Search Results (53)

Psychotic disorder remains a major global health burden despite the plethora of anti-psychotic medications currently available. Poor adherence owing to numerous adverse effects and cost burden is a major challenge to treating psychosis. In view of this, the use of ethnomedicinal plants has become more common. In Nigeria, West Africa, the seeds of Phaseolus lunatus (Lima bean) are used to treat psychosis-like illness. Despite its extensive use, there are not many scientific studies that validate its efficacy. Therefore, this study evaluated the antipsychotic, anxiolytic-like, and sleep-enhancing properties of the seed extract. Pulverized dried seeds were extracted in a mixture (1:1) of water and methanol and screened for phytoconstituents. Using murine models, oral doses of 400, 800, and 1600 mg/kg of the extract were evaluated for antipsychotic, anxiolytic, and sleep-enhancing properties. Brain malondialdehyde (MDA), superoxide dismutase (SOD), catalase, glutathione peroxidase, and glutathione reductase (GR) levels were estimated after administering the doses of extract to mice for 14 consecutive days. The seed extract significantly inhibited d-amphetamine-induced stereotypy and ketamine-induced hyperlocomotion in a dose-dependent manner. It also exhibited significant anxiolytic-like activity at 800 mg/kg, as indicated by increased time spent on the open arm of the elevated plus maze and an increased number of head dips on the hole board. Compared with untreated controls, sleep onset was significantly faster, and sleep duration was longer in mice that received 1600 mg/kg of the extract. There was a decrease in MDA levels at a dose of 1600 mg/kg and an increase in SOD and GR levels in the mice brains. Our findings suggest that Lima bean extract exhibited antipsychotic-like, anxiolytic-like, sedative–hypnotic, and antioxidant activities in mice likely due to its flavonoid and alkaloidal constituents. Our study provides preliminary evidence in mice that supports the ethnomedicinal use of Lima beans as a functional food for psychosis-like illness. Full article

Imaginative suggestibility is an important component of hypnotic responsiveness. However, a validated German version of the Creative Imagination Scale (CIS) is lacking. This study aimed to evaluate the psychometric properties and convergent validity of the German CIS against the short form of the Harvard Group Scale of Hypnotic Susceptibility (HGSHS-5:G) in individuals with mild to moderate depressive symptoms. In this post hoc validation study, the German CIS was evaluated using reliability analyses, exploratory and confirmatory factor analyses, and mixed polychoric–tetrachoric correlations with the HGSHS-5:G. Among 97 participants, the CIS showed good internal consistency (α = 0.85, ω = 0.87). A two-factor model showed better fit than a unidimensional model, although absolute model fit remained suboptimal and the factors were highly correlated (r = 0.80). CIS and HGSHS-5:G scores were moderately correlated (r = 0.52, p < 0.001), supporting convergent validity. This first validation of the German CIS demonstrated good reliability and preliminary evidence for a two-factor structure, warranting replication in larger samples. The CIS may complement behavioral measures of hypnotic responsiveness in research and clinical applications. Full article

Hypnotic hypoalgesia effectively reduces various types of pain, but its neurophysiological mechanisms remain unclear. EEG and somatosensory event-related potentials (SERPs) can help elucidate how hypnotic suggestions influence pain processing across sensory, emotional, and cognitive domains. This review synthesizes evidence on EEG oscillatory activity and SERP correlates in hypnotic pain modulation and interprets the findings through predictive coding and active inference frameworks. The review integrated relevant studies on EEG frequency-band oscillations, SERPs, and the modulation of pain by hypnosis, focusing on a convergent neurophysiological account of hypnotic pain modulation rather than on individual studies. Research indicates that hypnotic hypoalgesia is associated with concerted changes across multiple EEG frequency bands. Theta activity is linked to focused internal attention and the maintenance of suggestion-consistent representations, while increased alpha activity may indicate inhibitory sensory gating and reduced nociceptive gain. Beta oscillations enhance pain relief in cognitive and motor functions, while decreased gamma activity indicates reduced significance of pain signals. SERP findings show that hypnotic suggestions primarily affect late evaluative components (e.g., P200/P250, P300) rather than early sensory elements, suggesting changes in salience assignment and affective-cognitive appraisal rather than uniform suppression of nociceptive input. Predictive coding and active inference explain how hypnotic suggestions change pain-related expectations and bodily perceptions. This insight is key to enhancing personalized pain management and guiding future neuroscience research. Full article

Background/Objectives: Insomnia is a prevalent clinical sleep disorder, with existing hypnotic therapies limited by safety concerns. There is an urgent clinical need for new safe, effective sleep-promoting candidates derived from natural products. Spinosin is one of the main active components of Semen Ziziphi Spinosae that exerts sedative and hypnotic effects. The adenosine receptor (AR) has been reported as a potential therapeutic target for insomnia; however, the hypnotic effect of spinosin through the A_2AR remains to be elucidated. Methods: In the study, the involvement of A_2ARs in spinosin’s hypnotic effect was investigated using caffeine and further elucidated in A_2AR-knockout (KO) mice. Diazepam was used as a positive control drug to validate the experimental model and evaluate the hypnotic effect of spinosin. Molecular docking and molecular dynamics (MDs) simulations were performed to validate the interaction of spinosin with the A_2AR. Results: The hypnotic effects of spinosin were effectively antagonized by caffeine. Compared with A_2AR-wild-type (WT) mice, spinosin-induced non-rapid eye movement (NREM) sleep and locomotor activity diminution were significantly reduced in A_2AR-KO mice. Spinosin significantly increased the activity of γ-aminobutyric acid (GABA)ergic medium spiny neurons (MSNs) in the nucleus accumbens (NAc) and significantly decreased the activity of orexin neurons in the lateral hypothalamus (LH), as revealed by c-Fos immunostaining. These effects were significantly reversed by caffeine pretreatment or in A_2AR-KO mice. Finally, the results of molecular docking showed that spinosin had a good binding potential with the A_2AR. MD simulations further demonstrated that spinosin had strong binding stability with the A_2AR. Conclusions: Our findings strongly suggest that spinosin exerts the hypnotic effects through the A_2AR, and thus may have therapeutic potential for insomnia. Our identification of spinosin’s direct molecular target supports its translational potential as a novel natural-origin candidate for clinical insomnia drug development. Full article

Background: Sleep disorders, particularly insomnia, represent a major public health concern, while currently available hypnotic drugs are often limited by adverse effects and poor long-term tolerability. Methods: In this study, we investigated the sleep-promoting effects of a mixture of Hypericum perforatum L. and Melissa officinalis L. extract (HME) and its underlying mechanisms in male ICR and C57BL/6 mice. In a pentobarbital-induced sleep model in mice, sleep onset latency and total sleep time were measured. Pharmacological studies using various antagonists and agonists were conducted to elucidate receptor-mediated mechanisms. Immunohistochemical and immunofluorescence analyses were performed to assess neuronal activity, and cortical mRNA expression was evaluated by quantitative analysis. HPLC analysis was used to identify the major constituents of HME, and their pharmacological profiles were functionally evaluated. Results: HME significantly reduced sleep onset latency and prolonged total sleep time. These hypnotic effects were shown to be mediated through adenosine and melatonin receptor signaling pathways. Immunohistochemical and immunofluorescence analyses showed that HME suppressed neuronal activity in wake-promoting cholinergic and orexinergic neurons of the basal forebrain and lateral hypothalamus, while enhancing activation of sleep-promoting GABAergic neurons in the ventrolateral preoptic nucleus. At the molecular level, HME increased cortical mRNA expression levels of adenosine A₁ receptor, adenosine A_2A receptor, melatonin receptor 1, and melatonin receptor 2. From the HPLC analysis, rosmarinic acid and hyperoside were identified as the major constituents of HME. Functional evaluation of these compounds revealed complementary pharmacological profiles, with hyperoside primarily acting through adenosine receptors and rosmarinic acid engaging both adenosine and melatonin receptor pathways. Conclusions: These findings suggest that HME enhances both sleep initiation and maintenance through adenosine and melatonin receptor signaling pathways, thereby supporting its potential as a multitarget therapeutic agent for improving sleep quality. Full article

Insomnia is increasingly recognized as a manifestation of multisystem dysregulation characterized by sustained physiological hyperarousal. This review situates insomnia within a framework of reciprocal disturbances across neuroendocrine, inflammatory, and autonomic pathways. It examines the potential roles of cannabidiol (CBD), polyunsaturated fatty acids (PUFAs) derived from hemp seed oil (HSO), and lignans from black sesame oil (BSO) as modulators of upstream biological processes relevant to sleep regulation. Rather than acting as direct hypnotics, these compounds are considered for their capacity to influence convergent mechanisms involved in sleep–wake stability. Preclinical evidence suggests that CBD modulates endocannabinoid and serotonergic signaling, potentially contributing to the regulation of physiological processes associated with hyperarousal. Concurrently, HSO-derived fatty acids support mitochondrial function and lipid-mediated resolution. Sesame lignans further contribute through antioxidant properties linked to redox balance, neurometabolic stability, and modulation of neural excitability. However, the current evidence base is predominantly preclinical, and definitive conclusions regarding therapeutic efficacy or optimal dosing in humans remain limited. Future research should prioritize integrative clinical studies that link these specific biological modulations to standardized sleep outcomes to determine their real-world applicability. Nevertheless, the pathways discussed align with biological domains consistently implicated in established insomnia phenotypes. This review integrates these compounds within a shared hyperarousal framework to highlight convergent upstream mechanisms that extend beyond their individual effects. Full article

Hypnosis has traditionally been conceptualized as a clinical technique for reducing physiological symptoms (e.g., pain, nausea) and psychological symptoms (e.g., anxiety, intrusive thoughts), yet emerging neuroscientific evidence suggests it operates through the fundamental mechanisms of emotional regulation and self-integration. This integrative review synthesizes research on clinical hypnosis from cognitive neuroscience, affective science, and clinical practice to examine how hypnotic phenomena modulate large-scale brain networks—particularly the default mode network (DMN), executive control network (ECN), and salience network (SaN)—to reorganize emotional experience and self-referential processing. We propose a formal mechanistic model in which hypnotic induction produces heightened experiential plasticity through coordinated network reconfiguration, enabling adaptive emotion regulation and reduced dissociative fragmentation. Central to this framework is the construct of Fundamental Peace (FP), operationalized as a dynamic neuro-experiential state characterized by: (1) flexible attentional control without effortful suppression; (2) emotional coherence across self-states; (3) reduced self-referential rigidity; (4) compassionate self-awareness. Unlike equanimity (affective neutrality) or well-being (positive evaluation), Fundamental Peace represents integrated regulatory capacity under changing conditions. Key findings from neuroimaging studies demonstrate that hypnotic states consistently reduce DMN activity, enhance ECN-SaN coupling, and modulate connectivity patterns associated with self-referential processing. Meta-analytic evidence from 85 controlled experimental trials shows robust pain reduction effects, while clinical studies document improvements in trauma-related dissociation and emotional dysregulation. We critically evaluate this framework against alternative theories (dissociated control, cold control, predictive processing, social-cognitive models), specify testable predictions, and assess evidence quality across neuroimaging and clinical domains. Implications for trauma treatment, clinical implementation, and future research integrating causal inference methods are discussed, alongside ethical and cultural considerations. Full article

Background: Hypnotizability is a psychophysiological trait measured by standardized scales whose scores indicate the proneness to modify perception, memory, and behavior according to specific suggestions, and to experience the hypnotic state. Hypnotizability exhibits physiological and behavioral correlates in the ordinary state of consciousness and brain morphological peculiarities. Among them, a reduced Grey Matter volume (GMV) of the insula and cerebellar lobules IV–VI has been observed in high hypnotizable individuals (highs) compared to low hypnotizables (lows). Theoretically, these structures could cooperate with the basal ganglia (BG) in hypnotizability-related sensorimotor and cognitive–emotional differences. Methods: Since no imaging study has focused on the BG as a function of hypnotizability, the present research investigated the morphometric characteristics of the BG in the highs (N = 12) and lows (N = 37) enrolled in a previous study focused on the cerebellum. Results: The results did not show any significant difference in the GMV of the caudate and pallidum. Conclusions: Thus, the hypnotizability-related behavioral and physiological difference, as well as the responsiveness to hypnotic suggestions associated with the insula and cerebellum variations, are not partially accounted for by BG structural differences. Full article

The Acronicta major larva is a toxic agricultural pest that poses severe ecological management challenges. This study presents a sustainable strategy to valorize this hazardous biological waste into functional nanotherapeutics for insomnia by leveraging its unique intrinsic chemical composition. Carbon dots derived from Acronicta major larva (AM-CDs) were synthesized via one-step pyrolysis, which facilitated the natural molecular pre-assembly of N,S-codoping. Their physicochemical properties and cytotoxicity were evaluated using a series of characterizations and the CCK-8 assay. The sedative and hypnotic effects were assessed in mice with PCPA-induced insomnia through hot plate, Open Field and pentobarbital-induced sleep tests, and their potential mechanism was explored via neurotransmitter detection. The thermal process effectively eliminated intrinsic toxicity while retaining bioactivity via in situ heteroatom doping. AM-CDs exhibited favorable biocompatibility and significant sedative–hypnotic activity, reducing anxiety-related agitation without motor impairment. Mechanistically, AM-CDs effectively restored the GABA/5-HT/glutamate axis. Unlike direct central receptor binding, our findings suggest that this therapeutic effect is likely mediated through a systemic or peripheral regulatory pathway. This study demonstrates the conversion of toxic pests into safe and intrinsically bioactive nanomaterials, providing a dual solution for ecological pest management and novel neuroactive agent development, and validating the “Waste-to-Wealth” concept in biomedicine. Full article

Mindful hypnotherapy is an intervention that integrates hypnotic induction and direct suggestions (hypnosis) to increase mindfulness and reduce distress. In the present study, a systematic review and meta-analysis were conducted to investigate the effects of mindful hypnotherapy on psychological distress and mindfulness in adults. Further, the study evaluated the methodological quality of the included studies. A total of five publications of randomized controlled trials were identified. This meta-analysis found that, when compared to both waitlist and active control groups, mindful hypnotherapy had a large effect on the reduction in psychological distress (Hedges’ g = 0.61, 95% CI [0.10, 1.12], z = 2.36, p = 0.0188) and stress (Hedges’ g = 0.75, 95% CI [0.34, 1.16]; z = 3.58, p = 0.0003). Further, results also found mindful hypnotherapy had a large effect on increasing mindfulness (Hedges’ g = 1.38, SE = 0.28; 95% CI [0.83, 1.92]; z = 4.9146, p < 0.001). Recommendations include conducting research examining mindful hypnotherapy in a wider range of clinical problems (i.e., generalized anxiety disorder, depression, post-traumatic stress). In addition, clinical trials of mindful hypnotherapy should include active controls and measures of hypnotizability. Further research is also needed with diverse populations. Full article

Ericksonian hypnotherapy (EH), a client-centered hypnotic approach characterized by indirect suggestion, individualized flexibility, collaboration, and the principle of Utilization, has seen increased interest as a therapeutic modality across diverse clinical settings. This systematic review and meta-analysis aimed to evaluate the efficacy of EH by synthesizing evidence from randomized controlled trials (RCTs) published between 2015 and 2025. Eight eligible RCTs (N = 676) were identified, spanning conditions such as acute pain, depression, grief, irritable bowel syndrome, disordered eating, and alcohol use. EH interventions consistently produced significant symptom reductions compared to waitlists or standard care, with a pooled standardized mean difference of 1.17 (95% CI: 0.70–1.64), indicating a large effect. Moreover, trials comparing EH to active treatments (e.g., CBT, motivational interviewing) revealed comparable efficacy, with pooled estimates supporting non-inferiority. Sensitivity analyses confirmed the robustness of these findings. Notably, some trials suggested that the indirect and personalized nature of EH may confer advantages in domains like grief and hypervigilance. Although evidence remains limited by sample size and heterogeneity, this review provides initial empirical support for EH and supports its inclusion in the evidence-based repertoire for both physical and psychological conditions. Future research should examine mechanisms of change and individual predictors of response to optimize the use of this distinctive hypnotic style. Full article

Background/Objectives: Polysomnography (PSG) is the gold standard for diagnosing sleep-disordered breathing (SDB). However, in a hospital testing setting, it may produce the first-night effect, viz., prolonged sleep latency, lower sleep efficiency, and uncertain apnea–hypopnea index (AHI). Here, we aim to determine the influences of hypnotic agents and gender. Methods: In this retrospective study, we reviewed the post-PSG questionnaires and electronic medical records of patients aged ≥20 years receiving overnight PSG for the diagnosis of SDB at Taichung Veterans General Hospital in a period between April 2024 and March 2025. Results: We studied a total of 1053 patients, aged 47.0 ± 14.7 years old. Compared to sleeping at home, 42.2% of patients reported worse perceived sleep quality (PSQ) with hypnotic agents, and 53.0%, without, before PSG testing in the hospital. For those without taking hypnotic agents, men had an odds ratio (OR) of 1.570 (95% CI: 1.127–2.189) for worsening PSQ compared to women (p = 0.008). Also, per increasing 1 Epworth Sleepiness Scale (ESS) score, the risk of worsening PSQ was reduced by OR of 0.963 (95% CI: 0.933–0.994) (p = 0.021). Once male patients had ESS < 10, as many as 57.3% of them reported the worse PSQ. Conclusions: Our study suggests a potentially more patient-centric approach to diagnosing sleep-disordered breathing. In some male patients with ESS scores < 10, short-acting hypnotics might be considered during in-lab PSG to improve subjective comfort, thereby potentially enhancing study reliability. Meanwhile, home sleep apnea testing can serve as a practical initial tool for selected patients—offering convenience, mitigating the first-night effect, and potentially reducing long wait times. However, its use in individuals with comorbid insomnia requires careful clinical judgment to avoid false-negative results, often making in-lab assessment the preferred option in such cases. Full article

Background/Objectives: 1,8-Cineole, an epoxy monoterpene, is a key volatile component of Sugmel-3, a traditional Mongolian medicine used for treating insomnia. Although previous studies suggest that 1,8-Cineole can cross the blood–brain barrier (BBB), its precise spatiotemporal distribution in the brain and its in situ association with alterations in neurotransmitter (NT) levels remain unclear. This study utilized ambient mass spectrometry imaging (AFADESI-MSI) to investigate the dynamic brain distribution of 1,8-Cineole and its major metabolite, as well as their correlation with NT levels. Methods: Sprague Dawley rats (n = 3 per time point) received oral administration of 1,8-Cineole (65 mg/kg). Brain tissues were harvested 5 min, 30 min, 3 h, and 6 h post dose and analyzed using AFADESI-MSI. The spatial and temporal distributions of 1,8-Cineole, its metabolite 2-hydroxy-1,8-Cineole, key neurotransmitters (e.g., 5-HT, GABA, glutamine, melatonin), and related endogenous metabolites were mapped across 13 functionally distinct brain microregions. Results: AFADESI-MSI demonstrated rapid brain entry of 1,8-Cineole and its metabolite, with distinct spatiotemporal pharmacokinetics. The metabolite exhibited higher brain exposure, with 1,8-Cineole predominant in the cortex (CTX) and hippocampus (HP), while its metabolite showed pronounced accumulation in the pineal gland (PG), alongside CTX/HP. Region-dependent alterations in neurotransmitter levels (notably in PG, HP) correlated with drug concentrations, with observed increases in key molecules of the serotonergic and GABAergic pathways. Conclusions: Using AFADESI-MSI, this study provides the first spatiotemporal map of 1,8-Cineole and its metabolite in the brain. The correlation between their region-specific distribution and local neurotransmitter alterations suggests a direct mechanistic link to Sugmel-3′s sedative–hypnotic efficacy, guiding future target identification. Full article

Oxidative stress has been shown to play an important role in the development of cataracts. Melatonin is an endogenous hormone that has been proposed to have a protective effect against oxidative stress; however, its association with the risk of cataracts is uncertain. This target trial emulation study aimed to investigate the relationship between the use of melatonin and the risk of cataracts using TriNetX electronic health records from 2015 to 2023. Adults aged 40 years or older who were diagnosed with a sleep disorder and initiated treatment with either melatonin or a hypnotic benzodiazepine (BZD) were included. Patients receiving hypnotic BZD therapy constituted the active comparator group. Propensity score matching (PSM) was performed to control for covariance. Exposure was defined as the initiation of melatonin or hypnotic BZD therapy. The primary outcomes were the incidence of age-related cataracts and other cataract types, assessed using Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to reduce potential bias. After PSM, 5507 participants were included in each group. Compared with hypnotic BZD users, melatonin users were associated with a significantly lower risk of age-related cataracts (HR, 0.741; 95% CI, 0.681–0.807) and other cataracts (HR, 0.503; 95% CI, 0.433–0.584). These associations remained consistent across all subgroups and sensitivity analyses. In this target trial emulation cohort study, the use of melatonin was associated with a reduced risk of cataracts, suggesting a potential protective effect that warrants further investigation. Full article

Although opioids are effective in treating pain, they cause serious side effects. The use of regional anesthesia, although effective in the perioperative period, may not be suitable if mobility and lack of numbness is desired. Hence, there is a clear need for novel pain therapies. Low-voltage activated (T-type) calcium channels (Ca_V3.2 isoform) could be a promising therapeutic target for the development of novel pain therapies. Indeed, our published findings suggest that novel neuroactive steroid (NAS) analogs that modulate the activity of Ca_V3.2 channels have unique anti-nociceptive properties. However, the concern with current NASs appears to be their hypnotic/sedative properties, thus potentially hindering the future development of NASs for novel pain therapies. Hence, we developed a new line of NASs that are effective blockers of neuronal Ca_V3.2 channels in pain pathways while having more favorable pharmacodynamic properties, i.e., lack of sedative/hypnotic side effects. We present two promising novel analogs of NASs—B372 ((3β,5α,17β)-3-Hydroxyandrostan-17-carbonitrile) and YX23 ((3β,5α,17β)-3-Methoxyestran-17-ol). Using an in vitro approach, we show that B372 and YX23 are effective in blocking Ca_V3.2 channels. Using an in vivo approach, we show that they are effective anti-nociceptives in wild-type but not Ca_V3.2 knock-out mice. Importantly, we show that they lack sedative/hypnotic effects. Full article