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A BRIEF REVIEW ON CANNABIDIOL (CBD)

A BRIEF REVIEW ON CANNABIDIOL (CBD) IJBPAS, June, 2022, 11(6): 2609-2618 ISSN: 2277–4998 1 1* 1 1 1 2 DAS M , BHATTACHARJEE M , SARMA M , PAUL DC , SAIKIA D AND SAIKIA AP 1: Department of Biotechnology, Assam downtown University, Sankar Madhav Path, Gandhi Nagar Pin-781068, Guwahati Assam 2: Department of Computer Science, Assam downtown University, Sankar Madhav Path, Gandhi Nagar Pin-781068, Guwahati Assam Corresponding Author: Dr. Minakshi Bhattacharjee:minakshibhattacharjee2007@gmail.com th th th st Received 18 June 2021; Revised 19 Aug. 2021; Accepted 18 Aug. 2021; Available online 1 June 2022 https://doi.org/10.31032/IJBPAS/2022/11.6.6046 ABSTRACT The present review focuses on cannabidiol (CBD) which is a cannabinoid derived from cannabis. Cannabidiol is non-toxic in comparison to delta-9-tetrahydrocannabinol (THC). Cannabidiol is non-psychoactive in comparison to THC. It is found in both the species of the cannabis plant, Cannabis sativa, and Cannabis indica but cannabidiol percentage is higher in Cannabis.sativa. The cannabidiol content in Cannabis sp can be determined by spectrophotometric assays and Liquid chromatography -Tandem Mass spectrometry (LC- MS). The general pharmacology is discussed, how the cannabidiol binds to the CB1 and CB2 receptors of the central nervous system. The antioxidant activity of cannabidiol and its implementation to prevent disease associated with redox imbalance and inflammation. Here, we have discussed how cannabidiol is related to lung cancer, breast cancer, arthritis. Nowadays CBD combined marketed authorized products are also discussed here like ARVISOL, Boheco Hemp seed oil. Keywords: Cannabidiol, North East India, Medicinal Property IJBPAS, June, 2022, 11(6) Das M et al Review Article INTRODUCTION Cannabidiol (CBD) is a chemical compound inhibits cancer cell invasiveness and derived from the cannabis plant that belongs metastasis. CBD has broad therapeutic to the cannabinaceae family of plant properties across a range of neuro- species. Isolation of first natural cannabinoid psychiatric disorders, stemming from diverse as CBN to be obtained in pure form by Wood central nervous system actions [2]. and colleagues in Cambridge in 1896 [1]. Studies have shown tetrahydrocannabinol Cannabis is in use for the last thousands of (THC) is the main factor responsible for the years for fiber, nutritional seed oil, and effect of cannabis, but several reports have medicinal use. In India, Uttara-khand state demonstrated that other cannabinoids government has permitted cultivation of including CBD have pharmacological hemp crop, a rich source of high-quality activity [3]. The antagonism of the effect of fiber, and a host of medicinal THC when both CBD and THC are use. Cannabidiol has had gained a major administered simultaneously to animals and interest of study over the past few years ago. humans. They concluded that although CBN Abundant literature is available since 2008 increased the effect of THC in certain over various search engines. Cannabidiol is psychophysiology but these modulations the phytocannabinoids of the cannabis plant; were not significant enough. In neurological it is one of the major cannabinoids of aspects, CBD is a cannabinoid 1 receptor cannabis out of 113 identified (CB1) negative allosteric modulator, is a cannabinoids. With the correct structure of partial agonist of dopamine D2 high receptor Cannabidiol as CBD later was discovered early in sub-type and it increases anandamide (AEA) the year 1940 [1]. CBD accounts for up signaling, possibly through inhibition of the to 40% of plant extracts. CBD devoid of AEA catabolic enzyme, fatty acid amide psychoactive activity rather than tetrahy- hydrolase (FAAH) [4]. drocannabinol besides, CBD has analgesic, anti- Chemistry inflammatory, antineoplastic and chemo- As per “Cannabidiol (CBD) Critical Review preventive activities. CBD can modulate Report (2018)”, the IUPAC Name of endoplasmic reticulum stress, cannabidiol is 2-[(6R)-3-methyl-6-prop-1-en-2- AKT/Motor signaling, thereby activating aut- ylcyclohex-2-en-1- yl]-5-pentylbenzene-1,3-diol. ophagy and promoting apoptosis. CBD Chemical structure- IJBPAS, June, 2022, 11(6) Das M et al Review Article and wide-leaflet drugs are found under this taxonomy. Analytical detection of CBD includes the following methods: a) Spectrophotometric determination (plant sample) Cannabidiol needs alkaline medium to Figure 1: Chemical structure of cannabidiol (Adams et react with 2, 4-dinitrophenol. The absorbance al. 1940) peak is at 500 nm. The detectable titer is Molecular formulae- C21H30O2 0.1 ug/10ml [5]. Molecular weight-314.469 g/mol b) Liquid Chromatography- Melting point: 62-63 °C Tandem Mass Spectrometry (detection of Solubility: approx. 23.6 mg/mL in DSMO cannabidiol in a whole blood sample) and ethanol c) The process of CBD extraction from blood Identification and analysis sample. In the 1st phase, protein precipitation is Cannabidiol is produced by both the species done with acetonitrile followed by of Cannabis sativa and Cannabis indica, but gradient elution for 16 min, and high- literature reveals that, it can be found more in performance liquid chromatography. that Cannabis sativa than Cannabis indica Electrospray ionization is utilized for CBD which has more psychoactive effect and a detection [6]. high percentage of tetrahydrocannabinol General Pharmacology (THC). Routes of administration: Currently, there Cannabis sativa: It is a herbaceous flowering is a lot of approved marketed cannabidiol plant found in eastern Asia. Flowers of the (CBD) infused products namely: plant are unisexual (male/female) and • Health Horizon Ayurvedic Sativa Hemp arranged in racemes and produce hundreds of Oil- Promotes cardiovascular health as it seeds. The major psychoactive ingredient is reduces the cholesterol rates can be used for THC and known to produce 113 an edible purpose, works on managing the cannabinoids. hormonal balance of the body, facilitates Cannabis indica: Found in hydration to the skin and provides Indian subcontinents. Tetrahydrocannabinol (THC) percentage is high both narrow-leaflet IJBPAS, June, 2022, 11(6) Das M et al Review Article nourishment to hair and nails, helps to fortify periphery on cells along with immune the immune system. function in the gastrointestinal tract and • CBD is generally administered orally as a experimented on humans and animals, capsule, or dissolved in an oil solution (eg cannabidiol had shown very different effects olive or sesame oil). A wide range of oral from those of THC. In mice models, CBD dosages has been reported in the literature, did not suppress locomotor activity, with most from 100-800 mg/day [7]. hypothermia due to CB1 activation. THC Pharmacokinetics: Cannabidiol (CBD) produced all of the effects which occur when induced a non-significant reduction of food CB1 is activated. In comparison to THC, intake, and it exerted beneficial effects on CBD has no effect on heart rate or blood bone formation and fracture healing. Canna- pressure remains controlled, but in animal bidiol (CBD), when given to children ages 4- models of stress, it reduces heart rate and 10 with a dose of 5, 10 and 20 mg/kg/d blood pressure [10-11]. with Dravet syndrome produced dose- CBD may also interact with proportional increases in plasma the endocannabinoid system through an concentrations of CBD. Aerosolised CBD indirect mechanism such as enhanced action accounts for greater bioavailability than oral of the endogenous cannabinoid ligand route of administration [8]. anandamide. This results from blockage of Cannabidiol (CBD) gets rapidly distributed anandamide reuptake and the inhibition of its in the tissue with a high rate of enzymatic degradation.CBD has been shown disruption. Cannabidiol is metabolized in the to modulate several non-endocann- liver and its primary route is hydroxyl- abinoid signaling systems [12]. Some of lation which is facilitated by the enzyme these mechanisms include: hydroxylases and further resulting in several • Inhibition of adenosine uptake, possibly metabolites that are excreted in feces and resulting in indirect agonist activity at urine [9]. adenosine receptors. Pharmacodynamics: The biological • Enhanced activity at the 5-HT1a receptor. and psychological effects of cannabidiol on • Enhanced activity at glycine receptor humans is further discussed as there are two subtypes. main cannabinoid receptors CB1 located in • Blockade of the orphan G-protein-coupled the central nervous system, CB2 found in the receptor GPR55. IJBPAS, June, 2022, 11(6) Das M et al Review Article CBD of Cannabis sativa plant has a possible Biological activity i) Antioxidant property: effect in breast cancer cell line and primarily The antioxidant and anti-inflammatory effects on key neoplastic pathways. CBD properties of cannabidiol has been found. binds to specific G-protein Coupled [13] have mentioned in their study that Receptor; downregulates ID1, a regulator of cannabidiol reduces oxidative conditions by metastasis in breast cancer cell lines. Some preventing the formation of super- review data regarding cannabidiol and its oxide radicals,which are mainly generated by effects on breast cancer state that, alertness xanthine oxidase and NADPH of breast tumor cells to anti-tumor agents oxidase. Cannabidiol also reduces reactive depends on in part of estrogen receptor oxygen species (ROS) production by status. CBD induces both apoptosis and chelating transition metal ions involved in autophagy in breast cancer cells.CBD the Fenton reaction to form extremely induces cell death via a mitochondria- hydroxyl radicals [23-24]. mediated signaling pathway. Mitochondrion ii) Anticancer property: plays a central role in apoptotic cell death CBD invade cancer cells by increasing tissue [17]. inhibitor of matrix metalloproteinase- iii) Antiarthritic property: Arthritis as 1(TIMP-1). Cannabidiol is one of the non- one of the major problems causing psychoactive constituents of cannabis and inflammation of one or multiple joints in the it is considered as an antineoplastic agent human body. Over 100 different types of based on its in vivo and in vitro activity arthritis are known; these mostly common against tumor cells [14]. Although by the use are Rheumatoid Arthritis (RA), of CBD it is effective against the tumor, but and Oslo Arthritis [18]. Cannabis-based the molecular mechanism of its action is medicine (CBM) is a treatment of pain not yet fully characterized [15]. Cannabidiol caused by rheumatoid arthritis. An (CBD) is likely one of the phytocannabinoid experiment was conducted and using Sativex present in cannabis which is lacking the (CBM) over a group of 58 patients suffering psychoactive effect that makes it a from RA [19]. Sativex is a blend of whole therapeutic agent. It has been reported that plant-based extracts that delivers an CBD can exert an effect on metastasis and approximately equal amount of THC and tumor angiogenesis [16]. CBD. Minor cannabinoids including IJBPAS, June, 2022, 11(6) Das M et al Review Article cannabidiol, cannabichromene, and canna- development. Some authorized CBD bigerol are also present and these three products are as follows: compounds have been found to have anti- • Arvisol® tablets contain pure CBD and still inflammatory properties found in lab [20]. under Phase I clinical trials. It has been iv) Antiepileptic property: In a study, developed by Echo Pharmaceuticals in the the clinical use of CBD is most advanced in Netherlands and is intended to be the treatment of epilepsy. In clinical trials, registered for the treatment of various CBD has been demonstrated as an effective neurological disorders, treatment for at least some forms of epilepsy, including schizophrenia and epilepsy. with one pure CBD product (Epidiolex) • BOHECO hemp seed oil is a light non- currently available. greasy oil that’s fortified with the goodness 15 patients with “secondarily generalized of the hemp plant and is derived from epilepsy with temporal focus” In response to (Cannabis sativa L.) seed. Some benefit of CBD, 50% showed no seizures whereas this product is that it is rich in vitamins and others showed partial clinical minerals, contains omega3 and omega6 fatty improvement. In the placebo group, there acids, boosts metabolism, increase energy was no change [21]. level, improves memory and brain function. A similar study recently on the safety and • Bionorica® (Germany) has produced a efficacy of CBD in patients with Lennox- purified powdered CBD product from hemp Gastaut syndrome, a severe form of plants. epileptic encephalopathy that produces • Nextgen Ayurveda Hemp seeds are seeds of various types of seizures (including drop Cannabis sativa L. that helps in improving seizures) that are often treatment-resistant. metabolism and digestion, good for joint They found that treatment with CBD lowered pains and muscles, super-rich in protein, safe drop seizures by median of 44% to have orally. approximately [22]. CONCLUSION Cannabidiol combined products In this present review on cannabidiol, certain (marketing authorization) data have come forward to how cannabidiol Currently, there are a lot of authorized CBD can be used for medicinal use and the general products. However, there are some in pharmacology of cannabidiol. However, the negative health effects are more. It is a IJBPAS, June, 2022, 11(6) Das M et al Review Article banned (synthetic drug) in India. Further, [4] Isac G. Karniol, Itiro Shirakawa, studies by many researchers are under Reinaldo N. Takahashi, Elias Knobel progress. and Richard E. Musty. Effect of Delta 9 – Tetrahydrocannabinol and CONFLICT OF INTEREST: NONE FINANCIAL DISCLOSURE: NONE Cannabinol in Man, 1975 ACKNOWLEDGEMENT: The authors Pharmacology13: 502-512. acknowledge the infrastructure support [5] Tehseen Aman, Abdul Rashid & received from the Assam down town Irshad Khokhar. Spectrophotometric University. Determination of Cannabidiol 1993; REFERENCES Analytical Letters, 26(10), 21 13- [1] Giovanni Appendino. The early 2125. history of cannabinoid research, 2020 [6] David M. Schwope, Karl B. Rendiconti Lincei. Scienze Fisiche e Scheidweiler & Marilyn A. Huestis. Naturali. Direct quantification of cannabinoids [2] Angelo A. Izzo, Francesca Borrelli, and cannabinoid glucuronides in Raffaele Capasso, Vincenzo Di whole blood by liquid Marzo and Raphael Mechoulam. chromatography–tandem mass Non-psychotropic plant cannabinoids: spectrometry 2011; Anal Bioanal new therapeutic opportunities from an Chem 401:1273–1283. ancient herb, 2009 Trends in [7] Pius S. Fasinu, Sarah Phillips, Pharmacological Sciences; Vol.30 Mahmoud A. ElSohly and Larry A. No.10. Walker. Current Status and [3] E. A. Carlini, M. Santos, U. Claussen, Prospects for Cannabidiol D. Bieniek, and F. Korte. Structure Preparations as New Therapeutic Activity Relationship of Four Agents 2016; Pharmacotherapy: The Tetrahydrocannabinols and the Journal of Human Pharmacology and Pharmacological Activity of Five Drug Therapy. Semi-Purified Extracts of Cannabis [8] Serena Deiana, Akihito Watanabe, sativa, 1970 Psychopharmacologia Yuki Yamasaki, Naoki Amada, (Berl.) 18, 82-93. Marlene Arthur, Shona Fleming, Hilary Woodcock, Patricia Dorward, IJBPAS, June, 2022, 11(6) Das M et al Review Article Barbara Pigliacampo, Steve Close, Pharmacology: Volume 8 | Article Bettina Platt & Gernot Riedel. Plasma 81. and brain pharmacokinetic profile of [12] Tiziana Bisogno, LumõÂr HanusÆ, cannabidiol (CBD), annabidivarine Luciano De Petrocellis, Susanna (CBDV), Δ9-tetrahydrocannabivarin Tchilibon, Datta E. Ponde, Ines (THCV) and cannabigerol (CBG) in Brandi, Aniello Schiano Moriello, rats and mice following oral and John B. Davis, Raphael Mechoulam ntraperitoneal administration and & Vincenzo Di Marzo. Molecular CBD action on obsessive–compulsive targets for cannabidiol and its behavior 2012; Psychopharmacology synthetic analogues: efect on 219:859–873. vanilloid VR1 receptors and on the [9] Sharon Rodner, Sznitman, Borje cellular uptake and enzymatic Olsson and Robin Room. A cannabis hydrolysis of anandamide 2001; reader: global issues and local British Journal of Pharmacology: experiences 2008; EMCDDA series 134, 845 ± 852. 8, Volume 1. [13] Sinemyiz Atalay, Iwona [10] Leonora E. Long, Rose Chesworth, Jarocka‐Karpowicz and Elzbieta Xu-Feng Huang, Iain S. McGregor, Skrzydlewska. Antioxidative and Jonathon C. Arnold and Tim Karl. Anti‐Inflammatory Properties of A behavioural comparison of acute Cannabidiol2020; Antioxidants: 9, and chronic D9-tetra-hydro- 21. cannabinol and cannabidiol in [14] SGB Neto, VI Moura and A C57BL/6JArc mice 2010; Solange. Increasing the anti- cancer International Journal of Neuro- effect of CBD through PE psychopharmacology 13, 861–876. supplementation to the cancer cell [11] Salahaden R. Sultan, Sophie A. 2021; preprint. Millar, Timothy J. England and [15] Vaccani A, Massi P, Colombo A Saoirse E. O’Sullivan. A Systematic and Rubino T, Parolaro D. Cannabid Review and Meta-Analysis of the iol inhibits human glioma cell Haemodynamic Effects of migration through a Cannabidi 2017; Frontiers in cannabinoid receptor- IJBPAS, June, 2022, 11(6) Das M et al Review Article independent mechanism 2005; Br J [20] Mark A. Lewis, Ethan B. Russo and Pharmacol 144:1032–6. Kevin M. Smith. Pharmacological [16] Robert Ramer, Jutta Merkord, Helga Foundations of Cannabis Rohde and Burkhard Hinz. Chemovars 2017; Thieme. Cannabidiol inhibits cancer cell [21] Jomar M. Cunha, E. A. Carlini, invasion via upregulation of tissue Aparecido E. Pereira, Oswaldo L. inhibitor of matrix Ramos, Camilo Pimentel, Rubens metalloproteinases 2010; Gagliardi, W. L. Sanvito, N. Lander Biochemical Pharmacology. 79: and R. Mechoulam.Chronic 955–966. Administration of Cannabidiol to [17] Ashutosh Shrivastava, Paula M. Healty Volunteers and Epileptic Kuzontkoski, Jerome E. Groopman, Patient 1980; Pharmacology 21:175- and Anil Prasad. Cannabidiol 185. Induces Programmed Cell Death in [22] Elizabeth A Thiele, Eric D Marsh, Breast Cancer Cells by Coordinating Jacqueline A French, Maria the Cross-talk between Apoptosis Mazurkiewicz-Beldzinska, Selim R and Autophagy 2011; Therapeutic Benbadis, Charuta Joshi, Paul D Discovery. Lyons, Adam Taylor, Claire [18] Sumner Burstein. Cannabidiol Roberts, Kenneth Sommerville, on (CBD) and its analogs: a review of behalf of the GWPCARE4 Study their effects on inflammation 2015; Group. Cannabidiol in patients with Bioorganic & Medicinal Chemistry: seizures associated with Lennox- S0968-0896(15)00083-8. Gastaut syndrome (GWPCARE4): a [19] D. R. Blake, P. Robson, M. Ho2, R. randomised, double-blind, placebo- W. Jubb and C. S. McCabe. controlled phase 3 trial 2018; Preliminary assessment of the Thelancet. efficacy, tolerability and safety of a [23] Sinemyiz Atalay, Iwona cannabis-based medicine (Sativex) Jarocka‐Karpowicz and Elzbieta in the treatment of pain caused by Skrzydlewska. Antioxidative and rheumatoid arthritis 2006; Anti‐Inflammatory Properties of Rheumatology: 45: 50–52. IJBPAS, June, 2022, 11(6) Das M et al Review Article Cannabidiol 2020; Antioxidants: 9, [24] Hao Pan, Partha Mukhopadhyay, Mohanraj Rajesh, Vivek Patel, Bani Mukhopadhyay, Bin Gao, Gyo¨ rgy Hasko´ , and Pa´ l Pacher. Cannabidiol Attenuates Cisplatin- Induced Nephrotoxicity by Decreasing Oxidative/Nitrosative Stress, Inflammation, and Cell Death 2009; The Journal Of Pharmacology And Experimental Therapeutics: 328,708–714. 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A BRIEF REVIEW ON CANNABIDIOL (CBD)

International Journal of Biology, Pharmacy and Allied Sciences – Jun 1, 2022
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IJBPAS, June, 2022, 11(6): 2609-2618 ISSN: 2277–4998 1 1* 1 1 1 2 DAS M , BHATTACHARJEE M , SARMA M , PAUL DC , SAIKIA D AND SAIKIA AP 1: Department of Biotechnology, Assam downtown University, Sankar Madhav Path, Gandhi Nagar Pin-781068, Guwahati Assam 2: Department of Computer Science, Assam downtown University, Sankar Madhav Path, Gandhi Nagar Pin-781068, Guwahati Assam Corresponding Author: Dr. Minakshi Bhattacharjee:minakshibhattacharjee2007@gmail.com th th th st Received 18 June 2021; Revised 19 Aug. 2021; Accepted 18 Aug. 2021; Available online 1 June 2022 https://doi.org/10.31032/IJBPAS/2022/11.6.6046 ABSTRACT The present review focuses on cannabidiol (CBD) which is a cannabinoid derived from cannabis. Cannabidiol is non-toxic in comparison to delta-9-tetrahydrocannabinol (THC). Cannabidiol is non-psychoactive in comparison to THC. It is found in both the species of the cannabis plant, Cannabis sativa, and Cannabis indica but cannabidiol percentage is higher in Cannabis.sativa. The cannabidiol content in Cannabis sp can be determined by spectrophotometric assays and Liquid chromatography -Tandem Mass spectrometry (LC- MS). The general pharmacology is discussed, how the cannabidiol binds to the CB1 and CB2 receptors of the central nervous system. The antioxidant activity of cannabidiol and its implementation to prevent disease associated with redox imbalance and inflammation. Here, we have discussed how cannabidiol is related to lung cancer, breast cancer, arthritis. Nowadays CBD combined marketed authorized products are also discussed here like ARVISOL, Boheco Hemp seed oil. Keywords: Cannabidiol, North East India, Medicinal Property IJBPAS, June, 2022, 11(6) Das M et al Review Article INTRODUCTION Cannabidiol (CBD) is a chemical compound inhibits cancer cell invasiveness and derived from the cannabis plant that belongs metastasis. CBD has broad therapeutic to the cannabinaceae family of plant properties across a range of neuro- species. Isolation of first natural cannabinoid psychiatric disorders, stemming from diverse as CBN to be obtained in pure form by Wood central nervous system actions [2]. and colleagues in Cambridge in 1896 [1]. Studies have shown tetrahydrocannabinol Cannabis is in use for the last thousands of (THC) is the main factor responsible for the years for fiber, nutritional seed oil, and effect of cannabis, but several reports have medicinal use. In India, Uttara-khand state demonstrated that other cannabinoids government has permitted cultivation of including CBD have pharmacological hemp crop, a rich source of high-quality activity [3]. The antagonism of the effect of fiber, and a host of medicinal THC when both CBD and THC are use. Cannabidiol has had gained a major administered simultaneously to animals and interest of study over the past few years ago. humans. They concluded that although CBN Abundant literature is available since 2008 increased the effect of THC in certain over various search engines. Cannabidiol is psychophysiology but these modulations the phytocannabinoids of the cannabis plant; were not significant enough. In neurological it is one of the major cannabinoids of aspects, CBD is a cannabinoid 1 receptor cannabis out of 113 identified (CB1) negative allosteric modulator, is a cannabinoids. With the correct structure of partial agonist of dopamine D2 high receptor Cannabidiol as CBD later was discovered early in sub-type and it increases anandamide (AEA) the year 1940 [1]. CBD accounts for up signaling, possibly through inhibition of the to 40% of plant extracts. CBD devoid of AEA catabolic enzyme, fatty acid amide psychoactive activity rather than tetrahy- hydrolase (FAAH) [4]. drocannabinol besides, CBD has analgesic, anti- Chemistry inflammatory, antineoplastic and chemo- As per “Cannabidiol (CBD) Critical Review preventive activities. CBD can modulate Report (2018)”, the IUPAC Name of endoplasmic reticulum stress, cannabidiol is 2-[(6R)-3-methyl-6-prop-1-en-2- AKT/Motor signaling, thereby activating aut- ylcyclohex-2-en-1- yl]-5-pentylbenzene-1,3-diol. ophagy and promoting apoptosis. CBD Chemical structure- IJBPAS, June, 2022, 11(6) Das M et al Review Article and wide-leaflet drugs are found under this taxonomy. Analytical detection of CBD includes the following methods: a) Spectrophotometric determination (plant sample) Cannabidiol needs alkaline medium to Figure 1: Chemical structure of cannabidiol (Adams et react with 2, 4-dinitrophenol. The absorbance al. 1940) peak is at 500 nm. The detectable titer is Molecular formulae- C21H30O2 0.1 ug/10ml [5]. Molecular weight-314.469 g/mol b) Liquid Chromatography- Melting point: 62-63 °C Tandem Mass Spectrometry (detection of Solubility: approx. 23.6 mg/mL in DSMO cannabidiol in a whole blood sample) and ethanol c) The process of CBD extraction from blood Identification and analysis sample. In the 1st phase, protein precipitation is Cannabidiol is produced by both the species done with acetonitrile followed by of Cannabis sativa and Cannabis indica, but gradient elution for 16 min, and high- literature reveals that, it can be found more in performance liquid chromatography. that Cannabis sativa than Cannabis indica Electrospray ionization is utilized for CBD which has more psychoactive effect and a detection [6]. high percentage of tetrahydrocannabinol General Pharmacology (THC). Routes of administration: Currently, there Cannabis sativa: It is a herbaceous flowering is a lot of approved marketed cannabidiol plant found in eastern Asia. Flowers of the (CBD) infused products namely: plant are unisexual (male/female) and • Health Horizon Ayurvedic Sativa Hemp arranged in racemes and produce hundreds of Oil- Promotes cardiovascular health as it seeds. The major psychoactive ingredient is reduces the cholesterol rates can be used for THC and known to produce 113 an edible purpose, works on managing the cannabinoids. hormonal balance of the body, facilitates Cannabis indica: Found in hydration to the skin and provides Indian subcontinents. Tetrahydrocannabinol (THC) percentage is high both narrow-leaflet IJBPAS, June, 2022, 11(6) Das M et al Review Article nourishment to hair and nails, helps to fortify periphery on cells along with immune the immune system. function in the gastrointestinal tract and • CBD is generally administered orally as a experimented on humans and animals, capsule, or dissolved in an oil solution (eg cannabidiol had shown very different effects olive or sesame oil). A wide range of oral from those of THC. In mice models, CBD dosages has been reported in the literature, did not suppress locomotor activity, with most from 100-800 mg/day [7]. hypothermia due to CB1 activation. THC Pharmacokinetics: Cannabidiol (CBD) produced all of the effects which occur when induced a non-significant reduction of food CB1 is activated. In comparison to THC, intake, and it exerted beneficial effects on CBD has no effect on heart rate or blood bone formation and fracture healing. Canna- pressure remains controlled, but in animal bidiol (CBD), when given to children ages 4- models of stress, it reduces heart rate and 10 with a dose of 5, 10 and 20 mg/kg/d blood pressure [10-11]. with Dravet syndrome produced dose- CBD may also interact with proportional increases in plasma the endocannabinoid system through an concentrations of CBD. Aerosolised CBD indirect mechanism such as enhanced action accounts for greater bioavailability than oral of the endogenous cannabinoid ligand route of administration [8]. anandamide. This results from blockage of Cannabidiol (CBD) gets rapidly distributed anandamide reuptake and the inhibition of its in the tissue with a high rate of enzymatic degradation.CBD has been shown disruption. Cannabidiol is metabolized in the to modulate several non-endocann- liver and its primary route is hydroxyl- abinoid signaling systems [12]. Some of lation which is facilitated by the enzyme these mechanisms include: hydroxylases and further resulting in several • Inhibition of adenosine uptake, possibly metabolites that are excreted in feces and resulting in indirect agonist activity at urine [9]. adenosine receptors. Pharmacodynamics: The biological • Enhanced activity at the 5-HT1a receptor. and psychological effects of cannabidiol on • Enhanced activity at glycine receptor humans is further discussed as there are two subtypes. main cannabinoid receptors CB1 located in • Blockade of the orphan G-protein-coupled the central nervous system, CB2 found in the receptor GPR55. IJBPAS, June, 2022, 11(6) Das M et al Review Article CBD of Cannabis sativa plant has a possible Biological activity i) Antioxidant property: effect in breast cancer cell line and primarily The antioxidant and anti-inflammatory effects on key neoplastic pathways. CBD properties of cannabidiol has been found. binds to specific G-protein Coupled [13] have mentioned in their study that Receptor; downregulates ID1, a regulator of cannabidiol reduces oxidative conditions by metastasis in breast cancer cell lines. Some preventing the formation of super- review data regarding cannabidiol and its oxide radicals,which are mainly generated by effects on breast cancer state that, alertness xanthine oxidase and NADPH of breast tumor cells to anti-tumor agents oxidase. Cannabidiol also reduces reactive depends on in part of estrogen receptor oxygen species (ROS) production by status. CBD induces both apoptosis and chelating transition metal ions involved in autophagy in breast cancer cells.CBD the Fenton reaction to form extremely induces cell death via a mitochondria- hydroxyl radicals [23-24]. mediated signaling pathway. Mitochondrion ii) Anticancer property: plays a central role in apoptotic cell death CBD invade cancer cells by increasing tissue [17]. inhibitor of matrix metalloproteinase- iii) Antiarthritic property: Arthritis as 1(TIMP-1). Cannabidiol is one of the non- one of the major problems causing psychoactive constituents of cannabis and inflammation of one or multiple joints in the it is considered as an antineoplastic agent human body. Over 100 different types of based on its in vivo and in vitro activity arthritis are known; these mostly common against tumor cells [14]. Although by the use are Rheumatoid Arthritis (RA), of CBD it is effective against the tumor, but and Oslo Arthritis [18]. Cannabis-based the molecular mechanism of its action is medicine (CBM) is a treatment of pain not yet fully characterized [15]. Cannabidiol caused by rheumatoid arthritis. An (CBD) is likely one of the phytocannabinoid experiment was conducted and using Sativex present in cannabis which is lacking the (CBM) over a group of 58 patients suffering psychoactive effect that makes it a from RA [19]. Sativex is a blend of whole therapeutic agent. It has been reported that plant-based extracts that delivers an CBD can exert an effect on metastasis and approximately equal amount of THC and tumor angiogenesis [16]. CBD. Minor cannabinoids including IJBPAS, June, 2022, 11(6) Das M et al Review Article cannabidiol, cannabichromene, and canna- development. Some authorized CBD bigerol are also present and these three products are as follows: compounds have been found to have anti- • Arvisol® tablets contain pure CBD and still inflammatory properties found in lab [20]. under Phase I clinical trials. It has been iv) Antiepileptic property: In a study, developed by Echo Pharmaceuticals in the the clinical use of CBD is most advanced in Netherlands and is intended to be the treatment of epilepsy. In clinical trials, registered for the treatment of various CBD has been demonstrated as an effective neurological disorders, treatment for at least some forms of epilepsy, including schizophrenia and epilepsy. with one pure CBD product (Epidiolex) • BOHECO hemp seed oil is a light non- currently available. greasy oil that’s fortified with the goodness 15 patients with “secondarily generalized of the hemp plant and is derived from epilepsy with temporal focus” In response to (Cannabis sativa L.) seed. Some benefit of CBD, 50% showed no seizures whereas this product is that it is rich in vitamins and others showed partial clinical minerals, contains omega3 and omega6 fatty improvement. In the placebo group, there acids, boosts metabolism, increase energy was no change [21]. level, improves memory and brain function. A similar study recently on the safety and • Bionorica® (Germany) has produced a efficacy of CBD in patients with Lennox- purified powdered CBD product from hemp Gastaut syndrome, a severe form of plants. epileptic encephalopathy that produces • Nextgen Ayurveda Hemp seeds are seeds of various types of seizures (including drop Cannabis sativa L. that helps in improving seizures) that are often treatment-resistant. metabolism and digestion, good for joint They found that treatment with CBD lowered pains and muscles, super-rich in protein, safe drop seizures by median of 44% to have orally. approximately [22]. CONCLUSION Cannabidiol combined products In this present review on cannabidiol, certain (marketing authorization) data have come forward to how cannabidiol Currently, there are a lot of authorized CBD can be used for medicinal use and the general products. However, there are some in pharmacology of cannabidiol. However, the negative health effects are more. It is a IJBPAS, June, 2022, 11(6) Das M et al Review Article banned (synthetic drug) in India. Further, [4] Isac G. Karniol, Itiro Shirakawa, studies by many researchers are under Reinaldo N. Takahashi, Elias Knobel progress. and Richard E. Musty. Effect of Delta 9 – Tetrahydrocannabinol and CONFLICT OF INTEREST: NONE FINANCIAL DISCLOSURE: NONE Cannabinol in Man, 1975 ACKNOWLEDGEMENT: The authors Pharmacology13: 502-512. acknowledge the infrastructure support [5] Tehseen Aman, Abdul Rashid & received from the Assam down town Irshad Khokhar. Spectrophotometric University. 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Published: Jun 1, 2022

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