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Oleamide cannabinoid receptor CB1 agonist downregulation effects?

oleamide cb1 agonist downregulation effects nrem sleep

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#1 CarlSagan

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Posted 28 July 2021 - 06:12 PM


I'm interested in Oleamide for its effects on increasing NREM sleep. derived from oleic acid (olive oil) and is found naturally in the body. interestingly Oleamide increases naturally in our bodies multiple times over when we are sleep deprived

 
But as cis-oleamide agonizes CB1 (maybe CB2 too) people taking it would get their receptors downregulated over time right, if standard doses do this? https://www.ncbi.nlm...les/PMC1574194/
 
so would frequent use of Oleamide bring similar side effects that some get from frequently smoking weed? (anxiety, irritability, insomnia, memory impairment). what doses are likely to have this agonizing effect on CB1?
 
 
it also works on GABA A probably the beta subunits https://journals.lww...subunit.56.aspx
 
Deletion of the GABAA receptor β3 subunit eliminates the hypnotic actions of oleamide in mice -
 
increases GABA signalling at GABA A, its effects are at different subunits than benzos but enhances signalling. 30mg/kg twice daily in rats for 10 days with an abrupt stop did not show withdrawals though its a short study. https://examine.com/...ments/oleamide/
 
"There is currently no evidence to suggest that oleamide has addictive potential, but due to one of its mechanisms of actions (enhancing GABAA signalling) it is still theoretically possible for oleamide to be somewhat addictive like a weak benzodiazepine. "
 
"May not have significant interactions with GABA or Benzodiazepine receptors directly, but may potentiate signalling of the receptors via other agents. Oleamide is likely a GABA synergist"
 
"Oleamide does not significantly affect ligand binding to the GABAA receptors, nor is GABA uptake into synaptosomes affected "
 
^ So I guess there's nothing to worry about on the GABA side, if it doesn't significantly increase GABA binding / uptake? just potentiates receptor signalling whatever that means.
 
Anything to be concerned about with the CB receptors though?
 
 
anxiolytic effect in mice at 10mg or 20mg  / kg  https://pubmed.ncbi....avior in mice.   
^ 50 - 100 mg human if oral
 
 


#2 CarlSagan

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Posted 29 July 2021 - 08:59 AM

https://www.research...ctivity_in_Rats

https://www.scripps....Huitron2001.pdf

 

^ significantly increased NREM slow wave 2 & significantly lowered REM

https://www.nature.c...les/1395784.pdf

 

table 1 - significantly increased slow wave sleep & lowered REM



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Also tagged with one or more of these keywords: oleamide, cb1, agonist, downregulation, effects, nrem, sleep

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