Frontiers in Psychiatry
July 15, 2023
M. Kati Lear, Sarah M. Smith, Brian Pilecki et al.
14 citations
An open-label pilot study will test MDMA-assisted therapy for social anxiety disorder. Twenty participants with moderate-to-severe generalized social anxiety will be randomly assigned to immediate or delayed treatment. The immediate group receives three preparation sessions, two MDMA medicine sessions, and six integration sessions over about 16 weeks. The primary outcome is symptom reduction measured by the Liebowitz Social Anxiety Scale at post-treatment and 6-month follow-up. Secondary outcomes include changes in functional impairment, safety, and processes like shame, belongingness, self-concealment, and self-compassion. Results will inform the design of larger randomized controlled trials.
Frontiers in Psychiatry
December 5, 2022
Geovan Menezes de Sousa, Vagner Deuel de Oliveira Tavares, Ana Cecília de Menezes Galvão et al.
14 citations
In a double-blind, placebo-controlled trial with 72 participants, ayahuasca's effects on depression-related biomarkers were examined two days after dosing. Larger reductions in depressive symptoms during the session were linked to higher serum cortisol levels in patients with treatment-resistant depression. Smaller changes in salivary cortisol during ayahuasca use were associated with higher brain-derived neurotrophic factor (BDNF) levels in patients who showed greater clinical improvement in depressive symptoms. No moderating effects were found for the cortisol awakening response, interleukin-6, or C-reactive protein in patients, nor for any biomarker in healthy controls or the placebo group. The findings suggest that acute emotional and physiological responses during ayahuasca sessions may influence key biomarkers of depression.
Frontiers in Psychiatry
September 27, 2022
William Barone, Michiko Mitsunaga-Whitten, Lia Osunfunláyò Blaustein et al.
14 citations
Anxiety related to life-threatening illness is a common problem that current treatments only partially address. In a pilot clinical trial of MDMA-assisted therapy for this condition, participants described key therapeutic experiences: processing trauma and grief, having mystical and existential experiences, engaging more fully with the present moment with less physiological arousal, and facing fears about illness and death. Outcomes included better ability to cope with their illness, reduced psychological symptoms, improved vitality and quality of life, and greater emotional resilience even after medical relapse. The findings suggest that MDMA-assisted therapy may help people reconnect to life and build emotional resources for dealing with existential distress.
Frontiers in Psychiatry
March 14, 2022
Edmund C. Neuhaus, George M. Slavich
14 citations
Psychedelics are being explored for treating mental health conditions like anxiety, depression, PTSD, and addiction, but there is no standard approach for combining them with psychotherapy or measuring their effectiveness. The authors propose the concept of behavioral psychedelics, defined as the study of using psychedelics to intentionally change habits and behaviors to improve health and resilience. They argue that psychedelics might reduce chronic disease risk linked to mental and behavioral rigidity, but the field needs to develop best practices and guidelines for inducing lasting behavioral changes.
Frontiers in Psychiatry
September 22, 2023
Haniya J Halim, Bradley G Burk, Rachel E Fargason et al.
13 citations
A 21-year-old male with a recent diagnosis of bipolar II disorder developed a manic episode after ingesting psilocybin in hallucinogenic mushrooms. Psilocybin is being studied as a treatment for depression and other conditions, but patients at risk for mania are typically excluded from research due to concerns about inducing mania. This case highlights the need for further investigation into the risks of psilocybin and other psychedelics in people with bipolar disorder, who may have high rates of depression, impulsivity, and substance use.
Frontiers in Psychiatry
May 25, 2022
Kevin Mintz, Brinn Gammer, Amanda Khan et al.
13 citations
Clinical trials for psychedelic therapies have increased but often exclude individuals with physical and sensory disabilities, risking structural ableism. Drawing on disability studies and medical ethics, the authors recommend prioritizing inclusion, providing accommodations, training facilitators in disability awareness, and practicing cultural humility. These steps aim to address mental health burdens faced by disability communities and spur further debate on accessibility.
Frontiers in Psychiatry
June 11, 2024
Sandra Szafoni, Piotr Gręblowski, Klaudia Grabowska et al.
12 citations
Psilocybin, a psychedelic substance, is being tested in clinical trials as an adjunct to psychotherapy for patients with major depressive disorder, obsessive-compulsive disorder, and substance use disorders (alcohol and nicotine dependence) that are resistant to traditional treatments. This article reviews current understanding of psilocybin, including data from clinical trials, its mechanism of action, safety profile, and associated risks.
Frontiers in Psychiatry
June 26, 2023
Simon Zhornitsky, Henrique Nunes Pereira Oliva, Laura A. Jayne et al.
12 citations
Ketamine and psychedelics can alter markers of synaptic density, which may relate to their abuse liability and potential therapeutic effects in substance use disorders. A scoping review of 84 studies found mixed results for ketamine: single or repeated doses under basal conditions produced inconsistent synaptic changes in the hippocampus and prefrontal cortex, but a single dose counteracted stress-related reductions in these markers, and repeated dosing also reversed stress effects. Psychedelics generally increased synaptic markers, though results varied by agent. The heterogeneity likely stems from differences in methods, drugs, sex, and marker types.
Frontiers in Psychiatry
May 26, 2022
Igor J. Pietkiewicz, Urszula Kłosińska, Radosław Tomalski
12 citations
A Caucasian Roman-Catholic woman who had undergone exorcisms for affect regulation problems, uncontrolled sexual impulses, and somatoform symptoms with altered consciousness received a diagnosis of Possession Trance Disorder. Using interpretative phenomenological analysis, the case study explores how she attributed meaning to "possession" as both a folk category and a medical diagnosis, and how this shaped her help-seeking. The diagnosis reinforced her belief in supernatural causation and discouraged professional treatment. The study also discusses dilemmas and uncertainties about the diagnostic criteria and validity of the disorder.
Frontiers in Psychiatry
September 6, 2021
Elena Argento, Devon Christie, Lindsay Mackay et al.
12 citations
The COVID-19 pandemic is expected to have lasting effects on mental health, adding to the pre-existing global burden where 1 billion people suffer from mental health disorders, with depression and anxiety costing US$1 trillion per year. Among hospitalized COVID-19 patients in China, about 96% experienced post-traumatic stress symptoms, and studies of ICU patients with previous coronaviruses show 30-40% rates of PTSD, depression, and anxiety persisting months after discharge. Indirect exposure through media or worry also triggers PTSD. Pandemic conditions—uncertainty, grief, isolation, economic instability, and reduced service access—exacerbate mental health problems and substance use, with fatal overdose spikes in North America disproportionately affecting racialized groups. The authors argue for considering psychedelic-assisted psychotherapy as a novel approach with potential antidepressant, anxiolytic, and anti-addictive effects that may foster connectedness.
Frontiers in Psychiatry
June 4, 2024
Julia Bornemann, James B Close, Kirran Ahmad et al.
11 citations
Psilocybin-assisted therapy may help treat fibromyalgia, a chronic widespread pain condition with limited treatment options. A protocol describes a mechanistic study with 20 participants who will attend 8 visits over 8 weeks, including two dosing sessions where psilocybin is given at least once, with doses up to 25 mg. The primary focus is on brain mechanisms, measured via electroencephalography during the acute psychedelic state and magnetic resonance imaging before and after treatment. Primary outcomes are Lempel-Ziv complexity from EEG and experiential avoidance via questionnaire. Secondary measures include pain, physical and mental function, and additional neuroimaging. Results aim to clarify how psilocybin-therapy works in the brain and inform a future randomized controlled trial.
Frontiers in Psychiatry
October 26, 2022
Tor-Morten Kvam, Ivar W Goksøyr, Lowan H. Stewart et al.
11 citations
A proof-of-principle, open-label clinical trial will test MDMA-assisted therapy for major depressive disorder. Twelve participants with a DSM-5 diagnosis of MDD will receive a flexible dose of MDMA during two dosing sessions over four weeks, each followed by three integration sessions. The primary outcome is change in depression severity measured by the MADRS scale from baseline to eight weeks after the second session. Secondary outcomes include functional impairment and safety measures such as adverse events and suicidality. The trial aims to inform larger studies and optimize the treatment protocol.
Frontiers in Psychiatry
September 27, 2021
Jason Luoma, M. Kati Lear
11 citations
Social anxiety disorder (SAD) often persists despite treatment, prompting interest in MDMA-assisted therapy (MDMA-AT) as an adjunct. A small randomized placebo-controlled trial in autistic adults showed encouraging results, but more research is needed. This review proposes how MDMA-AT may alter four disrupted systems in SAD: social anhedonia and reduced reward sensitivity, heightened threat perception, shame regulation, and dysfunctional interpersonal behaviors. The authors suggest MDMA-AT could enhance social motivation, increase feelings of safety and affiliation, reduce shame through self-transcendent emotions, and improve social skills, potentially boosting extinction learning and relationship quality.
Frontiers in Psychiatry
January 23, 2024
Johannes Hauser, Jan Sarlon, Timur Liwinski et al.
10 citations
Listening to music during intranasal (es)ketamine treatment for therapy-resistant depression is linked to reduced anxiety and lower blood pressure, stable or increased dissociation, and tolerance for higher doses. In a review of 494 sessions from 37 patients, those who listened to music received higher average doses (131.5 mg vs. 116.7 mg), reported less anxiety (0.4 vs. 1.4 points), and had lower peak systolic blood pressure (137.9 vs. 140.3 mmHg) compared to those who did not. Music did not affect depression scores between sessions.
Frontiers in Psychiatry
January 8, 2024
N. Jones, Laura M. Wagner, Molly C. Pellitteri Hahn et al.
10 citations
Psilocybin, a psychedelic compound used in psychotherapy research, is converted in the body to the active metabolite psilocin. Psilacetin (4-AcO-DMT) has long been thought to be an alternative prodrug for psilocin, but direct evidence was lacking. In mice, psilocybin produced 10–25% higher psilocin concentrations than psilacetin at 15 minutes after injection. The half-life of psilocin was about 30 minutes from either prodrug. Overall, psilacetin fumarate yielded about 70% of the psilocin exposure that psilocybin did. These results confirm that psilacetin acts as a psilocin prodrug in vivo and suggest it can be used as a substitute for psilocybin in mechanistic research with mice.
Frontiers in Psychiatry
December 8, 2023
Alina Wilkowska, Wiesław Jerzy Cubała
10 citations
Bipolar depression is a serious psychiatric condition linked to high suicide risk, treatment resistance, chronicity, and poor quality of life. Approved treatments are limited and often insufficient, creating an urgent need for new strategies. Intranasal esketamine, a ketamine enantiomer, is a rapid-acting antidepressant proven effective for treatment-resistant depression. Research on bipolar depression, though less extensive, suggests esketamine may be a safe alternative with low risk of mood polarity shifts. Reports indicate ketamine treatment may reduce suicidal thoughts, anhedonia, and anxiety. Ketamine's potential mood-stabilizing properties are hypothesized. This narrative review examines ketamine as an add-on to standard medication for acute bipolar depression.
Frontiers in Psychiatry
August 24, 2023
Grant Jones, Patrick Mair, Maha Al‐suwaidi et al.
10 citations
Lifetime psilocybin use is associated with lower odds of arrest for property crime, assault, serious violence, and miscellaneous crimes in a large US sample. However, race and ethnicity moderate these associations: psilocybin conferred reduced odds of at least one crime arrest outcome for White, Indigenous, Asian, and Multiracial participants, but not for Black or Hispanic participants. The authors suggest that structural factors such as systemic racism may underlie these differences and call for intersectional research on sociodemographic factors, psychedelic use, and crime.
Frontiers in Psychiatry
February 9, 2023
Anya Ragnhildstveit, Miriam Kaiyo, Matthew Brian Snyder et al.
10 citations
A 28-year-old woman with complex dissociative posttraumatic stress disorder (D-PTSD) underwent ten sessions of cannabis-assisted psychotherapy (CAP) over five months, combined with cognitive behavioral therapy. After treatment, her pathological dissociation score, measured by the Multidimensional Inventory of Dissociation, dropped by 98.5%, and she no longer met criteria for D-PTSD. She also experienced reduced cognitive distractibility, less emotional suffering, and improved psychosocial functioning. The patient has maintained these gains for over two years. The authors suggest CAP, which produced subjective effects similar to psychedelics like psilocybin and ketamine, warrants further research as a potential treatment for D-PTSD.
Frontiers in Psychiatry
January 9, 2024
Terence H W Ching, Lucia Amoroso, Calvin Bohner et al.
9 citations
A randomized controlled trial will test whether two doses of psilocybin (25 mg followed by either 25 or 30 mg), given with non-directive support, reduce obsessive-compulsive disorder (OCD) symptoms more than a single dose or a waitlist control. Thirty adults with treatment-refractory OCD will be enrolled. OCD symptoms will be measured with the Yale-Brown Obsessive-Compulsive Scale – Second Edition by a blinded rater at baseline and after the second dosing week. Participants will be followed for up to 12 months. The trial also aims to identify psychological mechanisms that may explain psilocybin's effects on OCD.
Frontiers in Psychiatry
September 20, 2022
9 citations
People who undergo MDMA- and psychedelic-assisted psychotherapy often adopt new beliefs about themselves and the world, and these changes are linked to mystical-type experiences during drug sessions. This paper argues that the sense of authenticity accompanying these belief changes arises from a simultaneous feeling of knowing and being known. The medications reduce defensive barriers, enabling the subject to share powerful feelings intersubjectively with the therapist or internalized others. The author draws on concepts such as existential feeling, ipseity, the True Self, transitional phenomena, implicit relational knowing, and predictive processing to propose a transitional space model for working through dissociated experience.
Frontiers in Psychiatry
June 17, 2022
Andrew Beswerchij, Dominic Sisti
9 citations
Adopting precise, non-stigmatizing terminology grounded in the medical model can advance both the science and public acceptance of psychedelics. Researchers and clinicians should distinguish between medical, recreational, and spiritual uses to set clear boundaries and expectations for patients. Replacing colloquial names with scientific names for medicines and therapies may help correct misconceptions held by professionals and the public. A harmonized medical lexicon provides a common language for important communication, such as informed consent. Recommendations draw on communications research in addiction medicine to encourage development and implementation of non-stigmatizing terminology in psychedelic research and treatment.
Frontiers in Psychiatry
October 24, 2019
Patrick Vizeli, Matthias E. Liechti
9 citations
MDMA (ecstasy), a recreational drug also studied as a treatment for PTSD, stimulates the dopamine system, which may contribute to its mood effects. Genetic differences in dopamine-related genes—including the D2 and D4 receptors and the dopamine transporter—were tested for their influence on subjective and autonomic responses to 125 mg of MDMA in 149 healthy volunteers across placebo-controlled crossover studies. After adjusting for multiple comparisons and individual differences in MDMA blood levels, none of the genetic variants significantly altered the drug's effects. Genetic variations in dopamine system genes are unlikely to explain why people respond differently to MDMA.
Frontiers in Psychiatry
August 13, 2017
Luisa Ponzoni, Daniela Braida, Gianpietro Bondiolotti et al.
9 citations
MDMA and its derivatives DOB and PMA increase social, rewarding, and anxiety-reducing behaviors in adult zebrafish. These effects are blocked by a V1a vasopressin antagonist (SR49059), suggesting the oxytocin/vasopressin system plays a key role. The drugs also raised brain levels of isotocin (fish oxytocin) 3–5 times above control levels. The findings indicate that the oxytocin/vasopressin system mediates the behavioral effects of these substances, linking it to substance abuse disorders.
Frontiers in Psychiatry
August 13, 2024
Mu-Hong Chen, Shu-Li Cheng, Yu-Chen Kao et al.
8 citations
A Bayesian meta-analysis of 10 clinical trials involving 515 adults with diagnosed depression found that psilocybin-assisted therapy produced a pooled mean reduction of 10.08 points on the 17-Item Hamilton Depression Rating Scale. The psychological protocols used alongside psilocybin varied: manualized directive psychotherapy, manualized nondirective psychological support, non-manualized nondirective psychological support, and non-manualized supportive psychotherapy. Compared with manualized nondirective psychological support, the other three approaches did not differ significantly in their effect on depressive symptoms. The improvement in depressive symptoms was not associated with the type of psychological protocol employed.
Frontiers in Psychiatry
November 3, 2022
Devon Christie, Berra Yazar-Klosinski, Ekaterina Nosova et al.
8 citations
Chronic pain and post-traumatic stress disorder (PTSD) frequently co-occur and worsen each other. In a Phase 2 open-label trial of MDMA-assisted therapy for PTSD, 84% of 32 participants reported pain and 75% reported pain-related disability. After treatment, those with the highest baseline pain showed significant reductions in pain intensity, disability, and overall severity grade; those with medium baseline pain also showed significant reductions in pain intensity. The findings suggest MDMA-assisted therapy may reduce chronic pain in people with severe PTSD, but the data are preliminary and encourage further research.