Edited by: Nora Mestorino, National University of La Plata, Argentina
Reviewed by: Jeremy Carlier, Sapienza University of Rome, Italy; Cengiz Gokbulut, Balikesir University, Turkey
This article was submitted to Veterinary Pharmacology and Toxicology, a section of the journal Frontiers in Veterinary Science
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Cannabidiol (CBD)-rich hemp extract use is increasing in veterinary medicine with little examination of serum cannabinoids. Many products contain small amounts of Δ9-tetrahydrocannabinol (THC), and precursor carboxylic acid forms of CBD and THC known as cannabidiolic acid (CBDA) and tetrahydrocannabinolic acid (THCA). Examination of the pharmacokinetics of CBD, CBDA, THC, and THCA on three oral forms of CBD-rich hemp extract that contained near equal amounts of CBD and CBDA, and minor amounts (<0.3% by weight) of THC and THCA in dogs was performed. In addition, we assess the metabolized psychoactive component of THC, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and CBD metabolites 7-hydroxycannabidiol (7-OH-CBD) and 7-nor-7-carboxycannabidiol (7-COOH-CBD) to better understand the pharmacokinetic differences between three formulations regarding THC and CBD, and their metabolism. Six purpose-bred female beagles were utilized for study purposes, each having an initial 7-point, 24-h pharmacokinetic study performed using a dose of 2 mg/kg body weight of CBD/CBDA (~1 mg/kg CBD and ~1 mg/kg CBDA). Dogs were then dosed every 12 h for 2 weeks and had further serum analyses at weeks 1 and 2, 6 h after the morning dose to assess serum cannabinoids. Serum was analyzed for each cannabinoid or cannabinoid metabolite using liquid chromatography and tandem mass spectroscopy (LC-MS/MS). Regardless of the form provided (1, 2, or 3) the 24-h pharmacokinetics for CBD, CBDA, and THCA were similar, with only Form 2 generating enough data above the lower limit of quantitation to assess pharmacokinetics of THC. CBDA and THCA concentrations were 2- to 3-fold higher than CBD and THC concentrations, respectively. The 1- and 2-week steady-state concentrations were not significantly different between the two oils or the soft chew forms. CBDA concentrations were statistically higher with Form 2 than the other forms, showing superior absorption/retention of CBDA. Furthermore, Form 1 showed less THCA retention than either the soft chew Form 3 or Form 2 at weeks 1 and 2. THC was below the quantitation limit of the assay for nearly all samples. Overall, these findings suggest CBDA and THCA are absorbed or eliminated differently than CBD or THC, respectively, and that a partial lecithin base provides superior absorption and/or retention of CBDA and THCA.
The use of cannabidiol (CBD)-rich hemp-extract supplements is increasing in companion animal medicine with very few publications on the efficacy of these products in clinical conditions. To date, there are only three clinical publications with positive outcomes in canine osteoarthritis and epilepsy (
With the measurement of serum CBD now published in canines conjures a presumption that CBDA may undergo biotransformation to CBD based on a single human study (
In conjunction with using CBDA to improve absorption or retention of CBD, current literature is suggesting that CBD absorption is enhanced by 3- to 5-fold when providing it in conjunction with a fatty meal (
Nearly all of the hemp-related products being utilized in the supplement market, including some labeled as CBD isolates, have varying levels of THC and tetrahydrocannabinolic acid (THCA), and although the THC and THCA levels are often below 0.3% by weight, there may be absorption of these cannabinoids, which are psychotropic and neuroprotective, respectively (
The aim of our study was 4-fold: (1) provide pharmacokinetic information on a hemp extract with known CBD and CBDA concentrations and to examine whether low THC and THCA concentrations could be detected when fed in three oral food-based forms using 24-h pharmacokinetic profiling as well as 1- and 2-week average serum concentrations; (2) elucidate the gastrointestinal absorption kinetics of CBDA and potentially THCA; (3) determine whether we could detect 11-OH-THC, the major intoxicating metabolite of THC, and 7-OH-CBD and 7-COOH-CBD as primary metabolites of CBD in human literature; and (4) examine the serum biochemical indicators of hepatic function before and after 2 weeks of twice-daily dosing to ensure that the liver is not affected by these particular forms at the 2 mg/kg dosing regimen.
Six purpose-bred intact female beagles between the ages of 14 and 18 months were acquired and housed under an Institutional Animal Care and Use Committee approved protocol at the University of Florida (2019-0024). The dogs were acclimated to the environment for 2 weeks and had initial bloodwork and physical examinations done by the Animal Care Service Veterinarians before beginning the study. All of the dogs were between 8.4 and 9.7 kg for the duration of the study. The dogs were weighed weekly to assess relative dosing with the three different forms of an oral cannabinoid-rich hemp product. After each 2-week phase of investigation, the dogs were provided a 3-week wash-out period before the next phase of study began. The first phase of study was with a mixed medium/long-chain triglyceride oil (Form 1); the second phase of study was with a lecithin and sesame oil base (Form 2). The third phase of study was done by providing a chewable form (Form 3). All dogs were fed 100 g of wet dog food immediately after administration of the form being studied at each dosing.
Three different forms of the same hemp extract (ElleVet Sciences, Portland, ME) were utilized in the study with Form 1 (Oil A) being a mix of 25% medium-chain triglycerides (Perfect Keto 100% MCT, Austin, TX) and 75% long-chain triglyceride-based organic sesame oil (Jedwards International Inc, Braintree, MA). Each milliliter of the oil contained 28 mg of CBD, 29 mg of CBDA, 1 mg of THC, 0.8 mg THCA, 0.7 mg of cannabigerolic acid (CBGA), and 1.3 mg of cannabichromene (CBC) proven with third-party analysis by a certified ISO/IEC 17025 Laboratory (ProVerde Laboratory, Milford, MA). Form 2 (Oil B) was exactly the same regarding cannabinoid concentration except that 25% of the base oil was from sunflower lecithin (NOW Sunflower Lecithin, Bloomingdale, IL), and the remaining 75% was the same organic sesame oil as Form 1. Form 3 was formulated with the same hemp extract to contain ~5 mg of CBDA and 5 mg of CBD in each soft chew with a similar profile as stated above. For consistency of dose across dogs, each dog was provided two chews of Form 3 every 12 h because more exact dosing in mg/kg was impractical; therefore, the dogs were receiving between 2.0 and 2.3 mg/kg body weight for this particular product. The manufacturing of Form 3 was done using a cold extrusion process after reconstitution of a dough-like consistency using a materials base of peanut butter, glycerin, defatted rice bran, water, molasses dry (cane), glucosamine HCL, dextrose (glucose-dry), sweet potato (powder), hemp oil, brewer's yeast (dehydrated), potato starch, guar gum, rice starch, dehydrated peanut butter, and sorbic acid, in descending order based on weight based on good manufacturing practices.
The dogs underwent a 24-h pharmacokinetic (PK) assessment with blood draws at 0, 1, 2, 4, 8, 12, and 24 h, with twice-a-day dosing starting the following morning of the 24-h PK experiment with daily dosing (~0.4 mL of oil using a 1 cc syringe or two soft chews) at 7 am and 6 pm for the duration of each phase of the study (2 weeks). For the 24-h PK assessment, dogs had ~4 mL of blood drawn from the jugular or cephalic vein using a 20-gauge needle, which was then placed in a red top coagulation tube and allowed to clot before centrifugation at 3,600 g for 10 min. Serum was collected and immediately frozen at −80°C. At the end of weeks 1 and 2 of twice-daily dosing, dogs were provided their 7 am dose and then had a follow-up blood draw 6 h after dosing to assess mean serum concentration at the halfway point between doses. The dogs also had initial blood draws prior to starting the trial at 6 a.m. on their first day of each arm of the trial, and 6 h after their last 2-week dose to assess serum hepatic enzymes due to prior reports of elevated liver enzymes with daily exposure to hemp-based extracts (
Serum hepatic biochemical analyses were performed at two time points during the study. A background and a steady state 2-week blood draw were collected to evaluated hepatic function looking at albumin, alanine amino transferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin, glucose, and cholesterol (Antech Diagnostics, Irvine, CA).
Samples were batched within 8 weeks of the end of experimentation on each form and were transported overnight on dry ice to the laboratory for analysis. Cannabinoids analysis was performed by a novel developed method allowing simultaneous measurement of 10 cannabinoids and their metabolites at the Toxicology Research Laboratory, University of Illinois at Chicago. Reference standards for CBD and CBDA were obtained from Restek Corporation (Bellefonte, PT); all other reference and internal standards mentioned below were obtained from Cerilliant Corporation (Round Rock, TX). The concentration of cannabinoids (CBD, CBDA, THC, THCA, CBN, and CBG) and their metabolites (11-OH-THC, 7-OH-CBD, 7-COOH-CBD, and COOH-THC-Glu) in dog serum was determined by high-performance LC-MS/MS (Nexera X2 and LCMS 8050, Shimadzu Corp., Kyoto, Japan).
Dog serum (40 μL) was mixed with 20 μL of internal standards [100 ng/mL of CBD-d3, THC-d3, 11-OH-THC-d3, and 7-OH-CBD-d5 in water:methanol (50:50)] in a 96-well plate. Proteins were precipitated, and compounds were extracted by adding 80 μL of ice-cold acetonitrile to each sample followed by vortexing (1–2 min) and centrifugation at 4,000 rpm for 10 min at 4°C. The supernatants (100 μL) were mixed with water (100 μL) in another 96-well plate and centrifuged again. The processed samples were injected (10 μL) into Waters Atlantis T3 HPLC column (3 μm 2.1 × 50 mm) coupled to LC-MS/MS. The column was equilibrated with mobile phase A (0.1% formic acid in water) and mobile phase B (acetonitrile) at ratio A: B 50:50 for 0.5 min. The compounds were eluted by a linear gradient from 50% B to 100% B over 6 min, and then held at 100% B for 1 min. Subsequently, the column was re-equilibrated at initial composition for 0.5 min at a flow rate of 0.3 mL/min. An autosampler and column temperature were set at 4 and 30°C, respectively. CBD, CBDA, THC, THCA, CBN, CBG, and 11-OH-THC were detected in electrospray ionization positive mode using transitions
A representative chromatogram of cannabinoids and their metabolites in fortified dog serum at upper limit of quantitation (1,000 ng/mL of each compound). The compound name with corresponding Multiple Reaction Monitoring (MRM) transition and polarity is given in the inset of each chromatogram. Dashed-line represents the diversion of MS detector for a particular MRM transition and time.
Concentrations of cannabinoids were calculated by LabSolutions software (Shimadzu Corp., Kyoto, Japan) using a quadratic calibration curve with 1/c2 weighing based on relative response (peak area of cannabinoids/peak area of internal standards). The calibration curve range was from 1 to 1,000 ng/mL for CBD, CBDA, THC, THCA, CBN, CBG, and 7-COOH-CBD, and from 2.5 to 1,000 ng/mL for 11-OH-THC, 7-OH-CBD, and COOH-THC-Glu in dog serum.
The 24-h pharmacokinetic analysis for each cannabinoid or its metabolite (CBD, CBDA, THC, THCA, CBG, CBN, 11-OH-THC, 7-OH-CBD, 7-COOH-CBD, and COOH-THC-Glu) was performed utilizing a commercial software system that allows for a one compartment model using 5 half-life assumption for mean serum concentration, which is reported (PK solutions 2.0, Summit PK, Montrose, CO). The results generated were time to maximal concentrations (Tmax), maximum serum concentration (Cmax), half-life (T½), area under the curve to the last time point (AUC0−24), AUC of the dose extrapolated to infinity (AUCinfin), mean retention time (MRT), and calculated predicted 5 half-life mean serum concentration (Predict Ave). All of these values and the standard error of the mean are reported with follow-up statistics of each parameter being completed using non-parametric statistics due to the small sample sizes. Friedman's testing with Dunn's
No differences were noted for Tmax, T½, AUC0−24, AUCinfin, MRT or predicted average concentration for all three oral forms of the hemp product when examining CBD pharmacokinetics. The only significant difference in CBD between the three oral delivery forms was with the Form 3 appeared to have a higher Cmax than Form 2, but not Form 1 (
Mean and SEM (
Form 1 | 145 ± 69 | 1.5 ± 0.5 | 4.1 ± 0.7 | 635 ± 399 | 656 ± 414 | 5.2 ± 1.4 | 53 ± 33 |
Form 2 | 124 ± 62 | 2.0 ± 1.1 | 4.4 ± 1.4 | 683 ± 146 | 707 ± 144 | 6.5 ± 2.1 | 63 ± 17 |
Form 3 | 226 ± 89 |
2.5 ± 1.2 | 3.8 ± 0.3 | 826 ± 74 | 845 ± 74 | 5.3 ± 1.4 | 70 ± 15 |
Form 1 | 383 ± 167 | 1.0 ± 0.0 | 4.4 ± 2.7 | 1,018 ± 308 | 1,152 ± 451 | 5.2 ± 3.3 | 88 ± 41 |
Form 2 | 386 ± 213 | 1.2 + 0.4 | 4.2 ± 1.0 | 1,619 ± 898 | 1,748 ± 855 | 6.8 ± 2.3 | 136 ± 66 |
Form 3 | 510 ± 350 | 2.3 + 0.6 | 2.4 ± 1.1 | 1,407 ± 585 | 1,419 ± 591 | 4.3 ± 1.5 | 191 ± 158 |
Form 1 | BQL | BQL | BQL | BQL | BQL | BQL | BQL |
Form 2 | 6 ± 3 | 1.7 ± 0.5 | 4.0 ± 3.9 | 22 ± 9 | 27 ± 9 | 6.3 ± 5.7 | 3.0 ± 0.5 |
Form 3 | BQL | BQL | BQL | BQL | BQL | BQL | BQL |
Form 1 | 35 ± 14 | 1.7 ± 1.2 | 6.5 ± 5.1 | 171 ± 57 | 209 ± 89 | 9.8 ± 7.6 | 18 ± 6 |
Form 2 | 27 ± 21 | 2.2 ± 1.0 | 5.9 ± 2.5 | 256 ± 114 | 291 ± 119 | 8.7 ± 3.7 | 25 ± 10 |
Form 3 | 45 ± 25 | 3.3 ± 1.0# | 3.9 ± 0.6 | 212 ± 69 | 223 ± 71 | 6.6 ± 1.7 |
25 ± 5 |
Form 1 | NA | NA | NA | NA | NA | NA | NA |
Form 2 | 13 ± 2 | 5.0 ± 0.7 | 8.4 ± 2.1 | 159 ± 36 | 168 ± 41 | 9.4 ± 1.0 | 19 ± 4 |
Form 3 | 21 ± 2 |
5.3 ± 0.8 | 4.8 ± 0.4 | 188 ± 19 | 196 ± 22 | 8.8 ± 0.7 | 24 ± 2 |
Due to the absence of the reference standards for 7-OH-CBD and 7-COOH-CBD at the time of analysis of Form 1, it is not possible to compare results for these compounds on this form and the other formulations. The 7-COOH-CBD concentrations could be compared between Form 2 and Form 3, and there were no significant differences in any pharmacokinetic parameters except for Cmax being slightly higher for Form 3 over Form 2 (
Seven-point 24-h pharmacokinetics of three oral hemp-based forms showing oral absorption kinetics (mean and SEM) of cannabidiol (CBD-blue), cannabidiolic acid (CBDA-red), Δ9-tetrahydrocannabinol (THC-green), tetrahydrocannabinolic acid (THCA-purple), and 7-carboxy- cannabidiol (7-COOH-CBD- light blue for Form 2 and Form 3 only).
The metabolites of THC, 11-OH-THC, and COOH-THC-Glu were all below the lower limit of quantitation (1 ng/mL for THC or 2.5 ng/mL for 11-OH-THC and COOH-THC-Glu), except in a few samples where 11-OH-THC was observed at 1 or 2 h (six samples Form 1, four samples Form 2, and two samples Form 3). 7-OH-CBD was undetectable in all samples assessed in Forms 2 and 3. Hence, 24-h pharmacokinetics analysis was not possible for any of these metabolites.
When examining the CBD concentrations in serum at weeks 1 and 2, Form 1 serum concentrations (mean ± SEM) were 79 ± 9 ng/mL and 94 ± 14 ng/mL at weeks 1 and 2. Form 2 serum concentrations (mean ± SEM) were 129 ± 10 ng/mL and 122 ± 10 ng/mL at weeks 1 and 2. Form 3 serum concentrations (mean ± SEM) were 115 ± 28 ng/mL and 60 ± 9 ng/mL at weeks 1 and 2, respectively. There were no statistically significant differences between CBD concentrations between the weeks of exposure or between the different formulations at the two time points (
One- and two-week serum cannabinoids concentrations (mean and SEM) 6 h after morning dosing when using Form 1, Form 2, or Form 3 for oral dosing.
CBDA serum concentrations were similar to CBD concentrations at weeks 1 and 2. Form 1 serum concentrations (mean ± SEM) were 75 ± 21 ng/mL and 44 ± 8 ng/ml at weeks 1 and 2. Form 2 serum concentrations (mean ± SEM) were 192 ± 36 ng/mL and 196 ± 42 ng/mL at weeks 1 and 2. Form 3 serum concentrations (mean ± SEM) were 52 ± 12 ng/mL and 44 ± 10 ng/mL at weeks 1 and 2, respectively. Statistically, the serum concentrations of CBDA at both weeks 1 and 2 were significantly higher for Form 2 when compared to Forms 1 and 3 (
THC serum concentrations were far lower than CBD or CBDA concentrations following similar absorption kinetic of CBD. Form 1 serum concentrations (mean ± SEM) were 2.7 ± 0.5 ng/mL and 2.9 ± 0.7 ng/mL at weeks 1 and 2. Form 2 serum concentrations (mean ± SEM) were 5.2 ± 0.4 ng/mL and 4.4 ± 0.5 ng/mL at weeks 1 and 2. Form 3 serum concentrations were 3.9 ± 1.2 ng/mL and 1.7 ± 0.4 ng/mL at weeks 1 and 2, respectively (
THCA serum concentrations were higher than THC concentrations and appear to follow kinetics of CBDA absorption and retention. Form 1 serum concentrations (mean ± SEM) were 10.4 ± 1.2 ng/mL and 7.0 ± 1.0 ng/mL at weeks 1 and 2. Form 2 serum concentrations (mean ± SEM) were 23.5 ± 22.0 ng/mL and 25.0 ± 2.2 ng/mL at weeks 1 and 2. Form 3 serum concentrations were 25.0 ± 3.0 ng/mL and 20.0 ± 2.2 ng/mL at weeks 1 and 2, respectively. Both Form 2 and Form 3 had significantly higher THCA concentrations than Form 1 at both weeks 1 and 2 (
Except for a few samples, COOH-THC-Glu was not detectable in the bloodstream during weeks 1 and 2 testing. 11-OH-THC levels were below the quantitation limit for Form 1, while Form 2 showed two of the six dogs having detectable levels at 2.6 and 6.4 ng/mL at week 1; and three of the six dogs showing detectable concentrations at 4.0, 2.7, and 6.7 ng/mL at week 2. Form 3 showed only one dog at week 2 having an 11-OH-THC concentration higher than the lower limit of quantitation at 2.8 ng/mL.
The CBD metabolites assessed at weeks 1 and 2 across all three oral formulations showed no 7-OH-CBD accumulation in dog serum, with all samples being below the lower limit of quantitation. 7-COOH-CBD concentrations were not determined in Form 1 due to lack of standards at the time of analysis, but 7-COOH-CBD concentrations in Form 2 across the six dogs were 24.5 ± 2.3 ng/mL and 26.1 ± 2.9 ng/mL at weeks 1 and 2, respectively. Serum concentrations of 7-COOH-CBD when using Form 3 were 27.9 ± 4.8 ng/mL at week 1, and 23.7 ± 4.7 ng/mL at week 2. There were no significant differences between weeks 1 and 2 for either dosing form, and no differences in concentrations were observed between the oral forms at each time point.
The major enzymes associated with hepatic injury or altered function include ALP, ALT, and AST. We did not observe any significant changes in any of the oral treatments in the serum concentrations of these enzymes prior to beginning of treatment and 2 weeks into twice-daily treatment (
Mean and standard error of the mean concentrations (
ALP (8–114 U/L) | 39 ± 3 | 46 ± 5 | 37 ± 4 | 40 ± 4 | 32 ± 4 | 35 ± 5 |
ALT (18–64 U/L) | 25 ± 1 | 23 ± 1 | 26 ± 2 | 25 ± 2 | 26 ± 3 | 29 ± 4 |
AST (15–52 U/L) | 27 ± 2 | 24 ± 1 | 25 ± 2 | 23 ± 1 | 24 ± 2 | 26 ± 2 |
Albumin (2.9–3.8 g/dL) | 3.1 ± 0.5 | 3.1 ± 0.3 | 3.1 ± 0.1 | 3.0 ± 0.1 | 3.3 ± 0.1 | 3.4 ± 0.1 |
Total Bilirubin (0.1–0.4 mg/dL) | 0.2 ± 0.1 | 0.2 ± 0.1 | 0.2 ± 0.0 | 0.2 ± 0.0 | 0.2 ± 0.0 | 0.2 ± 0.0 |
Cholesterol (124–334 mg/dL) | 210 ± 10 | 250 ± 29 | 199 ± 22 | 223 ± 19 | 211 ± 20 | 226 ± 19 |
Glucose (79–120 mg/dL) | 91 ± 4 | 105 ± 6 | 100 ± 3 | 89 ± 6 | 102 ± 2 | 91 ± 9 |
This is the first pharmacokinetic serum assessment of cannabinoids and major metabolites using a whole hemp plant derived extract in dogs, most notably for the major cannabinoid acid forms, CBDA and THCA, which are not routinely assessed. The increase in oral use of whole hemp extract in veterinary and human medicine warrants further investigation into the native acid derivatives of CBD and THC, since existing products that do not undergo heat extraction will contain CBDA and THCA. In much of the prior research on inhaled forms of cannabis, these derivatives were not assessed since the heat-induced decarboxylation of CBDA to CBD and THCA to THC (
The pharmacokinetics of CBDA over a 2-week period shows nearly equal serum concentrations to CBD, suggesting absorption and retention of oral dosing. More interestingly, is that Form 2, which contains a 25% sunflower lecithin base, showed slightly higher AUC0−24 and mean retention time in 24-h pharmacokinetics, which may have translated into the significantly higher weeks 1 and 2 serum concentrations when compared to Form 1 (25% medium chain triglyceride base) or Form 3. The implications of this are unknown from a clinical perspective; however, CBDA may have some unique properties as an anti-inflammatory as well the ability to mitigate nausea through 5HT 1a receptor activation (
This investigation is the first of its kind to assess both THC and THCA as minor cannabinoids that are found in most CBD-rich hemp products at lower than 0.3% combined. The quantity of THC and THCA delivered to these dogs was <0.1 mg/kg body weight, which is far lower than prior long-term dosing (25 mg/kg) that resulted in minimal clinical side effects (
Not surprisingly, the 11-OH-THC metabolite, which has been associated with intoxicating effects, showed variable measurable quantities in the 24-h pharmacokinetic profile and could not be universally detected in all dogs at multiple time points, which did not allow for 24-h pharmacokinetic analysis. However, weeks 1 and 2 concentrations were above the lower limit of quantitation (2.5 ng/mL) in a few dogs on Form 2 (
From a metabolic perspective, the metabolism of CBD was also interrogated by assessing the major metabolites identified in humans (7-OH-CBD and 7-COOH-CBD), which are not prevalent in dogs. The levels of 7-OH-CBD could not be measured in our dogs, while 7-COOH-CBD was in the 20–30 ng/mL range as a mean concentration after 1 and 2 weeks of use. These results are dramatically higher than what was recently observed in a study where dogs received 62 mg/kg in a short-term study, suggesting that there may be some adaptation to CBD metabolism or differences in absorption and retention in this study (
It must also be noted that our experimental design utilized feeding at the time of administration to promote cannabinoid absorption. These are not new findings since older literature suggests that THC uptake is 3- to 4-fold greater in primates when provided with a mixed meal in the form of a cookie (
The use of cannabinoid-rich hemp-based oils for health and disease is in its infancy in human and veterinary clinical medicine. CBD use is proving efficacious in seizure disorders, multiple-sclerosis-based spasm and pain, oncologic side effects of chemotherapy, with a more recent indication in anxiety and schizophrenic disorders using single or twice-a-day dosing between 5 and 20 mg/kg per day in humans (
Overall, this study is the first to show that CBDA and THCA are readily absorbed and retained in dogs with some differences observed in CBDA absorption and/or retention depending on the medium used to deliver the oral treatment. The finding of mid dosing concentrations of 75 ng/mL of CBD and CBDA or greater suggests potential for therapeutic use when delivered at 1 mg/kg body weight for each of these cannabinoids with food. A more interesting finding is the retention of THCA in the serum of between 10 and 25 ng/mL. The exact functions of CBDA and THCA physiologically suggest similar therapeutic benefits to CBD that may have the potential to work synergistically with CBD. These synergistic properties known as the “entourage effect” are currently thought to be the primary reason that lower CBD whole hemp extract dosing can be therapeutic when compared to purified CBD (
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
The animal study was reviewed and approved by University of Florida Institutional Animal Care and Use Committee.
JW, WS, and SC were responsible for conceptualization and study design. All authors were involved in acquisition and analysis of portions of the data, involved in manuscript preparation/revisions, and approved this manuscript before submission. The manuscript was drafted by JW.
JW is currently a paid consultant for Ellevet Sciences, and SC is currently an employee of Ellevet Sciences. The funding for this study was provided to JW at the University of Florida by Ellevet Sciences. The funder was involved in the study design under the guidance of author JW. The funder was not involved in the collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We would like to thank Ms. Amanda Howland and Mr. Reece Prussin for their efforts in analysis and material preparation used for this study.
Cannabidiol
Cannabidiolic Acid
7-Hydroxycannabidiol
7-Nor-7-carboxycannabidiol
Cannabigerol
Cannabinol
(-)-Δ9-Tetrahydrocannabinol
Δ9-Tetrahydrocannabinolic Acid
(±)-11-Hydroxy-Δ9-THC
(+)-11-nor-9-Carboxy-Δ9-THC glucuronide.