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cannabinoid complex reviews

Although a range of analytical methods have been published in recent years [48], there is no general agreement on which analytical method is most suitable and accurate. Additionally, there are currently no generally accepted guidelines or certifications to determine the qualifications of cannabis labs. As a result, cannabinoid analysis can differ significantly between labs [49], even when the exact same sample is analyzed multiple times [50]. This not only poses a risk to consumers (who do not know how trust the label on their product) but may also lead to business-to-business conflicts about the quality or value of intermediate products. Additionally, inaccurate analytical results may lead to legal problems if the THC content of a CBD product unexpectedly turns out to be higher than the maximally allowed limit. It seems clear that a better agreement on the conditions for lab testing of cannabinoids is urgently needed.

If CBD oil was used mainly by adult, well-informed, and reasonably healthy consumers, the impact of its widespread use would perhaps be quite acceptable and limited. However, this is not the case, as CBD is actively marketed for use by children (e.g., for Dravet syndrome, ADHD, autism), elderly people (Alzheimer’s disease, dementia, Parkinson’s disease), patients suffering from complex diseases (cancer, multiple sclerosis, chronic pain), and even pets (anxiety, appetite, sleep). Indiscriminate use of CBD may lead to various issues among these consumers. For example, CBD shows an exciting potential for treating epilepsy in children, but the long-term effects of high-dose CBD on these children’s brain functions remain unclear, while there are strong clues that the endocannabinoid system is central in the proper neuronal development of the adolescent brain [23]. In order to halt the unchecked advertising of CBD products, health authorities in various countries have begun sending official warning letters to stop producers and sellers from making unfounded health claims [24, 25].

Additionally, as many as 26/46 samples (57%) had a THC content > 1%, with one sample peaking at 57.5%. In 18/46 samples (39%) the oil contained virtually only THC (with CBD < 0.1%). Although many of the samples analyzed were purposely made to contain a high THC content, it is unclear whether oil consumers are always aware they are consuming THC, and thereby exposing themselves to the adverse effects of this psychotropic compound, such as intoxication, panic attacks, or disorientation. It should be noted that although the exact legal status of CBD may be debatable, THC-rich extracts are strictly prohibited in virtually all countries.

What Studies Tell Us

Cannabis oils may contain various concentrations of CBD, tetrahydrocannabinol (THC), and minor cannabinoids, mainly depending on the cannabis variety used for extraction. The most popular product currently is CBD oil, but for example cannabigerol (CBG)-rich oil has been spotted as well [2], and others will very likely follow soon. The THC-rich type of cannabis oil has already been known for some years, and is generally known under the name “Simpson oil” [3]. Terpenes may or may not be present in these products, depending on the preparation method used [4]. Because they are highly volatile, elevated temperatures (such as those applied during drying of plant materials, or during the evaporation of solvents) may result in a significant loss of terpene components [5]. However, it is possible to capture evaporated terpenes by condensation, and reintroduce them back into the final oil. Additional ingredients may be added to further adjust properties such as color, viscosity, taste, or shelf-life stability.

It is well known that cannabis plants obtained from uncontrolled sources may be contaminated with various harmful substances [39], sometimes leading to severe health issues or hospitalization [40]. Contaminants include chemicals that were intentionally added in order to increase yield, weight, or potency (e.g., pesticides, metal particles [41], synthetic cannabinoids [42]) but also agents that entered the plant unintentionally (e.g., heavy metals, molds and bacteria [43], aflatoxins). For example, pesticides are frequently present in cannabis sold by Dutch coffee shops [44], but were also found in cannabis offered under state law in California [45] as well as medicinal cannabis from licensed producers in Canada [46]. If any of these contaminants were present in hemp used for CBD extraction, they would likely end up in a concentrated form in the final oil. One contaminant specifically relevant to cannabis (CBD or THC) oils is the residual presence of toxic solvents used during the extraction procedure [3].

In just a few years, cannabidiol (CBD) has become immensely popular around the world. After initially being discovered as an effective self-medication for Dravet syndrome in children, CBD is now sold and used to treat a wide range of medical conditions and lifestyle diseases. The cannabinoid CBD, a non-psychoactive isomer of the more infamous tetrahydrocannabinol (THC), is available in a growing number of administration modes, but the most commonly known is CBD oil. There are currently dozens, if not hundreds, of producers and sellers of CBD oils active in the market, and their number is increasing rapidly. Those involved vary from individuals who prepare oils on a small scale for family and (Facebook) friends to compounding pharmacies, pharmaceutical companies, and licensed cannabis producers. Despite the growing availability of CBD, many uncertainties remain about the legality, quality, and safety of this new “miracle cure.” As a result, CBD is under scrutiny on many levels, ranging from national health organizations and agricultural lobbyists to the WHO and FDA. The central question is whether CBD is simply a food supplement, an investigational new medicine, or even a narcotic. This overview paper looks into the known risks and issues related to the composition of CBD products, and makes recommendations for better regulatory control based on accurate labeling and more scientifically supported health claims. The intention of this paper is to create a better understanding of the benefits versus the risks of the current way CBD products are produced, used, and advertised.

Today, CBD is used for the treatment of a wide range of medical conditions. This started with the somewhat serendipitous discovery (by parents experimenting with self-medication for their children) that CBD had a therapeutic effect on a serious form of epilepsy in children, called Dravet syndrome [8]. This effect is now under clinical investigation with the pharmaceutical CBD product Epidiolex®, which is currently in phase 3 trials with encouraging results [9, 10]. The media attention generated by its effect on severely ill children gave CBD the push needed to become a much desired medicine almost overnight [11]. Other medical indications that may be treated with CBD, and are supported to some extent by clinical proof, include Parkinson’s disease [12], schizophrenia [13], and anxiety disorder [14]. However, although research into the therapeutic effects of CBD is rapidly increasing, most current uses of CBD are not (yet) supported by clinical data. The popular use of these products means that physicians may be confronted with the effects of CBD oil even when they do not prescribe it themselves.

From Table 3, it is clearly obvious that C18 is the most popular column as it is mentioned earlier. The main difference between HPLC and GC is the operating temperature. That is why HPLC is used when preserving the acidic form of cannabinoids are matter. The only disadvantage of HPLC is, it is not able to analyse the volatile compounds like terpenes.

Because consumers have limited means to analyse the chemical composition of the cannabis products, consumers may be inadvertently purchasing products with undesired properties given that different cannabinoids produce different effects (Fischedick et al. 2010b). As a result, it is important to implement methods of quality control so that consumers can be certain that what they are consuming will have the desired effects (Dussy et al. 2005; Fischedick et al. 2010a; Fischedick et al. 2010b). As cannabis use becomes progressively accepted, it becomes increasingly important to quantify the cannabinoid profile and content of cannabis preparations to ensure the uniformity and quality of the preparations (Omar et al. 2014).


Based on the information presented in this review, the ideal cannabinoid quantification method is HPLC- MS/MS for the cannabinoids.

HPLC-electrospray ionization-quadrupole time of flight (HPLC-ESI-qTOF) is very effective in identifying complex and common compounds and can identify the main component of the sample in addition to enhancing the signal to noise ratio in the peaks (Aminah Jatoi et al. 2002). Citti, Ciccarella (Aminah Jatoi et al. 2002) analyzed cannabinoid concentrations in olive oil, ethanol, and supercritical CO2 and found that UV-DAD and qTOF detectors produced similar results, thus suggesting that these two detection systems are equally useful in cannabinoid analysis. Pellati and Brighenti (Brighenti et al. 2017; Pellati et al. 2018) used HPLC-ESI-MS both in positive and negative ion mode for the analysis of cannabinoids. By developing HPLC methods, they improved resolution, peak shape, and separation performance together with the improvement of the ionization in HPLC-ESI-MS (Brighenti et al. 2017; Pellati et al. 2018).

Although MS offers many benefits, the use of qTOF mass spectrometers is ideal when trying to differentiate between two compounds with different compositions but the same nominal mass (Citti et al. 2018). qTOF mass spectrometers can provide accurate mass identification with a threshold less than 5 ppm for precursor and product ions; this allows for differentiation between isomers of cannabinoids (Aizpurua-Olaizola et al. 2014; Citti et al. 2018) such as Δ8-tetrahydrocannabinol and Δ9-tetrahydrocannabinol which have the same m/z because these cannot be differentiated by MS (Citti et al. 2018). Such isomers may have different therapeutic properties and may need to be separated for manufacture, so it is important to adopt an analytical technique that can differentiate between them.