Research is showing CBD to be a potential therapeutic for gut and digestive disorders such as irritable bowel syndrome and leaky gut. One of the lesser known benefits of CBD is its amazing ability to improve the digestive system. It seems that CBD is capable of treating an. It's essential to understand the ECS if you want to understand how CBD works. Let's not forget the role of stress and anxiety when it comes to digestion! CBD has been shown to promote stress resilience and decrease anxiety, adding and in methotrexate-treated rats. J Mol Med 85, – (). 5.
Digestive Your 5 System CBD Can Ways Improve
The plasma concentration-time profiles following oral administration of THC, the main psychoactive natural cannabinoid, in lipid-free vehicle and lipid-based formulation are presented in Figure 1. IV bolus administration was used to calculate the absolute bioavailability.
The pharmacokinetic parameters derived from these concentration-time profiles are summarised in Table 2. The absolute bioavailability of THC was increased by more than 2.
The plasma concentration-time profiles following the oral administration of CBD, the main non-psychoactive natural cannabinoid, in lipid-free vehicle and lipid-based formulation are presented in Figure 2. The pharmacokinetic parameters derived from these concentration-time profiles are summarised in Table 3.
The absolute bioavailability of CBD was increased by almost 3-fold following oral administration in lipid-based formulation compared to lipid-free vehicle. The intraluminal processing of cannabinoids co-administered with dietary fats or pharmaceutical lipid excipients has been assessed in this work using an in vitro lipolysis model. The results are shown in Figure 3. Upon lipolysis of sesame oil, around one-third of THC The intestinal lymphatic transport potential of THC and CBD was assessed using incubation studies with artificial lipid emulsion and with natural rat and human CM [ 27 , 29 ].
The results of the uptake are shown in Figure 4. No significant differences were seen between the uptake of cannabinoids by artificial lipid particles, rat CM or human CM Figure 4. Differences between data sets were statistically non-significant. Over the last few years, the medicinal use of cannabis has gained growing interest after a long period of marginalization [ 9 ].
The legalisation of medical cannabis programs has noticeably increased the access of patients to cannabis and cannabis-based medicines in many countries [ 8 ]. For many patients, orally administered cannabis and cannabis-based medicines are preferred [ 1 , 11 ].
Orally administered cannabis is often consumed with dietary fat-containing food such as cookies. Lipids are also commonly used in pharmaceutical formulations of cannabis or cannabinoids. The rationale for the use of dietary fats and lipids is to enhance the extraction of the lipid-soluble active constituents [ 1 , 12 , 13 ].
However, the impact of dietary fats or pharmaceutical lipid excipients on the systemic exposure of patients to the cannabinoids has not previously been explored.
This could be of particular importance when it comes to therapeutic efficacy or potential toxicity. In this study we aimed to assess the effect of lipids on the systemic exposure to the main constituents of cannabis, THC and CBD, following oral consumption of cannabis with dietary fats or oral administration of cannabis-based medicines. Our results show that the co-administration of cannabinoids with lipids enhances the bioavailability of THC in rats by more than 2.
Such a profound increase in systemic exposure can significantly affect the therapeutic effects or toxicity of these cannabinoids. To the best of our knowledge there are no previously reported studies of absolute oral bioavailability of these cannabinoids in rats. To explore the mechanism s by which lipids could enhance the oral bioavailability of THC and CBD, we first assessed the effect of lipids on intraluminal intestinal solubilisation of cannabinoids using in vitro lipolysis experiments.
In vitro lipolysis is a commonly used model in pharmaceutics to assess the intraluminal processing of drugs administered orally with lipid-based formulation, or following high-fat meals [ 26 ]. The results of our lipolysis experiments showed that around one-third of THC and CBD was solubilised in mixed micelles. This suggests that two-thirds of the administered dose of THC and CBD is not readily available for absorption when cannabinoids are administered orally in the presence of lipids.
Long intestinal transit times and increased bile salt and phospholipid levels due to concomitant food intake might permit more efficient solubilisation of the drugs in vivo [ 35 ]. To assess post-luminal inside the enterocytes effects of lipids on the absorption of THC and CBD, we evaluated the role of the intestinal lymphatic transport in the absorption process of cannabinoids.
The association of lipophilic compounds with CM in the enterocyte is a pre-requisite for their intestinal lymphatic transport.
The affinity of compounds for CM ex vivo has previously been shown to be predictive for the intestinal lymphatic absorption of drugs [ 29 ]. In this study, the lymphatic transport potential was initially investigated by assessing the uptake of THC and CBD by artificial CM-like lipid particles. However, lipid particles lack the surface apoproteins found in natural CM which might affect the process of association [ 27 ].
Association experiments were also performed with natural CM isolated from rats and showed association values of Therefore, the data suggest that CM serve as carriers to transfer THC and CBD to the systemic circulation via the intestinal lymphatic system following oral administration with lipids. Drugs that are transported via the intestinal lymphatic system avoid hepatic first-pass metabolism and therefore achieve significantly higher bioavailability than after administration in lipid-free formulation Figure 5.
Indeed, higher bioavailabilites were reported after administration by routes that avoid first-pass metabolism such as inhalation of THC [ 37 , 42 ] and CBD [ 39 ], or rectal administration of THC [ 40 ].
In addition, it was found in that study that about two-thirds of the absolute bioavailability of PRS, was solely due to a contribution of the intestinal lymphatic transport. These observations support our proposed mechanism of intestinal lymphatic transport as a primary mechanism underlying the enhanced exposure to THC and CBD when co-administered with LCT in rats.
In order to assess if intestinal lymphatic transport might affect bioavailability of cannabinoids in humans, the uptake of THC and CBD by CM isolated from human volunteers was also assessed in our study. Association values observed in these experiments were similar to the uptake profile seen in rat CM Figure 4. Therefore, it is reasonable to assume that similar effects of increased systemic exposure to orally administered cannabinoids when co-administered with lipids would occur in humans.
It is unclear if there is a minimal volume of lipids that is required to activate intestinal lymphatic transport mechanism. Some studies show that as little as 1 g of lipid emulsion was sufficient to activate intestinal lymphatic transport of a highly lipophilic compound in dogs [ 43 ].
In contrast, it has been demonstrated that the administration of a low dose of lipids to rats equivalent to 1 g in humans was not sufficient to enhance intestinal lymph flow. However, a higher lipid dose equivalent to 10 g in humans significantly increased lymph flow [ 44 ]. These amounts of lipids can easily be obtained from the average meal in Western diet [ 45 ].
Indeed, low bioavailability of cannabinoids were reported in humans after oral administration in low volumes of lipid-based formulations 0. However, our results suggest that the same lipid-based formulation-containing capsule administered with a meal, or lipid-rich cannabis-containing cookies, may result in a profound increase in systemic exposure, similar to what has been observed in this study in a rat model.
In conclusion, co-administration of dietary lipids or pharmaceutical lipid excipients may substantially increase the systemic exposure to orally administered cannabis or cannabis-based medicines. Our data suggest that the primary mechanism of the increased absorption of cannabinoids in the presence of lipids is intestinal lymphatic transport. The amount of lipids present in cannabis-containing foods, or following a high-fat meal, is sufficient to activate intestinal lymphatic transport and lead to increased systemic exposure to cannabinoids.
The increase in systemic exposure to cannabinoids in humans is of potentially high clinical importance as it could turn a barely effective dose of orally administered cannabis into a highly effective one, or indeed a therapeutic dose into a toxic one. Therefore, it is important for cannabis-prescribing clinicians and those who self-medicate with cannabis to carefully consider the effect of the co-administration of lipids on the therapeutic outcomes of orally administered cannabis or cannabis-based medicines.
National Center for Biotechnology Information , U. Am J Transl Res. Author information Article notes Copyright and License information Disclaimer.
Received Apr 11; Accepted Jul 3. This article has been cited by other articles in PMC. Abstract There has been an escalating interest in the medicinal use of Cannabis sativa in recent years.
Introduction Cannabis sativa , commonly called hemp, has thousands of years-long history of medical use. In vitro lipolysis The effect of LCT on intestinal processing of lipophilic cannabinoids was assessed using an in vitro lipolysis model.
Association of cannabinoids with artificial chylomicron-like lipid particles and natural rat and human chylomicrons Preparation of artificial lipid particle emulsions: Preparation of rat plasma-derived chylomicrons The protocol for this study was approved by the Home Office in accordance with the Animals [Scientific Procedures] Act Open in a separate window. Results Effect of lipids on systemic exposure to orally administered cannabinoids The plasma concentration-time profiles following oral administration of THC, the main psychoactive natural cannabinoid, in lipid-free vehicle and lipid-based formulation are presented in Figure 1.
Unpaired t -test was used for statistical analysis. Intraluminal processing of cannabinoids co-administered with dietary fats or pharmaceutical lipid excipients The intraluminal processing of cannabinoids co-administered with dietary fats or pharmaceutical lipid excipients has been assessed in this work using an in vitro lipolysis model.
Intestinal lymphatic transport potential of cannabinoids The intestinal lymphatic transport potential of THC and CBD was assessed using incubation studies with artificial lipid emulsion and with natural rat and human CM [ 27 , 29 ]. Discussion Over the last few years, the medicinal use of cannabis has gained growing interest after a long period of marginalization [ 9 ]. Conclusions In conclusion, co-administration of dietary lipids or pharmaceutical lipid excipients may substantially increase the systemic exposure to orally administered cannabis or cannabis-based medicines.
Disclosure of conflict of interest None. The Science of Marijuana. Oxford University Press; History of cannabis as a medicine: Revista Brasileira De Psiquiatria. US History and Policy. Journal of Social Science for Policy Implications.
Where they are and what they do. Innovative Therapeutics or Designer Drugs of Abuse? Sznitman SR, Zolotov Y. Cannabis for therapeutic purposes and public health and safety: Int J Drug Policy. Barriers to access for Canadians who use cannabis for therapeutic purposes. Hall W, Solowij N. Adverse effects of cannabis. Adverse effects of medical cannabinoids: Chronicle Books LLC; Wright S, Guy G.
Cannabidiol in patients with treatment-resistant epilepsy: Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis CAMS study: Pain relief with oral cannabinoids in familial Mediterranean fever. The effect of cannabis on urge incontinence in patients with multiple sclerosis: Evaluation of the in-vitro digestion profiles of long and medium chain glycerides and the phase behaviour of their lipolytic products.
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