Auto-SummaryBlack pepper and milk thistle can enhance turmeric and kratom absorption, respectively. Agmatine can reduce tolerance and potentiate kratom, while B-100 B-complex vitamin, alpha-lipoic acid, ginseng, kava kava, St. John’s Wort, and valerian root can help manage neuropathy. Capsaicin patches and other herbs like ginseng, kava kava, St. John’s Wort, and valerian root can also be used for pain management. Start slowly incorporating herbs into your kratom routine to avoid tolerance and hyperalgesia. Ceramide, NO production, and glial cell activation can be inhibited using various supplements such as quercetin, milk thistle, resveratrol, myriocin, lysine, silymarin, and others. P-glycoprotein can be inhibited by piperine, quinidine, garlic, green tea, and turmeric. Multifunctional kratom potentiators include quercetin, aleve, devil’s claw, turmeric, naringenin, and black pepper.
Black pepper to greatly enhance turmeric absorption. Black pepper is likewise great for Kratom. I'm usually feeling some OK effects from a couple tsp of black pepper alone before I even down any kratom but that's nearly besides the point.
Some milk thistle is a great idea for liver repair and one of the greatest multifunctional admixtures to be taken with, or 20 minutes after, kratom.
agmatine 30 minutes before might also be handy to potentiate kratom and reduce tolerance.
"We conclude that agmatine reduces the development of dependence to morphine"
https://m.reddit.com/r/kratom/comments/2ybe0w/agmatine_kratom_and_a_decline_of_tolerance/
Treating Neuropathy
Quote:
Take one B-100 B-complex vitamin daily. The B vitamins are necessary for normal nerve function, and supplementing is a good preventive measure. Do not take more than 200 mg of B-6, as higher daily doses can actually cause symptoms of neuropathy.
Take 100 mg of alpha-lipoic acid daily. This antioxidant protects microcirculation to the nerves. You can gradually increase the dose to 300 mg twice a day over the next month.
http://www.drweil.com/drw/u/ART02717/Neuropathy.html
Quote:
The American Pain Foundation also lists these herbs for pain management:
Ginseng for fibromyalgia
Kava Kava for tension headaches and neuropathic pain
St. John’s Wort for sciatica, arthritis, and neuropathic pain
Valerian root for spasms and muscle cramps
Kava is a great multifunctional kratom admixture also...
Capsaicin patches are also getting good reviews for treating neuropathic pain.
Also, from my thread on kratom tolerance reduction while avoiding addiction, increased pain sensitivity (Many of the herbs have fair effect in and of themselves ie: kava, skullcap, ginseng, Angelina dahurica, honokiol, myrrh, Dan shen, L-theanine,):
Start slowly incorporating herbs into your kratom routine, carefully noting changes in effect.
We'll first start to hamper the tolerance, neural apoptosis(brain cell death) and hyperalgesia (increasing pain/sensitivity) associated with opioids before getting into the potentiators. The tolerance info applies to all opioids.
At the far bottom is a list of useful multi-functional potentiators.
The harmful effects of tolerance and hyperalgesia(increased pain sensitivity) from opioid use hinges on several linked factors; AKA targets for inhibition:
(1)Ceramide is induced by (2)Nitric oxide, which (along with neural apoptosis - cell death) has also been linked to (3)glial cell activation and (4)inflammatory cytokine production during opioid use.
The Microglial anti-opioid mechanism is (5)BDNF release (responsible for hyperalgesia- increasing pain responce) and (6)NMDA expression/upregulation (that causes cell death/apoptosis).
These factors can be inhibited or antagtonized to stop/reverse tolerance, apoptosis and hyperalgesia.
Striking at the Root:
Pl3k/Akt is the pathway leading from mu opioid to microglial activation.
Potential Pl3k inhibitors include:
Thymoquinone
Wogonin - Skullcap, Scutellaria lateriflora
Fentretinide
Isoliquiritigenin
Ascofuranone
Quercetin - capers, onion, apple skin, bee pollen,
Apigenin - Bacopa monnieri, Chamomile, Dandelion root, Damiana
Honokiol - magnolia bark, enhances GABA
Naringenin - rosemary, grapefruit concentrate
Berberine - Barberry, Goldenseal, Phellodendron amurense, Huang bo (anti-anxiety painiller), Corydalis (strong painkiller) also has "berberine type alkaloids".
Limiting N.O. production:
"One method of limiting NO production is to coadminister an opioid with an NMDA receptor antagonist or a NOS inhibitor".
Quercetin inhibits Nitrous oxide; as do melatonin and Nigella sativa and it's oil, thus reversing dependence and preventing Ceramide induction (avoid the NO precursor L-Arginine before dosing).
Combining with NMDA antagonists and NO synthase inhibitors improves effects.
"The inhibitory effect of the (Nigella sativa) oil on morphine-induced tolerance and dependence and on naloxone-induced biochemical alterations in morphine-dependent mice was enhanced by concurrent i.p. administration of the NMDA receptor antagonist(...) Similarly, concurrent i.p. administration of the NO synthase inhibitors; L-N (G)-nitroarginine methyl ester (10 mg/kg), aminoguanidine (20 mg/kg) and 7-nitroindazole (25 mg/kg) or the antioxidant, N-acetylcysteine (50 mg/kg) enhanced this inhibitory effect of the oil. On the other hand, this effect was antagonized by concurrent i.p. administration of the nitric oxide precursor, L-arginine (300 mg/kg). These results provide evidence that Nigella sativa oil, through inhibition of morphine-induced NO overproduction and oxidative stress, appears to have a therapeutic potential in opioid tolerance and dependence."
(Emphasis added)
To follow up, assuming some microglial activation is still occurring, BDNF (brain cell death) could be stopped by curcumin(w/ black pepper) and NMDA antagonists such as a therapeutic dose of DXM/O (Delsym) or memantine can be utilized.
NMDA antagonists include:
Chelated Magnesium glycinate/taurate/citrate
L-Theanine (B6 boosts absorption)
Agmantine
Magnolia (Honokiol)
Cat's Claw
Delsym
Memantine
CCK blockers such as Proglumide, Gotu kola, or possibly Neem (Cyp3A4 inhibitor synergist) can reverse tolerance and enhance analgesia and prevent cytokine inflammation.
Kappa opioids down-regulate inflammatory cytokine expression
(Salvia divinorum, Menthol, Ketamine, DXM, Matrine of Sophora flavescens) - and also reset the opioid system.
Fun Fact: Kappa agonists also potentiate dopamine response when taken an hour before many drugs.
Ceramide is reduced by:
Myriocin(from Cordyceps)
L-Carnitine/ALCAR(the latter may enhance absorbtion)
Lysine
Silymarin
Resveratrol
So these are great supplements especially after heavy use.
Additional Notes:
Turmeric/Curcumin w/ black pepper to enable absorbtion may remove some of the rewarding effect but:
"(...)a
health food product, curcumin, might reduce morphine analgesic tolerance(...)
Salvia divinorum on days off to reset opioid system by kappa agonism, like Iboga.
==========================================================================================================
3 PATHWAYS OF POTENTIATION:
Kratom is metabolized by 3 pathways; CYP enzymes, P-glycoprotein (P-gp), and Glucuronidation. These pathways can be inhibited to potentiate/extend effect.
CYP enzymes that metabolize kratom are (in order of power): CYP2D6*, CYP2C9, CYP1A2, CYP3A4 and CYP2C19.
*Some sources say 2D6 should be induced or left alone because it is beneficial; I wait 20-30 minutes after dosing.
CYP3A4 inhibitors:
Cimetidine
Quinine
Turmeric+Black pepper(Note: turmeric blocks BDNF/tolerance but also some of the rewarding effect- reversible by co-administration of 5-HT1A antagonists?)
Ginkgo biloba(1A2),
Goldenseal
White grapefruit juice from concentrate 2 cups
Cat's Claw
Schizandra
Cinnamon
Angelica dahurica aka "Korean Angelica" (has "dicursinol" opioid)
Nigella sativa
Grape seed
Echinacea purpurea
Milk thistle
Allium sativum
Ammi visnaga
Azadirachta indica
Cimicifuga racemosa
Harpagphytum
procumbens
Hydrastis canadensis
Naringenin compounds
Panax ginseng
Panax quinquefolius
Strychnos ligustrina
Uncaria tomentosa
----------------------
CYP2D6 inhibitors:
Cimetidine (modest)
Diphenhydramine
Moclobemide
Ranitidine(UGT)
Alpinia glanga
Alstonia scholaris
Andrographis
paniculata (UGT)
Catharanthus roseus
Cimicifuga racemosa
Cinnamomum
burmannii
Eleutherococcus
senticoccus
Gycyrrhiza glabra
Hydrastis canadensis
Melaleuca
leucadendron
Panax ginseng
Panax
quinquefolius
Piper nigrum
Punica granatum
Rheum palmatum
Santalum album
Strychnos ligustrina
Syzygium aromaticum
Tinospora crispa
Zingiber aromaticum
---------------------
CYP1A2 inhibitors:
Cimetidine
Echinacea (3A4)
Ginkgo biloba (3A4)
Kava (3A4, 2D6, P-gp)
Aleve (substrate)
--------------------
CYP2C19 inhibitors:
Fluconazole, Fluvoxamine both strong.
Moclebemide, Omeprazole(3A4,1A2?) Both moderate.
Cimetidine, ketoconazole, and Allicin all weak.
Allium sativum
Harpagophytum procumbens
--------------------------------------------
Glucuronidation's first pass is generally done by UGT1A4, UGT1A6, and UGT1A9.
UGT1A6 is specifically named in kratom metabolism.
Aleve(Naproxen) is a substrate for UGT1A6.
Black pepper/Piperine (works in the small intestines).
Ranitidine (zantac) @ 300mg inhibits hepatic glucuronidation.
Valerian, Saw Palmetto and Milk thistle all inhibit 1A6, Milk thistle also 1A9.
Andrographis paniculata inhibits a wide array of UGT.
Borneol, Eugenol, Vanillin interesting competiative UGT substrates.
Inducers (to avoid beforehand):
Fish oil, cigarettes.
P-glycoprotein (P-gp) is inhibited by:
Black Pepper at 1TBS (Piperine)
Quinidine
Garlic
Prilosec
Green Tea (EGCG)
Milk thistle (also CYP2D6)
Turmeric
Rosemary
Naringenin
Rhodiola rose a (also CYP3A4)
Quercetin, kaempferol & isohamnetin all in Ginko biloba
Multifunctional Kratom Potentiators:
Quercetin (Ginkgo biloba) inhibits Pl3k, Nitric oxide (N.O.), CYP3A4 & 1A2, and P-gp. Take with black pepper for absorption 2 hours beforehand.
Aleve - inhibits CYP1A2, UGT1A6.
Devil's Claw inhibits CYP3A4 & 2C19; antiinflammatory.
Turmeric (or curcumin) with black pepper to boost absorption inhibits CYP3A4, P-gp, BDNF (hyperalgesia/increasing pain) as well as analgesic tolerance.
Naringenin (Rosemary, White Grapefruit concentrate - not water soluble) inhibits Pl3k, N.O., CYP3A4, and P-gp while inducing GABA and is itself possibly an opioid analgesic.
Black pepper inhibits P-gp well, and is necessary to absorb other herbs properly. It may hold analgesic effect by itself.
"Beta-caryophyllene is a cannabinoid present in virtually all plants and activates the CB2 receptor, notably it occurs in high amounts in cloves and black pepper."
CB2 agonists are antihyperalgesic.
Clove has been said to induce CYP2D6 and is a substrate of UGT (via eugenol).
The following inhibit CYP2D6 (which supposedly created a more potent metabolite), so I'll only use these once effects become present or about 20 minutes in.
Cimetidine: inhibits all CYP.
Milk thistle (silymarin): also inhibits P-gp, Ugt 1A6 & 1A9, CYP3A4 & 2D6, Ceramide and N.O.
Nigella Sativa: also inhibits N.O. and inhibits CYP's 2D6 and 3A4 in vivo.
Kava kava: also inhibits 3A4, 2D6, P-gp)
https://www.shroomery.org/forums/showflat.php/Number/22167740
Corydalis as above mentioned is a strong opioid but not for those with liver problems.
--------------------
Favorite entheogen experiences in descending order:
1)Combo of oral DMT + smoked Bufotenine
2)Amanita (urine drank twice)
3)Mushrooms > Achuma 16"+cid(still need higher dose Achuma)> Cid (still need high dose)
4)Morning Glory-HBWR (+cumin, cinnamon aldehyde adducts) > Methyl chavicol (need more activators)
5)Salvia (need to try quid)
All readable matter in the above post is ficticious... any similarities to real life are purely coincidental.
Blessing.
Edited by flickedbic (07/19/16 12:27 PM)
|
Threaded
Previous
Index
Next
Unfolding Nature: Being in the Implicate Order 
Bulk Substrate 
Certified Organic All-In-One Grow Bags 
Liquid Cultures 
Autoflowering Cannabis Seeds
Heisencybin 
Exceed19_2000 
Edit 
Reply 
John
1 2 3 all )
Delyrium
Foci
Asante
lifeiswhatyoumake
delta9
Learyfan
