Acute Adverse Effects of Therapeutic Doses of Psilocybin: A Systematic Review and Meta-Analysis.

Importance: Psilocybin has been studied in the treatment of depression and anxiety disorders. Clinical studies have mainly focused on efficacy, with systematic reviews showing favorable efficacy; however, none have primarily focused on psilocybin safety. Objective: To evaluate the acute adverse effects of psilocybin at therapeutic doses in the treatment of depression and anxiety. Data Sources: MEDLINE via PubMed, Web of Science, and ClinicalTrials.gov were searched for publications available between 1966 and November 30, 2023. Study Selection: Randomized, double-blind clinical trials that reported adverse effects of psilocybin in patients treated for depression and anxiety were screened. Data Extraction and Synthesis: Data were independently extracted by 2 authors and verified by 2 additional authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The inverse variance method with the Hartung-Knapp adjustment for the random-effects model was used, with a continuity correction of 0.5 for studies with 0 cell frequencies. Sensitivity analysis was conducted by sequentially removing 1 study at a time to assess the robustness of the results. Main Outcomes and Measures: The primary outcome was considered as the adverse effects of psilocybin at high and moderate (ie, therapeutic) dose regimens and compared with placebo, low-dose psilocybin, or other comparator in the treatment of depression and/or anxiety. Results: Six studies met the inclusion criteria with a total sample of 528 participants (approximately 51% female; median age 39.8 years; IQR, 39.8-41.2). Seven adverse effects were reported in multiple studies and included in the analysis. Among these, headache (relative risk [RR], 1.99; 95% CI 1.06-3.74), nausea (RR, 8.85; 95% CI, 5.68-13.79), anxiety (RR, 2.27; 95% CI, 1.11-4.64), dizziness (RR, 5.81; 95% CI, 1.02-33.03), and elevated blood pressure (RR, 2.29; 95% CI, 1.15- 4.53) were statistically significant. Psilocybin use was not associated with risk of paranoia and transient thought disorder. Conclusions and Relevance: In this meta-analysis, the acute adverse effect profile of therapeutic single-dose psilocybin appeared to be tolerable and resolved within 48 hours. However, future studies need to more actively evaluate the appropriate management of adverse effects.

Analgesic and Sedative-Hypnotic Potentiality of Crude Methanolic Extract of Gomphandra tetrandra (Wall.) Sleumer Leaves.

Objectives: Gomphandra tetrandra (Wall.) Sleumer (leaves) belonging to the family Stemonuraceae was investigated for preliminary phytochemical screening and evaluating their pharmacological activities in various pharmacological models. Materials and Methods: The crude methanolic extract was screened with different chemical reagents for the qualitative detection of different phytochemical groups. The peripheral analgesic function was determined using the acetic acid-induced writhing procedure and sedative-hypnotic behaviors were assessed using hole-board, open field, and hole-cross tests using different doses of the extract (200 mg/kg and 400 mg/kg body weight). Results: Phytochemical screening revealed that methanolic extract of G. tetranda leaves contains steroids, gums, mucilages, phytosterols, carbohydrates, and flavonoids. The crude methanolic extract at 200 mg/kg and 400 mg/kg doses showed statistically significant activity in acetic acid-induced writhing inhibition test with 60% (p<0.01) and 76.47% (p<0.01) inhibition, respectively, compared to control. The extract also had dose-dependent substantial (p<0.01) sedative-hypnotic activities compared with diazepam in the hole-board, open field, and hole-cross tests. Conclusion: It may be assumed that the methanolic leaf extract of G. tetrandra possesses a strong possibility of having analgesic and sedative-hypnotic activity due to the presence of bioactive compounds in its leaves. Moreover, observed results have opened a new era of in-depth research to discover the possible mechanism of analgesic and sedative-hypnotic activity.

Prevalence of Covid-19 Associated Symptoms, Their Onset and Duration, and Variations Among Different Groups of Patients in Bangladesh.

Objective: This study aimed to assess the prevalence, onset, and duration of COVID-19 associated symptoms, hospitalization, and recovery time from the infection in Bangladesh. Methods: A retrospective study was designed adopting the snowball sampling technique (n = 439). The association of gender, age, and comorbidity on COVID-19 associated complications was determined using chi-square and binary logistic regression analysis (p < 0.05). Result: Fever, exhaustion, cough, loss of taste, sore throat, body ache, and hair-loss were prevalent among more than 50% of the participants and developed within fourth days in above 90% of the patients. Shortness of breath was significantly higher in males (χ2 = 5.671; OR 1.641). Significant comorbidity association on the shortness of breath (χ2 = 40.119; OR 2.564), vomiting (χ2 = 4.422; OR 1.018), and loss of speech (χ2 = 17.299; OR 3.430) was observed. Patients (>40 years) exerted higher association in shortness of breath (χ2 = 24.083; OR 2.901). Age and comorbidity were significantly associated with COVID-19 associated hospitalization (χ2 = 16.890 and χ2 = 23.638, respectively) and recovery time (χ2 = 12.870 and χ2 = 26.924, respectively). Conclusion: The study suggests that the hospitalization rate increased for older (>40 years) and comorbid patients. Comorbid patients demonstrated higher susceptibility to have shortness of breath, vomiting, loss of speech, and confusion, whereas male patients showed significant increase in the prevalence of sore throat, loss of smell, and vomiting compared to female patients.

In vivo and in silico evaluation of antinociceptive activities of seed extract from the Holarrhena antidysenterica plant.

The objective of the study was to investigate the analgesic activity of seeds extracted from the Holarrhena antidysenterica plant (Family: Apocynaceae). The seeds of H. antidysenterica were extracted with pure ethanol and administered to the experimental Swiss albino mice at three different doses (50, 100, and 150 mg/kg body weight) in pain models. Peripheral analgesic activity was evaluated using the acetic acid-induced writhing test, and heat-induced (hot plate and tail immersion test) pain models were applied for central anti-nociceptive activity evaluation. Formalin induced licking test was applied to evaluate both peripheral and central anti-nociceptive activity on mice. Computational studies were performed by Schrödinger Maestro v10.1 for molecular docking and the SwissADME online server for ADME prediction of compounds. In acetic acid-induced writhing test, dose-dependent reduction of writhing response was observed with 43.94% (p < 0.001) writhing inhibition at 150 mg/kg dose compared to standard 60.98% (p < 0.001). 150 mg/kg caused a maximum decrease in licking and biting time in both early and late phases of the formalin-induced licking test (71.2 ± 5.67, p < 0.05, and 36.6 ± 5.62, p < 0.01 respectively). In both tests of central analgesic activity, the extract also showed dose-dependent anti-nociceptive activity. In the hot plate method, the highest %MPE was 67.39 (p < 0.001) at 30 min at 150 mg/kg dose, which was even better than the standard drug. In the case of the tail immersion method, the highest %MPE was 69.84 at a dose of 150 mg/kg at 30 min (p < 0.001). In molecular docking study, Conimine, Conarrhimin, Conessine, and Funtudienine showed the best binding affinities against the COX-1 enzyme. The study indicates that the ethanolic seed extract of H. antidysenterica has the strong potentiality of having central analgesic activity and moderate peripheral analgesic activity due to the presence of bioactive compounds in its seeds.

In vivo analgesic, antipyretic and anti-inflammatory potential of leaf extracts and fractions of Eria javanica.

Background The objective of the study was to evaluate the antinociceptive, antipyretic and anti-inflammatory activities of ethanolic extract, methanolic extract and n-hexane and chloroform-soluble fractions of methanolic extract of Eria javanica leaves in animal model (rat and mice). Methods The anti-nociceptive potentials of the extracts were studied using the acetic acid-induced writhing test in mice and the antipyretic activity was investigated using yeast-induced pyrexia in rats. Anti-inflammatory activity test was done on rats at a dose by using carrageenan-induced paw edema test. Results In acetic acid-induced writhing inhibition study in Swiss albino mice, the crude methanolic extract at 200 mg/kg and 400 mg/kg doses and the n-hexane soluble fraction of crude methanolic extract at 400 mg/kg showed statistically significant activity with 53.21 % (p<0.001), 50.36 % (p<0.001) and 67.86 % (p<0.001) inhibition respectively compared to control. The crude ethanolic extract showed statistically significant antipyretic activity from 1 hours and onwards after administration at doses of 200 mg/kg body weight (p<0.005 at 1st hour and p<0.001 at 2nd, 3rd and 4th hour respectively) and 400 mg/kg body weight (p<0.05 at 1st hour and p<0.001 at 2nd, 3rd and 4th hour respectively). The crude methanolic extract showed statistically significant antipyretic activity from 2 hours and onwards at 400 mg/kg body weight (p<0.05 at 2nd hour and p<0.001 at 3rd and 4th hour respectively) and 200 mg/kg body weight dose showed statistically significant antipyretic activity from 3 hours and onward(p<0.001) in Brewer's yeast-induced pyrexia test in albino Wister rats. In carrageenan-induced rat's paw edema test, crude methanolic extract showed statistically significant anti-inflammatory activity from 2nd hour and onwards. The chloroform-soluble fraction of methanolic extract also showed significant activity from 1st hour onwards. Conclusions This study thereby indicates that leaves of E. javanica possess peripheral analgesic, antipyretic and anti-inflammatory activities and therefore a suitable candidate for further study.