If anyone is considering taking caryophyllene, caryophyllene oxide and Humulene containing substances please check medications- CYP3A

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The b-caryophyllene being discussed interfere with CYP3A....
I'm not sure if the caryophylline inhibits the CYP3A4 pathway ..... I used up all my remaining 2 brain cells tring to break it down into English for you, so will need some time to recharge so I can re-read all the posts related to this.

Or not.
 

CSMLSM

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I'm going to take a stab at translating this into English, or something approximate ....


The short explanation is that naltrexone hydrocloride will inhibit the metabolic action of 3 liver enzymes that metabolize various drugs and substances, and help move them out of your system.

This means that anything else you take, which would include quite a few herbs, that clears thru those 3 pathways will be held in your system far longer than it should be, which could lead to unintentional cross-potentiations and also potential overdoses, with doses piling up on still unmetabolized doses. I'm assumig that your prscribing Dr too naltrexone's inhibition of 3 main liver pathways into account when he/she decided on your dosage, since it would also inhibit its own metabolosis ....

I hvae no idea what the half-life for naltrexone is, but a safe guess would be about 5 to 8 hours, which would be longer given its inhibition of the clearing pathways.

There. Clear as mud .... but the best I can do with something so opaque ....
Thank you very much. I assume we should take a closer look at RM`s herbal meds alongside the LDN and Metroprol to make sure we are not taxing the enzymes involved beyond what is safe.
When you refer to CYP3A, I'm assuming you mean CYP3A4 ... yes? No?
This below I copied and pasted and I am very new to liver enzymes, yes I mean CYP3A4.
What drugs are metabolized by CYP3A?
Up to 60% of the liver's total cytochrome P-450 is CYP3A, and nearly 50% of all clinically relevant medications are metabolized by CYP3A. The presence of CYP3A in the small intestine results in decreased bioavailability of many ingested drugs. CYP3A inducers include the glucocorticoids, rifampin, carbamazepine, phenobarbital, and phenytoin.
There are about 56 or 57 P450 genes in total, and yes, the most traveled pathway for a staggering number of drugs, herbs, and even vitamins is thru the CYP3A4 ...
Thats what I understood from what I read and thought it meant the lower dose of Metroprol and low dose naltrexone would mean a low amount of this CYP3A4 abundant enzyme being used. I also thought as long as we monitor the blood pressure throughout we could see if the enzyme was being taxed if the blood pressure fell from where it was at before taking caryophyllene. I also realise CBD uses this enzyme also and found this on that-
Is CBD Safe for You and Your Liver? I LiverSupport.com

Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes - PubMed (nih.gov)

I have been consuming alot of cannabis over decades with the view I was so sick if this works then I do not care about the liver but now I am well and have to think of others I need to know this.

I feel that due to the blood pressure meds being taken, if we monitor it and it changes noticeably we know the enzyme is being taxed, that or the new meds help and confuse the issue. My point is if the blood pressure does change that is a warning sign we can look out for. This is not ideal and what we need is an actual knowledgeable person on this.

Do you know anyone we could ask, I do not unfortunately.

We have the fact it is the most abundant enzyme but thats not really good enough, we need to be safe here. I can take all the gambles I want but others its not good.

Thanks for your input and help :)
 
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We have the fact it is the most abundant enzyme but thats not really good enough, we need to be safe here. I can take all the gambles I want but others its not good.
thanks for this, I really appreciate the help.

Years ago, it was obvsiou THC lowers my BP, so that could raise issues with POTS and etc. I thought I was an atypical case.

So why did my tachycardia and POTs symptoms improve half an hour after some THC? If lowering my BP is bad for blood reaching brain?
 

CSMLSM

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my blood pressure can drop pretty low late in the day due to all this stuff
Is this when you consume the THC ect could be either liver enzyme being taxed or affects of the variety of compounds in the inhaled substance.

We need to be careful here, we do not want to make you sick from this.

We need a pharmacologist I think. THC is less inhibitory based on this (only has abstract),
Cannabinoids and Cytochrome P450 Interactions - PubMed (nih.gov)
The enzymes CYP2C9, CYP2C19, and CYP3A4 catalyze most of their hydroxylations. Similarly, CYP represents a major metabolic pathway for both synthetic cannabinoids used therapeutically and drugs that are abused. In vitro experiments document the mostly CYP inhibitory activity of the major phytocannabinoids, with cannabidiol as the most potent inhibitor of many CYPs.

CBD seems the most potent inhibitor of the enzymes involved so if we can figure that out we should have an idea hopefully.

We need someone in the know!

I am still alive thankfully :)
 
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Thats what I understood from what I read and thought it meant the lower dose of Metroprol and low dose naltrexone would mean a low amount of this CYP3A4 abundant enzyme being used.
That's not really how it works, it's more complex, but yes, the higher the dose, the LONGER and more pronounced the inhibition is. Once a drug/herb/supp inhibits an isoenzyme pathway, anything that uses that pathway will metabolize slowly ....
I feel that due to the blood pressure meds being taken, if we monitor it and it changes noticeably we know the enzyme is being taxed, that or the new meds help and confuse the issue.
I think that you may be playing with fire here.


If you let air out of a tire, it's going to 'inhibited'. If you inhibit the CYP3A4, it's not being taxed, it's functioning in response to stimuli. Changing its direction is a little like turning a ship. It's gonna do what it's doing until the effect that's causing that reaction moves on. Which will be slowly

Some people use that CYP3A4 reaction to take a lower does of a med, and keep it working in their system longer.

To confuse the issue further, along with inhibitors, there are inducers, which do the exact opposite, and can also be dangerous. It's why grapefruit, either whole or in juice form, is a bad idea with certain meds.
We have the fact it is the most abundant enzyme
It's the most frequently utilized enzyme pathway, not sure if it's the most abundant. I think it shares that honor with one or two others.
 

CSMLSM

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So why did my tachycardia and POTs symptoms improve half an hour after some THC? If lowering my BP is bad for blood reaching brain?
This is not straight forward.
Effects of Marijuana on Blood Pressure. Does weed lower or increase Hypertension? (leaf.expert)
1660603284316.png


Maybe you would benefit from a trial of CBD sublingually in place of the THC, at lower dose through the day and see how it affects your blood pressure. As it raises endogenous cannabinoids it may improve things in a more natural way and be better without intoxication. Maybe a starting point to assess how you can move forward with this. Instead of taking it with caryophyllene.
Or take caryophyllene without THC or CBD as there appears to be no mention of it affecting blood pressure from a quick look online and trial that.

At the end of the day it is your body and your life, the decision is yours. Hopefully we can find a pharmacologist to help us on this.
 
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thanks for this, I really appreciate the help.
Lemme see if I understand this. I spend 45 minutes trying to simplify a fairly complex reaction that you said you didnt understand, and you thank the guy who posted the stuff you didnt undertstand (no offense @CSMLSM .... I'm fatigued and cranky)?

I cant quite put my finger on it, but I think that's making me peevish.
 

CSMLSM

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That's not really how it works, it's more complex, but yes, the higher the dose, the LONGER and more pronounced the inhibition is. Once a drug/herb/supp inhibits an isoenzyme pathway, anything that uses that pathway will metabolize slowly ....

I think that you may be playing with fire here.

If you let air out of a tire, it's going to 'inhibited'. If you inhibit the CYP3A4, it's not being taxed, it's functioning in response to stimuli. Changing its direction is a little like turning a ship. It's gonna do what it's doing until the effect that's causing that reaction moves on. Which will be slowly

Some people use that CYP3A4 reaction to take a lower does of a med, and keep it working in their system longer.

To confuse the issue further, along with inhibitors, there are inducers, which do the exact opposite, and can also be dangerous. It's why grapefruit, either whole or in juice form, is a bad idea with certain meds.

It's the most frequently utilized enzyme pathway, not sure if it's the most abundant. I think it shares that honor with one or two others.
Thanks for this, do you know anyone we can ask with qualifications. I am a complete novice in liver affects from drugs as I only had one option, find what works and focus on that. I suppose looking into liver enzymes in my mind was pointless if I was going to kill myself if I did not get better.

This I really need help on.
 

CSMLSM

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Lemme see if I understand this. I spend 45 minutes trying to simplify a fairly complex reaction that you said you didnt understand, and you thank the guy who posted the stuff you didnt undertstand (no offense @CSMLSM .... I'm fatigued and cranky)?

I cant quite put my finger on it, but I think that's making me peevish.
I think RM meant the protocol from someone else I took alook at. I am super tired myself I need to sleep.

Goodnight :)
 
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I think I may have been intending to thank you. Maybe I even thought I did, or already did. My life is imperfectly executed.

However, I'm moving across several paragraphs of information,p going back and forth between pages and posts..trying to make some sense and Im a sick person.

I am not able to keep track of the level of details the rest of you are.

I appreciate the help, it make more sense now.
 
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Maybe you would benefit from a trial of CBD sublingually in place of the THC, at lower dose through the day and see how it affects your blood pressure. As it raises endogenous cannabinoids it may improve things in a more natural way and be better without intoxication. Maybe a starting point to assess how you can move forward with this. Instead of taking it with caryophyllene.
Or take caryophyllene without THC or CBD as there appears to be no mention of it affecting blood pressure from a quick look online and trial that.
good advice....will experiment with that.
 
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I don't wish to crash anybody else into a ditch!
I was already in it. I made a quick assessment of how much deeper it could get, decided to take the leap.


Like you, I like to reach out and share shite that I worked hard to learn with others who seem interested or in need of that particular information.

But every now and then, I do need a little pat on the head and a Kitty Treat ...
1660610321059.png


EDIT ... for touching graphic ....
 
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Maybe you would benefit from a trial of CBD sublingually in place of the THC, at lower dose through the day and see how it affects your blood pressure.
Tiny Experiment # 1: I took one CBD capsule 15 mgs 2 hours after breakfast (which was lunch)

Before BP:

124/87...HR 80

About twenty minutes later:

115/80...HR 65

( I take my one Metropol around midnite, so its likely worn off by noon)

(my eyes are really hurting, which is both normal but also I am uptight..I am supposed to go run an errand and I do not want to.)
 

CSMLSM

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About twenty minutes later:
This is maybe too soon for it to take affect by swallowing.

Interesting fact the placebo effect is mediated by the cannabinoid system. It is likely you spike your own Anadamide with the placebo effect, this is encouraging because you must at least believe it will work.

Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors - PubMed (nih.gov)
Abstract
Placebo analgesia is mediated by both opioid and nonopioid mechanisms, but so far nothing is known about the nonopioid component. Here we show that the specific CB1 cannabinoid receptor antagonist 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (rimonabant or SR141716) blocks nonopioid placebo analgesic responses but has no effect on opioid placebo responses. These findings suggest that the endocannabinoid system has a pivotal role in placebo analgesia in some circumstances when the opioid system is not involved.
This also indicates that when you take CBD at the right dose it will raise anadamide again and lowering your blood pressure again.
I am uptight..I am supposed to go run an errand and I do not want to.)
This will have opposed the placebo affect likely why you see the change after the hour.
an hour later, it was back up to the prior BP numbers......

(need multi day data)
Fascinating!