On the basis of numerous previous studies, the serotonergic system plays a role in the pathogenesis of obsessive-compulsive disorder (OCD) and effective agents in this pathway, such as 5-hydroxytryptophan, can potentially contribute to treatment of patients with this disorder. Evaluating the efficacy of 5-hydroxytryptophan in treating OCD was the aim of the present randomized, double-blind, placebo-controlled 12-week trial. In a 12-week, randomized double-blind study, 60 patients with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of moderate to severe OCD and a Yale–Brown Obsessive Compulsive Scale (Y-BOCS) score of >21 were randomly assigned to receive either fluoxetine plus placebo or fluoxetine plus 5-hydroxytryptophan (100 mg twice daily). All patients, regardless of their treatment group, received fluoxetine at 20 mg/day for the initial 4 weeks of the study followed by 60 mg/day of fluoxetine for the rest of the trial course. Symptoms were assessed using the Y-BOCS at baseline and weeks 4, 8 and 12. General linear model repeated measure showed significant effects for time × treatment interaction on total Y-BOCS (F = 12.07, df = 2.29, P-value <0.001), obsession (F = 8.25, df = 1.91, P-value = 0.001) and compulsion subscale scores (F = 6.64, df = 2.01, P-value = 0.002). 5-Hydroxytryptophan augmentation therapy demonstrated higher partial and complete treatment response rate (P = 0.032 and P = 0.001, respectively) according to the Y-BOCS total scores. The results of this study confirm that 5-hydroxytryptophan may be effective as an augmentative agent in treatment of moderate-to-severe OCD.
For years, the low productivity of drug discovery has been a dilemma. More surprising has been the fact that our current productivity is far lower than 70 years ago. How could our ancestors, from thousands to a hundred years ago, discover drug-leads, like opioids, that we still rely on, yet we, with incomparably advanced technologies and knowledge, are desperate to do so? Based on massive evidence, I argue that the primary cause is the dominance of the reductionist “rational” drug discovery which tries to reduce the effects of molecules on highly complex phenotypes to single variables: affinity toward single hypothesized “targets.” Detailed analysis of the discovery origins of all currently used small-molecule drugs shows that, despite decades of dominance, only about 9% of them have “target-based” origins. More conclusively, even this minimal contribution depends on luckiness rather than sheer “rationality” as these “target-based” drugs have numerous “off-target” therapeutic mechanisms. These observations reveal the real-world inefficacy of “rational” drug discovery and imply that currently, powerful assets like artificial intelligence and deep learning are being employed by an ultimately inefficient paradigm.
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. Sever cognitive and memory impairments, huge increase in the prevalence of the disease, and lacking definite cure have absorbed worldwide efforts to develop therapeutic approaches. Since many drugs have failed in the clinical trials due to multifactorial nature of AD, symptomatic treatments are still in the center attention and now, nootropic medicinal plants have been found as versatile ameliorators to reverse memory disorders. In this work, anti-Alzheimer’s activity of aqueous extract of areca nuts (Areca catechu L.) was investigated via in vitro and in vivo studies. It depicted good amyloid β (Aβ) aggregation inhibitory activity, 82% at 100 µg/mL. In addition, it inhibited beta-secretase 1 (BACE1) with IC50 value of 19.03 µg/mL. Evaluation of neuroprotectivity of the aqueous extract of the plant against H2O2-induced cell death in PC12 neurons revealed 84.5% protection at 1 µg/mL. It should be noted that according to our results obtained from Morris Water Maze (MWM) test, the extract reversed scopolamine-induced memory deficit in rats at concentrations of 1.5 and 3 mg/kg.
Despite the considerably high prevalence of cutaneous warts, no optimally effective and safe treatment is available. Leaves of date palm (Phoenix dactylifera L.; Arecaceae) have long been used in Iran's folk medicine as a remedy for warts. To assess the state-of-the-art evidence on using P. dactylifera L. for warts, we conducted a systematic review using CINAHL (via EBSCO), Embase, Medline (via PubMed), ProQuest, Scopus, and Web of Science. We conducted an open-label uncontrolled pilot clinical study to evaluate the efficacy and safety of a proprietary topical date palm leaf-based ointment for the treatment of various types of nongenital warts. This study consisted of an 8-week treatment phase and a 4-week follow-up phase. The assessed outcomes included complete clearance, patient satisfaction (on Likert scale), and the occurrence of any adverse effect. The systematic review demonstrated that the effects of date palm on warts have not been scientifically studied. Thirty patients entered the study with a mean age of 29.5 years (SD = 14.04); among which 17 were female and 13 were male. The patients presented diverse types of warts: verruca vulgaris 15 (50%), plantar 9 (30%), plane 2 (7%), periungual 2 (7%), and warts at multiple sites 2 (7%). In this trial, 19 patients (63.3%) experienced complete clearance and 5 patients (16.6%) experienced partial clearance. Eight patients (26.67%) dropped out during the study. 21 (70%) patients were very satisfied (score on Likert scale = 5) while 1 (3.3%) patient with partial clearance was somewhat satisfied (score on Likert scale = 4). No adverse effect was observed. The results of this pilot study indicate that the date palm leaf-based ointment is a promising treatment whose efficacy and safety should be further investigated in a randomized controlled clinical trial.
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