Methods to reduce cardiotoxicity

[Vastness]

Obviously cocaine is a highly toxic and dangerous drug, and the best way to mitigate the cardiotoxic effects is simply to never use it. However, given that people are going to use cocaine, and that this is a harm reduction form, what methods can be used to reduce the harmful cardiotoxic effects of cocaine?


I had a look on Pubmed for "cocaine cardiotoxicity", and will try to sum up my own findings...

Selenium diet-supplementation improves cocaine-induced myocardial oxidative stress and prevents cardiac dysfunction in rats.

... The goal of this study was to evaluate whether an enhanced antioxidant pool, induced by the administration of selenium, may prevent the myocardial dysfunction induced by cocaine. Cocaine was administered for 7 days (15 mg/kg/day, i.p.) to rats pretreated for 4 weeks with selenium (1.16 mg/L/day, p.o.). Cardiac function was evaluated by cardiac index and left ventricular (LV) fractional shortening (FS) measured by echocardiography. The redox ratio and enzymatic activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured in the LV myocardium. Cocaine administration induced a cardiac dysfunction, as evidenced by a decrease in cardiac index and LV FS as well as by an increase in LV diameters. Moreover, antioxidant markers and redox ratio were altered in rats after cocaine exposure. Selenite supplementation induced a significant limitation of cardiac index and FS alterations observed after cocaine administration. This improvement in cardiac function was associated with a redox ratio recovery while SOD and GPX activities remained unchanged. Thus, selenite reversed both the oxidative stress and the contractile dysfunction induced by cocaine administration. These results suggest a major role of oxidative stress in the cocaine-induced cardiotoxicity.

That's about it as far as I could tell in terms of actionable things...

Interestingly, there seems to be some indication that estrogen actually enhances the cardiotoxic effects - and this study finds that the emergency contraceptive, Mifepristone, reduces the cardiotoxicity in rats:

Progesterone antagonist mifepristone (RU 486) decreases cardiotoxicity of cocaine.

RU 486, a potent progesterone antagonist, was used to determine whether RU 486 blocks the enhanced cardiotoxicity of cocaine mediated by progesterone upon rat papillary muscles. Groups of nonpregnant rats were pretreated with: progesterone for 3 days (n = 12); progesterone + RU 486 for 3 days (n = 12); progesterone for 3 days + single low dose RU 486, progesterone for 3 days + single high dose RU 486, and RU 486 for 3 days (n = 6); or were untreated (n = 12). Papillary muscles from these groups were electrically paced during exposure to cocaine concentrations ranging from 10(-14) M to 10(-3) M. One group (n = 6) was pretreated with RU 486, but not exposed to cocaine. The results showed that all muscles from rats pretreated with RU 486 for 3 days were functional when exposed to cocaine concentrations one to four orders of magnitude higher than tolerated by muscles from untreated or progesterone-treated rats. As indicated by alterations in contraction response patterns, RU 486 treatment for 3 days reversed progesterone-enhanced cardiotoxicity of cocaine. Single low dose and high dose RU 486 administrations also reversed progesterone's effects upon cocaine-induced cardiotoxicity.

It is worth noting that in this study the rats exposed to cocaine were all pre-treated with progesterone, therefore it is not clear if Mifepristone administration would have any significant effect on cocaine cardiotoxicity in rats, let alone humans, without artificially elevated levels of progesterone. Additionally, it is perhaps up for debate whether messing with your hormone levels would have significant enough negative effects to outweight any potential benefits.



An indication that morphine (and hence likely other opiates) actually increases the cardiac risk of cocaine:

Effects of morphine pretreatment on cocaine cardiotoxicity in anesthetized guinea-pigs.

Cardiovascular and lethal effects of intravenous cocaine infusion were compared in guinea-pigs pretreated chronically with morphine or saline. Alzet minipumps filled with either morphine solution (30 micrograms/kg/hr for 6 days) or isotonic saline were implanted subcutaneously in animals 6 days before cocaine infusion. On the morning of the 7th day, animals were anesthetized with urethane (1000 mg/kg i.p.) and an i.v. infusion of cocaine was begun at a rate of 1.9 mg/kg/min. All animals were spontaneously breathing room air throughout the experiments. Death occurred by respiratory arrest in all animals; however, there was a significant decrease in the time to respiratory arrest in the morphine-pretreated guinea-pigs. All animals showed a gradual increase in the atrio-ventricular conduction interval (PR-interval) and in mean arterial pressure up until the time that respiration ceased. There were no disturbances in cardiac rhythm before respiratory arrest. This suggests that the predominant cardiovascular and lethal effects of cocaine in urethane-anesthetized guinea-pigs are the result of its local anesthetic (membrane stabilizing) action, and that morphine potentiates this effect of cocaine, but does not alter the pattern of cocaine toxicity.

This study, I believe, finds that the selective D1 receptor antagonist Ecopipram may have a protective effect:

Acute deleterious effects of cocaine on cardiac conduction, hemodynamics, and ventricular fibrillation threshold: effects of interaction with a selective dopamine D1 antagonist SCH 39166.

Cocaine has demonstrated cardiotoxicity that has led to sudden death by unknown mechanisms. SCH 39166, a selective dopaminergic D1-receptor antagonist, suppresses the compulsive drug-intake actions of cocaine in primates. ... SCH 39166 did not potentiate the cardiotoxic effects of cocaine. It displayed a protective trend by suppressing the arrhythmogenic effects and the hemodynamic compromise caused by cocaine.

However the Wikipedia for this substance suggests that it also suppresses the psychological effects of cocaine meaning it is unlikely to be useful as a harm reduction agent. A more recent study notes that by the 7th day of administration of Ecopipram, it no longer blocks the euphoric effects (so we can probably surmise that the cardioprotective effects are also insignificant by this point). However I think this substance is perhaps still of interest as a potential protective agent to have on hand, like cocaine's naloxone, although this may not be fast acting enough.

Another such protective agent is Cocaine Hydrolase, which seems to be an enzyme which rapidly increases the metabolism of cocaine, as I understand it Long-acting cocaine hydrolase for addiction therapy

Cocaine abuse is a world-wide public health and social problem without a US Food and Drug Administration-approved medication. An ideal anticocaine medication would accelerate cocaine metabolism, producing biologically inactive metabolites by administration of an efficient cocaine-specific exogenous enzyme. Our recent studies have led to the discovery of the desirable, highly efficient cocaine hydrolases (CocHs) that can efficiently detoxify and inactivate cocaine without affecting normal functions of the CNS. Preclinical and clinical data have demonstrated that these CocHs are safe for use in humans and are effective for accelerating cocaine metabolism. However, the actual therapeutic use of a CocH in cocaine addiction treatment is limited by its short biological half-life (e.g., 8 h or shorter in rats). Here we demonstrate a novel CocH form, a catalytic antibody analog, which is a fragment crystallizable (Fc)-fused CocH dimer (CocH-Fc) constructed by using CocH to replace the Fab region of human IgG1. The CocH-Fc not only has a high catalytic efficiency against cocaine but also, like an antibody, has a considerably longer biological half-life (e.g., ∼107 h in rats). A single dose of CocH-Fc was able to accelerate cocaine metabolism in rats even after 20 d and thus block cocaine-induced hyperactivity and toxicity for a long period. Given the general observation that the biological half-life of a protein drug is significantly longer in humans than in rodents, the CocH-Fc reported in this study could allow dosing once every 2-4 wk, or longer, for treatment of cocaine addiction in humans.

Personally I am a little concerned by the extremely long half life of this substance. As is often the case, this substance is engineered with the goal of being a long-term preventative for problem users rather than something that facilitates safer use for occasional users. Regardless, at present it is purely an interesting curiousity as I'm sure a similar substance is not going to be available in pill form anytime soon.



I didn't include any studies on alcohol, because I presumed everyone knows by this point that alcohol increases the cardiotoxicity of cocaine, but for anyone not aware, combining alcohol and cocaine is far more dangerous for your heart than either alcohol or cocaine alone!

Unfortunately it does seem that there is practically no way to mitigate these cardiotoxic effects, bar the obvious, which is take less, or none at all. At present I think it is possible I will never do cocaine again as I just don't think I can justify risking my health for such a fleeting and minor high. That said, it is a very inexplicably fun drug, especially, unfortunately, when combined with alcohol. Unlike many other substances there does not, in my view, seem to be much information regarding ways to do it safely, although actually this is likely because few ways actually exist... it is just not a safe drug.

Nonetheless I hope the above information is, at the very least, of interest to some, and I would be very interested to hear anything else significant that I have missed!

 

[Speed King]

Nice research. I still would suggest that using less or none would be best. I'm willing to look into your research. Good job. You say alcohol or cocaine by itself is better. They are still not very good for your heart.

Safe coke would be interesting.

 

[kleinerkiffer]

I think this is more suited for N&PD

 

[Nagelfar]

http://www.bluelight.org/vb/threads/804641-intralipid-effective-in-treating-severe-cardiotoxicity-in-local-anaesthetic-overdose

Intralipid rescue injection is most novel method to negate cardiotoxicity; has brought IV anesthetic overdose case back from what would otherwise be a fatal contraindication.

 

[keldor]

Good method is to use kava brew in place of alcohol. It takes the edge off, increases sociability, works on gaba and doesn't create the shitty damaging and dangerous combo. Alcohol+coke=no no kava+coke= woopwoop. Honestly SWIM likes the effects of the combo better its more euphoric and it kills the coke anxiety better than alcohol in SWIMS opinion. Plus since we are talking cardio toxicity, kava increases oxidation in the brain and is a great herb for preventing and or lower your risk of strokes. Also SWIM trys to have a ginger brew to drink while blowin down. SWIM is talking about REAL ginger ale/brew all natural with fresh ginger root ground up in it. Ginger is great for your cardiovascular system. SWIM gets a kind that has 26 grams of fresh ginger root in a bottle or the other has 39 grams. Its called reeds ginger brew you can get it at most grocery stores. Anyway thats my advice on lowering the cardio toxicity effects of cocaine. Also just taking a few jogs every week and eating healthy can make a big difference.

 

[CFC]

I wouldn't recommend using RU-486/mifepristone as a male, it's really quite unpleasant.

Typical free-radical scavengers, metabolic assists (eg ATP production), and membrane stabilisers like you may typically use for amphetamines would also likely help with cocaine: so NAC, taurine, phosphatidylserine, nicotinamide, Vit E, sodium butyrate, melatonin etc.

Low-dose aspirin may offset the coagulative effect (by suppressing thromboxanes). COX inhibitors can also attenuate some of the acute myocardial inflammatory effects.

L-type calcium channel blockers (like verapamil) should also counteract the increase in L-type Ca2+ channel current, thus averting the common risk of arrhythmia. They may also dampen the desired stimulatory effects of cocaine a little though.