Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis.

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.

Along the microbiota-gut-brain axis: Use of plant polysaccharides to improve mental disorders.

With the development of gut microbiota-specific interventions for mental disorders, the interactions between plant polysaccharides and microbiota in the intestinal and their consequent effects are becoming increasingly important. In this review, we discussed the role of plant polysaccharides in improving various mental disorders via the microbiota-gut-brain axis. The chemical and structural characteristics and metabolites of these plant polysaccharides were summarised. Plant polysaccharides and their metabolites have great potential for reshaping gut microbiota profiles through gut microbiota-dependent fermentation. Along the microbiota-gut-brain axis, the consequent pharmacological processes that lead to the elimination of the symptoms of mental disorders include 1) regulation of the central monoamine neurotransmitters, amino acid transmitters and cholinergic signalling system; 2) alleviation of central and peripheral inflammation mainly through the NLRP3/NF-κB-related signalling pathway; 3) inhibition of neuronal apoptosis; and 4) enhancement of antioxidant activities. According to this review, monosaccharide glucose and structure -4-α-Glcp-(1→ are the most potent compositions of the most reported plant polysaccharides. However, the causal structure-activity relationship remains to be extensively explored. Moreover, mechanistic elucidation, safety verification, and additional rigorous human studies are expected to advance plant polysaccharide-based product development targeting the microbiota-gut-brain axis for people with mental disorders.

Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders.

Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson's diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson's disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.

Mind, Mood and Microbiota-Gut-Brain Axis in Psychiatric Disorders.

Psychiatric disorders represent a primary source of disability worldwide, manifesting as disturbances in individuals' cognitive processes, emotional regulation, and behavioral patterns. In the quest to discover novel therapies and expand the boundaries of neuropharmacology, studies from the field have highlighted the gut microbiota's role in modulating these disorders. These alterations may influence the brain's processes through the brain-gut axis, a multifaceted bidirectional system that establishes a connection between the enteric and central nervous systems. Thus, probiotic and prebiotic supplements that are meant to influence overall gut health may play an insightful role in alleviating psychiatric symptoms, such as the cognitive templates of major depressive disorder, anxiety, or schizophrenia. Moreover, the administration of psychotropic drugs has been revealed to induce specific changes in a microbiome's diversity, suggesting their potential utility in combating bacterial infections. This review emphasizes the intricate correlations between psychiatric disorders and the gut microbiota, mentioning the promising approaches in regard to the modulation of probiotic and prebiotic treatments, as well as the antimicrobial effects of psychotropic medication.

Psychiatric risks for worsened mental health after psychedelic use.

BACKGROUND: Resurgent psychedelic research has largely supported the safety and efficacy of psychedelic therapy for the treatment of various psychiatric disorders. As psychedelic use and therapy increase in prevalence, so does the importance of understanding associated risks. Cases of prolonged negative psychological responses to psychedelic therapy seem to be rare; however, studies are limited by biases and small sample sizes. The current analytical approach was motivated by the question of whether rare but significant adverse effects have been under-sampled in psychedelic research studies. METHODS: A "bottom margin analysis" approach was taken to focus on negative responders to psychedelic use in a pool of naturalistic, observational prospective studies (N = 807). We define "negative response" by a clinically meaningful decline in a generic index of mental health, that is, one standard error from the mean decrease in psychological well-being 4 weeks post-psychedelic use (vs pre-use baseline). We then assessed whether a history of diagnosed mental illness can predict negative responses. RESULTS: We find that 16% of the cohort falls into the "negative responder" subset. Parsing the sample by self-reported history of psychiatric diagnoses, results revealed a disproportionate prevalence of negative responses among those reporting a prior personality disorder diagnosis (31%). One multivariate regression model indicated a greater than four-fold elevated risk of adverse psychological responses to psychedelics in the personality disorder subsample (b = 1.425, p < 0.05). CONCLUSION: We infer that the presence of a personality disorder may represent an elevated risk for psychedelic use and hypothesize that the importance of psychological support and good therapeutic alliance may be increased in this population.

The Labyrinthine Journey: Unveiling Obstacles in addressing Mental Health Challenges in Prisons and its Confluence with Medico-Legal and Pharmacological Perspectives.

This paper delves into the intricate realm of mental health issues within prisons including other correctional facilities, the intersectionality with legal and medical aspects, and the potential of pharmacology as a viable treatment modality. The prevalence and diverse array of mental disorders among incarcerated individuals are thoroughly examined, underscoring the imperative for all-encompassing interventions. The legal structure, hurdles encountered in delivering mental healthcare, and the indispensability of interdisciplinary cooperation are scrutinized. Furthermore, the effectiveness and moral implications of pharmaceutical interventions in correctional environments are deliberated upon. Conclusive suggestions are put forth to enhance mental healthcare provisions in prisons. The research paper endeavors to penetrate the labyrinthine complexities of mental health predicaments within correctional institutions, with a specific emphasis on the convergence of medico-legal facets and the plausible impact of pharmacological interventions. The study strives to elucidate the intricate nature of mental health challenges among incarcerated populations, considering the intricate interplay of socio-cultural, environmental, and psychological factors that contribute to their pervasiveness. By delving into these interconnected dimensions, the research aims to unlock prospective remedies capable of efficaciously meeting the mental health requisites of incarcerated individuals.

Attitude toward patients with mental disorders: what is going on amongst Iranian pharmacies?

INTRODUCTION: As the incidence of mental disorders continues to rise, and pharmacy staff can significantly affect the willingness of patients with mental disorders to seek help; we aimed to evaluate the stigmatizing attitude of the pharmacy staff toward these patients in Iran. METHODS: We conducted this cross-sectional study between April 2020 and December 2021 in Tehran, Iran, and included pharmacists, pharmacy technicians and pharmacy students, with the experience of working in a pharmacy for at least three months. The social distance scale (SDS) and dangerousness scale (DS) were used to measure the stigmatizing attitude of the participants. Higher scores indicated more stigmatizing attitudes. RESULTS: We included a total of 186 participants with a mean age of 32.97 ± 9.41 years, of which 101 (54.3%) were male, and 75 (40.3%) were pharmacists, 101 (54.3%) were pharmacy technicians, and 8 (4.3%) were pharmacy students. The mean SDS score was 14.2 ± 4.13, and the mean DS score was 33.85 ± 8.92. The greatest tendency for social distance was reported for a patient with a mental disorder, 'being the caretaker of their children for an hour or two' and 'marrying their children.' The most perceived dangerousness was reported for a patient with a mental disorder 'owning a gun.' Positive personal history of psychopharmacological treatment was statistically correlated with lower DS (P = 0.001) and SDS (P = 0.007) scores. Positive family history of psychiatric inpatient admission was significantly correlated with higher DS (P = 0.05) and SDS (P = 0.03) scores. Higher rates of 'received psychiatric prescriptions per month' was associated with lower DS scores (P = 0.04). CONCLUSION: Our participants did not have an overall positive attitude toward patients with mental disorders. Although, compared to previous studies, they held a more positive attitude. Positive personal history of psychopharmacological treatment predicted a more positive attitude and positive family history of psychiatric inpatient admission predicted a more negative attitude.

Integrative Research of Neuropharmacology and Informatics Pharmacology for Mental Disorder.

Mental illness poses a huge social burden, accounting for approximately 14% of all deaths. Depression, a major component of mental illness, affects approximately 300 million people worldwide, mainly in developed countries, and is not only a major social burden but also a cause of suicide. The social burden of depression is estimated to increase further in developing countries, and overcoming it is a pressing issue for all countries, including Japan. Although clinical evidence has demonstrated the efficacy of serotonergic neurotransmission enhancers in the treatment of depression, the full picture of their therapeutic effects has not yet been fully elucidated. In this review, we show that the hyperactivity of serotonin neurons, especially those in the dorsal raphe nucleus, is commonly induced by various antidepressants within a period corresponding to the onset of their clinical efficacy. We established quantitative prediction methods for pharmacological activity using only chemical structures to translate the biological understanding of mental disorders, including major depressive disorders, into clinically effective therapeutics. Our method exhibited better performance than the previously reported methods of quantitative prediction, while targeting a larger number of proteins. Our article suggests the importance of integrative neuropharmacology and informatics-based pharmacology studies to understand the biological basis of mental disorders and facilitate drug development for these disorders.

Psychotropic Medication Administration in Pediatric Emergency Departments.

BACKGROUND AND OBJECTIVES: Visits by youth to the emergency department (ED) with mental and behavioral health (MBH) conditions are increasing, yet use of psychotropic medications during visits has not been well described. We aimed to assess changes in psychotropic medication use over time, overall and by medication category, and variation in medication administration across hospitals. METHODS: We conducted a retrospective cross-sectional study of ED encounters by youth aged 3-21 with MBH diagnoses using the Pediatric Health Information System, 2013-2022. Medication categories included psychotherapeutics, stimulants, anticonvulsants, antihistamines, antihypertensives, and other. We constructed regression models to examine trends in use over time, overall and by medication category, and variation by hospital. RESULTS: Of 670 911 ED encounters by youth with a MBH diagnosis, 12.3% had psychotropic medication administered. The percentage of MBH encounters with psychotropic medication administered increased from 7.9% to16.3% from 2013-2022 with the odds of administration increasing each year (odds ratio, 1.09; 95% confidence interval, 1.05-1.13). Use of all medication categories except for antianxiety medications increased significantly over time. The proportion of encounters with psychotropic medication administered ranged from 4.2%-23.1% across hospitals (P < .001). The number of psychotropic medications administered significantly varied from 81 to 792 medications per 1000 MBH encounters across hospitals (P < .001). CONCLUSIONS: Administration of psychotropic medications during MBH ED encounters is increasing over time and varies across hospitals. Inconsistent practice patterns indicate that opportunities are available to standardize ED management of pediatric MBH conditions to enhance quality of care.

Discovery of potential TAAR1 agonist targeting neurological and psychiatric disorders: An in silico approach.

Trace amine-associated receptor 1 (TAAR1) is a G-protein-coupled receptor which is primarily expressed in the brain. It is activated by trace amines which play a role in regulating neurotransmitters like dopamine, serotonin and norepinephrine. TAAR1 agonists have potential applications in the treatment of neurological and psychiatric disorders, especially schizophrenia. In this study, we have used a structure-based virtual screening approach to identify potential TAAR1 agonist(s). We have modelled the structure of TAAR1 and predicted the binding pocket. Further, molecular docking of a few well-known antipsychotic drugs was carried out with TAAR1 model, which showed key interactions with the binding pocket. From screening a library of 5 million compounds from the Enamine REAL Database using structure-based virtual screening method, we shortlisted 12 compounds which showed good docking score, glide energy and interactions with the key residues. One lead compound (Z31378290) was finally selected. The lead compound showed promising binding affinity and stable interactions with TAAR1 during molecular dynamics simulations and demonstrated better van der Waals and binding energy than the known agonist, ulotaront. Our findings suggest that the lead compound may serve as a potential TAAR1 agonist, offering a promising avenue for the development of new therapies for neurological and psychiatric disorders.

Stimulant Patterns, Alone or with Other Psychotropic Classes, in Medicaid-Insured Youth Continuously Enrolled for 3-8 Years.

Objective: Little U.S. pharmacoepidemiologic study is based on treatment during continuous enrollment for periods more than a year. This study aims to show pediatric patterns of stimulant use (alone or with other psychotropic classes) from Medicaid administrative claims data for stimulant patterns of 3- to 8-year continuous enrollees. Methods: A retrospective cohort study was derived from Medicaid enrollment, pharmacy, and diagnosis claims data (2007-2014) in a mid-Atlantic state. Youth aged 2-17 years with 3-8 years of continuous enrollment treated with stimulants were compared with a date-matched comparison group treated without stimulants. Major outcomes include prevalence and duration of stimulant use and patterns of stimulant polypharmacy across relatively long enrollments (3-8 years). Results: Among 264,518 unique 2- to 17-year olds with 3-8 years of continuous enrollment, 16.5% had stimulant prescription dispensings, doubling the annual national prevalence of 8.1%. Subgroup analysis showed that the highest prevalence of stimulant use was for 6- to 11-year olds (20.4%), foster care eligible youth (42.3%), and those with 7-8 years of continuous enrollment (20.1%). Externalizing psychiatric disorders were far more common in those treated with stimulants than in those treated without stimulants. The duration of stimulant exposure overall was a median of 487 days, half that of foster care stimulant users. Stimulant polypharmacy with two or more psychotropic classes concomitantly characterized 29.8% of stimulant users. Among those with three or four or more class polypharmacy, 85% and 88%, respectively, had concomitant stimulant and antipsychotic use. The adjusted odds ratio (AOR) of three or more class polypharmacy significantly increased in 12- to 17-year-old age group (AOR = 1.8), foster care eligibility (AOR = 4.5), and among those with the longest enrollment (AOR = 1.7). Conclusions and Relevance: Stimulant prevalence in Medicaid-insured youth with continuous enrollment of 3-8 years was twice as common as in annual data sets. Future research should investigate three to five interclass stimulant polypharmacy effectiveness in reliably diagnosed community populations.

Psychotropic Polypharmacy Among Youths Enrolled in Medicaid.

This cross-sectional study aims to identify temporal changes and characteristics associated with psychotropic polypharmacy among youths aged 17 years or younger who were enrolled in Medicaid in Maryland.

PI3K-AKT/mTOR Signaling in Psychiatric Disorders: A Valuable Target to Stimulate or Suppress?

Economic development and increased stress have considerably increased the prevalence of psychiatric disorders in recent years, which rank as some of the most prevalent diseases globally. Several factors, including chronic social stress, genetic inheritance, and autogenous diseases, lead to the development and progression of psychiatric disorders. Clinical treatments for psychiatric disorders include psychotherapy, chemotherapy, and electric shock therapy. Although various achievements have been made researching psychiatric disorders, the pathogenesis of these diseases has not been fully understood yet, and serious adverse effects and resistance to antipsychotics are major obstacles to treating patients with psychiatric disorders. Recent studies have shown that the mammalian target of rapamycin (mTOR) is a central signaling hub that functions in nerve growth, synapse formation, and plasticity. The PI3K-AKT/mTOR pathway is a critical target for mediating the rapid antidepressant effects of these pharmacological agents in clinical and preclinical research. Abnormal PI3K-AKT/mTOR signaling is closely associated with the pathogenesis of several neurodevelopmental disorders. In this review, we focused on the role of mTOR signaling and the related aberrant neurogenesis in psychiatric disorders. Elucidating the neurobiology of the PI3K-AKT/mTOR signaling pathway in psychiatric disorders and its actions in response to antidepressants will help us better understand brain development and quickly identify new therapeutic targets for the treatment of these mental illnesses.

Prescriptions of psychotropic and somatic medications among patients with severe mental disorders and healthy controls in a naturalistic study.

PURPOSE: Psychotropic and somatic medications are both used in treating severe mental disorders (SMDs). Realistic estimates of the prevalence of use across medication categories are needed. We obtained this in a clinical cohort of patients with SMD and healthy controls (HCs). MATERIALS AND METHODS: Prescriptions filled at Norwegian pharmacies the year before and after admittance to the Thematically Organized Psychosis (TOP) study were examined in 1406 patients with SMD (mean age 32.5 years, 48.2% women) and 920 HC (34.1 years, 46.2% women). Using data from the Norwegian Prescription Database (NorPD), the number of users in different anatomical therapeutic chemical (ATC) categories was compared using logistic regression. Population estimates were used as reference data. RESULTS: Use of antipsychotics (N05A), antiepileptics (N03A), antidepressants (N06A), anxiolytics (N05B), hypnotics and sedatives (N05C), anticholinergics (N04A), psychostimulants, attention deficit hyperactivity disorder and nootropic agents (N06B) and drugs for addiction disorders (N07B) was significantly more prevalent in patients with SMD than HC. Use of diabetes treatment (A10), antithrombotic drugs (B01), beta blockers (C07), lipid modifiers (C10), and thyroid and endocrine therapeutics (H03) was also more prevalent in patients with SMD, but with two exceptions somatic medication use was comparable to the general population. Among HC, there was low prevalence of use for most medication categories. CONCLUSION: Patients were using psychiatric medications, but also several types of somatic medications, more often than HC. Still, somatic medication use was mostly not higher than in the general population. The results indicate that HC had low use of most medication types.

Factors Associated With Oral Anticoagulant Use in Patients With Atrial Fibrillation and Mental Disorders.

Objective: This study aims to identify how mental illness severity interacts with oral anticoagulant (OAC) patterns among people with atrial fibrillation (AF).Methods: AF patients with comorbid mental illness (classified using ICD-10) were identified from the South London and Maudsley Biomedical Research Centre Case Register. CHA2DS2-VASc and ORBIT scales were used to calculate stroke and bleeding risks, respectively, whereas Health of the Nation Outcome Scales (HoNOS) assessment was used for functional impairment.Results: Overall, 2,105 AF patients were identified between 2011 and 2019. Serious mental illness (SMI) was associated with lower prescription of any OAC (adjusted risk ratio [aRR]: 0.94; 95% CI, 0.90-0.99). A total of 62% of SMI patients at risk of stroke were not prescribed an OAC. In the AF cohort, alcohol or substance dependence and activities of daily living (ADL) impairment were associated with lower prescription of warfarin (aRR: 0.92; 95% CI, 0.86-0.98 and aRR: 0.96; 95% CI, 0.93-0.99, respectively). Among people with AF and SMI, warfarin was less likely to be prescribed to people with self-injury (aRR: 0.84; 95% CI, 0.77-0.91), hallucinations or delusions (aRR: 0.92; 95% CI, 0.85-0.99), ADL impairment (aRR: 0.91; 95% CI, 0.84-0.99), or alcohol or substance dependence (aRR: 0.92; 95% CI, 0.87-0.98). Among people with AF and comorbid substance use disorder, self-injury (aRR: 0.78; 95% CI, 0.64-0.96), cognitive problems (aRR: 0.84; 95% CI, 0.70-0.99), and other mental illnesses (aRR: 0.83; 95% CI, 0.70-0.99) were associated with lower prescription of warfarin.Conclusions: An OAC treatment gap for AF patients with comorbid SMI relative to other mental illnesses was identified. The gap was wider in those with dependence comorbidities, positive symptoms, self-injury, or functional impairment.J Clin Psychiatry 2024;85(1):23m14824. Author affiliations are listed at the end of this article.