The words hemp, cannabis, and pot have commonly been used interchangeably, and this has Hemp Flower—the Non-Psychoactive Bud. It is the primary non-psychoactive chemical of the cannabis plant, beneficial in the treatment of a variety of conditions from epilepsy to chronic. But whole plant marijuana, the only natural source of THC, continues to first,” said Dr. Tod Mikuriya, “that happens to have some psychoactive properties, of whole plant cannabis remedies, not just the low THC medicine.
Bud Non-Psychoactive Hemp Flower—the
Retrieved 14 May National Conference of State Legislatures. Retrieved 13 January Retrieved 6 November Retrieved January 3, The Farm Bill. Retrieved January 29, Retrieved December 4, Retrieved June 2, Retrieved 19 October Retrieved 1 January Retrieved 1 February Annales de Toxicologie Analytique in French.
Swedish Medical Products Agency. Retrieved 31 July BBC News - Health. Retrieved 8 February Retrieved May 20, Is Cannabidiol the Answer for Disorders of Motivation? Annual Review of Neuroscience. Williams, Alex October 27, The New York Times.
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Ethadione Paramethadione Trimethadione ; Succinimides: In late medieval Germany and Italy , hemp was employed in cooked dishes, as filling in pies and tortes , or boiled in a soup. The use of hemp as a cloth was centered largely in the countryside, with higher quality textiles being available in the towns. The Spaniards brought hemp to the Americas and cultivated it in Chile starting about As early as , the first Virginia House of Burgesses passed an Act requiring all planters in Virginia to sow "both English and Indian" hemp on their plantations.
George Washington pushed for the growth of hemp and even grew hemp himself, as it was a cash crop commonly used to make rope and fabric. In May he noted in his diary about the sowing of seeds each day until mid-April. Then he recounts the harvest in October which he grew 27 bushels that year. There is some speculation that George Washington smoked the flower of the cannabis plant in order to achieve a recreational high "Like all farmers, Washington probably sampled the quality and potency of what he grew, and he may have used this hemp to treat his chronic tooth aches" ,  but there is no evidence in any of his writings that he grew hemp for anything other than industrial purposes.
It is sometimes supposed that an excerpt from Washington's diary, which reads "Began to seperate [ sic ] the Male from the Female hemp at Do. However, the editorial remark accompanying the diary states that "This may arise from their [the male] being coarser, and the stalks larger"  In subsequent days, he describes soaking the hemp  to make the fibers usable and harvesting the seeds,  suggesting that he was growing hemp for industrial purposes, not recreational.
George Washington also imported the Indian Hemp plant from Asia, which was used for fiber and, by some growers, for intoxicating resin production. In a letter to William Pearce who managed the plants for him Washington says, "What was done with the Indian Hemp plant from last summer?
It ought, all of it, to be sown again; that not only a stock of seed sufficient for my own purposes might have been raised, but to have disseminated seed to others; as it is more valuable than common hemp. Historically, hemp production had made up a significant portion of antebellum Kentucky's economy.
Before the American Civil War , many slaves worked on plantations producing hemp. In , the Marihuana Tax Act of was passed in the United States, levying a tax on anyone who dealt commercially in cannabis, hemp, or marijuana. One claim is that Hearst believed [ dubious — discuss ] that his extensive timber holdings were threatened by the invention of the decorticator which he feared would allow hemp to become a cheap substitute for the paper pulp used for newspaper.
Further, decorticators did not perform satisfactorily in commercial production. Another claim is that Mellon, Secretary of the Treasury and the wealthiest man in America at that time, had invested heavily in DuPont 's new synthetic fiber, nylon , and believed [ dubious — discuss ] that the replacement of the traditional resource, hemp, was integral to the new product's success.
Joe "Daddy Burt" Burton, a recognized top Kentucky hemp farmer with harvested hemp, United States "Marihuana" production permit. In the United States, hemp cultivation is legally prohibited , but during World War II farmers were encouraged to grow hemp for cordage, to replace Manila hemp previously obtained from Japanese -controlled areas. Hemp has been grown for millennia in Asia and the Middle East for its fibre.
Commercial production of hemp in the West took off in the eighteenth century, but was grown in the sixteenth century in eastern England. In the early s, world production of hemp fiber ranged from to metric tonnes, Russia was the biggest producer. In Western Europe, the cultivation of hemp was not legally banned by the s, but the commercial cultivation stopped by then, due to decreased demand compared to increasingly popular artificial fibers. The world production of hemp fiber fell from over , metric tons to about 75, metric tons in the early s and has after that been stable at that level.
In Japan , hemp was historically used as paper and a fiber crop. Many Kimono designs portray hemp, or asa Japanese: In , marijuana was restricted as a narcotic drug. The ban on marijuana imposed by the United States authorities was alien to Japanese culture, as the drug had never been widely used in Japan before. Though these laws against marijuana are some of the world's strictest, allowing five years imprisonment for possession of the drug, they exempt hemp growers, whose crop is used to make robes for Buddhist monks and loincloths for Sumo wrestlers.
Because marijuana use in Japan has doubled in the past decade, these exemptions have recently been called into question. The cultivation of hemp in Portuguese lands began around the fourteenth century onwards, it was raw material for the preparation of rope and plugs for the Portuguese ships.
Colonies for factories for the production of flax hemp, such as the Royal Flax Hemp Factory in Brazil. After the Restoration of Independence in , in order to recover the ailing Portuguese naval fleet, were encouraged its cultivation as the Royal Decree of D.
John IV in In , the cultivation of hemp became illegal, and the production was substantially reduced. From Wikipedia, the free encyclopedia.
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Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Industrial hempseed harvesting machine in France. List of hemp diseases. The use of hemp in Taiwan dates back at least 10, years. Hemp portal Cannabis portal Agriculture portal. The Free Dictionary, Farlex, Inc. The Plant with a Divided History. Specialty Oils and Fats in Food and Nutrition: Properties, Processing and Applications.
The archaeo-linguisitic stratigraphy of technological change in holocene Australia" , in Henning Andersen, Language Contacts in Prehistory: Studies in Stratigraphy , John Benjamins Publishing, p. Archived from the original on 27 December Retrieved 19 June Conde Nast, Custom Analysis. Retrieved 19 February Journal of Agricultural and Food Chemistry.
Retrieved 20 September Retrieved 8 July European hemp industry till Cultivation, raw materials, products and trends, " PDF. Paper and Board grades.
Papermaking Science and Technology. Journal of the International Hemp Association. Archived from the original on September 27, In the US, pet manufacturers use hemp in dog and cat bedding.
Using Plants to Clean Soil". Archived from the original on The paper then discusses the potential of hemp as an alternative crop. The geography of a controversial plant". In other words, smoking hemp cannot create a 'high.
The dense growth of hemp eliminates other weeds The best growing technique for hemp, planting to plants per square meter, also helps authorities easily tell the hemp from marijuana, which is a plant that is less densely cultivated.
Archived from the original PDF on Retrieved January 8, E; Myles, S Phytochemistry of Cannabis sativa L. Progress in the Chemistry of Organic Natural Products. Indica plants are shorter but a lot more dense than sativas. According to Amplified Fragment Length Polymorphisms". Journal of Forensic Sciences.
Industrial hemp's double dividend: Risula, and others, Saskatchewan Ministry of Agriculture, October ". Cultivation, processing and applications for fibres, shivs and seeds" PDF. European Industrial Hemp Association.
Archived from the original on December 20, Industrial Hemp Production in Canada, February 2, ". Retrieved 18 May Retrieved 25 June Naringenin chalcone is rapidly isomerized by the enzyme chalcone isomerase CHI to form naringenin, the branch point of flavonols on one hand and flavones on the other one. Dihydrokaempferol and dihydroquercetin are substrates of flavonol synthase FLS , which catalyzes the production of the flavonols kaempferol and quercetin, respectively.
Naringenin may alternatively be converted to apigenin, by a reaction catalised by a flavone synthase FNS. In plants, phenolic compounds may act as antioxidants under certain physiological conditions and, thereby, protect plants against oxidative stress. In humans, it was shown that there is a correlation between dietary phenolic compound intake and a reduced incidence of chronic diseases such as cancers, cardiovascular and neurodegenerative diseases Arts and Hollman, , but these positive health effects may not be entirely explained by the phenolic antioxidant properties, as they are poorly bioavailable.
Phenolic compounds may induce the up-regulation of endogenous antioxidant enzymes in vivo , due to their ability to act as pro-oxidants and generate Reactive Oxygen Species ROS Halliwell et al.
They may also exert their action through non-specific protein binding interactions Gertsch et al. The flavones and flavonols found in Cannabis exert a wide range of biological effects, including properties shared by terpenes and cannabinoids. They present anti-inflammatory, anti-cancer and neuro-protective properties as reviewed in Andre et al.
In addition, apigenin has been shown to possess anxiolytic Murti et al. The specific cannflavin A et B are potent anti-inflammatory compounds, via inhibition of prostaglandin E2 and 5-lipoxygenase Werz et al.
Health-related studies concerning lignanamides are scarce and showed in vitro anti-inflammatory Sun et al. Lignans in general show a wide array of health-promoting properties including antioxidant, antiviral, antidiabetic, antitumorigenic and anti-obesity activities.
Interestingly, secoisolariciresinol, lariciresinol and pinoresinol are converted into enterolignans by the anaerobic intestinal microflora, which are mammalian oestrogen precursors phyto-oestrogens Wang et al.
Due to the structural similarity of enterolignans with mammalian oestrogens, these compounds are potentially interesting for combating some hormone-dependent cancers.
The mechanisms of action of the lignans are, however, complex, with multiple targets involved Sainvitu et al. It is now well accepted that the health benefits of fruits, vegetables and other plant foods are due to the synergy or interactions between the different bioactive compounds or other nutrients present in the whole foods, and not to the action of a sole compound Liu, Similarly, Cannabis -based therapeutics exert their pharmacological effects in humans via synergistic or antagonistic interactions between the various phytochemicals described above.
These interactions may occur through various mechanisms including: A good example is the stronger muscle-antispastic effect of a Cannabis extract compared to pure THC, which represents an important finding for the treatment of multiple sclerosis Wagner and Ulrich-Merzenich, Non-THC cannabinoids have shown positive influence on the side effects induced by THC such as anti-anxiety activities. CBD may also reduce the induced cognitive and memory deficits in subjects smoking Cannabis Wright et al.
Terpenes may also alter the pharmacokinetics of THC by increasing the blood-brain barrier permeability. This characteristic has notably been used to patent a transdermal patch, which delivers cannabinoids into the bloodstream by using a terpene as a permeation agent Smith, Terpenes may also modulate the affinity of THC for the CB1 receptor and interact with neurotransmitter receptors, which may support contributions of terpenes on cannabinoid-mediated analgesic and psychotic effects McPartland and Russo, ; Russo, In view of the potential of phytocannabinoid-terpene synergy, it has been suggested to tailor novel therapeutic treatments such as CBD-terpene extracts to be used against acne, MRSA, depression, anxiety, insomnia, dementia and addiction Russo, Finally, there is an example of predator-targeted synergy between terpenes and phytocannabinoids in the Cannabis plant itself: Trichomes are epidermal protuberances covering the leaves, bracts and stems of plants and some of them, like the glandular trichomes, are capable of secreting or storing secondary metabolites as a defense mechanism.
Several papers have focused on the characterization of these specialized structures using -omics Wang et al. An -omics database TrichOME; available at: Additionally, several procedures in some instances supported by a video demonstration; e. Hemp has different types of trichomes Figures 3A—F which belong to two categories, i. Capitate sessile, capitate stalked and bulbous hemp trichomes are secretory structures Figures 3C—F.
A Unicellular non-glandular trichome; B cystolythic trichomes; C capitate sessile trichome; D capitate-stalked trichome; E simple bulbous trichome; F complex bulbous trichome.
Images kindly provided by Dr. In Cannabis THCA is accumulated in the heads glands of both capitate-stalked and capitate sessile trichomes, but in the former the content is higher Mahlberg and Kim, The accumulation in the storage cavity is due to the cytotoxicity of cannabinoids: Heterologous expression of THCAS fused to GFP in tobacco leads to fluorescence of the trichome heads, thereby confirming the localization of the enzyme in the storage cavity Sirikantaramas et al.
Depending on their color, hemp glandular trichomes show different secretory phases Mahlberg and Kim, According to the current model cannabinoids are produced via terpenes secreted by plastids present in the disk cells and phenols stored in their vacuole Mahlberg and Kim, Subsequently vesicles are released into the cavity together with fibrillar matrix originating from the cell walls of the disk cells.
The fibrillar matrix is transported to the subcuticular cell wall and contributes to its thickening via yet unidentified mechanisms Mahlberg and Kim, Besides cannabinoids, Cannabis trichomes produce other secondary metabolites, namely terpenes see previous paragraph on Cannabis phytochemicals , which are responsible for the typical plant aroma Russo, Among the Cannabis terpenes of low abundance, is nerolidol 0.
Given the pharmacological importance of these compounds, it would be interesting to devise engineering strategies aiming at either boosting the secondary metabolism, or increasing the density of trichomes in Cannabis. Among the possible genetic engineering approaches, it is here worth mentioning two examples recently reported in Artemisia annua.
We will here discuss only these two examples, as further discussion on how to scale up the production of cannabinoids is presented later in this review. It has been recently shown that the transformation of A. The rol genes are known for their stimulatory action on plant secondary metabolism Bulgakov, The study on A. An additional study on A. The hydrolytic enzyme favors the release of active plant growth regulators from the conjugates stored in the plastids, thereby favoring trichome formation, as well as biomass production and leaf area Singh et al.
It would be interesting to devise an engineering strategy aimed at increasing the density of trichomes in Cannabis , by adopting a similar strategy. In this section of the review we will: The cultivation of Cannabis is severely regulated in many countries; therefore alternative in vitro growth techniques are receiving a lot of attention. Methods to multiply C. It was shown that micro-propagated plants are genetically stable; therefore the method is appropriate and useful for the clonal multiplication of this important crop Lata et al.
A protocol has also been developed for the propagation of hemp via the synthetic seed technology. According to this procedure, axillary buds or nodal segments are encapsulated in calcium alginate beads Lata et al. This system was shown to allow the successful growth of homogeneous and genetically stable Cannabis plants even after 6 months of storage Lata et al.
To set up a successful Cannabis transformation protocol, the mastery of in vitro culture techniques is necessary: Organ regeneration, in particular shoots, can be quite cumbersome and therefore the screening of different plant growth regulator concentrations and combinations has to be carried out to find the right culture medium composition.
Cannabis sativa is a notorious recalcitrant plant to transformation, because the regeneration efficiencies are quite low and dependent upon the cultivar, tissue, plant age and growth regulator combination Slusarkiewicz-Jarzina et al.
As an example, although successful transformation of hemp calli via Agrobacterium tumefaciens was reported by Feeney and Punja , the undifferentiated cells failed to regenerate the shoots. The cells were transformed with phosphomannose isomerase and colorimetric assays showed successful expression of the transgene.
Nevertheless some success in hemp regeneration was reported and shown to be linked to the choice of specific plant growth regulators. For example the addition of thidiazuron TDZ , which has cytokinin-like activity, was shown to increase the development of shoots in hemp explants Lata et al.
Cannabis transformation protocols using plant explants thereby avoiding the passage to undifferentiated cells have been described for several important crops e. Notably, successful transformation of hemp plants was reported by MacKinnon et al.
Additionally a patent application was filed describing Cannabis transformation using 1—2 cm hypocotyl explants, the plant growth regulators zeatin and 6-benzylaminopurine BAP for shoot regeneration Sirkowski, An additional system offering interesting applications for the industrial production of compounds showing pharmaceutical effects in humans is the hairy root system, a type of Agrobacterium -transformed plant tissue culture used to study plant metabolic processes.
Transformation of hemp and subsequent establishment of hairy root culture has been described by Wahby et al. In this study hypocotyls were found to be the most responsive tissue for infection. The hairy root system is very interesting for the production of secondary metabolites in medicinal plants Jiao et al. The hairy root system is characterized by hormone-independent high growth rate and by the same metabolic potential as the original organ Pistelli et al.
A protocol for the establishment of hairy roots from Cannabis callus cultures has also been described Farag and Kayser, The authors found that after 28 days of cultivation in the dark, a peak could be observed in the accumulation of cannabinoids in culture media supplemented with different concentrations of indoleacetic acid IAA. The production of cannabinoids in hemp hairy root cultures can be then further implemented with adsorbents to avoid toxicity issues a more detailed discussion concerning possible ways to avoid toxicity is present in the section dedicated to heterologous plant hosts.
In alternative, inducible promoters can be used, like for instance the glucocorticoid-inducible promoter, which was already shown to be effective in inducing a controlled, reversible and dosage-dependent expression of GFP in Catharanthus roseus hairy roots Hughes et al.
Plant cell suspension cultures offer important advantages, as they can be transformed and then cultivated in bioreactors for the production of useful metabolites Weathers et al. Cannabis callus cultures are not able to produce any cannabinoids, irrespective of the chemotypes drug-, hybrid-, or fiber-type used as mother plants or growth regulators used in the culture medium Pacifico et al.
The transformation of hemp cell suspension cultures with genes involved in specific metabolic pathways can offer the possibility of enhancing the production of important classes of metabolites such as cannabinoids but also of others with potential pharmacological use.
In this paragraph we will discuss about potential biotechnological approaches to boost the production of cannabinoids in Cannabis cell suspension culture. It is important to mention here that two transcription factors belonging to the MYB family were already shown to be preferentially expressed in Cannabis glands Marks et al.
These genes show homology with Arabidopsis thaliana MYB and MYB12, which are known to be involved in the tolerance to oxidative stress and flavonol biosynthesis, respectively Marks et al. The expression of these transcription factors in an inducible manner is a strategy worth being tested for the production of cannabinoids. The inducible expression will limit the negative effects caused by the toxicity of the accumulating cannabinoids during the growth of the transformed plant cells as more thoroughly described in the next section.
Workflow showing the achievements in green and potential future approaches in light blue to produce cannabinoids in cultures of Cannabis , as well as other plant hosts. In addition to the genetic engineering approach, plant cell suspension cultures can be elicited to boost the production of secondary metabolites. The literature is rich in examples concerning the increased expression of secondary metabolites in plant cells elicited with different factors reviewed recently by Ncube and Van Staden, Both biotic and abiotic stress factors can indeed be used to re-direct the plant metabolism: In hemp suspension cells, elicitation with biotic and abiotic elicitors did not induce an increase in cannabinoids Flores-Sanchez et al.
It is here worth mentioning the effect of a so far neglected element, silicon Si. Despite being a non-essential element for plant growth, Si is known to increase plant vigor and to alleviate the effects of exogenous stresses Epstein, Very recently Si was shown to alleviate the effects of salt stress and to induce the production of chlorogenic acid in Lonicera japonica Gengmao et al.
Given the stimulatory effects that Si has on plant metabolism, it is interesting to further investigate, from a molecular perspective, the effects of Si supplementation on Cannabis secondary metabolite production.
Cyclodextrins have also been used in plant cell suspension cultures to enhance the production of various non-polar metabolites such as stilbenes Yang et al.
They are known to form inclusion complexes with lipophilic compounds, including cannabinoids Hazekamp and Verpoorte, , in their hydrophobic cavity, thereby improving metabolite solubility in an aqueous environment. It would therefore be worth investigating the effect of cyclodextrins on the production of the non-polar cannabinoids in hemp suspension cell cultures. For example synthetic biology could be used to recreate the cannabinoid biosynthetic pathway in heterologous plant cells via the expression of THCAS, together with the upstream enzymes involved in the synthesis of CBG, i.
Examples for the occurrence of metabolons exist in plants for pathways involving, e. Entire metabolic pathways can be engineered via the use of synthetic metabolons enabling the association of enzymes in close proximity: One possible way to assemble a synthetic metabolon is via the use of a scaffolding protein enabling the association of the enzymes Singleton et al. The assembly of multimodular constructs for expression in plants is no longer an insurmountable challenge, thanks to the development of methods like the Gateway-mediated cloning reviewed by Dafny-Yelin and Tzfira, , Golden Gate Binder et al.
When cannabinoids are produced in heterologous plant hosts, toxicity effects have to be taken into account, as it was shown that THCA and CBGA cause cell death via apoptosis in cells of Cannabis and tobacco BY-2 Sirikantaramas et al.
For plant cell suspension cultures cultivated in bioreactors, the in situ product removal via a two-phase culture system might be useful to favor the accumulation of the toxic metabolites produced in sites which are separated from the cells Cai et al. The use of adsorbents in the culture medium can not only sequester the toxic compounds, but also stimulate the secondary metabolite biosynthesis Cai et al. This approach has been recently proposed in A.
The authors induced the formation of an artificial compartment generated by membranes deriving from endocytosis and the endoplasmic reticulum-vacuole trafficking via the expression of a truncated SNARE protein, AtSYP The creation of an artificial compartment can be used for the production of cannabinoids, because it can trap and stabilize the toxic secondary metabolites until extraction is performed, in a manner analogous to what discussed for artemisinin. Hemp is a unique versatile plant, which can provide high biomass quantities in a short time.
Hemp stem is used as a source of woody and bast fibers for the construction and automotive industries, while hemp seeds are used as a source of dietary oil and hemp leaves and flowers as a source of bioactive components.
To date, more than phytochemicals have been described in hemp Gould, , and their pharmacological properties appear to go much beyond psychotic effects, with the capacity to address needs like the relief of chemotherapy-derived nausea and anorexia, and symptomatic mitigation of multiple sclerosis.
Nature has already provided a large source of new molecules and new skeletons. Cannabis presents a colossal potential for enlarging the library of bioactive metabolites. Compounds can be obtained from hemp trichomes, cell suspension cultures, hairy root systems, or via the biotransformation of THCA or CBDA using fungal, bacterial, or plant cells Akhtar et al.
Apart from the importance of studies focused on improving Cannabis genetic transformation, it is necessary to know more about the regulatory mechanisms involved in secondary metabolite production in C. For example enzymological and structural studies will help devise protein engineering approaches to improve the catalytic functions of key enzymes Taura et al.
However, further studies would still be needed to elucidate other key genes involved in biosynthetic pathways of, for instance, less-abundant cannabinoid derivatives. For that purpose, the combination of metabolomics with genome-based functional characterizations of gene products would provide an accelerated path to discovering novel biosynthetic pathways to specialized metabolites.
Indeed, the functions of numerous genes have been identified and characterized through the correlation of gene expression and metabolite accumulation Sumner et al. Classical approaches used focused on the spatial and temporal distribution of the targeted phytochemicals and on the plant transcriptome, as influenced by the developmental stage and environmental stresses.
With respect to the resurgence of interest in Cannabis phytochemicals nowadays, the results of such studies will be soon available. CA was involved in the review writing, J-FH was involved in manuscript refinement, and GG initiated the idea of the review and was involved in the manuscript writing.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors are grateful to Dr David J. National Center for Biotechnology Information , U. Journal List Front Plant Sci v. Published online Feb 4. Author information Article notes Copyright and License information Disclaimer. This article was submitted to Plant Biotechnology, a section of the journal Frontiers in Plant Science.
Received Oct 27; Accepted Jan 8. The use, distribution or reproduction in other forums is permitted, provided the original author s or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
This article has been cited by other articles in PMC. Abstract Cannabis sativa L. Introduction The current climatic and economic scenario pushes toward the use of sustainable resources to reduce our dependence on petrochemicals and to minimize the impact on the environment.
A Source of Fibers with Antibacterial Properties Plant lignocellulosic biomass is an abundant renewable resource, which can provide biopolymers, fibers, chemicals and energy Guerriero et al.
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The cannabis-derived chemical is non-psychoactive, and – while the first time the agency approves a drug derived from the marijuana plant. First off, let's be clear — Cannabis, Hemp and Marijuana are not the same thing. “high”), while CBD does not contain any psychoactive properties. THC is also commonly extracted from the plant and used in a variety of. CBD flower is cannabis bud that helps people relax without feeling for cannabidiol (CBD) for a therapeutic and non-psychoactive experience.