Cannabis sativa is an annual herbaceous flowering plant indigenous to eastern Asia but now of cosmopolitan distribution due to widespread cultivation. It has. The therapeutic effects of hemp (Cannabis sativa L.) have been used for many millennia – Shen-Nung, the mythical founder of Chinese herbal medicine. Marijuana (Cannabis sativa) contains bioactive cannabinoids, with δ tetrahydrocannabinol being the primary active ingredient responsible for the pleasurable.
Moreover, the finding that the acidic precursor of CBD cannabidiolic acid, CBDA is able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 COX-2 highlights the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms, which might be responsible for its anticancer activity.
It has been used as a psychoactive drug, as a folk medicine ingredient, and as a source of textile fibre since ancient times [ 2 ]. The taxonomic classification of this plant has always been difficult, due to its genetic variability [ 1 , 3 ]. Firstly, the genus Cannabis has been divided into three main species [ 1 , 3 , 4 ]: Due the easy crossbreeding of these species to generate hybrids, a monotypic classification has been preferred, in which one species C. On the basis of their cannabinoid profiles, five chemotypes have been recognised: For both medicinal and forensic purposes, the most important classification of Cannabis types is that into the drug-type and the fibre-type: Fibre-type Cannabis also known as hemp or industrial hemp is at the moment underemployed for pharmacological purposes, while drug-type C.
However, there has also been a growing interest in fibre-type C. Many European countries have recognized the commercial value of hemp and a legal limit of 0. Cannabinoids are meroterpenoids specifically C 21 or C 22 terpenophenolic compounds , obtained from the alkylation of an alkyl resorcinol with a monoterpene unit [ 3 ].
They are mainly synthesized in glandular trichomes, which are more abundant in female inflorescences [ 2 ]. More than cannabinoids have been isolated, characterised, and divided into 11 chemical classes [ 4 , 6 ]. It should be pointed out that cannabinoids are biosynthesized in the acid form in plant tissues; then, they can generate their decarboxylated counterparts under the action of heat and light, by means of a spontaneous decarboxylation [ 1 , 3 , 4 , 7 — 10 ].
CB 2 receptors are also considered to be involved in neuroinflammation, atherosclerosis, and bone remodelling [ 3 ]. In the ambit of nonpsychoactive compounds, CBD represents the most valuable one from the pharmaceutical point of view, since it has been found to possess a high antioxidant and anti-inflammatory activity, together with antibiotic, neuroprotective, anxiolytic, and anticonvulsant properties [ 1 , 3 , 11 — 14 ].
CBDA has antimicrobial and antinausea properties [ 1 , 11 , 13 ], while CBG has anti-inflammatory, antimicrobial, and analgesic activities [ 1 , 11 , 13 , 15 ]. Thanks to its lack of psychoactivity, CBD is one of the most interesting compounds, with many reported pharmacological effects in various models of pathologies, from inflammatory and neurodegenerative diseases, to epilepsy, autoimmune disorders like multiple sclerosis, arthritis, schizophrenia, and cancer [ 16 ].
CBD has also been found to be a negative allosteric modulator of the CB 1 receptors and an inverse agonist of CB 2 receptors, the second activity partly explaining its anti-inflammatory activity [ 16 ]. Concerning other phenolics present in C. Cannabis flavonoids exert several biological effects, including properties possessed also by cannabinoids and terpenes [ 2 ].
Anti-inflammatory, neuroprotective, and anti-cancer activities have been described for these compounds [ 2 ]. In particular, cannflavin A and B are known to possess an anti-inflammatory action [ 2 ]. An antimicrobial and antileishmanial activity has also been demonstrated for cannflavin B [ 17 ]. Cannflavin A has shown a good antileishmanial activity and a moderate antioxidant action [ 17 ]. In the ambit of Cannabis phenolics, canniprene, which is a dyhydrostilbene unique to C.
If compared with cannflavin A, which is the most potent cannflavin, canniprene has been found to be superior at inhibiting 5-LO, but it is less effective for mPGES-1 inhibition [ 19 ]. As regards the other compounds present in C.
Both mono- and sesquiterpenes have been detected in roots and aerial parts of Cannabis and they are mainly produced in secretory glandular hairs [ 2 ]. Several interactions between Cannabis secondary metabolites have been described in the literature [ 2 ]. Many studies have expanded the concept that inflammation is a critical component of tumour progression [ 20 ]. Indeed, several cancers originate from infection, chronic irritation, and inflammation [ 20 ]. Tumour microenvironment, which is largely regulated by inflammatory cells, displays a key role in the neoplastic process, fostering proliferation, survival, and migration [ 20 ].
In addition, cancer cells have co-opted some of the signalling molecules of the innate immune system for invasion, migration, and metastasis [ 20 ]. By focusing the attention on hemp nonpsychoactive cannabinoids, CBD has been demonstrated to be useful in the treatment of different inflammatory ailments, including bowel diseases e. As regards cancer, CBD has exhibited antiproliferative and proapoptotic activities, thus demonstrating modulating the tumorigenesis in different types of cancer, including breast, lung, colon, brain, and others [ 21 ].
In this context, this review is focused on the effects and the molecular mechanisms of CBD and related compounds on inflammation and cancer processes, highlighting also the role of other related nonpsychoactive cannabinoids and noncannabinoids constituents of fibre-type hemp.
Endocannabinoids and their metabolic enzymes and receptors have been identified in monocytes, macrophages, basophils, lymphocytes, and dendritic cells. In these cells their role is to modulate immune function in an autocrine and paracrine way [ 22 ]. CB 2 expression in human B cells increases after the activation by anti-CD40 antibody.
However, differentiation of B cells is accompanied by decreased expression of CB 2. CB 2 levels in macrophages undergo changes correlated with cell activation or with inflammation. Indeed, macrophages express higher levels of CB 2 ; so, the functions of macrophages in these states of activation may be the most sensitive to the actions of cannabinoids.
These data suggest a physiological role of the endocannabinoid system in the functions of immune cells with respect to inflammation [ 24 ]. Moreover, a relationship between the endocannabinoid system and toll-like receptors TLR has been reported, with TLR activation enhancing the production of endocannabinoids and cannabinoids suppressing TLR-induced inflammatory response [ 25 ].
The study of the anti-inflammatory effects of cannabinoids from C. CBDA has been found to possess a dual inhibitory effect on COX, through downregulation [ 40 ] and enzyme inhibition [ 35 ]. More recently, CBD has been found to significantly reduce cytokines production in an in vitro model of allergic contact dermatitis, using HaCaT cells [ 43 ]. Concerning the effect of other C.
As far as peripheral inflammation is concerned, C. Recent investigations have highlighted the involvement of the endocannabinoid system in the physiology of the gastrointestinal function and its possible deregulation in gastrointestinal pathology [ 49 ]. The precise mechanisms across tissue departments that are under the regulatory control of the endocannabinoid system have not been fully understood [ 49 ]. Cannabinoids have been found to modulate intestinal permeability in an in vitro model.
These data suggest that endocannabinoids may play a role in the modulation of gut permeability and that Cannabis -based medicines may possess therapeutic benefit in a variety of gastrointestinal diseases characterized by abnormal intestinal permeability, such as inflammatory bowel disease IBD and shock [ 50 ]. These findings have been further confirmed in another in vitro model of intestinal inflammation. The effects of cytokines on increased permeability were inhibited by a CB 1 receptor antagonist and a 2-AG synthesis inhibitor and were enhanced by inhibitors of the degradation of AEA or 2-AG, suggesting that local production of endocannabinoids activating CB 1 may play a role in the modulation of gut permeability during inflammation [ 51 ].
CBD anti-inflammatory effects on the acutely inflamed human colon have also been investigated in combination with palmitoylethanolamide PEA in cultured cell lines and this effect was compared with experimentally inflamed explant human colonic tissue [ 52 ].
In particular, Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease IBD , or acute appendicitis resections were used.
These effects extend into chronic inflammatory processes, such as IBD, but also acute inflammatory conditions, such as appendicitis. Since these two compounds are well tolerated in humans with few side effects, their clinical use in treating IDB can be very useful [ 52 ]. In another study, CBD has been demonstrated to improve Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of CB 1 receptors [ 53 ].
Clostridium difficile infection is the leading cause of hospital-acquired diarrhea and pseudomembranous colitis. Clostridium difficile toxin A significantly affects enterocytes permeability leading to apoptosis and colonic mucosal damage.
Given the absence of any significant toxic effect in humans, CBD may ideally represent an effective adjuvant treatment for Clostridium difficile -associated colitis [ 53 ]. In addition to the protective role of Cannabis components on the inflamed intestine, an additional positive aspect is their potential role in preventing imbalances of gut microbiota. This aspect not only is relevant for the treatment of several gastrointestinal disorders, such as IBD and obesity, but also has implications for the treatment of colorectal cancer CRC.
The impact of the endocannabinoid system on gut microbiota is a relatively new and emerging field wherein the interplay between cannabinoids and metabolic syndrome has been the focus so far. Bacteroidetes ratio typically found in obesity, resulting in weight-loss, indicating that Cannabis may play a role in CRC prevention as well [ 54 ].
Further studies are needed to determine whether CBD has the same effect on gut microbiota with respect to the balance of Firmicutes: Bacteroidetes to evaluate its application in halting the progression of the obese microbiota profile present in CRC, with the hopes of delaying this disease onset [ 54 ]. CB 1 receptors are much more expressed in the brain if compared to CB 2 [ 55 ].
However, CB 2 can be upregulated under neuroinflammatory conditions and as a result of the invasion of peripheral cells expressing CB 2 [ 56 ]. The neuroprotective effect of endocannabinoids involves the suppression of proinflammatory cytokines and the increase of anti-inflammatory cytokines production.
Cytokines may regulate the normal activity of the endocannabinoid system in different ways: Indeed, these cytokines have pro- and anti-inflammatory properties, depending on a variety of factors.
This activity leads to a promotion of stem cells proliferation and migration that might have important implications for brain self-repairing processes [ 60 ]. The cannabinoid system and cytokine network are directly related. Evidences suggest that controlled neuroinflammation is crucial for tissue repair within the brain [ 62 , 63 ].
The inhibition of ATP-induced intracellular calcium increase, together with the inhibition of NO production, has been suggested as a mechanism by which CBD can reduce microglia activation [ 75 ].
In another work, CBD has also inhibited the neurotoxic effects of protease-resistant prion protein PrPres and it has affected PrPres-induced microglial cell migration in a concentration-dependent manner; so, it may protect neurons against the multiple molecular and cellular factors involved in the different steps of the neurodegenerative process, which takes place during prion infection [ 77 ]. More recently, the neuroprotection of fibre-type hemp extracts and CBD was assessed in human neuroblastoma SH-SY5Y and microglial BV-2 cell lines in the presence of rotenone as the toxic agent, also in serum-free conditions [ 78 ].
The decarboxylated hemp extract has shown a mild neuroprotective activity on BV-2 cells treated with rotenone, higher than that of pure CBD [ 78 ]. As regards serum-free experiments, the nondecarboxylated hemp extract was the most effective neuroprotective agent toward SH-SY5Y cells, while BV-2 cells were better protected from the toxic insult by the decarboxylated extract and CBD [ 78 ].
Concerning other cannabinoids, the anti-inflammatory properties of CBG have been described in an in vitro model of neuroinflammation, using NSC motor neurons conditioned with the medium of LPS-stimulated murine macrophages. CBG treatment in macrophages has prevented neuronal cytotoxicity by reducing inflammation, i. As regards other C. Cancer is the second leading cause of death worldwide, and it accounts for about 8.
This is considered to be the oldest piece of paper ever recovered. According to Vavilov, domestication of hemp probably occurred independently in several centres in northeast Asia around six millennia ago. In Egypt, the presence of hashish was found in the body tissues of mummies, dating back to about BC. The Greeks and Romans used hemp for the production of rope and coarse fabric.
They probably did not use it as a drug. During the s, servants from India carried seeds to Jamaica, and from here drug cultivation spread within the Gulf of Mexico. There is considerable evidence for the diffusion of hemp in Europe and the Middle East. From the 16th to the 18th centuries, hemp was an important fibre crop in Europe and North America.
Hemp production declined in the 19th and 20th centuries due to the large-scale cultivation of cotton, the advent of synthetic fibres and because the growing of hemp has been made illegal in many countries. Today the distribution of hempcultivation is poorly documented. Nova Institute Karus et al. A list of major centres of cultivation for a minor crop such as hemp, is liable to change and become out of date. The drug cannabis, for instance, is grown almost globally the ODCCP cites countries , but few countries are consistent and have significant exportation.
The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.
Early vegetative growth is often slow, but later growth may be quite rapid. Generally, canopy closure when leaves of adjacent plants mesh together and shade the soil occurs when fibre crops are approximately 50 cm in height. Duke determined that optimal growth of C. It has a growth period of months, which is dependent on the latitude. Duke found that C. It flowers in the autumn, when the photoperiod drops below hours per day, depending on the variety and location.
The plant is a nitrophile and requires much nutrients. Fibre crops require high levels of nitrogen and potassium, and in descending order of importance calcium, phosphorous and magnesium. However, seed crops extract less potassium and more phosphorous from the soil, and drug crops have a high demand for phosphorus Frank and Rosenthal, Duke suggests that a soil pH of 6. Fibre The long, strong, mildew-resistant fibre in hemp was traditionally used for rope, sails, tarpaulin, canvas bags, and carpets.
Fine yarn can be spun for clothing, handbags, and other textiles. The low lignin level present in hemp fibre and hurds make these materials ideal for production of paper, fibreboard, composite wood products; or may be mixed with lime to create reinforced concrete. The fibres also serve as a fibreglass substitute, for pressed insulation and moulded panels for the car industry.
Hempseed The seed is technically an achene, a small, dry nut. For example field-grown crops yield an average of g seeds per plant, or about 22, seeds per plant McPartland et al. Approximately one-third of hempseed is oil, which is used in lighting, lubrication, soaps, detergents and cosmetic creams. The fatty acids are quick drying and so hemp oil is useful for paints, varnishes and printing inks. Hemp oil can also be burned as a fuel. In China, hempseed is commonly eaten, roasted or raw. Hemp oil contains a high percentage of essential fatty acids, it is therefore a valuable food supplement, and is useful in salad dressings and margarine.
After the oil has been pressed out of the seed, the remaining seed cake is rich in protein and is suitable for use as a flour or an animal feed Pate, Two types of drug are produced: More resin is produced in tropical than in temperate climates.
Tetrahydrocannabinol THC is the primary active ingredient in the drug cannabis, but THC activity is modulated by dozens of other cannabinoids, terpenoids, and flavonoids.
These compounds are synthesized in specialized leaf hairs called glandular trichomes, which are most dense on the surface of the leafy female flowers. The upper head of the glands consists of secretory cells and is covered by a tough but distensible sheath. Air-dried herbal products such as marijuana, sinsemilla dominate the illicit market in North America, South America, and South Africa. For legitimate medicinal use, clinical trials have demonstrated the efficacy of the drug cannabis for treating many diseases and syndromes, including arthritis, muscle spasms, headaches, menstruation, multiple sclerosis, epilepsy, anorexia, glaucoma, insomnia, anxiety, depression and even drug addiction.
In Western medicine, the use of C. In the past ten years, however, the drug has been re-introduced. Synthetic forms of THC are widely prescribed, and several pharmaceutical companies are currently developing cannabis plant extracts. The essential oil which contains no THC can be used in cosmetics, perfumes, food additives, and it may be fractionated for pharmaceutical use. The oil has antibacterial, antifungal and pest-repellent properties, and is being developed as an organic pesticide McPartland, The First 12, Years.
Botanik, Sorten, Anbau und Ernte. Botany, Varieties, Cultivation and Harvesting, ]. Sinsemilla Tips, 8 3: Advances in Hemp Research. University of Florida Press. Frank M; Rosenthal E, Gettman J; Armentano P, The marijuana crop report. National Organization for the Reform of Marijuana Laws,.
Karus M; Kaup M, Use of natural fibres in the German automotive industry. International Hemp Association, 6 2: Study on markets and prices for natural fibres. UV-B radiation effects on photosynthesis, growth and cannabinoid production of two Cannabis sativa chemotypes.
Cannabis as a repellent crop and botanical pesticide. International Hemp Association, 4 2: Hemp Diseases and Pests: Management and Biological Control. Meier C; Mediavilla V, Factors influencing the yield and the quality of hemp Cannabis sativa L. International Hemp Association, 5 1: Cannabis as a licit crop: Bulletin on Narcotics, 49 Global Illicit Drug Trends Small E; Cronquist A, A practical and natural taxonomy for Cannabis.
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Cannabis sativa L. is an important herbaceous species originating from Central Asia, which has been used in folk medicine and as a source of. Because Hemp and Marijuana both derive from the Cannabis Sativa family, they do share certain similarities; however, due to each plant's. The two major types of cannabis plants are Indica and Sativa. Each strain has it's own range of effects on the body and mind resulting in a wide range of.