ACE Inhibitors attenuate subjective, cardiac, and sympathetic effects of METH

[Jabberwocky]

Apparently the renin-angiotensin-aldosterone system is implicated with respect to the effects of methamphetamine.

ACE Inhibitors and AT(2)1-R receptor blockers attenuate the subjective and sympathomimetic effects of methamphetamine.

Subjective and Cardiovascular Effects of Intravenous Methamphetamine during Perindopril Maintenance: A Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study

Our pilot study suggested that the angiotensin-converting enzyme inhibitor perindopril might reduce some subjective effects produced by i.v. methamphetamine. We characterized the impact of a wider range of perindopril doses on methamphetamine-induced ...

www.ncbi.nlm.nih.gov

Of interest is that Vitamin C inhibits ACE2, and down regulates ACE expression. Perhaps that is the reason that vitamin c seemingly attenuates the effects of amphetamine and methamphetamine.

It also indicates that people on ACE inhibitors like Lisinopril, perindopril, quinapril, etc likely have a blunted response to amphetamine/methamphetamine.

The literature states that the effects of methamphetamine are mainly mediated through norepinephrine. Blocking ACE attenuates the adrenergic effects of norpinephrine and epinephrine.

For people that are experiencing uncomfortable locomotor activity, taking moderate doses of Ace inhibitors will likely help, without risking side effects from atypical antipsychotics.

 

[SpiralusSancti]

I thought vitamin C speeds up excretion of amphetamine and therefore speeding up comedown and time until being able to sleep and that’s more or less my experience but I never really tried it before until after peak so who knows.

 

[Jabberwocky]

I thought vitamin C speeds up excretion of amphetamine and therefore speeding up comedown and time until being able to sleep and that’s more or less my experience but I never really tried it before until after peak so who knows.

No. Vitamin c does not acidify urine unless you take tens of grams. So it doesn't appreciably increase excretion.

It does however, deaminate amphetamine, and likely methamphetamine.

"Ascorbic acid may play a rôle in the inactivation of amphetamine. By means of in vitro experiments it was shown that the drug was deaminated in the presence of ascorbic acid and oxygen, buffered at pH 7.0."

THE ACTION OF VITAMIN C AND PHENOL OXIDASE IN THE INACTIVATION OF BETA PHENYLISOPROPYLAMINE (AMPHETAMINE)

That amphetamine is capable of undergoing inactivation in the body and the means whereby this may be accomplished have been described. Through the intermediation of a monohydric phenolic compound ( p -cresol) phenol oxidase has been shown to be capable of activating the deamination of beta...

jpet.aspetjournals.org

At high doses it acts as a dopamine receptor antagonist.

It also has some sort of action at the adrenergic receptors as well, but that's unclear.

 

[Jabberwocky]

I just found a citation that said the dopamine transporter clears dopamine most efficiently and at the highest rates when it is hyperpolarized.

Supra-physiological concentrations of ascorbate as AA and DHA may hyperpolarize the DAT and rescue function that had been inhibited by methamphetamine, thereby increasing clearance of dopamine as well as reducing the amount of dopamine available to be converted to norepinephrine.

This would reduce the sympathomimetic effects normally seen after the initial high from methamphetamine passes.

This is what individuals that take mega doses of vitamin c report, a major decrease in locomotor activity and other sympathomimetic effects of methamphetamine than expected.

Other references that I've posted in different threads identify that dopamine levels are rescued (the dopamine depletion normally seen post methamphetamine use is attenuated or prevented) and dopamine receptor density as well as transporter density is also preserved when large doses of vitamin c is taken prior to during methamphetamine use.