Studies

Safety

1.“Preliminary Investigation of the Safety of Escalating Cannabinoid Doses in Healthy Dogs”

Canopy Animal Health, Canopy Growth Corporation, Toronto, Canada, February 2020

This set of clinical trials tested for adverse reactions based on escalating doses of oral CBD and THC for dogs, with a maximum dose of 640 mg and 597 mg respectively. No lethal dose detected and adverse events were mild.

2.CBD clinical trial results on seizure frequency in dogs ‘encouraging’

Colorado State University, 2019

In this study conducted 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.

3. “Comparison of acute oral toxicity of cannabinoids in rats, dogs and monkeys”

Mason Research Institute Thompson GR, Rosenkrantz H, Schaeppi UH, Braude MC.

In this study, scientists sought to find a lethal dose for THC in dogs, rats and chimpanzees. Even at a single intravenous dose of 9000 mg, there was no lethal dose for dogs.

4. Preliminary Investigation of the Safety of Escalating Cannabinoid Doses in Healthy Dogs

Canopy Animal Health, Canopy Growth Corporation, Toronto, ON, Canada. 2020

In this study, 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.

5. SAFETY AND TOLERABILITY OF ESCALATING CANNABINOID DOSES IN HEALTHy CATS

J Feline Med Surg, December 2021

This is the first feline study to explore the safety and tolerability of CBD and THC, alone and in combination, in a controlled research setting. These findings will inform veterinarians of the safety profile of cannabinoids, particularly when considering the potential therapeutic use of CBD in cats or recognizing clinical signs associated with accidental exposure to THC-containing products.

Full-Spectrum vs. Isolated Extracts

1. “Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis”

UNICAMP, Campinas, Brazil 2018

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.”

2. “Overcoming the Bell‐Shaped Dose‐Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol”

The Lautenberg Center for General and Tumor Immunology, The Hadassah Medical School, The Hebrew University of Jerusalem, Jerusalem, Israel

“Our findings that CBD in the presence of other plant constituents improve the dose-response are supported by some recent reports showing that CBD in a standardized Cannabis sativa extract is more potent or efficacious than pure CBD. The higher efficiency of plant extract might be explained by additive or synergistic interactions between CBD and minor phytocannabinoids or non-cannabinoids presented in the extracts.”

Arthritis, Pain and Inflammation

1. Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University 2018

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:

2. “A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain”

Baylor College of Medicine, September 2020

“In the veterinary study, CBD significantly decreased pain and increased mobility in a dose-dependent fashion among animals with an affirmative diagnosis of OA. ”

2. Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes

Current Neuropharmacology, Volume 4, Number 3, 2006

This study states that CBD has therapeutic benefits for both people and pets suffering from chronic pain and acute chronic pain episodes.

3. CB₂ cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies

Arévalo-Martín A, García-Ovejero D, Gómez O, et al. Br J Pharmacol. 2008

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

4. CANNABIDIOL-RICH NON-PSYCHOTROPIC CANNABIS SATIVA L. OILS ATTENUATE PERIPHERAL NEUROPATHY SYMPTOMS BY REGULATION OF CB2-MEDIATED MICROGLIAL NEUROINFLAMMATION

Borgonetti V, Anceschi L, Brighenti V, Corsi L, Governa P, Manetti F, Pellati F, Galeotti N. 2022 Dec.

“…oral administration attenuated NP symptoms by reducing spinal neuroinflammation and underline the important role of the synergism between cannabinoids and terpenes.”

Cancer and Tumors

1. Cannabinoids, endocannabinoids, and cancer

Hermanson, D.J., Marnett, L.J. Cannabinoids, endocannabinoids, and cancer. Cancer Metastasis Rev30, 599–612 (2011)

“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.”

2. Combination therapy with cannabidiol and chemotherapeutics in canine urothelial carcinoma cells

Ontario Veterinary College, August 5, 2021, Samuel E. Hocker, Anthony J. Mutsaers,

In-vitro study on canine bladder cancer from OVC  in Canada. This study represents the first evaluation of pharmacological interactions between CBD and vinblastine, mitoxantrone, carboplatin, and piroxicam. CBD reduced cell viability and induced apoptosis in canine urothelial cells 

3. “The effect of cannabidiol on canine neoplastic cell proliferation and MAP Kinase activation during autophagy and apoptosis.”

Henry, J.G., Shoemaker, G., Prieto, J.M., Hannon, M.B. and Wakshlag, J.J. (November, 2020)

“CBD is effective at hindering cell proliferation and induction of autophagy and apoptosis rapidly across neoplastic cell lines and further clinical trials are needed to understand its efficacy and interactions with traditional chemotherapy”

4. GPR55 signalling promotes proliferation of pancreatic cancer cells and tumour growth in mice, and its inhibition increases effects of gemcitabine

Ferro, R., Adamska, A., Lattanzio, R. et al.

This study 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.

5. Frankincense oil derived from Boswellia carteri induces tumor cell specific cytotoxicity

 Oklahoma Medical Research Foundation Microarray Research Facility, Oklahoma City, OK 73104, USA 2009

Frankincense oil is presented as an promising alternative therapy 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.

6. The endocannabinoid system of the skin. A potential approach for the treatment of skin disorders

Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain 2018

“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 “

7. Statement by 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.”

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.

Seizures

1.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.

Colorado State University, Journal of the American Veterinary Medical Association, 2019

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.

2. “Cannabidiol as a potential anti-epileptic dietary supplement in dogs with suspected epilepsy:three case reports”

Yamazaki University of Animal Health Technology, Japan, 2018

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.

3. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures

School of Pharmacy, University of Reading, UK 2012

Nutrition and GI tract

1. Cannabis in Veterinary Medicine: Cannabinoid Therapies for Animals

Nutraceuticals in Veterinary Medicine (pp.121-155) 2019

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.

2. Cannabis induces a clinical response in patients with Crohn’s disease: a prospective placebo-controlled study

Department of Gastroenterology and Hepatology, Meir Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Kfar Saba, Israel.

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.

3. Cannabis Therapeutics and the Future of Neurology

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

Allergies and Autoimmune Conditions

1. Article: Molecular Mimicry: The Role of Cannabis in Healing Autoimmune Disease

“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. ”

2. CB₂ cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies

“Resident immune and CNS cells express functional CB₂ receptors. The activation of CB₂ receptors results in the modulation of the inflammatory response…”

3.Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma

“CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels. CBD seems to be a potential new drug to modulate inflammatory response in asthma.”

Absorption Rates, Bioavailability, Half-Life

1. “Pharmacokinetics of cannabidiol in dogs”

Department of Pharmacy, School of Pharmacy, Hebrew University, Jerusalem, Israel

This study conducted by the Department of Pharmacy, School of Pharmacy at Hebrew University in Jerusalem, studied the distribution of CBD throughout the bloodstream after oral and IV application. They also studied the half-life of the to determine how long it would take to eliminate form the bloodstream (avg. 9 hrs).

2. Cellular Distribution of Canonical and Putative Cannabinoid Receptors in Canine Cervical Dorsal Root Ganglia

 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 and brain. Interestingly it was found that dogs had more receptors than humans in these areas.

3. “Pharmacokinetics of cannabidiol administered by 3 delivery methods at 2 different dosages to healthy dogs”

Department of Clinical Sciences, Colorado State University 2018

The Canadian Journal Of Veterinary Research reports that this study shows various rate of absorption for three methods of administration, as well as the corresponding half life for each method. (Micro-Encapsulated, Orally, and Transdermally)

4. Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats

Department of Comparative Diagnostic Population Medicine, University of Florida College of Veterinary Medicine 2019

In this study researchers found that cats absorbed CBD much less readily than dogs. They ended up with around one fifth the blood concentration at a proportional dose. They found CBD was readily absorbed and present throughout the body of both species after administration.

Liver

1. Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

Department of Human Nutrition and Metabolism, Braun School of Public Health, Hadassah-Hebrew University Medical School, Jerusalem, Israel

In a recent study published by the British Journal of Pharmacology, researchers found that administering CBD to test subjects with acute liver disease actually resulted in repair to the damages tissue.

2. “Observed Impact of Long-term Consumption of Oral Cannabidiol on Liver Function in Healthy Adults”

Kaufmann R, Aqua K, Lombardo J, Lee M (2021)

This study found that during a long term trial, only a small number of test subjects experienced raised levels of ALT and the degree to which that enzyme was increased was deemed insignificant. Full-spectrum hemp oil was used by 55.7%, CBD-isolate by 40.5%, and broad spectrum by 3.8%.

Anxiety, Stress, and Sleep Disorders

1.Evidences for the Anti-panic Actions of Cannabidiol

CBD is renowned for its anti-anxiolytic effects for both people and pets for good reason. This study published in Current Neuropharmacology states: “CBD seems to be a promising drug for the treatment of various ‘panic disorders’.”

2. A current overview of cannabinoids and glucocorticoids in facilitating extinction of aversive memories: Potential extinction enhancers

Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Trindade, 88040-900 Florianópolis, SC, Brazil

“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.

3. Cannabidiol in Anxiety and Sleep: A Large Case Series

Research like this shows CBD may be a viable treatment option for sleep disorders in people and pets. This study reports 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.

4. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects

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.

Cardiovascular Effects

1. Acute administration of cannabidiol in vivo suppresses ischaemia-induced cardiac arrhythmias and reduces infarct size when given at reperfusion

School of Pharmacy & Life Sciences, Institute for Health & Welfare Research, Robert Gordon University, Schoolhill, Aberdeen, UK

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.

2. A Systematic Review and Meta-Analysis of the Haemodynamic Effects of Cannabidiol

Vascular Medicine, Division of Medical Sciences and Graduate Entry Medicine, Royal Derby Hospital Centre, School of Medicine, University of Nottingham, Derby, UK

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).

Diabetes

1. The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications

Laboratory of Physiological Studies, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health 2012

“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.”

2. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice

Hadassah University Hospital, Department of Bone Marrow Transplantation & Cancer Immunotherapy, POB 12000, Jerusalem, 91120, Israel.

This study found that full spectrum hemp extract CBD actually lowered the instance of diabetes in non-obese diabetic mice.

3. Cannabinoids alter endothelial function in the Zucker rat model of type 2 diabetes

Division of Vascular Medicine, School of Graduate Entry Medicine and Health, University of Nottingham, Royal Derby Hospital,  UK.

This study found that full spectrum hemp extract CBD may also improve circulation and improve overall health in diabetic rats.

Thyroid

1. Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions

Lakiotaki E, Giaginis C, Tolia M, et al. Biomed Res Int. 2015

This study they assert that:  “These results supported evidence that CB receptors and especially CB2 receptor may interfere with molecular pathways participating in thyroid malignant transformation and could be considered as potential therapeutic targets to suppress tumor progression.”

Brain Health

1.Review of the neurological benefits of phytocannabinoids

Department of Neurosurgery, University of Pittsburgh Medical Center, 2019

“Current research indicates the phytocannabinoids have a powerful therapeutic potential in a variety of ailments primarily through their interaction with the ECS. CBD is of particular interest due to its wide-ranging capabilities and lack of side effects in a variety of neurological conditions and diseases.”

2. Understanding the Modulatory Effects of Cannabidiol on Alzheimer’s Disease

Wonkwang University Brain Sci. 2021

Many studies reviewed here suggest that CBD can provide symptomatic relief or even arrest AD progression through effects such as anti-inflammatory, Antioxidative, neurogenesis. These effects on AD can be inferred to have similar benefits to pets suffering from related diseases like CCD

3. A Review of the Potential Use of Pinene and Linalool as Terpene-Based Medicines for Brain Health: Discovering Novel Therapeutics in the Flavours and Fragrances of Cannabis

Infections

1.The antimicrobial potential of cannabidiol

Commun Biol. Blaskovich et al. 2021

“More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae.”

2.Antibacterial cannabinoids from cannabis sativa

J Nat Prod. Appendino et al. 2008

“All five major cannabinoids (cannabidiol (1b), cannabichromene (2), cannabigerol (3b), Delta (9)-tetrahydrocannabinol (4b), and cannabinol (5)) showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains of current clinical relevance.”

3. Anti-Bacterial Effect of Cannabidiol against the Cariogenic Streptococcus mutans Bacterium

Barak T, Sharon E, Steinberg D, Feldman M, Sionov RV, Shalish M. 2022 Dec.

“In conclusion, we show that CBD has a strong inhibitory effect against cariogenic bacteria, suggesting that it is a potential drug adjuvant for reducing oral pathogenic bacterial load as well as protecting against dental caries.”

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