Rationale
Alcohol use disorder is a common and devastating mental illness for which satisfactory treatments are still lacking. Nalmefene, as an opioid receptor modulator, could pharmacologically ...support the reduction of drinking by reducing the (anticipated) rewarding effects of alcohol and expanding the range of treatment options. It has been hypothesized that nalmefene acts via an indirect modulation of the mesolimbic reward system. So far, only a few imaging findings on the neuronal response to nalmefene are available.
Objectives
We tested the effect of a single dose of 18 mg nalmefene on neuronal cue-reactivity in the ventral and dorsal striatum and subjective craving.
Methods
Eighteen non-treatment-seeking participants with alcohol use disorder (67% male,
M
= 50.3 ± 13.9 years) with a current high-risk drinking level (
M
= 76.9 ± 52 g of pure alcohol per day) were investigated using a cue-reactivity task during functional magnetic resonance imaging (fMRI) in a double-blind, placebo-controlled, cross-over study/design. In addition, self-reported craving was assessed before and after exposure to alcohol cues.
Results
An a priori defined region of interest (ROI) analysis of fMRI data from 15 participants revealed that nalmefene reduced alcohol cue-reactivity in the ventral, but not the dorsal striatum. Additionally, the subjective craving was significantly reduced after the cue-reactivity task under nalmefene compared to placebo.
Conclusion
In the present study, reduced craving and cue-reactivity to alcohol stimuli in the ventral striatum by nalmefene indicates a potential anti-craving effect of this drug via attenuation of neural alcohol cue-reactivity.
ABSTRACT
Aims During the development of drug addiction, initial hedonic effects decrease when substance use becomes habitual and ultimately compulsive. Animal research suggests that these changes ...are represented by a transition from prefrontal cortical control to subcortical striatal control and within the striatum from ventral to dorsal domains of the striatum, but only limited evidence exists in humans. In this study we address this hypothesis in the context of alcohol dependence.
Design, setting and participants Non‐abstinent heavy social drinkers (n = 21, 5.0 ± 1.5 drinks/day, 13 of them were alcohol‐dependent according to DSM‐IV) and light social drinkers (n = 10, 0.4 ± 0.4 drinks/day) were examined.
Measurements We used a cue‐reactivity functional magnetic resonance imaging (fMRI) design during which pictures of alcoholic beverages and neutral control stimuli were presented.
Findings In the dorsal striatum heavy drinkers showed significant higher activations compared to light drinkers, whereas light social drinkers showed higher cue‐induced fMRI activations in the ventral striatum and in prefrontal areas compared to heavy social drinkers region of interest analyses, P < 0.05 false discovery rate (FDR)‐corrected. Correspondingly, ventral striatal activation in heavy drinkers correlated negatively with obsessive‐compulsive craving, and furthermore we found a positive association between cue‐induced activation in the dorsal striatum and obsessive‐compulsive craving in all participants.
Conclusions In line with our hypothesis we found higher cue‐induced activation of the ventral striatum in social compared to heavy drinkers, and higher dorsal striatal activation in heavy drinkers. Increased prefrontal activation may indicate that social drinkers activate cortical control when viewing alcohol cues, which may prevent the development of heavy drinking or alcohol dependence. Our results suggest differentiating treatment research depending on whether alcohol use is hedonic or compulsive.
Cannabis use and the development of schizophrenic psychoses share a variety of similarities. Both start during late adolescence; go along with neuropsychological deficits, reduced activity, ...motivation deficits, and hallucinations suggesting impairment of similar brain structures. In cannabis heavy users diminished regional gray and white matter volume was reported. Similar alterations were observed in the large literature addressing structural abnormalities in schizophrenia. Furthermore, in cannabis using schizophrenic patients, these brain alterations were especially pronounced. Close relatives of schizophrenic patients showed greater cannabis-associated brain tissue loss than non-relatives indicating a genetically mediated particular sensitivity to brain tissue loss. Possible mechanisms for the induction of structural brain alterations are here discussed including impairments of neurogenesis, disturbance of endocannabinoids and diminished neuroplasticity. Especially direct THC effects (or via endocannabinoids) may mediate diminished glutamatergic neurotransmission usually driving neuroplasticity. Correspondingly, alterations of the kynurenic acid blocking NMDA receptors may contribute to brain structure alterations. However, different cannabis compounds may exert opposite effects on the neuroanatomical changes underlying psychosis. In particular, cannabidiol (CBD) was shown to prevent THC associated hippocampal volume loss in a small pilot study. This finding is further supported by several animal experiments supporting neuroprotective properties of CBD mainly via anti-oxidative effects, CB2 receptors or adenosine receptors. We will discuss here the mechanisms by which CBD may reduce brain volume loss, including antagonism of THC, interactions with endocannabinoids, and mechanisms that specifically underlie antipsychotic properties of CBD.
Opioid-dependent patients frequently show deficits in multiple cognitive domains that might impact on their everyday life performance and interfere with therapeutic efforts. To date, the ...neurobiological underpinnings of those deficits remain to be determined. We investigated working memory performance and gray matter volume (GMV) differences in 17 patients on opioid maintenance treatment (OMT) and 17 healthy individuals using magnetic resonance imaging and voxel-based morphometry. In addition, we explored associations between substance intake, gray matter volume, and working memory task performance. Patients on OMT committed more errors during the working memory task than healthy individuals and showed smaller insula and putamen GMV. The duration of heroin use prior to OMT was associated with working memory performance and insula GMV in patients. Neither the substitution agent (methadone and buprenorphine) nor concurrent abuse of illegal substances during the 3 months prior to the experiment was significantly associated with GMV. Results indicate that impaired working memory performance and structural deficits in the insula of opioid-dependent patients are related to the duration of heroin use. This suggests that early inclusion into OMT or abstinence-oriented therapies that shorten the period of heroin abuse may limit the impairments to GMV and cognitive performance of opioid-dependent individuals.
Background
Chronic alcohol abuse leads to severe damage of the nervous system, including a change in cerebral metabolism and brain morphology. Global volume reductions of gray matter (GM) and white ...matter and an increase in cerebrospinal fluid (CSF) occur after severe alcohol consumption, but abstinent alcoholics also demonstrate a brain volume recovery. The aim of this study was to investigate whether volumetric amelioration takes place already within the first 2 weeks of abstinence.
Methods
All 49 alcohol‐dependent patients included in this study were scanned within the first 24 hours of detoxification and after 2 weeks of supervised abstinence. Amelioration of volumetric brain loss in alcohol‐dependent patients has been investigated, and brain volumes have been compared with 55 healthy control subjects using whole‐brain segmentation and a voxel‐based morphometric approach.
Results
On the first day of abstinence, the global CSF volume was larger and the GM volume was smaller in alcohol‐dependent patients compared with healthy controls. The largest clusters with significant volumetric differences were in the cingulate gyrus, precentral and middle frontal gyrus, cerebellum, and insula. Already after 2 weeks of abstinence, a significant albeit partial recovery of GM volume occurred in several brain regions.
Conclusions
Our results show that recovery of GM volume in alcohol‐dependent patients starts within a few days after detoxification but varies between brain regions. This suggests that the general ability to recover and the rate as well as onset of the recovery diverges for different brain regions.
Pharmacological treatment in alcohol use disorder suffers from modest effect sizes. Efforts have been undertaken to identify patient characteristics that help to select individuals that benefit from ...pharmacological treatment. Previous studies indicated that neural alcohol cue-reactivity (CR) might provide a marker that identifies patients, which benefit from naltrexone treatment.
We investigated the reproducibility of the association between ventral striatum (VS) activation and naltrexone (NTX) treatment response by analyzing data from a recent longitudinal clinical trial in
N
= 44 abstinent treatment-seeking alcohol-dependent patients. A follow-up was conducted over 3 months. We computed the percentage of significant voxels in VS and tested main effects and interactions with NTX treatment on relapse risk using Cox Regression models.
We found a significant interaction effect between pre-treatment cue reactivity in the VS and NTX treatment on time to first heavy relapse (Hazard Ratio = 7.406, 95% CI 1.17–46.56,
p
= 0.033), such that the patient group with high VS activation (defined by a mean split) showed a significant medication effect (Hazard Ratio = 0.140, 95% CI 0.02–0.75,
p
= 0.022) with a number needed to treat of 3.4 95% CI 2.413.5, while there was no significant effect in the group with low VS activation (Hazard Ratio = 0.726,
p
= 0.454).
Thus, using an independent sample we replicated the previously described positive association between VS activation and NTX efficacy. Although our results should be considered cautiously in light of the small sample size, our results support the potential of neural alcohol CR as a tool for precision medicine approaches in alcohol dependence.
Cannabis Use and Car Crashes: A Review Preuss, Ulrich W.; Huestis, Marilyn A.; Schneider, Miriam ...
Frontiers in psychiatry,
05/2021, Letnik:
12
Journal Article
Recenzirano
Odprti dostop
In this review, state-of-the-art evidence on the relationship between cannabis use, traffic crash risks, and driving safety were analyzed. Systematic reviews, meta-analyses, and other relevant papers ...published within the last decade were systematically searched and synthesized. Findings show that meta-analyses and culpability studies consistently indicate a slightly but significantly increased risk of crashes after acute cannabis use. These risks vary across included study type, crash severity, and method of substance application and measurement. Some studies show a significant correlation between high THC blood concentrations and car crash risk. Most studies do not support this relationship at lower THC concentrations. However, no scientifically supported clear cut-off concentration can be derived from these results. Further research is needed to determine dose-response effects on driving skills combined with measures of neuropsychological functioning related to driving skills and crash risk.
In this report, we present cross-sectional and longitudinal findings from single-voxel MEGA-PRESS MRS of GABA as well as Glu, and Glu + glutamine (Glx) concentrations in the ACC of treatment-seeking ...alcohol-dependent patients (ADPs) during detoxification (first 2 weeks of abstinence). The focus of this study was to examine whether the amount of benzodiazepine administered to treat withdrawal symptoms was associated with longitudinal changes in Glu, Glx, and GABA. The tNAA levels served as an internal quality reference; in agreement with the vast majority of previous reports, these levels were initially decreased and normalized during the course of abstinence in ADPs. Our results on Glu and Glx support hyperglutamatergic functioning during alcohol withdrawal, by showing higher ACC Glu and Glx levels on the first day of detoxification in ADPs. Withdrawal severity is reflected in cumulative benzodiazepine requirements throughout the withdrawal period. The importance of withdrawal severity for the study of GABA and Glu changes in early abstinence is emphasized by the benzodiazepine-dependent Glu, Glx, and GABA changes observed during the course of abstinence.
Theory of mind (ToM) is an aspect of social cognition impaired in different addictive disorders, including opioid addiction. This study aimed at replicating ToM deficits in opioid dependent patients ...undergoing opioid maintenance treatment (OMT) and exploring the influence of substance use related variables, executive functions and childhood maltreatment on ToM in opioid dependent patients. 66 opioid dependent patients were tested using the Movie for Assessment of Social Cognition (MASC) and compared with the data of healthy controls. Furthermore, the opioid dependent patients underwent testing for executive functions and filled in the Childhood Trauma Questionnaire (CTQ). Performance on the MASC was significantly poorer in the opioid dependence group than in the control group, even when recent additional drug use and psychiatric comorbidities were controlled for. No correlations were found between ToM and substance use related factors. Aspects of ToM performance in opioid dependent patients correlated significantly with different EF domains. ToM correlated significantly with the CTQ scales for physical maltreatment. The results confirm impaired ToM in opioid dependent patients and highlight executive functions and childhood maltreatment as influential factors. The lack of associations between ToM and substance use related variables and the association with childhood maltreatment suggest that ToM impairments might be a risk factor predating substance abuse.
Childhood maltreatment (CM) leads to detrimental mental health outcomes, such as substance use disorders (SUD). This study examined prevalence and severity of all five types of CM with respect to ...specific substances and sex in treatment-seeking individuals with SUD. The influences of type of CM and symptoms of depressiveness, anxiety, and perceived stress on substance craving at admission as well as craving reduction during SUD treatment were examined.
= 546 patients in treatment for SUD and
= 109 individuals in opioid maintenance treatment filled out questionnaires regarding CM (Childhood Trauma Questionnaire) and psychopathologies. Substance craving was assessed throughout treatment using the Mannheim Craving Scale. Group differences in CM, type of substance and sex were examined. General linear models were applied to examine influences on substance craving.
Higher prevalence and severity of all five subtypes of CM were observed in individuals with SUD compared to the general population. Women were more severely affected by emotional and sexual abuse than men. Patients with cannabis use disorder reported more severe experiences of emotional abuse compared to all other substances. Craving at admission to treatment was influenced by emotional abuse, however, symptoms of depressiveness, anxiety, and perceived stress contributed to craving at admission or craving reduction during treatment.
CM relates to SUD and should be incorporated in prevention and treatment of SUD. Underlying mechanisms of the association might relate to impairments in processing and regulation of stress, emotions, and interpersonal relations following a history of CM.
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