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Artificial intelligence (AI) and psychedelic medicines are among the most high-profile evolving disruptive innovations within mental healthcare in recent years. Although AI and psychedelics may not have historically shared any common ground, there exists the potential for these subjects to combine in generating innovative mental health treatment approaches. In order to inform our perspective, we conducted a scoping review of relevant literature up to late August 2024 via PubMed intersecting AI with psychomedical use of psychedelics. Our perspective covers the potential application of AI in psychedelic medicine for: drug discovery and clinical trial optimization (including pharmacodynamics); study design; understanding psychedelic experiences; personalization of treatments; clinical screening, delivery, and follow-up (potentially delivered via chatbots/apps); application of psychological preparation, integration, and general mental health support; its role in enhancing treatment via brain modulatory devices (including virtual reality and haptic suits); and the consideration of ethical and security safeguards. Challenges include the need for sufficient data protection and security, and a range of necessary ethical protections. Future avenues of exploration could involve directly administering psychedelics (or providing algorithm-generated effects) to inorganic AI-interfaced neural networks that may exceed human brain activity (i.e., cognitive capacity) and intelligence., (© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)

The nutritional management of depression has long been discussed, due to the perceived benefit of a nutritional product having less side effects than pharmaceutical agents. Candidate nutrients for managing depression include vitamin D, B vitamins, tryptophan, branch chain amino acids, probiotics, omega-3 fatty acids, folate/methylfolate (also known as vitamin B9), and s-adenosylmethionine. This paper provides a narrative review of three nutrients which have significant scientific support for the management of depression. A deficiency in each nutrient is associated with depression, and interventional studies indicate that the correction of the nutritional deficiency may provide clinical benefit. We present epidemiological evidence, a mechanistic explanation and a review of interventional studies for these nutrients. Finally, relevant nutritional guidelines are presented with their conclusion for the role of each nutrient in the management of depression.

The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of preclinical, clinical, epidemiological, and pharmacovigilance data (as well as pertinent reviews and case studies) was conducted for articles using the electronic databases of PubMed and Web of Science (to 6 July 2023) and PsycINFO, ClinicalTrials.gov, and Embase (to 21 September 2022) and included articles in English in peer-reviewed journals. Additionally, reference lists were searched. Due to the breadth of the area covered, we presented the relevant data in a thematic format. Our searches revealed 78 relevant articles. Data showed that ayahuasca or DMT is generally safe; however, some adverse human events have been reported. Animal models using higher doses of ayahuasca have shown abortifacient and teratogenic effects. Isolated harmala alkaloid studies have also revealed evidence of potential toxicity at higher doses, which may increase with co-administration with certain medications. Harmaline revealed the most issues in preclinical models. Nevertheless, animal models involving higher-dose synthetic isolates may not necessarily be able to be extrapolated to human use of therapeutic doses of plant-based extracts. Serious adverse effects are rarely reported within healthy populations, indicating an acceptable safety profile for the traditional use of ayahuasca and DMT in controlled settings. Further randomized, controlled trials with judicious blinding, larger samples, and longer duration are needed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions., Methods: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively., Results: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses., Conclusion: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions., Competing Interests: Declaration of competing interest Abraham Zangen is an inventor of Deep TMS coils developed to study and treat neurological and psychiatric disorders and has financial interest in BrainsWay which produces and markets these coils. Daniel L.C. Costa received honoraria from Janssen, Lundbeck and Schwabe pharmaceuticals. David Mataix-Cols receives royalties for contributing articles to UpToDate, Inc. David Shannahoff-Khalsa reports royalties from two books published by W.W. Norton & Co, Inc. that includes the Kundalini Yoga meditation protocol, personal sales for a DVD for the protocol, and OCD patient fees. Eric A. Storch receives research funding for his institution from the Ream Foundation, International OCD Foundation, and NIH. He is a consultant for Brainsway and Biohaven Pharmaceuticals. He owns stock less than $5000 in NView (for distribution of the Y-BOCS and CY-BOCS) and Limbix. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, Routledge, and Jessica Kingsley. Juliana B. Diniz has received speaker's fees from Lundbeck and Janssen Cilag for lectures. Michael H. Bloch has received grant/research support from Therapix Biosciences, Emalex Biosciences, Janssen Pharmaceuticals, Biohaven Pharmaceuticals, NIH, Lesbian Health Fund, Yale Foundation for Lesbian and Gay Studies (FLAGS), and Patterson Foundation, has served on the advisory board/data monitoring and safety board of Therapix Biosciences, and serves as associate editor of Journal of Child Psychology and Psychiatry and on the editorial boards of Journal of Child and Adolescent Psychopharmacology and Depression & Anxiety. He has received royalties from Wolters Kluwer for Lewis's Child and Adolescent Psychiatry: A Comprehensive Textbook, Fifth Edition and moonlighting pay from the VA. Roseli G. Shavitt has received consultancy honoraria from Lundbeck and research grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) in the past three years. Sabine Wilhelm is a presenter for the Massachusetts General Hospital Psychiatry Academy in educational programs supported through independent medical education grants from pharmaceutical companies. She has received royalties from Elsevier Publications, Guilford Publications, New Harbinger Publications, Springer, and Oxford University Press, speaking honoraria from various academic institutions and foundations, including the International Obsessive Compulsive Disorder Foundation, the Tourette Association of America, and the Centers for Disease Control and Prevention, and payment from the Association for Behavioral and Cognitive Therapies for her role as Associate Editor of the Behavior Therapy journal and John Wiley & Sons, Inc. as Associate Editor of the journal Depression & Anxiety. She has also received honoraria for her role on the Scientific Advisory Board for One-Mind (PsyberGuide), Koa Health, Inc, and Noom, Inc. She has received research and salary support from Koa Health, Inc. None of the remaining co-authors have any conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We investigated whether mood and lifestyle-related indicators of physical health are differentially expressed according to self-reported levels of depressive symptoms among young adults with a current episode of major depression. In a cross-sectional study, we recruited 94 young adults (females = 67, 71.3%; males = 27, 28.7%; aged 18-35 years) with a current episode of major depression. We assessed their mood with the Profile of Mood States (POMS), and Beck Anxiety Inventory-(BAI), sleep with the Pittsburgh Sleep Quality Index (PSQI), physical activity with the Simple Physical Activity Questionnaire (SIMPAQ), and their cardiorespiratory fitness. Participants' depression levels were classified as follows using established cut-points: (a) Mild Depressive Symptoms (MIDS, BDI-II 14-19 points, n = 17), (b) Moderate Depressive Symptoms (MODS, BDI-II 20-28 points, n = 37) or (c) Severe Depressive Symptoms (SEDS, BDI-II 29-63 points, n = 40). As expected, we found that young adults with SEDS, when compared to those with MODS and MIDS, showed higher depressive mood on the POMS, and they exhibited greater anxiety symptoms, lower reported 'vigor' on physical activity measures, worse sleep quality as expressed by their global score sleep; daytime dysfunction; and sleep disturbance, and they showed lower cardiorespiratory fitness. Those with moderate depressive symptoms only differed from those with mild symptoms with respect to hostility, fatigue and mood disturbance. Although there was a gradient whereby worse mental and physical health indicators were more closely related to the SEDS depression categorization, while healthier indicators were associated with the MIDS category, some parameters were not different between the MDD severity groups, particularly when comparing MIDS and MODS. Clinicians treating patients with MDD should consider these factors when designing lifestyle-based interventions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: This study examined the cumulative risk of unhealthy lifestyle behaviors and the associations between overall lifestyle and common mental disorders (CMDs), insomnia, stress, health-related quality of life (HRQOL), and functional impairment. Additionally, the treatment preferences for managing CMDs and insomnia were examined., Methods: A survey was conducted on 1487 Chinese Hong Kong adults, assessing their lifestyle behaviors (i.e., diet and nutrition, substance use, physical activity, stress management, restorative sleep, social support, and environmental exposures), mental health-related outcomes, and treatment preferences via a vignette., Results: The findings revealed significant additive relationships between the number of 'worse' lifestyle domains and the risk of all outcomes. A healthier overall lifestyle was significantly associated with reduced risks of all outcomes (AORs = 0.88 to 0.93). Having healthier practices in diet and nutrition, substance use, stress management, restorative sleep, and social support domains were significantly associated with lower risks of all outcomes (AORs = 0.93 to 0.98), except that substance use was not significantly associated with stress. Physical activity was inversely associated with only depressive symptoms (AOR = 0.98), anxiety symptoms (AOR = 0.99), and stress (AOR = 0.99). Environmental exposures were not significantly associated with functional impairment but with all other outcomes (AORs = 0.98 to 0.99). Besides, lifestyle interventions (55 %) were significantly more preferred for managing CMDs and insomnia relative to psychotherapy (35.4 %) and pharmacotherapy (9.6 %)., Conclusions: Our findings underscore the importance of considering lifestyle factors when managing CMDs, insomnia, stress, HRQOL, and functional impairment, with a particular emphasis on adopting a multicomponent treatment approach., Competing Interests: Declaration of competing interest JS has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from companies which sell Kava products (i.e., Integria Healthcare & MediHerb, Taki Mai, FIT-BioCeuticals and Blackmores). He also has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments Pfizer, Scius Health, Key Pharmaceuticals, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Kantar Consulting, Grunbiotics, Research Reviews, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, SPRIM, Terry White Chemists, ANS, Australian Natural Therapies Group, Society for Medicinal Plant and Natural Product Research, Sanofi-Aventis, Omega-3 Centre, the National Health and Medical Research Council, CR Roper Fellowship. CHN participated as a consultant for Lundbeck, Grunbiotics, Servier, Janssen-Cilag, and Eli Lilly, received research grant support from Lundbeck, and speaker honoraria from Servier, Lundbeck, Sumitomo, Bristol-Myers Squibb, Organon, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Astra-Zenaca, and Pfizer, unrelated to this work. Financial disclosure EKY received student research support from The Chinese University of Hong Kong, and JS received the NHMRC Clinical Research Fellowship (grant number APP1125000). The funding source had no involvement in study design, collection, analysis, and interpretation of data, writing of the manuscript, or the decision of article submission for publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To prevent the exacerbation of mental health burdens, a growing body of research has recommended a balanced approach that emphasizes both the delivery of mental health treatments to individuals with common mental disorders (CMDs) and the strengthening of protective factors for CMDs among nonclinical populations. This randomized controlled trial (RCT) evaluated the efficacy of a smartphone-delivered multicomponent lifestyle medicine (LM) intervention, Lifestyle Hub, for improving mental health among a nonclinical population of Chinese adults., Methods: A total of 106 participants with Patient Health Questionnaire-9 total score < 10 and Generalized Anxiety Disorder 7-Item Scale <8 were randomly assigned to either the Lifestyle Hub intervention group (LH, n  = 53) or the waitlist control group (WL, n  = 53). Lifestyle Hub is an 8-week smartphone-delivered multicomponent LM intervention developed based on the transtheoretical model. The intervention components included lifestyle psychoeducation, physical activity, diet and nutrition, stress management, sleep management, and motivation and goal-setting techniques. Assessments were conducted at baseline, immediate post-intervention, and 1-month follow-up (LH only)., Results: The linear mixed effect model based on the intention-to-treat principle indicated that Lifestyle Hub significantly improved overall mental health, depressive symptoms, anxiety symptoms, stress, insomnia severity, overall health-promoting behaviors, dietary quality, and stress management compared to the WL group at immediate post-intervention ( d  = 0.13-0.56). No significant between-group differences were observed in terms of functional impairment, health-related quality of life, health responsibility, physical activity level, spiritual growth, and interpersonal relations. The intervention gains in the LH group were maintained at 1-month follow-up. The LH participants indicated that Lifestyle Hub was an acceptable intervention for improving mental health, although a significantly higher level of study attrition was observed in the LH group (20.8%) relative to the WL group (5.7%)., Conclusion: Lifestyle Hub may serve as an efficacious and acceptable intervention for improving mental health in nonclinical adult populations. To extend the benefits of LM interventions at the population level, future studies are warranted to examine a stepped-care approach to delivering LM interventions. Trial registration : This randomized controlled trial was pre-registered with ClinicalTrials.gov (NCT04295369)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wong, Tong, Shi, Ng, Sarris and Ho.)

Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are potent psychoactive substances that have been studied for their physiological and psychological effects. However, our understanding of the potential interactions and outcomes when using these substances in combination with other drugs is limited. This systematic review aims to provide a comprehensive overview of the current research on drug-drug interactions between classic psychedelics and other drugs in humans. We conducted a thorough literature search using multiple databases, including PubMed, PsycINFO, Web of Science and other sources to supplement our search for relevant studies. A total of 7102 records were screened, and studies involving human data describing potential interactions (as well as the lack thereof) between classic psychedelics and other drugs were included. In total, we identified 52 studies from 36 reports published before September 2, 2023, encompassing 32 studies on LSD, 10 on psilocybin, 4 on mescaline, 3 on DMT, 2 on 5-MeO-DMT and 1 on ayahuasca. These studies provide insights into the interactions between classic psychedelics and a range of drugs, including antidepressants, antipsychotics, anxiolytics, mood stabilisers, recreational drugs and others. The findings revealed various effects when psychedelics were combined with other drugs, including both attenuated and potentiated effects, as well as instances where no changes were observed. Except for a few case reports, no serious adverse drug events were described in the included studies. An in-depth discussion of the results is presented, along with an exploration of the potential molecular pathways that underlie the observed effects., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JS and DP are directors of a not-for-profit research institute which has in the past received commercial funding to undertake psychedelic medicines research.

Objective: The placebo response in depression studies is the change in symptoms amongst those who receive an inactive treatment. Many well-designed randomized controlled trials (RCTs) of depression have a high proportion of placebo responders, with little understanding as to why. The present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo responders., Methods: This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo (n = 69 in placebo group). We investigated participant characteristics such as socio-demographics, clinical features, and recruitment methods, and their association with the placebo response. Monoaminergic genetic polymorphisms were also assessed. Placebo response was measured based on change in Montgomery-Asberg Depression Rating Scale score. The association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects models., Results: Greater levels of education, particularly pursuing post-high school education, better self-reported general health, marriage/de facto, greater improvement in the first trial week, and more failed antidepressant therapies in the current depressive episode were associated with greater placebo response. An increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant therapy. Single nucleotide polymorphisms from the tryptophan hydroxylase 1 (TPH1) gene (A779C and A218C) were weakly associated with greater placebo response, although the evidence was attenuated after accounting for multiple comparisons., Conclusion: This is, to our knowledge, the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo response. Several variables appeared to predict the placebo response. Such findings may encourage future trial designs which could dampen placebo response, improve assay sensitivity, and allow for treatment effects to be potentially more detectable. Please cite this article as: Arnold R, Murphy-Smith J, Ng CH, Mischoulon D, Byrne GJ, Bousman CA, Stough C, Berk M, Sarris J. Predictors of the placebo response in a nutraceutical randomized controlled trial for depression. J Integr Med. 2024; 22(1): 46-53., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JMS has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from: Integria Healthcare & MediHerb, Pfizer, Scius Health, Key Pharmaceuticals, Taki Mai, Fiji Kava, FIT-BioCeuticals, Blackmores, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Kantar Consulting, Grunbiotics, Australian Natural Therapeutics Group, Research Reviews, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, SPRIM, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, Sanofi-Aventis, Omega-3 Centre, the National Health and Medical Research Council, CR Roper Fellowship. CHN had served as a consultant for Lundbeck, Grunbiotics, Servier, Janssen-Cilag, Wyeth and Eli Lilly, received research grant support from Wyeth and Lundbeck, and speaker honoraria from Servier, Lundbeck, Bristol-Myers Squibb, Organon, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Astra-Zenaca, Wyeth, and Pfizer. DM has received research support from Nordic Naturals and Heckel Medizintechnik GmbH. He has received honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy, Harvard Blog, and PeerPoint Medical Education Institute, LLC. He also works with the MGH Clinical Trials Network and Institute (CTNI), which has received research funding from multiple pharmaceutical companies and National Institute of Mental Health (NIMH). MB is supported by a NHMRC Senior Principal Research Fellowship (1059660 and 1156072). MB has received grant/research support from the National Institute of Mental Health (NIMH), Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 Milk Company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Lundbeck, Merck and Pfizer, and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Lundbeck Merck, Pfizer and Servier—all unrelated to this work., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Kava is a South Pacific plant-based medicine with anxiolytic properties, but little is known about the impact kava has on gene expression or whether gene expression can serve as a marker of kava response. This study aimed to determine whether kava treatment alters the expression of genes with physiological relevance to anxiety pathophysiology and whether the baseline expression of these physiologically relevant genes modifies the efficacy of kava treatment. In this post hoc analysis, we examined the expression of 48 genes relevant to the pathophysiology of anxiety collected from a double-blind randomized controlled trial that assessed the efficacy of kava treatment in generalized anxiety disorder. Peripheral blood gene expression was measured in 71 (34 kava, 37 placebo) adults at baseline and in 40 (19 kava, 21 placebo) after 8 weeks of treatment by reverse transcription polymerase chain reaction (PCR). Results revealed that kava decreased the expression of a subunit of the GABA A -rho receptor gene (GABRR2) and catechol-O-methyltransferase (COMT), a gene related to catecholamine metabolism. Kava efficacy was not found to be modified by baseline (pretreatment) expression of relevant genes. Although these results did not withstand statistical correction for multiple comparisons and require external validation, they support the notion that kava's mechanism of action includes interaction with GABAergic and catecholaminergic systems., (© 2023 John Wiley & Sons Ltd.)

Generalised Anxiety Disorder (GAD) is a prevalent, chronic mental health disorder. The measurement of regional brain gamma-aminobutyric acid (GABA) offers insight into its role in anxiety and is a potential biomarker for treatment response. Research literature suggests Piper methysticum (Kava) is efficacious as an anxiety treatment, but no study has assessed its effects on central GABA levels. This study investigated dorsal anterior cingulate (dACC) GABA levels in 37 adult participants with GAD. GABA was measured using proton magnetic resonance spectroscopy ( 1 H-MRS) at baseline and following an eight-week administration of Kava (standardised to 120 mg kavalactones twice daily) ( n = 20) or placebo ( n = 17). This study was part of the Kava for the Treatment of GAD (KGAD; ClinicalTrials.gov: NCT02219880), a 16-week intervention study. Compared with the placebo group, the Kava group had a significant reduction in dACC GABA ( p = 0.049) at eight weeks. Baseline anxiety scores on the HAM-A were positively correlated with GABA levels but were not significantly related to treatment. Central GABA reductions following Kava treatment may signal an inhibitory effect, which, if considered efficacious, suggests that GABA levels are modulated by Kava, independent of reported anxiety symptoms. dACC GABA patterns suggest a functional role of higher levels in clinical anxiety but warrants further research for symptom benefit. Findings suggest that dACC GABA levels previously un-examined in GAD could serve as a biomarker for diagnosis and treatment response.

Ayahuasca is a psychedelic plant brew originating from the Amazon rainforest. It is formed from two basic components, the Banisteriopsis caapi vine and a plant containing the potent psychedelic dimethyltryptamine (DMT), usually Psychotria viridis . Here we review the history of ayahuasca and describe recent work on its pharmacology, phenomenological responses, and clinical applications. There has been a significant increase in interest in ayahuasca since the turn of the millennium. Anecdotal evidence varies significantly, ranging from evangelical accounts to horror stories involving physical and psychological harm. The effects of the brew on personality and mental health outcomes are discussed in this review. Furthermore, phenomenological analyses of the ayahuasca experience are explored. Ayahuasca is a promising psychedelic agent that warrants greater empirical attention regarding its basic neurochemical mechanisms of action and potential therapeutic application., Competing Interests: Simon G. D. Ruffell, Nige Netzband, and WaiFung Tsang are directors of a not‐for‐profit research institute. Jerome Sarris and Daniel Perkins are directors of a not‐for‐profit medicinal psychedelics research institute. Simon G. D. Ruffell, Tessa Cowley‐Court, and Diana McHerron are employed at this not‐for‐profit medicinal psychedelics research institute. Jerome Sarris is supported by an National Health and Medical Research Council (NHMRC) Clinical (Fellowship APP1125000)., (© 2023 The authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Previous quantitative research has shown that cannabis use, mostly illicit, is used for symptom management amongst those with endometriosis living in Australia or New Zealand, but the drivers and barriers for use of legal, medicinal cannabis in this population are currently unclear. This study sought to investigate, via online focus-groups, the perceptions, barriers, drivers, and experiences associated with cannabis use, whether legal or illicit, amongst 37 Australians and New Zealanders, aged 18-55, with a medical diagnosis of endometriosis. Previous cannabis usage was not required to participate. Discussion topics included strategies employed to manage symptoms, exploration of current medications, previous use of cannabis for pain management, and interest in using medicinal cannabis as a management strategy. Participants with moderate to severe symptoms of medically diagnosed endometriosis reported inadequacies with their current medical and self-management strategies and were inclined to try medicinal cannabis, both as part of their medical management and as part of a clinical trial. Barriers to medicinal cannabis adoption identified in this cohort included high costs of legal cannabis products, lack of clarity and fairness in current roadside drug testing laws and workplace drug testing policies, concern over the impact of stigma affecting familial, social and workplace life domains, and subsequent judgement and the lack of education/engagement from their medical providers regarding cannabis use. Given the interest in medicinal cannabis and the reported lack of effective symptom management, clinical trials are urgently required to determine the potential role that medicinal cannabis may play in reducing the symptoms of endometriosis.

Physician categorizations of electronic health record (EHR) data (e.g., depression) into sensitive data categories (e.g., Mental Health) and their perspectives on the adequacy of the categories to classify medical record data were assessed. One thousand data items from patient EHR were classified by 20 physicians (10 psychiatrists paired with ten non-psychiatrist physicians) into data categories via a survey. Cluster-adjusted chi square tests and mixed models were used for analysis. 10 items were selected per each physician pair (100 items in total) for discussion during 20 follow-up interviews. Interviews were thematically analyzed. Survey item categorization yielded 500 (50.0%) agreements, 175 (17.5%) disagreements, 325 (32.5%) partial agreements. Categorization disagreements were associated with physician specialty and implied patient history. Non-psychiatrists selected significantly ( p = .016) more data categories than psychiatrists when classifying data items. The endorsement of Mental Health and Substance Use categories were significantly ( p = .001) related for both provider types. During thematic analysis, Encounter Diagnosis (100%), Problems (95%), Health Concerns (90%), and Medications (85%) were discussed the most when deciding the sensitivity of medical information. Most (90.0%) interview participants suggested adding additional data categories. Study findings may guide the evolution of digital patient-controlled granular data sharing technology and processes.

Objectives: Randomized controlled trials (RCTs) on the efficacy of multicomponent lifestyle medicine (LM) interventions for improving sleep quality have yielded inconsistent findings. This study marks the first meta-analysis to evaluate the efficacy of multicomponent LM interventions in improving sleep quality., Methods: We searched six online databases for RCTs that compared multicomponent LM interventions to an active or inactive control group in an adult population and assessed subjective sleep quality as a primary or secondary outcome using validated sleep measures at any post-intervention time-point., Results: A total of 23 RCTs with 26 comparisons involving 2534 participants were included in the meta-analysis. After excluding outliers, the analysis revealed that multicomponent LM interventions significantly improved sleep quality at immediate post-intervention (d = 0.45) and at short-term follow-up (i.e.,

Purpose: Evidence suggests that yoga may help improve cancer-related symptoms though knowledge of the experiences, barriers and preferences of people diagnosed with cancer is limited. This study sought to examine the use of yoga in an Australian sample and identify the experiences and preferences associated with undertaking yoga practice as formative research to help inform a future yoga intervention., Methods: Adults diagnosed with any type of cancer completed a cross-sectional survey including questions regarding their demographics, experiences and preferences for yoga practice., Results: Sixty-eight people who had been diagnosed with cancer completed the survey. Most of the participants (70.8%) had practiced yoga since their diagnosis. A variety of reasons for practice were endorsed, and benefits experienced included physical and psychological factors. The most common barrier to practice was related to the physical ability to undertake yoga. Participants indicated a preference for group classes (44.1%), with a frequency of practice of 2-3 times per week (60.3%), 60 min in length (75%). The preferred time of practice was 9am-12pm (51.5%) and travel distance 5-10 km (44.1%). Online yoga delivery was endorsed, with participants preferring pre-recorded sessions., Conclusions: Results from this study provide insights into the experiences, barriers and preferences for yoga practice in people with cancer which will assist in developing yoga programs in this cohort to investigate the effects on cancer and treatment-related symptoms., (Copyright © 2022. Published by Elsevier Inc.)

Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized by increased temporal coherence at rest have been termed the Default Mode Network (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind wandering, and autobiographical memories. Altered connectivity in the DMN has been associated with a range of neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder, attention deficit hyperactive disorder, schizophrenia, and obsessive-compulsive disorder. To date, several studies have investigated how psychedelics modulate this network, but no comprehensive review, to our knowledge, has critically evaluated how major classical psychedelic agents-lysergic acid diethylamide, psilocybin, and ayahuasca-modulate the DMN. Here we present a systematic review of the knowledge base. Across psychedelics there is consistent acute disruption in resting state connectivity within the DMN and increased functional connectivity between canonical resting-state networks. Various models have been proposed to explain the cognitive mechanisms of psychedelics, and in one model DMN modulation is a central axiom. Although the DMN is consistently implicated in psychedelic studies, it is unclear how central the DMN is to the therapeutic potential of classical psychedelic agents. This article aims to provide the field with a comprehensive overview that can propel future research in such a way as to elucidate the neurocognitive mechanisms of psychedelics., (© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.)

Background: Preliminary evidence supports the use of dietary interventions and gut microbiota-targeted interventions such as probiotic or prebiotic supplementation for improving mental health. We report on the first randomised controlled trial (RCT) to examine the effects of a high-prebiotic dietary intervention and probiotic supplements on mental health., Methods: "Gut Feelings" was an 8-week, 2 × 2 factorial RCT of 119 adults with moderate psychological distress and low prebiotic food intake. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). The primary outcome was assessment of total mood disturbance (TMD; Profile of Mood States Short Form) from baseline to 8 weeks. Secondary outcomes included anxiety, depression, stress, sleep, and wellbeing measures., Results: A modified intention-to-treat analysis using linear mixed effects models revealed that the prebiotic diet reduced TMD relative to placebo at 8 weeks [Cohen's d = -0.60, 95% confidence interval (CI) = -1.18, -0.03; p = 0.039]. There was no evidence of symptom improvement from the probiotic ( d = -0.19, 95% CI = -0.75, 0.38; p = 0.51) or synbiotic treatments ( d = -0.03, 95% CI = -0.59, 0.53; p = 0.92). Improved anxiety, stress, and sleep were noted in response to the prebiotic diet while the probiotic tentatively improved wellbeing, relative to placebo. No benefit was found in response to the synbiotic intervention. All treatments were well tolerated with few adverse events., Conclusion: A high-prebiotic dietary intervention may improve mood, anxiety, stress, and sleep in adults with moderate psychological distress and low prebiotic intake. A synbiotic combination of high-prebiotic diet and probiotic supplement does not appear to have a beneficial effect on mental health outcomes, though further evidence is required. Results are limited by the relatively small sample size., Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372753, identifier ACTRN12617000795392., Competing Interests: JS has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from: Integria Healthcare and MediHerb, Pfizer, Scius Health, Key Pharmaceuticals, Taki Mai, Fiji Kava, Noetic Foundry, FITBioCeuticals, Blackmores, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Kantar Consulting, Angelini Pharmaceuticals, Grunbiotics, Polistudium, Australian Natural Therapeutics Group, Research Reviews, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, SPRIM, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, Sanofi-Aventis, Omega-3 Centre, the National Health and Medical Research Council, CR Roper Fellowship. CN has served as a consultant for Lundbeck, Grunbiotics, Servier, Janssen-Cilag, and Eli Lilly, received research grant support from Wyeth and Lundbeck, and speaker honoraria from Servier, Lundbeck, Bristol-Myers Squibb, Organon, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Astra-Zeneca, and Pfizer. JR has received research funding in last 5 years from Health Research Council (NZ), Waterloo Foundation, Vic Davis Memorial Trust, UC Foundation, Canterbury Medical Research Foundation, GAMA Foundation, Foundation for Excellence in Mental Health Care, and book royalties from Harper Collins. FJ is supported by an NHMRC Investigator Grant (#1194982). She has received: (1) competitive Grant/Research support from the Brain and Behaviour Research Institute, the National Health and Medical Research Council (NHMRC), Australian Rotary Health, the Geelong Medical Research Foundation, the Ian Potter Foundation, The University of Melbourne; (2) industry support for research from Meat and Livestock Australia, Woolworths Limited, the A2 Milk Company, Be Fit Foods, Bega Dairy; (3) philanthropic support from the Fernwood Foundation, Wilson Foundation, the JTM Foundation, the Serp Hills Foundation, the Roberts Family Foundation, the Waterloo Foundation and; (4) travel support and speakers honoraria from Sanofi-Synthelabo, Janssen Cilag, Servier, Pfizer, Network Nutrition, Angelini Farmaceutica, Eli Lilly, Metagenics, and The Beauty Chef. FJ has written two books for commercial publication. JH is Chief Research Officer for ProbioticAdvisor.com. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Freijy, Cribb, Oliver, Metri, Opie, Jacka, Hawrelak, Rucklidge, Ng and Sarris.)

Ayahuasca is a psychoactive Amazonian plant brew. It is usually made from the Banisteriopsis caapi vine (Spruce ex Griseb. Morton, Malpighiaceae), which contains three primary harmala alkaloids, along with the leaves of Psychotria viridis (Ruiz et Pavon, Rubiaceae) in which the potent psychedelic dimethyltryptamine (DMT) is found. DMT-harmaloid concoctions have gained popularity in recent years, due to growing anecdotal and scientific reports of therapeutic benefits associated with their consumption. Ayahuasca is now ingested in a variety of different settings across the globe, from traditional ethnobotanical to so called "neo-shamanic" ceremonies. Furthermore, related preparations involving alternative sources of DMT and harmala alkaloids are becoming increasingly common as knowledge of ayahuasca continues to spread internationally. This article reviews the existing literature and draws on original qualitative data from a large cross-sectional study of ayahuasca drinkers, to propose a model of psychotherapeutic processes associated with the consumption of ayahuasca. We assert that it is these processes, facilitated by a range of neurobiological effects, that lead to beneficial mental health and wellbeing outcomes. Our proposed model identifies five key psychotherapeutic processes or effects inherent to the ayahuasca experience; somatic effects; introspection and emotional processing; increased Self-connection; increased spiritual connection, and finally the gaining of insights and new perspectives. We note some important differences in these processes compared with other classic psychedelics as well as the implications of the model for the therapeutic use of ayahuasca. Improved understanding of the psychotherapeutic processes involved with the ayahuasca experience will better equip practitioners to work with this potentially transformative concoction and enable the optimization of therapeutic treatment models for potential clinical use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Perkins, Ruffell, Day, Pinzon Rubiano and Sarris.)

Introduction: The understanding of biological responses to psychedelics with antidepressant potential is imperative. Here we report how a set of acute parameters, namely emotional (depressive symptoms), cognitive (psychedelic experience), and physiological (salivary cortisol), recorded during an ayahuasca dosing session, modulated serum brain-derived neurotrophic factor (BDNF), serum cortisol (SC), serum interleukin 6 (IL-6), plasma C-reactive protein (CRP), and salivary cortisol awakening response (CAR)., Methods: Results were analyzed 2 days after the psychedelic intervention (ayahuasca) versus placebo in both patients with treatment-resistant depression and healthy volunteers. These measures were assessed as part of a randomized double-blinded, placebo-controlled trial ( n = 72)., Results: Results revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients. Whereas lesser changes in salivary cortisol levels during the ayahuasca intervention were related to higher BDNF levels in patients with a larger clinical response in the reduction in depressive symptoms. No moderator was found for patient's CAR, IL-6, and CRP responses to ayahuasca and for all biomarker responses to ayahuasca in healthy controls and in the placebo group., Discussion: In summary, some specific emotional and physiological parameters during experimental ayahuasca session were revealed as critical moderators of the improvement of major depression biomarkers, mainly BDNF and SC two days after ayahuasca intake. These findings contribute to paving the way for future studies investigating the biological antidepressant response to psychedelic therapy., Competing Interests: JS and DP were directors of a not-for-profit Medicinal Psychedelics Research Institute. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sousa, de Oliveira Tavares, de Menezes Galvão, de Almeida, Palhano-Fontes, Lobão-Soares, de Morais Freire, Nunes, Maia-de-Oliveira, Perkins, Sarris, de Araujo and Galvão-Coelho.)

Background and Hypothesis: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, yet a significant proportion of individuals on clozapine continue to experience disabling symptoms, despite being treated with an adequate dose. There is a need for adjunct treatments to augment clozapine, notably for negative and cognitive symptoms. One such potential agent is the glutathione precursor N-acetylcysteine (NAC)., Study Design: A randomized double-blind, multi-center, placebo-controlled trial for clozapine patients with enduring psychotic symptoms (n = 84) was undertaken to investigate the efficacy of adjunctive NAC (2 g daily) for negative symptoms, cognition and quality of life (QoL). Efficacy was assessed at 8, 24, and 52 weeks., Study Results: NAC did not significantly improve negative symptoms (P = .62), overall cognition (P = .71) or quality of life (Manchester quality of life: P = .11; Assessment of quality of life: P = .57) at any time point over a 1-year period of treatment. There were no differences in reported side effects between the groups (P = .26)., Conclusions: NAC did not significantly improve schizophrenia symptoms, cognition, or quality of life in treatment-resistant patients taking clozapine. This trial was registered with "Australian and New Zealand Clinical Trials" on the 30 May, 2016 (Registration Number: ACTRN12615001273572)., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Naturalistic and placebo-controlled studies suggest ayahuasca, a potent psychedelic beverage originating from Indigenous Amazonian tradition, may improve mental health, alter personality structure, and reduce alcohol and drug intake. To better understand ayahuasca's therapeutic potential and to identify factors that influence therapeutic efficacy, we conducted a naturalistic, longitudinal study of facilitated ayahuasca consumption in naïve participants using a comprehensive battery of self-report questionnaires. Materials and Methods: Ayahuasca naive individuals registering for ayahuasca ceremonies were asked to complete a range of validated questionnaires assessing mental health, alcohol/cannabis use, relationships, personality, and connection to self and spirituality, prior to and 1 month after attending an ayahuasca ceremony. Data for two mental health measures (the DASS-21 and PANAS) and acute subjective effects via the MEQ-30 were also assessed 7 days post-ceremony. Repeated measures ANOVA were used to examine pre-to-post changes, and Pearson correlations explored predictors of improvement in outcomes. Results: Fifty-three attendees (32 women, 21 men) completed pre and post ayahuasca assessments with 55.6% of the sample reporting a complete mystical experience based on the MEQ-30. One-month post-ayahuasca, significant reductions were identified in depression, anxiety, stress, alcohol and cannabis use, body dissociation, accepting external influence, self-alienation, impulsivity, and negative affect/emotionality. Significant increases were identified in positive mood, self-efficacy, authentic living, extraversion, agreeableness, open-mindedness, spirituality, and satisfaction with relationships. While facets of the mystical experience held little predictive validity on outcome measures, baseline traits, particularly high negative emotionality and body dissociation, and low sense of self-efficacy, robustly predicted improvements in mental health and alcohol/cannabis use, and alterations in personality structure which are linked to better mental health. Discussion: This study suggests facilitated ayahuasca consumption in naïve participants may precipitate wide-ranging improvements in mental health, relationships, personality structure, and alcohol use. Associations between baseline traits and therapeutic improvements mark an important first step toward personalized, precision-based medicine and warrant randomized controlled trials to confirm and elaborate on these findings. Contribution Statement: Longitudinal, observational studies and randomized clinical control trials suggest ayahuasca may exert therapeutic effects on mental health and alcohol/cannabis use, and alter personality structure. However, it is unclear if improvements are diagnosis-specific and factors that predict therapeutic gains have yet to be extensively elucidated. This longitudinal, observational study examined the effects of facilitated ayahuasca consumption in naive participants on mental health, alcohol and substance use/abuse, personality traits, relationships, and connection to self and spirituality. We found wide-ranging improvements 1-month post-treatment across these domains, and identified baseline traits which predict pre-to-post changes on primary outcome measures. Improvements were not diagnostic-specific, suggesting ayahuasca may be generally efficacious. Personality traits, body dissociation, and self-efficacy were strong predictors of therapeutic improvements, marking an important first step toward personalized, precision-based medicine. Randomized controlled trials are warranted to confirm and elaborate on these findings., Competing Interests: DP and JS are the codirectors of Psychae Institute, a non-profit research centre that receives funding from the biotechnology sector to study psychedelic medicines, as well as holding equity in Psychae Therapeutics, a commercial entity that raises capital to support psychedelic research. JS has also received honoraria, research support, royalties, or consultancy or travel grant funding from: Integria Healthcare and MediHerb, Pfizer, Scius Health, Key Pharmaceuticals, Taki Mai, FIT-BioCeuticals, GrunBiotics, Blackmores, SPRIM, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, Global Pharma Solutions, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, Sanofi-Aventis, Omega-3 Centre, Medical Research Future Fund, the National Health and Medical Research Council, and the CR Roper Fellowship., (Copyright © 2022 Perkins, Pagni, Sarris, Barbosa and Chenhall.)

Background: Obsessive-compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach., Objective: To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N -acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5' phosphate, and selenium., Methods: A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Scale (YBOCS), administered every 4 weeks., Results: An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of -7.13 (95% confidence interval = -9.24, -5.01), with a mean reduction of -1.21 points per post-baseline visit ( P  ≤ .001). At 20-weeks, 23% of the participants were considered "responders" (YBOCS ≥35% reduction and "very much" or "much improved" on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD., Conclusions: While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.

Background: Adaptogens are generally referred to the substances, mostly found in plants, which non-specifically increase resilience and chances of survival by activation of signaling pathways in affected cells., Purpose: This literature review was conducted to summarize the investigation, until March 2021, on selected adaptogenic plants and plant-derived substances., Study Design: Electronic databases were searched (up to March 2021) for in vitro and animal studies, as well as clinical trials. Moreover, all modes of action connected with the adaptogenic effects of plants and phytochemicals were collected., Methods: The search of relevant studies was performed within electronic databases including Scopus, Science Direct, PubMed, and Cochrane library. The most important keywords were adaptogen, plant, phytochemical, and plant-derived., Results: The most investigated medicinal herbs for their adaptogenic activity are Eleutherococcus senticosus, Panax ginseng, Withania somnifera, Schisandra chinensis, and Rhodiola spp., salidroside, ginsenosides, andrographolide, methyl jasmonate, cucurbitacin R, dichotosin, and dichotosininare are phytochemicals that have shown a considerable adaptogenic activity. Phytochemicals that have been demonstrated adaptogenic properties mainly belong to flavonoids, terpenoids, and phenylpropanoid glycosides., Conclusion: It is concluded that the main modes of action of the selected adaptogenic plants are stress modulatory, antioxidant, anti-fatigue, and physical endurance enhancement. Other properties were nootropic, immunomodulatory, cardiovascular, and radioprotective activities., (Copyright © 2022. Published by Elsevier GmbH.)

Introduction: Endometriosis is a difficult to manage condition associated with a significant disease burden. High levels of illicit cannabis use for therapeutic purposes have been previously reported by endometriosis patients in Australia and New Zealand (NZ). Although access to legal medicinal cannabis (MC) is available through medical prescription via multiple federal schemes, significant barriers to patient access remain. Methods: An anonymous cross-sectional online survey was developed and distributed through social media via endometriosis advocacy groups worldwide. Respondents were asked about legal versus illicit cannabis usage, their understanding of access pathways and legal status, and their interactions with health care professionals. Results: Of 237 respondents who reported cannabis use with a medical diagnosis of endometriosis, 186 (72.0%) of Australian and 51 (88.2%) NZ respondents reported self-administering cannabis illicitly. Only 23.1% of Australian and 5.9% of NZ respondents accessed cannabis through a doctor's prescription, with 4.8% of Australian and no NZ respondents reporting to legally self-administer cannabis. Substantial substitution effects (>50% reduction) were observed in users of nonopioid analgesia (63.1%), opioid analgesia (66.1%), hormonal therapies (27.5%), antineuropathics (61.7%), antidepressants (28.2%) and antianxiety medications (47.9%). Of Australian respondents, 18.8% and of NZ respondents, 23.5% reported not disclosing their cannabis use to their medical doctor, citing concern over legal repercussions, societal judgment, or their doctors' reaction and presumed unwillingness to prescribe legal MC. Conclusions: Respondents self-reported positive outcomes when using cannabis for management of endometriosis, demonstrating a therapeutic potential for MC. Despite this, many are using cannabis without medical supervision. While evidence for a substantial substitution effect by cannabis was demonstrated in these data, of particular concern are the clinical consequences of using cannabis without medical supervision, particularly with regard to drug interactions and the tapering or cessation of certain medications without that supervision. Improving doctor and patient communication about MC use may improve levels of medical oversight, the preference for legal MC adoption over acquisition via illicit supply and reducing cannabis-associated stigma.

Background: Lifestyle medicine (LM) is gaining increasing attention as a treatment option for anxiety, but the current state of evidence has not yet been systematically examined., Methods: Six electronic databases were systematically searched from inception to February 2022. Randomized controlled trials (RCTs) comparing the effects of multicomponent LM interventions on anxiety symptoms with either care-as-usual, waitlist, no intervention, or attention control group on anxiety symptoms were identified., Results: A total of 53 RCTs with 18,894 participants were included for qualitative synthesis, in which 45 RCTs with data available were included for meta-analysis. Multicomponent LM intervention was significantly more effective than the control groups in reducing anxiety symptoms at immediate posttreatment (d = 0.19, p < .001) and at short-term follow-up (d = 0.29, p < .001). However, no significant difference at medium-term was found (p = .14), whereas more studies are needed to study the long-term effects. The subgroup analyses suggested that baseline anxiety symptoms was a significant moderator, suggesting that those with moderate level of baseline anxiety symptoms appeared to have greater improvements (d = 0.66, p < .05)., Limitations: Minimal anxiety symptoms at baseline contributed to the floor effect and influenced the degree of improvement. The included RCTs had a high risk of bias in general with potential publication bias detected., Conclusion: The findings of this meta-analysis provided support for the positive effects of multicomponent LM interventions for anxiety symptoms. Future research is needed to determine the long-term effects of multicimponent LM and the optimal baseline anxiety severity., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Preliminary evidence has suggested that adjunctive N-acetylcysteine (NAC), an antioxidant precursor to glutathione, may reduce symptoms of obsessive-compulsive disorder (OCD). We conducted a 20-week, multi-site, randomized controlled trial to investigate the safety and efficacy of the adjunctive use of NAC in OCD., Methods: The study was a phase III, 20-week, double-blind, randomized controlled trial across multiple sites in Australia investigating 2 g to 4 g per day of NAC (titrated according to response) in 98 participants with DSM-5 diagnosed OCD. Data were analysed using linear mixed effects models for the 89 participants who attended at least one follow-up visit., Results: A modified intention-to-treat analysis of the primary outcome found no evidence that NAC reduced symptoms of OCD measured on the Yale-Brown Obsessive-Compulsive Scale, relative to placebo (mean difference at week 20 = 0.53, 95% compatibility interval = -2.18, 3.23; p = 0.70; favouring placebo). There was also no evidence that NAC, compared to placebo, improved outcomes on the secondary measures including anxiety, depression, quality of life, functioning, or clinician/participant impression. NAC was well-tolerated with only mild gastrointestinal adverse events associated with the treatment., Conclusion: We found no evidence supporting the efficacy of the adjunctive use of NAC in OCD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations., Methods: The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence - meta-analysis or two or more RCTs - due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the 'level of evidence' (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was 'Recommended' (+++), 'Provisionally Recommended' (++), 'Weakly Recommended' (+), 'Not Currently Recommended' (+/-), or 'Not Recommended' (-) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isolated RCTs, open label studies, case studies, preclinical research, and interventions with only traditional or anecdotal use, were not assessed., Results: Amongst nutraceuticals with Grade A evidence, positive directionality and varying levels of support ( recommended, provisionally recommended, or weakly recommended) was found for adjunctive omega-3 fatty acids (+++), vitamin D (+), adjunctive probiotics (++), adjunctive zinc (++), methylfolate (+), and adjunctive s-adenosyl methionine (SAMe) (+) in the treatment of unipolar depression. Monotherapy omega-3 (+/-), folic acid (-), vitamin C (-), tryptophan (+/-), creatine (+/-), inositol (-), magnesium (-), and n-acetyl cysteine (NAC) (+/-) and SAMe (+/-) were not supported for this use. In bipolar disorder, omega-3 had weak support for bipolar depression (+), while NAC was not currently recommended (+/-). NAC was weakly recommended (+) in the treatment of OCD-related disorders; however, no other nutraceutical had sufficient evidence in any anxiety-related disorder. Vitamin D (+), NAC (++), methylfolate (++) were recommended to varying degrees in the treatment of the negative symptoms in schizophrenia, while omega-3 fatty acids were not, although evidence suggests a role for prevention of transition to psychosis in high-risk youth, with potential pre-existing fatty acid deficiency. Micronutrients (+) and vitamin D (+) were weakly supported in the treatment of ADHD, while omega-3 (+/-) and omega-9 fatty acids (-), acetyl L carnitine (-), and zinc (+/-) were not supported. Phytoceuticals with supporting Grade A evidence and positive directionality included St John's wort (+++), saffron (++), curcumin (++), and lavender (+) in the treatment of unipolar depression, while rhodiola use was not supported for use in mood disorders. Ashwagandha (++), galphimia (+), and lavender (++) were modestly supported in the treatment of anxiety disorders, while kava (-) and chamomile (+/-) were not recommended for generalised anxiety disorder. Ginkgo was weakly supported in the adjunctive treatment of negative symptoms of schizophrenia (+), but not supported in the treatment of ADHD (+/-). With respect to safety and tolerability, all interventions were deemed to have varying acceptable levels of safety and tolerability for low-risk over-the-counter use in most circumstances. Quality and standardisation of phytoceuticals was also raised by the taskforce as a key limiting issue for firmer confidence in these agents. Finally, the taskforce noted that such use of nutraceuticals or phytoceuticals be primarily recommended (where supportive evidence exists) adjunctively within a standard medical/health professional care model, especially in cases of more severe mental illness. Some meta-analyses reviewed contained data from heterogenous studies involving poor methodology. Isolated RCTs and other data such as open label or case series were not included, and it is recognised that an absence of data does not imply lack of efficacy., Conclusions: Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders. However several had only a weak endorsement for potential use; for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings; while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use. It is the intention of these guidelines to inform psychiatric/medical, and health professional practice globally.

Disruptive innovation is a cornerstone of various disciplines, particularly in the business world, where paradigm-altering approaches are often lauded. As a construct, disruptive psychiatry can be considered to embody such an approach by the pursuit of innovations within the field which test boundaries and shake up the status quo. Given the importance of addressing the current mental health pandemic, and the deficit of highly effective pharmacological treatments for various conditions, innovative disruptive thinking is required. Significant promise exists via the provision of potentially more effective innovative therapeutic options, including digital interventions, psychedelic medicines, microbiome-altering treatments, brain stimulation technology, and nanotechnology-based delivery systems. These approaches may be further advanced by individualization of the treatments using computational technology (including quantum computing, machine learning, and artificial intelligence) and genomics., (© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

Objective: There is often a shortfall in recovery following treatment for an episode of bipolar disorder (BD). Exploration of participant's experience provides vital information to enhance statistical outcomes for novel therapy trials. This study used mixed-methods to explore participants' experience of a trial testing N -acetyl cysteine (NAC) and mitochondrially active nutraceuticals for BD depression., Case: report forms from a randomised controlled trial (RCT) of BD depression (n = 148) were analysed using a pragmatic adaption of grounded theory and thematic analysis., Results: Thematic analysis of 148 study participants indicated numerous changes in participant experience over time. For example, perceived environmental stressors reported by participants decreased over the trial in both treatment groups. Quantitative analysis of the themes revealed more positive theme reports in the combination treatment arm compared to the placebo arm and there were more negative themes identified in the placebo arm, compared to the NAC arm., Conclusion: This approach revealed additional results not elucidated in the primary quantitative analysis. This emphasises the value of mixed-methods research in capturing participants' experiences in RCTs and detecting possible latent benefits and risks. Such methods can detect latent target signals in novel therapy trials conducted in BD and generate novel hypotheses.

Study Objectives: The aim of this study was to test the efficacy and safety of Zao Ren An Shen (ZRAS) capsule, a Chinese herbal medicine product, for the treatment of insomnia., Methods: We conducted a double-blind randomized placebo-controlled trial. After a one-week placebo run-in, a total of 85 people with insomnia were randomly allocated to receive ZRAS or placebo for 4 weeks. The primary outcomes were insomnia severity assessed with the Insomnia Severity Index (ISI) and the number of participants with adverse events (AEs). Secondary outcomes included objective and subjective sleep parameters, psychological status, fatigue level, quality of life, acceptability, and tolerability., Results: A nonsignificant (p > .05) difference of 0.7 points in ISI in favor of ZRAS capsule was found at the end of the treatment. The number of participants with AEs was not significantly different (p > .05) between the two groups. Except for subjective sleep onset latency, which had a nonsignificant (p > .05) medium effect (Cohen's d = 0.5), the effects in secondary efficacy outcomes were all small (Cohen's d < .4) and nonsignificant (p > .05). The acceptability and tolerability were high in the active group., Conclusions: ZRAS capsule is safe, acceptable, and tolerable, yet not more effective than placebo in the treatment of insomnia. As previous evidence showed that Chinese herbal medicine was effective for insomnia, these results may be explained by the dose of the product, which was lower than the dose generally used in the clinic.Registration: This clinical trial was registered in Australia New Zealand Clinical Trial Registry (registration number ACTRN12619000140156) under the name "Impact of Zao Ren An Shen (ZRAS) capsule on chronic insomnia patients' insomnia severity: A randomized-controlled trial" (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376730&isReview=true)., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The current study investigated the efficacy of extract of Bacopa monnieri (BM; CDRI 08®) in reducing levels of inattention and hyperactivity in young children. BM has demonstrated improvements in cognitive outcomes in adults, yet little research is available on its effects in younger populations. A 14-week randomized, double-blind, placebo-controlled clinical trial, with placebo run-in and run-out phases, investigated the effects of BM on behavioural, cognitive, mood, and sleep effects in male children aged 6 to 14 years against placebo. One-hundred and twelve participants were recruited into the trial, with 93 datasets available for analysis. No significant behavioural differences were noted between treatment groups. Cognitive outcomes indicated decreased error-making in children taking CDRI 08® (p = .04) and increased speed of reaction time in those taking placebo (p = .04) at study end. Improvements in cognitive flexibility (p = .01), executive functioning (p = .04), interpersonal problems (p = .02), and sleep routine (p = .04) were noted in those consuming CDRI 08® over placebo. CDRI 08® did not improve behavioural outcomes, but may have cognitive, mood and sleep benefits in children aged 6 to 14 years. Further study is required to support the findings presented here., (© 2022 John Wiley & Sons Ltd.)

Introduction: Emerging evidence suggests that psychedelic compounds, including the Amazonian botanical decoction ayahuasca, may provide clinical benefit in the treatment of alcohol or other drug use disorders. This study investigates associations between ayahuasca consumption in naturalistic settings and current alcohol and other drug use., Methods: Online cross-sectional study of people who have consumed ayahuasca in religious, traditional and non-traditional settings in over 40 countries. A total of 8629 participants (53% male, average age 40 years) were included in the analysis. Logistic regressions were used to explore associations between ayahuasca drinking variables and the current use of alcohol and other drugs, as well as the influence of confounding factors, such as church or community membership., Results: The number of times ayahuasca had been consumed was strongly associated with increased odds of never or rarely drinking alcohol, never or rarely engaging in 'risky drinking' and having not consumed a range of drugs in the past month, with these effects greater for those with a prior substance use disorder compared to those without. The strength of ayahuasca drinkers subjective spiritual experience, number of personal self-insights obtained and drinking ayahuasca with an ayahuasca church were also associated with lower substance use in some models., Discussion and Conclusions: Consumption of ayahuasca in naturalistic settings is associated with lower self-reported current consumption of alcohol and other drugs for those with and without prior substance use disorders, with such effects present after adjusting for religious or social group effects., (© 2021 Australasian Professional Society on Alcohol and other Drugs.)

Purpose of Review: Despite advances in treatment modalities for mood disorders over recent decades, further therapeutic options are still required. Increased research is occurring, with the pursuit of psychedelic-based pharmacotherapies for a range of mood disorders and other conditions., Recent Findings: Serotonergic psychedelics have been found to modulate brain networks underlying various psychiatric disorders, as well promoting neurogenesis and neuroplasticity. Randomized placebo-controlled trials have found psilocybin with psychological support effective at treating depression, including treatment-resistant depression; with emergent research also signalling N,N-dimethyltryptamine/ayahuasca also as a potential option for the treatment of depression. Lysergic acid diethylamide has been found to have anxiolytic effects, whereas 3,4-methylenedioxymethamphetamine (MDMA) has been used effectively to treat post-traumatic stress disorder (PTSD), with Phase III clinical trial evidence. Microdosing of psychedelics is a growing phenomenon that has shown benefits in some preclinical data; however, a recent self-directed controlled trial reported no evidence of improved mood., Summary: Current research with medicinal psychedelics, usually as an adjunct to psychotherapy, has shown encouraging results in treating mood disorders. However, there are challenges regarding blinding and sample sizes remain small, and there have been no definitive Phase III studies (aside from MDMA for PTSD). Further work exploring novel formulations, interface with pharmacogenomics and the microbiome, and inflammatory pathways can be advised., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Objective: to perform a systematic literature review to examine the effects of high-dose, B-complex multivitamin/mineral supplementation on physical, mental, and energy outcomes in healthy and 'at-risk' (suboptimal nutritional status/subclinical symptoms at baseline) adult populations. Methods: PubMed was searched for relevant randomized controlled trials until January 2020. Results: overall, 136 publications were identified. In the seven randomised, double-blind, placebo-controlled studies considered eligible for inclusion, supplementation in healthy populations predominantly showed improvements in perceived stress, physical stamina, concentration, and general mental health, and significant reductions in anxiety and improvements in self-reported vigour. However, not all of these outcomes were significant, and statistical correction for multiple outcomes was not commonly employed. Studies investigating brain mapping following supplementation indicated increased functional activity in brain regions related to processing of attention, executive control, and working memory during cognitive tasks. Conclusions: while there is certainly a need for further studies on the neurocognitive and physical benefits of micronutrient supplementation, this review provides generally supportive evidence for the benefits of a high-dose, B-complex multivitamin/mineral supplement in healthy and at-risk populations in terms of physical, mental, and energy outcomes.

Objective: To evaluate the efficacy and credibility of a smartphone-delivered multicomponent lifestyle medicine (LM) intervention, Lifestyle Hub, as a primary modality for managing depressive symptoms in an adult Chinese population., Method: Participants with at least a moderate level of depressive symptoms (n = 79), as indicated by a Patient Health Questionnaire-9 score of ≥10, were randomly assigned to an LM intervention group (LMG; n = 39; eight weekly sessions) or a waitlist control group (WLG; n = 40)., Results: The intention-to-treat analysis revealed significant improvements in depressive symptoms (d = 0.66), generalized anxiety symptoms (d = 0.93), insomnia symptoms (d = 0.20), functional impairment (d = 0.22), and health-related quality of life (HRQoL; d = 0.11) from Week 0 (baseline) to Week 9 (immediate post-intervention assessment) in the LMG relative to the WLG. Moreover, significantly more health-promoting behaviors (overall health behaviors, health responsibility, physical activity level, nutrition, spiritual growth, and stress management) (d = 0.40-0.89) and higher levels of total activity (d = 0.55) and walking activity (d = 0.55) were found at Week 9 in the LMG relative to the WLG. However, no significant differences were observed in interpersonal relationships, vigorous and moderate exercise levels, sedentary behavior levels, or food frequency questionnaire measures at Week 9 between the LMG and the WLG. From Week 9 to Week 13 (1-month follow-up assessment), a significant within-group reduction in HRQoL (d = 0.50) and an increase in alcohol intake (d = 0.41) were observed in the LMG., Conclusions: The smartphone-delivered multicomponent LM intervention Lifestyle Hub may serve as a primary modality for managing depressive symptoms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the 'Clinical Memorandum on Psychedelics' recently released by the Royal Australian and New Zealand College of Psychiatrists and note subsequent developments including the application for down-scheduling of psilocybin and 3,4-methylenedioxymethamphetamine presently being considered by the Therapeutic Goods Administration and approvals for access via the Special Access Scheme. We suggest that this field is worthy of rigorous research to assess potential benefits, address safety parameters and clarify therapeutic mechanisms. To this end, we outline recent research findings, provide an overview of current knowledge relating to mechanisms of action and discuss salient aspects of the psychedelic-assisted psychotherapy treatment model. The sum of this research points towards medicinal psychedelics as a potential new class of psychiatric treatments when used within a medically supervised framework with integrated psychotherapeutic support. However, before widespread translation into clinical use can occur, appropriately designed and sufficiently powered trials are required to detect both potential positive and negative outcomes. Unique safety and regulatory challenges also need to be addressed. As for any new medical therapy, psychedelic research needs to be conducted in a rigorous manner, through the dispassionate lens of scientific enquiry. Carte blanche availability to practitioners, without specific protocols and appropriate training, would be potentially harmful to individuals and detrimental to the field.

Background: Recent shifting attitudes towards the medical use of cannabis has seen legal access pathways established in many jurisdictions in North America, Europe and Australasia. However, the positioning of cannabis as a legitimate medical product produces some tensions with other regulatory frameworks. A notable example of this is the so-called 'zero tolerance' drug driving legal frameworks, which criminalise the presence of THC (tetrahydrocannabinol) in a driver's bodily fluids irrespective of impairment. Here we undertake an analysis of this policy issue based on a case study of the introduction of medicinal cannabis in Australia., Methods: We examine the regulatory approaches used for managing road safety risks associated with potentially impairing prescription medicines and illicit drugs in Australian jurisdictions, as well as providing an overview of evidence relating to cannabis and road safety risk, unintended impacts of the 'zero-tolerance' approach on patients, and the regulation of medicinal cannabis and driving in comparable jurisdictions., Results: Road safety risks associated with medicinal cannabis appear similar or lower than numerous other potentially impairing prescription medications. The application of presence-based offences to medicinal cannabis patients appears to derive from the historical status of cannabis as a prohibited drug with no legitimate medical application. This approach is resulting in patient harms including criminal sanctions when not impaired and using the drug as directed by their doctor, or the forfeiting of car use and related mobility. Others who need to drive are excluded from accessing a needed medication and associated therapeutic benefit. 'Medical exemptions' for medicinal cannabis in comparable jurisdictions and other drugs included in presence offences in Australia (e.g. methadone) demonstrate a feasible alternative approach., Conclusion: We conclude that in medical-only access models there is little evidence to justify the differential treatment of medicinal cannabis patients, compared with those taking other prescription medications with potentially impairing effects., Competing Interests: Declarations of Interest IM has acted as a consultant to Kinoxis Therapeutics, has sat on the Medical Advisory Board of BOD Australia, and has received honoraria from Janssen. He is an inventor on several patents relating to novel cannabinoid therapeutics. J Sarris has received consultancy payment from Australian Natural Therapeutics Group (as an independent scientific advisor to a manufacturer of cannabis products). Other authors report no competing interests. J Sinclair has pro bono appointments on the scientific advisory boards of United in Compassion and the Australian Medicinal Cannabis Association., (Copyright © 2021. Published by Elsevier B.V.)

Background: The use of cannabis for symptoms of endometriosis was investigated utilising retrospective archival data from Strainprint Technologies Ltd., a Canadian data technology company with a mobile phone application that tracks a range of data including dose, mode of administration, chemovar and their effects on various self-reported outcomes, including pelvic pain., Methods: A retrospective, electronic record-based cohort study of StrainprintTM users with self-reported endometriosis was conducted. Self-rated cannabis efficacy, defined as a function of initial and final symptom ratings, was investigated across the included symptom clusters of cramps, pelvic pain, gastrointestinal pain, nausea, depression, and low libido. Cannabis dosage form, dose and cannabinoid ratio information was also recorded., Results: A total number of 252 participants identifying as suffering endometriosis recorded 16193 sessions using cannabis between April 2017 and February 2020. The most common method of ingestion was inhalation (n = 10914, 67.4%), with pain as the most common reported symptom being treated by cannabis (n = 9281, 57.3%). Gastrointestinal symptoms, though a less common reason for cannabis usage (15.2%), had the greatest self-reported improvement after use. Inhaled forms had higher efficacy for pain, while oral forms were superior for mood and gastrointestinal symptoms. Dosage varied across ingestion methods, with a median dose of 9 inhalations (IQR 5 to 11) for inhaled dosage forms and 1 mg/mL (IQR 0.5 to 2) for other ingested dosage forms. The ratio of THC to CBD had a statistically significant, yet clinically small, differential effect on efficacy, depending on method of ingestion., Conclusions: Cannabis appears to be effective for pelvic pain, gastrointestinal issues and mood, with effectiveness differing based on method of ingestion. The greater propensity for use of an inhaled dosage delivery may be due to the rapid onset of pain-relieving effects versus the slower onset of oral products. Oral forms appeared to be superior compared to inhaled forms in the less commonly reported mood or gastrointestinal categories. Clinical trials investigating the tolerability and effectiveness of cannabis for endometriosis pain and associated symptoms are urgently required., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: As a medical research institute, NICM Health Research Institute receives research grants and donations from foundations, universities, government agencies, individuals and industry. Sponsors and donors also provide untied funding for work to advance the vision and mission of the Institute. The authors declare no competing financial interests. JS is the recipient of a Western Sydney University Postgraduate Research Scholarship. J.Sarris has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from: Australian Natural Therapeutics Group (being a scientific advisor to Australian Natural Therapeutics Group: a cannabis grower and manufacturer), Integria Healthcare & MediHerb, Pfizer, Scius Health, Key Pharmaceuticals, Taki Mai, Fiji Kava, FIT-BioCeuticals, Blackmores, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Kantar Consulting, Angelini Pharmaceuticals, Grunbiotics, Polistudium, Research Reviews, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, SPRIM, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, Sanofi-Aventis, Omega-3 Centre, the National Health and Medical Research Council, CR Roper Fellowship. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Given the growing evidence that a range of lifestyle factors are involved in the etiology of depression, a 'lifestyle medicine' approach can be potentially safe and cost-effective to prevent or treat depression. To examine the effects and acceptability of a group-based, integrative lifestyle medicine intervention as a standalone treatment for managing depressive symptoms, a pilot randomized controlled trial (RCT) was conducted in a Chinese adult population in 2018. Participants (n = 31) with PHQ-9 score above the cut-off of ≥ 10, which was indicative of moderate to severe depression, were recruited from the general community in Hong Kong and randomly assigned to lifestyle medicine group (LM group) or care-as-usual group (CAU group) in a ratio of 1:1. Participants in the LM group received 2-hour group sessions once per week for six consecutive weeks, which covered diet, exercise, mindfulness, psychoeducation, and sleep management. Linear mixed-effects model analyses showed that the LM group had a significant reduction in PHQ-9 scores compared to the CAU group at immediate posttreatment and 12-week posttreatment follow-up (d = 0.69 and 0.73, respectively). Moreover, there were significantly greater improvements in anxiety, stress, and insomnia symptoms (measured by DASS-21 and ISI) at all time points in the LM group (d = 0.42-1.16). The results suggests that our 6-week group-based, integrative lifestyle intervention program is effective in lowering depressive, anxiety, stress, and insomnia symptoms in the Chinese population. Further studies in clinical populations with a larger sample size and longer follow-up are warranted., Competing Interests: None.

Objectives: Plant-based medicines have had a long-standing history of use in psychiatric disorders. Highly quantified and standardized extracts or isolates may be termed "phytoceuticals," in a similar way that medicinal nutrients are termed as "nutraceuticals." Over the past 2 decades, several meta-analyses have examined the data for a range of plant-based medicines in the treatment of psychiatric disorders. The aim of this international project is to provide a "meta-review" of this top-tier evidence., Methods: We identified, synthesized, and appraised all available up to date meta-analyses... of randomized controlled trials (RCTs) reporting on the efficacy and effectiveness of individual phytoceuticals across all major psychiatric disorders., Results: Our systematic search identified 9 relevant meta-analyses of RCTs, with primary analyses including outcome data from 5,927 individuals. Supportive meta-analytic evidence was found for St John's wort for major depressive disorder (MDD); curcumin and saffron for MDD or depression symptoms, and ginkgo for total and negative symptoms in schizophrenia. Kava was not effective in treating diagnosed anxiety disorders. We also provide details on 22 traditional Chinese herbal medicine formulas' meta-analyses (primarily for depression studies), all of which revealed highly significant and large effect sizes. Their methodology, reporting, and potential publication bias were, however, of marked concern. The same caveat was noted for the curcumin, ginkgo, and saffron meta-analyses, which may also have significant publication bias., Conclusions: More rigorous international studies are required to validate the efficacy of these phytoceuticals before treatment recommendations can be made. In conclusion, the breadth of data tentatively supports several phytoceuticals which may be effective for mental disorders alongside pharmaceutical, psychological therapies, and standard lifestyle recommendations.

Background: Molecular biomarkers are promising tools to be routinely used in clinical psychiatry. Among psychiatric diseases, major depression disorder (MDD) has gotten attention due to its growing prevalence and morbidity., Methods: We tested some peripheral molecular parameters such as serum mature Brain-Derived Neurotrophic Factor (mBDNF), plasma C-Reactive Protein (CRP), serum cortisol (SC), and the salivary Cortisol Awakening Response (CAR), as well as the Pittsburgh sleep quality inventory (PSQI), as part of a multibiomarker panel for potential use in MDD diagnosis and evaluation of disease's chronicity using regression models, and ROC curve., Results: For diagnosis model, two groups were analyzed: patients in the first episode of major depression (MD: n = 30) and a healthy control (CG: n = 32). None of those diagnosis models tested had greater power than Hamilton Depression Rating Scale-6. For MDD chronicity, a group of patients with treatment-resistant major depression (TRD: n = 28) was tested across the MD group. The best chronicity model (p < 0.05) that discriminated between MD and TRD included four parameters, namely PSQI, CAR, SC, and mBDNF (AUC ROC = 0.99), with 96% of sensitivity and 93% of specificity., Conclusion: These results indicate that changes in specific biomarkers (CAR, SC, mBDNF and PSQI) have potential on the evaluation of MDD chronicity, but not for its diagnosis. Therefore, these findings can contribute for further studies aiming the development of a stronger model to be commercially available and used in psychiatry clinical practice., Competing Interests: The authors have declared that no competing interests exist.

The comprehension of the pathophysiology of the major depressive disorder (MDD) is essential to the strengthening of precision psychiatry. In order to determine the relationship between the pathophysiology of the MDD and its clinical progression, analyzed by severity of the depressive symptoms and sleep quality, we conducted a study assessing different peripheral molecular biomarkers, including the levels of plasma C-reactive protein (CRP), serum mature brain-derived neurotrophic factor (mBDNF), serum cortisol (SC), and salivary cortisol awakening response (CAR), of patients with MDD ( n = 58) and a control group of healthy volunteers ( n = 62). Patients with the first episode of MDD ( n = 30) had significantly higher levels of CAR and SC than controls ( n = 32) and similar levels of mBDNF of controls. Patients with treatment-resistant depression (TRD, n = 28) presented significantly lower levels of SC and CAR, and higher levels of mBDNF and CRP than controls ( n = 30). An increased severity of depressive symptoms and worse sleep quality were correlated with levels low of SC and CAR, and with high levels of mBDNF. These results point out a strong relationship between the stages clinical of MDD and changes in a range of relevant biological markers. This can assist in the development of precision psychiatry and future research on the biological tests for depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Menezes Galvão, Almeida, de Sousa, Leocadio-Miguel, Palhano-Fontes, de Araujo, Lobão-Soares, Maia-de-Oliveira, Nunes, Hallak, Schuch, Sarris and Galvão-Coelho.)

Objective: Cancer and its treatment can lead to a variety of physical and emotional concerns impacting on those affected, including subclinical or clinical depression and anxiety, which in turn have a significant impact on wellbeing, quality of life and survival. The aim of this review was to evaluate the effect of yoga-based interventions on self-reported depression and anxiety symptoms in people with cancer in randomized controlled trials., Method: Six databases were searched to identify relevant studies. Systematic review procedures were followed including a quality assessment. Meta-analysis of suitable studies was conducted., Results: 26 studies from our search criteria were eligible for inclusion for depressive and 16 for anxiety symptoms. Meta-analyses revealed evidence for significant medium effects of yoga on depression symptoms (N = 1,486, g = -0.419, 95% confidence interval [CI] = -0.558 to -0.281, p < 0.001) and anxiety (N = 977, g = -0.347, 95% CI = -0.473 to -0.221, p < 0.001) compared to controls. Subgroup analyses for depressive symptoms revealed significant effects for all analyses performed (type of cancer, type of control, treatment status, duration of intervention or frequency of yoga sessions), with effect sizes being comparable between subgroups. Similar findings were found for anxiety symptoms except for treatment status, where the only significant effect was found when yoga was delivered during active treatment., Conclusions: This review provides evidence that in people with cancer, yoga-based interventions are associated with amelioration of depression and anxiety symptoms and therefore a promising therapeutic modality for their management. However, the potential for risk of bias together with control group design challenges means the results should be interpreted with caution., (© 2020 John Wiley & Sons Ltd.)

Objective: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to clarify the effect of vitamin C supplementation on mood in both depressed and non-depressed populations., Methods: A systematic search of PubMed, EMBASE, ISI web of science and Scopus databases was conducted, from inception to 1 March 2020. Random-effects meta-analyses were used to estimate the effect size (as Hedge's g) of vitamin C supplementation on depressive symptoms., Results: Finding from 10 trials with 836 participants revealed no significant improvement in mood status in overall analysis (n = 10, Hedge's g = 0.09; 95% confidence interval: -0.15 to 0.33; P = 0.465). However, subgroup analysis showed beneficial effects of vitamin C supplementation in patients who were not prescribed antidepressants (subclinical depressed) (n = 5, Hedge's g: -0.18; 95% CI: -0.35, -0.01, P = 0.041; I 2  = 0.00%,)., Conclusions: Although no significant effect on mood status was observed in overall population, this meta-analysis tentatively suggests that vitamin C may produce mood-elevating effects in patients with subclinical depression. Further research is recommended to reach a firm conclusion., Protocol Registration: The study protocol was registered in the international prospective register of systematic reviews database (http://www.crd.york.ac.uk/PROSPERO, registration no: CRD42018086677)., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background/study context : F 2 -Isoprostanes are putative markers of oxidative stress, one of the processes associated with biological senescence. Evidence exists for elevated F 2 -Isoprostanes in chronic conditions including psychiatric disorders. Few studies have examined the relationship between oxidative stress and mood in older healthy samples, to establish the influence on mental health. Given current aging demographics in many nations, management of brain and mental health is crucial for longevity, chronic disease management, and quality of life. Method : We investigated the relationship between F 2 -Isoprostanes, a marker for oxidative stress, and anxiety and mood in 262 healthy adults aged 60-75 years, using baseline data from the Australian Research Council Longevity Intervention (ARCLI; ANZCTR12611000487910), a 12-month nutraceutical intervention study. Results : Higher F2 levels significantly predicted increased Depression-dejection and Anger-hostility subscale scores from the Profile of Mood States (POMS). Fatigue-inertia subscale was predicted by increased Body Mass Index. Spielberger State-Trait Inventory (STAI) scores were significantly higher in females. Conclusion : While the primary outcome data did not find a definitive relationship between F2 and total mood or general anxiety levels, the sub-scale data adds weight toward growing literature that biological processes such as oxidative stress are in part related to mood. This is a modifiable risk factor contributing to physical and mental wellbeing that are crucial to healthy aging.