Frontiers in psychiatry
January 1, 2024
Giulia Menculini, Gianmarco Cinesi, Francesca Scopetta et al.
10 citations
Major depressive disorder (MDD) is a major health issue in adolescents and young adults, causing high disability and impairing functioning. Its clinical presentation can differ from that in adults, and standard antidepressant treatments often yield suboptimal responses. About 40% of youths with MDD experience treatment-resistant depression (TRD), which is linked to higher rates of comorbid conditions and suicidality. Various biological, environmental, and clinical factors contribute to TRD, which may also signal an unrecognized bipolar disorder, complicating diagnosis. This review summarizes evidence on TRD's epidemiology and clinical features in this age group and discusses possible treatments, including novel fast-acting antidepressants. These drugs show promise but require careful risk-benefit assessment within integrated care models.
Frontiers in psychiatry
January 1, 2024
Aleksander Kwaśny, Alina Wilkowska, Wiesław Jerzy Cubała
10 citations
A systematic review of clinical trials on 5-MeO-DMT, an atypical psychedelic being studied as a rapid-acting antidepressant, found that the drug has a good short-term safety and tolerability profile. Three trials involving 78 participants (two with healthy volunteers, one with treatment-resistant depression patients) reported no serious adverse events and no drop-outs. The authors conclude that 5-MeO-DMT administration in humans is safe in the short term, but call for larger, placebo-controlled trials with longer follow-up to assess potential chronic adverse events.
Frontiers in psychiatry
January 1, 2024
Matthew X Lowe, Hannes Kettner, Del R P Jolly et al.
9 citations
Ceremonial ayahuasca use is associated with significant improvements in mental health, well-being, and psychological functioning among Middle Eastern and North African (MENA) immigrants and refugees. In a longitudinal online survey of 15 primarily female participants, reductions in depression, anxiety, and shame were reported, along with increases in cognitive reappraisal and self-compassion. Most participants reported no lasting adverse effects and experienced positive behavioral changes persisting months after ingestion. The findings suggest naturalistic ayahuasca use might hold therapeutic potential for MENA populations exposed to trauma prior to and during migration, though data are preliminary.
Frontiers in psychiatry
January 1, 2024
Zhangyi Zhong, Hongyu Jiang, Huilin Wang et al.
9 citations
Mindfulness and self-regulation are inversely linked to impulsive behavior in athletes, while social evaluation anxiety is positively linked. Self-regulation and social evaluation anxiety mediate the relationship between mindfulness and impulsive behavior. A survey of 403 athletes from Chinese youth training centers, universities, sports academies, and clubs used structural equation modeling to confirm these associations. The findings suggest that mindfulness meditation in competitive settings may reduce social evaluation anxiety and improve self-regulation, thereby decreasing impulsive behavior and supporting psychological health.
Frontiers in psychiatry
January 1, 2024
Haixia Chen, Xinxin Zhao, Xinxu Ma et al.
9 citations
A single dose of esketamine rapidly alleviated depressive- and anxiety-like behaviors in mice exposed to chronic variable stress, an effect comparable to seven days of repeated fluoxetine treatment. The stress protocol increased plasma levels of multiple inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17A, TNFα, IL-4, IL-9, IL-24, IL-37, IFN-β, and CXCL12) and decreased IL-10 and IL-33. Both esketamine and fluoxetine partially normalized these inflammatory disturbances. The findings suggest that esketamine's rapid antidepressant action may involve normalizing inflammatory cytokine expression.
Frontiers in psychiatry
January 1, 2023
Linn Nyjordet Evanger, Elisabeth Flo-Groeneboom, Lin Sørensen et al.
9 citations
Mindfulness-based cognitive therapy (MBCT) for recurrent depression improved certain insomnia symptoms in a randomized trial. Among 55 remitted participants with at least three prior depressive episodes (74.5% female, mean age 40.7 years), 83.6% screened positive for insomnia at baseline. After 8 weeks, MBCT completers reported significantly less severe insomnia symptoms, shorter time to fall asleep, and fewer nighttime awakenings compared to a waitlist control group. No differences were found for early morning awakening, daytime impairment, or sleep dissatisfaction. The findings suggest MBCT helps some sleep problems, but additional sleep-focused treatments may be needed.
Frontiers in psychiatry
January 1, 2023
Deborah Rudin, Alexander Areesanan, Matthias E Liechti et al.
9 citations
Classic psychedelics LSD, psilocin, DMT, and mescaline do not directly alter the proliferation or cytokine release of primary human T lymphocytes, nor do they stimulate NF-κB induction in monocytes. These findings indicate no relevant direct immune-modulatory effects of these substances on the tested human immune cells in vitro. The results support the safety of using classic psychedelics in assisted psychotherapy for patients with life-threatening conditions where immune suppression would be harmful.
Frontiers in psychiatry
January 1, 2025
Yongyao Wu, Haojie Zhang, Lei Jiang et al.
8 citations
A 12-week program of daily home-based mindfulness meditation combined with progressive muscle relaxation, practiced for at least half an hour, significantly improved sleep quality, reduced anxiety and depression, and enhanced quality of life in hemodialysis patients with sarcopenia and sleep disorders. Twenty-five patients in the intervention group showed better scores on sleep, anxiety, and depression measures compared to 24 controls receiving standard care. The approach is simple and unrestricted, but the study had a small sample and short follow-up.
Frontiers in psychiatry
January 1, 2024
C Khalifian, K Rashkovsky, E Mitchell et al.
8 citations
Intimate relationship distress is common and linked to worse health and mortality. Evidence-based couple therapies target cognitive, behavioral, and emotional processes. Ketamine-assisted psychotherapy (KAP) shows efficacy for depression, anxiety, and PTSD, and its mechanisms—such as increased neuroplasticity, changes in functional connectivity, adaptive dissociation, decreased inhibition, and reduced avoidance—may also enhance couple therapy interventions. The paper reviews evidence for KAP and outlines how these mechanisms could augment existing couple therapies. It proposes a framework for ketamine-assisted couple therapy, addressing preparation, dosing, and integration into a dyadic context. This framework may help clinicians improve couple therapy outcomes, especially when one or both partners have mental health concerns.
Frontiers in psychiatry
January 1, 2025
Valerio Ricci, Maria Celeste Ciavarella, Carlotta Marrangone et al.
7 citations
Substance-induced psychoses (SIPs) triggered by novel psychoactive substances differ from endogenous psychoses like schizophrenia in three key ways: dissociation, mental automatism, and temporality. Dissociation in SIPs causes fragmentation of consciousness and identity detachment, distinct from the spaltung seen in schizophrenia. Mental automatism, as described by De Clerambault, appears early in SIPs with cognitive disruptions preceding delusions. Temporally, SIPs trap individuals in an eternal present, disconnected from past and future, unlike the fragmented temporality in schizophrenia. The paper argues that a phenomenological approach aids clinical differentiation and targeted interventions.
Frontiers in psychiatry
January 1, 2025
Miriam Olivola, Filippo Mazzoni, Barbara Tarantino et al.
7 citations
In treatment-resistant depression, esketamine—a glutamatergic modulator approved in 2019—may improve not only depressive symptoms but also key psychological factors such as mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity. In a six-month observational study of 36 patients with treatment-resistant depressive episodes, depressive symptoms significantly decreased, as measured by the Montgomery-Åsberg Depression Rating Scale. By six months, 69% of patients achieved remission, indicating a robust and sustained response. The findings suggest esketamine may be particularly beneficial in reducing cognitive rigidity and improving mentalization, potentially breaking the inflexible thinking patterns that sustain depression. Personalized treatment approaches are emphasized.
Frontiers in psychiatry
January 1, 2024
Aleksander Kwaśny, Wiesław Jerzy Cubała, Adam Włodarczyk
7 citations
Anhedonia, a reduced ability to experience pleasure, is a core depression symptom that often persists despite standard treatments. Ketamine appears to have antianhedonic effects. In a naturalistic study of 28 inpatients with treatment-resistant depression, both responders and non-responders to ketamine therapy showed significant reductions in anhedonia over time, as measured by the Snaith-Hamilton Pleasure Scale. Non-responders also reported significant improvement in self-reported depression at the seventh infusion, but not at follow-up. Changes in depressive symptoms and anhedonia did not fully overlap, suggesting ketamine may alleviate anhedonia as a separate symptom domain regardless of overall treatment response.
Frontiers in psychiatry
January 1, 2023
Christian Yavorsky, Elizabeth Ballard, Mark Opler et al.
7 citations
Rapid acting antidepressants (RAADs), including ketamine and its derivatives along with GABA receptor modulators, can produce mood improvements within hours or days rather than weeks. There is also renewed interest in psychedelic compounds affecting multiple receptor sites. However, the rating instruments used to measure antidepressant response, such as the Hamilton and Montgomery-Åsberg depression rating scales, were designed decades ago for older drugs and assess symptoms over a seven-day timeframe. This review describes adaptations made to these existing scales for use with RAADs, including modifications for items like sleep and appetite that cannot be assessed in short time frames, and examines additional domains such as daily activities, side effects, suicidal ideation, and role functioning. Recommendations for future studies and implementation challenges are discussed.
Frontiers in psychiatry
January 1, 2024
Bruno Pedraz-Petrozzi, Moritz Spangemacher, Anton Deicher et al.
6 citations
Higher baseline absolute monocyte count (AMC) predicts greater symptom improvement during intravenous ketamine therapy for treatment-resistant depression. In 27 participants receiving six ketamine infusions over three weeks, baseline AMC showed a strong negative correlation with depression severity change after the first infusion and before the last infusion, meaning higher monocyte levels were associated with more symptom reduction. Baseline AMC distinguished responders and partial responders from non-responders but not between partial and full responders. Absolute neutrophil count correlated weakly with early improvement, while C-reactive protein showed no correlation. AMC may serve as a simple clinical marker for predicting ketamine treatment response.
Frontiers in psychiatry
January 1, 2024
Marija Franka Žuljević, Nando Breški, Mariano Kaliterna et al.
6 citations
Psychiatrists in Europe who are not involved in psychedelic research see both promise and risk in psychedelic-assisted psychotherapy (PAP). Based on interviews with 12 specialists and trainees from 8 countries, four themes emerged: psychedelics hold potential, they are dangerous, their future is uncertain, and psychiatry is ambivalent toward them. Respondents acknowledged PAP's potential but considered its evidence base not yet robust enough. They reported that education on psychedelics is lacking in medical and psychiatric training and should be improved to help mental health experts participate in decisions about PAP.
Frontiers in psychiatry
January 1, 2024
Michael Bayrhammer-Savel, Martin Ortner, Marie-Claire Van Hout et al.
6 citations
People in prison have a fundamental right to health care that matches community standards, which includes access to effective medications for mental health conditions. Standard antidepressants often fail for those with depression and high suicide risk, a common problem in prisons. This article argues that denying effective treatment, such as ketamine therapy, may violate human rights under international law and UN standards. The authors discuss the psychiatric and legal arguments for and against using ketamine in prisons, noting potential benefits for severe depression and suicidality but also risks like unknown long-term effects and abuse. They conclude that more research is urgently needed given the lack of data on ketamine's use in prison populations.
Frontiers in psychiatry
January 1, 2023
Shanthi Sarma, Arulmathy Arunachalam, Memunatu Kamara et al.
6 citations
Two patients with catatonic depression in bipolar disorder who were not medically fit for electroconvulsive therapy (ECT) received intravenous ketamine instead. Both patients' symptoms resolved and they returned to their baseline level of functioning. During the COVID-19 pandemic, when ECT poses risks as an aerosol-generating procedure and resources are limited, ketamine therapy for catatonia may be a beneficial alternative or supportive treatment to ECT, warranting further research.
Frontiers in psychiatry
January 1, 2023
Angela N Phan, Garth E Terry
6 citations
Cannabis use disorder affects about 2-5% of adults in the United States, and rates are expected to rise as cannabis restrictions loosen and THC content increases. No FDA-approved medications exist for this condition. Psychedelics have shown promise for other substance use disorders, and surveys suggest potential benefits for cannabis use disorder. A systematic review of the literature found only one study using the non-classical psychedelic ketamine for cannabis use disorder and three additional relevant articles. The review notes that psychedelics generally have a high therapeutic index with rare serious adverse effects, but risks such as psychosis and cardiovascular events should be considered in this population. More research is needed given rising incidence and interest in psychedelic treatments.
Frontiers in psychiatry
January 1, 2022
Otto Simonsson, José Carlos Bouso, Florian Kurth et al.
6 citations
The corpus callosum, a brain structure connecting the two hemispheres, was thicker in the isthmus region among 22 ayahuasca users compared to 22 matched controls. A positive correlation was observed between callosal thickness in the rostral body and the number of past ayahuasca sessions, though neither finding survived correction for multiple comparisons. No brain region was thicker in controls than in ayahuasca users, and no region was negatively linked to ayahuasca use. This provides preliminary evidence of an association between ayahuasca use and callosal structure, but replication with larger samples and longitudinal designs is needed.
Frontiers in psychiatry
January 1, 2025
Alexa E Albert, Anthony L Back
5 citations
Pathological narcissism is a complex, treatment-resistant disorder involving unstable self-esteem that swings between grandiosity and vulnerability, making a stable self-image difficult to maintain. Few empirically supported therapies exist, and long-term psychoanalytic approaches often have high dropout rates. Recent research suggests combining psychedelics like MDMA with psychoanalytic therapy may offer a novel treatment. MDMA enhances empathy, trust, and social bonding, and can reopen critical periods for social learning in adults. It promotes psychological flexibility and openness, strengthening the observing ego—key for recognizing and changing maladaptive patterns.
Frontiers in psychiatry
January 1, 2025
Justin Dwyer, Robert B Johnston, Clare O'Callaghan et al.
5 citations
Music in psychedelic-assisted psychotherapy (PAP) is not merely a predictable amplifier of the experience but undergoes a profound transformation for participants. In a trial of PAP at end of life, participants described music as becoming internally generated, multisensory, deeply personal experiences that arrive fully formed and are instantly known. Some of these experiences become actors that collaborate with the participant and therapist in ongoing psychotherapy. This contrasts sharply with the everyday properties of music reported by the placebo group. The findings suggest that music should not be viewed as something simply administered, with major implications for PAP practice and research.
Frontiers in psychiatry
January 1, 2021
Sylvana Vilca-Melendez, Malin V Uthaug, Julian L Griffin
5 citations
A systematic review found that proton nuclear magnetic resonance (1H NMR) spectroscopy has been used primarily for structural elucidation and analytical characterization of psychedelic molecules such as psilocin, LSD, DMT, and bufotenin, but no studies have applied 1H NMR to metabolic profiling of biofluids in psychedelic research, revealing a research gap. The review compared 1H NMR with mass spectrometry, noting both techniques are suitable for biofluid analysis in other fields. Future directions identified include real-time NMR, in vivo magnetic resonance spectroscopy, and gut microbiome studies. Further research is needed to determine whether 1H NMR will be an effective approach for analyzing metabolites in peripheral biofluids and in vivo.
Frontiers in psychiatry
January 1, 2026
Ngo Cheung
4 citations
Rapid-acting antidepressants can lift mood within hours by shifting glutamatergic circuits from an NMDA-dominant to an AMPA-dominant state. Intravenous ketamine achieves this but causes dissociation and logistical challenges, while dextromethorphan plus bupropion (Auvelity) provides slower, less durable benefit. The authors hypothesize that a fully oral, low-cost, four-component regimen—dextromethorphan for NMDA antagonism, a potent CYP2D6 inhibitor to prolong DXM exposure, piracetam as an AMPA positive allosteric modulator, and micronized L-glutamine to restore presynaptic glutamate pools—may approximate ketamine's full plasticity cascade. Preclinical evidence supports mechanistic synergy, but the combination remains untested in humans, warranting formal evaluation.
Frontiers in psychiatry
January 1, 2025
Human-Friedrich Unterrainer
4 citations
Using the Icarus myth as a metaphor, this essay argues that addiction represents a distorted pursuit of transcendence—the human desire to go beyond ordinary limits. Addiction, a chronic disorder involving compulsive substance use or behavior, offers only fleeting euphoria and perpetuates dependency, unlike healthy transcendence achieved through practices like meditation. Concepts such as Sigmund Freud's oceanic feelings and Abraham Maslow's peak experiences parallel the addict's search for unity, but addiction undermines genuine fulfillment. Spirituality plays a key role in both the development of addiction and recovery, reconnecting individuals to meaning and purpose. Neuroscientific insights point to ancient brain regions like the periaqueductal grey as underlying the drive for transcendence. The essay advocates for addiction therapy that balances the desire for transcendence with sustainable growth, avoiding Icarus's fatal extremes.
Frontiers in psychiatry
January 1, 2025
Sofia Abramsky-Sze, Elliot Marseille, Richard Matzopoulos et al.
4 citations
A cross-sectional survey of 6,869 American adults found that those who used psychedelic mushrooms in the past year reported lower mental health scores and higher levels of anxiety and depression than non-users. The 256 psychedelic users (3.7% of the sample) included 122 who used only psilocybin mushrooms and 134 who used multiple psychedelics; the multi-psychedelic group had the poorest mental health. These differences persisted even after controlling for past-year anxiety and depression, suggesting that psychedelic use is associated with poorer mental health in some contexts. The authors call for more population-based research on exclusive psilocybin and combined psychedelic use.