Journal of addiction research & therapy最新文献

Background: Polymorphisms in the μ-, δ- and κ-opioid receptor genes (OPRM1, OPRD1 and OPRK1) have been reported to be associated with substance (alcohol or drug) dependence. The influence of an individual gene on a disease trait should be more evident when analyzed in the context of gene-gene interactions. Thus, we assessed the joint effect of variants in these three opioid receptor genes on alcohol, cocaine, or opioid dependence.

Methods: Genotype data for 13 OPRM1 Single Nucleotide Polymorphisms (SNPs), 11 OPRD1 SNPs and seven OPRK1 SNPs were obtained from 382 European Americans (EAs) affected with substance dependence [among them, 318 with Alcohol Dependence (AD), 171 with Cocaine Dependence (CD), and 91 with Opioid Dependence (OD)] and 338 EA control subjects. We assessed the joint effect of OPRM1, OPRD1 and OPRK1 variants on AD, CD, or OD using a pattern discovery-based association test. Specific marker patterns (consisting of alleles of OPRM1, OPRD1 and OPRK1) that were significantly more frequent in AD, CD, or OD cases than in controls were identified.

Results: 12 significant patterns in the AD dataset, four significant patterns in the CD dataset, and 18 significant patterns in the OD dataset were identified. Moreover, the significance of most marker patterns was due primarily to OPRM1 variants and, to a lesser degree, OPRD1 variants.

Conclusion: Our findings suggest that variation in the above three opioid receptor genes can jointly influence the vulnerability of individuals to alcohol or drug dependence. Evidence provided by this study also supports previous biological findings that the interaction of the three opioid receptors can modulate the action of opioid and non-opioid drugs and alcohol.

Alterations in memory function due to alcohol exposure have been observed in both animal models and human populations. The human literature on neurocognitive consequences of binge alcohol use in emerging adults has not systematically investigated its potential negative impacts on visuospatial memory. For instance, these impacts have not yet been assessed using a human analogue of the Morris Water Maze Task (WMT), a key memory measure in the animal literature. Accordingly, this study compared performance between emerging adult binge drinkers (BD, n=22) and age- and sex-matched light drinkers (LD, n=29) using the Morris WMT, as well as verbal memory using the California Verbal Learning Test (CVLT). Emerging adult BD demonstrated worse performance on verbal learning and memory relative to LD. However, no significant group differences were observed on spatial learning and memory. Furthermore, no sex differences or interactions with drinking status were observed on either memory domain. These data suggest that in emerging adults who are at a heightened risk for alcohol abuse disorders, but who do not yet meet diagnostic criteria, verbal learning is uniquely impacted by the neurotoxic effects of binge drinking, whereas spatial learning is relatively spared between bouts of intoxication.

Marijuana (MJ) remains the most widely used illicit drug of abuse, and accordingly, is associated with adverse effects on mental and physical health, and neurocognitive decline. Studies investigating the neurobiology of underlying MJ effects have demonstrated structural and functional alterations in brain areas that contain moderate to high concentrations of cannabinoid (CB1) receptors and that are implicated in MJ-related cognitive decrements. Proton magnetic resonance spectroscopy (¹H MRS), a non-invasive imaging technique used to assess neurochemistry, has been widely applied to probe a variety of substance-abusing populations. To date, however, there is a relative paucity of MRS published studies characterizing changes in neurometabolite concentrations in MJ users. Thus, the current review provides a summary of data from the eight existing MRS studies of MJ use in adolescents and adults, as well as interpretations and implications of study findings. Future MRS studies that address additional factors such as sex differences, onset and duration of use, abstinence and age, are warranted, and would lead to a more thorough characterization of potential neurochemical correlates of chronic MJ use, which would fill critical gaps in the existing literature.

Background: While numerous studies support the efficacy of methadone and buprenorphine for the stabilization and maintenance of opioid dependence, clinically significant opioid withdrawal symptoms occur upon tapering and cessation of dosage.

Methods: We present a case study of a 35 year old Caucasian female (Krissie) who was prescribed increasing dosages of prescription opioids after carpel tunnel surgery secondary to chronic pain from reflex sympathetic dystrophy and fibromyalgia. Over the next 5 years, daily dosage requirements increased to over 80 mg of Methadone and 300 ug/hr Fentanyl transdermal patches, along with combinations of 12-14 1600 mcg Actig lollipop and oral 100 mg Morphine and 30 mg oxycodone 1-2 tabs q4-6hr PRN for breakthrough pain. Total monthly prescription costs including supplemental benzodiazepines, hypnotics and stimulants exceeded $50,000. The patient was subsequently transferred to Suboxone® in 2008, and the dosage was gradually tapered until her admission for inpatient detoxification with KB220Z a natural dopaminergic agonist. We carefully documented her withdrawal symptoms when she precipitously stopped taking buprenorphine/naloxone and during follow-up while taking KB220Z daily. We also genotyped the patient using a reward gene panel including (9 genes 18 alleles): DRD 2,3,4; MOA-A; COMT; DAT1; 5HTTLLR; OPRM1; and GABRA3.

Findings: At 432 days post Suboxone® withdrawal the patient is being maintained on KB220Z, has been urine tested and is opioid free. Genotyping data revealed a moderate genetic risk for addiction showing a hypodopaminergic trait. This preliminary case data suggest that the daily use of KB220Z could provide a cost effective alternative substitution adjunctive modality for Suboxone®. We encourage double-blind randomized -placebo controlled studies to test the proposition that KB220Z may act as a putative natural opioid substitution maintenance adjunct.

Smoking is frequently co-morbid with depression. Although it is recognized that depression increases the risk for smoking, it is unclear if early smoking exposure may increase the risk for depression. To test this possibility we assessed the effects of adolescent nicotine exposure on the Forced Swim Test (FST), which is used as a measure of passive coping, and depressive-like behavior in rodents, and on the open field test (OFT), which is used as a measure of locomotion and exploratory behavior. Male and female mice received daily saline or nicotine (0.3 or 0.6 mg/kg) injections from postnatal day (PD) 30 to PD 44. FST and OFT were performed either 1 or 30 days after the last injection (PD 45 and PD 74, respectively). In females, treatment with 0.3 mg/kg nicotine lead to increased FST immobility (64%) and decreased OFT locomotor activity (12%) one day following the last nicotine injection (PD 45); while no effects were observed in adulthood (PD 74). In contrast, on PD45, nicotine treatment did not change the male FST immobility but lead to lower OFT locomotor activity (0.6 mg/kg, 10%). In adulthood (PD 74), both nicotine doses lead to higher FST immobility (87%) in males while 0.6 mg/kg nicotine to lower OFT locomotor activity (13%). The results (i) identify females as more vulnerable to the immediate withdrawal that follows nicotine discontinuation in adolescence and (ii) suggest that adolescent nicotine exposure may enhance the risk for passive response towards unavoidable stress in adult males.

The effects of chronic marijuana (MRJ) use on neurochemistry are not well characterized. Previously, altered global myo-Inositol (mI) concentrations and distribution in white matter were associated with impulsivity and mood symptoms in young MRJ-dependent men. The objective of this study was to retrospectively examine previously collected data, to investigate the potential regional specificity of metabolite levels in brain regions densely packed with cannabinoid receptors. Spectra were acquired at 4.0 Tesla using 2D J-resolved proton magnetic resonance spectroscopic imaging (MRSI) to quantify the entire J-coupled spectral surface of metabolites from voxels in regions of interest. For the current regional spectral analyses, a 2D-JMRSI grid was positioned over the central axial slice and shifted in the x and y dimensions to optimally position voxels over regions containing thalamus, temporal lobe, and parieto-occipital cortex. MRJ users exhibited significantly reduced mI levels in the left thalamus (lThal), relative to non-using participants, which were associated with elevated cognitive impulsivity. Other regional analyses did not reveal any significant group differences. The current findings indicate that reduced mI levels are regionally specific to the lThal in MRJ users. Furthermore, findings suggest that mI and the lThal uniquely contribute to elevated impulsivity.

Methylone is a member of the designer drug class known as synthetic cathinones which have become increasingly popular drugs of abuse in recent years. Commonly referred to as "bath salts", these amphetamine-like compounds are sold as "legal" alternatives to illicit drugs such as cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy). Following their dramatic rise in popularity along with numerous reports of toxicity and death, several of these drugs were classified as Schedule I drugs in the United States in 2012. Despite these bans, these drugs and other new structurally similar analogues continue to be abused. Currently, however, it is unknown whether these compounds possess the potential for compulsive use and addiction. The present study sought to determine the relative abuse liability of methylone by employing intravenous self-administration (IVSA) and intracranial self-stimulation (ICSS) paradigms in rats. We demonstrate that methylone (0.05, 0.1, 0.2, and 0.5 mg/kg/infusion) dose-dependently functions as a reinforcer, and that there is a significant positive relationship between methylone dose and reinforcer efficacy. Furthermore, responding during short access sessions (ShA, 2 hr/day) appeared more robust than previous IVSA studies with MDMA. However, unlike previous findings with abused stimulants such as cocaine or methamphetamine, long access sessions (LgA, 6 hr/day) did not lead to escalated drug intake or increased reinforcer efficacy. Finally, methylone produced a dose-dependent, but statistically non-significant, trend towards reductions in ICSS thresholds. Together these results reveal that methylone may possess an addiction potential similar to or greater than MDMA, yet patterns of self-administration and effects on brain reward function suggest that this drug may have a lower potential for abuse and compulsive use than prototypical psychostimulants.