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Cannabis and Cannabinoid Research Publishes Data Demonstrating the Degradation of Cannabidiol to Psychoactive Cannabinoids when Exposed to Simulated Gastric Fluid
“This study demonstrated the acid-catalyzed conversion of CBD to the psychoactive cannabinoids Δ9-THC and Δ8-THC, compared to no evidence of CBD conversion in neutral pH physiological buffer,” said
In recent studies, pediatric patients with epilepsy who received orally administered CBD, showed a relatively high incidence of adverse events (≤44%), with somnolence (≤21%) and fatigue (≤17%) among the most common.1 2 Previous research3 suggests that when CBD is exposed to an acidic environment, it degrades to THC and other psychoactive cannabinoids.
Zynerba undertook the current study to assess the formation of psychoactive cannabinoids when CBD is exposed to SGF. The study showed that CBD was degraded to Δ9-THC and Δ8-THC with less significant levels of other related cannabinoids formed. The degradation followed first-order kinetics at a rate constant of -0.031 min-1 (R2 = 0.9933). CBD in physiological buffer performed as a control did not degrade to THC. Confirmation of THC formation was demonstrated by comparison of mass spectral analysis, mass identification, and retention time of Δ9-THC and Δ8-THC in the SGF samples against authentic reference standards.
The conversion of CBD into the psychoactive components Δ9-THC and Δ8-THC suggests that the oral route of administration may increase the potential for psychoactive adverse effects. The results from this in vitro study suggests that the acidic gastric environment during normal gastrointestinal transit may expose patients treated with oral CBD to levels of THC and other psychoactive cannabinoids that exceed the threshold for a physiological response.
ZYN002 is currently being evaluated in a Phase 1 multiple rising dose trial in healthy volunteers and patients with epilepsy. Zynerba expects to report results from this Phase 1 study by the end of the first half of 2016 and to begin three Phase 2 studies of ZYN002 in each of epilepsy, osteoarthritis and Fragile X syndrome (FXS) patients in the second half of 2016.
About ZYN002 CBD Gel
Zynerba’s ZYN002 CBD gel is the first and only synthetic CBD formulated as a patent-protected permeation-enhanced gel and is being studied in refractory epilepsy, Fragile X syndrome and osteoarthritis. ZYN002 is a clear, permeation-enhanced gel that is designed to provide consistent, controlled drug delivery transdermally with convenient once- or twice-daily dosing. Transdermal therapeutics are absorbed through the skin directly into the systemic circulation, avoiding first-pass liver metabolism and potentially enabling lower dosage levels of active pharmaceutical ingredients and rapid and reliable absorption with high bioavailability. In addition, transdermal delivery avoids the gastrointestinal tract and potential stomach acid degradation of CBD into THC (associated with psychoactive effects).
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company's current expectations. For example, there can be no guarantee that the Company will obtain approval for ZYN002 or ZYN001 from the
1 Press, C., Knupp, K., Chapman K., Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy. Epilepsy Behav. 2015;45:49–52.
2 Devinsky, O., Sullivan, J., Friedman, D., et al. Epidiolex (cannabidiol) in treatment- resistant epilepsy. Poster presented at 67th Annual Meeting of the
3 Watanabe, K., Itokawa, Y., Yamaori, S., et al. Conversion of cannabidiol to D9-tetrahydrocannabinol and related cannabinoids in artificial gastric juice, and their pharmacological effects in mice. Forensic Toxicol. 2007;25:16–21.
Richard Baron, CFO Zynerba Pharmaceuticals484.581.7505 firstname.lastname@example.org Angeli Kolhatkar Argot Partners212.600.1902 email@example.com Media Contact Eliza Schleifstein Argot Partners973.361.1546 firstname.lastname@example.org