Search Results (209)

Background/Objectives: Patients in palliative care often experience multifaceted forms of suffering that extend beyond physical symptoms, including existential distress, loss of meaning, and emotional pain. Ketamine-assisted psychotherapy (KAP) has emerged as a promising intervention for alleviating such complex forms of suffering, yet models specifically tailored to palliative populations remain scarce. This narrative review synthesizes current evidence on ketamine’s neurobiological, psychological, and experiential effects relevant to end-of-life care, and presents a novel, time-limited KAP model designed for use in palliative settings. Methods: Drawing from both biochemical and psychedelic paradigms, the review integrates findings from neuroscience, phenomenology, and clinical practice. In particular, it incorporates a dual-level experiential framework informed by recent models distinguishing ketamine’s differential effects on self-processing networks: the Salience Network (SN), related to embodied self-awareness, and the Default Mode Network (DMN), associated with narrative self-construction. This neurophenomenological perspective underpins the rationale for using two distinct dosing sessions. Results: The article proposes a short-course, time-limited KAP model that integrates preparatory and integrative psychotherapy, two ketamine dosing sessions (one low-dose and one moderate-dose), concurrent psychotherapy, goals of care discussion (GOCD), and optional pharmacological optimization. The model emphasizes psychological safety, meaning-making, and patient-centered care. The sequential dosing strategy leverages ketamine’s unique pharmacology and experiential profile to address both bodily and narrative dimensions of end-of-life distress. Conclusions: This dissociative-psychedelic model offers a compassionate, pragmatic, and theoretically grounded approach to relieving psychological and existential suffering in palliative care. By integrating neurobiological insights with psychotherapeutic processes, it provides a flexible and patient-centered framework for enhancing meaning, emotional resolution, and quality of life at the end of life. Further research is needed to evaluate its clinical feasibility, safety, and therapeutic efficacy. Full article

Objectives: This study investigates psychedelic drugs to treat substance use disorder (SUD). Researchers have recently begun conducting clinical trials of psychedelic treatment for SUD. The current meta-analysis investigates the extent of efficacy in alleviating SM behaviours (P) using psychedelic therapy (I), concurrent with determining which psychedelic enables the greatest effect (C) as a treatment tool for reducing SUD (O). Methods: The inclusion criteria in this study include evaluating the efficacy of LSD, psilocybin, ketamine, or ibogaine in human beings with an SUD. The exclusion criteria include studies on rodents, patients with schizophrenia, case studies, incomplete or ongoing trials, and studies with insufficient quantitative data. The search criteria obtained 1278 articles, acquired through PubMed and PsycINFO. After excluding literature, 30 papers were kept in the final meta-analysis. A random-effects model analysis was applied to investigate individual psychedelic interventions, with a corresponding combined psychedelic intervention analysis. Results: The results favoured psychedelics as an SM treatment, with ibogaine evidencing the most prominent. We also found a non-significant difference between the effectiveness of psychedelic treatment paired with psychotherapy and psychedelic treatment alone. This study aims to contribute knowledge to future clinical research on the psychedelic treatment of SUD. Full article

The paper critically discusses whether mystical experiences induced by psychedelics should be considered inauthentic or counterfeit forms of mystical experiences. It examines three arguments against the authenticity of these experiences: pimes are too easy; pimes do not have lasting spiritual or moral effects; pimes do not involve divine grace. Positive arguments for the authenticity of pimes discussed are as follows: pimes rely on similar neural mechanisms as other mystical experiences; pimes are phenomenologically similar to other mystical experiences. The paper argues that the positive arguments are more convincing than the negative ones. It thereby presents a case in favor of the authenticity of psychedelically induced mystical experiences. Full article

Psychedelic-assisted therapy offers rapid and profound benefits for treatment-resistant psychiatric conditions but remains constrained by the need for intensive, clinic-based administration. Concurrently, advances in digital health technologies have introduced scalable tools. This systematic review evaluates the safety, efficacy, and implementation of digitally enabled psychedelic-assisted therapy delivered in non-clinical settings. A comprehensive search of five databases, registered in PROSPERO (CRD420251020968) and conducted in accordance with PRISMA guidelines, identified six eligible studies including real-world analyses, clinical trials, qualitative research, and case reports, representing a total of 12,731 participants. Most studies examined at-home ketamine or esketamine therapy supported by telehealth platforms or mobile applications. Data were synthesized narratively given the heterogeneity of designs and outcomes. Digital enablement was associated with high response rates (ranging from 56.4% to 62.8% for depression) and rapid symptom improvement, particularly in depression and anxiety. Remote monitoring and digital tools demonstrated feasibility and acceptability, but serious safety concerns—including psychiatric adverse events and one unintentional overdose—underscore the need for strict oversight. Risk of bias was moderate to serious across non-randomized studies, limiting confidence in the findings. One study on virtual ayahuasca rituals highlighted the sociocultural potential and limitations of online practices. Despite promising preliminary findings, the field is marked by low methodological rigor and absence of controlled trials. Digitally supported at-home psychedelic therapy represents a transformative but high-stakes frontier, requiring robust research and safeguards to ensure safe, equitable, and effective implementation. No funding was received for this review, and the authors declare no conflicts of interest. Full article

Background: Substance use disorders (SUDs) are highly prevalent, affecting over 48.5 million Americans. Available treatments for SUD remain insufficient, and many patients do not respond to existing interventions despite adequate adherence to treatments. While novel therapies for SUD are urgently needed, the use of psychedelic drugs for the treatment of SUDs has shown promise. Objectives: This overview of systematic reviews summarizes existing evidence on hallucinogens—serotonergic psychedelics and ketamine—for the treatment of SUD. Methods: A comprehensive search of the literature was conducted to identify relevant evidence for using serotonergic and non-serotonergic psychedelics for the treatment of SUDs. After initial screening (n = 468 studies), 62 studies were retrieved and assessed for eligibility, and a total of 16 systematic reviews were included. Conclusions: Although preliminary, evidence suggests that the use of serotonergic and non-serotonergic psychedelics for the treatment of SUD may provide advantages over traditional therapeutics, and these compounds may eventually become part of the next generation of treatments for SUD under specific circumstances. Research with these drugs has faced significant challenges, though, and caution when interpreting results is warranted, given high risk of bias and several other methodological limitations from the studies to date. Furthermore, risks associated with these drugs are not negligible. For now, the use of psychedelic drugs for the treatment of SUDs remains experimental, and existing evidence is insufficient to support its use in clinical practice. Full article

Psychedelic compounds are gaining renewed attention across disciplines for their profound psychological and neurobiological effects. Emerging research highlights their efficacy in treating mood disorders, PTSD, and addiction by enhancing neuroplasticity and disrupting maladaptive cognitive patterns. From a psychological standpoint, psychedelics facilitate introspection, emotional processing, and therapeutic breakthroughs. Neuroscientific findings reveal altered brain network dynamics, while anthropological and philosophical perspectives contextualize their cultural and existential significance. In medicine, they offer novel interventions for chronic pain and palliative care. The present review article underscores the need for rigorous, ethically grounded research to explore psychedelics’ potential in reshaping mental health paradigms and cognitive science from a multidisciplinary perspective. Full article

Background/Objectives: This study examines the development of clinical trials investigating psilocybin for the treatment of psychopathologies, with a comparative focus on the United States (US) and the European Union (EU). The objective is to identify regional differences in trial progression, research infrastructure, and regulatory frameworks. Methods: A mixed-methods approach was applied, combining case studies, qualitative and quantitative research. Key variables included trial phase, geographical distribution, demographic factors, funding, governmental support, and public health policies. Results: The US demonstrated a substantially higher number of psilocybin trials across both early and advanced phases. This reflects a strong research infrastructure, growing financial investment, and increasing interest in psychedelic-assisted therapies. In contrast, the EU showed fewer trials and slower advancement, reflecting a more cautious stance that emphasizes patient safety and therapeutic efficacy. These divergences are shaped by differences in regulation, funding mechanisms, and sociocultural attitudes toward psychedelics in psychiatry. Conclusion: This comparative analysis highlights the uneven pace of psilocybin research across different regions. It also emphasizes the importance of international collaboration, harmonization of public health policies, and the development of standardized procedures prioritizing safety and effectiveness. Integrating psilocybin-assisted interventions into psychiatric practice has the potential to expand treatment options and strengthen mental health care, but coordinated global efforts are essential to ensure both scientific rigor and patient protection. Full article

Psychedelic drugs show promise in treating a wide range of mental health conditions. These drugs are beneficial in part because they disrupt prior ideas and patterns of behavior and because they increase neurogenesis and neuroplasticity. It is important therefore to consider the causal impact of the social context not just during but also following psychedelic experiences. Modern cultural or social contexts might thwart or discourage spiritual integration, but local integration support groups are shown to be helpful, especially for those seeking to reflect the meaning of spiritual or religious themes. These groups might be offered within Christianity, which can provide (1) a connection to a community or a social context at the local level together with (2) a set of theological beliefs as an interpretive context that supports spiritual growth in general and psychedelic spiritual integration in particular. Full article

Schizophrenia is a highly polygenic disease, and several genetic variants associated with the disease converge on altered synaptic homeostasis. In particular, the gene encoding complement component 4 (C4) showed the strongest association with schizophrenia, and this protein is involved in complement-dependent and microglia-mediated synaptic pruning. As a matter of fact, microglia are overactive in schizophrenia, and reduced synaptic arborization, especially in the prefrontal cortex (PFC), is an established hallmark of schizophrenia, likely associated with gray matter loss, cortical thinning, hypofrontality, and deficit syndrome. The recent development of a new radioligand targeting the synaptic vesicle glycoprotein 2A (SV2A) demonstrated in vivo lower synaptic density at the PFC level in individuals with schizophrenia, corroborating the synaptic hypothesis of thedisease first proposed by Feinberg in 1982. Interestingly, robust preclinical evidence (in vitro and animal models) showed the ability of psychedelics to promote neuroplasticity and synaptogenesis, potentially counteracting the excessive synaptic loss, restoring volume loss, and possibly explaining improvements in negative and cognitive symptoms described by old clinical studies. Overall, microdoses should be explored first as a possible treatment in a selected sample of patients affected by deficit schizophrenia, followed by low and full doses if encouraging results were to emerge. Full article

Addiction remains a persistent public health crisis, marked by poor treatment retention and limited pharmacotherapy options. Emerging treatments, such as psychedelic-assisted psychotherapy and neuromodulation, offer promising avenues for circuit-level interventions in behavioral addictions. This narrative review synthesizes the current landscape of psychedelic compounds and neuromodulation techniques with a focus on their mechanisms of action, applications in specific behavioral addictions, and translational potential. By targeting disrupted reward, executive control, and stress regulation networks, these interventions may facilitate meaningful recovery and long-term remission in otherwise treatment refractory cases. We highlight key findings, current research limitations, and future directions in integrating these novel therapies into the treatment of gambling disorder; internet gaming disorder/gaming disorder, predominantly online; internet use disorder; and compulsive sexual behavior disorder. Full article

Background: Evidence is growing that psychedelic substances have positive effects in the setting of Palliative Care (PC), focusing on special needs in this patient population. After a scoping review of the literature, no published expert recommendations guiding best practice for psychedelic-assisted therapy (PAT) towards the end of life were identified. Objective: To draw conclusions from first-hand experienced professionals on PAT in PC (PATPC). Setting, Design, Participants: An international workshop with experts was held in Wasserfallen, Switzerland. A thematic analysis of a semi-structured, questionnaire-based qualitative study with 13 experts in PC, oncology, psychiatry/psychology, and PAT from Europe, the United States, and Oceania was made. Measurements: The questionnaire was designed to elicit the participant’s perspectives on (A) special considerations on PATPC, (B) specific characteristics of PATPC (versus mental illness), and (C) the relevance of these differences during preparation, substance dosing session, and integration in PATPC. Results: (A) Special Considerations included (non-medicalized) setting, potential need, and possibility to reduce preparation time. (B) Distinguishing characteristics included the patient’s intrinsic motivation for treatment success, the importance of anxiety, depression, and spiritual distress as indications for PATPC, and the importance of sufficient integration of the psychedelic experience into life in the face of limited time due to the life-limiting illness. (C) Flexibility in setting and timing of preparation, choosing the appropriate dosage of the psychedelic substance depending on the patient’s intended focus, low/medium (relational issues), higher for transcendental experiences, considering mental capacity and vulnerability for the individual. In addition, respondents noted that for therapists, knowledge about transcendental states, such as mystical experiences, existential aspects of life-threatening illness, and the role of therapists’ own self-experience/inner work, as well as good knowledge of the theoretical basis for treatment, was highlighted. Conclusions: This study highlights special considerations for PAT PC and could be a first step towards specific treatment recommendations (guidelines) for PATPC. Full article

Czechia has recently approved the medical use of psilocybin, marking a pivotal shift in the country’s drug policy landscape. This development paves the way for regulated therapeutic applications of psilocybin within clinical settings, while simultaneously prompting a timely discussion on the potential uses of psychedelics beyond strictly medical contexts. This commentary first outlines the legal status of psilocybin for therapeutic use in Czechia and situates this reform within broader international policy trends. Drawing on the publication How to Regulate Psychedelics and qualitative findings from a ketamine-assisted therapy program conducted as part of the Czech Destigmatizing the Therapeutic Use of Psychedelics in Psychiatry project, it then examines the regulation of non-clinical psychedelic use, while also highlighting the persistent legal ambiguity surrounding the Czech offence of “spreading toxicomania.” The commentary advocates for a rational, evidence-based regulatory approach, arguing that while the medicalization of psilocybin constitutes a significant legal milestone, the framework will remain incomplete without clear pathways for non-clinical use to ensure safety and legal clarity. Full article

Whilst “nootropics” are meant to treat a range of medical disorder-related cognitive impairments, the typically healthy “smart drugs” user ingests a range of drugs/molecules to achieve improved mental performance. Given the increasing levels of related concerns, this study aimed to provide an overview of the clinical pharmacological issues relating to both the most popular nootropics and the vast range of drugs that are being used as putative cognitive enhancers/smart drugs. In terms of the cognitive decline associated with neurological degenerative disorders, a significant variation in research methodology was observed. Therefore, the overall usefulness of these pharmaceuticals in various central nervous system disorders as supplements/adjuvant therapy needs to be better established before their widespread use can be recommended. The most popular smart drugs, self-administered to cope with high-perceived stress and academic/work-related pressure, were methylphenidate, modafinil, amphetamine-based compounds, and psychedelics. At present, however, there are relevant levels of uncertainty in terms of smart drugs’ effectiveness in improving executive functions. Addressing the health harms associated with cognitive enhancers’ intake remains challenging due to the lack of updated and contextualized epidemiological data. In particular, there appears to be a range of clinical concerns relating to the non-prescribed intake of stimulant smart drugs by otherwise healthy individuals. Enhanced training for prescribers, pharmacists, and healthcare professionals can strengthen monitoring and early intervention efforts. Full article

This study investigated the effects of low-dose 1cp-LSD, a prodrug of LSD, on canine anxiety, while exploring the influence of owner psychopathology on treatment outcomes. Seven dogs exhibiting anxiety-related behaviors were recruited and received 2.5, 5, or 10 µg of 1cp-LSD orally every three days for 30 days. One additional dog, which did not meet clinical criteria for anxiety but whose owner perceived it as anxious, received a placebo (saccharin) as an observational case. Anxiety levels were assessed using validated scales at baseline, post-treatment, and one month after treatment cessation. Owners’ neuroticism and psychopathological dimensions were evaluated using the IPIP and SA-45 scales. Linear regression analyses examined associations between anxiety reduction, administered dose, and owner psychological traits. A significant reduction in separation anxiety scores was observed post-treatment (mean: 11.3 ± 3.0, p = 0.023). Higher 1cp-LSD doses correlated with greater anxiety reduction (B = −1.15, 95% CI = [−2.29, −0.003], p = 0.050). Additionally, higher owner psychoticism scores were associated with smaller improvements in canine anxiety (p = 0.035). Anxiety levels remained low one month after treatment, with significant associations between canine anxiety and the owners’ hostility, interpersonal sensitivity, and paranoid ideation. These findings support the potential role of low-dose serotonergic psychedelics in managing canine anxiety and suggest an association between caregiver psychological traits and treatment outcomes. The sustained reduction in anxiety behaviors also suggests a meaningful and lasting improvement in animal welfare. However, significant results should be interpreted cautiously due to the small sample size. Further blinded, controlled studies are needed to validate these preliminary observations and assess broader applications in veterinary behavioral medicine. Full article

States like Hawai‘i are decriminalizing psychedelics based on emerging evidence linking their use to improved psychological well-being. Yet, in many cultural contexts, stigma surrounding mental illness may lead individuals to pursue non-traditional forms of healing, including psychedelics, in place of formal care. This study examines how psychedelic use relates to mental health treatment-seeking behaviors among Asians and Native Hawaiians and Other Pacific Islanders (NHOPIs). Using the National Survey of Drug Use and Health (NSDUH) data from 2008 to 2019 (n = 458,372), the analysis compares Non-Hispanic Whites with Asian and NHOPI respondents to assess associations between MDMA and lifetime classic psychedelic use, psychological distress (K6 scale), and formal mental health service utilization. Nested logistic regression models conducted in Stata 18 indicate that psychedelic use among White individuals is associated with a lower likelihood of seeking formal treatment. In contrast, among NHOPI individuals, psychedelic use is associated with increased odds of accessing mental health care. These findings suggest that psychedelic use may serve culturally distinct roles in coping with distress, shaped by structural stigma and the perceived trustworthiness of formal treatment systems. Full article