Therapeutic Prospects of Cannabidiol for Alcohol Use Disorder and Alcohol-Related Damages on the Liver and the Brain.

Background: Cannabidiol (CBD) is a natural component of cannabis that possesses a widespread and complex immunomodulatory, antioxidant, anxiolytic, and antiepileptic properties. Much experimental data suggest that CBD could be used for various purposes in alcohol use disorder (AUD) and alcohol-related damage on the brain and the liver. Aim: To provide a rationale for using CBD to treat human subjects with AUD, based on the findings of experimental studies. Methods: Narrative review of studies pertaining to the assessment of CBD efficiency on drinking reduction, or on the improvement of any aspect of alcohol-related toxicity in AUD. Results: Experimental studies find that CBD reduces the overall level of alcohol drinking in animal models of AUD by reducing ethanol intake, motivation for ethanol, relapse, anxiety, and impulsivity. Moreover, CBD reduces alcohol-related steatosis and fibrosis in the liver by reducing lipid accumulation, stimulating autophagy, modulating inflammation, reducing oxidative stress, and by inducing death of activated hepatic stellate cells. Finally, CBD reduces alcohol-related brain damage, preventing neuronal loss by its antioxidant and immunomodulatory properties. Conclusions: CBD could directly reduce alcohol drinking in subjects with AUD. Any other applications warrant human trials in this population. By reducing alcohol-related steatosis processes in the liver, and alcohol-related brain damage, CBD could improve both hepatic and neurocognitive outcomes in subjects with AUD, regardless of the individual's drinking trajectory. This might pave the way for testing new harm reduction approaches in AUD, in order to protect the organs of subjects with an ongoing AUD.

Dehumanization of psychiatric patients: Experimental and clinical implications in severe alcohol-use disorders.

Dehumanization, defined as the denial of one's membership to humanity, is a process repeatedly reported in extreme contexts (e.g., genocides) but also in everyday life interactions. Some antecedents of dehumanizing experiences (e.g., social exclusion, negative stereotypes) have been reported among patients presenting psychiatric disorders, but dehumanization's experience remains completely unexplored in addictive disorders. We propose a theoretical model and research agenda to overcome this limitation and to improve our understanding of dehumanization's experience in psychiatry, with a special focus on alcohol-related disorders. We also propose much-needed clinical avenues to reduce dehumanization in clinical contexts, centrally by (1) improving dehumanization awareness among medical workers; (2) reducing the need for healthcare workers to use dehumanization to alleviate professional exhaustion; and (3) optimizing medical training to increase empathy toward patients. Finally, some additional improvements are proposed to promote patient's choices, comfort, dignity, and ultimately humanity in hospitals.

Impaired affective prosody decoding in severe alcohol use disorder and Korsakoff syndrome.

Recognizing others' emotions is a fundamental social skill, widely impaired in psychiatric populations. These emotional dysfunctions are involved in the development and maintenance of alcohol-related disorders, but their differential intensity across emotions and their modifications during disease evolution remain underexplored. Affective prosody decoding was assessed through a vocalization task using six emotions, among 17 patients with severe alcohol use disorder, 16 Korsakoff syndrome patients (diagnosed following DSM-V criteria) and 19 controls. Significant disturbances in emotional decoding, particularly for negative emotions, were found in alcohol-related disorders. These impairments, identical for both experimental groups, constitute a core deficit in excessive alcohol use.

Dissociation between implicit and explicit expectancies of cannabis use in adolescence.

Cannabis is one of the most commonly drugs used by teenagers. Expectancies about its effects play a crucial role in cannabis consumption. Various tools have been used to assess expectancies, mainly self-report questionnaires measuring explicit expectancies, but implicit measures based on experimental tasks have also been developed, measuring implicit expectancies. The aim of this study was to simultaneously assess implicit/explicit expectancies related to cannabis among adolescent users and non-users. 130 teenagers attending school (55 girls) were enrolled (Age: M=16.40 years); 43.84% had never used cannabis ("non-users") and 56.16% had used cannabis ("users"). They completed self-report questionnaires evaluating cannabis use, cannabis-related problems, effect expectancies (explicit expectancies), alcohol use, social and trait anxiety, depression, as well as three Implicit Association Tests (IAT) assessing implicit expectancies. Adolescents manifested more implicit affective associations (relaxation, excitation, negative) than neutral ones regarding cannabis. These were not related to explicit expectancies. Cannabis users reported more implicit relaxation expectancies and less negative explicit expectancies than non-users. The frequency of use and related problems were positively associated with the explicit expectancies regarding relaxation and enhancement, and were negatively associated with negative explicit expectancies and negative implicit expectancies. Findings indicate that implicit and explicit expectancies play different roles in cannabis use by adolescents. The implications for experimentation and prevention are discussed.

Facial, vocal and musical emotion recognition is altered in paranoid schizophrenic patients.

Disturbed processing of emotional faces and voices is typically observed in schizophrenia. This deficit leads to impaired social cognition and interactions. In this study, we investigated whether impaired processing of emotions also affects musical stimuli, which are widely present in daily life and known for their emotional impact. Thirty schizophrenic patients and 30 matched healthy controls evaluated the emotional content of musical, vocal and facial stimuli. Schizophrenic patients are less accurate than healthy controls in recognizing emotion in music, voices and faces. Our results confirm impaired recognition of emotion in voice and face stimuli in schizophrenic patients and extend this observation to the recognition of emotion in musical stimuli.

Adaptation to vocal expressions reveals multistep perception of auditory emotion.

The human voice carries speech as well as important nonlinguistic signals that influence our social interactions. Among these cues that impact our behavior and communication with other people is the perceived emotional state of the speaker. A theoretical framework for the neural processing stages of emotional prosody has suggested that auditory emotion is perceived in multiple steps (Schirmer and Kotz, 2006) involving low-level auditory analysis and integration of the acoustic information followed by higher-level cognition. Empirical evidence for this multistep processing chain, however, is still sparse. We examined this question using functional magnetic resonance imaging and a continuous carry-over design (Aguirre, 2007) to measure brain activity while volunteers listened to non-speech-affective vocalizations morphed on a continuum between anger and fear. Analyses dissociated neuronal adaptation effects induced by similarity in perceived emotional content between consecutive stimuli from those induced by their acoustic similarity. We found that bilateral voice-sensitive auditory regions as well as right amygdala coded the physical difference between consecutive stimuli. In contrast, activity in bilateral anterior insulae, medial superior frontal cortex, precuneus, and subcortical regions such as bilateral hippocampi depended predominantly on the perceptual difference between morphs. Our results suggest that the processing of vocal affect recognition is a multistep process involving largely distinct neural networks. Amygdala and auditory areas predominantly code emotion-related acoustic information while more anterior insular and prefrontal regions respond to the abstract, cognitive representation of vocal affect.

The neural network sustaining crossmodal integration is impaired in alcohol-dependence: an fMRI study.

INTRODUCTION: Crossmodality (i.e., the integration of stimulations coming from different sensory modalities) is a crucial ability in everyday life and has been extensively explored in healthy adults. Still, it has not yet received much attention in psychiatry, and particularly in alcohol-dependence. The present study investigates the cerebral correlates of crossmodal integration deficits in alcohol-dependence to assess whether these deficits are due to the mere accumulation of unimodal impairments or rather to specific alterations in crossmodal areas. METHODS: Twenty-eight subjects [14 alcohol-dependent subjects (ADS), 14 paired controls] were scanned using fMRI while performing a categorization task on faces (F), voices (V) and face-voice pairs (FV). A subtraction contrast [FV-(F+V)] and a conjunction analysis [(FV-F) ∩ (FV-V)] isolated the brain areas specifically involved in crossmodal face-voice integration. The functional connectivity between unimodal and crossmodal areas was explored using psycho-physiological interactions (PPI). RESULTS: ADS presented only moderate alterations during unimodal processing. More centrally, in the subtraction contrast and conjunction analysis, they did not show any specific crossmodal brain activation while controls presented activations in specific crossmodal areas (inferior occipital gyrus, middle frontal gyrus, superior parietal lobule). Moreover, PPI analyses showed reduced connectivity between unimodal and crossmodal areas in alcohol-dependence. CONCLUSIONS: This first fMRI exploration of crossmodal processing in alcohol-dependence showed a specific face-voice integration deficit indexed by reduced activation of crossmodal areas and reduced connectivity in the crossmodal integration network. Using crossmodal paradigms is thus crucial to correctly evaluate the deficits presented by ADS in real-life situations.

Latent deleterious effects of binge drinking over a short period of time revealed only by electrophysiological measures.

BACKGROUND: Episodic excessive alcohol consumption (i.e., binge drinking) is now considered to be a major public health problem, but whereas short-and long-term harmful consequences of this behaviour are clearly established at medical, social and cognitive levels, the cerebral correlates of these impairments are still unknown. Our study explores the midterm cerebral effects of binge-drinking behaviours among young adults. METHODS: We selected 2 groups of first-year university students with no history of drinking habits, paired for psychological and behavioural measures on the basis of their expected alcohol consumption during the forthcoming academic year. The binge drinker group expected to have high personal alcohol consumption, whereas the control group expected low consumption. We used a test-retest paradigm within a 9-month period (session 1 in September 2005, session 2 in May 2006). At each testing session, we recorded auditory event-related potentials while the participants performed an emotional valence judgment task. RESULTS: There were no differences between the groups in behavioural or electrophysiological measures at baseline. After 9 months, the binge drinkers had significantly delayed latencies for all event-related potential components (P1, N2, P3b) of emotional auditory processing compared with the control group (p < 0.006), with no behavioural differences. LIMITATIONS: As the present study explored the electrophysiological correlates of binge drinking with an emotional task only, the results will have to be extended to other cognitive processes using various experimental tasks. CONCLUSION: We report the first direct evidence that short-term binge drinking can produce marked cerebral dysfunction undetectable by behavioural measures alone. The observed latency abnormalities, similar to those observed in long-term alcoholism, constitute an electrophysiological marker of slowed cerebral activity associated with binge drinking.