Does anyone know if palmitoylethanolamide (PEA) interacts with antidepressants and / or benzos?

[[he...]]

 

Hi everyone

I am interested in this supplement for dealing with CFS symptoms, to have an alternative for anti-inflammatories that is more stomach friendly, and, hopefully, that doesn't cause or worsen tinnitus.

I am currently on Luvox, Valium and pregabalin and I wasn't able to find if palmitoylethanolamide interacts with any of those. As this is a niched supplement where I live, most doctors aren’t familiar with it and most surely would not know and maybe even say it's okay to take.

Trying to do some research on Google I just found out that it interacts with some enzymes of the P450 cytochrome but it’s vague and didn’t specify which.

Luvox inhibits the following enzymes:

• CYP1A2 (strongly)
• CYP3A4 (moderately)
• CYP2D6 (weakly)
• CYP2C9 (moderately)
• CYP2C19 (strongly)
• CYP2B6 (weakly)

As for Valium, it inhibits CYP3A4 and CYP2C19.

Maybe I missed something in my research regarding if PEA could inhibit any of these. Does anyone know anything about this or have a lead?

Your views and experiences are welcomed.

 

[[Ar...]]

I don't know the answer to your question but you seem to be thinking along similar lines to myself recently. PEA doesn't likely inhibit CYP enzymes but the body does use them for breaking it down so it would reduce their levels. I am currently trying to raise my microbiome production of endocannabinoids like anandamide and 2-arachidonoylglycerol in order to try to improve my own withdrawal symptoms so have been working at trying to raise my microbiomes production of PEA in order to achieve this.

I am currently trying to work out which enzymes various benzodiazepines may inhibit in causing our symptoms. An example of this is how some benzodiazepines inhibit F1F0 ATP hydrolase. https://www.sciencedirect.com/science/article/abs/pii/S0960894X03012447   Presuming that the wrong enzymes were inhibited by whichever benzodiazepine we were given then this might well lead to the mitochondrial dysfunctions experienced by many of us in withdrawal.

[[Ar...]]

Further to last I found this article, detailing how diazepam is similar to newer benzodiazepines in inhibiting both acetylcholinesterase and ATPD'ase. https://link.springer.com/article/10.1023/A:1007500424392    As acetylcholinesterase breaks down acetylcholine it leads to excessive levels. Too much acetylcholine causes muscle cramps, depression, jitters, restlessness, damage to the immune system, increased stress and anxiety, disruption of the circadian rhythm and sleep patterns, confusion, and respiratory depression. In severe cases it can cause convulsions, depression of respiratory activity, improper processing of information on every level of the body and brain, and decreased behavioural inhibition. Nicotinic/acetylcholine receptors, which are the target of benzodiazepines, regulate aggressive behaviour so dysregulation can lead to increased aggression.

ATPD'ase reduces ATP to ADP, releasing a molecule of phosphate for cellular production of energy in aerobic respiration. So inhibition of this process switches cells around the body over to using anaerobic respiration to produce energy; a far less efficient process leaving some of us fatigued during effort.

So if anyone wants to understand why they're experiencing so many symptoms in withdrawal you now have some answers.

[[Ar...]]

ATP hydrolysis alleviates tinnitus so benzodiazepine inhibition of ATPD'ase will be the most likely cause of the exacerbation of tinnitus which occurs in withdrawal (section 2.12.1). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235102/ Argument still exists over how acetylcholine influences this yet also seems to have some kind of involvement.