Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Substance Addiction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1997

High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers.

Allelic variants at the catechol-O-methyltransferase (COMT) locus are candidates to contribute to genetic components of interindividual differences in vulnerability to substance abuse. COMT plays a prominent role in dopaminergic circuits important for drug reward, and COMT alleles encode enzymes whose activities vary from three- to four-fold. We compared COMT allele frequencies in control research volunteers reporting insignificant lifetime use of addictive substances with those in volunteers reporting substantial polysubstance use. Homozygosity for the high-activity COMT allele was found in 18% of controls, 31% of volunteers with high lifetime substance use, and 39% meeting DSMIII-R substance abuse criteria [odds ratio (relative risks) 2.0 (control vs. use; 95% confidence interval 1.2-3.5; P < 0.013) and 2.8 (control vs. DSM; 1.3-6.1; P < 0.008)]. Individuals with the high-activity COMT variant may have greater genetic vulnerability to drug abuse.

Alleles↗
PubMed1992

Addictive drugs: the cigarette experience.

Cigarettes are among the most addictive substances of abuse and by far the most deadly. In this country smokers know it and try to stop. Their success has been dramatic but partial and excruciatingly slow, and until recently quite uncoerced by government. Cigarettes and nicotine have characteristics distinct among addictive drugs, and some of these help explain why efforts to quit smoking are so often frustrated. Nicotine itself is the most interesting chemical in the treatment of addiction and, in some forms, can pose a dilemma: compromise by settling for pure nicotine indefinitely, or stay with cigarettes and keep trying to quit. Nicotine is not alone among addictive drugs in becoming increasingly identified with the poorer classes.

Humans↗
PubMedDate not supplied

Smokeless tobacco use by youth: a health concern.

Smokeless tobacco use in the United States has increased over the last two decades largely due to increased consumption by young people. Rates of use are highest among teenage and young adult males, and the most popular form of smokeless tobacco is moist snuff. Peer pressure as well as use of other addictive substances such as cigarettes, drugs, and alcohol, seem to correlate with current use. Frequent users of smokeless tobacco have an increased risk of developing gingival recession, leukoplakia, and oral cancer at the placement site. Other health concerns are related to the cardiovascular effects and addictive nature of nicotine. Because the smokeless tobacco habit is difficult to break, public health efforts have been largely aimed at prevention. The dental professional also can play an important role in recognizing the smokeless tobacco user and facilitating cessation.

Adolescent↗
PubMed1996

Comparisons of alcohol and other drugs: experience from the WHO Collaborative Cross-Cultural Applicability Research (CAR) Study.

Current psychiatric classificatory systems commonly provide similar criteria for the identification of disorders relating to the use of alcohol and other drugs. However, since cultural views of substance use disorders are influenced by prevailing norms in the society, it is unlikely that a given culture will have identical threshold for the identification of disorders relating to the use of alcohol, commonly socially approved, and those relating to the use of other mood-altering substances, commonly socially disapproved. Using data derived from the WHO nine-country Cross-Cultural Applicability Research (CAR) study, we studied the cultural views on the use and abuse of alcohol and other drugs. Our observations suggest that, with a few notable exceptions, any use of addictive substances other than alcohol is commonly considered socially aberrant. Most cultures set a much lower threshold for the identification of disorders relating to these substances than they do for alcohol-related ones.

Alcoholism↗
PubMed2002

Sigma(1) (sigma(1)) receptor antagonists represent a new strategy against cocaine addiction and toxicity.

Cocaine is a highly addictive substance abused worldwide. Its mechanism of action involves initially inhibition of neuronal monoamine transporters in precise brain structures and primarily the dopamine reuptake system located on mesolimbic neurons. Cocaine rapidly increases the dopaminergic neurotransmission and triggers adaptive changes in numerous neuronal circuits underlying reinforcement, reward, sensitization and the high addictive potential of cocaine. Current therapeutic strategies focus on counteracting the cocaine effects directly on the dopamine transporter, through post-synaptic D(1), D(2) or D(3) receptors or through the glutamatergic, serotoninergic, opioid or corticotropin-releasing hormone systems. However, cocaine administration also results in the activation of numerous particular targets. Among them, the sigma(1) (sigma(1)) receptor is involved in several acute or chronic effects of cocaine. The present review will first bring concise overviews of the present strategies followed to alleviate cocaine addiction and animal models developed to analyze the pharmacology of cocaine addiction. Evidence involving activation of the sigma(1) receptor in the different aspects of cocaine abuse, will then be detailed, following acute, repeated, or overdose administration. The therapeutic potentials and neuropharmacological perspectives opened by the use of selective sigma(1) receptor antagonists in cocaine addiction will finally be discussed.

Animals↗
PubMed2006

Insights from recent positron emission tomographic studies of drug abuse and dependence.

PURPOSE OF REVIEW: Recent positron emission tomographic studies demonstrate a variety of abnormalities in the brains of addicted individuals. This review aims to discuss and highlight these findings. RECENT FINDINGS: The recent findings are as follows: (a) the reward response to an addictive substance is associated with increased dopamine release in the striatum. (b) Activation of the orbitofrontal region is involved in the reinforcing properties of a drug. (c) Behavioral, cognitive and affective abnormalities are associated with alterations in specific brain networks and regions (e.g., prefrontal cortices) in drug abusers. (d) Personality traits may play a role in the susceptibility to addiction and the brain's responses to drugs. (e) Sex-differences exist for cue-induced craving. (f) Several studies have confirmed decreased D2 receptors in drug users, which is associated with increased salience to drug cues. (g) Serotonergic transporters are decreased in the current users of 3,4-methylene-deoxy-methamphetamine but found normal in the past users of 3,4-methylene-deoxy-methamphetamine. SUMMARY: Abnormalities in the dopaminergic, opioid, and serotonergic systems in drug abusers are seen in positron emission tomography scans. Decreased D2 receptor densities in drug users, whether premorbid or the consequence of substance misuse, imply a source of the susceptibility to relapse of this population. Insights from these studies could lead to better treatment approaches targeting specific neurotransmitter systems.

Brain↗
PubMed2002

Characterization of the discriminable stimulus produced by 2-BFI: effects of imidazoline I(2)-site ligands, MAOIs, beta-carbolines, agmatine and ibogaine.

1. The molecular nature and functions of the I(2) subtype of imidazoline binding sites are unknown but evidence suggests an association with monoamine oxidase (MAO). Rats can distinguish the selective imidazoline I(2)-site ligand 2-BFI from vehicle in drug discrimination, indicating functional consequences of occupation of these sites. We have used drug discrimination to investigate the nature of the discriminable stimulus, especially in relation to MAO inhibition. 2. Following training to distinguish 2-BFI 7 mg kg(-1) i.p. from saline vehicle in two-lever operant-chambers, male Hooded Lister rats underwent sessions where test substances were given instead and the proportion of lever presses on the 2-BFI-associated lever (substitution) recorded. 3. 2-BFI; its cogeners BU216, BU224, BU226 and LSL60101; the reversible MAO-A inhibitors moclobemide and RO41-1049; the beta-carbolines harmane, norharmane and harmaline which also reversibly inhibit MAO-A, and the anti-addictive substance ibogaine exhibited potent, dose-dependent substitution for 2-BFI. 4. Agmatine, and LSL60125 substituted at one dose only. The reversible MAO-B inhibitors lazabemide and RO16-1649; the sigma(2)-site ligand SKF10,047 and the I(2A)-site ligand, amiloride, failed to substitute. The irreversible inhibitor of MAO, deprenyl, substituted for 2-BFI while clorgyline did not. 5. These results suggest imidazoline I(2) site ligands produce a common discriminable stimulus that appears associated with reversible inhibition of MAO-A rather than MAO-B, possibly through increases in extracellular concentration of one or more monoamines. Ibogaine exhibits a commonality in its subjective effects with those of I(2)-site ligands.

Agmatine↗
PubMed2005

The impact of early life stress on psychophysiological, personality and behavioral measures in 740 non-clinical subjects.

Early Life Stress (ELS) has been associated with a range of adverse outcomes in adults, including abnormalities in electrical brain activity [1], personality dimensions [40], increased vulnerability to substance abuse and depression [14]. The present study seeks to quantify these proposed effects in a large sample of non-clinical subjects. Data for the study was obtained from The Brain Resource International Database (six laboratories: two in USA, two in Europe, two in Australia). This study analyzed scalp electrophysiological data (EEG eyes open, closed and target auditory oddball data) and personality (NEO-FFI), history of addictive substance use and ELS) data that was acquired from 740 healthy volunteers. The ELS measures were collected via a self-report measure and covered a broad range of events from childhood sexual and physical abuse, to first-hand experience of traumatizing accidents and sustained domestic conflict [41]. Analysis of covariance, controlling for age and gender, compared EEG data from subjects exposed to ELS with those who were unexposed. ELS was associated with significantly decreased power across the EEG spectrum. The between group differences were strongest in the eyes closed paradigm, where subjects who experienced ELS showed significantly reduced beta (F1,405=12.37, p=.000), theta (F1,405=20.48, p=.000), alpha (F1,405=9.65, p=.002) and delta power (F1,450=36.22, p=.000). ELS exposed subjects also showed a significantly higher alpha peak frequency (F1,405=6.39, p=.012) in the eyes closed paradigm. Analysis of covariance on ERP components revealed that subjects who experienced ELS had significantly decreased N2 amplitude (F1,405=7.73, p=.006). Analyses of variance conducted on measures of personality revealed that subjects who experienced ELS had significantly higher levels of neuroticism (F1,264=13.39, p=.000) and openness (F1,264=17.11, p=.000), but lower levels of conscientiousness, than controls (F1,264=4.08, p=.044). The number of ELS events experienced was shown to be a significant predictor of scores on the DASS questionnaire [27], which rates subjects on symptoms of depression (F3,688=16.44, p=.000, R2=.07), anxiety (F3,688=14.32, p=.000, R2=.06) and stress (F3,688=20.02, p=.000, R2=.08). Each additional early life stressor was associated with an increase in these scores independent of age, gender and the type of stressor. Furthermore, the number of ELS experiences among smokers was also found to be a positive predictor of the nicotine dependency score (Faegstrom Test For Nicotine Dependence, [19]) (F3,104=10.99, p=.000, R2=.24), independent of age, gender and type of stressor. In conclusion, we highlight the impact of a history of ELS showed significant effects on brain function (EEG and ERP activity), personality dimensions and nicotine dependence.

Adolescent↗
PubMed2002

[Toxicomania in servicemen].

The authors substantiate the urgency of toxicomania among the servicemen. The circumstances of toxicomania, its morphological manifestations, toxic agents used by the toxic substance addicts were analyzed using the materials of 98 observations from medicolegal practice with lethal outcome. The measures to prevent and diagnose the toxicomania are proposed.

Adolescent↗
PubMed2004

A differential activation of dopamine output in the shell and core of the nucleus accumbens is associated with the motor responses to addictive drugs: a brain dialysis study in Roman high- and low-avoidance rats.

Addictive substances like morphine and psychostimulants induce a preferential increase in dopamine (DA) output in the nucleus accumbens (NAC), a major terminal field of the mesolimbic dopaminergic projection. Two subregions of the NAC, the dorsolateral core and the ventromedial shell, are thought to subserve different functions related to the reinforcing properties of natural and drug rewards. The selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats, respectively, for rapid vs. extremely poor active avoidance acquisition in a shuttle-box has resulted in two phenotypes that differ in their behavioural and neurochemical responses to addictive drugs. We used brain dialysis to assess whether such differences in the responsiveness to drugs of abuse are related to differences in mesolimbic DA neuron function. In RHA rats, morphine, cocaine, and amphetamine caused a larger increase in DA efflux in the NAC shell vs. the NAC core, whereas the profile for the drug-induced increases in DA output was almost completely superimposable in the NAC shell and NAC core of RLA rats. Moreover, morphine, cocaine, and amphetamine caused a larger increment in basal DA output in the NAC shell of RHA rats vs. the NAC shell of RLA rats. These drugs also elicited a more robust increase in locomotion, rearing, sniffing, and grooming in RHA than in RLA rats. These results demonstrate that genetically determined differences in the functional properties of DA neurons projecting to the NAC shell may critically influence the behavioural response patterns to addictive drugs that distinguish the Roman lines.

Animals↗
PubMed1999

Chocolate: food or drug?

Although addictive behavior is generally associated with drug and alcohol abuse or compulsive sexual activity, chocolate may evoke similar psychopharmacologic and behavioral reactions in susceptible persons. A review of the literature on chocolate cravings indicates that the hedonic appeal of chocolate (fat, sugar, texture, and aroma) is likely to be a predominant factor in such cravings. Other characteristics of chocolate, however, may be equally as important contributors to the phenomena of chocolate cravings. Chocolate may be used by some as a form of self-medication for dietary deficiencies (eg, magnesium) or to balance low levels of neurotransmitters involved in the regulation of mood, food intake, and compulsive behaviors (eg, serotonin and dopamine). Chocolate cravings are often episodic and fluctuate with hormonal changes just before and during the menses, which suggests a hormonal link and confirms the assumed gender-specific nature of chocolate cravings. Chocolate contains several biologically active constituents (methylxanthines, biogenic amines, and cannabinoid-like fatty acids), all of which potentially cause abnormal behaviors and psychological sensations that parallel those of other addictive substances. Most likely, a combination of chocolate's sensory characteristics, nutrient composition, and psychoactive ingredients, compounded with monthly hormonal fluctuations and mood swings among women, will ultimately form the model of chocolate cravings. Dietetics professionals must be aware that chocolate cravings are real. The psychopharmacologic and chemosensory effects of chocolate must be considered when formulating recommendations for overall healthful eating and for treatment of nutritionally related health issues.

Animals↗
PubMed2002

D1 dopamine receptor: a putative neurochemical and behavioral link to cocaine action.

Cocaine is one of the most abused psychostimulants known to man and as such, researchers have been steadfast in their attempts to understand the neurobiological mechanisms responsible for its abuse. Cocaine undoubtedly wreaks havoc on a number of mammalian neuronal neurotransmitter systems, and it is maintained that this dysregulatory effect supports cocaine abuse. Cocaine's mechanism of action has been well described. Cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons (Heikkila et al., 1975, Biochem Pharmacol 24(8):847-852; Reith et al., 1986, Biochem Pharmacol 35(7):1123-1129; Ritz et al., 1987, Science 237:1219-1223). Inhibition of re-uptake subsequently elevates the synaptic concentrations of each of these neurotransmitters. In addition to this direct effect, cocaine also produces a number of indirect actions, which alter other neuromodulatory systems (i.e., opioidergic, glutamatergic, and GABAergic systems). Many of these effects are just beginning to be elucidated, but nonetheless contribute to this agent's diverse pharmacological profile. Interestingly, it is the indirect actions of this mellifluous molecule, which mediate most of its sought and unsought effects. The intricacy with which cocaine produces neuronal alterations beyond its direct effects on neurotransmitter re-uptake appear to be most relevant to cocaine abuse, and hence the phenomenon of addiction. In light of cocaine's multifarious effects on numerous neuronal systems, its effect on dopaminergic neurotransmission has attracted the most attention, particularly because of the implicated role of dopamine in brain reward. Pharmacologically, the psychostimulant effects of cocaine appear to be mediated by its ability to enhance dopaminergic activity within the mesocorticolimbic circuit (Roberts et al., 1977, Pharmacol Biochem Behav 6(6):615-620). Additionally, it is the intensity with which cocaine produces alterations in dopaminergic circuitry that have enabled this drug to prevail as one of the most addictive substances known to man. This review will summarize findings relevant to cocaine-induced alterations in dopamine-mediated signal transduction. Specifically, it will concentrate on the D1 dopamine receptor and intracellular signaling mediated by this receptor subtype. It will describe cocaine-induced cellular and behavioral alterations relevant to this pathway and how these changes potentially effect gene transcription and protein expression. This article too will review a common behavioral manifestation associated with repeated cocaine exposure, sensitization, and why the D1 dopamine receptor and its associated signaling pathway have been implicated in this phenomenon. Lastly, this article will discuss how targeting the D1 dopamine receptor and its signaling pathway may offer some insight into understanding cocaine addiction, a somewhat elusive brain disease.

Animals↗
PubMed2000

Evaluating the spiritual perspectives of homeless men in recovery.

The purpose of this study was to describe the self-reported spiritual perspectives of 100 homeless male residents living in a communal shelter. The residents, in recovery from substance addiction, were asked to complete Reed's 10-item Spiritual Perspective Scale (SPS) as part of their initial health database. Their responses were described within the context of their participation in 12-Step recovery programs, demographic characteristics, and perceived health status. Findings suggest that spirituality is an important health component for this population.

Adult↗
PubMed2002

Nicotine intervention during detoxification and treatment for other substance use.

This preliminary study evaluated the efficacy of a brief smoking cessation intervention (30 controls, 34 intervention groups) on a smoke-free inpatient unit for substance use detoxification. Controls received usual care, including the transdermal nicotine patch and referral to an outpatient smoking program. The intervention group additionally received a structured motivational enhancement program. Biochemically confirmed smoking cessation rate and abstinence/reduction of alcohol or other drug use were the main outcome measures taken 6 months after treatment initiation. The smoking cessation intervention did not result in greater participation in formal outpatient smoking cessation treatment and was not associated with either enhanced smoking cessation (6 vs. 0%) or greater smoking reduction at follow-up. Both groups significantly reduced the number of cigarettes smoked per day (cpd) from about 24 at baseline to 10cpd. The groups did not differ on abstinence from nonnicotine addictive substances. Smoking cessation treatment in substance users undergoing detoxification resulted in little or no smoking cessation advantage.

Adult↗
PubMedDate not supplied

[The risk factors for the transmission of HIV infection among intravenous narcotic users in Russia].

Blood sera (316,281 specimens) from registered drug and toxic substance addicts were examined revealing no subjects seropositive to HIV. A special epidemiological questionnaire was developed and used for questioning of 86 drug addicts using drugs prepared domestically by the intravenous route. The group included 56 men and 30 women varying in age from 17 to 33 years. Lack of registered cases of HIV infection among drug addicts in Russia was explained by some peculiar features of using drugs. Intravenous inoculation of drugs with the same syringe and needle without sterilization, and large numbers of sexual contacts without the use of condoms suggest that as soon as HIV gets into this environment it will spread very rapidly.

Adolescent↗
PubMed2005

Opposite effects of MK-801 on the expression of food and morphine-induced conditioned place preference in rats.

Behavioural studies have provided strong evidence for common substrates in the rewards of natural and addictive substances, but it is still unclear whether there is a common glutamatergic NMDA receptor mechanism involved in the processing of reward for both. The present study was designed to investigate the effects of MK-801 (0.1mg/kg) on the expression of place preference conditioned with food and morphine (5.0mg/kg) in rats. The data indicates that MK-801 potentiates the expression of food-induced conditioned place preference (CPP) but retards that of morphine CPP. It also demonstrates that the opposite effects of MK-801 on food and morphine CPP expression were caused neither by hyperactivity nor by the impairment of memory retrieval. These results suggest that MK-801 enhances food craving and inhibits morphine craving in rats, and that the roles of glutamatergic NMDA receptor mechanisms in the reward processing of natural reinforcers and addictive drugs may be dissociable.

Animals↗
PubMed2000

Biological aspects of the link between smoking and depression.

A link between smoking and depressive symptoms has been described in the literature for over a decade. The neurotransmitter systems affected by cigarette smoke mirror the neurotransmitter pathways thought to be involved in the biological mechanisms of depression. Cigarette smoke contains several psychoactive chemicals; nicotine is the best studied among these and is widely accepted to be the addictive substance in tobacco. Nicotine binds to nicotinic receptors in the brain, augmenting the release of numerous neurotransmitters, including dopamine, serotonin, norepinephrine, acetylcholine, gamma-aminobutyric acid, and glutamate. Cigarette smoke has other psychoactive properties apart from nicotinic receptor stimulation. For example, it inhibits monoamine oxidase (the enzyme responsible for breaking down the biogenic amine neurotransmitters norepinephrine, serotonin, and dopamine) in the brain. Various antidepressants act through modulation of the biogenic amine neurotransmitter pathways. That the neural substrates modified by both smoking and antidepressant drugs overlap has relevance to smoking cessation. The use of antidepressants as adjuvants to smoking-cessation treatment can enhance cessation success rates. Understanding the neurobiological mechanisms underlying the association between smoking and depression may improve physicians' ability to assist smokers in their efforts to quit and will contribute to a more thorough comprehension of both the biology of addiction and the etiology of depression.

Affect↗
PubMed2002

Neurokinin-1 (NK-1) receptor antagonists abrogate methamphetamine-induced striatal dopaminergic neurotoxicity in the murine brain.

Methamphetamine (METH) is an addictive substance that also causes extensive neural degeneration in the central nervous system. Because METH augments striatal substance P (SP) levels, we hypothesized that this neuropeptide plays a role in methamphetamine-induced toxicity and neural damage in the striatum. In this study we present evidence demonstrating that signaling through the neurokinin-1 (NK-1) receptor by SP plays an important role in methamphetamine-induced toxicity in the striatum. We tested the effects of the selective NK-1 receptor antagonists WIN-51,708 and L-733,060 on several markers of dopaminergic terminal toxicity in the mouse striatum. Administration of NK-1 receptor antagonist prevented the loss of dopamine transporters assessed by autoradiography and western blotting, the loss of tissue dopamine assessed by high-pressure liquid chromatography, and the loss of tyrosine hydroxylase, as well as the induction of glial fibrillary acidic protein determined by western blotting. Pre-treatment with NK-1 receptor antagonist had no effect on METH-induced hyperthermia. Pre-exposure of mice to either of the NK-1 receptor antagonists alone was without effect on all of these neurochemical markers. These results provide the first evidence that tachykinins, particularly SP, acting through NK-1 receptors, play a crucial role in the pathogenesis of nigrostriatal dopaminergic terminal degeneration induced by METH. This finding could lead to novel therapeutic strategies to offset drug addictions as well as in the treatment of a number of disorders including Parkinson's and Huntington's diseases.

Androstanes↗