seen with NMDA receptor antagonists (192).

Clinical Trials

NMDA Receptor Antagonists in the Treatment of Drug Withdrawal 4.1.1. Opiate Detoxification In an open-label study, Alper et al. (41) reported that 25 out of 33 opioid-dependent patients who received a single dose of ibogaine had complete resolution of withdrawal signs and symptoms, including drug-craving, within 24 h of receiving ibogaine and this improvement was maintained over 3 d of observation. In a recent prospective study, 27 opiate and cocaine-dependent individuals treated with ibogaine reported statistically significant improvement in depressive symptoms and craving for heroin and cocaine as compared to pretreatment baseline (43). No control group was used however, so it is not known if the symptom improvement after ibogaine treatment would differ from the improvement that is a part of a natural course of the withdrawal syndrome. Additionally, the withdrawal severity and many other details of the study were not reported. Treatment outcomes reported after brief treatment...

Other Substances

Other substance-related disorders with brief description of cultural variants in the DSM-IV (1994) include Amphetamine-Related Disorders, Cannabis-Related Disorders, Cocaine-Related Disorders, Hallucinogen-Related Disorders, Cocaine-Related Disorders, Inhalant-Related Disorders, Nicotine-Related Disorders, and Opioid-Related Disorders. In general, the DSM-IV does not consider these disorders as unique to specific cultures. Cultural acceptability of such disorders, however, might vary across cultures. For example, the hallucinogen peyote is culturally accepted by many American Indians during their religious services, but they rarely abuse this substance some members in the Southeast Asian community accept opium use, but they do not sanction or promote the use of this substance among members of this community (Westermeyer, 1995).

Alcohol and drugs

Alcohol misuse (see Chapter 13) may become a problem in old age, but is often concealed. Depression, loneliness, and boredom, perhaps following the death of a spouse, are common precipitants. Drug misuse (see Chapter 12) usually involves prescribed drugs, such as benzodiazepines, which often cause ataxia and cognitive impairment in this age group. If an elderly person with unrecognized alcohol or drug dependence develops an intercurrent illness and or is admitted to hospital, withdrawal symptoms may ensue.

Treatments

Acute methamphetamine intoxication is often handled by observation in a safe, quiet environment. When extreme anxiety or panic is part of the reaction, treatment with anti-anxiety medications may be helpful. In cases of methamphetamine-induced psychoses, short-term use of antipsychotic medications is usually successful.

Prevention

NIDA Notes 14, no. 4, November, 1999. NIDA Notes 16, no. 5, December 2001. NIDA Notes 16, no. 6, February 2002. NIDAInfofax 13567, Nationwide Trends Notes. NIDA Infofax 13552. Methamphetamine. 91409. (818) 780-3951. National Institute on Drug Abuse (NIDA). U.S. Department of Health and Human Services, 5600 Fishers Ln., Rockville, MD 20857. (301) 443-6245. .

Conduct disorder

Conduct Disorder Symptoms

The negative consequences of conduct disorder, particularly childhood onset, may include illicit drug use, dropping out of school, violent behavior, severe family conflict, and frequent delinquent acts. Such behaviors often result in the child's eventual placement out of the home, in special education and or the juvenile justice system. There is evidence that the rates of disruptive behavior disorders may be as high as 50 in youth in public sectors of care such as juvenile justice, alcohol and drug

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