CBD is a negative allosteric modulator of CB1 and CB2 cannabinoid receptors.
This has several implications.
- Firstly, negative modulation of CB1 receptors reduces the perceived effects of cannabinoid agonists, like THC.
- Secondly, it causes upregulation of the same CB1 receptors, which improves signaling and reduces the likelihood of endocannabinoid deficiency  .
What is the role of cannabinoid receptors?
Cannabinoid receptors are the most widely expressed G protein-coupled receptors in humans: they’re more numerous than all other GPCRs combined.
This well-established fact of human biology has been overlooked for years, thanks in part to the stigma against the only known agonist of these receptors, marijuana. Nonetheless, CB1 receptors specifically are immensely important in the regulation of neurotransmission patterns, especially inhibitory GABAergic transmission in the cortex, hippocampus, and amygdala.
Depolarization-Induced Suppression of Inhibition
The functional role of cannabinoid receptors in the brain is to facilitate depolarization-induced suppression of inhibition. Also known as agonist-induced disinhibition, this phenomenon occurs when a presynaptic action potentially causes the retrograde release of endocannabinoids from the postsynaptic dendrite which activate inhibitory CB1 receptors found on the inhibitory basket cells serving to tonically inhibit the activity of neuron A.
In other words, when neuron A signals Glutamate to neuron B, neuron B releases endocannabinoids which inhibit the basket cells serving to inhibit neuron A, with the ultimate effect of increasing the likelihood that neuron A will generate another action potential.
Because the endocannabinoid system (ECS) regulates the activity of several other neurotransmitter systems, ECS dysregulation can have far-reaching implications that are equally difficult to elucidate. On the other hand, many common conditions from Acne to Alzheimer’s disease have unknown pathogenesis but affect areas of the body known to express cannabinoid receptors. Taken together, these facts suggest that the endocannabinoid system could be a novel and highly-effective target in the treatment of diverse disorders of the central and peripheral nervous systems.
CBD demonstrates dose-dependent in vivo inhibition of key pro-inflammatory factors including iNOS and IL-1β.
The anti-inflammatory properties of CBD are different from NSAIDs or steroids in that CBD chemically alters the proinflammatory process, as opposed to blocking a single step in the inflammatory pathway.
Moreover, CBD also reduces inflammatory responses through direct involvement with PPARγ nuclear receptors . Certain tonic cellular processes produce highly reactive oxygen species which, over time, alter the inflammatory response to become pathologically sensitive to ROS stimuli. CBD reduces this sensitivity without eradicating the immune response to protect against ROS damage.
In addition, CBD potently reduces sebocyte activity and inflammation, which are key processes in the pathogenesis of acne   .
CBD is an inhibitor of tryptophan degradation, which leads to increased levels of brain serotonin.
Serotonin is one of the most ubiquitous signaling molecules in mammals. It is intricately involved in both mood and cognition, and immune system signaling.
- The limiting factor in serotonin (5-hydroxytryptamine) synthesis in humans is the synthesis of serotonin’s immediate precursor, 5-hydroxytryptophan (5-HTP), from the amino acid tryptophan. When this process is limited, or tryptophan follows a metabolic pathway other than [tryptophan → 5-HTP → serotonin], serotonin levels will fall, causing mood to become dysregulated and inflammation to become disinhibited.
- Regulation of the serotonin system is one of the primary roles of the endocannabinoid system (ECS), and when the ECS fails to maintain serotonin homeostasis, CBD can help to reinstate balance within the ECS, which indirectly improves the condition of the serotonin system.
Furthermore, CBD acts as a partial agonist of serotonin 5-HT1a receptors  .
CBD also acts as an antioxidant with similar efficacy to α-tocopherol, preventing glutamate-induced neurotoxicity and ROS-induced cell death in vivo.
Thanks to the presence of two phenolic hydroxyl groups, CBD is a potent antioxidant comparable to Vitamins C and E in terms of reduction of oxidative free radicals in vivo and in vitro. This contributes to anti-inflammatory and neuroprotective properties of CBD as well as to its antifungal and antibacterial effects.
The property of CBD which has garnered the greatest degree of publicity has been its ineffable anti-seizure activity.
Through several different mechanisms, CBD is able to relieve intractable seizures when more than 6 traditional AEDs have been ineffective (Δ seizure frequency ≤ 5%).
CBD is biphasic and has multiple biological targets as well as several interactive endogenous compounds that contribute to a unique spectrum of activity in the pathological human system. The class of disorders for which CBD is most effective appears to be epileptic and non-epileptic seizure disorders. Through agonism of 5-HT1a, as well as negative modulation of “disinhibitory” cannabinoid receptors, CBD is able to reduce the frequency and severity of many types of seizure, because it stabilizes neuronal excitability as well as reducing excitatory transmission.