The Ability of Cannabinoids CBD, CBG, THC and their Combination to Inhibit Capsaicin Responses

Will THC Turn into CBD when Exposed to Gastric Fluid?

Cannabidiol products – known more commonly by its abbreviated name, ‘CBD’ – have become increasingly common in recent years as both the medical and the wellness industries continue to learn more of the compound’s potential effects. CBD is one of the major cannabinoids produced by the Cannabis plant alongside Δ9 -tetrahydrocannabinol (THC). Unlike THC, CBD is non-intoxicating and therefore is not associated with the development of euphoria that can be associated with THC. 

A number of cannabis-based medical products (CBMPs) contain CBD, either alone or in combination with other cannabinoids, including THC. Furthermore, CBD can now be found in a vast number of health and wellness products. In order to be sold as wellness products or within foods in the UK, the products which list CBD as an ingredient must contain no more than 0.2% THC. Despite the non-intoxicating nature of CBD, some anecdotal reports state that some motorists and participants of an abstinence control program claiming to exclusively consume CBD products tested positive for THC or its metabolites.

CBD and THC are formed through the decarboxylation of their precursors tetrahydrocannabinolic acid (THC-A) and cannabidiolic acid (CBD-A). Spontaneous conversion of CBD to THC in an acidic environment has been reported in existing scientific literature; however, results of in vitro experiments of this conversion have not been consistent. Furthermore, in vivo conversion of CBD to THC has only been reported in rats and has not been observed in in vivo studies in animals and humans. 

CBD Conversion to THC

The researchers of a recent study explain that the conversion of CBD to THC has been observed in simulated gastric fluid experiments. Furthermore, they theorise that users who orally administer CBD in combination with an emulsifier or food that may improve the solubility of the compound may experience the intoxicating effects of converted THC. As a result, participants of an abstinence control program and motorists will be at risk of being tested positive for THC or its metabolites. 

To test this theory, the researchers performed an in-human experiment. The primary aim of the study was to prove if a conversion of CBD to THC is possible under “optimised” solubility conditions. Another objective was to investigate whether the consumption of CBD liquid can produce relevant blood concentrations of THC, 11-hydroxy-Δ9 -THC (THC-OH), and 11-nor-9-carboxyΔ9 -THC (THC-COOH). Finally, the researchers also checked if the concentration of THC-COOH in urine exceeded the cut-off (10 ng/ml) according to the German evaluation guideline for driving ability. 

Design and Methods of the Study

A total of nine healthy volunteers participated in this study. Each participant consumed 2 ml of water-soluble CBD liquid (approximately 400 mg of CBD; 0.24 mg THC) in 6 ml of ethanol (42% vol), containing 500 mg lecithin (an emulsifier). During the hour following ingestion of the CBD solution, participants were able to consume no more than 100 ml of fluid.

A number of samples were collected from each of the nine participants at regular intervals following ingestion of the CBD solution: Blood samples were taken at 0, 1, 2, and 4 hours following ingestion; serum was immediately obtained by centrifugation; spot urine samples were submitted at 0, 2, 6, 12, 24, and 46 hours after ingestion.

Results of the Study

The blood and urine samples were assessed for the presence of THC and its metabolites (THC-OH and THC-COOH). Neither THC, THC-OH, nor THC-COOH was detectable in any of the submitted serum samples. The highest mean concentrations of CBD and its metabolites (7-OH-CBD and 7-CBD-COOH) were detected 2 hours after ingestion of the CBD solution. 

All samples that were investigated tested negative for THC-COOH at 0, 2, and 48 hours following ingestion. The highest THC-COOH values were observed in four samples 6 hours after ingestion. Urine samples of one participant were positive for THC-COOH up to 24 hours following ingestion. Trace amounts of THC-COOH below the limit of quantification were detected in the samples of one participant after 12 and 24 hours, and four participants tested negative for THC-COOH in all urine samples.

This study aimed to determine whether a conversion of CBD to THC occurs under “optimised” solubility conditions in human gastric fluid. These results show that, even under these favourable conditions, all serum samples were negative for THC and its metabolites; however, some positive results were obtained from urine samples. According to the German evaluation guideline for driving safety, only one of the nine participants exceeded the threshold of 10 ng THC-COOH/ml urine at 6 and 12 hours after ingestion. Similarly, only one sample surpassed the threshold of 15ng/ml according to the mandatory guidelines for federal workplace drug testing.

CBD Conversion in Existing Literature

The first study to observe the conversion of CBD to THC in acidic conditions was published in 1965. A number of subsequent in vitro studies have also observed the conversion of CBD to ∆8 -THC and cannabinol (CBN) with the addition of hydrochloric acid. Hlozek et al reported positive readings for THC in serum and brain in rats following the administration of CBD. However, there are also a number of studies (including in rats and in man) in which conversion of CBD to THC has not been observed. 

Researcher Conclusions

The present study is the first to apply CBD in combination with an emulsifier and ethanol as a solubilising agent. While, in theory, the addition of these components created “optimised” conditions for the conversion of CBD to THC, this did not lead to substantial conversion of CBD to THC or its metabolites in most of the examined samples. The researchers consider that the trace amounts of THC present in the ingested CBD solution may be at least partly responsible for the low concentrations of THC-COOH in several urine samples. 

The researchers conclude that ingestion of an oral dose of 400mg CBD under optimised conditions did not result in clinically relevant conversion to THC. Despite the detection of small amounts of THC-COOH in some urine samples, it is unlikely that CBD consumption will lead to positive serum samples for THC and its metabolites. Nonetheless, the authors of this study conclude that there is a reasonable risk for consumers of CBD products to test positive for THC or THC metabolites; however, they note that is probably not caused by CBD cyclization into THC in human gastric fluid but most likely due to a THC impurity of CBD products resulting either from improper extraction or storage conditions.