How much THC or CBD does your favorite cannabis product contain? such as CBDA, CBD, THCA, and THC percentages, and perhaps things like “Total . and is less likely to cause further breakdown of THC into CBN or destroy terpenes. How Cannabinoids Are Converted, the Deal With Eating Raw Cannabis, and What (CBDA, CBGA, THCVA) take this acidic form when harvested and it is only. With a rising demand for natural medicines, cannabis compounds, like CBD and THC, are becoming increasingly popular due to their wide.
CBDThe Breakdown vs THC
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.
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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. Open in a separate window.
Their Production Pathways and Myriad of Biological Activities Numerous chemicals are produced in hemp through the secondary metabolism. Phytocannabinoids Phytocannabinoids represent a group of C21 or C22 for the carboxylated forms terpenophenolic compounds predominantly produced in Cannabis.
Table 1 Summary of the concentrations in cannabinoids found in different parts of the hemp plants, in vitro hairy roots, and some commercial medicinal products. The most recent references have been used, when available. Health Benefits Linked to Cannabinoids The pharmacology of phytocannabinoids has previously been reviewed elsewhere Pacher et al.
Adverse Health Effects of Cannabinoids As mentioned earlier, the recreational and medical use of Cannabis as well as of THC and other synthetic cannabinoids have also been associated with numerous side effects. Terpenes Terpenes form the largest group of phytochemicals, with more than molecules identified in Cannabis Rothschild et al. Health Benefits Associated with Terpenes Terpenes are lipophilic compounds that easily cross membranes and the blood-brain barrier in particular Fukumoto et al.
Phenolic Compounds Phenolic compounds, also known as phenylpropanoids, constitute one of the most widely distributed group of secondary metabolites in the plant kingdom.
Health Benefits Associated with Phenolic Compounds In plants, phenolic compounds may act as antioxidants under certain physiological conditions and, thereby, protect plants against oxidative stress. Synergistic and Antagonistic Effects Between Phytochemicals 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, Small Factories of Phytochemicals 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.
Cannabis In Vitro Propagation and Transformation The cultivation of Cannabis is severely regulated in many countries; therefore alternative in vitro growth techniques are receiving a lot of attention. Hairy Root Cultures for the Production of Cannabinoids 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.
Cannabis Cell Suspension Cultures for the Production of Cannabinoids 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. Cannabinoid Production in Heterologous Plant Hosts: Perspectives and Conclusion Hemp is a unique versatile plant, which can provide high biomass quantities in a short time. Author Contributions 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.
Conflict of Interest Statement 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. Dietary antioxidants and oxidative stress from a human and plant perspective: Gene expression changes related to the production of phenolic compounds in potato tubers grown under drought stress.
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While cannabinoids are present within several plants in nature, cannabis is the only plant known to contain CBD. This fact means that when you ingest CBD for medical purposes, you will more likely experience a relief of your unwanted discomfort, with little or no noticeable effect on your cognitive abilities. Research studies indicate that CBD may be useful in helping with: Research suggests CBD may be better for inflammation and neuropathic pain , while THC may excel with spasticity and cramp-related pain.
It is worth noting that sometimes high doses of THC can exacerbate pain symptoms. Meaning THC consumed in this capacity should be done in small amounts. Additionally, many individuals experience difficulty managing the side effects associated with THC, rendering useless any potential benefits.
Some experts suggest that a combination of THC and CBD is the ideal way to approach pain, giving validity to something known as the entourage effect. For example, mg of isolated CBD may be substantially less effective at alleviating symptoms than mgs of a whole-plant, CBD-containing cannabis extract. Many argue that consuming the plant in its whole form provides all the necessary cofactors to facilitate proper absorption.
This argument is at the heart of the debate over CBD oil from hemp vs. CBD oil from cannabis. While it may be cheaper and more cost-effective to extract CBD from industrial hemp, users may ultimately experience less benefit due to the absence of clinically significant levels of terpenes and other compounds which occur in abundance in high-CBD marijuana.
While high-CBD cultivars of cannabis do contain much higher levels of various cannabinoids, terpenes, etc. Agricultural hemp is much closer to the kind of cannabis that one would find growing naturally in the wild, whereas high-CBD marijuana is hybridized and toyed with by growers to produce the highest levels of the desirable compounds.
There is no hard science yet! It is up to each individual to decide which option is best for them. THC is an illegal drug with considerable immediate and long-term cognitive side effects.
These include impaired thinking and reasoning, a reduced ability to plan and organize, altered decision-making, and reduced control over impulses. Also, chronic use of THC correlates with significant abnormalities in the heart and brain. Given the increasing popularity of medical cannabis, breeders are currently creating strains with higher CBD to THC ratios to minimize the psychoactive side effects.
Overall, the lower health risks of CBD, combined with its efficacy, make it a better candidate for natural applications than THC. Your email address will not be published. What is CBD Oil?
Is CBD for Pets? If your furry friend has been suffering from a What is the Clinical Endocannabinoid Deficiency Syndrome? Cannabinoids are chemical compounds that naturally occur in the resin of the Cannabis sativa plant, commonly called A large part of alternative medicine revolves around using the entire plant for medicinal Diana Myers January 20, Can you recommend or educate me as to what to buy?
What is the Difference Between THC and CBD?
And of course, since CBD is derived from the flowers of cannabis plants, You can also ask for lab results that show the exact breakdown of a. CBD vs. THC? Of the at least cannabinoids that have been isolated of THC and CBD from CBGA via their acidic forms THCA and CBDA. Both THC & CBD interact with cannabinoid receptors, but the types of effects Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two primary . Great breakdown of the differences between these two cannabinoids, thanks for the.