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In pre-clinical animal studies, the ECS has been shown to modulate seizure threshold and severity of seizure activity (Wallace, Martin, & DeLorenzo 2002). According to Hampson et al. (2003) in U.S. Patent 6,630,507 B1, damaging chemicals associated with hypoxia can be minimized if glutamate levels are modulated:
The brain has many redundant blood supplies, which means that its tissue is seldom completely deprived of oxygen, even during acute ischemic events caused by thromboembolic events or trauma. A combination of the injury of hypoxia with the added insult of glutamate toxicity is therefore believed to be ultimately responsible for cellular death. Hence if the additive insult of glutamate toxicity can be alleviated, neurological damage could also be lessened.
As a modulator of synaptic activity in the brain (Parker 2017), the ECS plays a central role in dampening down glutamate activity in excitotoxic neurons (Parker 2017; Russo 2016a), with CB1 receptors located directly on glutamatergic neurons (Howlett et al. 2002). This dampening down of glutamate is accomplished through “retrograde signaling.” In contrast with other neurotransmitters that travel “forward” across the neuron, eCBs are synthesized on the post-synaptic side of the neuron, and then travel “backward” to regulate levels of glutamate and other neurotransmitters (Lu & Mackie 2016).
In addition to its anti-glutamatergic effect, the ECS is also protective against secondary pathways of damage associated with inflammation. In the presence of tissue-trauma, CB2 receptors that are normally found in peripheral tissues express on microglial (Atwood & Mackie 2010; Benito et al. 2008), dendritic (Maresz et al. 2005; Pertwee 2008), and endothelial cells of the brain (Golech et al. 2004). This mechanism provides neuroprotection via the inhibition of proinflammatory mediators and reduction of leukocyte chemotaxis into brain tissue (Pancher & Hasko 2008). In short, ECS appears to reorganize its receptors in the context of CNS-trauma in order to modulate the damage associated with pro-inflammatory chemicals.
NEUROPSYCHIATRIC SYMPTOMS ASSOCIATED WITH THE “DIFFICULT ROAD”
The anti-inflammatory effects of the ECS have been shown to improve
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