What is Oleamide?
Oleamide is a derivative of Oleic Acid (major omega-9 fatty acid form Olive Oil) with a nitrogen group, and appears to be naturally associated with sleep; injections induce sleep and activate the same receptors as Marijuana.
Sources
Oleamide (cis-9,10-octadecenoamide) is a molecule produce endogenously from Oleic Acid (the omega-9 fatty acid known to be associated mostly with Olive oil) and first isolated in human serum in 1989. Oleamide appears to accumulate in the brain and cerebrospinal fluid (CSF) during sleep deprivation, with the extension of sleep deprivation 6 hours beyond normal sleep time causing a 4-6 fold increase in Oleamide content of CSF, and is likely to be relevant to all species investigated as Oleamide is common across species.
Oleamide is a naturally occurring metabolite of Oleic acid which appears to be involved as a neuropeptide related to sleep. It may also be found in a traditional chinese medicine involved in sedation Oleamide tends to refer to cis-oleamide and the trans-isomer appears to be unable to mediate numerous biological effects on gap junctions, serotonin receptors (5-HT2A and 5-HT2C), and GABAA receptors. There is limited efficacy on the 5-HT1A receptor, with about half the efficacy as the cis isomer and injections of the trans isomer appear to be around half as effective as the cis isomer.
Biosynthesis
Oleamide has been noted to be synthesized in brain slices incubated with both oleic acid and ammonia which is mediated by enzymes as boiling the brain slices (denaturing enzymes) abolished the synthesis.
Oleamide can be degraded into Oleic acid via the membrane enzyme Fatty acid amide hydrolase (FAAH), the same enzyme that metabolites anandamide (arachidonoyl ethanolamide) and bioactives in marijuana. Interestingly, inhibiting this enzyme has been noted to inhibit synthesis of oleamide (mouse N18TG2 cells) although the exact biosynthesis route is note yet determined. What appears to be known is that oleic acid is converted into Oleoyl-CoA and then N-Oleoylglycine where oxidative cleavage of N-Oleoylglycine by the enzyme peptidylglycine α−amidating monooxygenase (PAM) creates oleamide. It should be noted that the intermediate N-Oleoylglycine appears to be biologically active as well.
Oleamide appears to be synthesized in the human body (due to circulating levels detected) from oleic acid and ammonia. Although the biosynthetic enzymes are not fully characterized yet, oleamide is degraded by the FAAH enzyme due to being a fatty acid amide
