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Publications

Advancing Cannabinoid Science:
Our Latest Research Findings

Cultivate Biologics’ research publications demonstrate our on-going dedication to advancing the understanding of cannabinoids, aiming to enhance human and animal health. Cultivate has been funding research since 2016 that explore the effects of cannabinoids as part of full spectrum extracts on a number of health conditions. We also conducted break-through research to determine the efficacy, bioavailability, safety and stability of cannabinoids for human and animal use.

Frontiers in Veterinary Science

The goal of this study was to perform a pharmacokinetic analysis of oral cannabidiol (CBD)-/cannabidiolic acid (CBDA)-rich hemp oil in juvenile cynomolgus macaques. The maximum mean serum concentration (Cmax) of CBDA was 28.6–36.2 times that of CBD at 4 and 8  mg/kg.

ICRS 2023

When examining the 4 species–dogs, cats, horses, and humans. Humans have a far greater absorption/retention capacity for CBDA when compared to the other species with a Cmax and AUC 3-fold superior to CBD.

Journal of Veterinary Pharmacology and Therapeutics

The objectives of this study were to obtain preliminary information regarding the in vitro metabolism of these compounds and their capacity to inhibit canine cytochrome p450 (CYP)-mediated drug metabolism and canine p-glycoprotein-mediated transport. CBD and CBDA were not substrates or competitive inhibitors of canine p-glycoprotein with minimal CYP inhibition at physiologic concentrations. This seminal study was the first to show CBDA direct glucuronidation. Results for cannabinoid-enriched hemp extracts were identical to those for pure cannabinoids.

Oxford ICSB

The objective of the study was to characterize the clinical pharmacokinetics of CBDA, CBD, and other cannabinoids administered as a novel CBD/CBDA-rich hemp product in humans. the AUC0-12h and Cmax for CBDA was ~18-fold and ~45-fold higher than that for CBD, respectively

AVMA Publications

The goal of pharmacokinetic (PK) studies is to provide a basis for appropriate dosing regimens with novel therapeutic agents.. In conclusion, CBD absorption and retention appear to be superior in dogs and cats as they can often achieve over 100 ng/mL as a Cmax while humans and horses are often 10-fold lower when utilizing similar dosing. Second, in veterinary species, the absorption of CBDA, and generally all of the acidic forms of cannabinoids, appears to be absorbed and retained at a higher level than CBD suggesting that further work in this area is warranted because it may be easier to reach therapeutic levels and there is a dearth of information regarding CBDA in the human literature.

Journal of the American Veterinary Medical Association (JAVMA)

This review will primarily focus on current scientific research on the efficacy of CBD on seizure, anxiety, osteoarthritis, and atopic dermatitis, following a brief discussion of endo- and exogenous cannabinoids, ECS, their molecular mechanism, and potential side effects in veterinary medicine.. It must be highlighted that all of these clinical studies are canine trials and there are currently no clinical studies of cats, horses, or other companion veterinary species to show any clinical benefits at the time of writing this review.

Frontiers in Veterinary Science

A pilot investigation using a CBD and CBDA-rich hemp product for the treatment of refractory epileptic seizures in dogs at a dose of 2 mg/kg of whole hemp extract. The number of dogs with a 50% reduction in epileptic activity while on treatment were 6/14, whereas 0/14 had reductions of 50% or greater while on the placebo.  

Journal of Veterinary Pharmacology and Therapeutics

Cannabigerolic acid (CBGA) is the precursor molecule to cannabinoid formation in the cannabis plant which may have medicinal properties as well, yet there are no publications related to CBGA or the neutral form cannabigerol (CBG) in higher vertebrate species species. Results suggest that when providing a hemp-derived CBG/CBGA formulation (1 mg/kg CBGA and 1 mg/kg CBG) in equal quantities, CBGA is absorbed approximately 40-fold better than CBG regardless of being given to fed or fasted dogs with better long term retention of CBGA in the bloodstream.

Veterinary Dermatology

Cannabidiol (CBD) and cannabidiolic acid (CBDA) are reported to have antinociceptive, immunomodulatory and anti-inflammatory actions. The objective of the study was to determine if CBD/CBDA is an effective therapy for canine atopic dermatitis (cAD). CBD/CBDA as an adjunct therapy decreased pruritus, and not skin lesions associated with cAD in dogs.

Veterinary and Comparative Oncology

CBD has been studied for its direct anti-neoplastic properties alone and in combination with standard cancer therapies, yielding encouraging results. The objectives of our study were to explore the anti-proliferative and cell death response associated with in vitro treatment of canine cancer cell lines with CBD alone and combination with common chemotherapeutics. CBD significantly reduced canine cancer cell proliferation far better than CBDA across as isolates with a whole hemp derived CBD/CBDA being more potent in cytotoxic activity across five canine neoplastic cell lines when treated with concentrations ranging from 1 to 10 μg/ml. CBD is effective at hindering cell proliferation and induction of autophagy and apoptosis rapidly across neoplastic cell lines and may be synergistic with vincristine chemotherapy in lymphoma cells.

Frontiers in Veterinary Science

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, at midpoint of dosing regimen. CBDA and THCA concentrations were 4 and 10 fold higher than CBD and thc concentrations, respectively. Overall, these findings suggest CBDA and THCA are absorbed/retained differently than CBD or THC, respectively, and that a partial lecithin base provides superior absorption and/or retention of CBDA and THCA.

Journal of Veterinary Pharmacology and Therapeutics

Information regarding systemic delivery of cannabinoids through transdermal routes is sparse. The purpose of this study was to determine pharmacokinetics of transdermal administration of a low-THC Cannabis sativa extract in healthy dogs. Results showed that CBDA and THCA were absorbed better systemically than CBD or THC.

White Paper

Phytocannabinoids, such as CBD, are thought to be an effective means of addressing anxiety in dogs, but there is a lack of evidence to support this, aside from a myriad of anecdotal reports of success. this open label pilot study is the first to objectively evaluate the success of minimizing clinical anxiety in dogs using a CBD and CBDA-rich hemp product. The results of the study showed that 83% (20/24) dogs responded positively and had decreased stress or anxiety-related behaviors according to owners. 60% of pet owners reported the effects lasting 1-6 hours, with a peak of onset between 0.5-2 hours. Based on the success of this pilot study another study is being conducted to determine effects on long-term separation anxiety.

Veterinary Medicine Reports (VMR)

29 commercially available products were analyzed that were using low-THC Cannabis sativa extracts in their production of supplements. All products were tested for major cannabinoids including cannabidiol (CBD), ∆9-tetrahydrocannabinol (THC), cannabigerol (CBG), and other minor cannabinoids, as well as their carboxylic acid derivatives (CBDA, THCA, CBGA) using an ISO/IEC 17025 certified laboratory. Products were also tested for major terpenes and heavy metals to understand constituents in the hemp plants being extracted and distributed. The products analyzed had highly variable concentrations of CBD or total cannabinoids with only 18 of 29 being appropriately labeled according to current FDA non-medication, non-dietary supplement or non-food guidelines.

Animals

The purpose of this study was to determine the single-dose oral pharmacokinetics of CBD, and to provide a preliminary assessment of safety and adverse effects during 12-week every 12 hour administration using a hemp-based product at a dose of 2 mg/kg in healthy dogs and cats.  Cats appear to absorb or eliminate CBD differently than dogs, showing lower serum concentrations and adverse effects of excessive licking and head-shaking during oil administration. More importantly physical examination and monthly bloodwork showed no alteration in transaminase enzymes with chronic consumption.

Frontiers in Veterinary Science

The objectives of this study were to determine basic oral pharmacokinetics which determined dosing of 2 mg/kg for a randomized placebo controlled cross over clinical investigation using a CBD/CBDA rich hemp extract. In the clinical study of dogs with moderate to severe OA for 4 weeks, no side effects were reported by owners, however, serum chemistry showed an increase in alkaline phosphatase during CBD treatment (p < 0.01). more importantly there was an analgesic effect with over 80% of dogs showing significant improvement in OA symptoms when treated with CBD:CBDA.