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Cannabidiol (CBD), a nonpsychoactive cannabinoid, was found to be converted to 9α-hydroxyhexahydrocannabinol (9α-OH-HHC) and
8-hydroxy-iso-hexahydrocannabinol (8-OH-iso-HHC) together with Δ9-tetrahydrocannabinol (Δ9-THC), a psychoactive cannabinoid, and cannabinol in artificial gastric juice. These cannabinoids were identified by gas chromatography...
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... addition to catalepsy, hypothermia, and barbitu- rate synergism, ∆ 9 -THC possesses antinociceptive effects in experimental animals [13,33,34]. Although 9α-OH- HHC and 8-OH-iso-HHC also exhibited an antinocicep- tive effect against the acetic acid-induced writhing test, their effects were much weaker than those of ∆ 9 -THC (Table 2). CBD did not show any signifi cant effect at 10 mg/kg i.v. in these experiments. ...
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Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa plant that produces antipsychotic effects in rodents and humans. It also reverses L-dopa-induced psychotic symptoms and improves motor function in Parkinson's patients. This latter effect raised the possibility that CBD could have beneficial effects on motor related striatal d...
Citations
... The gut microbiota possesses enzymes such as β-glucuronidase, which can deconjugate glucuronide metabolites of THC, releasing the active form back into circulation [72]. Gut bacteria can metabolize THC into 11-hydroxy-THC (11-OH-THC), which is more potent than THC, and 11-nor-9-carboxy-THC (THC-COOH), which is inactive but used as a marker in drug tests [73]. CBD is metabolized into 7-hydroxy-CBD, a compound with potential anti-inflammatory properties [74]. ...
Historically, the multiple uses of cannabis as a medicine, food, and for recreational purposes as a psychoactive drug span several centuries. The various components of the plant (i.e., seeds, roots, leaves and flowers) have been utilized to alleviate symptoms of inflammation and pain (e.g., osteoarthritis, rheumatoid arthritis), mood disorders such as anxiety, and intestinal problems such as nausea, vomiting, abdominal pain and diarrhea. It has been established that the intestinal microbiota progresses neurological, endocrine, and immunological network effects through the gut–microbiota–brain axis, serving as a bilateral communication pathway between the central and enteric nervous systems. An expanding body of clinical evidence emphasizes that the endocannabinoid system has a fundamental connection in regulating immune responses. This is exemplified by its pivotal role in intestinal metabolic and immunity equilibrium and intestinal barrier integrity. This neuromodulator system responds to internal and external environmental signals while also serving as a homeostatic effector system, participating in a reciprocal association with the intestinal microbiota. We advance an exogenous cannabinoid–intestinal microbiota–endocannabinoid system axis potentiated by the intestinal microbiome and medicinal cannabinoids supporting the mechanism of action of the endocannabinoid system. An integrative medicine model of patient care is advanced that may provide patients with beneficial health outcomes when prescribed medicinal cannabis.
... In vitro investigations have demonstrated the possibility of CBD undergoing conversion into D-THCs. One such in vitro study revealed that within simulated gastric fluid (without pepsin), CBD transformed into a mixture of D-THCs, yielding a 2.9% product alongside other cannabinoid derivatives (Watanabe et al. 2007). In 2016, a study conducted by Zynerba Pharmaceuticals revealed that CBD underwent conversion into D 8 -THC and D 9 -THC (yielding 49%) within 2 h when exposed to simulated gastric fluid. ...
Cannabis sativa, the debatable plant, contains a vast array of phytocannabinoids, with a significant presence of cannabidiol. This cannabinoid possesses numerous medicinal properties, with its analgesic capabilities being one of the earliest subjects of study. While the exact mechanism of how CBD works remains somewhat unclear, its mode of action varies depending on the route of administration, including oral, sublingual, rectal, transdermal, and inhalation. Despite CB’s versatility in addressing various symptoms through multiple administration methods, a noteworthy challenge lies in its limited absorption and bioavailability. The compound's high lipophilicity and low water solubility contribute to its suboptimal bioavailability. To address this issue, extensive research has explored CBD-loaded nanoformulations, encompassing nanomicelles, nanoparticles, SNEDDS (self-nanoemulsifying drug delivery systems), liposomes, and pro-nano-lipospheres. Both preclinical and clinical studies are underway at a substantial pace to establish the safety and efficacy of this cannabinoid. Some CBD nanoformulations have even met FDA regulations and are available in the market. CBD's multifaceted nature, with its potential application against various diseases, has captivated researchers, leading to an increased interest in this compound. This heightened interest has resulted in the filing of numerous patents worldwide. Additionally, research has demonstrated CBD's effects on conditions such as Parkinson's disease, epilepsy, multiple sclerosis, Huntington's disease, Alzheimer's disease, various cancers, pain, and inflammation, which will be discussed in the concluding section of this article.
... Similarly, the chemical stability of CBD in the SEDDS formulation was investigated in the simulated GI tract fluid, focusing on the possibility of protecting the drug from the acidic pH of the stomach. In fact, CBD was found to be highly unstable at low pH values, with significant drug loss that can reach 98 % due to CBD conversion in multiple products (Merrick et al., 2016;Watanabe et al., 2007). As shown in Table 3, the obtained SEDDS demonstrated to guarantee the maintenance of the drug stable passing through low pH value of 1.2 to pH 6.8. ...
... Further literature survey revealed that product 5 has characterization spectra that largely matches those for 8-hydroxy-iso-tetrahydrocannabinol [32] ( Figure 2) which is an impurity found in commercial samples of 2, and that was also observed up to 10 % by treatment of CBD with mineral acids and artificial gastric juice. [33] It is therefore possible to determine that the reaction of CBD with R 6 at 40°C enabled to reverse the traditional selectivity of the reaction towards pathway B with (1 + 2):(3 + 4 + 5) corresponding to 47 : 53 (Table 3). The unusual product selectivity is not only related to the use of mild reaction temperature. ...
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.
... Levels of THC were greatly increased for eight of the nine vape liquids analyzed from the quantification performed after 15 months compared to when purchased using the LC. The samples were greater than one-year-old, and with time, CBD is expected to convert to THC and subsequently to CBN [30,68,77,78]. Likewise, acidity and increased sample temperature are also expected to expedite this conversion [78]. ...
... The samples were greater than one-year-old, and with time, CBD is expected to convert to THC and subsequently to CBN [30,68,77,78]. Likewise, acidity and increased sample temperature are also expected to expedite this conversion [78]. However, a study suggested CBN contributes to negative physiological changes in the mobility and heart rate of zebrafish embryos [82]. ...
... This is concerning given the different effects each cannabinoid can have on the body[6,[83][84][85]. Increased levels of THC, due to improper storage and handling of vape liquids, could cause undesirable psychoactive effects to the consumer believing the purchased product contained only CBD[69,78,86]. Therefore, storage assessments of vape liquids should be thoroughly investigated, and guidance on proper storage and handling conditions should be pro-vided to consumers. ...
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.
... For example, ∆THC, the primary psychoactive compound in cannabis, is metabolized by gut bacteria into 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THC-COOH) [88]. These metabolites exhibit distinct pharmacological properties compared to parent THC, with 11-OH-THC reported to be more potent than THC, while THC-COOH is considered inactive but is often used as a plasma marker of cannabis consumption in drug tests [51,88]. ...
... For example, ∆THC, the primary psychoactive compound in cannabis, is metabolized by gut bacteria into 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THC-COOH) [88]. These metabolites exhibit distinct pharmacological properties compared to parent THC, with 11-OH-THC reported to be more potent than THC, while THC-COOH is considered inactive but is often used as a plasma marker of cannabis consumption in drug tests [51,88]. Additionally, certain gut bacteria can metabolize CBD into 7-hydroxy-CBD, a compound with potential anti-inflammatory properties [89]. ...
Emerging research has revealed a complex bidirectional interaction between the gut microbiome and cannabis. Preclinical studies have demonstrated that the gut microbiota can significantly influence the pharmacological effects of cannabinoids. One notable finding is the ability of the gut microbiota to metabolise cannabinoids, including Δ9-tetrahydrocannabinol (THC). This metabolic transformation can alter the potency and duration of cannabinoid effects, potentially impacting their efficacy in cancer treatment. Additionally, the capacity of gut microbiota to activate cannabinoid receptors through the production of secondary bile acids underscores its role in directly influencing the pharmacological activity of cannabinoids. While the literature reveals promising avenues for leveraging the gut microbiome–cannabis axis in cancer therapy, several critical considerations must be accounted for. Firstly, the variability in gut microbiota composition among individuals presents a challenge in developing universal treatment strategies. The diversity in gut microbiota may lead to variations in cannabinoid metabolism and treatment responses, emphasising the need for personalised medicine approaches. The growing interest in understanding how the gut microbiome and cannabis may impact cancer has created a demand for up-to-date, comprehensive reviews to inform researchers and healthcare practitioners. This review provides a timely and invaluable resource by synthesizing the most recent research findings and spotlighting emerging trends. A thorough examination of the literature on the interplay between the gut microbiome and cannabis, specifically focusing on their potential implications for cancer, is presented in this review to devise innovative and effective therapeutic strategies for managing cancer.
... Several studies have demonstrated that gut bacteria possess the enzymatic machinery necessary to metabolize cannabinoids into different compounds, which can significantly alter their pharmacological activity (Minakata et al., 2017). For example, ΔTHC, the primary psychoactive compound in cannabis, is metabolized by gut bacteria into 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THC-COOH) (Watanabe et al., 2007). These metabolites exhibit distinct pharmacological properties compared to parent THC, with 11-OH-THC reported to be more potent than THC, while THC-COOH is considered inactive but is often used as a plasma marker of cannabis consumption in drug tests (Huestis et al., 2019;Watanabe et al., 2007). ...
... For example, ΔTHC, the primary psychoactive compound in cannabis, is metabolized by gut bacteria into 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THC-COOH) (Watanabe et al., 2007). These metabolites exhibit distinct pharmacological properties compared to parent THC, with 11-OH-THC reported to be more potent than THC, while THC-COOH is considered inactive but is often used as a plasma marker of cannabis consumption in drug tests (Huestis et al., 2019;Watanabe et al., 2007). Additionally, certain gut bacteria can metabolize CBD into 7-hydroxy-CBD, a compound with potential anti-inflammatory properties (Borrelli et al., 2014). ...
Emerging research has revealed a complex bidirectional interaction between the gut microbiome and cannabis. Preclinical studies have demonstrated that the gut microbiota can significantly influence the pharmacological effects of cannabinoids. One notable finding is the ability of the gut microbiota to metabolise cannabinoids, including Δ^9-tetrahydrocannabinol (THC). This metabolic transformation can alter the potency and duration of cannabinoid effects, potentially impacting their efficacy in cancer treatment. Additionally, the capacity of gut microbiota to activate cannabinoid receptors through the production of secondary bile acids underscores its role in directly influencing the pharmacological activity of cannabinoids. While the literature reveals promising avenues for leveraging the gut microbiome-cannabis axis in cancer therapy, several critical considerations must be accounted for. Firstly, the variability in gut microbiota composition among individuals presents a challenge in developing universal treatment strategies. The diversity in gut microbiota may lead to variations in cannabinoid metabolism and treatment responses, emphasising the need for personalised medicine approaches. The growing interest in understanding how the gut microbiome and cannabis may impact cancer has created a demand for up-to-date, comprehensive reviews to inform researchers and healthcare practitioners. This review provides a timely and invaluable resource by synthesizing the most recent research findings and spotlighting emerging trends. A thorough examination of the literature on the interplay between the gut microbiome and cannabis, specifically focusing on their potential implications for cancer, is presented in this review to devise innovative and effective therapeutic strategies for managing cancer.
... CBD accumulates during hemp growth. In recent years, CBD has demonstrated that it can be converted into THC under some conditions, such as acidic environment [6,7] and e-cigarettes [8]. Up until now, CBD safety for humans has not been clearly defined. ...
In order to facilitate monitoring of cannabidiol (CBD), we devised a gold immunochromatographic sensor based on a specific monoclonal antibody (mAb). To prepare the antigen, a novel hapten with CBD moiety and a linear carbon chain was employed. By utilizing hybridoma technology, a specific mAb was screened and identified that exhibited a 50% maximal inhibitory concentration against CBD ranging from 28.97 to 443.97 ng/mL. Extensive optimization led to the establishment of visual limits of detection for CBD, achieving a remarkable sensitivity of 8 μg/mL in the assay buffer. To showcase the accuracy and stability, an analysis of CBD-spiked wine, sparkling water, and sports drink was conducted. The recovery rates observed were as follows: 88.4–109.2% for wine, 89.9–107.8% for sparkling water, and 83.2–95.5% for sports drink. Furthermore, the coefficient of variation remained impressively low, less than 4.38% for wine, less than 2.07% for sparkling water, and less than 6.34% for sports drink. Importantly, the developed sensor exhibited no cross-reaction with tetrahydrocannabinol (THC). In conclusion, the proposed paper sensor, employing gold nanoparticles, offers a user-friendly and efficient approach for the precise, rapid, and dependable determination of CBD in products.
... At first sight it seems counter-productive to obtain alkylated derivatives, since a major disadvantage of CBD is its high lipophilicity, which impacts negatively in its pharmacokinetics parameters, especially when it comes to absorption and bioavailability rates. However, here, this strategy was intentionally designed to investigate the importance of free phenolic hydroxyls to activity, to explore further hydrophobic interactions, to improve stability and block conversion of CBD to its metabolites via cyclization [21,22]. ...
Cannabis is a general name for plants of the genus Cannabis. Used as fiber, medicine, drug, for religious, therapeutic, and hedonistic purposes along the millenia, it is mostly known for its psychoactive properties. One of its major constituents, cannabidiol (CBD), a non-psychoactive substance, among many other biological activities, has shown potential as an anti-SARS-CoV-2 drug. In this work, seven derivatives and three analogues of CBD were synthesized, and cell viability and antiviral activities were evaluated. None of the compounds showed cytotoxicity up to a maximum concentration of 100 μM and, in contrast, displayed a significant antiviral activity, superior to remdesivir and nafamostat mesylate, with IC50 values ranging from 9.4 to 1.9 μM. In order to search for a possible molecular target, the inhibitory activity of the compounds against ACE2 was investigated, with expressive results (IC50 ranging from 3.96 μM to 0.01 μM).
... MgSO 4 , Na 2 SO 4 , NaCl, MgCl 2 , CH 3 COONH 4 , HCOONH 4 ) [11][12][13]. As demonstrated in [14,15], if an acidic precipitation agent is used, a significant amount of CBD or Δ9-THC in a sample analyzed by GC transforms to their derivatives, making it difficult to accurately quantify these cannabinoids. This is why organic solvent, acetonitrile, was used as precipitation agent in the reported experiments. ...
... MgSO 4 , Na 2 SO 4 , NaCl, MgCl 2 ). The use of acidic precipitating agents (in PP procedure) might allow to receive higher recovery degrees of the examined cannabinoids; yet they should not be used in CBD and Δ9-THC quantification, as an acidic environmental catalyses the transformation of CBD to Δ9-THC and the isomerization of Δ9-THC to Δ8-THC [14,15] -HPLC is a more convenient and reliable analytical method than GC to quantitate the examined cannabinoids in the PP supernatant. The Table 1 Binding degree of CBG, CBD, Δ9-THC and CBN (in %) with human plasma proteins. ...
... occurrence of matrix effect during GC analysis of cannabinoids in PP supernatants limits the use of this technique to plasma samples containing cannabinoids to high concentration levels at which the influence of matrix effect on the final result is irrelevant (see bars with two asterisks in part I of Fig. 1C). The use of GC for the analysis of PP supernatants from plasma samples containing low levels of cannabinoids, usually found in human blood, requires the removal of substances that cause matrix effect (e.g. by performing d-SPE after the PP procedure), or the use of calibration methods eliminating errors resulting from matrix effect (e.g. the use of deuterated analytes as internal standards in the internal calibration method [14,15]). ...
The sensitivity of complex analytical procedures depends not only on the sensitivity of the analytical instrument used, but also on the recovery degree of the examined analyte by the employed sample preparation method. The recovery degrees of individual cannabinoids reported in literature, estimated using the same sample preparation method, are unexpectedly divergent. Therefore, the aim of this study was a thorough assessment of the most commonly used sample preparation methods, such as protein precipitation, LLE, QuEChERS and SPE, in the context of the reliability of the obtained results. The presented report shows that the highest sensitivity, precision and reliability of the chromatographic analysis of CBG, CBD, ∆9-THC and CBN in human plasma can be obtained using SPE. The recovery degrees of these cannabinoids by SPE are highly repeatable and exceed 95 %, while they are significantly lower for such sample preparation methods as protein precipitation, LLE and QuEChERS (ca. 80, 65 and 87, respectively). Moreover, the supernatants obtained by the latter methods contain interferents evoking matrix-effect, which makes reliable quantification of the listed cannabinoids by GC difficult. To our knowledge, the paper is the first such extensive comparison of sample preparation procedures used for the determination of cannabinoids in plasma by GC-MS and HPLC-MS. The presented results and the discussion allow to understand why different recovery degrees for the same xenobiotic can be find in literature despite they have been estimated using the same or different sample preparation method or different chromatography types.
