Frontiers in psychiatry
January 1, 2025
Jonathan David, José Carlos Bouso, Maja Kohek et al.
correction
A correction was issued for a published article: the average number of ayahuasca uses in the ayahuasca group was revised from 69.4 to 55.7 (standard deviation 82.1). Participants had used ayahuasca 5.2 times more than psilocybin, 4.6 times more than mescaline, and 5.6 times more than LSD. The authors state the error does not alter the scientific conclusions.
Frontiers in psychiatry
January 1, 2025
Leonard Marx, Zümrüt Duygu Sen, Lena Vera Danyeli et al.
Ketamine's rapid antidepressant effects are thought to involve glutamate signaling and brain-derived neurotrophic factor (BDNF), but how these two factors interact is unclear. In a randomized, placebo-controlled crossover study with 35 healthy men, researchers measured glutamate levels in the pregenual anterior cingulate cortex using 7 Tesla magnetic resonance spectroscopy and plasma BDNF levels before and after infusions of S-ketamine or placebo. A significant interaction emerged between treatment condition and changes in glutamate on BDNF level changes, with a trend-level positive correlation between glutamate and BDNF changes only in the ketamine group. These findings offer initial in vivo evidence that ketamine's influence on BDNF is tied to its glutamatergic action.
Frontiers in psychiatry
January 1, 2025
Zrinka Sosic-Vasic, Max Bergmann, Julia Kroener
Adding Acceptance and Commitment Therapy (ACT) to standard inpatient care for depression and insomnia may improve symptoms more than usual care alone. Eight psychiatric inpatients received eight ACT sessions alongside cognitive behavioral therapy and medication. Depressive symptoms, insomnia, psychological flexibility, acceptance of sleep problems, and quality of life all improved significantly from before treatment to one week and three months after treatment. No significant changes occurred during the baseline period before ACT began. The findings suggest ACT is a promising transdiagnostic adjunct for inpatients, but results are preliminary due to the small sample and lack of a control group.
Frontiers in psychiatry
January 1, 2025
Ahmad H Almadani, Ayedh H Alghamdi, Fahad B Alfahad et al.
In a survey of 283 adults with depression, about half (52.3%) were willing to receive nasal esketamine, and 51.2% preferred its weekly or biweekly dosing over daily antidepressants. However, 79.5% cited cost as a barrier, and major concerns included medication unavailability (59.7%), fear of addiction (50.5%), anticipated stigma (24.4%), and first-month dosing frequency (21.2%). Notably, 77.4% were nonadherent to their current psychiatric medication. Adherence was higher among those who had previously used esketamine and among those who had someone to stay with them during and after treatment. The findings underscore the need for patient education, family involvement, and logistical support to address barriers and improve acceptance.
Frontiers in psychiatry
January 1, 2025
Pablo Sabucedo, Óscar Andión, Robert A Neimeyer et al.
correction
A three-arm, non-randomized controlled trial protocol compares Ayahuasca-assisted Meaning Reconstruction therapy (A-MR) with Meaning Reconstruction therapy alone and a no-treatment control for people who lost a first-degree relative within the prior 12 months. The authors hypothesize that A-MR will produce greater reductions in normal and pathological grief symptoms, and greater improvements in quality of life and posttraumatic growth, than either control condition. The rationale draws on neurobiological evidence that ayahuasca stimulates neuroplasticity and on psychological evidence that psychedelic experiences can facilitate meaning reconstruction and cognitive reappraisal. No controlled studies have tested psychedelic-assisted therapy for prolonged grief disorder.
Frontiers in psychiatry
January 1, 2025
Kyndra Purcell
Bipolar II disorder involves not only mood dysregulation but also autonomic nervous system function, which shapes the depth and duration of depressive episodes. The paper introduces regulation as modulation, where autonomic flexibility acts as a physiological buffer influencing mood stability. Heart-rate variability, vagal tone, and neurovisceral integration are key biomarkers linking emotional resilience and physiological coherence. When these systems are compromised, recovery from depressive episodes slows; when strengthened through breathwork, interoception, grounding, and somatic awareness, recovery accelerates. The argument integrates existing studies and longitudinal self-monitoring data, noting consistent patterns between autonomic dysregulation and bipolar lows. Somatic regulation should be regarded as a core therapeutic pathway alongside medication and psychotherapy.
Frontiers in psychiatry
January 1, 2025
Rocco Miazzi, Clara Cestonaro, Silvia Righetto et al.
Adolescent MDMA use is linked to psychological disturbances such as increased depression, anxiety, suicidal ideation, and attempts, as well as neuropsychological deficits in memory, attention, and executive functioning. Neuroimaging evidence suggests MDMA disrupts serotonergic pathways, potentially causing persistent brain changes. The review synthesizes 14 human studies but notes methodological limitations like small sample sizes, high rates of polydrug use, and lack of longitudinal designs, complicating causal conclusions. The findings underscore the need for targeted prevention and harm reduction for adolescents.
Frontiers in psychiatry
January 1, 2025
Valerio Ricci, Domenico De Berardis, Giovanni Martinotti et al.
Cannabis use, especially high-potency THC products, is consistently linked to elevated dissociative experiences in patients with first-episode psychosis. Users scored 11-13 points higher on the Dissociative Experiences Scale-II than non-users, and daily high-potency use tripled the odds of clinically significant dissociation (OR: 3.21). These dissociative symptoms, along with more severe anomalous self-experiences, predicted poorer functional outcomes at 12 months (GAF scores: 52 ± 14 vs. 67 ± 12). About 75% of patients showed reduced dissociation after stopping cannabis, suggesting potential reversibility. The evidence certainty was moderate for dissociation severity and low for self-disturbance outcomes.
Frontiers in psychiatry
January 1, 2025
Julia Marek, Magdalena Domek-Gumprecht, Agata Macionga et al.
A biennial online survey of 2,447 people aged 13–63 in Poland found that marijuana is the most commonly used illicit psychoactive substance, though consumption is infrequent (35.6% use once every few months or less) and mainly occurs in social settings (50.2%) or at home (52.3%). Most respondents (83.6%) never tested substance composition, and 51.4% relied on visual estimation for dosing. Sixty percent had neglected daily responsibilities, and 16.8% faced legal issues. Nearly half had seen a psychiatrist, primarily for depression; of those, 41.1% had attempted suicide and 70.5% used illicit substances before their first consultation. Only 40% consistently disclosed substance use to a physician. Stimulant use and related medical consultations are rising, psychedelic use is declining, and solitary use now exceeds 25%.
Frontiers in psychiatry
January 1, 2024
Angelika Ecker, Charlotte Fritsch, Daniel Schleicher et al.
A single mindfulness exercise did not produce immediate observable changes in mood, stress, state mindfulness, heart rate, or heart rate variability among healthy adolescents aged 12 to 19. The study assigned 78 adolescents to either a mindfulness or an active control group, measuring subjective and physiological parameters before and after the intervention. While no significant interactions between time and intervention were found, heart rate showed a main effect of time, and all subjective parameters showed a main effect of trait mindfulness. Age influenced heart rate and state mindfulness. Trait mindfulness correlated strongly with trait anxiety and depression scores. The findings suggest that a single mindfulness session may not have immediate effects in healthy adolescents, though mindfulness may still support resilience over time.
Frontiers in psychiatry
January 1, 2023
Yan Li, Yan Chen, Charlotte Martial et al.
A Chinese version of the Near-Death Experience Content (NDE-C) scale was translated and validated on 79 near-death experience testimonies. The translation used Brislin's back-translation model, and the scale showed good internal consistency (Cronbach's α = 0.846). Confirmatory factor analysis supported the scale's structure. This new Chinese NDE-C scale is now available to screen people who have had near-death experiences or near-death-like experiences (e.g., from meditation) and to quantify their subjective experiences, enabling further research on this phenomenon in Eastern cultural contexts.
Frontiers in psychiatry
January 1, 2026
Lena Palaniyappan
Biological psychiatry struggles to find valid targets for mechanistic research because both diagnostic categories and individual symptoms are abstract symbols defined circularly within a closed interpretive system, creating a symbol grounding problem that blocks discovery of biomarkers. The author argues that progress requires separating ungrounded symptoms like delusions and hallucinations, which are co-constructed through personal and clinical interpretation, from grounded signs—directly observable features anchored in shared sensorimotor reality. A Minimal Grounding Set (MGS) can be recovered from common psychosis criteria, exemplified by disorganization and impoverishment. This MGS offers a privileged pathway for neuroscientific inquiry, with predictions that biological correlates will be most replicable for MGS, that MGS will serve as modular anchors in symptom networks, and that precision psychiatry programs depend on separating MGS from ungrounded symptoms.
Frontiers in psychiatry
January 1, 2026
Aleš Oblak, Sara Rigler, Nika Kovačič et al.
Ruminations are persistent, repetitive, distressing thoughts about negative events and moods, linked to psychiatric disorders and suicidality. This study provides a detailed description of ruminating from a lifeworld perspective, using micro-phenomenological interviews with 51 participants (107 interviews, 79 episodes). Ruminating is an epistemic practice driven by a need to resolve uncertainty after a collapse of commonsense understanding, leading to intellectualization and detachment from embodied responses. It involves paralysis, emptiness, and problematic relationships with knowledge. Rather than a maladaptive thought pattern, ruminating constitutes a complex lifeworld, suggesting a reconceptualization from a unified symptom to a system of interrelated altered experiences.
Frontiers in psychiatry
January 1, 2026
Agnieszka Suchocka Capuano
A three-pillar psychotherapeutic model for migrant populations combines revised cognitive behavioral therapy, hypnosis-derived consciousness activation techniques, and yoga-inspired postural and interoceptive training. Emotions are treated as perceptual signals for flexible behavioral adaptation rather than targets for regulation. The model includes a five-session transdiagnostic psychotherapy and a single-session 'One-Shot Concentration Group' integrating mindful breathing, detached awareness, and simple body-mind postures. Preliminary clinical observations indicate immediate benefits like increased attentional flexibility and reduced physiological tension, with longer-term improvements in sleep, concentration, memory, and decreases in anxiety, depressive symptoms, and dissociative episodes. The model is designed for allophone patients with interpreter support and minimal verbal processing.
Frontiers in psychiatry
January 1, 2025
Rebecca Paetow, Maike Franziska Dohrn, Michelle Finner-Prével et al.
Among 287 patients in a German psychiatric hospital, 22 (7.67%) reported having used nitrous oxide (N2O) recreationally at some point in their lives. Users tended to be younger (mean age 28 years) and most obtained the substance through friends or social events. The most common psychiatric diagnoses among users were major depressive disorder, cannabis-related disorder, and attention deficit hyperactivity disorder. The findings suggest that recreational N2O use is relatively common in psychiatric populations and that clinicians should routinely ask about it.
Frontiers in psychiatry
January 1, 2025
Rayyan Raja Zafar, Patrick Kleine, Danielle Kurtin et al.
Only 1.8% of people with substance use disorders receive effective treatment, revealing a gap between neuroscience research and clinical care. This paper argues that addiction neuroscience should shift from a diagnostic focus to a theragnostic framework that uses biomarkers to guide treatment decisions. Integrating fMRI, EEG, and PET biomarkers within psychedelic addiction research offers an opportunity for this change. Psychedelics like psilocybin engage neuroplasticity and reward networks central to addiction. The authors review neuroimaging paradigms for indexing drug effects and propose a roadmap for embedding biomarkers in clinical trials. They outline ongoing work at Imperial College London co-developing biomarkers for gambling and opioid use disorders to identify biotype-specific responses, aiming for regulatory-grade tools similar to those in oncology.
Frontiers in psychiatry
January 1, 2025
Aslihan Uyar, Ali Saffet Gonul
Major depressive disorder (MDD) remains a major global health problem, and traditional antidepressants often work slowly or not at all—up to 60% of patients do not respond adequately. This review describes emerging pharmacologic treatments that target neurobiological pathways beyond the usual monoamine systems. Ketamine and S-ketamine produce rapid antidepressant effects, often within hours, by blocking NMDA receptors and enhancing synaptic plasticity; these effects can last several days after a single dose, especially in treatment-resistant cases. A combination of dextromethorphan and bupropion also shows quicker and more durable benefits than either drug alone. Neurosteroids like brexanolone (given intravenously) and zuranolone (oral) effectively treat postpartum depression by modulating GABA-A receptors. New agents acting on opioid pathways, such as esmethadone and selective kappa receptor antagonists, offer additional novel approaches.
Frontiers in psychiatry
January 1, 2025
Congyi Li, Zhihui Wang, Xinman Ye et al.
Several anesthetic agents—ketamine, propofol, nitrous oxide, sevoflurane, and isoflurane—show promise as rapid antidepressants, especially for treatment-resistant depression. Their effects appear to involve modulation of glutamate and GABA signaling, interactions with serotonin, dopamine, and norepinephrine, activation of BDNF and VGF pathways, regulation of the HPA axis, and suppression of inflammation. These mechanisms overlap with core depression-related changes. While traditional antidepressants have limited efficacy and delayed onset, anesthetics offer faster alternatives. However, their precise mechanisms, long-term safety, and optimal clinical use remain unclear. This review summarizes recent experimental and clinical research on these agents, highlighting molecular mechanisms, therapeutic potential, and current limitations.
Frontiers in psychiatry
January 1, 2024
David J Heal, Jane Gosden, Sharon L Smith
Cannabis has moderate levels of abuse and dependence risk, substantially lower than those of many illegal and legal substances like tobacco and alcohol, but far from negligible. Delta-9 tetrahydrocannabinol (Δ9-THC) and other psychoactive cannabinoids have moderate reinforcing effects, rapidly induce pharmacological tolerance, and produce a withdrawal syndrome of moderate severity lasting 2 to 6 days. Non-psychoactive cannabinoids do not produce intoxicating, cognitive, or rewarding properties in humans. Most evidence shows cannabidiol (CBD) does not attenuate the central nervous system effects of Δ9-THC, though uncertainty warrants further research. Potent synthetic cannabinoid receptor agonists pose substantial risk for abuse and harm.
Frontiers in psychiatry
January 1, 2023
Clementine J Edwards, Oliver Owrid, Lucy Miller et al.
A novel 10-item tool, the Voice Characterisation Checklist (VoCC), reliably assesses how much people personify the voices they hear. Among 170 participants who heard distressing voices, 94% reported some degree of voice personification. Most described voices as distinct auditory experiences with basic attributes like gender and age, and many attributed intentions and personalities to them. However, fewer than half attributed mental states to the voice or identified a known historical relationship. The VoCC showed acceptable internal consistency and good inter-rater reliability, making it useful for testing whether voice characterisation influences treatment outcomes in therapies like AVATAR therapy.
Frontiers in psychiatry
January 1, 2023
Emily Whinkin, Therry Rose J Eparwa, Michelle C Julseth et al.
In patients with problematic substance use, ketamine-assisted psychotherapy (KAP) was associated with significant reductions in anxiety and depression symptoms, as measured by the GAD-7 and PHQ-9 scales. The average GAD-7 score decreased by 6.71 points, and the average PHQ-9 score decreased by 7.44 points. Improvements in psychosocial and spiritual well-being, measured by the NIH-HEALS scale, increased by an average of 5.13 points but were not statistically significant. Compared to the broader KAP patient population, those with problematic substance use showed significantly greater reductions in anxiety and depression. Undergoing one to six KAP sessions may be a useful therapy for reducing these symptoms in this population.
Frontiers in psychiatry
January 1, 2023
Alexander Kaltenboeck, Elisa Foerster, Sabrina Strafner et al.
A 28-year-old man with severe obsessive-compulsive disorder (OCD) and depression, who had not responded to cognitive-behavioural therapy, selective serotonin reuptake inhibitors, clomipramine, or antipsychotics, received off-label esketamine combined with psychotherapy. Over about 2 months he had 10 esketamine-plus-psychotherapy sessions, then two maintenance sessions, and later continued maintenance esketamine every 4-6 weeks with independent cognitive-behavioural therapy. His OCD symptoms improved markedly (Y-BOCS fell from >35 before treatment to 23 at week 8 and 14 at week 26), and depressive symptoms also decreased (MADRS fell from 47 before treatment to 12 at week 9 and 3 at week 26). At week 66, OCD symptoms remained mild (Y-BOCS 13) and depression was in remission (MADRS <6). This case suggests esketamine plus psychotherapy may be promising for difficult-to-treat OCD and depression.
Frontiers in psychiatry
January 1, 2022
Joshua Willms, Ben McCauley, Lindsay Kerr et al.
A 30-year-old medical student with treatment-resistant depression, generalized anxiety disorder, PTSD, and 5 years of daily suicidal ideation, who had not responded to therapy, lifestyle changes, or six antidepressants, achieved remission from suicidality and PTSD within 1 month and from depression and anxiety within 7 months after an 8-month regimen of IV ketamine infusions and ketamine-assisted psychotherapy. The Patient Health Questionnaire (PHQ-9) score dropped from 25 (severe depression) to 1 (not depressed). These results suggest ketamine and KAP may be effective for mental health conditions in healthcare professionals. The patient also typed real-time narrative journals during four ketamine infusions, providing first-person accounts of ketamine-induced non-ordinary states.
Frontiers in psychiatry
January 1, 2022
Mark A Gillman
Medication dosages must be individualized; no single dose works for everyone. This paper contrasts fixed 25-50% concentrations of nitrous oxide (N2O) with the variable, titrated concentrations of Psychotropic Analgesic N2O (PAN) used in dentistry and neuropsychiatry. PAN is always titrated via an open nasal mask to the minimum concentration ensuring full consciousness, cooperation, comfort, and relaxation, guided by each subject's responses. Fixed concentrations, given via closed facial masks, ignore individual dose-response and may cause unconsciousness or adverse effects in sensitive subjects, requiring an anesthesiologist. PAN has been safely used in dentistry for over 70 years and in neuropsychiatry for over 40 years, with applications including substance abuse detoxification, depression amelioration, and investigations of schizophrenia, human orgasm, pain perception, and basic neuroscience. Experience with fixed doses in psychiatry is limited.
Frontiers in psychiatry
January 1, 2022
Shannon Dames, Pamela Kryskow, Crosbie Watler
correction
This notice corrects an error in a previously published article. No new findings, data, or arguments are presented.