Frontiers in Psychiatry
July 12, 2022
Kwonmok Ko, Gemma Knight, James Rucker et al.
296 citations
Mystical experience—characterized by oceanic boundlessness, ego dissolution, and universal interconnectedness—may be a psychological mechanism influencing outcomes in psychedelic therapy. A review of 12 studies using psilocybin, ayahuasca, or ketamine found that 10 reported a significant association (correlation, mediation, or prediction) between mystical experience and symptom reduction across cancer-related distress, substance use disorder, and depressive disorders including treatment-resistant depression. However, most studies had small, non-diverse samples, and half were open-label, introducing potential bias. Future research needs larger, more diverse randomized designs and deeper exploration of mystical experience's nature and predictors to maximize therapeutic benefits while minimizing anxiety.
Frontiers in Psychiatry
September 10, 2021
Cato M. H. de Vos, Natasha L. Mason, Kim P. C. Kuypers
259 citations
A review of 16 preclinical and 4 clinical studies (20 total) shows that a single dose of a psychedelic—such as ayahuasca, DMT, psilocybin, or LSD—rapidly alters molecular, neuronal, synaptic, and dendritic plasticity mechanisms. These changes include increased expression of plasticity-related genes and proteins like Brain-Derived Neurotrophic Factor (BDNF) and greater dendritic complexity that outlasts the drug's acute effects. Repeated administration directly stimulates neurogenesis and elevates BDNF mRNA levels for up to a month. The evidence suggests these neuroplasticity adaptations parallel and may underlie the antidepressant, anxiolytic, and antiaddictive clinical effects of psychedelics.
Frontiers in Psychiatry
February 21, 2020
Max Wolff, Ricarda Evens, Lea J. Mertens et al.
188 citations
A conceptual model proposes that psychedelic-assisted therapies reduce experiential avoidance and increase acceptance through mechanisms similar to those in cognitive behavioral therapy. In controlled clinical settings, psychedelics relax avoidance-related beliefs, boosting motivation for acceptance via operant conditioning. This allows relatively avoidance-free exposure to intensified private events, where relaxed beliefs encounter corrective information and become revised. Such belief revision may explain lasting increases in acceptance and decreases in psychopathology. The article outlines open research questions and clinical implications.
Frontiers in Psychiatry
January 21, 2020
Juan José Fuentes, Francina Fonseca, Matilde Elices et al.
176 citations
A systematic review of controlled and randomized clinical trials evaluated the therapeutic potential of lysergic acid diethylamide (LSD) in psychiatry. Following PRISMA guidelines, 11 randomized-controlled trials involving 567 patients who received LSD doses from 20 to 800 mcg were identified. Despite heterogeneous study designs, positive results emerged, particularly for reducing psychiatric symptoms in alcoholism. Many authors reported significant short-term improvements, though some studies found long-term outcomes homogenized between LSD and control groups. The evidence is strongest for LSD's use in treating alcoholism, but the review notes that most older studies did not meet contemporary standards and that new, properly designed double-blind trials are needed.
Frontiers in Psychiatry
September 12, 2019
Allison A. Feduccia, Lisa Jerome, Berra Yazar‐klosinski et al.
172 citations
MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) shows a large effect size in pooled analyses, substantially improving safety and efficacy over approved medications paroxetine and sertraline, which have only small to moderate effects. The treatment involves up to three monthly 8-hour sessions with MDMA administered under direct observation, plus preparatory and integrative psychotherapy. Dropout rates are lower than in medication trials, and risks of diversion, overdose, or withdrawal are minimal. Breakthrough Therapy Designation from the FDA has accelerated phase 3 trials, with a planned submission for approval in 2021.
Frontiers in Psychiatry
October 4, 2021
Maxemiliano V. Vargas, Retsina Meyer, Arabo A. Avanes et al.
162 citations
Psychedelics, part of a broader class called psychoplastogens, promote structural and functional neural plasticity in brain circuits relevant to mental health. They produce lasting therapeutic effects after a single dose and show promise for depression, PTSD, anxiety, and substance use disorders. A theoretical framework explains their broad efficacy. Challenges like scalability and hallucinogenic effects may be addressed by non-hallucinogenic psychoplastogens. This shift in neuropsychiatry aims to cure mental illness by repairing underlying pathophysiology, not just treating symptoms.
Frontiers in Psychiatry
January 22, 2020
Earth Erowid, Fire Erowid, Albert Garcia‐romeu et al.
155 citations
A cross-sectional, self-report survey found that people who use psychedelics reported reductions in problematic substance use, including alcohol, opioids, and stimulants. The authors note that because the study is cross-sectional and relies on self-reports, it cannot determine whether psychedelics caused these changes. However, the results suggest a potential for psychedelics to reduce problematic substance use and support further clinical research into psychedelic-assisted treatment for substance use disorders.
Frontiers in Psychiatry
March 20, 2019
Ben Sessa, David Nutt, Laurie Higbed
141 citations
This review describes the history, pharmacology, safety, and clinical uses of MDMA. Most clinical research has focused on MDMA-assisted psychotherapy for PTSD, which is now in Phase 3 trials with a target for FDA and EMA licensing in 2021. The paper also covers other potential applications, including treating anxiety in autism and the authors' ongoing study on MDMA-assisted psychotherapy for alcohol use disorder. If efficacy criteria are met, MDMA would become a licensed medicine.
Frontiers in Psychiatry
December 23, 2021
A. Fiorentini, Filippo Cantù, Camilla Crisanti et al.
123 citations
Abuse of methamphetamines, cannabis, cocaine, and newer synthetic drugs (cannabinoids, cathinones) can trigger acute psychotic episodes that resemble psychotic disorders. The severity of substance use and addiction correlates with the likelihood of developing psychosis. Clinicians can identify some phenomenological features to help distinguish substance-induced psychosis from a primary psychotic disorder, though patients with existing psychotic disorders often abuse psychotomimetic drugs, complicating diagnosis. There is a notable lack of information on outcomes, treatments, and best practices for substance-induced psychotic episodes.
Frontiers in Psychiatry
February 9, 2023
Kees Kramers, Arnt Schellekens, Metten Somers et al.
119 citations
A systematic review of psilocybin-assisted therapy for substance use disorders identified four clinical trials (six articles) involving 151 patients, with doses from 6 to 40 mg. Three studies focused on alcohol use disorder and one on tobacco use disorder. In a pilot study (n=10), heavy drinking days decreased significantly. In another single-arm study (n=31), 32% achieved complete alcohol abstinence over an average of 6 years. A double-blind, placebo-controlled RCT (n=95) found significantly fewer heavy drinking days with psilocybin versus placebo. In a pilot study (n=15), smoking abstinence at 26 weeks was 80% and at 52 weeks 67%. All trials indicated beneficial effects, but larger RCTs are needed.
Frontiers in Psychiatry
May 21, 2020
110 citations
Four weeks of Bhastrika pranayama, a yoga breathing exercise, significantly reduced anxiety and negative affect in thirty healthy young adults. Brain scans showed that the practice modulated activity in emotion-processing regions including the amygdala, anterior cingulate, anterior insula, and prefrontal cortex, and decreased functional connectivity between the anterior insula and lateral prefrontal cortex. Changes in connectivity between the ventrolateral prefrontal cortex and right anterior insula correlated with changes in anxiety. The authors note these analyses were preliminary and exploratory.
Frontiers in Psychiatry
August 7, 2020
Richard J. Zeifman, Anne Catherine Wagner, Ros Watts et al.
104 citations
In two prospective studies with convenience samples of people planning to use a psychedelic (total N=358), participants completed questionnaires before use and at 2 and 4 weeks afterward. Across both studies, significant decreases occurred in experiential avoidance, depression severity, and suicidal ideation after psychedelic use. Decreases in experiential avoidance were significantly associated with decreases in depression severity and suicidal ideation. These results suggest that psychedelics may reduce experiential avoidance, depression severity, and suicidal ideation, and that reduced experiential avoidance may be a transdiagnostic mechanism in psychedelic therapy. Integrating psychedelics with therapies targeting experiential avoidance, such as acceptance and commitment therapy, may enhance outcomes.
Frontiers in Psychiatry
May 8, 2018
Ana Cecília de Menezes Galvão, Raíssa Nóbrega de Almeida, Erick Allan Dos Santos Silva et al.
102 citations
In treatment-resistant depression, a single dose of ayahuasca normalizes the blunted awakening salivary cortisol response observed in patients, bringing it to levels similar to those in healthy controls. During the dosing session, both patients and healthy volunteers who received ayahuasca showed higher increases in salivary cortisol than those who received placebo. No significant changes in plasma cortisol were detected 48 hours after dosing. These findings suggest that ayahuasca modulates salivary cortisol, a hormone involved in depression's etiology, and support further investigation into its antidepressant potential.
Frontiers in Psychiatry
November 20, 2017
Laura Orsolini, Gabriele Duccio Papanti, Domenico de Berardis et al.
99 citations
Hallucinogen-persisting perception disorder (HPPD) is a syndrome of prolonged or recurring perceptual symptoms resembling acute hallucinogen effects. It has been linked to LSD, cannabis, MDMA, psilocybin, mescaline, and psychostimulants, and more recently to novel psychoactive substances. Symptoms are mainly visual, including geometric pseudo-hallucinations, haloes, flashes of light, motion-perception deficits, afterimages, and micropsia, though depressive and thought disorders may co-occur. First described in 1954, HPPD was formally recognized as a syndrome in the DSM-IV-TR in 2000. Its neural substrates, risk factors, and causes remain largely unknown. This mini review surveys psychopathological bases, etiological hypotheses, and psychopharmacological approaches, including associations with novel substances, based on a literature search of PubMed/Medline, Google Scholar, and Scopus without time restrictions.
Frontiers in Psychiatry
June 12, 2023
Rayyan Zafar, Maxim Siegel, Rebecca Harding et al.
95 citations
Psychedelic therapy is regaining scientific and medical interest, with growing evidence for its safety and efficacy in treating psychiatric disorders, including addiction. This review charts research on these interventions for addiction, starting with the socioeconomic impact of addiction and current treatment options. It examines historical studies from the mid-late 1900s, real-world evidence from naturalistic and survey-based studies, and modern clinical trials from first-in-human to phase II. The review also covers translational neuropsychopharmacology techniques like fMRI and PET that help explain therapeutic mechanisms. A better understanding of these treatment effects can optimize psychedelic therapy development and improve patient outcomes.
Frontiers in Psychiatry
December 1, 2022
Jagpaul Kaur Deol, Caroline A. Maccallum, Lindsay A. Lo et al.
95 citations
Interest in psilocybin as a therapeutic approach has grown rapidly, yet health care professionals lack practical guidance on the topic, especially given the medical complexity and vulnerability of patients who may receive psilocybin-assisted psychotherapy. This article reviews basic psilocybin pharmacology and pharmacokinetics, indications, practical therapeutic strategies such as dosing, administration, and monitoring, and safety considerations including contraindications, adverse events, and drug interactions. The goal is to increase health care professionals' knowledge and comfort to discuss and counsel patients on psilocybin therapy, ultimately improving patient care and safety.
Frontiers in Psychiatry
July 19, 2021
Rita Kočárová, Jiřı́ Horáček, Robin Carhart‐Harris
95 citations
Psychedelic therapy may work across many psychiatric disorders by increasing neuronal and mental plasticity, which enhances the potential for change. Combined with psychotherapy, this plasticity can promote healthy adaptability and resilience, protecting long-term well-being. The authors propose that psychedelics' core action is transdiagnostic, offering prophylactic benefits beyond current treatments. They link candidate neurological and psychological markers to a predictive processing model, suggesting broad public health impact.
Frontiers in Psychiatry
April 24, 2018
Paulo César Ribeiro Barbosa, Luís Fernando Tófoli, Michael P. Bogenschutz et al.
95 citations
Members of the Brazilian União do Vegetal (UDV) who drink ayahuasca in ceremonies show lower rates of current alcohol and tobacco use disorders compared to the general Brazilian population, even though their lifetime use of these substances is higher. Among 1,947 UDV members aged 18 and older, those who attended more ceremonies in the previous year and had longer membership reported greater reductions in alcohol and tobacco problems. The findings suggest that regular ceremonial ayahuasca use, within a religious context, is associated with reduced substance misuse, particularly for adults over 24 years old.
Frontiers in Psychiatry
September 19, 2023
Hillary Jackson, Sara So, Abigail Yaffe et al.
87 citations
A large prospective survey of adults planning to take psilocybin outside clinical settings found that, on average, participants reported lasting reductions in anxiety, depression, and alcohol misuse, along with improvements in cognitive flexibility, emotion regulation, spiritual wellbeing, and extraversion, and decreases in neuroticism and burnout after use. However, a minority reported persisting negative effects: 11% at 2–4 weeks and 7% at 2–3 months after use, including mood fluctuations and depressive symptoms. The study included 2,833 respondents at baseline, 1,182 at 2–4 weeks, and 657 at 2–3 months post-use. Participants were primarily college-educated White men in the United States, mean age 40, who used dried psilocybin mushrooms (mean dose 3.1 grams) for self-exploration.
Frontiers in Psychiatry
February 3, 2021
Sara Tai, Elizabeth M. Nielson, Molly Lennard-Jones et al.
87 citations
A therapist training program for psilocybin therapy, developed for a phase IIb international, multicenter, randomized controlled study of treatment-resistant depression, is described. The manualized approach, based on evidence-based psychotherapeutic methods and approved by the FDA, includes online learning, in-person training, applied clinical training, and ongoing mentoring. After training 65 health care professionals across the US, Canada, and Europe, feedback indicated that didactic and experiential learning helped build conceptual understanding and skills. Clinical training and participant care under experienced therapists were most beneficial and challenging. Rigorous, scalable training requires collaboration among public, academic, and industry partners.
Frontiers in Psychiatry
June 20, 2023
Johannes T Reckweg, Cees J van Leeuwen, Cécile Henquet et al.
86 citations
In a small clinical trial with 16 adults suffering from treatment-resistant depression, an inhaled form of the psychedelic drug 5-MeO-DMT (GH001) was well tolerated and produced rapid antidepressant effects. An individualized dosing regimen of up to three increasing doses within a single day led to 87.5% of patients achieving remission (a depression score of 10 or less on the MADRS scale) by day 7, compared to 50% and 25% for single doses of 12 mg and 18 mg, respectively. Remission occurred as early as two hours after dosing for some patients. The findings suggest that individualized dosing may be more effective than a single dose.
Frontiers in Psychiatry
March 31, 2020
Kristin Heuschkel, Kim P.C. Kuypers
82 citations
Mindfulness meditation (MM) and psilocybin both show promise for treating depression, and their combined use may produce complementary therapeutic effects. This review of 93 articles found that MM and psilocybin similarly improve mood, social skills, and neuroplasticity, but differ in their effects on executive functioning, neural core networks, and neuroendocrine and neuroimmune markers. MM likely works through enhanced affective self-regulation and stress reactivity adjustments, while psilocybin may act via cognitive disinhibition and global neural network disintegration. The authors suggest that combining them could potentiate or prolong positive effects, such as MM facilitating psilocybin-induced peak experiences, and call for future placebo-controlled double-blind randomized trials of psilocybin-assisted mindfulness-based therapy.
Frontiers in Psychiatry
October 20, 2021
Meg J. Spriggs, Hannah Douglass, Rebecca J. Park et al.
78 citations
Anorexia nervosa is a severe psychiatric condition with few approved treatments. This paper describes how individuals with lived experience of anorexia nervosa helped shape a pilot study of psilocybin-assisted therapy through two online focus groups involving eleven people, and presents the protocol for that study at Imperial College London. Twenty female participants aged 21–65 with a body mass index of 15 kg/m² or above will receive three oral doses of psilocybin (up to 25 mg) over six weeks, supported by psychological preparation and integration, with a 12-month remote follow-up.
Frontiers in Psychiatry
September 13, 2019
Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al.
78 citations
People who microdose psychedelics report that it relieves symptoms of mental and physiological disorders more effectively than conventional treatments, especially for ADHD/ADD and anxiety disorders. However, regular (full) doses of psychedelics are rated as more effective than microdoses for mental disorders like anxiety and depression, while for physiological disorders there is no difference in effectiveness between microdoses and regular doses. These findings come from an online survey of 410 adults diagnosed with at least one disorder by a medical professional. The authors call for future randomized controlled trials to objectively test these claims.
Frontiers in Psychiatry
June 9, 2021
Simon Ruffell, Nige Netzband, WaiFung Tsang et al.
74 citations
A naturalistic study of 63 people who participated in ayahuasca ceremonies at a retreat in the Peruvian Amazon found significant improvements in depression, anxiety, and overall psychological distress, along with increased self-compassion, immediately after the retreat and sustained at six months. Depression scores on the Beck Depression Inventory dropped from 13.9 to 6.1, anxiety scores on the State-Trait Anxiety Inventory fell from 44.4 to 34.3, and scores on the Clinical Outcomes in Routine Evaluation-Outcome Measure decreased from 37.3 to 22.3. Changes in memory valence were linked to these improvements. Epigenetic results were inconclusive but suggested further research on the SIGMAR1 gene is warranted.