Frontiers in Psychiatry
December 2, 2022
Torsten Passie, Jeffrey Guss, Rainer Krähenmann
71 citations
Lysergic acid diethylamide (LSD) and similar psychoactive drugs have been used in psychotherapy since 1949, when the first clinical study with lower-dose LSD showed therapeutically relevant effects. Psycholytic therapy, named in 1960, involved serial lower-dose LSD or psilocybin sessions within a psychoanalytical framework, conducted in clinical settings on both inpatient and outpatient bases. Over 15 years, it was established at 30 clinical treatment centers and by more than 100 outpatient psychotherapists in Europe, while North America favored high-dose psychedelic therapy. Professor Hanscarl Leuner in Germany was the leading figure, providing a detailed analysis of the LSD reaction in a 1962 monograph. The article reviews evidence for psycholytic therapy's efficacy and argues for its inclusion in substance-assisted psychotherapy.
Frontiers in Psychiatry
April 25, 2022
Peter Oehen, Peter Gasser
70 citations
In Switzerland, a restricted medical use of scheduled psychotropic drugs is permitted for treatment-resistant conditions with preliminary evidence of efficacy. Since 2014, clinicians have obtained 50 licenses and developed a psychedelic-assisted group therapy model using MDMA and LSD. Most patients had chronic complex post-traumatic stress disorder (c-PTSD), dissociative, and other post-traumatic disorders. The model uses MDMA first to enhance motivation and therapeutic alliance, then introduces LSD to deepen processing once emotional regulation and trauma tolerance improve. Most participants improved by clinical judgment, with no serious adverse events. C-PTSD required more psychedelic sessions than single-trauma PTSD. Recurrent depression was a frequent problem needing special attention.
Frontiers in Psychiatry
June 7, 2018
70 citations
People who report near-death experiences (NDEs) without facing a life-threatening situation score higher on fantasy proneness than those who have NDEs during actual danger, those whose experiences do not meet NDE criteria, and healthy controls. In contrast, individuals who have classical NDEs (during a life-threatening event) show no difference in fantasy proneness compared to matched controls. The intensity of the reported experience correlates positively with engagement in fantasy. These findings suggest that strong fantasy proneness may make some individuals more likely to report NDE-like experiences under suitable physiological or psychological conditions, such as meditation or syncope.
Frontiers in Psychiatry
July 1, 2014
John W. Thomas, Marc Cohen
70 citations
After more than 50 years of research, no clear neurophysiological signatures have been found for states of consciousness induced by meditation practices. The failure is largely due to the narrow range of variables examined, with most studies focusing only on correlations between neurophysiological measures and specific practices while ignoring content and context. The authors argue that more meaningful results require expanding the methodological paradigm to include the cultural setting, the meditator's life situation, details of the practice, and the meditator's state of consciousness. Including all these domains will improve predictions of psychophysiological variables associated with specific meditation states and help explore the mysteries of human consciousness.
Frontiers in Psychiatry
January 20, 2022
Darron T. Smith, Sonya C. Faber, NiCole T. Buchanan et al.
69 citations
Psychedelic medicine is an emerging field that uses substances like MDMA to produce non-ordinary states of consciousness. MDMA is in phase-3 FDA trials for treating PTSD and was designated a breakthrough therapy in 2017 due to its safety and efficacy when combined with manualized therapy. Historical and contemporary racial mistreatment triggers physiological stress responses in Black people, similar to those in anxiety disorders. The paper explores how entheogens in psychedelic-assisted therapy could address negative race-based experiences and promote healing among BIPOC. It also discusses the ethical need for culturally competent providers and for recruiting BIPOC into research and training.
Frontiers in Psychiatry
December 3, 2019
Katrin H. Preller, Franz X. Vollenweider
67 citations
Hallucinogens and entactogens can modulate social processing, which is crucial for everyday functioning and often impaired in psychiatric disorders. This review of controlled human studies examines how these substances influence social cognition and identifies the neurobiological and neuropharmacological mechanisms involved. The authors highlight current knowledge gaps and suggest implications for hallucinogen-assisted treatments and the development of new medications targeting trans-diagnostic social cognition deficits.
Frontiers in Psychiatry
December 17, 2021
John R. Kelly, Claire M. Gillan, Jack Prenderville et al.
66 citations
Psychedelic therapy, combining psychedelic drugs with psychological support, shows promise for treating disorders marked by rigid and unhealthy patterns of emotion, thought, and behavior, including depression, treatment-resistant depression, addiction, and potentially anxiety, OCD, PTSD, and eating disorders. This review examines preclinical and clinical evidence through the Research Domain Criteria (RDoC) framework, mapping the drugs' effects across molecular, cellular, and network levels to RDoC constructs like negative and positive valence, arousal, social processing, cognition, and sensorimotor systems. The goal is to clarify the specific clinical dimensions psychedelics affect and their underlying neurobiology, aiming toward a mechanistic understanding and personalized psychedelic therapy.
Frontiers in Psychiatry
March 25, 2022
David E. Nichols
65 citations
MDMA (ecstasy) is structurally very similar to the hallucinogenic amphetamine MDA, yet its effects are fundamentally different. N-methylation normally reduces hallucinogenic activity, but MDMA retains potency. A key clue is stereochemistry: the dextro isomer of MDMA is more active, whereas the levo isomer is more active for hallucinogens. Also, extending the alpha-methyl to an alpha-ethyl group abolishes hallucinogenic activity but not MDMA-like effects, as shown with the analog MBDB. These three structural differences led to MDMA being classified as an "entactogen" in 1986, a drug that promotes social bonding, reduces anxiety, and induces introspection rather than hallucination. Its mechanism involves serotonin transporter-mediated release of stored serotonin.
Frontiers in Psychiatry
June 29, 2021
Keri Mans, Hannes Kettner, David Erritzøe et al.
65 citations
Psychedelic substances like LSD and psilocybin have regained legitimacy in clinical research. In this naturalistic observational study of volunteers intending to take a psychedelic, well-being was assessed using fourteen measures at four time points: 1 week before and 2 weeks, 4 weeks, and 2 years after the experience (sample sizes 654, 315, 212, and 64, respectively). Changes clustered into three factors: 'Being well,' 'Staying well,' and 'Spirituality.' Repeated measures analysis showed improvements in Being Well and Staying Well in the weeks following the experience, and mixed model analyses indicated these improvements remained statistically significant up to 2 years, despite high attrition. Spirituality did not show significant change.
Frontiers in Psychiatry
August 18, 2017
Zurina Hassan, Oliver G. Bosch, Darshan Singh et al.
62 citations
Human culture involves learning to consume natural or synthetic psychoactive compounds that alter mental states and behavior. After a novel psychoactive substance (NPS) emerges and is experimentally used, its benefits and harms can be estimated, leading to legal classifications ranging from medical use to complete bans. However, banned drugs often continue to be used, allowing better understanding of their properties, and views on a drug can shift from harmful to medically useful. This review summarizes recent neuropharmacological progress on several NPS, including mitragynine, synthetic cannabinoids, dimethyltryptamine, novel serotonergic hallucinogens, cathinones, ketamine, novel dissociatives, gamma-hydroxybutyrate, gamma-butyrolactone, and 1,4-butanediol, highlighting both emerging harm potentials and potential medical applications.
Frontiers in Psychiatry
April 5, 2023
Sharday Mosurinjohn, Leor Roseman, Manesh Girn
54 citations
Research on psychedelics often measures 'mystical' effects using psychometric tools, and clinical studies link such experiences to better mental health. However, this research rarely engages with scholarship from religious studies or anthropology, which reveal that the concept of 'mysticism' in psychedelic science carries unacknowledged biases—particularly a perennialist and Christian bias that fails to historicize the term. The authors trace the concept's history in psychedelic research, propose more culturally sensitive operationalizations, and advocate for complementary 'non-mystical' approaches to study these phenomena, aiming to build interdisciplinary bridges for stronger theoretical and empirical work.
Frontiers in Psychiatry
December 5, 2022
Elliot Marseille, Stefano Bertozzi, James G Kahn
51 citations
Psychiatry is seeing renewed interest in using psychedelic drugs to treat mental health disorders like depression, PTSD, and addictions, with clinical evidence showing substantial potential. New therapies could become available by 2024 for patients who do not respond to traditional treatments. However, research on economic factors such as costs, cost-effectiveness, pricing, and the economic effects of widespread implementation has lagged. These issues are critical for making psychedelic therapies widely accessible. The authors describe six types of economic analyses relevant to decisions and planning, including the needs of healthcare payers, and outline desirable features of such research, including scientific rigor, long-term horizons, equity, and a global perspective.
Frontiers in Psychiatry
February 10, 2023
Muhammad Ishrat Husain, Nicole Ledwos, Elise Fellows et al.
47 citations
A narrative review examined the neurobiological mechanisms that may explain the rapid antidepressant effects of serotonergic psychedelics such as psilocybin, LSD, and ayahuasca. The drugs act as agonists or partial agonists at serotonin 5HT2A receptors, and their rapid effects may involve downregulation of these receptors. They also influence brain-derived neurotrophic factor and immune responses. Neuroimaging studies suggest that psychedelics may disrupt the default mode network, a brain system involved in self-referential thinking that is overactive in major depressive disorder. The review concludes that multiple competing theories are being investigated and more research is needed to identify the most robust evidence.
Frontiers in Psychiatry
February 11, 2020
James D. Sexton, Charles D. Nichols, Peter S. Hendricks
45 citations
Lifetime use of classic tryptamine psychedelics is linked to lower odds of past-month psychological distress and past-year suicidal thinking, while lifetime use of novel phenethylamines is linked to higher odds of past-year suicidal thinking and planning. These findings, from a large nationally representative U.S. survey, suggest that classic tryptamines may hold greater therapeutic potential than novel phenethylamines, which may pose risks for harm. No significant associations were found for other psychedelic classes.
Frontiers in Psychiatry
January 3, 2022
Richard Matzopoulos, Robert Morlock, Amy Morlock et al.
43 citations
A national survey of American adults from November 2020 to March 2021 found that psychedelic mushroom use is common, with 63.6% of users citing general mental health and well-being as a reason. Users reported higher depression and anxiety scores on standard measures. Factors predicting use included being male and having a higher comorbidity burden, while having health insurance, older age, and living outside the western US reduced the likelihood. The findings indicate that many Americans are self-medicating with psychedelic mushrooms, and the link between use and poor mental health warrants further policy-relevant research.
Frontiers in Psychiatry
November 12, 2021
Julia Bornemann, James B. Close, Meg J. Spriggs et al.
43 citations
Eleven individuals with chronic pain who self-medicate with psychedelic drugs described their experiences in a group discussion. Pain scores improved substantially during and after psychedelic experiences across a range of substances and doses. Two processes—Positive Reframing and Somatic Presence—were reliably identified as contributing to improvements in mental wellbeing, relationship with pain, and physical (dis)comfort. Additional strategies such as mindfulness, breathwork, and movement were also widely reported. The authors note that due to the subjective nature of the data, no claims on causality or generalisability can be made. These results will inform the design of a forthcoming controlled trial testing psychedelic therapy for chronic pain.
Frontiers in Psychiatry
October 13, 2021
Mihai Avram, Helena Rogg, Αλεξάνδρα Κορδά et al.
43 citations
Classic psychedelics and acute psychosis share overlapping disruptions in brain connectivity, particularly involving the thalamus and its connections to cortical regions. Both states exhibit hyperconnectivity between the thalamus and sensorimotor cortices, linked to altered perceptions and hallucinations. Psychosis also shows hypoconnectivity between the thalamus and prefrontal cortices, associated with cognitive disturbances. These patterns of thalamocortical dysconnectivity extend to cortico-striato-pallido-thalamo-cortical circuitry. The review synthesizes neuroimaging and neuropharmacological evidence to highlight shared and distinct neurophysiological changes, suggesting clinically relevant parallels that may inform future research on perception and cognition.
Frontiers in Psychiatry
September 8, 2020
L. Silberbauer, B. Spurny, P. Handschuh et al.
43 citations
Two hours after a single intravenous dose of ketamine (0.8 mg/kg over 50 minutes), healthy adults showed a reduction in the ratio of GABA to total creatine in the hippocampus, as measured by magnetic resonance spectroscopic imaging. No significant changes were observed in the glutamate-plus-glutamine ratio or the GABA-to-glutamate-plus-glutamine ratio across seven brain regions. Plasma levels of ketamine and its metabolites norketamine and dehydronorketamine were not significantly associated with changes in any neurotransmitter ratio. The findings suggest that ketamine may alter GABA turnover in the hippocampus, a region relevant to its emerging antidepressant effects.
Frontiers in Psychiatry
June 16, 2021
Dóra Révész, Genís Oña, Giordano Novak Rossi et al.
42 citations
During the first strict COVID-19 lockdown (April–July 2020), people who had used psychedelic drugs regularly (more than once per six months) reported less psychological distress, less peritraumatic stress, and more social support than occasional or non-users. Regular users also scored higher on novelty-seeking and self-transcendence and lower on cooperativeness. The findings suggest that lifetime psychedelic use may be a protective factor for mental health under stressful confinement, or that pre-existing personality traits make some individuals more likely to use psychedelics. The study surveyed 2,974 English, Portuguese, and Spanish speakers online.
Frontiers in Psychiatry
July 7, 2020
Michael Specka, Thomas Kuhlmann, Jürgen Sawazki et al.
42 citations
Among patients undergoing in-patient detoxification from illicit drugs in Germany, use of novel psychoactive substances (NPS) was rare. About 32% reported having tried synthetic cannabimimetics at least once in their lifetime, but usually only a few times, and nearly no one had used them in the 30 days before admission. Urine analysis confirmed the low recent use. In contrast, lifetime and current use of opiates, alcohol, cocaine, benzodiazepines, and cannabis was high. An important reason given for trying NPS was that they were not detected by drug testing in prisons or treatment facilities. A notable finding was that 18% reported regular unprescribed pregabalin use during their lifetime, and 20% had recently used it, indicating diversion of legal medications is a serious concern.
Frontiers in Psychiatry
May 28, 2021
V. B. Cavenaghi, Leandro Paulino da Costa, A. Lacerda et al.
41 citations
Subcutaneous (SC) ketamine shows promise as a rapid and effective antidepressant for unipolar and bipolar depression, with response and remission rates ranging from 50 to 100% after single or multiple doses. Doses of 0.1 to 0.5 mg/kg of racemic ketamine and 0.5 to 1 mg/kg of esketamine were used, administered weekly or twice-weekly, often with dose titration. Side effects were temporary. This systematic review of 12 studies (two randomized trials, five case reports, and five retrospective studies) found SC ketamine to be a convenient and cost-effective route, particularly relevant for developing countries, though a meta-analysis was not possible due to heterogeneity. Further research comparing SC with intravenous and intranasal protocols is needed.
Frontiers in Psychiatry
November 20, 2019
Laura Orsolini, Stefania Chiappini, Duccio Papanti et al.
41 citations
The spread of novel psychoactive substances (NPS), especially among young people, raises concerns about psychosis linked to synthetic drugs. These 'new psychoses' differ clinically from classical psychosis. This mini-review synthesizes clinical and psychopathological features of NPS-induced psychoses and their treatment, based on a PubMed/Medline search for synthetic cannabinoids and cathinones. It contrasts classical psychoses with NPS-induced ones and offers therapeutic guidelines for clinicians in addiction psychiatry.
Frontiers in Psychiatry
December 6, 2023
Elliot Marseille, Manish Agrawal, Paul Thambi et al.
40 citations
Group psychedelic-assisted therapy, compared with individual therapy, reduces clinician costs by 50.9% for MDMA treatment of PTSD and 34.7% for psilocybin treatment of major depressive disorder, saving $3,467 and $981 per patient respectively. Using 2023 data from two trial sites and published prevalence estimates, treating all eligible U.S. adults with PTSD or MDD over ten years with group therapy would require 6,711 fewer full-time clinicians for MDMA-PTSD and 1,159 fewer for psilocybin-MDD, saving up to $10.3 billion and $2.0 billion. Adopting group protocols could lower costs, ease clinician shortages, and expand patient access.
Frontiers in Psychiatry
October 10, 2022
Christopher S. Stauffer, Melanie Brown, Dee Adams et al.
40 citations
Transgender and gender diverse (TGD) people face higher rates of stigma, discrimination, trauma, and PTSD, yet are underrepresented in PTSD research. Clinical trials of MDMA-assisted psychotherapy show promise for treating PTSD, but issues of equitable access, power imbalances, and vulnerable states of consciousness are magnified for TGD people. Through three virtual focus groups with 17 TGD participants who had trauma-related mental health care, the study identified barriers to adequate gender-affirming and trauma-informed care, frustration with providers lacking cultural humility, and suggested protocol amendments including routine collection of trans-inclusive gender identity data, an explicit gender-affirming treatment approach, culturally safe settings, and diverse co-therapy dyads. Inclusion of TGD voices promotes equitable access and helps tailor research to community needs.
Frontiers in Psychiatry
November 26, 2021
Ahmad Rehman, Habib Syed, Kathryn Forcer et al.
40 citations
A pilot study of NHS psychiatrists found that while 77.2% believe there should be a role for controlled or therapeutic use of psychedelics, psychiatrists at all levels do not feel prepared to deliver psychedelic-assisted psychotherapy. Trainees were better informed than non-training grade psychiatrists. Thematic analysis of focus groups revealed three main themes: need for knowledge, openness to change, and uncertainty. The study suggests that significant training needs and both professional and societal shifts are required before psychedelic-assisted therapy could become a mainstream treatment option in psychiatry.