I just wanted to show briefly the comparison of Caryophyllene and LDN.

CSMLSM

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I am sure you know that LDN affects IL6, NF-κB, TLR and microglia activation state. Also that it is used to treat opiate addiction.
Also I am sure you are aware that elevated Leptin has been seen by many in ME/CFS and Fibromyalgia separately in the research community.


Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic Inflammation - PMC (nih.gov)
Taken from the above-
Experimental results show the ability of BCP to reduce pro-inflammatory mediators such as tumor necrosis factor-alfa (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), thus ameliorating chronic pathologies characterized by inflammation and oxidative stress, in particular metabolic and neurological diseases. Through the binding to CB2 cannabinoid receptors and the interaction with members of the family of peroxisome proliferator-activated receptors (PPARs), BCP shows beneficial effects on obesity, non-alcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) liver diseases, diabetes, cardiovascular diseases, pain and other nervous system disorders.

Cannabinoid receptor 2 is necessary to induce toll‐like receptor‐mediated microglial activation - Reusch - 2022 - Glia - Wiley Online Library

Taken from above-
We show that the CB2-mediated attenuation of TLR-induced microglial activation is mainly p38 MAPK-dependent. Taken together, we demonstrate that CB2 expression and signaling are necessary to fine-tune TLR-induced activation programs in microglia.

β-Caryophyllene protects against ischemic stroke by promoting polarization of microglia toward M2 phenotype via the TLR4 pathway - PubMed (nih.gov)
Taken from above-

The objective of the study was to determine whether β-caryophyllene (BCP) exerts a neuroprotective effect in cerebral ischemia-reperfusion (I/R) injury by inhibiting microglial activation and modulating their polarization via the TLR4 pathway.

The decrease in TLR4 activity mediated, at least in part, the anti-inflammatory effects of BCP and its ability to shift microglia polarization from the M1 to M2 phenotype.

The protective effects of β-caryophyllene on LPS-induced primary microglia M1/M2 imbalance: A mechanistic evaluation | Request PDF (researchgate.net)

Taken from above-
In conclusion, the low concentration of BCP has higher selective anti-inflammatory effects rather than high levels. On this occasion, BCP by modulating the microglia is able to have potential therapeutic effects in neuro-inflammation conditions and microglia cells such as MS and AD.

Fatty Acid Amide Hydrolase (FAAH) Inhibition Modulates Amyloid-Beta-Induced Microglia Polarization - PMC (nih.gov)
Taken from above-
fatty acid amide hydrolase (FAAH), the main catabolic enzyme of anandamide (AEA) (an endogenous cannabinoid)

these data suggest that FAAH inhibition promotes cytoskeleton reorganization, regulates phagocytosis and cell migration processes, thus driving microglial polarization towards an anti-inflammatory phenotype.

Anandamide enhances IL-10 production in activated microglia by targeting CB(2) receptors: roles of ERK1/2, JNK, and NF-kappaB - PubMed (nih.gov)
Taken from above-
This suggests that by altering the cytokine network, AEA could indirectly modify the type of immune responses within the central nervous system (CNS). Accordingly, pharmacological modulation of AEA uptake and degradation might be a useful tool for treating neuroinflammatory diseases.



Leptin Activates the Anandamide Hydrolase Promoter in Human T Lymphocytes through STAT3 - ScienceDirect

Taken from above-
these results suggest that leptin, by up-regulating the FAAH promoter through STAT3, enhances FAAH expression, thus tuning the immunomodulatory effects of anandamide.

Leptin modulates cell morphology and cytokine release in microglia - PubMed (nih.gov)
Taken from above-
These results suggest that leptin has an important role in microglial function in inflammation and given that its circulating levels fluctuate across a number of conditions, these findings can have important implications for an individual's ability to mount an efficient and complete response to invading pathogens.


Effects of CB2 Receptor Modulation on Macrophage Polarization in Pediatric Celiac Disease - PMC (nih.gov)
Taken from above-

CB2 stimulation switches macrophage polarization towards the anti-inflammatory M2 phenotype thus reducing inflammation but also limiting the epithelial dysfunction. Therefore, we suggest CB2 receptor as a possible novel therapeutic target for CD by regulating macrophages polarization and by preventing mucosal barrier damage.


Beta-caryophyllene inhibits cocaine addiction-related behavior by activation of PPARα and PPARγ: repurposing a FDA-approved food additive for cocaine use disorder - PubMed (nih.gov)

Taken from above-
It also failed to maintain self-administration in a drug substitution test, suggesting that BCP has no abuse potential.

We found that BCP is more effective in attenuation of cocaine-enhanced oICSS than eICSS, the former driven by optical activation of midbrain dopamine neurons in DAT-cre mice. These findings indicate that BCP may be useful for the treatment of CUD, likely by stimulation of PPARα and PPARγ in the mesolimbic system.

Naltrexone a potential therapeutic candidate for COVID-19 - PMC (nih.gov)
Taken from above-
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of Coronavirus Disease (COVID-19) that has resulted in a global pandemic. At the time of writing, approximately 16.06 million cases have been reported worldwide. Like other coronaviruses, SARS-CoV-2 relies on the surface Spike glycoprotein to access the host cells, mainly through the interaction of its Receptor Binding Domain (RBD) with the host receptor Angiotensin-Converting Enzyme2 (ACE2). SARS-CoV-2 infection induces a profound downstream pro-inflammatory cytokine storm. This release of the pro-inflammatory cytokines is underpinning lung tissue damage, respiratory failure, and eventually multiple organ failure in COVID-19 patients. The phosphorylation status of ERK1/2 is positively correlated with virus load and ERK1/2 inhibition suppressed viral replication and viral infectivity. Therefore, molecular entities able to interfere with binding of the SARS-CoV-2 Spike protein to ACE2, or damping hyperinflammatory cytokines storm, blocking ERK1/2 phosphorylation have a great potential to inhibit viral entry along with viral infectivity. Herein, we report that the FDA-approved non-peptide opioid antagonist drug, naltrexone suppresses high fat/LPS induced pro-inflammatory cytokine release both from macrophage cells and Adipose Tissue Macrophage. Moreover, Low Dose Naltrexone (LDN) also showed its activity as an ERK1/2 inhibitor. Notably, virtual docking and simulation data also suggest LDN may disrupt the interaction of ACE2 with RBD. LDN may be considered as a target as the treatment and (or) adjuvant therapy for coronavirus infection. Clinical toxicity measurements may not be required for LDN since naltrexone was previously tested and is an approved drug by the FDA.


β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19 - PubMed (nih.gov)
Taken from above-
Based on its pharmacological properties, molecular mechanisms, and the therapeutic potential of BCP as an immunomodulator, anti-inflammatory, organ-protective, and antiviral, we hypothesize that BCP could be a promising therapeutic and/or preventive candidate to target the triad of infection, immunity, and inflammation in COVID-19. In line with numerous studies that proposed the potential of cannabinoids in COVID-19, BCP may be a novel candidate compound for pharmaceutical and nutraceutical development due to its unique functional receptor selectivity, wide availability and accessibility, dietary bioavailability, nonpsychoactivity, and negligible toxicity along with druggable properties, including favorable pharmacokinetic and physicochemical properties. Based on reasonable pharmacological mechanisms and therapeutic properties, we speculate that BCP has potential to be investigated against COVID-19 and will inspire further preclinical and clinical studies.




So with LDN you have an issue with having to stop pain medication before you start and this is an issue obviously because ME/CFS causes pain. Caryophyllene treats pain also.
Caryophyllene is safe and Copaiba which contains high amounts of Caryophyllene is deemed safe-

From Wiki
The Food and Chemicals Codex lists copaiba oil as safe as a flavoring agent for foods.[9] Copaiba oil has both an acute oral and dermal LD50 exceeding 5 g/kg,[10] which classifies it as non-toxic.[

Copaiba oil-resins extracted have been used in folk medicine dating back to the 16th century by the natives of north and northeastern Brazil. The folk remedies were administered orally or used as an ointment in the treatment of various diseases.[5] In Panama, the Yaviza people mix the resin with honey and give it to newborns to impart knowledge and ward off hexes.[6] Within the Peruvian Amazon near Iquitos, it is also used as an insect repellent.


As you can see it has a long human use with proven safety and has no legal barriers to use at all, not even a prescription required, no need to prove safety and is relatively low cost.
 
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all super fascinating, Thank You For posting this great info.....

I currently use LDN (3.5 mgs daily) and I continue the Copaiba experiment. Oh, that makes me more happy than the idea of another booster.

I "paused"...the Copaiba while I check out this new probiotic I"m also trying out. I think this new probiotic is somehow helpful and is supposed to fine tune my HLA axis.

I"m stretching isn the morning- unheard of. I seem to need less sleep. Maybe I'm a tad less out of it....
 

CSMLSM

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all super fascinating, Thank You For posting this great info.....

I currently use LDN (3.5 mgs daily) and I continue the Copaiba experiment. Oh, that makes me more happy than the idea of another booster.

I "paused"...the Copaiba while I check out this new probiotic I"m also trying out. I think this new probiotic is somehow helpful and is supposed to fine tune my HLA axis.

I"m stretching isn the morning- unheard of. I seem to need less sleep. Maybe I'm a tad less out of it....
I am glad it made you happy. I myself have not had a vaccine for the covid virus as it itself can trigger Post Viral Condition and thus can have an affect on ME/CFS.

Gut microbiome is very important and many opportunistic viruses and bacteria take advantage of our disrupted immune systems which extends to our guts. Vagus nerve is affected by the microbiome and links to the HPA axis via its connection to the brain.
So yes, you are spot on :)

I would like to hear of your experience of LDN if you would like to share, I would personally think based on the science and my experience think that Caryophyllene is going to work better. So comparing the experiences would seem appropriate.
 
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I would like to hear of your experience of LDN if you would like to share,
I need to fully pin down WHEN I started the LDN. I have too many small notebooks to wade thru to figure it out.

But figure I've been on LDN since maybe around 2015......

It seemed to mostly be reducing the intensity of symptoms. I don't consider it: a cure. I'm still sick and I can get much worse, as was evident in 2019. I'm less worse than summer of 2019 so that something.

Alot of mouth tissue swelling, very painful, including blood blisters forming on my spleen meridian under my tongue where the salivary glands are located/ Bright purple. I just looked, and one blood blister is there, right now.

If I run out of LDN, after a few days, I start to notice more swelling up..part of my daily inflammatory cycle and maybe some pain increases...like fibromyalgia type pain is less.

I do really need to find notes that may exist from the earlier days....
 
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links to the HPA axis via its connection to the brain.
I'm trying these new probiotics for the HPA axis. I did them for about a week, now taking a few days break.

Mood Probiotics.

The odd thing outside of immediate shifts in my gut condition- it seems I"m not needing as much sleep, and when I wake up...I"m doing this huge stretch. I never stretch, the body doesn't do this stuff. I' ve noticed it every day.

I'm thinking some shifts in cortisol might be happening.

I am having a hard time handling the heaviness in the bowels, on the probiotics. Plus I was doing natto....so I was crash-y all week.
 

CSMLSM

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I need to fully pin down WHEN I started the LDN. I have too many small notebooks to wade thru to figure it out.

But figure I've been on LDN since maybe around 2015......

It seemed to mostly be reducing the intensity of symptoms. I don't consider it: a cure. I'm still sick and I can get much worse, as was evident in 2019. I'm less worse than summer of 2019 so that something.

Alot of mouth tissue swelling, very painful, including blood blisters forming on my spleen meridian under my tongue where the salivary glands are located/ Bright purple. I just looked, and one blood blister is there, right now.

If I run out of LDN, after a few days, I start to notice more swelling up..part of my daily inflammatory cycle and maybe some pain increases...like fibromyalgia type pain is less.

I do really need to find notes that may exist from the earlier days....
Rufous McKinney said:
part of my daily inflammatory cycle

Hi RM, this is interesting.

Rufous McKinney said:
It seemed to mostly be reducing the intensity of symptoms. I don't consider it: a cure. I'm still sick and I can get much worse,

So it helps but only slightly, am I getting that right? and you have a daily inflammatory cycle regardless of taking LDN but it is much worse when not taking LDN?
It sounds like you are doing the right things with LDN in your body but it is just not enough.

In contrast the Caryophyllene (and CBD sometimes) for me has given me at this point 5 months on (taking CBD prior for some time) almost no symptoms and I just need to figure out how best to take it. I have to figure out the dosing regime. I found out some good information from a paper the other day suggesting that taking too much can have less effect so level I take is going to be key. But hey winging it so far (sort of joking) has had amazing results.

I found out also that Copaiba has an LD50 of ^5g/kg so deemed non-toxic and safe to consume. It may even work with LDN and work better who knows we need someone to do the science for us!

Rufous McKinney said:
The odd thing outside of immediate shifts in my gut condition- it seems I"m not needing as much sleep, and when I wake up...I"m doing this huge stretch. I never stretch, the body doesn't do this stuff. I' ve noticed it every day.

This seems oddly familiar to me, I have experienced this near beginnings of upticks of health as I was experimenting through the years. Sounds like you are doing the right things, maybe just not enough of it? The immune system maybe needs more of a shove :)
 
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So it helps but only slightly, am I getting that right? and you have a daily inflammatory cycle regardless of taking LDN but it is much worse when not taking LDN?
yes.

I inflame daily and the daily cycle is quite consistent.

In contrast the Caryophyllene (and CBD sometimes) for me has given me at this point 5 months on (taking CBD prior for some time) almost no symptoms and I just need to figure out how best to take it.
I may reach the point where I try it internally soon.
 

CSMLSM

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yes.

I inflame daily and the daily cycle is quite consistent.



I may reach the point where I try it internally soon.
What I have done is buy a Copaiba steam distilled essential oil so no solvents are used in its production. Given that the Copaiba is deemed safe to consume I use this steam distilled stuff to be as pure as possible and safe for me to consume. Caryophyllene is used in the plant kingdom as a protective molecule against bacteria and fungi.
Here is some interesting research-
The Anticancer, Antioxidant and Antimicrobial Properties of the Sesquiterpene β-Caryophyllene from the Essential Oil of Aquilaria crassna - PubMed (nih.gov)
Abstract
The present study reports a bioassay-guided isolation of β-caryophyllene from the essential oil of Aquilaria crassna. The structure of β-caryophyllene was confirmed using FT-IR, NMR and MS. The antimicrobial effect of β-caryophyllene was examined using human pathogenic bacterial and fungal strains. Its anti-oxidant properties were evaluated by DPPH and FRAP scavenging assays. The cytotoxicity of β-caryophyllene was tested against seven human cancer cell lines. The corresponding selectivity index was determined by testing its cytotoxicity on normal cells. The effects of β-caryophyllene were studied on a series of in vitro antitumor-promoting assays using colon cancer cells. Results showed that β-caryophyllene demonstrated selective antibacterial activity against S. aureus (MIC 3 ± 1.0 µM) and more pronounced anti-fungal activity than kanamycin. β-Caryophyllene also displayed strong antioxidant effects. Additionally, β-caryophyllene exhibited selective anti-proliferative effects against colorectal cancer cells (IC50 19 µM). The results also showed that β-caryophyllene induces apoptosis via nuclear condensation and fragmentation pathways including disruption of mitochondrial membrane potential. Further, β-caryophyllene demonstrated potent inhibition against clonogenicity, migration, invasion and spheroid formation in colon cancer cells. These results prompt us to state that β-caryophyllene is the active principle responsible for the selective anticancer and antimicrobial activities of A. crassnia. β-Caryophyllene has great potential to be further developed as a promising chemotherapeutic agent against colorectal malignancies.

So it is like an antibiotic, chemotherapeutic agent for cancer, immune modulator towards anti inflammatory state throughout the body including the brain, pain reliever and safe to consume as Copaiba with an LD50 of ^5g/kg so deemed non toxic.

So because I have ME/CFS I have/had problematic infections, I am at greater risk of cancer and autoimmune diseases, I have inflammation driving my condition in my brain and oh my do/did I have pain.

I am basically over ME/CFS now I just got to fix an old weak body which will take time. I am however loving the little things in life so much. Now life is about the journey and not the destination like it used to be, I wanted death to come or get better, a destination. Now I want to enjoy every little thing now that I can and thats amazing to feel that way finally.

I hope others can benefit from this amazing molecule and if you do decide to try I hope sincerely that it works for you as well as it is working for me because it is amazing. The fact I have no one to share this with and a mother who seems indifferent to the micracle that has occurred makes me feel a little deflated in my achievement if you know what I mean.
 
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What I have done is buy a Copaiba steam distilled essential oil so no solvents are used in its production. Given that the Copaiba is deemed safe to consume I use this steam distilled stuff
they were out of the steam distilled brand when I ordered.

Mine is 100% Copaiba...and the company looks pretty good but I don't think I was successful in determining how it was isolated.

Hence, I've only done topical and need to resume after a break.

I think I told you the guy who runs our dispensary cured his Stage Iv colon cancer with b-caryophyllene

I should check and see if I can find distilled....again.
 
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These results prompt us to state that β-caryophyllene is the active principle responsible for the selective anticancer and antimicrobial activities of A. crassnia. β-Caryophyllene has great potential to be further developed as a promising chemotherapeutic agent against colorectal malignancies.
I know one person who cured their colon cancer with b-caryophyllene...
 
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Caryophyllene is used in the plant kingdom as a protective molecule against bacteria and fungi.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554841/

excerpts on plants with high b-caryophylene:

A systematic analysis of plant species with essential oils containing a BCP percentage > 10% provided almost 300 entries with species belonging to 51 families. The essential oils were found to be extracted from 13 plant parts and samples originated from 56 countries worldwide.

Article lists various genera and species.

B-caryophyllene is in a lot of plants and I suspect they've only looked at a limited array.

I'd like to solve: why order this stuff from Brazil if its in an abundant weed down the block?

Its in some mints..(Scutelaria; Salvia) and Bursura is rather abundant in deserts and subtropics North America.

Why go to New Guinea?
 

CSMLSM

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they were out of the steam distilled brand when I ordered.

Mine is 100% Copaiba...and the company looks pretty good but I don't think I was successful in determining how it was isolated.

Hence, I've only done topical and need to resume after a break.

I think I told you the guy who runs our dispensary cured his Stage Iv colon cancer with b-caryophyllene

I should check and see if I can find distilled....again.
I remembered you had told me and also that you like herbal medicines so thats why I thought you would find it interesting.