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

[CSMLSM]

The inhibitory effects of β-caryophyllene, β-caryophyllene oxide and α-humulene on the activities of the main drug-metabolizing enzymes in rat and human liver in vitro - PubMed (nih.gov)
Abstract
Sesquiterpenes, the main components of plant essential oils, are often taken in the form of folk medicines and dietary supplements. Several sesquiterpenes possess interesting biological activities but they could interact with concurrently administered drugs via inhibition of drug-metabolizing enzymes. Therefore, the present study was designed to test the potential inhibitory effect of tree structurally relative sesquiterpenes β-caryophyllene (CAR), β-caryophyllene oxide (CAO) and α-humulene (HUM) on the activities of the main drug-metabolizing enzymes. For this purpose, rat and human hepatic subcellular fractions were incubated with CAR, CAO or HUM together with specific substrates for oxidation, reduction and conjugation enzymes and their coenzymes. HPLC, spectrophotometric and spectrofluorimetric analyses of product formations were used. All tested sesquiterpenes significantly inhibited cytochromes P4503A (CYP3A) activities in rats as well as in human hepatic microsomes, with CAO being the strongest inhibitor. A non-competitive type of inhibition was found. On the other hand, none of the tested sesquiterpenes significantly affected the activities of carbonyl-reducing enzymes (CBR1, AKRs, NQO1) or conjugation enzymes (UGTs, GSTs, SULTs, COMT). As CYP3A enzymes metabolize many drugs, their inhibition by CAO, CAR and HUM might affect the pharmacokinetics of concurrently administered drugs. Similar results obtained in rat and human hepatic microsomes indicate that rats could be used for further testing of possible drug-sesquiterpenes interactions in vivo.

 

[Rufous McKinney]

might affect the pharmacokinetics of concurrently administered drugs

fascinating...

so translated?

did it refer to any particular types of Pharma drugs?

and I wonder if this CYP3A effect has some benefits....as opposed to be a negative its part of how they might be helpful?

sounds very complex chemistry. Let me know if you figure more.

(I only take two Pharma pills now)

 

[CSMLSM]

fascinating...

so translated?

did it refer to any particular types of Pharma drugs?

and I wonder if this CYP3A effect has some benefits....as opposed to be a negative its part of how they might be helpful?

sounds very complex chemistry. Let me know if you figure more.

(I only take two Pharma pills now)

The enzyme CYP3A is one of the P4503A enzymes that metabolise the majority of drugs.

This means that if you take things metabolised by this enzyme such as the blood pressure medication Nifedipine it may cause leves of it to be above what is expected, essentially like you are taking a higher dose.

Sorry I did not want to simplyfy and patronise anyone. I thought you were a biology teacher or something anyway?

 

[Rufous McKinney]

such as the blood pressure medication Nifedipine it may cause leves of it to be above what is expected, essentially like you are taking a higher dose.

sorry I can't read very much material due to this crap.

So it might affect my one BP pill...

patronise anyone. I thought you were a biology teacher or something anyway?

The enzyme CYP3A is one of the P4503A enzymes that metabolise the majority of drugs.

This means that if you take things metabolised by this enzyme such as the blood pressure medication Nifedipine it may cause leves of it to be above what is expected, essentially like you are taking a higher dose.

Sorry I did not want to simplyfy and patronise anyone. I thought you were a biology teacher or something anyway?

I worked as a scientist. And now I"m too sick to do science. I can't seem to get past abstracts. Into the paper.

and those paragraphs. I just can't make it through them.

 

[CSMLSM]

sorry I can't read very much material due to this crap.

So it might affect my one BP pill...





I worked as a scientist. And now I"m too sick to do science. I can't seem to get past abstracts. Into the paper.

and those paragraphs. I just can't make it through them.

If you tell me the medication I will look for you if you like, ramapril is fine I know from today.

I was the same unless I smoked cannabis and now after the recent 2year recovery (6months copaiba, rest CBD) I can do way way more. I am stubborn also, I do not give up easilly. I used to read and reread the same sentence even over and over until I could remember or get what I was reading and would repeat things over and over to hold the info. I was about 30 at the time riding the amazing recovery from major B12 deficiency basically having dementia, nervous system damage and feeling loss. I was determined to survive and repair all the damage I had. It has not been easy at all.

 

[Rufous McKinney]

I was determined to survive and repair all the damage I had. It has not been easy at all.

not easy at all, and you are to be commended. Whatever happened, you've improved remarkably and so you will continue to do what works for you.

May it continue to improve.

I take one 50 mg Metroprol

Doctor wanted me taking more..I resisted.

Oh I also take 3.5 LDN...but thats it.

(my brain is odd in my opinion, because I still have an odd and very good recall for things yet will entirely forget I watched that movie, until I get a reminder trigger. Oh yes I saw that whole movie).

So yesterday I was lecturing on CPY3A

Brain decided to remember that. Doesn't know what it is yet.

so if I watch a film during the daytime, chances are I'll get really exhausted part way through and maybe even start crashing.

On CBD and related products, in the evening I can watch the whole movie and I am not affected.

 

[Treeman]

now just take it pure as I do not mind the taste, 1 maybe 2 drops.

How long was it before you noticed any improvements?

 

[CSMLSM]

How long was it before you noticed any improvements?

Based loosely on 20 years worth of experience of recoveries of some degree.

At first some benefits that are mild but positive. Things like bowels improve, focus, memory, pain. Do not expect a miracle straight away. The dysfunction needs to be stopped and then the mess left over needs to clear before we can really get going.

In 2-6 weeks you should see bigger changes like way more energy(hold back when this happens or you could mess up), but also see some of that functional immune activation like the spots and bowel disturbances. As you will be starting from a first time try I would expect 4-6 weeks possibly but may be that you are at a severity level that means you get major changes after 2 weeks. It has to do with cytokines reducing and microbiome stuff rebalancing as your bodies ability to keep things in homeostasis improves. This is my belief.

 

[CSMLSM]

How long was it before you noticed any improvements?

Also now at present I first notice my lower legs start to feel fatigued/ache if I need to take more copaiba/caryophyllene as I am on my feet quite a bit at the moment and obviously they are doing most of the work holding me upright and moving around.

I have been very naughty drinking bitter (low alcohol) and yesterday had a vindaloo from pataks. It did set the nerves in my stomach off and into my spine from there. However it was gone in an hour or two. It is probably nerve damage/demyelination from my severe B12 deficiency. But the caryophyllene is helping with that also I believe.
β-Caryophyllene causes remyelination and modifies cytokines expression in C57BL/6 mice with experimental autoimmune encephalomyelitis (japsonline.com)
Abstract
The aim of this study is to evaluate the effect of β-Caryophyllene (BCP) on the production of IL-17, transcription factors (T-bet and GATA-3), and remyellination in C57BL/6 mice induced for experimental autoimmune encephalomyelitis (EAE), the model for studying pathogenesis and new therapies for multiple sclerosis. EAE was induced in three groups of C57BL/6, with administration of BCP in two groups (25 and 50 mg/kg/day) by gavage, after the 10th day of induction. At 9 days of treatment, mice were euthanized and CNS was removed for the analysis. The profiles of IL-17, T-bet, GATA-3, and the possible remyelination properties were investigated in the central nervous system (CNS) by immunohistochemistry and Weigert–Pal–Russel’s method, respectively. BCP group (50 mg/kg/day) showed a reduction of IL-17 in brain, cerebellum, and medulla (p < 0.05) and a decrease of T-bet (p < 0.05) in medulla and cerebellum, while GATA-3 was increased (p < 0.05) in cerebellum. In both BCP-treated groups were observed remyelination and better organization of myelin. In conclusion, BCP possesses markedly in vivo anti-inflammatory and neuroprotective activities and remyelination properties in EAE-mice.

I know its in mice but we cannot do these things in humans- At 9 days of treatment, mice were euthanized and CNS was removed for the analysis.

 

[Treeman]

@CSMLSM I also read that it helps mitrochndria

 

[CSMLSM]

not easy at all, and you are to be commended. Whatever happened, you've improved remarkably and so you will continue to do what works for you.

May it continue to improve.

I take one 50 mg Metroprol

Doctor wanted me taking more..I resisted.

Oh I also take 3.5 LDN...but thats it.

(my brain is odd in my opinion, because I still have an odd and very good recall for things yet will entirely forget I watched that movie, until I get a reminder trigger. Oh yes I saw that whole movie).

So yesterday I was lecturing on CPY3A

Brain decided to remember that. Doesn't know what it is yet.

so if I watch a film during the daytime, chances are I'll get really exhausted part way through and maybe even start crashing.

On CBD and related products, in the evening I can watch the whole movie and I am not affected.

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.

An evaluation of the CYP2D6 and CYP3A4 inhibition potential of metoprolol metabolites and their contribution to drug-drug and drug-herb interaction by LC-ESI/MS/MS - PubMed (nih.gov)
In vitro CYP2D6 and CYP3A4 inhibition by MET, HM and ODM study revealed that MET, HM and ODM were not inhibitors of CYP3A4-catalyzed midazolam metabolism and CYP2D6-catalyzed dextromethorphan metabolism. However, DIM only met the criteria of >10% of the total drug related material and <25% of the parent using unbound concentrations. If CYP inhibition testing is solely based on metabolite exposure, DIM metabolite would probably not be considered. However, the present study has demonstrated that DIM contributes significantly to in vitro drug-drug interaction.

I would say based on my limited knowledge that this means it should be considered but because you are not on the highest does and CYP3A is so abundant, as long as you are taking nothing else that uses this enzyme you should be fine if you do not over do the dosing of caryophyllene/copaiba. I am however not a doctor or chemist and teach myself all of thisvso do not take this as direct advise.

What do you think with your science background?

 

[CSMLSM]

Oh I also take 3.5 LDN...but thats it.

Effect of Naltrexone Hydrochloride on Cytochrome P450 1A2, 2C9, 2D6, and 3A4 Activity in Human Liver Microsomes - PubMed (nih.gov)
Abstract
Background and objective: Cytochrome P450 (CYP) 1A2, 2C9, 2D6, and 3A4 are the most important phase I drug-metabolizing enzymes in the liver, but there is a dearth of literature available on the effects of naltrexone hydrochloride on these major enzymes present in the human liver. Thus, in the present study, the effect of naltrexone hydrochloride on the activity of CYP1A2, 2C9, 2D6, and 3A4 using human liver microsomes (HLM) was investigated.

Results: The activity of all the studied CYP enzymes except 1A2 was significantly inhibited by naltrexone hydrochloride 1 µM. Furthermore, 1 µM naltrexone hydrochloride inhibited CYP3A4 enzyme activity, the most by 37.9% followed by CYP2C9 (36.5%) and CYP2D6 (31.8%). The CYP2C9 and CYP2D6 metabolic activities were greatly affected by naltrexone hydrochloride, which even at the lowest concentration of naltrexone hydrochloride (0.01 µM) significantly decreased the metabolic activity by 34.9 and 16.0%, respectively. The half maximal inhibition concentration (IC50) values for CYP2C9 and CYP2D6 inhibition were 3.40 ± 1.78 and 5.92 ± 1.58 µM, respectively.

Conclusion: These outcomes advocate that there is a great possibility of drug interactions resulting from the concurrent administration of naltrexone hydrochloride with actives that are metabolized by these CYP enzymes, particularly CYP2C9 and CYP2D6. Nevertheless, further clarification is needed through detailed in vivo pharmacokinetic studies.

I think someone is likely ok if they are careful and monitor blood pressure. If it drops then they are likely over burdening the enzyme. As before I am not a doctor and this is not advice.

What do you think?

my brain is odd in my opinion, because I still have an odd and very good recall for things yet will entirely forget I watched that movie, until I get a reminder trigger. Oh yes I saw that whole movie).

Yes mine too but getting better now. Why I wanted people to ask me questions so they can remind me of what I know lol I too indeed have a memory that cannot be accessed easilly but a trigger opens the flood gates of information stored. The memory connections are managed by the microglia and astocytes I think, need to do more research on that though.

On CBD and related products, in the evening I can watch the whole movie and I am not affected.

I believe that is because the CBD raises anandamide (cannabinoid) that then acts on the microglia as the caryophyllene does. THC does bind to CB2 but almost not, it is very weak. Caryophyllene however binds very strongly to it. CBD is limited by the way it acts on the receptor by increasing anadamide a little like LDN and endorphins. By partially blocking receptors, it slows degradation of anandamide and receptors being bound to, leading to more anadamide that has more affect on the now more sensitive receptors. Caryophyllene is the molecule for the job!

 

[CSMLSM]

@CSMLSM I also read that it helps mitrochndria

Yes I believe so. It helps lipid metabolism. Induces a fasting state in cells.

 

[Treeman]

Hi, I had been trying Caryophyllene for only about a week and noticed that my ibs-c had improved, less sensitivity to the touch of my digestive system and the stools became softer ( and more smelly) . I have had to stop for a few days and the ibs-c has returned to its previous state.

I'm going to restart it probably tomorrow

 

[CSMLSM]

Hi, I had been trying Caryophyllene for only about a week and noticed that my ibs-c had improved, less sensitivity to the touch of my digestive system and the stools became softer ( and more smelly) . I have had to stop for a few days and the ibs-c has returned to its previous state.

I'm going to restart it probably tomorrow

great news fella, how exactly are you taking it. I find putting it in gelatin capsules works wonders for bowel issues.

I started with 2 drops pure in a gelatin capsule. I now use 5-6 drops first thing and a few times through the day.
At first I would take every 4-6hours until I was almost symptom free. When I first wake and right before bed also.

I did not know about the IBS-C term (IBS was not believed when I first got it about 20+ years ago), this is what I had at times. I had alternating constipation and diarrhoea several times in a day sometimes, sometimes when just constipation and sometimes just diarrhoea or anything inbetween. I was so bad (Had B12 deficiency also so may be why) that I could feel the stool moving through my intestines, going round the bends. I also suffered incontinence but only infrequently most of the time fortunately.

ASGE | Understanding Irritable Bowel Syndrome with Constipation (IBS-C)
What Causes IBS-C-?
The cause of IBS-C is not known. Some experts think that it relates to changes in how the intestines move and contract, or changes in how the gut senses pain. In some patients, IBS-C may happen after a past infection in the gut. It could also be related to changes in the messages between the brain and the intestines. There is evidence that bacteria which are normally found in the gut, or changes to the composition of those bacteria, play a role. In addition, researchers are looking into possible roles of genetics and/or changes in the immune system.

Thanks for the info

 

[Rufous McKinney]

What do you think with your science background?

I have to ponder this further, as I am again on the roller coaster of read three sentences, process a bit, become exhausted, move to stupor, stop reading paragraph, etc.

I can't seem to stay on a topic for any amount of time. Its noon and I want to fall asleep again.

 

[CSMLSM]

I have to ponder this further, as I am again on the roller coaster of read three sentences, process a bit, become exhausted, move to stupor, stop reading paragraph, etc.

I can't seem to stay on a topic for any amount of time. Its noon and I want to fall asleep again.

Please do not worry about it I wish I was not in moderation still so I could tell you now while your online.

Please rest.

 

[YippeeKi YOW !!]

I have to ponder this further, as I am again on the roller coaster of read three sentences, process a bit, become exhausted, move to stupor, stop reading paragraph, etc.

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

Furthermore, 1 µM naltrexone hydrochloride inhibited CYP3A4 enzyme activity, the most by 37.9% followed by CYP2C9 (36.5%) and CYP2D6 (31.8%).

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 ....

 

[YippeeKi YOW !!]

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.

A couple of thoughts, and a couple of questions.

When you refer to CYP3A, I'm assuming you mean CYP3A4 ... yes? No?

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 ...

OK, bad brain day, The other thought and question escapes me right now ....

Ah'll beee bahhhk .....

 

[Rufous McKinney]

There. Clear as mud ..

....I"m still only skipping surface rocks here......across the mud puddle.

The b-caryophyllene being discussed interfere with CYP3A....

so Naltrexone is ALSO doing this?

so two things are doing this, and I'll need to figure it out somehow.