Stimulants Coronary vasospasm from alpha-1 receptors. UPDATE: Solved

[amorphousOne]

Background: After 4 months of very productive stim usage (consistent 4x10mg adderall/day), I experienced sudden serious chest pain and had to go to the ER. They detected nothing (EKG, bloods, stress echo). These symptoms have persisted, and I am unable to use stimulants at the same effective dosage. Anything over the 2.5mg d-amph or equivalent and I get variant (prinzmetal's) angina. I realize this is a unique reaction specific to my body, but I can't be the only one. Hoping to find someone who's been down the same path and found a solution.

Stimulants/stimulant-analogs tried:
Racemic amph, adderall, dexedrine, methylphenidate, focalin, phenylpriacetam, ephedrine - all very effective. All caused angina.
strattera, reboxetine - made me more robotic and concrete, but caused some lethargy. Both caused angina.
Modafinil, amfonelic acid, caffeine - no help. Produced wakefulness and creativity, but without the focus that comes from NE.
guanfacine/clonidine - no help. Lethargy, reduced motivation.
The popular "nootropics" like piracetam, herbal stuff, etc - incomparable to proper stimulants

Drugs to alleviate symptoms tried:
Calcium channel blockers, nicorandil, alpha blockers, various benzos, alcohol - prevent angina to various degrees, but their effects counter the motivational aspects of stimulants that I find useful, both in studies and in my experience (ex: though prazosin improves spatial working memory, it blocks stimulant-induced release of DA in the striatum by interfering with the a1b adrenoreceptor).
Nitrates, Beta-blockers, Levosalbutamol, L-citrulline, guanadrel, ARB's, HCTZ, and a few other BP meds - Ineffective, but I found they also don't interfere mental effects of stimulants (except for the lipid-solube beta blockers). I bet the nitrates would work at a high enough dose, but at just 10mg of isosorbide dinitrate I get a headache.
Exercise or vigorous movement is the only thing that alleviates stim symptoms without interfering with mental effects. In the early days of experimentation I had to go to the ER a few more times when I felt the chest pain coming on. Now I can just start shadow boxing or stationary biking and the pain subsides. Even opening and closing my hand quickly and forcefully slowly attenuates my chest pain during an episode, but if I stop it returns. Now I'm asking myself, by what mechanism that I'm unaware of does physical exertion attenuate coronary alpha-1 vasoconstriction?
The smoking gun: phenylephrine - Recently I tried some sudafed PE after my mom recommended it for my cold. After 40 mins it caused the exact same chest pain that I resolved with prompt exercise as well as temazepam and l-citrulline. Given phenylephrine's pharmacology, clearly the problem lies with local(peripheral) alpha-1 adrenergic stimulation in the coronary artery.

Unfortunately, I've found that even those drugs that specifically counter the effects of alpha-1 receptors and possess little blood brain barrier permeability (alfuzosin, amlodipine) still cancel out the central effects of stimulants at doses necessary to prevent angina.


TLDR: Does anyone know how to prevent stimulant-induced alpha-1 coronary vasoconstriction? The only real clue I've found is everything that blocks this also blocks the mental effects of stimulants except vigorous exercise.

An enormous thanks to anyone who can help me crack this.

 

[kleinerkiffer]

On top of my head I could think of Molsidomin (non-enzymatic NO release), Riociguat (stimulation of the sGC), Minoxidil (potassium-channel-opener), maybe Selexipaq (IP-receptor agonisz) or a PDE-inhibitor. But all those drugs come with side effects and don't just prevent alpha-1 coronary vasoconstriction
You're better off just not taking any stimulants
And don't forget that prinzmetal angina increases the risk of myocardial infarction

Edit: sometimes SNRIs, TCAs or a MAO-B inhibitor is used off-label for ADHD, at least in germany

Edit2: iirc beta-blocker are contraindicated in prinzmetal angina

 

[CFC]

Nice to see you've been working hard on the "cake and eat it" conundrum ;-)

You don't mention having tried any ACE inhibitors (bradykinin) or PDE5 inhibitors, though I would imagine you must have given everything else you've tried?

Also, most B-Blockers largely block positive subjective effects for me, but since they don't for you, have you tried specifically nebivolol?

I can't honestly remember all I've tried over the years, but NOx boosting supplements tend to have some effect, as does 30-40g raw cacao.

 

[amorphousOne]

Will def look into Riociguat and Selexipaq. I had some experiences with minox. I'd guess Molsidomin would be similar to nitrates, but correct me if I'm wrong there.

I've tried SNRI's as well as selegiline & rasagiline. SNRI's gave me the same old angina, and mentally felt like the other NE-selective drugs. Sele/rasa felt more like modafinil or caffeine - motivation but little effect on focus.

I hear you, but I'm pretty careful with my trials now, and after finding that I can reliably stop any angina with immediate physical activity, I really don't have any crises anymore.

 

[kleinerkiffer]

Both riociguat and selexipaq are only indicated for pulmonary hypertension afaik, so don't get your hopes up too much

Yes, molsidom should be similar to nitrates, but imo may be worth a shot as iirc nitrates work more on the veins while molsidomin isn't selective for either veins or arteries

Edit: molsidomin has the same selectivity for veins than nitrates

 

[amorphousOne]

Lol CFC you turned up in a google search earlier. You got some really interesting posts. Also saw you had the same problems as me with the beta-blockers, CCB's, etc blunting stims

So ACEI/ARBs and PDE5 & PDE3 inhibitors did nothing for my angina unfortunately

I found nebivolol actually gives me a bit of relief on the scale of high-dose l-citrulline - which is very slight, but unfortunately blunts the effects of stims like the other beta blockers. Just found this graph at the bottom of this study that shows how important beta receptors are in the effect of stims https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965894/

Currently looking into Fasudil

 

[kleinerkiffer]

Here are another few vasodilatants I found in one of my lectures:
Iloprost and epoprostenol
Bosentan and ambrisentan

 

[CFC]

Yeah interesting chart in the paper. Studies on drug addicts have shown conflicting results in terms of beta blockers (mostly propranolol) on positive subjective parameters of amps. Several studies suggest no ability to attenuate high or pleasurable effect. You also get folks on here also claiming no negative effect. But for me all types of B-blockers dull things, while rebound (ie cessation from long term use) intensifies effects substantially. I've meant to try amps with something like ketotifen to see what happens.

Anyway, other suggestions off my list of meds to try include moxonidine (ie imidazoline) and agmatine. GABA might also have some useful peripheral effect (ie sipped throughout the day in a drink).

 

[Phobos]

Have you tried Huperzine A?
It is an acetylcholinesterase inhibitor and mild NMDA antagonist.
Available as a food supplement, no prescription needed.
Extremely effective in my experience.
Has the added benefit of giving a mild boost to GH release as the increase in acetylcholine will cause a reduction in the release of somatostatin (a hormone that stops GH production).
Some research suggests it does also boost BNDF production.