Studies

Hemp extract is the new frontier, and for many it simply seems like the next gold rush for companies looking to strike it rich. But, as more research is conducted, the positive uses of full spectrum hemp extract and cannabidiol (CBD) for pets is being revealed.

As with any treatment for your pet, evidence-based treatments are vital, which is why studies into the numerous effects of CBD on pets are ongoing. While the FDA has yet to approve CBD or hemp extract, it is worth noting that the FDA typically does not approve many supplements or medications in the pet industry. Regardless of the FDA’s stance on CBD products, research is continually finding that hemp extract can be life saving for pets and people alike.

What does "full spectrum" mean?

Full spectrum means that all naturally occurring compounds such as cannabinoids and terpenes are extracted in their raw form and proportion. CBD is just one of over 114 known cannabinoids, including THC, CBG, CBN and many more.

Full-spectrum extracts are preferable to other, more processed and isolated extracts because of the synergistic relationship of the many different compounds. This effect (called the entourage effect), described the way all those different pieces work together, boosting and supporting each other’s various therapeutic effects.

A study conducted by UNICAMP in Campinas, Brazil found that full spectrum, CBD-rich extracts are more beneficial to people and pets when compared to a CBD isolate. In fact, the study states:

“Adverse effects were more frequent in products containing purified CBD than in CBD-rich extracts. CBD-rich extracts seem to present a better therapeutic profile than purified CBD, at least in this population of patients with refractory epilepsy.”

Absorption rates and Bioavailability

Research shows that CBD is effectively absorbed into the bloodstream through various means of administration.

A study conducted by the Department of Pharmacy, School of Pharmacy at Hebrew University in Jerusalem, Israel concluded that: “CBD was observed to have a large volume of distribution [in dogs studied].”

In a study conducted by the Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy, dogs were found to have a substantial amount of receptors in their endocannabinoid system, specifically in the spine, which allows dogs to more effectively use CBD.

Gums, Ears, Trans-Dermal

A study by Canadian Journal Of Vetenairy Research conducted the pharmacokinetics of cannabidiol (CBD) in healthy dogs.  This study shows various rate of absorption for three methods of administration, as well as the corresponding half life for each method.

Cats vs. Dogs

In this study by University of Florida’s Veterinary College, they found that cats absorbed CBD much less readily than dogs. They ended up with around one fifth the blood concentration at a proportional dose.

Anxiety, stress, and sleep disorders

CBD is renowned for its anti-anxiolytic effects for both people and pets for good reason. A study published in Current Neuropharmacology states:

“CBD seems to be a promising drug for the treatment of various ‘panic disorders’.”

2013 article published in Neuropharmacology also found that:

“In addition to modulating basal anxiety states, recent studies suggest an important role for the endocannabinoid (eCB) and glucocorticoid systems in the modulation of emotional states and extinction of aversive memories in animals.”

This means that CBD can help in facilitating extinction of aversive memories which treats PTSD and anxiety or panic disorders in people and animals.

Research is also promising that CBD is a viable treatment option for sleep disorders in people and pets. A 2019 study published in the Permanente Journal found that CBD has a calming effect on the central nervous system and can improve the amount and depth of sleep in those suffering sleep disorders and CBD is better tolerated than other psychiatric medications.

A 1993 study published in the Journal of Psychopharmacology found that pain relief, reduction of anxiety, and reduction of inflammation were the most common reasons for the use of cannabis in dogs, and when tested in animal models, CBD was shown to have anxiolytic properties (Zuardi and Karniol 1993), as confirmed in a number of studies in humans.

Autoimmune Disease

CBD also has immune-boosting properties because it acts as a regulator to bring the body back to homeostasis. In fact, CB2 receptors regulate many complex pathways of the immune system, and preclinical studies show that triggering CB2 receptors can suppress immune response, which can be beneficial for those suffering with autoimmune disease, according to this study. The same study also states:

“There has been some preclinical investigation focusing on the role of particular cannabinoids in AI disease models. CBD has been found to modulate the immune system instead of suppressing it. Cannabidiol also slows down T-cell production and suppresses immune system memory, meaning that CBD could cut down on the likelihood of future autoimmune attacks. CBD has also been found to increase the expression of genes that deal with oxidative stress, which may reduce cell damage from autoimmune attacks. “

Cancer and tumors

One of the primary uses of hemp extract is to treat cancer and tumors. Research conducted by A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt Ingram Comprehensive Cancer Center concluded that “The antiproliferative and apoptotic effects produced by some of these pharmacological probes [CBD] reveal that the endocannabinoid system is a promising new target for the development of novel chemotherapeutics to treat cancer.”

Another study published in 2018 found that CBD inhibits the growth of cancerous cells in mice with pancreatic and bladder cancer. Not only did CBD inhibit cancerous cell growth, but also proved to prevent future cancerous growths in the mice treated with CBD. The conclusion of this study noted that CBD could be a viable option to treat cancer in both humans and animals.

A study published by BMC Complementary Medicine and Therapies in 2009 claimed that Frankincense oil (in our EASE Tinctures) might be an alternative for bladder cancer treatment. In this study, Frankincense oil was was investigated in human bladder cancer J82 cells and immortalized normal bladder urothelial UROtsa cells. Within a range of concentration, frankincense oil suppressed cell viability in bladder transitional carcinoma J82 cells but not in UROtsa cells.

A study published by IMIBIC in Spain states:

“Local administration of CB1 and CB2 agonists (similar to CBD and THC) induced growth inhibition of malignant skin tumors generated by intradermal inoculation of tumorigenic PDV.C57 mouse keratinocytes into nude mice. This growth inhibition was accompanied by enhanced intra-tumor apoptosis and impaired tumor vascularization “

One of the most astounding ways CBD and cannabis differs from traditional cancer therapies, is that it is selective about which cells it targets. When CBD works to eliminate cancer cells, it does not eliminate the good cells.
According to The National Cancer Institute:

“Cannabinoids appear to kill tumor cells but do not affect their non-transformed counterparts and may even protect them from cell death.”

Safety

CBD
In a study conducted by Colorado State University, 10 mg/kg/day or 20mg/kg/day was administered to dogs for 6 days. CBD was tolerated in the study population. There was an elevation in serum ALP in 36 percent of patients, and all other blood parameters were normal. Six of the 30 dogs had vomiting and all had mild diarrhea. 11 of 30 dogs experienced erythema of pinna and 10 of 30 dogs experienced nasal and ocular discharge. These effects were significantly safer than many side effects of prescription medications.

THC
THC is one of the foremost reasons cannabis has been such a taboo subject in the medical community. Even today after the therapeutic benefits have been well documented time and time again, discussions of its toxicity still take up most of the airtime. Here’s a study where researchers showed there is no possible lethal dose of THC in humans or dogs:
“Comparison of acute oral toxicity of cannabinoids in rats, dogs and monkeys.” – Mason Research Institute

CBD and THC 

Another study conducted by Canopy Animal Health, 20 healthy Beagle’s were tested to determine the safety and tolerance of escalating CBD, THC, or CBD and THC dosage in the dogs. 10 females, and 10 males, the dogs were given up to 10 escalating doses of oils in a three-day span. Overall, the dogs tolerated the escalation dosages very well only experiencing mild AEs. 

 

Cardiovascular Effects

CBD specifically has been found to have direct effects on arteries, influencing vaso-relaxation, which is clinically observed as a mild hypotensive effect when CBD is administered. CBD has a protective effect against the vascular damage caused by hyperglycemia, as with type 2 diabetes, diabetic angiopathies, and systemic inflammatory processes. It is the antioxidant and anti-inflammatory effects of CBD that mediate these benefits (Stanley et al. 2013).

CBD has been found to have anti-arrhythmic effects in an in vivo rat model of coronary artery occlusion which may not be mediated through the CB1 receptors found on myocardial cell membranes, but may have other non-receptor-mediated pathways that allow its control over cardiac rhythm (Hepburn et al. 2011).

Diabetes

At its core, diabetes is often caused by issues of inflammation, with which CBD can help. In fact, a recent study states:

“Oxidative stress and inflammation play critical roles in the development of diabetes and its complications… Studies provided compelling evidence that the newly discovered lipid signaling system (ie, the endocannabinoid system) may significantly influence reactive oxygen species production, inflammation, and subsequent tissue injury, in addition to its well-known metabolic effects and functions.”

Another recent study found that full spectrum hemp extract CBD actually lowered the instance of diabetes in non-obese diabetic mice. Another study found that full spectrum hemp extract CBD may also improve circulation and improve overall health in diabetic rats. These studies are promising that full spectrum hemp CBD can help treat diabetes in animals (and humans). Please note: although studies are promising, you should always speak to your veterinarian before changing a diabetic pet’s diet or insulin.

Nutrition and GI tract

Research published in Nutraceuticals in Veterinary Medicine titled “Cannabis in Veterinary Medicine: Cannabinoid Therapies for Animals” states that hemp oil is a significant source of proteins and essential fatty acids, including gamma-linolenic acid (GLA). Of note: the same study found that CBD interacts with the endocannabinoid system in dogs to treat cancer, improve sleep, prevent obesity and metabolic diseases, resolve anxiety and stress, treat inflammatory conditions, improve pulmonary and cardiac conditions, and acts as a neuro-protectant.

An 8-week project of THC rich cannabis produced significant clinical, steroid-free benefits to 10 to 11 patients with active Crohn’s disease as compared with placebo, without side effects (Naftali).

CANNABIS AND THE MICROBIOME

From “Cannabis Therapeutics and the Future of Neurology” Published in Inter Neurosis, 2018:

  • THC alters microbiome balance and prevents obesity
    • CBD has both anti-inflammatory and bacteriostatic effects in the gut
    • CB2 levels correlate to Lactobacillus concentrations and negatively with potentially pathogenic Clostridium species.
    • Orally administer lactobacillus induces mRBA expression of the gene that encodes for CB2 receptors (CNR2)

Pain and inflammation

Research has consistently shown that CBD can help humans who suffer from osteoarthritis, but it is also a promising treatment for dogs suffering the same ailment.

Cornell University’s College of Veterinary Medicine recently conducted pharmacokinetics study on cannabinoids for dogs. This 8-month double-blind study was the first of its kind for Cornell and studied dogs suffering from osteoarthritis. Dogs in the study saw a significant decrease in pain and increase in activity, with no side effects. In fact, the study concluded the following:

“Pharmacokinetics revealed an elimination half-life of 4.2 h at both doses and no observable side effects. Clinically, canine brief pain inventory and Hudson activity scores showed a significant decrease in pain and increase in activity (p < 0.01) with CBD oil. Veterinary assessment showed decreased pain during CBD treatment (p < 0.02). No side effects were reported by owners… This pharmacokinetic and clinical study suggests that 2 mg/kg of CBD twice daily can help increase comfort and activity in dogs with OA.”

Another study titled “Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs” found that 2 mg/kg of CBD twice daily can help increase comfort and activity in dogs with Osteoarthritis.

A study published in 2006 in Current Neuropharmacology also states that CBD has therapeutic benefits for both people and pets suffering from chronic pain and acute chronic pain episodes.

Compounds found in cannabis that reduce inflammation are abundant and diverse. The most abundant phytocannabinoids in cannabis, THC and CBD, both have strong anti-inflammatory properties, while CBC, CBG, and THCV have also demonstrated anti-inflammatory properties. Cannabinoids act as anti-inflammatory agents by inducing apoptosis, inhibiting of cell proliferation, suppressing cytokine production, and inducing T regulatory cells. Apoptotic mechanisms induced by cannabinoids in immune cells include activation of CD95 to induce Bcl-2 and caspase cascades in immune cells. Cannabinoids have also been demonstrated to promote the production of anti-inflammatory interleukins such as IL-10 while inhibiting the production of pro-inflammatory cytokines such as TNF-α in a CB1-dependent fashion (Klein et al. 2000).

Additionally, the University of Pennsylvania School of Veterinary Medicine is currently conducting clinical trials to better understand the effects of cannabis on osteoarthritic dogs. The study will take 12 months and results are expected to be published in 2020.

Seizures

In a 2017 double-blind study conducted by Colorado State University’s James L. Voss Veterinary Teaching Hospital, neurologist Stephanie McGrath assessed the short-term effect of CBD on seizure frequency in 16 dogs. Dogs in the trial were randomly assigned a placebo or a hemp-derived CBD treatment for 12 weeks. Nine dogs received CBD while seven were given a placebo. All of the dogs in the study suffered from seizures.

Through the study, McGrath found that 89 percent of dogs who received CBD in the clinical trial had a reduction in the frequency of seizures. Additionally, McGrath saw a significant association between the degree of seizure reduction and the amount of CBD concentration in the dog’s blood.

This was not the only study to find CBD to be a successful anti-epileptic supplement for pets. Yamazaki University of Animal Health Technology in Japan conducted a similar experiment wherein three dogs who suffered epileptic seizures were given hemp-derived CBD for eight weeks. Researchers found a decrease in seizure intervals in two of the three dogs studied. The dogs were given varying amounts of CBD, and the dog who received the lowest number of mg of active CBD showed little to no improvement, while the dog who was administered 1700 mg showed the highest level of improvement. Of note: the same study’s findings show that the dogs showed a decrease in barking even when other dogs nearby were excitable.

Another study done by ScienceDirect shows CBD has resulted in (like previously published data) being of potential therapeutic use (alone or as an adjunct) in the treatment of epilepsies or seizures.

This article will be updated as research is continually conducted and published. Below is a list of resources, research, and studies with additional information regarding full spectrum hemp CBD and its therapeutic uses. 

Citations

Greg Gerdeman on Cannabinoid Treatment for Rheumatism. (2016, June 5). Retrieved from https://www.projectcbd.org/medicine/cannabinoid-treatment-rheumatism-greg-gerdeman-phd

Gamble L-J, Boesch JM, Frye CW, Schwark WS, Mann S, Wolfe L, Brown H, Berthelsen ES and Wakshlag JJ (2018) Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs. Front. Vet. Sci. 5:165. doi: 10.3389/fvets.2018.00165

Kukanich B, Bidgood T, Knesl O. Clinical pharmacology of nonsteroidal anti-inflammatory drugs in dogs. Vet Anaesth Analg. (2012) 39:69–90. doi: 10.1111/j.1467-2995.2011.00675.x

Lomas AL, Grauer GF. The renal effects of NSAIDs in dogs. J Am Anim Hosp Assoc. (2015) 51:197–203. doi: 10.5326/JAAHA-MS-6239

Monteiro-Steagall BP, Steagall PV, Lascelles BD. Systematic review of nonsteroidal anti-inflammatory drug-induced adverse effects in dogs. J Vet Intern Med. (2013) 27:1011–9. doi: 10.1111/jvim.12127

Luna SP, Basílio AC, Steagall PV, Machado LP, Moutinho FQ, Takahira RK, et al. Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. Am J Vet Res. (2007) 68:258–64. doi: 10.2460/ajvr.68.3.258

Di Marzo V, Bifulco M, De Petrocellis L. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov. (2004) 3:771–84. doi: 10.1038/nrd1495

Ben-Shabat S, Hanuš LO, Katzavian G, Gallily R. New cannabidiol derivatives: synthesis, binding to cannabinoid receptor, and evaluation of their antiinflammatory activity. J Med Chem. (2006) 49:1113–7. doi: 10.1021/jm050709m

Maione S, Piscitelli F, Gatta L, Vita D, De Petrocellis L, Palazzo E, et al. Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. Br J Pharmacol. (2011) 162:584–96. doi: 10.1111/j.1476-5381.2010.01063.x

Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA. (1990) 875:1932–6. doi: 10.1073/pnas.87.5.1932

Galiègue S, Mary S, Marchand J, Dussossoy D, Carrière D, Carayon P, et al. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem. (1995) 232:54–61. doi: 10.1111/j.1432-1033.1995.tb20780.x

Cabral GA, Raborn ES, Griffin L, Dennis J, Marciano-Cabral F. CB2 receptors in the brain: role in central immune function. Br J Pharmacol. (2008) 153:240–51. doi: 10.1038/sj.bjp.0707584

Richardson D, Pearson RG, Kurian N, Latif ML, Garle MJ, Barrett DA, et al. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther. (2008) 10:R43. doi: 10.1186/ar2401

Rapaka RS, Makriyannis, A, editors. NIDA Research Monograph 79 A RAUS Review Report. Struct-Activ Relationsh Cannabin (1987) 79:1–210.

Zhornitsky S, Potvin S. Cannabidiol in humans – the quest for therapeutic targets. Pharmaceuticals (2012) 5:529–52. doi: 10.3390/ph5050529

Sacerdote P, Martucci C, Vaccani A, Bariselli F, Panerai AE, Colombo A, et al. The nonpsychoactive component of marijuana cannabidiol modulates chemotaxis and IL-10 and IL-12 production of murine macrophages both in vivo and in vitro. J Neuroimmunol. (2005) 159:97–105. doi: 10.1016/j.jneuroim.2004.10.003

Costa B, Giagnoni G, Franke C, Trovato AE, Colleoni M. Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation. Br J Pharmacol. (2004)143:247–50. doi: 10.1038/sj.bjp.0705920

Comelli F, Giagnoni G, Bettoni I, Colleoni M, Costa B. Antihyperalgesic effect of a Cannabis sativa extract in a rat model of neuropathic pain: mechanisms involved. Phytother Res. (2008) 22:1017–24. doi: 10.1002/ptr.2401

Shiue SJ, Peng HY, Lin CR, Wang SW, Rau RH, Cheng JK. Continuous intrathecal infusion of cannabinoid receptor agonists attenuates nerve ligation–induced pain in rats. Reg Anesth Pain Med. (2017) 42:499–506. doi: 10.1097/AAP.0000000000000601

Cui JH, Kim WM, Lee HG, Kim YO, Kim CM, Yoon MH. Antinociceptive effect of intrathecal cannabinoid receptor agonist WIN 55,212-2 in a rat bone tumor pain model. Neurosci Lett. (2011) 493:67–71. doi: 10.1016/j.neulet.2010.12.052

Malfait AM, Gallily R, Sumariwalla PF, Malik AS, Andreakos E, Mechoulam R, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA. (2000) 97:9561–6. doi: 10.1073/pnas.160105897

Zgair A, Wong JC, Sabri A, Fischer PM, Barrett DA, Constantinescu CS, et al. Development of a simple and sensitive HPLC–UV method for the simultaneous determination of cannabidiol and Δ(9)-tetrahydrocannabinol in rat plasma. J Pharm Biomed Anal. (2015) 114:145–51. doi: 10.1016/j.jpba.2015.05.019

Kirkwood JS, Broeckling CD, Donahue S, Prenni JE. A novel microflow LC-MS method for the quantitation of endocannabinoids in serum. J Chromatogr B Analyt Technol Biomed Life Sci. (2016) 1033–1034:271–7. doi: 10.1016/j.jchromb.2016.08.035

MacLean B, Tomazela DM, Shulman N, Chambers M, Finney GL, Frewen B, et al. Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics (2010) 26:966–8. doi: 10.1093/bioinformatics/btq054

Broccardo CJ, Schauer KL, Kohrt WM, Schwartz RS, Murphy JP, Prenni JE. Multiplexed analysis of steroid hormones in human serum using novel microflow tile technology and LC–MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. (2013) 934:16–21. doi: 10.1016/j.jchromb.2013.06.031

Shrivastava A, Gupta VB. Methods for the determination of limit of detection and limit of quantitation of the analytical methods. Chron Young Sci. (2011) 2:21–5. doi: 10.4103/2229-5186.79345

McCarthy G, O’Donovan J, Jones B, McAllister H, Seed M, Mooney C. Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis. Vet J. (2007) 174:54–61. doi: 10.1016/j.tvjl.2006.02.015

Brown DC, Bell M, Rhodes L. Power of treatment success definitions when the Canine Brief Pain Inventory is used to evaluate carprofen treatment for the control of pain and inflammation in dogs with osteoarthritis. Am J Vet Res. (2013) 74:1467–73. doi: 10.2460/ajvr.74.12.1467

Brown DC, Boston RC, Coyne JC, Farrar JT. Ability of the canine brief pain inventory to detect response to treatment in dogs with osteoarthritis. J Am Vet Med Assoc. (2008) 233:1278–83. doi: 10.2460/javma.233.8.1278

Hudson JT, Slater MR, Taylor L, Scott HM, Kerwin SC. Assessing repeatability and validity of a visual analogue scale questionnaire for use in assessing pain and lameness in dogs. Am J Vet Res. (2004) 65:1634–43. doi: 10.2460/ajvr.2004.65.1634

Fahie MA, Ortolano GA, Guercio V, Schaffer JA, Johnston G, Au J. A randomized controlled trial of the efficacy of autologous platelet therapy for the treatment of osteoarthritis in dogs. J Am Vet Med Assoc. (2013) 243:1291–7. doi: 10.2460/javma.243.9.1291

Lubke, Gitta H, Muthen, Bengt O. Applying multigroup confirmatory factor models for continuous outcomes to likert scale data complicates meaningful group comparisons. Struct Equat Model. (2004) 11:514–34. doi: 10.1207/s15328007sem1104_2

Carifio J, Perla R. Ten common misunderstandings, misconceptions, persistent myths and urban legends about likert scales and likert response formats and their antidotes. J Soc Sci. (2007) 2:106–16.

Samara E, Bialer M, Mechoulam R. Pharmacokinetics of cannabidiol in dogs. Drug Metab Dispos. (1988) 16:469–72.

Garrett ER, Hunt CA. Physicochemical properties, solubility, and protein binding of delta9-tetrahydrocannabinol. J Pharm Sci. (1974) 63:1056–64. doi: 10.1002/jps.2600630705

Harvey DJ, Samara E, Mechoulam R. Comparative metabolism of cannabidiol in dog, rat and man. Pharmacol Biochem Behav. (1991) 40:523–32.

Conzemius mg, Evans RB. Caregiver placebo effect for dogs with lameness from osteoarthritis. J Am Vet Med Assoc. (2012) 241:1314–9. doi: 10.2460/javma.241.10.1314

Bornheim LM, Correia MA. Effect of cannabidiol on cytochrome P-450 isozymes. Biochem Pharmacol. (1989) 38:2789–94. doi: 10.1016/0006-2952(89)90432-2

Khanna P, Gupta MB, Gupta GP, Sanwal GG, Ali B. Influence of chronic oral intake of cannabis extract on oxidative and hydrolytic metabolism of xenobiotics in rat. Biochem Pharmacol. (1991) 41:109–13. doi: 10.1016/0006-2952(91)90017-Y

Yamamoto I, Watanabe K, Narimatsu S, Yoshimura H. Recent advances in the metabolism of cannabinoids. Int J Biochem Cell Biol. (1995) 27:741–6. doi: 10.1016/1357-2725(95)00043-O

Kogan LR, Hellyer PW, Robinson NG. Consumers’ perceptions of hemp products for animals. J Am Holist Vet Med Assoc. (2016) 42:40–8.

Campora L, Miragliotta V, Ricci E, Cristino L, Di Marzo V, Albanese F, et al. Cannabinoid receptor type 1 and 2 expression in the skin of healthy dogs and dogs with atopic dermatitis. Am J Vet Res. (2012) 73:988–95. doi: 10.2460/ajvr.73.7.988

Karler R, Turkanis SA. The cannabinoids as potential antiepileptics. J Clin Pharmacol. (1981) 21:437S−48S. doi: 10.1002/j.1552-4604.1981.tb02624.x

Kathmann M, Flau K, Redmer A, Trankle C, Schlicker E. Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn Schmiedebergs Arch Pharmacol. (2006) 372:354–61. doi: 10.1007/s00210-006-0033-x

Cabral GA, Griffin-Thomas L. Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation. Expert Rev Mol Med. (2009) 11:e3. doi: 10.1017/S1462399409000957

(2019). Retrieved 19 September 2019, from https://www.sciencedaily.com/releases/2019/05/190521101450.htm

Stephanie McGrath, Lisa R. Bartner, Sangeeta Rao, Rebecca A. Packer, Daniel L. Gustafson. Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy. Journal of the American Veterinary Medical Association, 2019; 254 (11): 1301 DOI: 10.2460/javma.254.11.1301

Mogi, C., & Fukuyama, T. (2019). Cannaibiol as a Potential Anti-Epileptic Dietary Supplement in Dogs with Suspected Epilepsy. Retrieved 19 September 2019, from https://www.uco.es/ucopress/ojs/index.php/pet/article/view/11800/10795

Bradford, B. (2019). AKC Canine Health Foundation. Retrieved 19 September 2019, from http://www.akcchf.org/news-events/news/clinical-trial-to-study.html

Samara E, e. (1988). Pharmacokinetics of cannabidiol in dogs. – PubMed – NCBI. Retrieved 19 September 2019, from https://www.ncbi.nlm.nih.gov/pubmed/2900742

Soares, V., & Campos, A. (2019). Evidences for the Anti-panic Actions of Cannabidiol. Retrieved 19 September 2019, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412699/

Bitencourt, R., Pamplona, F., & Takahashi, R. (2019). A current overview of cannabinoids and glucocorticoids in facilitating extinction of aversive memories: Potential extinction enhancers. Retrieved 19 September 2019, from https://doi.org/10.1016/j.neuropharm.2012.05.039

Manzanares, J., Julian, M., & Carrascosa, A. (2019). Role of the Cannabinoid System in Pain Control and Therapeutic Im…: Ingenta Connect. Retrieved 19 September 2019, from https://www.ingentaconnect.com/content/ben/cn/2006/00000004/00000003/art00009

Pamplona, F., Rolim da Silva, L., & Can, A. (2019). Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis. Retrieved 19 September 2019, from https://www.frontiersin.org/articles/10.3389/fneur.2018.00759/full?utm_source=FRN&utm_medium=EMAIL_IRIS&utm_campaign=EMI_FRN_ARTICLEPUBLISHED_FOLLOWERS&utm_content=ARTICLE_TITLE

Scott, S., Lewis, N., Lee, H., & Hughes, S. (2019). Cannabidiol in Anxiety and Sleep: A Large Case Series. Retrieved 19 September 2019, from http://www.thepermanentejournal.org/issues/2019/winter/6960-cannabis.html

Chiocchetti, R., Galiazzo, G., Tagliavia, C., Stanzani, A., Giancola, F., Menchetti, M., … Mandrioli, L. (2019, September 19). Cellular Distribution of Canonical and Putative Cannabinoid Receptors in Canine Cervical Dorsal Root Ganglia. Retrieved October 19, 2019, from https://www.ncbi.nlm.nih.gov/pubmed/31608295/.

Hartsel, J. A., Boyar, K., Pham, A., Silver, R. J., & Makriyannis, A. (2019). Cannabis in Veterinary Medicine: Cannabinoid Therapies for Animals. Nutraceuticals in Veterinary Medicine, 121–155. doi: 10.1007/978-3-030-04624-8_10

Russo, E. B., & Mcpartland, J. M. (2002). Cannabis is more than simply Δ9-tetrahydrocannabinol. Psychopharmacology, 164(4), 431-432. DOI:10.1007/s00213-002-1348-z

Kathmann M, Flau K, Redmer A, Tränkle C, Schlicker E (February 2006). “Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors”. Naunyn Schmiedebergs Arch. Pharmacol372 (5): 354–61.

Pertwee RG (2006). “The pharmacology of cannabinoid receptors and their ligands: an overview”. International Journal of Obesity, 30: S13-S18

Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS (December 2012). “Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders”. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences (Review). 367(1607): 3364–78.

Takeda S1, Okajima S, Miyoshi H, Yoshida K, Okamoto Y, Okada T, Amamoto T, Watanabe K, Omiecinski CJ, Aramaki H. Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration. Toxicol Lett. 2012 Nov 15;214(3):314-9

Berman, Paula et al. “A New ESI-LC/MS Approach for Comprehensive Metabolic Profiling of Phytocannabinoids in Cannabis.” Scientific Reports 8 (2018): 14280. PMC Web 19 September 2018

Booth, Judith K., Jonathan E. Page, and Jörg Bohlmann. “Terpene Synthases from Cannabis Sativa.” Ed. Björn Hamberger. PLoS ONE 12.3 (2017): e0173911. PMC. Web. 19 September 2019.

Andre, Christelle M.; Hausman, Jean-Francois; Guerriero, Gea, “Cannabis Sativa: The Plant of the Thousand and One Molecules”, Frontiers in Plant Science, 7 (2016):19, PMC Web. 19 September 2019

Gertsch, Jürg; Pertwee, Roger G; Di Marzo, Vincenzo (2010). Phytocannabinoids beyond the Cannabis plant – do they exist? British journal of Pharmacology, 160.3 (2010), 523-529. PMC.

Goldstein, B. (2016). Cannabis revealed: How the world’s most misunderstood plant is healing everything from chronic pain to epilepsy. Bonni S. Goldstein MD INC

Munro S, Thomas KL, Abu-Shaar M. (Sep 1993). “Molecular characterization of a peripheral receptor for cannabinoids”. Nature. 365 (6441): 61-5

Cabral GA, Griffin‐Thomas L (2009). Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation. Expert Rev Mol Med 11: e3.

Mark A. Twardowski et al, Effects of Cannabis Use on Sedation Requirements for Endoscopic Procedures, The Journal of the American Osteopathic Association (2019).  DOI: 10.7556/jaoa.2019.052

Herkenham M, Lynn AB, Little MD, Cannabinoid receptor localization in brain. Proceedings of the National Academy of Sciences of the United States of America. 1990:87 (5): 1932-196

Sultan, A.S., Marie, M.A. & Sheweita S.A. (2018). Novel Mechanism of Cannabidiol-induced Apoptosis in Breast Cancer Cell Lines. Breast (Edinburgh, Scotland), 41, 34–41.

Zuardi AW, Cosme RA, Graeff FG, Guimarães FS. Effects of ipsapirone and cannabidiol on human experimental anxiety. J Psychopharmacol. 1993;7:82–88.

Naftali T, Bar-Lev Schleider L, Dotan I, Lansky EP, Sklerovsky Benjaminov F, Konikoff FM. Cannabis induces a clinical response in patients with Crohn’s disease: a prospective placebo-controlled study. Clin Gastroenterol Hepatol. 2013 Oct;11(10):1276-1280.e1. doi: 10.1016/j.cgh.2013.04.034.

Stephanie McGrath, DVM, MS, Lisa R. Bartner, DVM, MS, Sangeeta Rao, BVSc, MVSc, PhD, Lori R. Kogan, PhD, Peter W. Hellyer, DVM, MS. “A Report of Adverse Effects Associated With the Administration of Cannabidiol in Healthy Dogs”.  AHVMA Journal, Volume 52 Fall 2018

Vaughn D, Kulpa J, Paulionis L. “Preliminary Investigation of the Safety of Escalating Cannabinoid Doses in Healthy Dogs” Front Vet Sci. 2020 Feb 11;7:51. doi: 10.3389/fvets.2020.00051. eCollection 2020.

Mark Barton Frank, Qing Yang, Jeanette Osban, Joseph T Azzarello, Marcia R Saban, Ricardo Saban, Richard A Ashley,  Jan C Welter, Kar-Ming Fung, Hsueh-Kung Lin. “Frankincense oil derived from Boswellia carteri induces tumor cell specific cytotoxicity” 2009 Mar 18. doi: 10.1186/1472-6882-9-6.

Nicholas A.Jones, Sarah E.Glyn, SatoshiAkiyama, Thomas D.M.Hill, Andrew J.Hill, Samantha E.Weston, Matthew D.A.Burnett, YukiYamasaki, Gary J.Stephens, Benjamin J.Whalley, Claire M.Williams. “Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures.” Volume 21, Issue 5, Just 2012, Pages 344-352

Lisa R. Bartner, Stephanie McGrath, Sangeeta Rao, Linda K. Hyatt, Luke A. Wittenburg. “Pharmacokinetics of cannabidiol administered by 3 delivery methods at 2 different dosages to healthy dogs.” 2018 Jul; 82(3): 178–183.

 

[{"code":""
[{"code":""
"label":"Not quite"
"label":"Not quite"
"win":false}
"win":false}
{"code":"SPIN-WIN-20"
{"code":"SPIN-WIN-20"
"label":"20% Off"
"label":"20% Off"
"win":true}
"win":true}
{"code":"FREESHIPPING"
{"code":"FREESHIPPING"
"label":"Free shipping"
"label":"Free shipping"
"win":false}
"win":false}
{"code":"10OFF"
{"code":"10OFF"
"label":"30% Off"
"label":"30% Off"
"win":false}
"win":false}
{"code":"SPIN-WIN-10"
{"code":"SPIN-WIN-10"
"label":"10% Off "
"label":"10% Off "
"win":true}
"win":true}
{"code":"SPIN-WIN-10"
{"code":"SPIN-WIN-10"
"label":"10% Off"
"label":"10% Off"
"win":true}
"win":true}
{"code":""
{"code":""
"label":"Spin again"
"label":"Spin again"
"win":false}
"win":false}
{"code":"SPIN-WIN-15"
{"code":"SPIN-WIN-15"
"label":"15% Off"
"label":"15% Off"
"win":true}
"win":true}
{"code":"25OFF"
{"code":"25OFF"
"label":"50% Off"
"label":"50% Off"
"win":false}
"win":false}
{"code":"FREESHIPPING"
{"code":"FREESHIPPING"
"label":"Free shipping"
"label":"Free shipping"
"win":false}
"win":false}
{"code":""
{"code":""
"label":"Almost"
"label":"Almost"
"win":false}
"win":false}
{"code":"SPIN-WIN-10"
{"code":"SPIN-WIN-10"
"label":"10% Off"
"label":"10% Off"
"win":true}]
"win":true}]