How Cannabis Works Pt.3 Cannabinoid Receptors CB1 CB2

CB1

The CB1 receptor was discovered in 1988 by, Allyn C. Howlett & her colleagues at St. Louis University. A short time & a lot of work later, studies conducted by Tamas F. Freund of the Institute of Experimental Medicine at the Hungarian Academy of Sciences in Budapest & Kenneth P. Mackie of the University of Washington would pinpoint the CB1 receptors neuronal location. Both studies would reveal that the CB1 receptor occurred only on certain neurons & in very specific positions on those neurons. The CB1 receptors are densely packed on neurons that release GABA (gamma-aminobutyric acid), which is the brain's inhibitory neurotransmitter (it tells recipient neurons to stop firing). The CB1 receptor also sits near the synapse, the contact point between two neurons.

“Conventional” neurotransmitters are water-soluble & are stored in high concentrations in little packets, or vesicles, as they wait to be released by a neuron. In contrast, endocannabinoids are fats & are not stored but rather are rapidly synthesized from components of the cell membrane. They are then released from places all over the cells when levels of calcium rise inside the neuron, or when certain G-protein-coupled receptors (CB1) are activated. This activity is what's known as a 'retorgrade' or backward signaling that before the early 1990s was known to occur only during the development of the nervous system. Endocannabinoids are the only neurotransmitters that engage in retrograde signaling, a form of intracellular (within the cell) communication that inhibits immune response, reduces inflammation, relaxes musculature, lowers blood pressure, dilates bronchial passages, & normalizes over stimulated nerves.

Before the early 1990s, science told us that signals in mature brains flowed across synapses in a one way only manner; from the presynaptic cell to the postsynaptic cell. Multiple studies conducted by various scientist in the early 1990s revealed the “new” kind of neuronal communication & dubbed the retrograding activity “depolarization-induced suppression of inhibition” or DSI. When DSI occurs endocanabinoid 2-AG travels from the postsynaptic cell to the presynaptic GABA-releasing cell, shutting off the neurotransmitter's release.

DSI is proven to be an important aspect of brain activity. Temporarily dampening inhibition enhances a form of learning called long-term potentiation, the process by which information is stored through the strengthening of synapses. DSI which is a short-lived local effect enables individual neurons to disconnect briefly from their neighbors & encode information.

 

CB2

Where the CB1 Receptor mediates psychoactive responses, the CB2 Receptor (discovered in 1993 by S. Munro) regulates immune responses. The CB2 Receptor is prevalent throughout the immune system the peripheral nervous system, in the stomach, spleen, liver, heart, kidneys, bones, blood vessels, lymph cells, endocrine glands & reproductive organs. Talk about a natural high...