THE ENDOCANNABINOID SYSTEM (Opinions and thoughts?)

First, allow us to preface our introduction and description by stating we are not interested in, nor are we advocating the administration of, the well-known psychotropic compound Δ9-tetrahydrocannabinol or Δ9-THC, in concentrations sufficient to produce the ‘high’ or psychotropic effects which are normally associated with marijuana. We are not advocating the administration of marijuana, by any route, in any form, to any animal in order to produce medical benefit or to produce any psychotropic effect.

Rather, we are advocating the administration and continued research into the non-psychotropic compounds called phytocannabinoids, terpenes and flavonoids for the purposes of adjunctive and palliative therapy in companion animals.

In early 2000, we became interested in the well-established and ongoing research from Europe, Canada and Jerusalem concerning the medical benefits derived from the more than 545 identified chemical compounds in Cannabis sativa L., or hemp. More specifically, we were interested in the approximately 111 terpenophenolic compounds named phytocannabinoids, which have not been detected in any other plant, and the more than 140 terpenes and 23 flavonoids produced by Cannabis sativa L. The combination of phytocannabinoids, terpenes and flavonoids has been scientifically demonstrated to modulate numerous physiologic and pathophysiologic processes. This modulation is achieved through the interaction between these compounds and the mammalian endocannabinoid system (ECS).

The ECS consists of four known receptor subtypes, signaling pathways, endogenous ligands (endocannabinoids), EMT and the synthetic and catabolic pathways for said ligands. There are five identified endocannabinoids. The most abundant and deeply researched are 2-arachidonoylglycerol (2-AG) and anandamide. The other lesser understood compounds are Noladin ether, Virodhamine and NADA. These endogenous compounds are classified as neurotransmitters and neuromodulators. Additionally, because these compounds are hydrophobic, their main actions are limited to paracrine and autocrine effects.

The other components of the ECS are numerous G-protein coupled cannabinoid receptors, which CB1-R and CB2-R appear to be the most abundant. The distribution of CB1-R is primarily the CNS, PNS, ANS, pituitary, thyroid, adrenal, male and female reproductive system, hepatic, adipocytes, pulmonary, renal, myocardium, vascular, gastrointestinal neuronal tissue. The distribution of CB2-R is primarily the immune system, spleen, tonsils, thymus, gastrointestinal tract, osteocytes, monocytes, macrophages, microglia, B-cells, T-cells, cerebral cortex, hippocampal pyramidal cells, globus pallidus, cerebellar purkinje cells, cerebellar granual cells, cerebellar nuclei, vestibular nuclei, dorsal motor nucleus of the vagus, nucleus ambiguous, spinal trigeminal, nucleus and spinal sensory neurons.

The final two receptors are newly discovered and the extent of their distribution and effects are currently being researched. CB4-R appears to be predominately located in endothelium and its function is as of yet unknown. CB6-R and its distribution is unclear, but it appears to impart an anti-inflammatory effect which is different from that of CB1-R and CB2-R.
The final components of the ECS are the metabolic and catabolic compounds responsible for production, regulation and degradation of endogenous ligands. A few of these compounds are FAAH, MAGL, DAGL, PLC, Phosphatase, NAPE-PLD, NAPE-PLC and NAT.

Latest research reveals that the endocannabinoid system is ubiquitous in vertebrates and has been discovered in over 50% of invertebrates.

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