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Piper nigrum - harmala potentiator?

Migrated topic.

azrael

Rising Star
been away from the spaceport for a few days, not going back for a few more. scrambled thoughts are keeping me up, and somehow I ended up looking around for info on cyp450 and ayahuasca. it had something to do with a brew using white grapefruit juice (probably bogus; just some random thought), but I did stumble upon something interesting.

So, harmaline is metabolized by cytochrome p450 2d6 (cyp2d6). somewhere else, harmine and thh were mentioned as being metabolized by cyp2d6 as well (too tired to find the link). Then, a search for safe cyp2d6 inhibitors yielded this, which lists black pepper as a reasonably obtainable source.

I promptly came to search the nexus, and found the thread called "Potentiation Blend?" and it's subsequent successful report. not sure if there's a connection, but it sounds like such a good synergy I thought I'd repost.


Anyway, does anyone have any experience mixing black pepper and any of the harmalas or other maois? spice? if so, dosage/timeframe/effects? if someone can look in to how much P. nigrum material would need to be consumed to be an effective (noticeably) cyp2d6 inhibitor, that'd be a good start.

I'm anxious to try it out, but am not going to be able to do any experimenting for a little while - I'll post up if I'm the first to get around to trying it 😉


EDIT: dug up this old thread, doesn't seem to be many experience reports. I think a bit with some aya sounds promising though.
 
As far as I'm aware using Black Pepper doesn't do that much (haven't tried it tho) however a Piperine/Bioperine extract (20mg/kg???) should/might increase the bioavailablilty of the harmalas and spice when ingested.

An interesting experiment - might be good with Curcumin as the MAO.
 
Cyp1a2 inhibitors may be good to check out too when it comes to harmine potentiation. Possible things to test is turmeric(curcumin), caffeine, theobromine, chamomile.

Here is a good list of possible herbs that interact with the cyp p450 system:

Here is an abstract from Contribution of Individual Cytochrome P450 Isozymes to the
O-Demethylation of the Psychotropic B-Carboline Alkaloids
Harmaline and Harmine


The psychotropic B-carboline alkaloids, showing high affinity
for 5-hydroxytryptamine, dopamine, benzodiazepine, and imidazoline
receptors and the stimulation of locus coeruleus neurons,
are formed endogenously from tryptophan-derived indolealkylamines
through the Pictet-Spengler condensation with
aldehydes in both plants and mammals. Cytochromes P450
1A1 (18.5), 1A2 (20), and 2D6 (100) catalyzed the O-demethylation
of harmaline, and CYP1A1 (98.5), CYP1A2 (35), CYP2C9
(16), CYP2C19 (30), and CYP2D6 (115) catalyzed that of
harmine (relative activities). The dehydrogenation/aromatization
of harmaline to harmine was not carried out by aromatase
(CYP19), CYP1A2, CYP2C9, CYP2D6, CYP3A4, pooled recombinant
cytochromes P450, or human liver microsomes (HLMs).
Kinetic parameters were calculated for the O-demethylations
mediated by each isozyme and by pooled HLMs. Kcat (min 1)
and Km ( M) values for harmaline were: CYP1A1, 10.8 and
11.8; CYP1A2, 12.3 and 13.3; CYP2C9, 5.3 and 175; CYP2C19,
10.3 and 160; and CYP2D6, 39.9 and 1.4. Values for harmine
were: CYP1A1, 45.2 and 52.2; CYP1A2, 9.2 and 14.7; CYP2C9,
11.9 and 117; CYP2C19, 21.4 and 121; and CYP2D6, 29.7 and
7.4. Inhibition studies using monoclonal antibodies confirmed
that CYP1A2 and CYP2D6 were the major isozymes contributing
to both harmaline (20% and 50%, respectively) and harmine
(20% and 30%) O-demethylations in pooled HLMs. The turnover
numbers for CYP2D6 are among the highest ever reported
for a CYP2D6 substrate. Finally, CYP2D6-transgenic mice were
found to have increased harmaline and harmine O-demethylase
activities as compared with wild-type mice. These findings
suggest a role for polymorphic CYP2D6 in the pharmacology
and toxicology of harmine and harmaline.
 
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