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Chemical structures of (a) hexahydrocannabinol (HHC), (b) cannabigerol (CBG) and (c) cannabichromene (CBC).
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Cannabidiol (CBD) is a naturally occurring, non-psychotropic cannabinoid of the hemp plant Cannabis sativa L. and has been known to induce several physiological and pharmacological effects. While CBD is approved as a medicinal product subject to prescription, it is also widely sold over the counter (OTC) in the form of food supplements, cosmetics a...
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Context 1
... discuss their psychotropic effects, the most common cannabinoids may be divided into two major groups according to the number of rings in the molecule. The first group is composed of tricyclic cannabinols including CBN, and all THC and hexahydrocannabinol (HHC, Figure 3a) isomers. The second group-which will be discussed later in this section-consists of bicyclic cannabinoids with CBD, cannabigerol (CBG, Figure 3b) and cannabichromene (CBC, Figure 3c) being the most prominent representatives. ...
Context 2
... first group is composed of tricyclic cannabinols including CBN, and all THC and hexahydrocannabinol (HHC, Figure 3a) isomers. The second group-which will be discussed later in this section-consists of bicyclic cannabinoids with CBD, cannabigerol (CBG, Figure 3b) and cannabichromene (CBC, Figure 3c) being the most prominent representatives. ...
Context 3
... first group is composed of tricyclic cannabinols including CBN, and all THC and hexahydrocannabinol (HHC, Figure 3a) isomers. The second group-which will be discussed later in this section-consists of bicyclic cannabinoids with CBD, cannabigerol (CBG, Figure 3b) and cannabichromene (CBC, Figure 3c) being the most prominent representatives. ...
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The use of cannabidiol (CBD) in electronic cigarettes is widespread. Previously, it was reported that CBD is partly transformed to THC in case smoking as a cigarette, however, the pyrolysis of this compound has not been assessed extensively. The aim of our study was to investigate the effect of temperature on the composition of pyrolysis products o...
Citations
... Acid catalyzed conversion of CBD into 1 and 2 is a highly debated topic, in particular for the possible occurrence of the reaction under biological conditions. [5] A recent contribution by Passarella and collaborators detailed the effect of different acids and experimental conditions on the product distribution for the ring closing reaction, observing in most cases larger amounts of isomers Δ 9 -THC 1 and Δ 8 -THC 2. [6] Resorcinarene R is an easily prepared compound that selfassembles in apolar media forming a hexameric capsule R 6 held together by a seam of 60 H-bonds (Scheme 2). The capsule has gained attention in the last decade thanks to its application in supramolecular catalysis as a nanoreactor to host metal and organocatalysts, [7][8][9][10][11] as well as a supramolecular organocatalyst itself. ...
... In particular the reaction provided 10 % of Δ 9 -THC 1 and 59 % of the more stable isomer Δ 8 -THC 2, both deriving by ring closing pathway A which is the most common under many acid catalyzed conditions. [5] It is worth noting that the reaction led also to the formation of 29 % of Δ 4(8) -iso-THC 4, which is generally one of the minor isomers observed in the literature, while in the reaction with R 6 it was the second product in terms of relative abundance. In Table 2 are reported for comparison the product distribution observed in our experiment with those reported in the literature. ...
... In Table 2 are reported for comparison the product distribution observed in our experiment with those reported in the literature. [5] Even considering the most similar literature reaction conditions, e. g. toluene at 50°C for 4 h ( Table 2, entry 4), no isomers corresponding to pathway B were observed. It is rather evident the difference in product distribution and the significant formation of the isomer 4 for the reaction in presence of the capsule R 6 . ...
The supramolecular hydrogen‐bonded self‐assembled resorcinarene hexameric capsule promotes the ring closing isomerization of cannabidiol through encapsulation of the intermediate carbocation species formed by protonation with HCl. The confinement effect imparted by the capsule steers product selectivity towards the uncommon products Δ⁸‐iso‐THC, Δ⁴⁽⁸⁾‐iso‐THC, together with the hydrated 8‐Hydroxy‐iso‐THC.
... Due to their interactions with the ECS, vape products marketed with CBD can be used for medicinal purposes to treat seizures and alleviate chronic pain symptoms [6,30]. However, vape liquids may present adverse effects caused by metabolites of chemicals generated in the system and the potency of active components of the vape liquid cartridge [14]. ...
... Authors have postulated that the degradation route of CBD started with a cyclization to Δ9-THC, followed by the thermal degradation to CBN [30,68,69]. All vape products' CBD content quantified using GC was statistically different from the labeled amounts, and the measured amount of CBD was also lower than the labeled amount for the samples. ...
... CBDA is known to convert to CBD after the heating processes, potentially explaining the increased amount of CBD after GC-MS analysis for the Air Factory sample ( Figure 3) [45,70,71]. Additionally, the CBDFx cannabis ingredient list reported a proprietary blend of CBD (Table 1) how these products will affect consumers [30,33,68,70,74]. ...
Cannabidiol (CBD) vape pen usage has been on the rise given the changing political and scientific climate as well as the promotion of these delivery systems as a more accessible and lower‐risk option for consumers. Despite being marketed as a safer way to use cannabis, CBD vape liquids are sold without restrictions or meticulous quality control procedures such as toxicological and clinical assessment, standards for product preservation, or investigative degradation analyses. Nine CBD‐labeled vape liquid samples purchased and manufactured in the United States were evaluated and assessed for cannabinoid content. Quantification and validation of cannabinoids and matrix components was accomplished using gas and liquid chromatography with mass spectrometry analysis (GC–MS and LC–MS/MS) following liquid–liquid extraction with methanol. Samples degraded by temperature (analyzed by GC–MS) showed a greater disparity from the labeled CBD content compared with samples analyzed as purchased (by LC–MS/MS). Thermal degradation of the vape liquids showed increased levels of tetrahydrocannabinol (THC). Also, extended time and temperature degradation were evaluated in vape liquids by storing them for 15 months and then varying temperature conditions before analysis, which indicated CBD transformed into other cannabinoids leading to different cannabinoid content within the vape samples. Evaluation conducted on these vape liquids indicated the route of exposure, storage conditions, and length of storage could expose consumers to unintended cannabinoids and showed a concerning level of disagreement between the products' labeled cannabinoid content and the results generated by these analyses.
... There is continuous interest in cannabinoids like ∆ 9 -tetrahydro cannabinol (∆ 9 -THC) and cannabidiol (CBD), which are the two most important cannabinoids [1,2]. CBD has a different medical and pharmacological profile than ∆ 9 -THC. ...
... However, the interest in CBD is not only explained by its favorable medical and pharmacological profile but also by its potential to be converted to ∆9-THC [2,6], which has caused controversy in the scientific literature. The latter can be easily understood, as CBD accounts for 40% of the cannabis plant extract [3]. ...
... Finally, in 2020, the UN, recognizing their medical applications, has reclassified cannabinoids and removed them from a list of potential very harmful products like various opioids [2,7]. This has undeniably led to renewed interest from the pharmaceutical industry in lesser-known cannabinoids because of possible new pharmacological profiles and the associated patentability, either of the substances or good synthetic routes. ...
There is a continuous interest in cannabinoids like Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Previous experimental research has described the conversion of CBD to either Δ8-THC or Δ9-THC, depending on the acid catalyst applied. The use of para-toluene sulfonic acid (pTSA) has led to the formation of Δ8-THC, while boron trifluoride etherate (BF3·Et2O) has mainly yielded Δ9-THC. The enormous difference in product selectivity between these two catalysts was investigated with Molecular Modeling, applying quantum chemical density functional theory. It was found that pTSA leads to fast isomerization of Δ9-CBD to Δ8-CBD and subsequent ring closure to Δ8-THC. BF3·Et2O catalysis leads to the formation of tertiary carbenium ions in the transition states, which yield Δ9-THC and some iso THC. Under dry conditions in refluxing toluene, it was found that pTSA is predominantly present as a dimer, and only a small fraction is available as monomeric catalyst. Applying the computationally derived activation barriers in transition state theory yielded reaction rates that predicted the amounts of cannabinoids that are in close agreement with the experimental findings from the previous literature.
... Products labeled as and containing Δ 8 -THC have a high probability of being synthetically derived, because it is not generally thought to be economically feasible to extract naturally occurring Δ 8 -THC given the low concentrations present in cannabis and hemp [19]. Depending on the reaction conditions and purification processes, synthetic Δ 8 -THC may be associated with unknown impurities, different degradants, and synthetic cannabinoid analogs that are not naturally produced in cannabis/hemp plant material and for which there may be little or no safety or toxicity data [20][21][22][23]. A common way that Δ 8 -THC is being obtained is through synthetic or semisynthetic conversion from hemp-derived CBD. ...
Concerns about health hazards associated with the consumption of trans-delta-8-tetrahydrocannabinol products were highlighted in public health advisories from the U. S. Food and Drug Administration and U. S. Centers for Disease Control and Prevention. Simple and rapid quantitative methods to determine trans-delta-8-tetrahydrocannabinol impurities are vital to analyze such products. In this study, a gas chromatography-flame ionization detection method was developed and validated for the determination of delta-8-tetrahydrocannabinol and some of its impurities (recently published) found in synthesized trans-delta-8-tetrahydrocannabinol raw material and included olivetol, cannabicitran, Δ ⁸-cis-iso-tetrahydrocannabinol, Δ ⁴-iso-tetrahydrocannabinol, iso-tetrahydrocannabifuran, cannabidiol, Δ 4,8-iso-tetrahydrocannabinol, Δ ⁸-iso-tetrahydrocannabinol, 4,8-epoxy-iso-tetrahydrocannabinol, trans-Δ ⁹-tetrahydrocannabinol, 8-hydroxy-iso-THC, 9α-hydroxyhexahydrocannabinol, and 9β-hydroxyhexahydrocannabinol. Validation of the method was assessed according to the International Council for Harmonization guidelines and confirmed linearity with R² ≥ 0.99 for all the target analytes. The limit of detection and limit of quantitation were 1.5 and 5 µg/mL, respectively, except for olivetol, which had a limit of detection of 3 µg/mL and a limit of quantitation of 10 µg/mL. Method precision was calculated as % relative standard deviation and the values were less than 8.4 and 9.9% for the intraday precision and inter-day precision, respectively. The accuracy ranged from 85 to 118%. The method was then applied to the analysis of 21 commercially marketed vaping products claiming to contain delta-8-tetrahydrocannabinol. The products analyzed by this method have various levels of these impurities, with all products far exceeding the 0.3% of trans-Δ ⁹-tetrahydrocannabinol limit for hemp under the Agriculture Improvement Act of 2018. The developed gas chromatography-flame ionization detection method can be an important tool for monitoring delta-8-tetrahydrocannabinol impurities in commercial products.
... Their popularity has increased in recent years but few scientific studies have investigated the actual effectiveness in animals and specifically horses (6)(7)(8). The predominant cannabis compounds include the phytocannabinoids cannabidiol (CBD) and Δ 9 -tetrahydrocannabinol (THC), which is known for its psychoactive properties (9)(10)(11). CBD is currently under investigation for its proposed relaxing and anxiolytic effects in humans, rodents and dogs (3,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). ...
As a remedy against stress and anxiety, cannabidiol (CBD) products are of increasing interest in veterinary medicine. Limited data is available describing the actual effectiveness of CBD in horses. The aim of this study (part 2 of 2) was to analyze stress parameters via behavioral observation, heart rate monitoring and assessment of blood and saliva cortisol levels in healthy horses treated repeatedly with a CBD containing paste. Twelve horses were randomly assigned to a treatment or a control group. Two pastes were orally administered in a double-blinded study design, one paste containing CBD and one paste without active ingredient. Both pastes were administered twice daily over 15 days (dose: 3 mg CBD/kg). Behavioral observations were conducted daily using a sedation score and a rating of facial expressions, based on the previously described facial sedation scale for horses (FaceSed) and the Horse Grimace Scale. Blood and saliva samples were obtained regularly to determine cortisol levels throughout the study. Cortisol levels were analyzed by means of liquid chromatography/tandem mass spectrometry (LC/MS/MS). Behavioral observations and cortisol levels were compared between groups. Prior to paste administration, a novel object test was performed and the horses’ reaction to loading on a trailer was recorded. Both tests were repeated after 13 days of paste application. Movement patterns such as different gaits during the novel object test were evaluated and an ethogram was designed to assess exhibited behavioral traits. Cardiac beat-to-beat (R-R) intervals were recorded throughout and evaluated using heart rate (HR) and heart rate variability (HRV) parameters. Blood and saliva samples for cortisol analysis were taken before and after the tests. Daily behavioral observations and cortisol levels did not differ between the treatment and the control group. Similarly, analysis of movement patterns, HR, HRV and cortisol levels during the novel object test and trailer test did not identify significant differences between the groups. Regularly administered oral CBD (3 mg/kg BID over 15 days) had no statistically significant effect on behavioral observations, cortisol levels, HR and HRV in horses. Further research is required to establish adequate doses and indications for the use of CBD in horses.
... These changes occur under specific conditions, predominantly involving acidic environments or elevated temperature. [15][16][17] Several studies have shown that CBD can be converted to Δ9-THC during sample processing and analysis when acidic reagents and high temperatures are used. Andrews and Paterson 18 reported that acidic derivatization reagents may result in the conversion of CBD to Δ9-THC, and Dybowski et al. 19 documented the conversion of CBD to Δ9-THC in plasma following the use of acidic protein precipitation agents. ...
... 31 The detection of Δ9-THC in CBD samples during analysis has been the subject of much debate, 32 and a comprehensive review of the conversion of CBD into psychotropic cannabinoids was recently published. 17 In that review, ...
... Golombek et al. 17 (Table 2). An injection volume of 1 μl was used with a split ratio of 20:1. ...
Gas chromatography–mass spectrometry (GC‐MS) is widely used for the identification of cannabinoids in seized plant material. Conditions used for instrumental analysis should maximize decarboxylation, while minimizing the in situ production of Δ9‐THC inside the GC inlet. In this study, decarboxylation of the acidic Δ9‐THC precursor and in situ degradation of cannabidiol (CBD) were investigated using seven commercial GC liners with different deactivation chemistries and geometries. While the inlet temperature was previously optimized at 250°C in a previously validated assay, we systematically examined the temperature‐dependent decarboxylation of tetrahydrocannabinolic acid‐A (Δ9‐THCA‐A) and cyclization of CBD between 230°C and 310°C using different liners using favorable and unfavorable conditions. Significant differences in decarboxylation rate and CBD cyclization were observed between different liner types. While no temperature‐dependent differences in decarboxylation rate were observed within liner type, liner‐dependent differences were observed (α = 0.05), particularly between those with different geometry. In contrast, temperature and liner‐dependent differences were observed for in situ formation of Δ9‐THC (α = 0.05). This was influenced by liner geometry and to a smaller extent by surface deactivation. Effects were exacerbated with liner usage. While significant differences were observed using new and used GC liners, differences between liners of the same type but different lot numbers were not observed. Inter‐instrument differences using the same liner were also evaluated and had minimal effect. Liner‐ and temperature‐dependent effects were also confirmed using more than 20 cannabis plant extracts. Careful selection of liner, inlet conditions, and regular preventive maintenance can mitigate the risks associated with in situ formation Δ9‐THC from CBD.
... For this reason, derivatization of the acidic cannabinoids is mandatory prior GC analysis, which can be time-consuming. Furthermore, temperature can also lead to conversion reactions [24][25][26][27][28], thus resulting in an inappropriate determination of the analyte. Further techniques, such as thin-layer chromatography (TLC) or nuclear magnetic resonance (NMR) have also been employed for the determination of cannabinoids [29,30]. ...
Cannabis sativa L. is an ancient cultivar that has found applications in various fields, e.g., medicine, due to its beneficial effects. However, due to its psychotropic effects, the regulation of this cultivar has increased throughout the decades. In this context, the need for rapid and reliable analytical methods to ensure the quality control of Cannabis cultivars has become of extreme importance. NIRS has arisen as a powerful tool in this field due to its multiple advantages, e.g., non-destructive, rapid, and cost-effective. In this article, the chemometric techniques commonly employed in NIRS method development are described, along with their application for the analysis of Cannabis samples. Regarding qualitative methods, different mathematical treatments and classification models are explained. As for quantitative methods, the representative linear and non-linear modelling techniques applied for the development of prediction equations are described, alongside their application in the Cannabis field. To the best of our knowledge, this is the first time this type of review is written, since there are several articles which address cannabinoid determination, but the main purpose of this review is to enhance the potential of NIRS over the traditional techniques employed for the analysis of Cannabis samples.
... It is possible that the Δ-8 THC found in these products was extracted, purified, and concentrated from cannabis plant material, however the amount of cannabis plant product and the degree of purification required to create mass quantities of the relatively pure/ high concentration products found in our sample population would make this impractical financially and logistically [3]. The proposed synthesis for Δ-8 THC is a well-described reaction that involves heating CBD in an acidic solution to synthesize THC analogs like Δ-8 THC [3,4,[26][27][28][29]. This simple reaction predictably converts CBD to Δ-8 THC and Δ-9 THC depending on the pH, temperature, and reagents used (Fig. 1b). ...
... This simple reaction predictably converts CBD to Δ-8 THC and Δ-9 THC depending on the pH, temperature, and reagents used (Fig. 1b). Similar reactions have been used to synthesize other derivative cannabinoids such as Δ-10 THC [28,30], hexahydrocannabinol (HHC) [28], and THC-O acetate [30]. There are even a variety of do-it-yourself guides on the Internet intended for lay public use [31,32]. ...
... This simple reaction predictably converts CBD to Δ-8 THC and Δ-9 THC depending on the pH, temperature, and reagents used (Fig. 1b). Similar reactions have been used to synthesize other derivative cannabinoids such as Δ-10 THC [28,30], hexahydrocannabinol (HHC) [28], and THC-O acetate [30]. There are even a variety of do-it-yourself guides on the Internet intended for lay public use [31,32]. ...
-8 tetrahydrocannabinol (THC) is a psychoactive cannabinoid and structural isomer of ∆-9 THC that is technically legal under United States Federal law. Commercial ∆-8-THC products being sold are currently unregulated. This study aims to (1) describe the advertising and labeling of Δ-8 THC retail products; (2) compare the advertised amount of Δ-8 THC for each product to that found during independent laboratory analysis; and (3) evaluate the presence and amount of other cannabinoids in those products.
Twenty ∆-8 THC products were purchased from retail stores in Pittsburgh, PA, USA. Samples were analyzed to determine cannabinoid content using a validated UPLC-MS/MS method. Descriptive statistics were calculated for all variables. Spearman’s rank order correlation was calculated for the labeled ∆-8 THC content compared to ∆-8 THC content found on our analysis. Differences in continuous variables were compared using ANOVA, Wilcoxon Rank Sum, or Kruskal–Wallis tests.
∆-8 THC was detected in 95% (N=19) of the sample products. A weakly positive correlation (Spearman’s rho =0.40) was found between the advertised ∆-8 THC content and our analysis results. Factors associated with decreased difference in these variables included (1) solid matrix (chocolate, gummies) and (2) absence of a “lab-tested” label. Δ-9 THC was found in 35% (N=7) of the products, and CBD was found in one.
A majority of the products analyzed contained ∆-8 THC in amounts that could cause intoxication. The range of ∆-8 THC content on independent analysis was wide and weakly correlated to the advertised content. ∆-8 THC, ∆-9 THC, and CBD were the only cannabinoids detected.
... This was demonstrated using decision-point controls in the presence of amounts of CBD that far exceed concentrations encountered in seized plant material. Cyclization of CBD to Δ9-THC is most favorable under acidic conditions [44][45][46], but its formation during GC-MS analysis must also be considered. When GC-MS is used, inlet and instrument conditions during method development should be selected to minimize its production. ...
... In addition, the potential conversion of CBD to other CBD compounds (with THC being of particular interest) has become a topic of debate. There is some evidence for CBD-to-THC conversion biologically and considerable evidence for this conversion under conditions commonly found during analytical identification (Golombek, Müller, Barthlott, et al., 2020;Hložek et al., 2017). ...
Cannabidiol (CBD), a plant-derived cannabinoid compound found in cannabis, has been readily available in the United States since the legalization of hemp products in 2018. With all 50 states legalizing some form of CBD, many products have appeared in the marketplace. The American public generally considers CBD a safe and effective way to manage pain, mental health conditions, and other health issues in children and adults, even though CBD has only been approved for the treatment of specific types of pediatric seizures. This report describes early findings from preclinical CBD studies, select clinical trials, and naturalistic observational studies of CBD users and identifies knowledge gaps in this emerging field, especially those relating to the developmental effects of CBD. The main goal of this report is to identify priorities for future CBD research, particularly those that will benefit the field of child and adolescent psychiatry.
