Help! Question about Mescaline + Medication interactions.

[Didgital]

Ok, so I know a lot about drugs, but mainly psychoactive ones and i suppose a few medications NOT to take. However an associate of mine would like to try mescaline, but they are on quite the list of meds.
I figured I'd get a better answer here, but I'll also do a bit of my own research. I obviously told her no medication is better, but mescaline is generally regarded as safe.

Are any of these drugs an absolute no no to take with mescaline?

Pristique/Desvenlaflaxine - an SNRI. ai says there is no inherent dangerous interaction but could increase the possibility of serotonin syndrome.
Lyrica/Pregabalin - a gabapentanoid - I assume this wouldn't cause any dangerous interactions but plz tell me.
Hydroxizine - an antihistamine
Tizandine - muscle relaxer
Ketotofin - antihistamine and mast cell stabilizer
Pantoprozole - Proton pump inhibitor
Ceterizine - antihistamine
Spyrolactone - potassium-sparing diuretic and anti-androgen prescription medication

Also a few hormones, estrogen and one other I forget.

Now that I've written this all out and done just basic research I feel like I need to tell her she should lay off the SNRI especially and probably the others.
She also expressed interest in LSD so.. I'm curious about interactions with that as well.

I WANT to tell her she should stop taking all these meds just for her own health, but she's convinced she needs them

 

[iom]

What bothers me the most about the drugs you posted is the ketotofin, not so much because of a possible interaction with mescaline but because of what the ketotofin may be prescribed for. If this associate of yours has MCAS, then she is likely prone to hypersensitivities and unusual reactions upon exposure to a wide variety of substances---foods, drugs, even scents. For example, the chances of serotonin syndrome (SS) from desvelafaxine combined with mescaline are likely to be very low normally, but MCAS is associated with a higher propensity for SS, possibly due to the serotonin dumping action of mast cells themselves.

As far as just the drugs go, the more likely problematic interaction is that the SNRI will mute or block the effects of the mescaline. Higher doses may be needed to achieve effects, and the effects may not be qualitatively the same as without the SSRI/SNRI. Unfortunately, skipping velafaxine doses is not likely to help, assuming the mechanism for the blocked effects is chronic 5-HT receptor downregulation. I also am not comfortable suggesting people on SSRIs/SNRIs ever skip doses because for some people this can trigger a crisis, and again people with MCAS are probably more likely to be sensitive to these kinds of disruptions.

I definitely would not advise anyone to cease taking these drugs without understanding what they are prescribed for and researching the propensity of each to cause withdraw syndromes. In particular, I know that both desvenlafaxine and pregabalin can cause debilitating withdrawl syndromes in some people who may need to taper over a period of months or even years to avoid severe symptoms. SSRI/SNRIs notorious for having hellish and protracted withdraws, and venlafaxine (which metabolizes to desvenlafaxine) has a reputation for being among the worst in this regard.

My approach in a person like this would be to start very small and titrate up over the course of multiple sessions. For a typical person on this list of drugs, I'd suggest starting at a threshold dose like 30 mg. However for someone with MCAS, I'd be inclined to start much smaller still---maybe an allergy test at 1 mg followed by something like 5-10 mg. Before doing any of this, I would have an extensive discussion with the person about their health history and set realistic expectations. Most people with MCAS already have experience with hypersensitivity reactions, but it's good to establish the possibilty as well as the more probable outcome that even full doses won't work due to the SSRI/SNRI.

Lastly, in case it wasn't obvious, a person who presents and identifies as a woman and is taking hormones including estrogen along with an androgen blocker is probably going to be very resistant to if not offended by the suggestion of giving up those drugs.

I hope this helps and only wish I knew how to do more for people who have a history of taking SSRI/SNRIs because IMO many of these people probably could have been better served with psychedelics instead.

 

[Allylbenzene]

Are any of these drugs an absolute no no to take with mescaline?
...
Also a few hormones, estrogen and one other I forget.
...
Hydroxizine - an antihistamine

The Hydroxyzine aldehyde intermediate might help potentiate mescaline. If that hormone you forgot is progesterone that'll help potentiate mescaline due to its inhibitory effect on ALDH.

Hydroxizine - an antihistamine
Ketotofin - antihistamine and mast cell stabilizer
Ceterizine - antihistamine

Looks like mescaline will affect histamine metabolism:

https://doi.org/10.1351/pac200173091393

She also expressed interest in LSD so.. I'm curious about interactions with that as well.
...
Desvenlaflaxine - an SNRI
Pantoprozole - Proton pump inhibitor

LSD [has] a strong potential to inhibit CYP2D6, which is highly polymorphic and therefore implicated in great toxicological interindividual variability. CYP3A4 which is involved in the metabolism of many drugs and food is also greatly inhibited by LSD and mescaline. (source)

The mechanism by which venlafaxine and desvenlafaxine cause liver injury is not known. Venlafaxine and desvenlafaxine are metabolized by the liver, mainly via the cytochrome P450 system (predominantly CYP2D6), and hepatotoxicity may be mediated by toxic intermediates of their metabolism. Both agents can also result in significant drug-drug interactions.

Pantoprazole is...metabolized by cytochrome P450 enzymes CYP2C19 and CYP3A4. (source)

 

[realgar]

Are any of these drugs an absolute no no to take with mescaline?

Pristique/Desvenlaflaxine - an SNRI. ai says there is no inherent dangerous interaction but could increase the possibility of serotonin syndrome.
Lyrica/Pregabalin - a gabapentanoid - I assume this wouldn't cause any dangerous interactions but plz tell me.
Hydroxizine - an antihistamine
Tizandine - muscle relaxer
Ketotofin - antihistamine and mast cell stabilizer
Pantoprozole - Proton pump inhibitor
Ceterizine - antihistamine
Spyrolactone - potassium-sparing diuretic and anti-androgen prescription medication

Hydroxyzine (IC₅₀ 170 nM) and Ketotifen (K_i 17-39 nM) are antagonists of 5-HT_2A receptors. Therefore, they can affect the trip or even act as trip killers.