-
The Primary Care Companion For CNS... Jan 2024To investigate the relationship between psychedelic microdosing and its effects on mental health, aiming to understand if microdosing can improve mental well-being....
To investigate the relationship between psychedelic microdosing and its effects on mental health, aiming to understand if microdosing can improve mental well-being. PubMed and Scopus were searched on December 25, 2022, using search terms related to psychedelics, microdosing, and mental health. The inclusion criteria focused on studies published between January 1, 2012, and November 30, 2022. There were no language restrictions for the initial search; however, for the study selection, only articles in English were considered. A total of 45 articles were initially identified. After removing duplicates, 27 unique articles were screened based on their titles and abstracts, resulting in 19 articles included in the final review. The studies were selected based on their relevance to the relationship between mental health and psychedelic microdosing. The extracted data from the selected studies included sample sizes, demographics, survey designs, and qualitative and quantitative analyses related to the outcomes of individuals with mental health issues who also engaged in psychedelic microdosing. The QualSyst Quality Assessment Checklist was used to assess the methodological rigor and quality of each study. The data extraction process involved systematically reviewing each article and summarizing key findings related to the impact of microdosing on mental health. The review revealed that microdosing psychedelics, such as lysergic acid diethylamide and psilocybin, showed potential benefits on mental health. Users reported positive effects, including improved mood, increased focus, and better daily function. However, there were also challenges reported, such as physiologic discomfort and increased anxiety. Some studies observed that positive expectations about microdosing led to positive outcomes. The studies varied in design, with some being observational, others placebo-controlled, and some relying on self-reported data. There is a growing body of evidence suggesting a positive correlation between psychedelic microdosing and improved mental well-being. However, due to the limited number of controlled studies and the small sample sizes in some of the studies, the causal relationship between microdosing and mental health improvement remains uncertain. The review calls for further research with double-blind experiments, control groups, and larger sample sizes that represent the general population to better understand the potential benefits and risks of psychedelic microdosing on mental health. . .
Topics: Humans; Hallucinogens; Mental Health; Psilocybin; Lysergic Acid Diethylamide; Anxiety; Randomized Controlled Trials as Topic
PubMed: 38228068
DOI: 10.4088/PCC.23r03581 -
Neuropsychopharmacology Reports Mar 2024This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy,... (Meta-Analysis)
Meta-Analysis
AIM
This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants.
METHODS
Outcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non-response rate; the non-remission rate; all-cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain.
RESULTS
A literature search identified three double-blind, randomized, placebo-controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible-dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day.
CONCLUSIONS
Overall BRE showed similar utility to ARI and a good risk-benefit balance.
Topics: Humans; Aripiprazole; Depressive Disorder, Major; Japan; Psychomotor Agitation; Network Meta-Analysis; Weight Gain; Randomized Controlled Trials as Topic; Thiophenes; Quinolones
PubMed: 38219278
DOI: 10.1002/npr2.12414 -
Frontiers in Pharmacology 2023Cancer is a neoplastic transformation that affects tissue. Among the many complications associated with cancer treatment, managing the distressing side effects of...
Cancer is a neoplastic transformation that affects tissue. Among the many complications associated with cancer treatment, managing the distressing side effects of chemotherapy-induced nausea and vomiting (CINV) is of main concern. Ondansetron is a selective serotonin 5-HT3 receptor antagonist that has emerged as an essential medication against CINV in adult cancer patients. Ondansetron efficacy and tolerability have made it a primary medication in CINV prophylaxis and treatment regimens. The study aims to offer a detailed overview of ondansetron's effectiveness, safety, and impact on patients' lives, ultimately contributing to the ongoing research to enhance the quality of cancer care. On 4 September 2023, a search was conducted of the ClinicalTrials.gov database using the search terms "cancer," "ondansetron," and "Zofran." Inclusion and exclusion criteria were defined to select relevant clinical trials. Included trials were completed with results and interventional studies that assessed the preventive effects of ondansetron on CINV in adult cancer patients. A total of 23 clinical trials were identified, with only 13 of them focusing on investigating the preventive effects of ondansetron on CINV in adult cancer patients. The collective findings from these trials showed an effective management of CINV using ondansetron. Through a comprehensive overview of clinical trials, the use of ondansetron in adult cancer patients represents a significant improvement in CINV management.
PubMed: 38074143
DOI: 10.3389/fphar.2023.1310455 -
Therapeutic Drug Monitoring Apr 2024Therapeutic drug monitoring of clozapine in children and adolescents has received insufficient attention. Calculation of concentration-to-dose (C/D) ratios from trough...
A Systematic Review of Clozapine Concentration-Dose Ratio from Therapeutic Drug Monitoring Studies in Children and Adolescents Treated with Clozapine for Mental Disorders.
BACKGROUND
Therapeutic drug monitoring of clozapine in children and adolescents has received insufficient attention. Calculation of concentration-to-dose (C/D) ratios from trough steady-state concentrations estimate drug clearance.
METHODS
A systematic electronic literature search was conducted in 3 article databases from inception until January 10, 2023, and articles reporting clozapine concentrations in children and adolescents were retrieved. The pharmacokinetic quality of the studies was assessed, and clozapine C/D ratios were calculated using the sample mean clozapine dose and concentration.
RESULTS
Of the 37 articles of potential interest, only 7 reported clozapine trough and steady-state concentrations. After excluding case reports and a study confounded by fluvoxamine, 4 studies on psychosis from Europe and the United States were included. The clozapine C/D ratios were similar to published adult values and ranged from 0.82 to 1.24 with a weighted mean of 1.08 ng/mL per mg/d. The weighted means were 334 mg/d for the dose and 380 ng/mL for the concentration. The stratified analysis of the weighted mean clozapine C/D ratios from 2 studies showed lower values in 52 male (1.05 ng/mL per mg/d) than in 46 female (1.46 ng/mL per mg/d) children and adolescents, with values similar to those reported for European adult nonsmokers. Two female adolescents had high clozapine C/D ratios (2.54 ng/mL per mg/d), an Asian American patient with borderline obesity and a patient with intellectual disability with low dosage (mean = 102 mg/d) and concentration (mean = 55 ng/mL).
CONCLUSIONS
Reports on clozapine therapeutic drug monitoring in children and adolescents are limited in number and quality. Future studies should focus on basic pharmacokinetic issues, such as stratification by sex, smoking, and relevant comedications with inductive or inhibitory properties.
Topics: Adult; Child; Male; Humans; Female; Adolescent; Clozapine; Antipsychotic Agents; Drug Monitoring; Mental Disorders; Psychotic Disorders
PubMed: 38018845
DOI: 10.1097/FTD.0000000000001154 -
Scientific Reports Nov 2023Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists in augmentation with selective serotonin reuptake inhibitors (SSRIs) in the treatment of moderate to severe obsessive-compulsive disorder: a systematic review and meta-analysis of randomized clinical trials.
Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its pharmacological treatment. About 40-60% of the cases are treatment-refractory, and this makes searching for second-line treatment necessary. 5-Hydroxytryptamine-3 (5-HT3) antagonists are among the many medications that have been used in augmentation with SSRIs. In this systematic review and meta-analysis, we assessed the efficacy and safety of 5-HT3 receptor antagonists in augmentation with SSRIs in treating moderate to severe OCD. We searched PubMed, Web of Science, Scopus, Cochrane library, and Google Scholar for relevant trials published up to December 2022. The effect size was the mean difference in Yale-Brown obsessive compulsive scale (Y-BOCS) scores before and after receiving 5-HT3 receptor antagonist drugs in augmentation with SSRIs in moderate to severe OCD patients. We included 6 randomized-controlled trails (RCTs) with 334 patients assessing the effect of the augmentation of SSRIs with ondansetron, granisetron, and tropisetron on treating moderate to severe OCD. Our results were in favor of the experimental group in total (Z = 8.37, P < 0.00001), in the compulsion subgroup (Z = 5.22, P < 0.00001), and in the obsession subgroup (Z = 8.33, P < 0.00001). They are well-tolerated, and have mild side effects and do not result in withdrawal. Augmentation of 5-HT3 antagonists with SSRIs can be beneficial in treating moderate to severe OCD. Further multi-center trials under adequate conditions in longer periods are needed to help come up with a comprehensive action plan.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Serotonin; Receptors, Serotonin, 5-HT3; Treatment Outcome; Randomized Controlled Trials as Topic; Obsessive-Compulsive Disorder; Drug Therapy, Combination
PubMed: 38012263
DOI: 10.1038/s41598-023-47931-x -
CNS Drugs Dec 2023The renewed interest in psychedelic research provides growing evidence of potentially unique effects on various aspects of reward processing systems. Using the Research...
BACKGROUND AND OBJECTIVES
The renewed interest in psychedelic research provides growing evidence of potentially unique effects on various aspects of reward processing systems. Using the Research Domain Criteria (RDoC) framework, as proposed by the National Institute of Mental Health, we aim to synthesize the existing literature concerning the impact of lysergic acid diethylamide (LSD) on the RDoC's Positive Valence Systems (PVS) domain, and to identify potential avenues for further research.
METHODS
Two LSD-related terms (lysergic acid diethylamide and LSD) and 13 PVS-related terms (reward, happiness, bliss, motivation, reinforcement learning, operant, conditioning, satisfaction, decision making, habit, valence, affect, mood) were used to search electronic databases such as PubMed, Scopus, PsychINFO, and Web of Science for relevant articles. A manual search of the reference list resulted in nine additional articles. After screening, articles and data were evaluated and included based on their relevance to the objective of investigating the effects of LSD on the PVS. Articles and data were excluded if they did not provide information about the PVS, were observational in nature, lacked comparators or reference groups, or were duplicates. A risk of bias assessment was performed using the National Toxicology Program's Office of Health Assessment and Translation (NTP OHAT) risk of bias (RoB) tool. Data from the included articles were collected and structured based on the RDoC bio-behavioral matrix, specifically focusing on the PVS domain and its three constituent constructs: reward responsiveness, reward learning, and reward valuation.
RESULTS
We reviewed 28 clinical studies with 477 participants. Lysergic acid diethylamide, assessed at self-report (23 studies), molecular (5 studies), circuit (4 studies), and paradigm (3 studies) levels, exhibited dose-dependent mood improvement (20 short-term and 3 long-term studies). The subjective and neural effects of LSD were linked to the 5-HT receptor (molecular). Animal studies (14 studies) suggested LSD could mildly reinforce conditioned place preference without aversion and reduce responsiveness to other rewards. Findings on reward learning were inconsistent but hinted at potential associative learning enhancements. Reward valuation measures indicated potential reductions in effort expenditure for other reinforcers.
CONCLUSION
Our findings are consistent with our previous work, which indicated classical psychedelics, primarily serotonin 2A receptor agonists, enhanced reward responsiveness in healthy individuals and patient populations. Lysergic acid diethylamide exhibits a unique profile in the reward learning and valuation constructs. Using the RDoC-based framework, we identified areas for future research, enhancing our understanding of the impact of LSD on reward processing. However, applying RDoC to psychedelic research faces limitations due to diverse study designs that were not initially RDoC-oriented. Limitations include subjective outcome measure selection aligned with RDoC constructs and potential bias in synthesizing varied studies. Additionally, some human studies were open-label, introducing potential bias compared to randomized, blinded studies.
Topics: Animals; Humans; Hallucinogens; Lysergic Acid Diethylamide; Serotonin Receptor Agonists; Affect; Self Report
PubMed: 37999867
DOI: 10.1007/s40263-023-01044-1 -
The 5-HT7 receptor system as a treatment target for mood and anxiety disorders: A systematic review.Journal of Psychopharmacology (Oxford,... Dec 2023Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this... (Review)
Review
BACKGROUND
Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this systematic review, we aimed to review the relationship between the 5-HT7 receptor system and mood and anxiety disorders, and to explore the pharmacology and therapeutic potential of medications that target the 5-HT7 receptor for their treatment.
METHODS
Medline, Cochrane Library, EMBASE, PsycINFO databases, the National Institute of Health website Clinicaltrials.gov, controlled-trials.com, and relevant grey literature were used to search for original research articles, and reference lists of included articles were then hand searched.
RESULTS
Sixty-four studies were included in the review: 52 animal studies and 12 human studies. Studies used a variety of preclinical paradigms and questionnaires to assess change in mood, and few studies examined sleep or cognition. Forty-four out of 47 (44/47) preclinical 5-HT7 modulation studies identified potential antidepressant effects and 20/23 studies identified potential anxiolytic effects. In clinical studies, 5/7 identified potential antidepressant effects in major depressive disorder, 1/2 identified potential anxiolytic effects in generalized anxiety disorder, and 3/3 identified potential antidepressant effects in bipolar disorders.
CONCLUSION
While there is some evidence that the 5-HT7 receptor system may be a potential target for treating mood and anxiety disorders, many agents included in the review also bind to other receptors. Further research is needed using drugs that bind specifically to 5-HT7 receptors to examine treatment proof of concept further.
Topics: Animals; Humans; Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Depressive Disorder, Major
PubMed: 37994803
DOI: 10.1177/02698811231211228 -
Journal of Psychopharmacology (Oxford,... Jan 2024Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT),... (Review)
Review
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.
Topics: Humans; Hallucinogens; Psilocybin; Mescaline; N,N-Dimethyltryptamine; Drug Interactions; Lysergic Acid Diethylamide
PubMed: 37982394
DOI: 10.1177/02698811231211219 -
Schizophrenia Research Jun 2024The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents.
BACKGROUND
The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents.
METHODS
Cases of clozapine-associated pericarditis and pancreatitis in children were studied using searches in: 1) PubMed (June 16, 2023), and 2) the World Health Organization's pharmacovigilance database (June 1, 2022), VigiBase. VigiBase uses a logarithmic measure of disproportionality called the information component (IC).
RESULTS
The PubMed search yielded 3 clozapine-associated pericarditis cases, 1 pancreatitis case and 1 with both. VigiBase provided a significant clozapine-associated pericarditis IC = 3.6 with an IC = 2.9 (only 3 cases were expected while 22 were observed). VigiBase provided a significant clozapine-associated pancreatitis IC = 2.2 with an IC = 1.4 (only 3 cases were expected while 16 were observed). In VigiBase clozapine-associated pericarditis and pericardial effusion in youth looked similar and on a continuum with myocarditis, as myocarditis, pericarditis and pancreatitis appeared to occur mainly during clozapine titration. Combining PubMed and VigiBase we identified: 1) 29 cases of at least possible clozapine-associated pericarditis/pericardial effusion (6 probable and 23 possible) including 7 cases with and 22 without myocarditis, and 2) 17 cases of clozapine-associated pancreatitis (1 definite and 16 possible). Two of the pancreatitis cases occurred during overdoses. No fatal outcomes were found in any clozapine-associated pericarditis and pancreatitis cases.
CONCLUSIONS
Despite the lack of attention in the literature to clozapine-associated pericarditis and pancreatitis, results demonstrate that they can happen in youth, particularly during titration. Pericarditis and pancreatitis appear to be forms of clozapine-associated inflammation during dose titration.
Topics: Humans; Pancreatitis; Clozapine; Pericarditis; Pharmacovigilance; Adolescent; Child; Antipsychotic Agents; Databases, Factual; Male; Female; Pericardial Effusion
PubMed: 37981478
DOI: 10.1016/j.schres.2023.10.027 -
Schizophrenia Research Jun 2024As access to an essential part of clozapine research from the former Union of Soviet Socialist Republics (USSR) states is very limited, quality aspects have not gained...
OBJECTIVE
As access to an essential part of clozapine research from the former Union of Soviet Socialist Republics (USSR) states is very limited, quality aspects have not gained attention so far, and harmonization with modern research standards remains unclear.
METHODS
We performed a systematic search in PubMed, Embase and scientific indexes from former USSR states for articles published in Russian language till January 2023 (PROSPERO Reg. Number CRD42023386737) and assessed their quality using the modified Strengthening the reporting of observational studies in epidemiology (STROBE)-Checklist. We compared quality aspects for papers published before and after 2000.
RESULTS
A total of 60 papers were considered. Conflicts of interests and funding sources were reported in 5 and 3 (8 % and 5 %) studies respectively; ethical approval was warranted in two studies (3 %). Statistical analysis was performed in 57 (95 %) studies, but statistical methods were described in 21 (35 %) studies. When comparing studies before and after 2000, there was a trend towards improvement for several aspects, with the only significant differences being the objectives' specification (43 vs 83 %, p < 0.003) and the reporting of statistical methodology (0.0 vs 46 %, p < 0.001), which were more frequently available in papers after 2000.
CONCLUSIONS
Clozapine papers in Russian language suffered from severe methodological drawbacks limiting generalizability. Changes regarding standardization, transparency, ethics, and good scientific practice are urgently required. Using reporting checklists and predefining protocols are the first steps towards quality upgrade and accelerate the integration of science from the former USSR states into the world scientific system.
Topics: Clozapine; Humans; Antipsychotic Agents; USSR; Biomedical Research; Schizophrenia
PubMed: 37977975
DOI: 10.1016/j.schres.2023.10.040