By Stephen Goldner
A very significant laboratory finding[*1] in-vitro shows how CBD dosed orally can convert to delta-9-THC in the human gut. If confirmed in-vivo, this finding may place CBD products, previously considered non-psychoactive, in the same category as psychoactive THC cannabis. The authors used simulated gastric juice, a standard methodology, with well-validated analytical techniques and the paper was published in the referred journal Cannabis and Cannabinoid Research.
This finding is particularly timely and significant because infants and children are dosed with CBD extracts from cannabis for various ailments. While CBD has a well-established safety profile, clinical observations of some children dosed with CBD have shown undesirable and unexpected THC-like effects.
Our laboratory previously demonstrated the chemical equilibrium reactions to convert THC to CBD and recognizes the excellent work shown by Zynerba Pharmaceuticals, in conjunction with University of California, San Diego (UCSD) that may explain some of the untoward and sporadically observed adverse effects in children dosed with oral CBD.
The authors described their rationale for their experiment: “In recent epilepsy research, pediatric subjects receiving orally administered CBD showed a relatively high incidence of adverse events (≤44%), with somnolence (≤21%) and fatigue (≤17%) among the most common. If CBD is non-psychoactive, we wondered whether these responses might be associated with a clinical manifestation of findings from experimental work, suggesting that when CBD is degraded in an acidic environment, it rapidly cyclizes to Δ9-THC and other psychoactive cannabinoids.”
They summarized the results as : “This study demonstrated the acid-catalyzed cyclization of CBD to THC in SGF [simulated gastric fluid]. CBD was degraded into the psychoactive cannabinoids Δ9-THC and Δ8-THC in SGF…The consistent CBD degradation in SGF led to a clear understanding of the kinetics of THC formation in an acidic environment, and the characterization of this rate enabled us to estimate the conversion of CBD to THC after oral dosing.”
“The quantity of THC formed after oral administration of CBD-containing medications can thus be calculated — provided that the proportion of the CBD dose that would be soluble in the acidic gastric environment and thus “available” for degradation is also known. In a true physiological environment, this proportion depends on multiple factors, including (but not limited to) partitioning out of the lipid dosage form, enzyme activity, emulsification, and fasting state. Determining actual CBD solubility in gastric fluid would require studies in human subjects. Based on our results, however, it is clear that at least some portion of an orally ingested dose of CBD will be soluble and degrade to THC.
“In a patient treated with 700 mg oral CBD formulated in a lipid environment (e.g., oil-based solution), even if just 1% of the CBD dose were soluble, total cannabinoid levels, primarily Δ9-THC and Δ8-THC with other degradation products, would be 6.5 mg after 30 min and 13 mg after 60 min. Although the precise activity cannot be definitively determined until in vivo data are available, the central finding remains — significant levels of psychoactive Δ9-THC, Δ8-THC, and other related compounds are formed when CBD is taken orally. With higher CBD doses, greater solubility, and/or longer gastric residence time, it is not difficult to envision scenarios in which Δ9-THC levels of 20–30 mg or higher are reached (i.e., 1–1.5 times the maximum recommended daily dose).
“Despite persistent challenges with dosing and administration, CBD-based therapies have a good safety profile and a potential for efficacy in the treatment of a variety of medical conditions. The rapidly evolving sciences of drug delivery and cannabinoid pharmacology1 may soon lead to breakthroughs that will improve access to the benefits of this pharmacological class of agents.”
Full Disclosure: This writer has developed formulations for the oral and non-oral dosing of CBD and THC.
*1 Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid. Merrick John, Lane Brian, Sebree Terri, Yaksh Tony, O’Neill Carol, and Banks Stan L.. Cannabis and Cannabinoid Research. April 2016, 1(1): 102–112. doi:10.1089/can.2015.0004. http://online.liebertpub.com/doi/full/10.1089/can.2015.0004