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FUTURE ACMES OF BHANGA (Cannabis sativa L.): AYURVEDA BACKGROUND AND CONTEMPORARY RESEARCHES

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ABSTRACT


Vijaya (Bhanga) or Cannabis sativa L. is a reputed plant ascribed in traditional system of medicine since centuries. Ayurveda enumerates the therapeutic use of Vijaya in the management of Shool (pain), Grahani rog (Irritable bowel syndrome), Nidra-naash (Insomnia), Jwara (Fever), Agnimandya (loss of appetite), Prameha (Diabeties) etc. Due to certain illegalities and drug abuse, the same has never received any recognition in the past decades despite hundreds of benefits. Recent studies suggest that the appropriate and ethical use of cannabis can help in treating number of diseases i.e. IBS, Epilepsy, multiple sclerosis, insomnia, anxiety and degenerative diseases. It has been found that various phytochemicals mainly cannabinoids are responsible for the therapeutic activity of Bhanga. Thus the salient observations of Bhanga are gathered from classical Ayurvedic and contemporary researches to highlight the therapeutic potential of the novel drug, Cannabis sativa in management of few important ailments, i.e. IBS, epilepsy and cancer and associated symptoms of ailments i.e. pain, insomnia etc.

BHANGA IN AYURVEDA LIERATURE:


Bhanga is one of the plant origin drug which has found its place in Ayurveda classics from medieval period due to its exceptional properties and actions. Since then, the detailed aspects of Bhanga has been explored including purification methods, therapeutic uses and contra-indications. Around 40 synonyms of Vijaya has been mentioned owing to its morphological characteristics i.e, Samvidmanjari (the drug having potent inflorescence), pharmacological properties i.e. Bahuvadini (it causes verbosity), Madini, Mohini, Ganja, Matulani (excessive use may cause delirium), Ananda (having soothing effect) and many more. Bhanga, Charas and ganja are three forms of its usage being Bhanga (dried leaves of plant) the most common (Acharya R. et al., 2015). It has tikta rasa, ushna virya, laghu tikshna gunas and katu vipaka. It alleviates kapha and vata doshas, increases pitta having dipana, pachana, ruchya, grahi, madkari and vyavayi properties. Rasshastra texts describes Vijaya as Upavisha vargaas the excessive use of the herb manifests toxic effects on the CNS. Sharangdhar also mentions this drug under madkaari dravyas which affects the buddhi (CNS) due to virtue of its tikshna, ushna properties and prabhav. It also increases agni (digestive fire) and pitta because of tikta rasa and ushna virya. It has been described for the treatment of various diseases which includes Nidranasha(insomnia), Atisara (diarrhea), Grahani rog (IBS), Mandagni(loss of appetite) (B.P.Ci.1.325), Kushtah(skin disorders) (VM.51.56-57 also SB.4.832), Prameh(Diabeties mellitus), Unmada( anxiety neurosis), Ardavabhedak(hemicrania), Nadi daurbalya (neurological weakness), Shosh (emaciation) and Dhanusthambha (stiffness of back). Besides its wide range of therapeutic utility, highest number of formulations is advised in Grahani (30), followed by Jwara (17), Atisara (9), Agnimandya (7) and Prameh (6) (Acharya R. et al., 2015).

CONTEMPORARY VIEW ON BHANGA:

Cannabis sativa is a dioecious and occasionally monoecious plant which belongs to cannabinaceae family and is found in regions ranging from sea level to the temperate and alpine foothills of the Himalayas. In the last few years, use of cannabis or medical marijuana is gaining momentum due to its wide range of therapeutic potential. According to WHO, it is the most commonly cultivated, trafficked and abused drug globally. Cannabis has bad reputation as it is the common psychotic and recreational drug. However, it has been used in folklore practices since ages as medicine, fuel source, source of paper, building materials and textiles (Small and marcus,2002). Marijuana is prepared from the dried flowering tops and leaves; hashish consists of dried cannabis resin and compressed flowers (Ashton, 2001) which are consumed by humans. Wide range of complex phytochemicals namely cannabinoids, terpenes and phenolic compounds have been found in cannabis which are responsible of its multipurpose therapeutic applications as well as psychotropic effects. Carbohydrates, fatty acids and their esters, simple amides, amino acids, phytosterols, phenolic compounds are also identified. Antibacterial (G. appendino, 2008), antimicrobial (Esra M. M. ali et al. 2011), analgesic and anti-inflammatory activities (formukong EA et al 1988) have also been reported. It is also used in the management of pain, chemotherapy-induced nausea and vomiting among cancer patients (Machado Rocha et al., 2008), post-traumatic stress disorder, epilepsy, cachexia, degenerative neurological conditions (CDPHE,2016; OHA-2016). and for relief of spasticity in multiple sclerosis patients (Sastre-Garriga et al., 2011) Pre-clinical and clinical studies conducted in recent era suggest its efficacy and medicinal importance, which is mainly due to the presence of cannabinoids. The Endocannabinoid system (eCBD) which consists of endogenously produced cannabinoids, receptors and metabolizing enzymes have been found in the various part of the human body including central nervous system, gastrointestinal system, connective tissues and immune cells. (M.B. Bridgeman,2017) plays an important role in the physiological and pathological processes. It acts as protective system against the pathology of certain diseases like IBS, migraine, anorexia, multiple sclerosis and schizophrenia. Lack or abnormalities in eCBD system ramificates these diseases. Hence, exogenous cannabinoids derived from cannabis sativa can act as potent medicine.

Phytochemicals


Delta 9 tetrahydracannabinol is the primary active cannabinoid present in cannabis sativa which is responsible for its pyschotic effects. It is a potent analgesic, antiemetic, anxioltic, appetite stimulant, hypnotic, antipyretic and anti-spastic agent (Jeffrey K Aronson 2014). The other important cannabinoid constituent of current interest is cannabidiol (CBD)The extract of Cannabis sativa contains more than 60 terpeno-phenolic compounds namely phytocannabinoids, cannabidiol and cannabinolic acid. Non-cannabinoid compounds are also found which are 30 times more efficacious than aspirin in pain. Proteins, amino acids, glycoproteins, sugars, ketones, aldehydes, fatty acids, steroids, flavonoids and vitamins are also identified. (Asati A. et al, 2017)

FUTURE PROSPETCS OF BHANGA FOR MEDICAL SCIENCE:


Pain
Pain is a crucial aspect of the body’s defence mechanism and it is a part of a rapid warning relay instruction the motor neurons of the central nervous system to minimize physical harm. (Emanuel LL et al, 1999; 1-37). In pathophysiology of neuropathic and inflammatory pain, receptors CB1 and CB2 along with prostaglandins, serotonin, bradykinin and epinephrine get involved in the mediation of inflammatory response. Cannabinoids present in cannabis are CB1 and CB2 agonist whereas Non cannabinoid compounds inhibit the release of prostaglandins and is 30 times more potent than aspirin. Preclinical and clinical studies have also been conducted which proves cannabis to be a promising analgesic. Thus, for quick and effective pain management, Bhanga may be used. The references for use of Bhanga in pain management can be retrieved from medieval Ayurvedic classics. Its rational use as a single or adjuvant drug candidate may be done in present scenario to relieve agony in a wide spectrum of diseases.

IBS
Irritable bowel syndrome or disease is characterized by abdominal pain, diarrhoea, constipation or a combination of both diarrhoea and constipation, mucus discharge along with stools and changes in the form (appearance) of stools. (Azpiroz F, Dapoigny M,2000). It is one of the most prevalent gastrointestinal problem affecting globally. Inflammation and hypersensitivity of the colon in response to stress, food, physical stimulant and idiopathic factors are of primary concern in the pathogenesis of IBS. Receptors CB1 and CB2 are found in all the layers of intestinal sections, including the mesenteric and sub mucosal plexus and the epithelium responsible for inflammatory response mediation. Cannabinoids by their agonist effects on CB1 and CB2 have proinflammatory effects and helps in the reduction of inflammation of intestinal mucosa which helps relieve the disease (Waseem Ahmed ,2016). In Ayurveda, Bhanga is the key plant for effective management of troublesome disease IBS.

Epilepsy
Epilepsy affects about 50 million people throughout the world and is especially common in childhood and in elderly people. “Epilepsy” is the condition of recurrent, unprovoked seizures which has numerous causes, each reflecting underlying brain dysfunction (Shorvon et al. 2011). Root cause of epilepsy may either be at circuit level primarily abnormal synaptic transmission or at the receptor level. It has been found that cannabinoid receptors CB1 and CB2 are present in the central nervous system and are termed as endogenous cannabinoids. Control in Synaptic transmission and regulation of the rate of neuronal firing are vital role of CB1 and CB2 receptor respectively. Activation of these receptors with cannabinoids results in the inhibition of synaptic transmission along with glutamate release (Zou S. et al,2018). Various studies suggest that the therapeutic use of cannabinoids targets the signalling pathway which results in epileptic seizures.

Cancer

WHO defines cancer as the uncontrolled growth and spread of cells which can affect almost any part of the body. The growths often invade surrounding tissue and can metastasize to distant sites. The global cancer burden is estimated to have risen to 18.1 million new cases and 9.6 million deaths in 2018. Inflammatory conditions and carcinogenesis share same common pathways such as proliferation, increased survival of cells and migration where cytokines and growth factors play an important role. In the formation of tumour, inflammatory mediators regulate a number of proinflammatory responses through inhibition of protective immune response. (F. pellati et al ,2018). The presence of CB1 and CB2 receptors on immune cells suggests their important role in the regulation of the immune system. By targeting the ECS, cannabinoids affect many essential cellular processes and signalling pathways which are crucial for tumour development. Experimental studies using cancer cell lines and genetically engineered mouse models reveals that the activation of CB receptors by cannabinoids is antitumorigenic in most cases mainly breast, prostate and glioma cancer cell lines. it inhibits tumour cell proliferation, induces apoptosis in vitro, blocks angiogenesis and tumour invasion/metastasis in vivo (Darris et al, 2019). Derivatives from Bhanga, cannabinoids and cannabis-based pharmaceutical drugs have been the subject of intensive research for their potential antitumor activity.

CONCLUSION

Bhanga or Cannabis sativa L. has tremendous potential in the field of medicine which was described hundreds of years ago in Ayurvedic scriptures. The use of Vijaya is described in the management of Shool (pain), Grahani (IBS) and Apasmar (Epilepsy) in different Ayurvedic texts. The pharmacodynamics of the drugs may be explained on the basis of pharmacodynamics attributes i.e. Rasa, Guna, Veerya, Vipaka and Prabhava of the plant. The dosha dominance in Shool (pain) is Vata which get alleviated by Ushna virya of Bhanga. One of the important properties of the drug is Grahi, deepana and pachana due to its tikta rasa and ushna virya. Due to this activity, it is very beneficial in the management of Grahani and Sangrahani (vata-kaphaj). Ushna, tikshna and vyavayi gunas helps it to get absorbed efficiently in the body specially Srotas. As Apasmar is a disease of Manovaha-srotas, these Gunas help pacifies the doshas infiltrated in these srotas. The contemporary researches reveal that the various phytochemicals or cannabinoids mainly delta 9 tetrahydrocannabinol and CBD (cannabinol) are the most promising compound present in Cannabis sativa which are responsible for its therapeutic potential. Cannabinoids derived from cannabis acts as CB1 and CB2 agonists and activate these endocannabinoid receptors where the pathology exists whether in the Gastrointestinal system, CNS or Immune system. Anti-inflammatory, Anti-oxidant, Anti-bacterial and anti-microbial activities have also been identified. Bhanga (Cannabis sativa) can be a promising drug in future however few issues regarding its legalization, availability, quality and safety should be in consideration. Moreover, further extensive research should be done in order to enlighten about the use and implication of cannabis in diseases described in Ayurveda along with its pharmacokinetic and pharmacodynamic studies.

References:
Acharya R. et al. (2015) ‘Vijaya (Cannabis sativa Linn.) and its therapeutic importance in Ayurveda; a review’ J.D.R.A.S. Vol.1 No.1 pp 1-12.
Ahmed W. et al. (2016) ‘Therapeutic use of cannabis in Inflammatory Bowel Disease.’ Gastroenterology & hepatology volume 12, issue 11
Ashton, (2001) ‘Pharmacological and effects of cannabis: A brief review’ British Journal of Psychiatry 178,101-106
Appendino G., (2008) ‘Antibacterial cannabinoids from Cannabis sativa:A structure-activity study’ J. Nat. Prod. 71,1427-1430
Asati A. et al, (2017) ‘Pharmacological and phytochemical profile of Cannabis sativa L.’ Int. J. Ind. herbs drugs, Vol-2, Issue 2
Azpiroz F, Dapoigny M (2000) ‘Nongastrointestinal Disorders in the Irritable Bowel Syndrome’ S. Karger AG, Basel Vol.62, No.1
Bhavprakash Samhita 1.325
CDPHE,2016; OHA-2016
Darris et al, (2019) ‘Cannabinoids in cancer treatment: Therapeutic potential and legislation’ Bosnian Journal of Basic Medical Sciences

Esra M. M. ali et al. (2011) ‘Antimicrobial Activity of Cannabis sativa L.’ Chinese Medicine, 2012, 3, 61-64
Formukong EA et al (1988) ‘Analgesic and Anti-inflammatory activity of constituents of Cannabis sativa L.’ SpringerLink pages361–371(1988)
F. Pellati et al (2018) ‘Cannabis sativa L. and Non-psychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer’ Hindawi BioMed Research International Journal
Jeffrey K Aronson (2014) ‘Plant Poisons and Traditional medicines’ Elsevier manson’s tropical infectious diseases (23rd edition)
M.B. Bridgeman (2017) ‘Medicinal Cannabis: History, Pharmacology,And Implications for the Acute Care Setting’ P & T Vol. 42 No. 3

Sastre-Garriga et al. (2011) ‘THC and CBD oromucosal spray (Sativex®) in the management of spasticity associated with multiple sclerosis’ Expert Review of Neurotherapeutics Volume 11, 2011
Shorvon et al. (2011) ‘The etiologic classification of epilepsy’ Epilepsia journal

Small and marcus (2002) ‘Hemp: A new crop with new uses for North America’ p. 284–326. In: J. Janick and A. Whipkey (eds.)
VrindaMadhav.51.56-57
Zou S. et al (2018) ‘Cannabinoid Receptors and the Endocannabinoid System: Signalling and Function in the Central Nervous System’ Int. J. Molecular Science

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