Frontiers in psychiatry
January 1, 2022
Charles L Raison, Rakesh Jain, Andrew D Penn et al.
75 citations
In a large online survey of 2,510 adults who had used psychedelics at least once, psychedelic use was linked to significant improvements in depression, anxiety, and emotional well-being. The benefits grew with more use but showed a ceiling effect; even a single use was associated with improvements. No single psychedelic agent proved clearly superior, but increases in mystical experiences and prosocial perspective-taking were tied to better mental health. However, 13% of participants (330 people) reported at least one harm from psychedelic use, and those individuals experienced less mental health benefit. The findings suggest that naturalistic psychedelic use may offer mental health benefits similar to those in clinical trials, while also posing some risk of harm for a minority.
Frontiers in psychiatry
January 1, 2021
O Merve Mollaahmetoglu, Johanna Keeler, Katherine J Ashbullby et al.
62 citations
Ketamine treatment, provided in a supportive clinical setting, led to a significant change in participants' relationship with alcohol. Interviews with 12 people who received up to three ketamine infusions (0.8 mg/kg) as part of a Phase II randomized controlled trial revealed six key themes: multifaceted motivations for joining the trial; the influence of set and setting on the acute experience; inherent contradictions such as dissociation versus feelings of connection; rapidly fluctuating experiences; meaningful, mystical, and spiritual experiences; and transformational effects of the infusions. Participants reported that ego dissolution and dissociation were linked to these transformative changes. The authors suggest that the acute psychoactive effects of ketamine transcend its traditional label as a dissociative anesthetic and recommend developing new measures to capture the full spectrum of these effects.
Frontiers in psychiatry
January 1, 2022
Joost J Breeksema, Alistair Niemeijer, Bouwe Kuin et al.
41 citations
Patients with treatment-resistant depression undergoing oral esketamine treatment often find the experience overwhelming and struggle with whether to let go or maintain control. Their ability to let go is influenced by preparation, emotional support, and the treatment setting. Better preparation, an optimized environment, and psychological support during sessions may improve patients' experiences and outcomes. The study provides recommendations for improving quality of care, including training for nurses and support staff.
Frontiers in psychiatry
January 1, 2021
Anne C Wagner, Rachel E Liebman, Ann T Mithoefer et al.
40 citations
Healing from trauma happens in relationships, and PTSD affects more than just the diagnosed individual. In a pilot trial of Cognitive Behavioral Conjoint Therapy (CBCT) for PTSD combined with two MDMA psychotherapy sessions, six romantic couples where one partner had PTSD showed improvements across multiple areas. Both partners reported increases in post-traumatic growth, relational support, and social intimacy. Partners also reported less behavioral accommodation and conflict, while patients with PTSD reported better psychosocial functioning and empathic concern. These gains lasted through a 6-month follow-up. The findings suggest that combining CBCT with MDMA can improve relational and growth outcomes, supporting a dyadic approach to holistic trauma recovery.
Frontiers in psychiatry
January 1, 2022
Eleanor Dawkins, Leola Cruden-Smith, Ben Carter et al.
37 citations
Catatonia involves both observable clinical signs and internal subjective experiences, yet the latter is understudied. Analyzing electronic health records of 1,456 patients with validated catatonia from a London mental health trust, the most common signs were mutism, immobility/stupor, and withdrawal. Cluster analysis yielded negative and positive clinical features; principal component analysis identified three components: parakinetic, hypokinetic, and withdrawal. The parakinetic component associated with women, neurodevelopmental disorders, and longer admissions; hypokinetic with catatonia relapse; withdrawal with men and mood disorders. Among 68 patients with phenomenological data, 35% expressed fear, but 72% provided a meaningful narrative explanation involving hallucinations, delusions, or non-psychotic rationales, suggesting subjective experiences are varied and often explanatory.
Frontiers in psychiatry
January 1, 2022
S Parker Singleton, Julie B Wang, Michael Mithoefer et al.
36 citations
In nine veterans and first-responders with chronic PTSD, MDMA-assisted therapy (MDMA-AT) did not significantly increase amygdala-hippocampus resting-state functional connectivity as hypothesized, showing only a trend. After treatment, brain activation during trauma memory recall decreased in the cuneus. Recovery from PTSD correlated with changes in four functional connections during autobiographical memory recall: left amygdala with left and right posterior cingulate cortex and left insula, and left isthmus cingulate with left posterior hippocampus. These findings suggest that amygdala, hippocampus, and insula functional connectivity may be a target of MDMA-AT, highlighting regions involved in memory processes.
Frontiers in psychiatry
January 1, 2023
Helena D Aicher, Michael J Mueller, Dario A Dornbierer et al.
34 citations
A standardized formulation combining the monoamine oxidase inhibitor harmine (100 mg orodispersible tablet) with incremental intranasal N,N-dimethyltryptamine (DMT, up to 100 mg) produced a psychedelic experience in 31 healthy male subjects, as measured by the 5D-ASC rating scale. The experience was characterized by psychological insights, emotional breakthroughs, and low scores on challenging experiences. Participants reported personal and spiritual significance and mainly positive persisting effects at 1- and 4-month follow-ups. No changes in trait personality, psychological flexibility, general well-being, or increases in psychopathology were observed. The formulation appears well tolerated and may support psychotherapy, but further studies in patients are needed.
Frontiers in psychiatry
January 1, 2024
Matteo Di Vincenzo, Vassilis Martiadis, Bianca Della Rocca et al.
31 citations
Treatment-resistant depression (TRD) is defined as failing at least two adequate antidepressant trials. Esketamine, the S-enantiomer of ketamine, has been approved for TRD by the U.S. FDA and European Medicines Agency, but misconceptions about it persist among clinicians and patients. This review searched databases for keywords including "esketamine" and "myth" to identify false beliefs. Common myths included misunderstandings about TRD prevalence, clinical features, and predictors, as well as esketamine's treatment criteria, dissociative symptoms, addiction potential, and administration. Evidence-based facts counter these myths, showing esketamine is effective for TRD with necessary precautions, and accurate diagnosis is key to recovery.
Frontiers in psychiatry
January 1, 2021
Raghuram Nagarathna, Akshay Anand, Manjari Rain et al.
31 citations
During the COVID-19 lockdown in India, people who practiced yoga reported less anxiety, stress, and fear, and had better coping strategies compared to those who did not practice yoga. Yoga practitioners also showed better physical ability, endurance, and sleep quality, while being less likely to use substances or eat unhealthy food. Among yoga practitioners, those who meditated had relatively better mental health. The findings suggest that incorporating yoga into daily routines may help reduce stress and improve immunity, potentially lowering COVID-19 risk if specific protocols are implemented through a global public health initiative.
Frontiers in psychiatry
January 1, 2023
Philip E Wolfson, Julane Andries, Daniel Ahlers et al.
27 citations
Ketamine-assisted psychotherapy (KAP) shows promise for treating adolescent mental disorders, though research is early. Four adolescents aged 14–19 with treatment-resistant depression, bipolar disorder, eating disorders, anxiety, panic, and trauma-related symptoms received sublingual ketamine followed by intramuscular ketamine. Each had symptomatic and functional improvements, and the treatment was well-tolerated. Rapid resolution of symptoms often occurs within months but is not inevitable. Family involvement appears essential to success. This modality may expand psychiatric treatment options.
Frontiers in psychiatry
January 1, 2023
Carson Chrenek, Bryan Duong, Atul Khullar et al.
23 citations
Intravenous ketamine and intranasal esketamine are effective for treatment-resistant depression but are limited by cost, availability, and monitoring requirements. A literature review up to June 2023 and a community case study from two public hospital sites in Edmonton, Canada, describe how evidence on ketamine for treatment-resistant depression can be applied in real-world settings. The paper synthesizes knowledge on off-label racemic ketamine versus FDA-approved esketamine, dosing, safety, and long-term maintenance. To overcome cost barriers, public programs may incorporate sublingual or intranasal ketamine. Three such sustainable treatment models are described, though large-scale randomized trials and long-term outcome data remain lacking.
Frontiers in psychiatry
January 1, 2021
Andreas Rosén Rasmussen, Andrea Raballo, Antonio Preti et al.
21 citations
Anomalies of imagination—disturbances in the basic structure of fantasies and imagery—are highly characteristic of schizophrenia-spectrum disorders and closely related to self-disorders. In a study of 81 participants, including patients with schizophrenia or other non-affective psychosis, schizotypal personality disorder, other mental illness, and healthy controls, these anomalies aggregated significantly in the schizophrenia-spectrum group compared to other mental illness and healthy controls, with no difference between schizophrenia and schizotypal disorder. Network analysis showed anomalies of imagination were closely interconnected with self-disorders, while correlations with perceptual disturbances and positive, negative, and general symptoms were moderate but separated in the network.
Frontiers in psychiatry
January 1, 2020
Ram P Sapkota, Alain Brunet, Laurence J Kirmayer
21 citations
In a systematic case-control study of 384 Nepalese adolescents aged 11-18 from 12 public schools, 194 students affected by mass psychogenic illness (MPI) were compared with 190 unaffected controls. MPI is understood as a dissociative phenomenon spread through social contagion among those prone to dissociation. Bivariate analyses linked caseness to childhood physical neglect and abuse, living in nuclear families, peritraumatic dissociation, dissociative tendencies, and depressive and post-traumatic stress symptoms. Hypnotizability was the strongest correlate among cognitive and personality traits. However, multivariable logistic regression found that common correlates of dissociation did not predict caseness, suggesting these factors do not adequately explain MPI. A Classification and Regression Trees analysis indicated that highly hypnotizable adolescents with high peritraumatic dissociation had a 73% probability of being a case.
Frontiers in psychiatry
January 1, 2020
Jonathan Levy, Oren Bader
19 citations
The neuroscience of empathy has relied on a simplified affective/cognitive dichotomy that cannot explain recent data from naturalistic and intergroup studies. Drawing on phenomenological philosophy, a new neuro-phenomenological account breaks through this dichotomy, emphasizing empathy as dynamic, subjective, and piecemeal. The graded empathy hypothesis postulates that attending to others' expressions always facilitates empathy, but the level of empathic experience varies parametrically with one's social interest in the observed other, such as through intergroup or interpersonal cues. This framework integrates neuroscience with phenomenology to offer a more accurate perspective for real-life experimentation.
Frontiers in psychiatry
January 1, 2024
Alexandros Matsingos, Marcel Wilhelm, Laila Noor et al.
18 citations
In double-blind randomized trials of ketamine and esketamine for major depressive disorder, the placebo response accounts for up to 72% of the overall treatment response. Across 14 studies with 1100 participants, the pooled effect size for placebo was -1.85, while the treatment effect was -2.57. Seven days after treatment, the placebo response accounted for 66% of the treatment response. Ketamine and esketamine show large antidepressant effects, but the placebo response plays a significant role and should be leveraged in clinical practice.
Frontiers in psychiatry
January 1, 2019
Jordan K Zjawiony, Antônio S Machado, Ricardo Menegatti et al.
18 citations
Pain reduces quality of life, health, and economic well-being. Opioids are effective analgesics but cause side effects and have contributed to an overuse crisis, prompting the search for new pain treatments. This review examines salvinorin A and its analogs, focusing on their structural and pharmacological profiles as a basis for developing safer analgesics. Ethnopharmacological reports and preclinical data show antinociceptive effects of salvinorin A and some analogs. Analogs modified at the C-2 position dominate the literature. Binding affinity correlates with chemical structure and in vivo effects. Salvinorin A's susceptibility to chemical modification makes it a valuable tool for probing cellular mechanisms and developing promising analgesic analogs, though more research is needed to confirm therapeutic potential.
Frontiers in psychiatry
January 1, 2022
Micaela Tirri, Sabrine Bilel, Raffaella Arfè et al.
17 citations
Psychedelic phenethylamines, especially -NBOMe compounds, impair sensorimotor function, reaction time, and sensory gating in mice more potently than LSD or their 2C analogs. Halogenated derivatives 25I-NBOMe and 25B-NBOMe were the most effective at altering visual and acoustic responses, motor activity, and prepulse inhibition. The rank order of potency showed these -NBOMe compounds were stronger than both 2C analogs and LSD. These sensory impairments affected spontaneous movement and reaction time without changing stimulated motor performance. The findings suggest that -NBOMe compounds pose potential public health risks, particularly for driving or hazardous work requiring intact sensorimotor skills.
Frontiers in psychiatry
January 1, 2021
Georgios Mikellides, Panayiota Michael, Lilia Psalta et al.
17 citations
Both intramuscular ketamine and repetitive transcranial magnetic stimulation (rTMS) effectively reduced depressive and anxiety symptoms in patients with treatment-resistant depression. In a naturalistic clinical setting, 24 patients received either eight sessions of ketamine or 30 sessions of left dorsolateral prefrontal cortex intermittent theta-burst stimulation. Both groups showed significant improvement from pre- to post-treatment on three clinical assessments, with no significant differences between the therapies in symptom reduction, remission, or response rates, indicating they were equally effective in this limited sample.
Frontiers in psychiatry
January 1, 2023
Ellen James, David Erritzoe, Tiffanie Benway et al.
16 citations
A phase 1 trial tested escalating intravenous doses of the psychedelic DMT (SPL026) in healthy volunteers who had never used psychedelics, to find a safe, tolerable dose for a future trial in people with major depressive disorder. Participants were randomly assigned to placebo or one of four doses (9, 12, 17, or 21.5 mg). The drug was well tolerated with no serious adverse events. Higher blood levels of DMT correlated with stronger ratings of mystical experience, ego dissolution, and intensity, though these trends need confirmation in larger studies. Based on safety and pharmacodynamic results, 21.5 mg given as a two-phase infusion was chosen for the patient trial.
Frontiers in psychiatry
January 1, 2024
Nicolas G Glynos, Jacob S Aday, Daniel Kruger et al.
15 citations
A large global survey of 5,268 adults who had used psychedelics found that nearly three-quarters (70.9%) reported ceasing or decreasing use of at least one non-psychedelic substance afterward. Among those who had previously used specific substances, 60.6% decreased alcohol use, 55.7% decreased antidepressant use, and 54.2% decreased cocaine or crack use. Over a quarter said the decrease lasted 26 weeks or longer. However, 19.8% reported increased or initiated use of other substances, most commonly illicit opioids (14.7%) and cannabis (13.3%). Factors linked to decreased use included motivation to reduce substance use or self-treat a medical condition; increased use was associated with higher income and residing in Canada or the US.
Frontiers in psychiatry
January 1, 2023
Macha Godes, Jasper Lucas, Eric Vermetten
14 citations
For people with severe PTSD, MDMA-assisted psychotherapy helps them articulate how the treatment changes their daily lives. Analysis of session transcripts from 7 participants in a Phase-II trial identified perceived mechanisms of change, showing how the therapy's proposed working mechanisms integrate into everyday functioning. The qualitative findings complement earlier quantitative results by providing real-life statements that clarify the treatment's effects.
Frontiers in psychiatry
January 1, 2024
Jenny J W Liu, Natalie Ein, Julia Gervasio et al.
13 citations
Ketamine shows promise for treating chronic pain, depression, and PTSD in military populations, including active-duty personnel and veterans. A meta-analysis of 11 studies (22 samples) found that ketamine use led to significant, moderate-to-large reductions in symptoms across all three conditions, with an overall effect size of g = 1.76. These benefits were consistent regardless of how ketamine was administered, dosage, treatment duration, or whether other treatments were used concurrently. The findings suggest ketamine may be a valuable alternative, especially for those who have not responded to conventional treatments. However, more research is needed to confirm these results.
Frontiers in psychiatry
January 1, 2022
Christophe Gauld, Kristopher Nielsen, Manon Job et al.
13 citations
Psychiatry cannot rely solely on reductionism; it requires a plurality of approaches. Enactivism, rooted in cognitive science, dynamic systems theory, systems biology, and phenomenology, offers an integrative framework for psychiatry. This paper compares the enactive approach with two forms of explanatory pluralism: non-integrative pluralism, which tolerates coexisting incompatible systems, and integrative pluralism, which aims to unite different levels of understanding. The authors propose that enactivism is inherently a form of integrative pluralism but also part of a broader explanatory pluralism. Understanding these theoretical positions is important for quality clinical practice, and studying the entanglements between analytical pluralism and enactivist pluralism could be fruitful.
Frontiers in psychiatry
January 1, 2022
Ryan Yip, Jennifer Swainson, Atul Khullar et al.
13 citations
Ketamine is increasingly used for treatment-resistant depression, but its intravenous administration often causes transient high blood pressure. Current psychiatric guidelines recommend aggressive monitoring and treatment of these hypertensive episodes. This review argues that those guidelines should be updated to align with standard best practices for managing hypertension, distinguishing between hypertensive emergency and asymptomatic hypertensive urgency. Adopting such an updated protocol could make ketamine therapy safer and more accessible for patients with depression.
Frontiers in psychiatry
January 1, 2025
Mary R Shen, Dylan E Campbell, Anika Kopczynski et al.
10 citations
A scoping review of eight studies found that ketamine may help reduce opioid cravings and use in people with opioid use disorder and can attenuate precipitated withdrawal symptoms, often as an adjunct to buprenorphine. The review searched two databases, yielding 998 studies, of which eight met inclusion criteria: two on opioid use disorder and six on opioid withdrawal. The evidence is preliminary, and more research is needed before widespread clinical use.