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. 2023 Apr 25;16(5):645.
doi: 10.3390/ph16050645.

Trial of a Novel Oral Cannabinoid Formulation in Patients with Hypertension: A Double-Blind, Placebo-Controlled Pharmacogenetic Study

Ana Batinic  1 , Davorka Sutlović  2   3 , Sendi Kuret  2 , Antonela Matana  2 , Marko Kumric  4 , Josko Bozic  4 , Zeljko Dujic  5
Affiliations

Trial of a Novel Oral Cannabinoid Formulation in Patients with Hypertension: A Double-Blind, Placebo-Controlled Pharmacogenetic Study

Ana Batinic et al. Pharmaceuticals (Basel). .

Abstract

Cannabidiol (CBD) is a non-psychoactive cannabinoid, and available evidence suggests potential efficacy in the treatment of many disorders. DehydraTECH™2.0 CBD is a patented capsule formulation that improves the bioabsorption of CBD. We sought to compare the effects of CBD and DehydraTECH™2.0 CBD based on polymorphisms in CYP P450 genes and investigate the effects of a single CBD dose on blood pressure. In a randomized and double-blinded order, 12 females and 12 males with reported hypertension were given either placebo capsules or DehydraTECH™2.0 CBD (300 mg of CBD, each). Blood pressure and heart rate were measured during 3 h, and blood and urine samples were collected. In the first 20 min following the dose, there was a greater reduction in diastolic blood pressure (p = 0.025) and mean arterial pressure MAP (p = 0.056) with DehydraTECH™2.0 CBD, which was probably due to its greater CBD bioavailability. In the CYP2C9*2*3 enzyme, subjects with the poor metabolizer (PM) phenotype had higher plasma CBD concentrations. Both CYP2C19*2 (p = 0.037) and CYP2C19*17 (p = 0.022) were negatively associated with urinary CBD levels (beta = -0.489 for CYP2C19*2 and beta = -0.494 for CYP2C19*17). Further research is required to establish the impact of CYP P450 enzymes and the identification of metabolizer phenotype for the optimization of CBD formulations.

Keywords: CYP P450 genes; GC-MS analysis; SNP genotyping; blood pressure; cannabidiol.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Plasma cannabidiol (CBD (dose A) and DehydraTECH™2.0 CBD (dose B)) concentration in venous blood (I,II) and urine (III). Individual data for 24 participants. Concentrations in plasma samples taken in 120th minute (I) and in 180th minute (II) after ingestion and in urine samples taken in 180th minute (III) after ingestion.
Figure 2
Figure 2
Changes in mean arterial blood pressure (MAP) between generic CBD control (dose A) and DehydraTECH™2.0 CBD (dose B). Data are grouped means (n = 24) with linear regression.
Figure 3
Figure 3
Changes in diastolic blood pressure between generic CBD control (dose A) and DehydraTECH™2.0 CBD (dose B). Data are grouped means (n = 24) with linear regression.
Figure 4
Figure 4
Systolic BP remained depressed throughout the entire 3 h duration of the study for both formulations.
Figure 5
Figure 5
Mean values of CBD plasma (AP1 and BP1 at 120 min; AP2 and BP2 at 180 min) and urine (AU1 and BU1 at 180 min) concentrations (ng/mL) after consumption of formulation A and B classified by CYP2C9*2*3 phenotype: normal metabolism (NM), intermediate metabolism (IM) and poor metabolism (PM)) (A) and CYP2C19*2*17 phenotype: normal metabolism (NM), intermediate metabolism (IM), rapid metabolism (RM) and ultra-rapid metabolism (UR), (B) (n = 24).
Figure 6
Figure 6
CONSORT flow diagram.
Figure 7
Figure 7
Schematic for Study. The full planned protocol lasted <4 h. Participants arrived in the laboratory after an overnight fast. A snack high in fat (muffin) was provided upon initial arrival. A 15 mL blood sample (red arrows) was collected at baseline and following 120 and 180 min. Automated blood pressure and heart rate were obtained, in triplicate, every 10 min. Before dosing and every 90 min thereafter, standardized questionnaires were used to assess GI symptoms and anxiety. See text below for dosing details.
See this image and copyright information in PMC

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