Dialogues in Clinical Neuroscience

Background: A severe form of pathological social withdrawal, 'hikikomori,' has been acknowledged in Japan, spreading worldwide, and becoming a global health issue. The pathophysiology of hikikomori has not been clarified, and its biological traits remain unexplored. Methods: Drug-free patients with hikikomori ( n  = 42) and healthy controls ( n  = 41) were recruited. Psychological assessments for the severity of hikikomori and depression were conducted. Blood biochemical tests and plasma metabolome analysis were performed...

Chemsex is an escalating public health issue among men who have sex with men, with potentially severe somatic and psychiatric consequences. Given the limited knowledge and lack of treatment recommendations available in this area, we proposed the use of noninvasive brain stimulation in order to reduce problematic chemsex behavior. This is the first open-label case report of a positive effect of transcranial direct current stimulation (tDCS) in a patient who was complaining of severe chemsex addiction. Total disappearance of chemsex behavior occurred after 5 days of daily sessions of right prefrontal cortex stimulation and did not return after 8 months of follow-up...

This brief report covers recent advances in cannabis and cannabinoid regulation and drug approval. The popularity of cannabis and cannabinoid products continues to rise, and these products are available for the majority of the population in the United States to purchase as easily as alcohol. Although many states have approved programs and research licenses, these activities and products all remain federally illegal. The solution may be for the United States to offer multiple pathways for product approval that adapt to the diversity of the products and the needs of the consumer...

As is the case for most drugs, cannabis use has costs and benefits, and so do the policies that attempt to minimize the first and maximize the second. This article summarizes what we know about the harmful effects of recreational cannabis use and the benefits of medical cannabis use under the policy of prohibition that prevailed in developed countries until 2012. It outlines three broad ways in which cannabis prohibition may be relaxed, namely, the depenalization of personal possession and use, the legalization of medical use, and the legalization of adult recreational use...

Mental disorders represent a significant public health burden worldwide due to their high prevalence, chronically disabling nature, and substantial impact on quality of life. Despite growing knowledge of the pathological mechanisms that underlie the development of these disorders, a high percentage of patients do not respond to first-line clinical treatments; thus, there is a strong need for alternative therapeutic approaches. During the past half-century, after the identification of the endocannabinoid system and its role in multiple physiological processes, both natural and synthetic cannabinoids have attracted considerable interest as putative medications in pathological conditions such as, but not exclusive to, mental disorders...

The endocannabinoid (eCB) system encompasses the eCBs anandamide and 2-arachidonoylglycerol, their anabolic/catabolic enzymes, and the cannabinoid CB1 and CB2 receptors. Its expansion to include several eCB-like lipid mediators, their metabolic enzymes, and their molecular targets, forms the endocannabinoidome (eCBome). This complex signaling system is deeply involved in the onset, progress, and symptoms of major neuropsychiatric disorders and provides a substrate for future therapeutic drugs against these diseases...

Cannabis can elicit an acute psychotic reaction, and its long-term use is a risk factor for schizophrenia. The main active psychoactive ingredient ∆9 -tetrahydrocannabinol (Δ9 -THC) activates cannabinoid 1 (CB1) receptors, which are localized to the terminals of glutamate and GABA neurons in the brain. The endogenous cannabinoids are involved in information processing and plasticity at synapses in the hippocampus, basal ganglia, and cerebral cortex. Exogenously applied CB1 receptor agonists disrupt neuronal dynamics and synaptic plasticity, resulting in cognitive deficits and impairment of the highest psychological functions...

The last decades have seen a major gain in understanding the action of cannabinoids and the endocannabinoid system in reward processing and the development of addictive behavior. Cannabis-derived psychoactive compounds such as Δ9 -tetrahydrocannabinol and synthetic cannabinoids directly interact with the reward system and thereby have addictive properties. Cannabinoids induce their reinforcing properties by an increase in tonic dopamine levels through a cannabinoid type 1 (CB1 ) receptor-dependent mechanism within the ventral tegmental area...

The endocannabinoid system is widely expressed in the limbic system, prefrontal cortical areas, and brain structures regulating neuroendocrine stress responses, which explains the key role of this system in the control of emotions. In this review, we update recent advances on the function of the endocannabinoid system in determining the value of fear-evoking stimuli and promoting appropriate behavioral responses for stress resilience. We also review the alterations in the activity of the endocannabinoid system during fear, stress, and anxiety, and the pathophysiological role of each component of this system in the control of these protective emotional responses that also trigger pathological emotional disorders...

This article retraces the story of cannabis from the earliest contacts of humans with the plant to its subsequent global expansion, its medicinal uses, and the discovery of the endocannabinoid system in the 20th century. Cannabis was attested to around 12 000 years ago near the Altai Mountains in Central Asia, and since then, cannabis seeds have accompanied the migration of nomadic peoples. Records of the medicinal use of cannabis appear before the Common Era in China, Egypt, and Greece (Herodotus), and later in the Roman empire (Pliny the Elder, Dioscorides, Galen)...

The endocannabinoid system (ECS) is a highly versatile signaling system within the nervous system. Despite its widespread localization, its functions within the context of distinct neural processes are very well discernable and specific. This is remarkable, and the question remains as to how such specificity is achieved. One key player in the ECS is the cannabinoid type 1 receptor (CB1 ), a G protein-coupled receptor characterized by the complexity of its cell-specific expression, cellular and subcellular localization, and its adaptable regulation of intracellular signaling cascades...

The use of cannabis as a drug has undergone a remarkable change of direction: considered as a symbol of countercultures in past decades, it is presently being hailed as a cure for any number of diseases and conditions. Thus, despite concerns about the safety of cannabis and cannabinoids, quite a few drugs that contain cannabinoids have recently been approved by several drug agencies, and the medicinal and recreational use of cannabis has been legalized in various countries and states. The promise of cannabinoids for therapeutic use, as well as potentially detrimental health risks and regulatory issues, will need to be carefully weighed...

Digital technology, including its omnipresent connectedness and its powerful artificial intelligence, is the most recent long wave of humanity's socioeconomic evolution. The first technological revolutions go all the way back to the Stone, Bronze, and Iron Ages, when the transformation of material was the driving force in the Schumpeterian process of creative destruction. A second metaparadigm of societal modernization was dedicated to the transformation of energy (aka the "industrial revolutions"), including water, steam, electric, and combustion power...

Emerging scientific evidence indicates that frequent digital technology use has a significant impact-both negative and positive-on brain function and behavior. Potential harmful effects of extensive screen time and technology use include heightened attention-deficit symptoms, impaired emotional and social intelligence, technology addiction, social isolation, impaired brain development, and disrupted sleep. However, various apps, videogames, and other online tools may benefit brain health. Functional imaging scans show that internet-naive older adults who learn to search online show significant increases in brain neural activity during simulated internet searches...

Virtual reality (VR) is a potentially powerful technology for enhancing assessment in mental health. At any time or place, individuals can be transported into immersive and interactive virtual worlds that are fully controlled by the researcher or clinician. This capability is central to recent interest in how VR might be harnessed in both treatment and assessment of mental health conditions. The current review provides a summary of the advantages of using VR for assessment in mental health, focusing on increasing ecological validity of highly controlled environments, enhancing personalization and engagement, and capturing real-time, automated data in real-world contexts...

Major depression (MD) is a highly prevalent and severe disorder with many patients having no access to efficient treatments such as pharmaco- and psychotherapy. Web-based interventions promise to be a method to provide resource-efficient and widespread access to psychotherapeutic support. Meta-analyses summarizing studies that use face-to-face psychotherapy as a comparator provide evidence for equivalent antidepressant efficacy. Web-based interventions seem to be particularly efficacious when they are accompanied by some form of professional guidance...

Media coverage of research on phones and social media over the last decade has prompted widespread concern and one-size-fits-all guidance to limit screen time. Recognizing the limitations of screen time as a metric, researchers are now studying technology use in terms of affordances, individual differences, and longitudinal patterns. The current review examines technology use by parents, caregivers, couples, and clinicians. Individuals in these roles navigate risks, such as privacy violations, with benefits such as improved communication, empathy, and progress toward shared goals...

Adolescents are constantly connected to their devices, and concerns have been raised that this connectivity is damaging their development more generally, and their mental health in particular. Recent narrative reviews and meta-analyses do not support a strong linkage between the quantity of adolescents' digital technology engagement and mental health problems. Instead, it appears that offline vulnerabilities tend to mirror and shape online risks in ways that may further amplify mental health inequalities among youth...

This review provides an overview of the literature regarding digital technology use and adolescent well-being. Overall, findings imply that the general effects are on the negative end of the spectrum but very small. Effects differ depending on the type of use: whereas procrastination and passive use are related to more negative effects, social and active use are related to more positive effects. Digital technology use has stronger effects on short-term markers of hedonic well-being (eg, negative affect) than long-term measures of eudaimonic well-being (eg, life satisfaction)...

The growing amount of screen time among adolescents has raised concerns about the effects it may have on their physical and psychological health. Although the literature is divided on whether the effects are mostly positive, neutral, or mostly negative, it is likely that the impacts will be highly individualized with a mixture of good and bad consequences for each person. Understanding behavioral and neurobiological phenomena of adolescence may help to guide research and interventions to optimize the benefits and minimize the risks...