effects of neuroprotective antioxidents on the drug high

[Neuroprotection]

I know that many drugs such as cocaine, amphetamine, mdma and to a lesser extent strong opioids can be neurotoxic, via inducing oxidative stress. This contributes to loss of serotonin and dopamine transporters and receptor down regulation, damage or desensitisation. Therefore, heavy drug users, or even occational users may, after a period of time find themselves perminantly unable to experience the same uforia they had the first time they used the drugs. Many people use antioxidents to try and negate some of the damage, although a lot of the antioxidents e.g. vitamin c are not well absorbed into the brain. I would like to know, from user experiences, and scientific studies if available, weather antioxidents capable of suppressing free radical formation or protecting cellular components can affect the uforic qualities of a drug. That is do they amplify or reduce the pleasureable aspects.

 

[T. Calderone]

Homeless ----- > NPD

 

[Cotcha Yankinov]

Hi there, Vitamin C in particular doesn't last very long so it should be taken multiple times before and after and in lower dosages to avoid gastro-intestinal side effects from it being very acidic, but because it is acidic it might decrease the absorption of MDMA ever so slightly but I don't think anyone has ever noticed this though so I wouldn't worry about it vitamin C is a good one. 500mg 3 times a day for a little while. Another good one is Vitamin E because its fat soluble, higher brain concentrations if I remember correctly.. 100 iu is okay a day. Alpha-Lipoic acid is good, 1000mg a day would be just fine. Coenzyme q10 is good for your mitochondria and is another anti-oxidant, 100 mg is fine. On the recovery in the days after something like MDMA I would take 5-HTP to help replenish serotonin, maybe 100mg. (I wouldn't take 5-HTP as a pre-load but only as a post-load) and then could take L-Tyrosine and L-Taurine for recovery from something like meth. but the other antioxidants are for starting 3 days before or so (the fat soluble ones anyways) and can take them during the roll/comedown whatever too. Drink lotsa water. But no anti-oxidants won't diminish your experience at all but probably won't enhance it either, although maybe less of a hangover and certainly less damage to brain cells, though expect damage with long term use regardless of anti-oxidant use. So to take everyday for a month or something dosages like Vitamin C 500mg 2 times a day, vitamin E 100 iu every day and alphalipoic acid 1000mg a day and then Coenzyme q10 100mg a day.

On the subject of MDMA one of the major theories of toxicity is that after MDMA depletes serotonin the serotonin reuptake transporter transports dopamine into the serotonin cell, then when dopamine is metabolized there it creates the reactive oxygen species that damage the cell. One theory that there are some studies behind for counter-acting this toxicity is to take a little SSRI like fluoxetine on the comedown, this will inhibit the serotonin reuptake transporters and stop them from being able to carry dopamine into the serotonin cell. But pre-loading with an SSRI would prevent you from tripping. Goodluck, any questions welcome.

 

[aced126]

Didn't someone on NPD mention that the MDMA neurotoxicity hypothesis mentioned above has been proven false using mephedrone? Are there any studies showing administration of SSRI after MDMA reduces neurotoxicity. I thought researchers gauged neurotoxicity using SSRIs itself (ratio of initial paroxetine to post MDMA paroxetine binding sites)?

 

[Cotcha Yankinov]

There are some studies showing fluoxentine might help, won't prevent all of the neurotoxicity though because the damage occurs soon after and you can't pre-load with Prozac without killing the trip and potato. http://www.ncbi.nlm.nih.gov/pubmed/19682588 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1572928/ http://jnumedmtg.snmjournals.org/cgi/content/meeting_abstract/49/MeetingAbstracts_1/207P and heres on citalopram http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347712/ So they might help on they tail end of a trip but honestly majorly only if its an overdose/abuse type scenario. Also MDMA can't get into the neurons that well after a Prozac dose because Prozac has higher affinity for the SERT than MDMA.

There are a couple different pieces of evidence of dopamine being behind the 5-HT degeneration, I haven't looked much into the matter of mephedrone and might be out of touch but I wouldn't count this theory of catecholamine breakdown in the serotonin neuron out. I do believe that SSRI's (specifically Prozac with a high affinity for SERT) attenuate the toxicity even when given 6 hours after MDMA. And I should mention at this point that it might be a metabolite of MDMA or MDMA itself that is causing the damage in the serotonin axons, and regardless of what it is, its probably getting in through the SERTS and a SERT inhibitor will protect against this damage Though drug abuse will always have consequences.

I would be wary of making an assumption about MDMA with research related to cathinones, but there is a lot of speculation on this subject. There was once a theory that because fenfluramine wasn't really free-radical toxic to 5-HT that MDMA wouldn't be either http://www.ncbi.nlm.nih.gov/pubmed/9222545 -"In vivo evidence for free radical involvement in the degeneration of rat brain 5-HT following administration of MDMA ('ecstasy') and p-chloroamphetamine but not the degeneration following fenfluramine."

I don't think there have been any studies that say for sure that its the dopamine being brought up into the 5-HT terminals that's causing the damage, only studies that show its possible and that methods to reduce toxicity along those lines of something be taken into the 5-HT neurons (MAO-B inhibitors/SERT inhibitors) work, and that increasing dopamine increases toxicity while taking away dopamine nullifies toxicity though that could be a temperature issue. But some of the researchers have mentioned in their papers that the 5-HT damage could be from catecholamine breakdown hence producing the ROS. The SERTs can carry dopamine and it makes sense theory-wise that when the serotonin is gone the SERTs start reuptaking dopamine and hence the axon problems associated with dopamine. You typically run out of serotonin around 3 hours but you still have plenty of dopamine left with lots of SERTs left standing around with no serotonin to transport (in the case of a more abusive dose anyways, which really are the ones we associate with toxicity).

http://thedea.org/neurotoxicity.html is a good read for someone interested in the toxicity of MDMA though.

 

[CFC]

As said most antioxidants/neuroprotectants (Vit E, C, D, selenium, niacinamide, ALA, NAC, ALC, CoQ10, glycerol, resveratrol, l-lysine, sodium butyrate, ibuprofen, omega 3 oils) seem to be fine, although I'd probably avoid taurine (and certainly melatonin) until afterwards due to GABAa activation. Regular dosed zinc (15mg BID) and curcurmin could potentially enhance the effect of some neurostimulants.