Joseph J Wakshlag, PhD
Cornell University, Cultivate Biologics
Co-Authors: Teddy Salan1, Varan Govind1, Eva Widerstrom-Noga1
1University of Miami
Background: Cannabidiolic acid (CBDA) has long been thought to be unstable and potentially converted to cannabidiol after ingestion. Full spectrum hemp CBDA has recently been shown to remain relatively stable at room temperature for up to 18 months.
Objective: A blend of CBDA and CBD from full spectrum hemp was examined for 24-hour pharmacokinetics across dogs (n=8), cats (n = 8), horses (n = 8), macaques (n = 4) and humans (n = 12) using similar dosing regimens of 1-1.3 mg per kilogram of CBD and similar proportions of CBDA to examine the pharmacokinetics using a commercially available product (Cultivate Biologics, Lewisville, CO).
Methods: Each species was dosed at a total of 2-2.5 mg/kg of CBD:CBDA at an equal portion with other minor cannabinoids delivered (< 0.1 mg/kg). The extract was emulsified in sesame oil for oral delivery. Fasted 24-hour pharmacokinetics for each species was performed before and at 0.5,1, 2, 4, 8, 12 and 24 hours after oral delivery. Serum was collected and transported frozen to the laboratory for liquid chromatography and mass spectroscopy (LS-MS/MS) analysis. Maximum serum concentration (Cmax) and time to maximal concentration (Tmax) is reported for all species mentioned. (PK solutions 2.0, Montrose, CA).
Results: The mean + SD CBD Cmax for dogs (1 mg/kg), cat (1.3 mg/kg), horse (1 mg/kg), macaque (1 mg/kg) and human (1 mg/kg) were 185 + 56, 282 + 149, 12 + 6, 9 + 6 and 32 + 19 ng/mL, respectively. Tmax for CBD was 1 + 1, 2 + 1, 2 + 1, 3 + 1 and 4 + 2 hr, respectively. The CBDA Cmax for dogs (1 mg/kg), cat (1.2 mg/kg), horse (1 mg/kg), macaque (1 mg/kg) and human (1 mg/kg) were 923 + 427, 1,011 + 495, 103 + 88, 159 + 87, 714 + 313 ng/mL, respectively. Tmax for CBDA was 1 + 0.5, 2 + 1, 1 + 0.5, 1 + 0.5, and 2 + 1.5 hr, in sequence of species.
Discussion: CBDA is absorbed/retained 5-20 fold more efficiently than CBD across species with a shorter Tmax. CBD and CBDA are absorbed differently across species providing evidence that animal models may differ with oral delivery. In addition, other cannabinoid acids were observed at higher serum concentration than the corresponding neutral cannabinoids (i.e. THCA:THC). These data have led to further clinical evaluation and proposals directed at CBDA as a therapeutic in ongoing proposals within the consortium.