RESEARCH STUDIES ON AYURVEDIC SEDATIVE DRUGS USED FOR THE MANAGEMENT OF ANIDRA (INSOMNIA) Panara Kalpesh and Prof. K. Nishteswar Dravyaguna Dept., IPGT&RA, Gujarat Ayurved University, Jamnagar 1 Charaka’s classification Aswapna Anidra Insomnia Nanatmaja-vata-vikara (ch/su/20) Vata & Pitta-dushti (Su/sha/4) प्रिष्ट Primary निशमत्ति् Secondary Associated symptoms & Consequences • निद्रािाशाद敍गमददशशरोगौरवजम्ृ भिका्| जा蕍य嵍ऱानिभ्रमापम्तििन्द्द्रा रोगाश्च वािजा्|| (A.h./Su/4) • Most of the symptoms can be correlated with symptom of insomnia given by Diagnostic and Statistical manual of Mental disorders IV – Text Revision (DSM IV-TR). 2 Need of Study Current Sedative Drugs = Symptomatic management Drugs Side effects Barbiturates physiological and psychological Benzodiazepines dependence, Drowsiness, dizziness, SSRI's Decreased libido, Depression, liver Tricyclic Antidepressants toxicity…….. In modern medical science, Hypnotics, sedative, anxiolytic, psychotropics are being prescribed for insomnia but they have hazardous adverse effects and their role in curing the disease is very limited. Hence, it becomes imperative to search out for drugs which are safe and effective from natural systems of medicine like Ayurveda that can help the patients of insomnia. 3 Objective • To review classical and non-classical herbs having sedative activity and clinical trials conducted on them Materials & Methods Ayurvedic Classical texts Databases on Medicinal Plants (CCRAS) Reviews on Indian medicinal plants- ICMR A Selection of Prime Ayurvedic Plant Drugs (Sukhadev) Clinical trials (ARD of IPGT&RA and internet database such as Ayush portal, Dhara) 4 Classical Single herbs Pippalimoola powder with Jaggery Powder of Bijapoora leaves with honey (Bhaisajyaratnavali) (Bhavprakash) Ashwagandha powder with sugar & Ghee Application of paste of Bhanga with milk 5 (Nighantuadarsh) of goat on soles (Bhaisajyaratnavali) Sedative Herbs Total 38 herbs have been reported for their sedative activity and among them 30 herbs are classical and 8 are non-classical. 30 + 8 = 38 6 Reported classical herbs n=30 Vacha- Acorus calamus Linn. Bhustrina- Cymbopogon citratus stapf Priyangu- Aglaia diepenhorstii Miq Musta- Cyperus rotundus Linn Kajutaka- Anacardium occidentale Linn. Karanja- Derris india (Lamk.) Puga- Areca catechu Linn. Nirvisha- Delphinium denudatum Wall. Nimba- Azadirachta indica A. Juss Paribhadra- Erithrina indica Lam Brahmi- Bacopa monnieri Linn. Jatamansi- Nardostachys jatamansi DC Sallaki- Boswellia serrata Roxb Kamala- Nelumbo nucifera Gaertn. Punnaga- Calophyllum inophyllum Linn. Tagara- Valeriana Jatamansi Jones Aragwadha- Cassia fistula Linn. Aswagandha- Withania somnifera (Linn.) Devadaru- Cedrus deodara (Roxb.) Dunal Jyotismati- Celastrus paniculatus Willd. Ahiphena- Papaver somniferum Linn Tarkari- Clerodendrum phlomidis Linn. Maricha- Piper nigrum Linn. Shankhpushpi- Convolvulus prostratus Jatiphala- Myristica fragrans Houtt. Forssk Parijata- Nyctanthes arbor-tristis Linn Aparajita- Clitoria ternatea Linn. Bhanga- Cannabis sativa Linn. Mandookaparni- Centella asiatica Linn 7 Vacha- Acorus calamus Linn. • Asarone and β-asarone (active principle of rhizome) possess tranquilizing actions, Among them β-asarone have more powerful actions. (Reviews, vol 1 ICMR) • But, some in vitro and in vivo studies have reported carcinogenic effect of β-asarone. (Singh C., 2001) 8 Long term use # Brahmi- Bacopa monnieri Linn Alcoholic extract of Brahmi (100 mg/kg ): potentiated the thiopental sleeping time in mice and barbiturate hypnosis in albino rats (Reviews, vol 4, ICMR) • Clinical trial (randomized, double-blind, placebo-controlled ) showed that B. monnieri has improved cognitive performance and reduced anxiety. (Carlo Calabrese et al, 2008) Aswagandha: Withania somnifera (Linn.) Dunal Extract Model Methanol extract of the seeds & Produced sedation in mice, dogs, Ethanolic extract of roots monkeys, rabbits and rats A trial (randomized- placebo-controlled, cross-over ) on herbal formulation containing Aswagandha showed that traditional herbal supplements may produce significant benefit to patients suffering from insomnia [onset type] (Faraq NH et al 2003) 9 Jyotismati- Celastrus paniculatus Willd. Part used Model Crude seed oil in a dose of 1 g Produced tranquilizing effect (on adrenaline and amphetamine-induced excitement in mice) Alcoholic extract of the plant in a Potentiated barbiturate sleeping time, (decrease dose of 100 mg/kg body weight acetylcholine and increase catecholamines in brain of albino rats) 10 Shankhapushpi- Convolvulus pluricaulis Choisy Best Medhya Rasayana Drug Plant shows maximum barbiturate hypnosis potentiating activity during spring season. (Mudgal V., 1975) Tagara- Valeriana Jatamansi Jones The hesperidin and methylapigenin are responsible for sedative and sleep- enhancing properties. (Sebastian F. et al.; 2004) 11 Jatamansi- Nardostachys jatamansi DC. Jatamansone (isolated from air-dried rhizomes), sesquiterpenes, valeranone prolonged barbiturate hypnosis and impaired rotarod performance of mice Clinical study with jatamansone reported reduced incidence of aggressiveness and restlessness in insomnia. (Gupta P.D. et al, 1968) Mandookaparni- Centella asiatica Linn. Its tranquillizing activity has been attributed to a triterpene, Brahmoside (Sushma et al, 2011) Clinical study: In double blind clinical trial conducted on 30 mentally retarded children, a significant improvement in both general ability and behavioral pattern was reported. (VM Tyler, 2012) 12 Reported non-classical herbs n= 8 1. Artemisia capillaries Thumb. 2. Canscora decussata Roxb 3. Carvia callosa (Nees) Bremek. 4. Cissus repens Lamk. 5. Artabotrys hexapetalus R.Br. 6. Catharanthus roseus Linn. 7. Diploknema butyracea (Roxb.) 8. Sarpagandha- Rauvolfia serpentina L Sarpagandha- Rauvolfia serpentina L • Reserpine, was used to treat high blood pressure and mental disorders • But it has many dangerous side effects like cancer (American Cancer Society 2002). disappeared 13 Clinical trials • Guda Pippalimoola Yoga (root of Piper longum with jaggery) with milk is found to be very effective in primary insomnia (Kavitha S, 2010) • Combined therapy of Apamargadi Vati with Shirodhara of Kshirabala Taila provided 89.50% relief in sleep quality and 95.27% relief in mood after awakening. (Nirmal Dhamini, 2004) • Tagaradi Kwatha with Shirodhara of Mahisha milk provided highly significant relief in symptoms: sleeplessness, restlessness and it improves total sleep time. (Muralidhar. P. 1999) . Apamargadi Vati : mentioned in Harita Samhita containing Apamarga, Kokilaksha, Kakajangha and Bakuchi . Tagaradi Kwatha : decoction of Tagara, Shankhapushpi, Brahmi, Musta, Aswagandha, Jatamansi, Munnakka, Raktachandana, Parpataka, Kutaki, Dashmula and Amaltasa 14 ….Trials Formulation Effect Dashamoola Shirodhara + Mamsyadi found better in increasing sleep time, Ghrita (Anil Kumar, 2007) sleep quality Tab. Insomrid (herbal formulation highly significant improvement in containing Ashwagandha, Sarpagandha, Primary insomnia Jatamansi, Parsika-yavani and Tagara) (S. Pokharel et al. 2010) Shirobasti (with Tungadrumadi-taila) significant role in relieving the symptoms mentioned in Sahastrayoga (Bina Vansh, of Nidranasha like angamarda, 2008) shirogourava, jadya, glani, bhrama Tagara (Indian Valerian) (Venkatesh A, supportive role in chronic insomnia, 2010) especially in the elderly population. 15 Conclusion • Most of the clinical studies conducted on insomnia reveal that the Shirodhara and herbal formulations, both improved patients individually, but its combined use enhanced the effect therapeutically. This observation support the classical phenomenon mentioned by Acharyas, in the form of holistic management of Anidra i.e. combination of specific procedure, herbal formulation and proper diet regimen. • Like Tab. Insomrid and Tagara Kwatha, new formulations can be also designed basing on Rasapanchaka (pharmaco- dynamics and pharmaco-kinetic principles), Karma (pharmacological actions), scientific activities and safety profile of herbs. 16 Thank you 17.