CYP2D6
Cytochrome P450 2D6 is an enzyme that in humans is encoded by the CYP2D6 gene and a member of the cytochrome P450 mixed-function oxidase system.It's one of the most important enzymes involved in the metabolism of xenobiotics in the body. In particular, CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, in a process referred to as O-demethylation.
CYP2D6 shows the largest phenotypical variability among the CYPs, largely due to genetic polymorphism.
There are 4 types:
poor metabolizer – little or no CYP2D6 function (those people won't feel much from codeine, as codeine is a prodrug and needs to be metabolized into morphine)
intermediate metabolizers – metabolize drugs at a rate somewhere between the poor and extensive metabolizers
extensive metabolizer – normal CYP2D6 function
ultrarapid metabolizer – multiple copies of the CYP2D6 gene are expressed, and therefore greater-than-normal CYP2D6 function
Warnings:
poor metabolizer -> Don't take Dextromethorphan, as even normal therapeutical doses can make you trip for hours or even days, because you don't metabolize DXM well. This could potentially be lethal
ultrarapid metabolizer -> Don't take codeine, as you will metabolise codeine rapidly into morphine, thus increasing the risk of an overdose
Drugs that are metabilized by CYP2D6:
All tricyclic antidepressants, e.g.
imipramine, amitriptyline
Most SSRIs , e.g.
fluoxetine, paroxetine, fluvoxamine
venlafaxine
duloxetine
mianserin
mirtazapine
opioids
codeine
tramadol
O-desmethyltramadol
N-desmethyltramadol
oxycodone
hydrocodone
tapentadol
antipsychotics, e.g.
haloperidol
risperidone
perphenazine
thioridazine
zuclopenthixol
iloperidone
aripiprazole
chlorpromazine
levomepromazine
remoxipride
minaprine
tamoxifen
beta-blockers
metoprolol
timolol
alprenolol
carvedilol
bufuralol
nebivolol
propranolol
debrisoquine
Class I antiarrhythmics
flecainide
propafenone
encainide
mexiletine
lidocaine
sparteine
ondansetron
donepezil
phenformin
tropisetron
stimulants
amphetamine
methoxyamphetamine
dextromethamphetamine
atomoxetine
chlorphenamine
dexfenfluramine
dextromethorphan
metoclopramide
perhexiline
phenacetin
promethazine
Drugs that inhibit CYP2D6 (this will result in higher and longer blood concentration of the drugs mentioned above, this could lead to increased side effects and could even be lethal or to no effects at all):
White grapefruit juice
Strong
Certain SSRIs
fluoxetine
paroxetine
bupropion
quinidine
cinacalcet
ritonavir
Moderate
sertraline
duloxetine
terbinafine
Weak
amiodarone
buprenorphine
cimetidine
citalopram
escitalopram
Unspecified potency
antipsychotics
haloperidol
perphenazine
thioridazine
zuclopenthixol
risperidone
chlorpromazine
hyperforin (St. Johns Wort)
antihistamines
promethazine
chlorphenamine
diphenhydramine
hydroxyzine
tripelennamine
clemastine
celecoxib
clomipramine
cocaine
doxorubicin
metoclopramide
methadone
moclobemide
doxepin
halofantrine
levomepromazine
mibefradil
midodrine
ticlopidine
cannabidiol
Inducers of CYP2D6:
Strong
glutethimide
Unspecified potency
dexamethasone
rifampicin
From Wikipedia
Done some 3-mmc , friday till sunday, this is my normal weekendroutine for me in 2021.
- aprox. 2-2.5 grams, not an insane ammount for me (125kg) + the habutation from continous weekly use.
Also tried aprox. 0.4gr. 3-cmc ;never did this cathinone before and will not do it again since it was almost unnoticable.
Saturdaynight 1mg etizolam and a beer to get a few hours sleep.
Sunday, when the 3-mmc bag was empty in the afternoon, I ate a big, healthy meal and took some etizolam so i dont feel the anxiety from the cathinone craving.
Also eat during my Cath-binge sessions; mostly fruits, berry's , mueslibars, banana's, soup, yogurt..., and take my daily omega's and antioxidants ,and magnesium.
Before i went to bed another 0.5mg eti and 125ug Flunitrazolam , gave my nose a good flush with my Rhino Horn and salt water, and a normal dose (1x pump per nostril) nasal spray and whent to bed.
Monday the usual mild hangover, (mostly from not enough sleep and too mutch cathinone) my usual clogged nose (ROA is 75% oral and 25% nasal, but sometimes more nasal than oral) cold feet that whent away after taking some L-arginin/citrullin.
Took 0.5mg eti , some L-Tyrosine hoping this helps with the dopamine depletion, some Taurine,curcuma and other suplements that help the liverfunction, some N.A.C. and did my job kinda okay-ish , sometimes hiding from my co-workers because of the stealty silent, but very noticable N.A.C. farts.
Just before I went to work applied 2x2 nasal sprays (double the maximum daily dose , because of the exessive nasal ROA this weekend) 'dexametasone nasal spray' (UNSPECIFIED POTENCY as an inductor of CYP2D6 says the list)
That night before bedtime, took some L-trypthofan and also 1mg eti. (tuesday till at least saturday normally no more benzo for me) and again, took some dexametasone nasal spray. and a puff from my RELVAR 92/22mcg fluticasone furoate/vilanterol inhaler (I don't use the inhaler when on cathinones/stims)
Tuesday morning felt like shit when i woke up...very weak, shivers, hot/ cold, anxiety, depersonalisation (never had that before!) took another double dose nasal spray (so I don't sound like a chronic cocaine user / 3-mmc snorter when I talk to co-workers) and had my weekdays puff from the inhaler and felt worse and worse.... massive panic attack. what is happening !! sweating, stiff muscles...felt sooo uncomfortable, reminded me of my once but never again little heroin adventure, 20 years ago...
Need to work at 15.00 , Took some eti, with no effect , and some more, and more... (5-6/7 half 1mg pellets within a few hours) and finally 2.5mg diclazepam because it felt like i was going trough a bad state of withdrawal.
First time I had this ! And I need to go to my job. can't call in sick. Felt like shit for the most part of my 8 hour work day, but the eti and diclazepam helped me get trough, but it was a struggle. Back home still shivers. hot / cold etc. again 1mg eti (normally no benzo's after monday) no effect, another one, and another one, this time with a beer glass full of wodka. finally that helped. no I am feeling okay-ish...
In retrospect, could it be that I had a mild case of serotonin syndrome? Maybe the added 3-cmc was the tipping point and my - more than usual - nasal ROA this weekend, which indirectly led to the overkill-use dexamethasone spray ?