Caapi and Propranolol (beta-blocker) interactions

[MuteUSO]

Hey there,

a friend who is planning to indulge in a caapi only experience is also taking a daily low dose of Propranolol. Propranolol is a beta-blocker (vasoconstrictor) which lowers blood pressure and is therefore often taken by patients to prevent migraines.

She is going to start off experimenting on a very low dose caapi only (like 20g or so). Any ideas of whether this combination may cause any problems? Thanks so much for any pointers!

 

[downwardsfromzero]

afaik, propranolol works by reducing the contractile strength of the heart muscle. The main thing to be aware of is the possibility of decreased metabolic clearance if caapi alkaloids share any metabolic pathways with propranolol.

Good info here: Propranolol: Uses, Interactions, Mechanism of Action | DrugBank Online - but harmine (as is commonly the case) is not listed. Interactions with licorice suggest there may be a CYP overlap going on. Cross reference to licorice CYP450 interactions: Identification of Key Licorice Constituents Which Interact with Cytochrome P450: Evaluation by LC/MS/MS Cocktail Assay and Metabolic Profiling and caapi pharmacology: Ayahuasca: Psychological and Physiologic Effects, Pharmacology and 
Potential Uses in Addiction and Mental Illness

There seems to be a small possibility that the level and duration of the effects of both the caapi and the propranolol could be increased, although I would suggest digging into the literature, specifically regarding the metabolism of both propranolol and the caapi alkaloids rather deeper for a more definitive answer. If you can, consult a sympathetic health professional (_Trip_?)

 

[_Trip_]

For memory there has been studies on animals that found harmala reduced BP and HR IIRC, but again that was a animal study. DMT in humans seems to have a opposite effect so its kind of a nice balance? But i don't recall personally reading any cardiovascular studies on harmala in humans.

In general terms beta-blockers target andrenergic receptors (b1 & b2 atagonist) on the heart while harmala primary inhibits monoamine oxidase in the brain (actually per-synapse on the neurons) resulting in more available neurotransmitters. Keep in mind harmala is technically a RIMA (reversible MAOI) therefore holds a lower risk for interactions as you would expect from a standard MAOI.

However that doesn't mean their different MOA can't contribute to compounding certain effects. Both compounds do actually bind to some of the same receptors (of course with different effects). However it should be noted not all of harmine's affinity for particular sites (usually the main harmala compound in caapi) has been mapped out in terms of receptor binding sites. So its hard to speculate much beyond that. I do recall something about propanalol stimulating a small amount noradrenaline which then combined with ther effect of a RIMA (harmine) would cause more to be available. Noradrenaline funnily enough is used to treat low BP so I would think this release is minimal.

Propanalol is a lipophilic beta-blocker meaning it crosses the blood brain barrier easily, of-course harmine does too.
I would believe a interaction of the compounds holds a minimal risk as they still do primary target very different sites with different effects. I've known (and I'm sure many nexians also know) people who take beta blockers before trips (including aya) with no negative or noticeable effects.
The potential issue is if your friend is on it for BP then i would conclude they are taking a much higher dose of propanalol than someone would for say for anxiety. Meaning there could be a slight increase in potential BP lowering effects (if animal studies are anything to go by). This would almost be a non issue for someone taking a lower dose. I also can't imagine harmine causing a "amplifying effect" as it does with other drugs, regardless propanalol overdose requires a very high dose.

If your friend is worried then perhaps your friend could switch to atentalol or another hydrophilic betablocker just to be extra cautious. Hydrophilic beta blockers don't cross the blood brain barrier. And I've seen no evidence that harmine effects contractility of the heart. Meaning this would be the safest option if you were worried.

If I hand more time at the moment I'd try to be more thorough with a reply. Keep in mind I'm not a pharmacist.