Cannabinoid abuse and addiction: Clinical and preclinical findings.
Ontology highlight
ABSTRACT:
SUBMITTER: Panlilio LV
PROVIDER: S-EPMC4446186 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
Publications
Cannabinoid abuse and addiction: Clinical and preclinical findings.
Panlilio L V LV Goldberg S R SR Justinova Z Z
Clinical pharmacology and therapeutics 20150502 6
Cannabinoid abuse disorders represent a widespread public health issue, but there are no approved medications for their treatment. This review describes efforts to understand the mechanisms of cannabinoid abuse and its adverse effects, to identify molecular targets for pharmacotherapy, and to evaluate potential treatments in human volunteers and animal models of cannabinoid reward, withdrawal, and relapse. ...[more]
Similar Datasets
Project description:The purpose of the current study was to evaluate possible overlapping substance abuse and internet addiction in a large, uniformly sampled population, ranging in age from 13 to 18 years. Participants (N=73,238) in the current study were drawn from the 6th Korea Youth Risk Behavior Web-based Survey (KYRBWS-V) for students from 400 middle schools and 400 high schools in 16 cities within South Korea. Of adolescent internet users, 85.2% were general users (GU), 11.9% were users with potential risk for internet addiction (PR), and 3.0% were users with high risk for internet addiction (HR). There was a difference in the number of students with alcohol drinking among the GU, PR, and HR groups (20.8% vs 23.1% vs 27.4%). There was a difference in the number of students who smoked among the GS, PR, and HR groups (11.7% vs 13.5% vs 20.4%). There was a difference in the number of students with drug use among the GU, PR, and HR groups (1.7% vs 2.0% vs 6.5%). After adjusting for sex, age, stress, depressed mood, and suicidal ideation, smoking may predict a high risk for internet addiction (OR=1.203, p=0.004). In addition, drug use may predict a high risk for internet addiction (OR=2.591, p<0.001). Because students with a high risk for internet addiction have vulnerability for addictive behaviors, co-morbid substance abuse should be evaluated and, if found, treated in adolescents with internet addiction.
| S-EPMC4651446 | biostudies-literature
Project description:OxyContin and other pharmaceutical opioids have been given special attention in the media, who frequently describe problematic users of the drug as previously drug-naive individuals who become addicted following legitimate prescriptions for medical reasons. The purpose of this study was to characterize the nature and origins of pharmaceutical opioid addiction among patients presenting at substance abuse treatment programs.The authors evaluated the prevalence and correlates of OxyContin use and abuse among a population of 27,816 subjects admitted to 157 addiction treatment programs in the United States from 2001-2004. The data collected included the lifetime and past 30-day use of OxyContin and other drugs prior to admission to addiction treatment, source of drug supply, and prior treatment history.Approximately 5% of all subjects who were admitted to the 157 addiction treatment programs reported prior use of OxyContin. Of those subjects, 4.5% reported using the drug on a regular basis for at least 1 year, and 2% reported use of the drug during the 30 days prior to admission. Seventy-eight percent of subjects who reported OxyContin use also reported that the drug had not been prescribed to them for any medical reason, 86% reported use of the drug to "get high or get a buzz," and 78% reported receiving prior treatment for a substance use disorder.The patients in this sample did not include individuals from private therapists or pain clinics. However, among treatment-seeking individuals who use OxyContin, the drug is most frequently obtained from nonmedical sources as part of a broader and longer-term pattern of multiple substance abuse.
| S-EPMC2785002 | biostudies-literature
Project description:The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.
| S-EPMC3462342 | biostudies-literature
Project description:BackgroundDespite the growing prevalence of prescription opioid dependence, longitudinal studies have not examined long-term treatment response. The current study examined outcomes over 42 months in the Prescription Opioid Addiction Treatment Study (POATS).MethodsPOATS was a multi-site clinical trial lasting up to 9 months, examining different durations of buprenorphine-naloxone plus standard medical management for prescription opioid dependence, with participants randomized to receive or not receive additional opioid drug counseling. A subset of participants (N=375 of 653) enrolled in a follow-up study. Telephone interviews were administered approximately 18, 30, and 42 months after main-trial enrollment. Comparison of baseline characteristics by follow-up participation suggested few differences.ResultsAt Month 42, much improvement was seen: 31.7% were abstinent from opioids and not on agonist therapy; 29.4% were receiving opioid agonist therapy, but met no symptom criteria for current opioid dependence; 7.5% were using illicit opioids while on agonist therapy; and the remaining 31.4% were using opioids without agonist therapy. Participants reporting a lifetime history of heroin use at baseline were more likely to meet DSM-IV criteria for opioid dependence at Month 42 (OR=4.56, 95% CI=1.29-16.04, p<.05). Engagement in agonist therapy was associated with a greater likelihood of illicit-opioid abstinence. Eight percent (n=27/338) used heroin for the first time during follow-up; 10.1% reported first-time injection heroin use.ConclusionsLong-term outcomes for those dependent on prescription opioids demonstrated clear improvement from baseline. However, a subset exhibited a worsening course, by initiating heroin use and/or injection opioid use.
| S-EPMC4407806 | biostudies-literature
Project description:?9 -tetrahydrocannabinol, the principal active component in Cannabis sativa extracts such as marijuana, participates in cell signalling by binding to cannabinoid CB1 and CB2 receptors on the cell surface. The CB1 receptors are present in both inhibitory and excitatory presynaptic terminals and the CB2 receptors are found in neuronal subpopulations in addition to microglial cells and astrocytes and are present in both presynaptic and postsynaptic terminals. Subsequent to the discovery of the endocannabinoid (eCB) system, studies have suggested that alcohol alters the eCB system and that this system plays a major role in the motivation to abuse alcohol. Preclinical studies have provided evidence that chronic alcohol consumption modulates eCBs and expression of CB1 receptors in brain addiction circuits. In addition, studies have further established the distinct function of the eCB system in the development of fetal alcohol spectrum disorders. This review provides a recent and comprehensive assessment of the literature related to the function of the eCB system in alcohol abuse disorders.
| S-EPMC6692638 | biostudies-literature
Project description:Background: The incidence of alcohol and tobacco co-abuse is as high as 80%. The molecular mechanism underlying this comorbidity is virtually unknown but interactions between these drugs have important implications for the development of, and recovery from drug dependence. Methods: We investigated the effects of chronic tobacco and alcohol abuse and the interaction of the two behaviours on global gene expression in the human nucleus accumbens using cDNA microarrays and 20 alcoholic and control cases, with and without smoking comorbidity. Changes in gene expression were established by two-way ANOVA. Unsupervised hierarchical clustering was utilized to probe the strength of the data sets. Results: Subjecting the data sets derived from microarray gene expression screening to unsupervised hierarchical clustering tied the cases into distinct groups. When considering all alcohol-responsive genes, alcoholics were separated from non alcoholics with the exception of one control case. All smokers were distinguished from non smokers based on similarity in expression of smoking-sensitive genes. In the nucleus accumbens, alcohol-responsive genes were associated with transcription, lipid metabolism and signalling. Smoking-sensitive genes were predominantly assigned to functional groups concerned with RNA processing and the endoplasmic reticulum. Both drugs influenced the expression of genes involved in matrix remodelling, proliferation and cell morphogenesis. Additionally, a gene set encoding proteins involved in the canonical pathway ‘regulation of the actin cytoskeleton’ was induced in response to alcohol and tobacco co-abuse and included. Conclusions: The region-specific modulation of alcohol-sensitive gene expression by smoking may have important consequences for alcohol-induced aberrations within the mesolimbic dopaminergic system. The data set contained individual RNA samples extracted from the nucleus accumbens from 5 non smoking non drinking control case, 5 non smoking alcoholics, 5 non drinking smokers, and 5 smoking alcoholics. An aliquot if each sample was combined to generate a reference pool. Each sample was amplified individually and labelled with Cy3 in the process, the reference samples was amplified and labelled with Cy5. Each sample was hybridised competitively against the reference sample to 1 array.
2010-07-01 | E-GEOD-20568 | biostudies-arrayexpress
Project description:PIK3CA mutations represent one of the most common genetic aberrations in breast cancer. They have been reported to be present in over one-third of cases, with enrichment in the luminal and in human epidermal growth factor receptor 2-positive subtypes. Substantial preclinical data on the oncogenic properties of these mutations have been reported. However, whilst the preclinical data have clearly shown an association with robust activation of the pathway and resistance to common therapies used in breast cancer, the clinical data reported up to now do not support that the PIK3CA mutated genotype is associated with high levels of pathway activation or with a poor prognosis. We speculate that this may be due to the minimal use of transgenic mice models thus far. In this review, we discuss both the preclinical and clinical data associated with PIK3CA mutations and their potential implications. Prospective clinical trials stratifying by PIK3CA genotype will be necessary to determine if the mutation also predicts for increased sensitivity to agents targeting the phosphoinositide 3-kinase pathway.
| S-EPMC4054885 | biostudies-literature
Project description:To date, few studies have evaluated the contribution of early life experiences to neurocognitive abnormalities observed in posttraumatic stress disorder (PTSD). Childhood maltreatment is common among individuals with PTSD and is thought to catalyze stress-related biobehavioral changes that might impact both brain structure and function in adulthood. The current study examined differences in brain morphology (brain volume, cortical thickness) and neuropsychological performance in individuals with PTSD characterized by low or high self-reported childhood maltreatment, compared with healthy comparison participants. Data were drawn from the INjury and TRaUmatic STress (INTRuST) Clinical Consortium imaging repository, which contains MRI and self-report data for individuals classified as PTSD positive (with and without a history of mild traumatic brain injury [mTBI]), individuals with mTBI only, and healthy comparison participants. The final sample included 36 individuals with PTSD without childhood maltreatment exposure (PTSD, n = 30 with mTBI), 31 individuals with PTSD and childhood maltreatment exposure (PTSD + M, n = 26 with mTBI), and 114 healthy comparison participants without history of childhood maltreatment exposure (HC). The PTSD + M and PTSD groups demonstrated cortical thinning in prefrontal and occipital regions, and poorer verbal memory and processing speed compared to the HC group. PTSD + M participants demonstrated cortical thinning in frontal and cingulate regions, and poorer executive functioning relative to the PTSD and HC groups. Thus, neurocognitive features varied between individuals with PTSD who did versus did not have exposure to childhood maltreatment, highlighting the need to assess developmental history of maltreatment when examining biomarkers in PTSD.
| S-EPMC7568209 | biostudies-literature
Project description:Background: The incidence of alcohol and tobacco co-abuse is as high as 80%. The molecular mechanism underlying this comorbidity is virtually unknown but interactions between these drugs have important implications for the development of, and recovery from drug dependence. Methods: We investigated the effects of chronic tobacco and alcohol abuse and the interaction of the two behaviours on global gene expression in the human nucleus accumbens using cDNA microarrays and 20 alcoholic and control cases, with and without smoking comorbidity. Changes in gene expression were established by two-way ANOVA. Unsupervised hierarchical clustering was utilized to probe the strength of the data sets. Results: Subjecting the data sets derived from microarray gene expression screening to unsupervised hierarchical clustering tied the cases into distinct groups. When considering all alcohol-responsive genes, alcoholics were separated from non alcoholics with the exception of one control case. All smokers were distinguished from non smokers based on similarity in expression of smoking-sensitive genes. In the nucleus accumbens, alcohol-responsive genes were associated with transcription, lipid metabolism and signalling. Smoking-sensitive genes were predominantly assigned to functional groups concerned with RNA processing and the endoplasmic reticulum. Both drugs influenced the expression of genes involved in matrix remodelling, proliferation and cell morphogenesis. Additionally, a gene set encoding proteins involved in the canonical pathway ‘regulation of the actin cytoskeleton’ was induced in response to alcohol and tobacco co-abuse and included. Conclusions: The region-specific modulation of alcohol-sensitive gene expression by smoking may have important consequences for alcohol-induced aberrations within the mesolimbic dopaminergic system.
2010-07-01 | GSE20568 | GEO
Project description:This review gives an overview of what we see as the key issues in the human pharmacology of drugs of addiction. We review evidence of efficacy and mechanisms by which treatments act and point out areas where further work is needed. The role of agonist, partial agonist and antagonist treatments for opioid addiction is detailed and current issues relating to the mechanisms of actions at the receptor level and how to improve on compliance are discussed. The role of the brain dopamine and GABA-A systems in drug dependence is considered in relation to the growing pharmacology of these receptor systems, and the current status of novel preclinical targets reviewed. In addition, the different roles of dynamic and kinetic factors in both addiction and its treatment are discussed in relation to the underlying neuropharmacology of the disorders as defined from human and preclinical studies. Finally, some pointers to future research and especially to drug development by pharma are elaborated.
| S-EPMC2442452 | biostudies-other