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LSD potentiation by CYP2D6 inhibition - anybody with experience? Options
#1 Posted : 12/7/2023 7:16:40 PM
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CYP2D6 seems to by main enzyme to "destroy" LSD it's inhibition in theory increase strength ant time of LSD effects. Lot of herbs can have effect on this enzyme so it may be useful for potentiation. Searching more info about it what herbs, dosage, safety, personal experience...

Links to studys/info i found so far: (last update 8.12 2023)

Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use

Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis
* in people with less active enzyme variant is LSD stronger and have longer effect

Half maximal inhibitory concentration (IC50) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. IC50 is a quantitative measure that indicates how much of a particular inhibitory substance (e.g. drug) is needed to inhibit, in vitro, a given biological process or biological component by 50%.

Quinine - Lots of dangerous side effects
In tonic water max 100mg/l in EU
Dietary levels of quinine in tonic water do not inhibit CYP2D6 in vivo (80mg - 1l tonic water)

Grapefruit juice

Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins

Strongest effect on CYP3A4
The effects last because grapefruit-mediated inhibition of drug metabolizing enzymes, like CYP3A4, is irreversible;[29] that is, once the grapefruit has "broken" the enzyme, the intestinal cells must produce more of the enzyme to restore their capacity to metabolize drugs that the enzyme is used to metabolize.[13] It takes around 24 hours to regain 50% of the cell's baseline enzyme activity and it can take 72 hours for the enzyme activity to completely return to baseline. For this reason, simply separating citrus consumption and medications taken daily does not avoid the drug interaction

*One study did not find any significant effect on CYP2D6 200ml juice 5days
Only abstract not much info

Significant difference between in vivo and in vitro data.

Curcuma longa[
Effect of Curcuma longa on CYP2D6- and CYP3A4-mediated metabolism of dextromethorphan in human liver microsomes and healthy human subjects

Curcumin inhibited CYP1A2 (IC(50), 40.0 microM), CYP3A4 (IC(50), 16.3 microM), CYP2D6 (IC(50), 50.3 microM), CYP2C9 (IC(50), 4.3 microM) and CYP2B6 (IC(50), 24.5 microM). Curcumin showed a competitive type of inhibition towards CYP1A2, CYP3A4 and CYP2B6, whereas a non-competitive type of inhibition was observed with respect to CYP2D6 and CYP2C9. The inhibitory activity towards CYP3A4, shown by curcumin may have implications for drug-drug interactions in the intestines, in case of high exposure of the intestines to curcumin upon oral administration. In spite of the significant inhibitory activities shown towards the major CYPs in vitro, it remains to be established, whether curcumin will cause significant drug-drug interactions in the liver, given the reported low systemic exposure of the liver to curcumin.

*Pure turmeric powder had the highest curcumin concentration, averaging 3.14% by weight.

*Bioaviability is very poor - The average serum concentrations after taking 4, 6, and 8 g of curcumin were 0.51 ± 0.11 μM, 0.63 ± 0.06 μM, and 1.77 ± 1.87 μM, respectively.

Moreover, powdered curcuminoids incorporated into buttermilk (300 mg curcuminoids/100 g of buttermilk, 0.3%), before yogurt manufacturing, resulted in increased in bioaccessibility (15-folds) of curcuminoids compared to that of neat curcuminoids. However, the enhanced bioaccessibility of curcuminoids in yogurt was still low (approximately 6%) (Fu et al., 2016)
Increase with lecitin or piperin but still seems too low to be usefull

*curcumin molar mass 368,38 g/mol

Ginseng ?
Camollmile ?

Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6

In vitro inhibition studies demonstrate that, at their therapeutic concentrations, both nicotinic acid and nicotinamide inhibit CYP2D6 (Ki=3.8±0.3 and 19 ± 4 mM, respectively). Nicotinamide also inhibits CYP3A4 (Ki=13±3 mM) and CYP2E1 (Ki=13±8 mM)

B3 as trip killer https://bibliography.map...hy/default/resource/3758


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