Send to

Choose Destination
Cannabis Cannabinoid Res. 2016 Apr 1;1(1):102-112. doi: 10.1089/can.2015.0004. eCollection 2016.

Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid.

Author information

Pace Analytical Services, Oakdale, Minnesota.
Zynerba Pharmaceuticals, Inc., Devon, Pennsylvania.
Department of Anesthesiology, University of California, San Diego, La Jolla, California.


Introduction: In recent research, orally administered cannabidiol (CBD) showed a relatively high incidence of somnolence in a pediatric population. Previous work has suggested that when CBD is exposed to an acidic environment, it degrades to Δ9-tetrahydrocannabinol (THC) and other psychoactive cannabinoids. To gain a better understanding of quantitative exposure, we completed an in vitro study by evaluating the formation of psychoactive cannabinoids when CBD is exposed to simulated gastric fluid (SGF). Methods: Materials included synthetic CBD, Δ8-THC, and Δ9-THC. Linearity was demonstrated for each component over the concentration range used in this study. CBD was spiked into media containing 1% sodium dodecyl sulfate (SDS). Samples were analyzed using chromatography with UV and mass spectrometry detection. An assessment time of 3 h was chosen as representative of the maximal duration of exposure to gastric fluid. Results: CBD in SGF with 1% SDS was degraded about 85% after 60 min and more than 98% at 120 min. The degradation followed first-order kinetics at a rate constant of -0.031 min-1 (R2=0.9933). The major products formed were Δ9-THC and Δ8-THC with less significant levels of other related cannabinoids. CBD in physiological buffer performed as a control did not convert 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. Conclusions: SGF converts CBD into the psychoactive components Δ9-THC and Δ8-THC. The first-order kinetics observed in this study allowed estimated levels to be calculated and indicated that the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a physiological response. Delivery methods that decrease the potential for formation of psychoactive cannabinoids should be explored.


THC; cannabidiol; degredation; drug discovery; gastric fluid; kinetics

Conflict of interest statement

J.M. and B.L. were paid consultants, and T.S., C.O., and S.L.B. are employees, of Zynerba Pharmaceuticals. T.Y. has no competing financial interests.

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center