Effect of Withania somnifera (L.) Dunal aqueous root extract on reinstatement using conditioned place preference and brain GABA and dopamine levels in alcohol dependent animals.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal (WS), a known'Rasayana' (rejuvenating agent) as per Ayurveda is prescribed to promote health, to increase longevity and to hasten recovery in disease convalescent stages. WS has demonstrated protective effect on alcohol dependence and withdrawal anxiety in previous experimental studies. AIM OF THE STUDY: To evaluate effect of WS on conditioned place behavioral paradigm (model of relapse) and on GABA and dopamine levels in critical brain areas in alcohol dependent animals. METHODOLOGY: Following Animal Ethics Committee permission, the mice (n = 24) were divided into the following study groups for experiment 1: 1 -distilled water (vehicle control), 2 -WS and 3 -Naltrexone. They were conditioned on conditioned place preference (CPP) using alcohol (2 gm/kg)/saline (1 ml) administered intraperitoneally for 8 days. WS and Naltrexone were administered during the period of extinction (6-8 days). Effect of WS (650 mg/kg) on reinstating behaviour of mice (time spent in alcohol paired compartment) primed with alcohol injection was noted. In experiment 2, effect of WS (450 mg/kg/) on GABA and dopamine levels in the midbrain, striatum and cortex (ng/gm) were measured in alcohol dependent rats (n = 24) following the first phase of standardisation assay (n = 36). The rats were made alcohol dependent for 15 days (intermittent access model) and WS was administered concurrently. GABA and dopamine levels were measured on Day 16. RESULTS: WS group showed decrease in time spent in alcohol paired compartment alike Naltrexone and it differed significantly compared to the distilled water control group (p < 0.05) Alcohol-dependent rats showed significant decrease in GABA and increase in dopamine levels vs distilled water in the midbrain, striatum and cortex. WS and Naltrexone administration showed rise in GABA and fall in dopamine in all the isolated brain parts in the respective groups (p < 0.05 vs alcohol treated group). CONCLUSION: Withania somnifera protected animals from relapse and showed beneficial effects on the brain neurotransmitters involved in alcohol dependence. The study provides substantial evidence for its potential application in alcohol use disorder.

Over-the-counter medicines: Global perspective and Indian scenario.

Patients often approach a pharmacist instead of visiting a doctor for minor ailments such as cough, cold, allergies, pain, fever, acidity, diarrhea, and skin-related conditions. Purchase of specific medicines over the counter is legally recognized in most countries. 'Over-the-Counter (OTC) Medicines' means drugs which are legally allowed to be sold by pharmacists without need for a prescription. The term does not have a legal definition in India. Technically, drugs are OTC unless they are specifically stated as prescription only drugs. OTC drugs allow faster and cheaper access to healthcare; however, their misuse and adverse health effects cause concerns. This article describes concept of OTC medicines and practices in India against the background of globally prevalent regulations and practices. A recognized category of OTC medicines by law, patient awareness programs, and support of pharmacists and pharmaceutical companies are required to optimize the use of OTC medicines in India.

Projects not initiated by investigators: a retrospective analysis of the queries raised by the institutional ethics committees of a teaching hospital.

BACKGROUND: Some investigators on receiving queries from Institutional Ethics Committee (IEC), either leave the queries unanswered or withdraw their studies. The present study was conducted to assess the queries raised by two IECs after reviewing studies that were not initiated and to identify reasons for the same. Clinical Trials Registry-India (CTRI) website was checked to review approval status of these studies at other sites. MATERIALS AND METHODS: A retrospective analysis of studies (submitted between January 2006 and December 2011) not initiated by investigators on receiving queries from IECs were identified. The nature of of these studies: whether sponsored (pharmaceutical industry (pharma)/government/investigator initiated), single-centre/multi-centric, and queries raised were analyzed. Status of multi-centric trials; not initiated at our site was checked at CTRI. Data was analyzed using descriptive statistics. RESULTS: A total of 219/2075 (11%) studies were not initiated. The proportions in pharma sponsored, investigator initiated, and government sponsored were 33%. 7.4%, and 8%, respectively. Out of a total of 1676 queries, the maximum queries were related to ethics (42%) and the least were administrative (7%). The largest proportion of queries in the pharma studies was ethical (47%), whereas majority were scientific queries (45.5%) for the investigator initiated studies. Twenty-one of the 94 multi-centric studies not initiated at our site were found registered at the CTRI and were ongoing or completed at 2-55 sites. CONCLUSION: Inability of investigators to defend studies due to lack of good clinical research practice (GCP) and research methodology training or unwillingness of sponsors to comply with local IEC requirements could be potential reasons for studies remaining uninitiated. Continued GCP training of investigators and IEC members and development of uniform ethical review standards across IECs are strongly recommended.