CBD & pathways
The endocannabinoid system: anandamide, 2-AG and the signalling map
A biochemical introduction to CB1, CB2, anandamide, 2-AG, FAAH and MAGL—and what an endocannabinoid pathway can and cannot tell us about hemp products.
Cell and animal experiments explain receptor biology. They do not by themselves show that a retail oil treats pain, sleep problems or a neurological disease.
Compounds & molecular formulae
Anandamide (AEA)
C₂₂H₃₇NO₂
An endogenous fatty-acid amide first isolated as a cannabinoid-receptor ligand.
PubChem compound record ↗2-arachidonoylglycerol (2-AG)
C₂₃H₃₈O₄
A second major endocannabinoid that can activate CB1 and CB2 in context.
PubChem compound record ↗Cannabidiol (CBD)
C₂₁H₃₀O₂
A plant cannabinoid with several non-identical molecular targets; it is not a direct CB1 intoxicating agonist like THC.
PubChem compound record ↗A synapse in four signals
- Postsynaptic activity raises Ca²⁺
- AEA or 2-AG is made on demand
- Endocannabinoid diffuses backward
- Presynaptic CB1 changes transmitter release
This retrograde model comes from hippocampal preparations. It describes a signalling event, not a promised outcome from a bottle [1][2].
CB1/CB2 → Gᵢ/ₒ → ↓adenylyl cyclase → ↓cAMP
Many cannabinoid-receptor experiments observe reduced cAMP after Gᵢ/ₒ coupling. The downstream result depends on cell type, receptor density and ligand concentration.
FAAH: AEA → arachidonic acid + ethanolamine
FAAH is one important route for terminating anandamide signalling. MAGL is a major route for 2-AG hydrolysis; neither equation means that CBD simply “replaces” an endocannabinoid.
What scientists mean by “endocannabinoid system”
The ECS is a distributed signalling system made from receptors, endogenous ligands, metabolic enzymes and transport or uptake processes. CB1 is abundant in the nervous system; CB2 is prominent in immune tissues but is also found in other cells. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are made on demand from membrane lipids rather than stored in synaptic vesicles. Early work identified anandamide as a brain constituent that binds cannabinoid receptors [1]. Electrophysiology then showed that depolarised hippocampal neurons can release endocannabinoids retrogradely to reduce presynaptic GABA release [2].
The receptor-to-pathway chain
CB1 and CB2 are G-protein-coupled receptors. In many experimental systems their Gᵢ/ₒ coupling reduces adenylyl cyclase activity and cAMP, modulates voltage-gated calcium channels, opens G-protein-regulated inwardly rectifying potassium channels and changes MAPK/ERK signalling. These are conditional pathways, not a single linear response: a receptor can recruit β-arrestins, internalise, or signal differently in another cell. A change in cAMP in a cultured cell is therefore mechanistic evidence, not evidence that a person will feel a particular symptom change.
FAAH, MAGL and the limits of a slogan
FAAH hydrolyses AEA, while MAGL is a major enzyme that hydrolyses 2-AG. Inhibiting these enzymes can raise endocannabinoid concentrations in preclinical models, but CBD is not equivalent to a selective FAAH or MAGL inhibitor. Product claims such as “supports ECS balance” should be read as a broad educational phrase unless a finished product has a measured composition and a clinical study. Enki’s oil is a commercial blend; this article does not measure its CBD concentration, THC level or enzyme activity.
What this means for a Kenyan buyer
Look for a current ingredient list, total CBD in milligrams, batch testing and intended route of use. A 50 ml bottle tells you volume, not dose. Ask the Enki team for product-specific information and speak with a clinician about medicines or a persistent symptom. Mechanistic diagrams can make biology clearer, but they should not be used to promise that an individual’s nerve problem, arthritis or sleep issue will disappear.
Sources & credits
- Devane et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor (Science, 1992) — Primary discovery study
- Wilson & Nicoll. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses (Nature, 2001) — Primary neuroscience study
- Cravatt et al. Molecular characterization of FAAH (Nature, 1996) — Primary enzyme study