Endogenous Cannabinoid Signaling

Various drugs of abuse have effects on our brains because they resemble the neurotransmitters that our brains produce. For example Endorphines and Enkephalins resemble exogenous morphine or heroin, Endogenous Anandamide resembles marijuana, acethylcholine resembles nicotine and cocaine/amphetamines resemble dopamine, etc.

The endogenous cannabinoid signaling (ECS) is a complex endogenous signaling system comprised of Cannabinoid receptors (CB1 and CB2), Endocannabinoid ligands, and proteins that are involved with endocannabinoid synthesis.

To learn more:

http://www.rtbot.net/play.php?id=B6QWT-WP09o

At present, there are two known types of cannabinoid receptors, termed CB1 and CB2, with mounting evidence of more.

CB1 receptors are found primarily in the brain, to be specific in the basal ganglia and in the limbic system, including the hippocampus. They are also found in the cerebellum and in both male and female reproductive systems. CB1 receptors are absent in the medulla oblongata, the part of the brain stem responsible for respiratory and cardiovascular functions. Thus, there is not a risk of respiratory or cardiovascular failure as there is with many other drugs. CB1 receptors appear to be responsible for the euphoric and anticonvulsive effects of cannabis.

CB2 receptors are almost exclusively found in the immune system, with the greatest density in the spleen. While found only in the peripheral nervous system, a report does indicate that CB2 is expressed by a subpopulation of microglia in the human cerebellum.

CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis

Anandamide was discovered in 1992 and is our endogenous cannabinoid. It is synthesized in the body from N-arachidonoyl phosphatidylethanolamine by multiple pathways.

Endogenous anandamide is present at very low levels and has a very short half-life due to the action of the enzyme fatty acid amide hydrolase (FAAH) which converts anandamide into ethanolamine and arachidonic acid.

Inhibitors of FAAH lead to elevated anandamide levels and are being pursued for therapeutic use. Fatty-acid amide hydrolase (FAAH) activity has been linked with arousability and aversive-memories extinction.

Paradoxically, Anandamide may help memory by helping us forget. The brain's ability to weaken unimportant memories and experiences enables it to function more efficiently. Just as long term potentiation (LTP) is important for remembering, long term depression (LTD) is important for forgetting. For this reason FAAH inhibitors are looked at in PTSD.

Learn more:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309545/

Cannabidiol

Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but inhibits the degradation of the endo cannabinoid anandamide by inhibiting FAAH. A study published May 20th, 2012 in Translational Psychiatry demonstrates that Canabidiol alleviates psychotic symptoms in schizophrenia just like the antipsychotic medication, without causing adverse effects:

http://www.nature.com/tp/journal/v2/n3/full/tp201215a.html

This is but one of the potential applications of Cannabidiol, but there are many more:

In neurodegenerative disorders

Cannabidiol acts as an anti inflammatory, anticonvulsant, antioxidant, antiemetic, anxiolytic and ‐antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti inflammatory and antioxidant ‐properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders.

http://onlinelibrary.wiley.com/doi/10.1002/wmts.64/full

ADONIS SFERA, MD