CBD and the Endocannabinoid System

 

The endocannabinoid system helps modulate neuro-immune responses via CB1 (pain/mood) and CB2 (immune system) receptors which are ubiquitous in  the CNS and body (1). The ECS is  thought to be involved in: neuroprotection, immunomodulation, fighting cancer, relieving pain, metabolic balance and GI motility. Phytocannabinoids from hemp and other cannabis species can act as partial agonists of the ECS, providing pain relief through co-activation with endogenous opioid receptors and  reduce excessive inflammatory responses in  chronic diseases and aging, causing minimal unwanted side effects.

Pharmacokinetics of cannabinoids

Preliminary data in dogs (2) indicate that therapeutic levels are most rapidly reached through trans-mucosal dosing, which avoids interaction with the liver CYP450 detoxification system. However, cannabinoids may compete for CYP450 binding sites (3), possibly changing drug clearance time for other medications. A partial list of drugs that may interact with CBD can be found on the Plena Curae website. This list includes, but is not limited to, certain anti-seizure medications, and several classes of antibiotics and chemotherapeutic drugs. Anecdotally, dosing with cannabinoids has not been found to alter phenobarbital serum levels (personal communication, G. Richter, DVM).

Cannabinoids have a bi-phasic dosing curve, with clinical effect increasing to a high level, then falling off with doses exceeding the peak efficacy for that individual. For this reason, some trial and adaptation is advisable when adding cannabidiol (CBD) to a treatment plan, and dosage may increase or decrease. Occasionally, behavioral disinhibition is  seen in  micro-dosing CBD which usually resolves with a further reduction of the dose.  Best results are achieved when evaluating dosage after one week.

Indications for use of exogenous cannabinoids in  animals

At this time, there are a few indications for THC (cancer, hospice) in veterinary care, but many useful applications for the non-psychoactive cannabinoid, CBD.  Uses most commonly include: reducing anxiety and phobias, regulating arthritis pain and inflammation (4), mitigating idiopathic and non-drug-responsive seizure activity (5), neurogenic pain, and regulation of diabetes (6) .  While cannabinoid research is in its infancy in the US, researchers worldwide have speculated that some neurodegenerative conditions, like degenerative myelopathy (7), may have their etiology in dysregulated function of the endogenous ECS.   For clinicians who have incorporated CBD into their treatment plans, it is  proving to be a useful adjunct in managing many common veterinary complaints, including those of old age.*

Though each individual animal’s response may vary, generally four levels of CBD dosing are used in  pets:

Dose (per kg body weight) Indications
Low (0.1 mg/kg) Anxiety, fear, stress, behavioral issues, mild pain, muscle tension
Medium (0.2-0.5 mg/kg) Osteoarthritis, moderate pain, muscle spasms
High (0.5-1.0 mg/kg) Moderate to severe pain, neurogenic pain, degenerative myelopathy, tremors, idiopathic epilepsy, diabetes regulation, IBD
Ultra (1.0-5.0 mg/kg) Refractory epilepsy, cancer, refractory pain, hospice care

In  a recent study at Colorado State (8), very high dose CBD treatment was associated with transitory mild diarrhea upon initiation of treatment, and, with long-term use, one third of dogs showed elevation of alkaline phosphatase.  However, this study had no control group to compare environmental and stress effects, and these observations were noted at doses of 10-20 mg/kg, compared with clinically recommended doses of 0.1-1 mg/kg from veterinarians with extensive experience in CBD’s clinical applications in  pets (personal communications, R.  Silver DVM, G. Richter DVM).

Plena Curae products are simple to dose and have consistent, reliable levels of CBD isolate. It is  always recommended to administer a CBD oil dose directly into the mouth, not on top of food, since trans-mucosal absorption is  optimal. Plena Curae ECS support is  compounded in  coconut oil, which is  highly palatable to most pets, so can be given on a clean plate 10  minutes before meals.

Plena Curae Endocannabinoid Support 900 contains 30  mg per ml, or 1 mg/ drop of product.

Plena Curae Endocannabinoid Support 1800 contains 60  mg per ml, or 2 mg/drop, for dosing giant breed dogs and equine patients.

Preliminary trials in horses suggest that pain and anxiety reduction can be achieved with as little as 20-25 mg CBD oil administered trans-mucosally, once or twice a day, (1/2 ml  of the ECS1800 product.)

Plena Curae products are always 3rd party lab tested, 100% THC-free, and made in  a GMP facility.

*These statements have not been evaluated by the Food and Drug Administration. This product is  not intended to diagnose, treat, cure or prevent any disease.

1  Freundt-Revilla J, Kegler K, Baumgärtner W, Tipold A Spatial distribution of cannabinoid receptor type 1 (CB1) in  normal canine central and peripheral nervous system. PLoS One. 2017 Jul 10;12(7):e0181064.

2  Bartner, McGrath et al.  (2018) Pharmacokinetics of cannabidiol administered by three delivery methods at two different dosages to healthy dogs. Can J Vet Res 82:178-183.

3  Zendulka O, Dovrtelova G, Noskova K, et al.  (2016) Cannabinoids and Cytochrome P450 Interactions. Curr Drug Metab. 17(3):206–226.

4  Gamble LJ, Boesch JM, et al.  (2018) Pharmacokinetics,Safety,and Clinical Efficacy of Cannabidiol Treatment in  Osteoarthritic Dogs. Front in Vet Sci 5:165.

5  Jones NA, Glyn SE, Akiyama S, et al.  (2012) Cannabidiol exerts anti- convulsant effects in  animal models of temporal lobe and partial seizures. Seizure. 21(5):344–352.

6  Gruden G, Barutta F, Kunos G, Pacher P. (2016) Role of the endocannabinoid system in  diabetes and diabetic complications. Br J Pharmacol. 173(7):1116-27.

7  Fernández-Trapero M,  Espejo-Porras F, Rodríguez-Cueto C, Coates JR, Pérez-Díaz C, de Lago E, Fernández-Ruiz J. (2017) Upregulation of CB2 receptors in  reactive astrocytes in  canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis.  Dis Model Mech. 10(5):551-558.

8  McGrath, Bartner et al.  (2018) A Report of Adverse Effects Associated with the Administration of Cannabidiol in  Healthy Dogs .  J AHVMA 52:34-38.