Current Reviews in Clinical and Experimental Pharmacology - Volume 18, Issue 2, 2023

Psychedelics might be the oldest psychoactive agents known to be used for inducing religious or mystical experiences. Their strong psychoactive effect was discovered accidentally in 1943 after the synthesis of Lysergic acid diethylamide (LSD) in 1937. These drugs became a mainstream area of research following the synthesis of LSD; however, several political and social factors led to their ban in 1966, after which research on psychedelics remained limited. These drugs became a major topic of scientific and ethical debate in the 1990’s and the recent times have seen a ‘Psychedelic renaissance’ where the therapeutic value of psychedelics is being reconsidered. This article reports the historical perspective of psychedelics, pharmacologic action by 5-HT2A receptor agonism, and psychological effects and compares the proposed therapeutic uses, including uses in depression, PTSD, anxiety- related disorders, drug and alcohol addiction, neurodegenerative diseases, and auto-immune diseases to potential harms including the development of tolerance, hallucinogen persisting perception disorder, and potential psychosis. An analysis of history, pharmacology, and comparison of benefits and harms lead to the conclusion that the potential therapeutic benefits significantly outweigh the potential harms; thus, further research and clinical trials need to be conducted across different countries and cultures for their legal approval in clinical use.

Background: Cognitive impairment is one of the most common problems experienced by patients receiving chemotherapy, and evidence suggests that cytokines might play an important role. Various studies were conducted to evaluate the role of cytokines in chemotherapy-related cognitive impairment (CRCI). However, the association between CRCI due to cytokines is not well-established. Thus, this systematic review aims to assess the role of cytokines in CRCI in breast cancer patients. Methods: This systematic review was conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) guidelines. An intense literature search was carried out for inclusion criteria in major databases, including PubMed and Clinicaltrials.gov, in August 2021. Studies assessing cognitive parameters through objective and subjective assessment in breast cancer patients receiving chemotherapy were included. Results: A total of 4052 studies were identified, and 15 studies were included in this systematic review. We found that IL-6, IL-1β, and TNF-α were associated with varying degrees of cognitive impairment in breast cancer patients receiving chemotherapy. Conclusion: This systematic review showed a correlation between various cytokines and chemotherapy- associated cognitive decline in breast cancer patients.

Background: A subpopulation of statin users such as subjects with chronic kidney disease (CKD), Human Immune virus (HIV), acute coronary syndrome (ACS), revascularization, metabolic syndrome, and/or diabetes may particularly benefit from pitavastatin pharmacotherapy. Aim: The current systematic review aimed systematically to evaluate the effect of pitavastatin on primary cardiac events in subjects receiving pitavastatin in comparison to the other four statin members. Methods: We conducted a systematic review on phases III and IV of randomized controlled trials (RCT-s, 11 trials) for subjects with primary cardiac events who received pitavastatin. Subjects diagnosed with any type of dyslipidemia (population 4804) and received pitavastatin (interventions) versus comparator (comparison) with the primary efficacy endpoint of minimization of LDL-C and non- HDL-C, had an increase in HDL-C and/or reduction in major adverse cardiac events (MACE, cardiovascular death, myocardial infarction (fatal/nonfatal), and stroke (fatal/nonfatal) and/or their composite (outcomes). The secondary safety endpoint was the development of any adverse effects. Results: In the included trials (11), participants (4804) were randomized for pitavastatin or its comparators such as atorvastatin, pravastatin, rosuvastatin, simvastatin and followed up for 12 to 52 weeks. In terms of the primary outcome (reduction in LDL-C), pitavastatin 4 mg was superior to pravastatin 40 mg in three trials, while the 2 mg pitavastatin was comparable to atorvastatin 10 mg in four trials and simvastatin 20 and 40 mg in two 2 trials. However, rosuvastatin 2.5 mg was superior to pitavastatin 2 mg in two trials. Pitavastatin increased HDL-C and reduced non-HDL-C in eleven trials. Regarding the safety profile, pitavastatin has proved to be tolerated and safe. Conclusion: The FDA-approved indications for pitavastatin included primary dyslipidemia and mixed dyslipidemia as a supplementary therapy to dietary changes to lower total cholesterol, LDL-C, apolipoprotein B (Apo B), triglycerides (TG), and enhance HDL-C. Pitavastatin might be suitable for subjects with diabetes, ACS (reduced revascularization), metabolic syndrome, CKD, HIV, and subjects with low levels of HDL-C. We highly recommend rational individualization for the selection of statin.

Background: Imatinib is one of the tyrosine kinase inhibitors used for the treatment of chronic myeloid leukemia (CML) patients. The exact association of imatinib with anemia in CML patients is still unclear. Aim: The current study aimed to find the prevalence of anemia in chronic myeloid leukemia patients treated with imatinib. Methods: The relevant articles were searched in PubMed, Google scholar, and Clinical trials registries till 31st July, 2021. The quality of the articles was assessed using the Newcastle-Ottawa Scale. The prevalence rate with 95% CI was calculated using StatsDirect Statistical analysis software V.3. Results: A total of 18 studies containing 3537 patients were found relevant for the analysis. The pooled prevalence of anemia in CML was found to be 34% (95% CI: 23%-46%). However, the heterogeneity among studies was found to be high. Conclusion: The monitoring of hemoglobin levels and identifying the cause of anemia are major concerns for the CML patients treated with Imatinib.

Aim: Various research was conducted during the last decade, with inconsistent findings regarding iron death anaemia (IDA) perils vis-à-vis utilization of proton-pump inhibitors (PPIs). Consequently, recent systematic review and meta-analysis were implemented to evaluate IDA-related perils concerning the utilization of proton-pump inhibitors. Methods: The databases of EBSCOhost, PubMed® and Cochrane Central were searched from the research outset until February 28, 2021 purposely to identify all research with objectives that align with the present research investigation. The Newcastle-Ottawa Scale (NOS) was utilized for the evaluation of the research investigation standard. The prime (1º) goal of the research was to gauge IDA peril among users of proton-pump inhibitors (PPI). For data processing, RevMan (Review Manager) version 5.4 was employed. Results: In total, fourteen investigations research was employed in this systematic review and metaanalysis. The combined relative risk of nine research exhibited a numerically consequential interrelation betwixt the utilization of proton-pump inhibitors and IDA peril (RR 2.56 [95% CI 1.43–4.61], p < 0.00001). Contemporary systematic review and meta-analysis examination posit that proton-pump inhibitor consumers are prone to greater peril of coming down with IDA in comparison to non-PPI users. Conclusion: In keeping with the findings of my research, prescriber physicians should exercise caution when prescribing PPIs to individuals taking it for a long time to avoid the peril of IDA. Additionally, their serum iron level should be checked to ensure that proton-pump inhibitors are safe.

Background: H. pylori infection, one of the most prevalent infectious diseases, can cause severe health problems. Therefore, it seems to be crucial to effectively counter the H. pylori infection with a well-tolerated eradication regimen. However, since the discovery of H. pylori, the optimal treatment for this disease is still unclear and remains controversial. Objectives: The present study aims to estimate the efficacy of standard triple therapy for eradicating H. pylori by systematic review and meta-analysis. Methods: We identified randomized clinical trials [RCTs] involving triple therapy PPIAC/M [Omeprazole, Amoxicillin, and Clarithromycin/Metronidazole] in the first-line treatment of H. pylori infection and reported eradication rate through electronic and manual searches in PubMed, ISI, EMBASE, the Cochrane Central Register, and Scopus databases. Data were analyzed using the random effect model, and the Cochrane Q test and I² statistics were used to assess heterogeneity. Statistical analyses were performed using STATA version 12. Results: Forty-seven RCTs [PPIAC: 40 RCTs and PPIAM: 7 RCTs] with 4,938 patients selected as eligible for the final analysis. Per-protocol eradication rate was 80% [95% CI: 74-84] and 80% [95% CI: 73-87] for PPIAC and PPIAM regimens, respectively. The eradication rate for PPIAC and PPIAM regimens was 83% [95% CI: 70%-95%] and 83% [95% CI: 75%-90%] and also 77% [95% CI: 68%- 88%] and 78% [95% CI: 69%-88%], respectively. Based on different treatment durations, the pooled estimates of PP [per-protocol analysis] treatment outcomes were found the highest in 14-day treatment in both regimens. Conclusion: Standard triple therapy PPIAC/M is recommended to be an effective and safe regimen, although adequate data are not available to suggest PPIAC/M as the first-line therapy for H. Pylori infection. Interestingly, our analysis demonstrated that PPIAC/M regimens were more effective in Asian than European populations.

Aim: The aim of the present work was to evaluate the neuroprotective potential of berberine, levetiracetam and their combination in lead acetate-induced neurotoxicity by applying a drug repositioning approach. Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by impairment of memory, disturbances in reasoning, planning, language and perception. Currently, there are only four drugs approved by US-FDA for AD; therefore, there is an extensive need for new drug development. The drug repositioning approach refers to the development of new uses for existing or abandoned pharmaceuticals. Several studies support the neuroprotective abilities of anti-oxidants resulting in neuronal protection against neurotoxins, suppression of oxidative stress and promotion of memory, learning and cognitive functions. Many natural polyphenols are being investigated as a potential therapeutic option for AD. Levetiracetam (LEV), a second-generation antiepileptic drug, is a new molecule that is clearly differentiated from conventional antiepileptic drugs by its pharmacologic properties. LEV also has been previously demonstrated to protect against oxidative stress-induced neurotoxicity in several models of seizures. Berberine (BBR) is an anti-inflammatory and anti-oxidant phytoconstituent. Objective: To study the therapeutic effect of berberine, levetiracetam and their physical mixture in lead acetate-induced neurotoxicity in Swiss albino mice for probable application in the management of Alzheimer's disease. Methods: Neurotoxicity was induced in Swiss albino mice by lead acetate. Behavioural parameters, such as transfer latency time and percentage alternation, were studied using Morris water maze (MWM), Elevated plus-maze test (EPM) and Y-maze for the assessment of improvement in learning and memory. Concentrations of acetylcholinesterase, MDA and GSH in the brain were also estimated. Brain samples were subjected to histopathological studies. Results: Results revealed that the combination of BBR and LEV exhibited a significant neuroprotective effect by decreasing escape latency time and increasing time spent in the target quadrant in MWM. The combination also decreases transfer latency time in EPM and acetylcholinesterase levels in the brain as compared to standard donepezil. Reduced neuronal damage was also confirmed by the histopathological report. Conclusion: Leveteracitam, berberin and their combination resulted in the significant conservation of various behavioural, biochemical, enzymatic and anti-oxidant parameters that were evaluated. The neuroprotective effect of plain leveteracitam and berberin was significantly better than their combination. The anticipated synergism or additive effect was not observed with the combination of leveteracitam and berberin in lead acetate–induced neurotoxicity.