Search Results (15)

Adolescent mental health conditions, particularly treatment-resistant depression (TRD), represent a growing public health challenge associated with high morbidity, functional impairment, and elevated suicide risk. Psychedelic-assisted therapies have shown robust antidepressant and transdiagnostic effects in rigorously controlled adult trials. Extending this work to adolescents is scientifically compelling yet ethically complex, given neurodevelopmental vulnerabilities and the paucity of pediatric data. This review examines the historical context of psychedelic use, summarizes adult efficacy and mechanistic insights, explores adolescent-specific opportunities and risks, and considers applications in co-occurring neurodevelopmental disorders. Conventional treatments, including selective serotonin reuptake inhibitors and psychotherapy, are often inadequate for a narrow but substantial subset of clinical phenotypes, prompting interest in novel and rapid-acting interventions. Psychedelic-assisted therapies have shown promising results in adults with refractory mood disorders, yet their applicability to adolescents remains uncertain due to ongoing neurodevelopment and ethical constraints. This review critically examines evidence from adult psychedelic and psychedelic-adjacent interventions, including esketamine, and evaluates their potential relevance to adolescent populations through a developmental, mechanistic, and ethical lens. Rather than advocating for premature clinical adoption, we highlight translational gaps, developmental risks, and research priorities paramount to responsibly assess these approaches in youth. Full article

Classic psychedelics such as lysergic acid diethylamide (LSD) and psilocybin induce mild cardiovascular activation in addition to their psychological effects. While these effects are well described in healthy adults, little is known about their dynamics in clinical populations undergoing psychedelic-assisted psychotherapy. This retrospective, observational, single-center study analyzed routinely collected data from 30 patients (mean age = 51.56 ± 12.19 years; 15/30 female) treated under compassionate use for treatment-resistant depression or anxiety disorders. Participants received either LSD (100–200 mcg) or psilocybin (15–30 mg) in supervised outpatient sessions. Heart rate and self-rated anxiety (VAS 0–100) were recorded at seven intervals from 30 to 300 min post-administration. Linear mixed models examined heart rate trajectories over time × substance, controlling for age and, in a second model, perceived anxiety. Linear mixed models revealed no significant main effect of time (F(6, 77.25) = 0.76, p = 0.60) or substance (F(1, 30.82) = 0.66, p = 0.42), but a significant time × substance interaction (F(6, 77.25) = 3.03, p = 0.01). LSD was associated with a delayed but sustained increase in heart rate peaking at 3–4 h, whereas psilocybin showed an earlier decline. These patterns persisted after adjustment for age and anxiety, and anxiety did not significantly modify the relationship between time and substance. No serious cardiovascular adverse events occurred. These preliminary findings suggest that LSD and psilocybin may produce distinct temporal patterns of cardiovascular activation in clinical settings. However, interpretation should be cautious due to the retrospective design, small sample size, and dose imbalance between substances. Full article

The past two decades have seen the reemergence of research investigating the therapeutic potential of psychedelic drugs across neuropsychiatric illnesses. One condition, alcohol use disorder (AUD), is of relevance given the broad public health implications and both limited effectiveness and attrition associated with currently available treatments. While emerging research has suggested that the benefits of psychedelic drugs in the treatment of AUD may be considerable, several fundamental aspects of this work limit the conclusions that can be drawn. These limitations include those that apply to research involving psychedelics generally—including functional unblinding and the role and definition of “psychedelic assisted psychotherapy” and some unique to AUD, including the nature of the mystical experience and how it relates to the “spiritual experience” as described in the literature of Alcoholics Anonymous (AA), of which the history of psychedelic research in AUD is closely intertwined. Additionally, current mechanistic neuroimaging studies examining the therapeutic effects of psychedelics in AUD are limited by design and do not directly interrogate the cognitive and circuit-level processes likely underlying treatment response. This review describes these limitations in detail by bridging historical, conceptual, and mechanistic aspects of psychedelic research in AUD and offers suggestions for future studies, the results of which may more clearly specify the role and utility of psychedelic drugs in the treatment of AUD. Full article

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

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

Psychedelic substances have experienced a resurgence of clinical interest in recent years, particularly for their promising effects in the treatment of psychiatric disorders such as depression and anxiety. While evidence regarding their role in chronic pain management remains limited, emerging studies suggest potential therapeutic benefits. This case report describes a patient with persistent somatoform pain disorder and recurrent depressive disorder who underwent four sessions of psilocybin-assisted psychotherapy. The intervention was associated with a reduction in the negative impact of pain on daily life, increased pain acceptance, improved quality of life, and reduction in depressive symptoms. These findings contribute to the growing body of literature suggesting that psychedelics, when combined with psychotherapy, may offer a novel and holistic approach to the treatment of chronic pain. Further controlled studies are needed to explore the safety, efficacy, and underlying mechanisms. Full article

Despite growing evidence supporting the efficacy of LSD-assisted psychotherapy in treating major depressive disorder (MDD), identifying reliable psychopharmacological biomarkers remains necessary. Oxytocin, a neuropeptide implicated in social bonding and flexibility, is a promising candidate due to its release following serotonergic psychedelic administration in healthy individuals; however, its dynamics in psychiatric populations are currently unexplored. This observational pilot study aimed to characterize salivary oxytocin dynamics during a single LSD-assisted psychotherapy session in our patients with treatment-resistant MDD. Participants received 100 or 150 µg LSD, and salivary oxytocin was measured at baseline, 60, 90, and 180 min post-LSD. Concurrently, participants rated subjective drug intensity (0–10 scale) at 60, 90, and 180 min. A linear mixed model revealed significant variation of oxytocin levels over time. Perceived psychedelic intensity also significantly varied over time. This supports oxytocin as a potential biomarker. Larger, controlled trials are warranted to replicate these findings and clarify the mechanistic links between oxytocin dynamics and clinical outcomes, including changes in depressive symptoms and mental flexibility. Full article

Psychedelic treatments are emerging as promising interventions for many mental health conditions. These interventions are not offered in a standardized fashion across studies and between different healthcare centers. Beyond differences in substances and doses, there is also a great heterogeneity in the interventions provided by therapists. The current review offers a summary of important elements that should be reported when describing psychedelic-assisted therapies. Clinical trials involving psilocybin for depression are systematically reviewed to synthesize available descriptions of their interventions. This review demonstrates that the exact nature of these psychotherapeutic interventions tends to be poorly defined in most scientific papers on psychedelic treatments. This problem and its implications are examined. The field stands to gain from optimized psychotherapeutic methods; however, insufficient documentation in scientific papers currently hinders the dissemination and improvement of evidence-based protocols. This article offers ideas to encourage the progress of research on psychedelic-assisted therapies. Full article

Lysergic acid diethylamide (LSD) is gaining renewed interest as a potential treatment for anxiety, depression, and alcohol use disorder, with clinical trials reporting significant symptom reductions and long-lasting effects. LSD modulates serotonin (5-HT2A) receptors, which, in turn, influence dysfunctional brain networks involved in emotional processing and cognition. It has also shown promise in psychedelic-assisted psychotherapy, where mystical-type experiences are linked to improved psychological well-being. This review examines LSD’s pharmacokinetics, neurobiological mechanisms, and safety considerations, including cardiovascular risks, emotional vulnerability, and the potential for hallucinogen-persisting perception disorder (HPPD). Challenges such as small sample sizes, variable dosing protocols, and regulatory restrictions limit large-scale trials. Future research should focus on standardization, pharmacogenetic influences, and personalized treatment strategies to ensure its safe and effective integration into clinical practice. Full article

Background and Objectives: Substance use disorders (SUDs) affect millions worldwide. Despite increasing drug use, treatment options remain limited. Psychedelic-assisted therapy (PAT), integrating psychedelic substances with psychotherapy, offers a promising alternative by addressing underlying neural mechanisms. Materials and Methods: This review’s purpose is to investigate the current understanding of psychedelic therapy for treating SUDs, including tobacco, alcohol, and drug addiction. The systematic review approach focused on clinical trials and randomized controlled trials conducted from 2013 to 2023. The search was performed using PubMed, Google Scholar, and Consensus AI, following PRISMA guidelines. Studies involving psychedelics like LSD, psilocybin, ibogaine, and ayahuasca for treating various addictions were included, excluding naturalistic studies and reviews. Results: Our results highlight the key findings from 16 clinical trials investigating psychedelic therapy for SUDs. Psychedelics like psilocybin and ayahuasca showed promise in reducing alcohol and tobacco dependence, with psilocybin being particularly effective in decreasing cravings and promoting long-term abstinence. The studies revealed significant improvements in substance use reduction, especially when combined with psychotherapy. However, the variability in dosages and study design calls for more standardized approaches. These findings emphasize the potential of psychedelics in SUD treatment, though further large-scale research is needed to validate these results and develop consistent protocols. Conclusions: This research reviewed the past decade’s international experience, emphasizing the growing potential of psychedelic therapy in treating SUDs pertaining to alcohol, tobacco, and cocaine dependence. Psychedelics such as psilocybin and ketamine can reduce cravings and promote psychological well-being, especially when combined with psychotherapy. However, regulatory barriers and specialized clinical training are necessary to integrate these therapies into mainstream addiction treatment safely. Psychedelics offer a promising alternative for those unresponsive to conventional methods. Full article

A set of interventions that can produce altered states of consciousness (ASC) have shown utility in the treatment of substance misuse. In this review, we examine addiction-related outcomes associated with three common interventions that produce ASCs: psychedelic-assisted psychotherapy (PP), Transcendental Meditation (TM) and hypnotherapy (HT). While procedurally distinct, all three interventions are associated with some common phenomenological, psychological, and neurobiological features, indicating some possible convergent mechanisms of action. Along with addiction and mental health outcomes, these common features are reviewed, and their impact on substance misuse is discussed. While our review highlights some mixed findings and methodological issues, results indicate that PP and TM are associated with significant improvements in substance misuse, alongside improvements in emotional, cognitive and social functioning, behavior-change motivation, sense of self-identity, and meaning. In contrast, and despite its broader acceptance, HT has been associated with mixed and minimal results with respect to substance misuse treatment. Authors identify key research gaps in the role of ASC interventions in addiction and outline a set of promising future research directions. Full article

The need to identify effective therapies for the treatment of psychiatric disorders is a particularly important issue in modern societies. In addition, difficulties in finding new drugs have led pharmacologists to review and re-evaluate some past molecules, including psychedelics. For several years there has been growing interest among psychotherapists in psilocybin or lysergic acid diethylamide for the treatment of obsessive-compulsive disorder, of depression, or of post-traumatic stress disorder, although results are not always clear and definitive. In fact, the mechanisms of action of psychedelics are not yet fully understood and some molecular aspects have yet to be well defined. Thus, this review aims to summarize the ethnobotanical uses of the best-known psychedelic plants and the pharmacological mechanisms of the main active ingredients they contain. Furthermore, an up-to-date overview of structural and computational studies performed to evaluate the affinity and binding modes to biologically relevant receptors of ibogaine, mescaline, N,N-dimethyltryptamine, psilocin, and lysergic acid diethylamide is presented. Finally, the most recent clinical studies evaluating the efficacy of psychedelic molecules in some psychiatric disorders are discussed and compared with drugs already used in therapy. Full article

Psilocybin has been suggested as a promising transdiagnostic treatment strategy for a wide range of psychiatric disorders. Recent findings showed that psychedelic-assisted/”psycholitic” psychotherapy should provide significant and sustained alleviation of depressive symptoms. However, to date, there have been several study limitations (e.g., small sample sizes, blinding, limited follow-up, highly screened treatment populations) and some health/political issues, including practitioners’ experience, lack of standardized protocols, psychedelics’ legal status, ethical concerns, and potential psychological/psychopathological/medical untoward effects. The focus here is on a range of clinical and methodological issues, also aiming at outlining some possible suggestions. We are confident that newer evidence, more precise protocols, and eventual reclassification policies may allow a better understanding of the real potential of psilocybin as a transdiagnostic therapeutic molecule. Full article

Eating disorders (EDs) are serious, life-threatening psychiatric conditions associated with physical and psychosocial impairment, as well as high morbidity and mortality. Given the chronic refractory nature of EDs and the paucity of evidence-based treatments, there is a pressing need to identify novel approaches for this population. The noncompetitive N-methyl-D-aspartate receptor (NMDAr) antagonist, ketamine, has recently been approved for treatment-resistant depression, exerting rapid and robust antidepressant effects. It is now being investigated for several new indications, including obsessive–compulsive, post-traumatic, and substance use disorder, and shows transdiagnostic potential for EDs, particularly among clinical nonresponders. Hence, the aim of this review is to examine contemporary findings on the treatment of EDs with ketamine, whether used as a primary, adjunctive, or combination psychopharmacotherapy. Avenues for future research are also discussed. Overall, results are encouraging and point to therapeutic value; however, are limited to case series and reports on anorexia nervosa. Further empirical research is thus needed to explore ketamine efficacy across ED subgroups, establish safety profiles and optimize dosing, and develop theory-driven, targeted treatment strategies at the individual patient level. Full article

Strategically timed trauma- and attachment-informed psychotherapy to address underlying emotional wounds, paired with ketamine administered in precision-calibrated doses to ensure high-entropy brain states, may be key to improving the quality and duration of ketamine’s therapeutic efficacy for treatment-resistant depression. This approach optimizes the opportunities for change created by ketamine’s known effects as a rapid antidepressant that stimulates synaptogenesis, normalizes neural connectivity and coherence, enhances neuroplasticity, reduces inflammation, and induces high-entropy brain states with associated subjective psychedelic experiences. Ketamine, a non-selective N-methyl-D-aspartate (NMDA) receptor antagonist is a safe, effective, fast-acting dissociative anesthetic that, as a standalone treatment, also exhibits rapid sustained antidepressant effects, even in many patients with treatment-resistant depression. A prior history of developmental trauma and attachment injuries are known primary factors in the etiology of treatment resistance in depression and other mental disorders. Thus, the adjunct of targeted psychotherapy attuned to trauma and attachment injuries may enhance and prolong ketamine efficacy and provide an opportunity for lasting therapeutic change. Psychotherapy engagement during repeated ketamine sessions for patient safety and integration of altered states, paired with separate individualized psychotherapy-only sessions timed 24–48 h post ketamine induction, takes advantage of peak ketamine-induced dendritic spine growth in the prefrontal cortex and limbic system, and normalized network connectivity across brain structures. This strategically timed paired-session approach also exploits the therapeutic potential created by precision-calibrated ketamine-linked high-entropy brain states and associated psychedelic experiences that are posited to disrupt overly rigid maladaptive thoughts, behaviors, and disturbing memories associated with treatment-resistant depression; paired sessions also support integration of the felt sense of happiness and connectivity associated with psychedelic experiences. Full article