Non-neurotoxic drugs.

[arohydro]

Okay, so there is plenty of discussion on the neurotoxic effects of some drugs. Dopaminergic damage from amphetamines, (some) NMDA receptor antagonists causing vacuoles, etc.

What about those drugs that are not neurotoxic? LSD for instance. Would anyone mind compiling a list of these drugs? I am insatiably curious. I have been researching drugs for quite some time and am now looking for something else to read up on. Plus, I wouldn't mind trying something new.

By the way, why is neurotoxic preferred over excitotoxic? I was under the impression that neurotoxins did not necessarily destroy neurons, but merely referred to toxins that had some effect on these cells. In which cases is either more appropriate than the other?

Thanks!

 

[Sentience]

LSD, Mescaline, Opiates, Cannabis....lots of drugs are not neurotoxic.

Excitotoxins can be just as bad if not worse, depending on what they excite the cells into doing.

 

[arohydro]

LSD, Mescaline, Opiates, Cannabis....lots of drugs are not neurotoxic.

Excitotoxins can be just as bad if not worse, depending on what they excite the cells into doing.

Opiates... with the exception of morphine and those and metabolize into morphine? I was under the impression that it had neurotoxic potential.

 

[Sentience]

People can end up taking massive amounts of opiates and be fine as long as they have tolerance. I dont know if there is a slight toxic effect or not but it must not be very high if people can end up taking hundreds of times their starting recreational dose and be fine as long as they have tolerance.

 

[Coolio]

Isn't methadone neurotoxic as well?

I think this thread is backwards though. Very, very few drugs are neurotoxic. We should list those and cite sources.

 

[starpaws]

5,6-Methylenedioxy-2-aminoindane - MDAI

but not the most particularly interesting substance..

 

[Coolio]

Is MDAI demonstrated to be non-neurotoxic, or just not to exert the same type of neurotoxicity as seen with methamphetamine and MDMA?

 

[skoat]

Benzodiazipines in regards to short-term use are not neurotoxic, I believe.

 

[arohydro]

Isn't methadone neurotoxic as well?

I think this thread is backwards though. Very, very few drugs are neurotoxic. We should list those and cite sources.

I was unaware of methadone's potential neurotoxicity. Interesting. Anyone have a source for this?

I wouldn't say it's backwards; for my specific intentions it's best to list those known not to be neurotoxic in any regard. I can't speculate as to whether or not drug A has been considered in the 'list of neurotoxicity'.

5,6-Methylenedioxy-2-aminoindane - MDAI

but not the most particularly interesting substance..

Really? Shown to lack any neurotoxicity whatsoever?

Benzodiazipines in regards to short-term use are not neurotoxic, I believe.

Aye. Benzos seem fairly safe in the short-term. Long-term use has been shown to induce a cognitive deficit, though whether or not that is permanent I can't conclude. It could simply be another case of neural adaptation.

 

[dread]

Is MDAI demonstrated to be non-neurotoxic, or just not to exert the same type of neurotoxicity as seen with methamphetamine and MDMA?

MDAI is non neurotoxic, at least according to Nichols' studies. It is even non-neurotoxic when co-administered with certain DRI:s:

http://www.ncbi.nlm.nih.gov/pubmed/1726189

 

[Jamshyd]

I believe Gabapentin is rather benign.

Also Nicotine.

 

[shibireru]

With the psychedelic hallucinogens doesn't there exist the potential for excitotoxicity?

Opioids can produce some mild damage in withdrawal, I would think. (Are we not talking about damage due to long-term use and subsequent withdrawal?) Opioids can produce alterations in salivary cortisol levels, usually in the negative direction. Upon withdrawal, you could almost certainly expect to see increases, if only by way of stress, in glucocorticoid levels, which are, I needn't say, not so very good for the brain. I wouldn't be surprised if there were excitotoxicity either.

Chronic marijuana (no pun intended) use can give rise to attrition of hippocampal density, if the studies on that subject are credible.

Basically, the brain seems a finicky, fragile piece of shit that can hardly withstand any stimulus at all without saying "Oh, dear, it's time to trigger apoptosis again".

BTW, it seems so very maladaptive that both excessive activity and excessive quiescence should both cause apoptosis. (E.G. NMDA agonists and NMDA antagonists)

 

[MurphyClox]

The question is quite imprecise. First, one needs to define the term "neurotoxicity". Maybe we just keep it with ICON's definition, which states that neurotoxicity is “any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical or physical agent and may result from direct or indirect actions or reflect permanent or reversible changes in the nervous system” (taken from Bilz0rs essay "Are Cannabinoids Neurotoxic?"; to be found within Bluelight's ADD).

Second thing is that neurotoxicity depends much on the dosage. I'm convinced that even the proven neurotoxin methamphetamine is benign at low dosed, single applications.

Considering the really broad possibilities for interpreting the original question, I'd say that an answer can't be given without defining some parameters first.

- Murphy

 

[arohydro]

With the psychedelic hallucinogens doesn't there exist the potential for excitotoxicity?

Opioids can produce some mild damage in withdrawal, I would think. (Are we not talking about damage due to long-term use and subsequent withdrawal?) Opioids can produce alterations in salivary cortisol levels, usually in the negative direction. Upon withdrawal, you could almost certainly expect to see increases, if only by way of stress, in glucocorticoid levels, which are, I needn't say, not so very good for the brain. I wouldn't be surprised if there were excitotoxicity either.

Chronic marijuana (no pun intended) use can give rise to attrition of hippocampal density, if the studies on that subject are credible.

Basically, the brain seems a finicky, fragile piece of shit that can hardly withstand any stimulus at all without saying "Oh, dear, it's time to trigger apoptosis again".

BTW, it seems so very maladaptive that both excessive activity and excessive quiescence should both cause apoptosis. (E.G. NMDA agonists and NMDA antagonists)

This is what I'm talking about. Quite interesting to read and leaves plenty of information for follow-up research. Thank you.

I believe Gabapentin is rather benign.

Also Nicotine.

It seems like most GABA related drugs are relatively safe.

The question is quite imprecise. First, one needs to define the term "neurotoxicity". Maybe we just keep it with ICON's definition, which states that neurotoxicity is “any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical or physical agent and may result from direct or indirect actions or reflect permanent or reversible changes in the nervous system” (taken from Bilz0rs essay "Are Cannabinoids Neurotoxic?"; to be found within Bluelight's ADD).

Second thing is that neurotoxicity depends much on the dosage. I'm convinced that even the proven neurotoxin methamphetamine is benign at low dosed, single applications.

Considering the really broad possibilities for interpreting the original question, I'd say that an answer can't be given without defining some parameters first.

- Murphy

I agree wholeheartedly! My definition is congruent with ICON's, although I would leave reversible out if it happened that the brain could not recover on its own with supplementation from household items. That is, without any medical intervention.

I'd also like to exclude any drug with the potential to cause neurotoxicity, as defined above, in any situation except in cases of extreme abuse and withdrawal.

Does that suffice, or is further clarification needed? Thanks for all the replies by the way, guys!

 

[theWorldWithin]

It seems like most GABA related drugs are relatively safe.

Not even close. Although most of the axiolytic benzos are fairly benign the same cannot be said for hypnotics which have shown definite toxicity. Not the mention that if we use the broader sense of the term as defined by ICON we could consider all GABA drugs horrifically toxic because of the maladaptive changes they cause despite most causing little physical damage or apoptosis.


Also it is difficult to define what exactly maladaptive is. How about nontoxic stimulants like methyphenidate which cause alterations to the DAT? It is not such a clear cut answer and they all have downsides and negatives on the mind in excess. However my vote for the safest choices would have to go to opiates and cannabis.

 

[oatmeel]

There's a very good paper about the potential of opiates to be neurotoxic as well as neuroprotective. The paper does not come to any definite conclusions, but assesses the potential of different opiates and different extents of use, and speculates to whether or not opiates are ultimately harmful to braincells.

http://nro.sagepub.com/cgi/content/abstract/14/6/561

Morphine: A Protective or Destructive Role in Neurons?

Morphine has received intensive research interest for a long time. However, until recently, the protective versus destructive roles of morphine in the neuronal system have not been studied. There is evidence suggesting that morphine induces apoptotic cell death in neuronal and glial cells, whereas controversial studies support a neuroprotective role for morphine. The exact mechanisms for both protective and destructive pathways are not clear and are still under investigation. Improved understanding of morphine neuroprotection and neurotoxicity will be helpful to control morphine side effects in medical applications and to identify new targets for potential therapies and prevention strategies to opioid addiction. NEUROSCIENTIST 14(6):561-570, 2008. DOI:

 

[Repulse]

Weird question. If the dosage is pushed far enough, a pretty vast array of substances are neurotoxic, but why ask? Even water is toxic, at least harmful at the right dose.

 

[oatmeel]

There's a difference between taking obscene and lethal levels of a compounds, including water, and ingesting sane, recreational or medicinal levels of a drug. Yes enough of anything will kill you, but that doesn't help the discussion very much.

It's a matter of X amount of Y opiate will do Z neurotoxic effects, to try to discern whether or not it's reasonable and/or safe to take a specific drug. There's a big difference between taking a theurapeutic dose of a drug to achieve optimial effects and taking vast quantities of potentially dangerous compounds.

I agree that assembling a list of drugs that are not "neurotoxic" might be a bit myopic, but I think it's a good basis for assembling a list of drugs that are not inherently, or realistically, neurotoxic.

 

[arohydro]

Not even close. Although most of the axiolytic benzos are fairly benign the same cannot be said for hypnotics which have shown definite toxicity. Not the mention that if we use the broader sense of the term as defined by ICON we could consider all GABA drugs horrifically toxic because of the maladaptive changes they cause despite most causing little physical damage or apoptosis.


Also it is difficult to define what exactly maladaptive is. How about nontoxic stimulants like methyphenidate which cause alterations to the DAT? It is not such a clear cut answer and they all have downsides and negatives on the mind in excess. However my vote for the safest choices would have to go to opiates and cannabis.

Interesting. These changes would abate with cessation of use, would they not? Do you know where I could read more about this?

Specifically, which hypnotics are you referring to?

There's a very good paper about the potential of opiates to be neurotoxic as well as neuroprotective. The paper does not come to any definite conclusions, but assesses the potential of different opiates and different extents of use, and speculates to whether or not opiates are ultimately harmful to braincells.

http://nro.sagepub.com/cgi/content/abstract/14/6/561

Morphine: A Protective or Destructive Role in Neurons?

Morphine has received intensive research interest for a long time. However, until recently, the protective versus destructive roles of morphine in the neuronal system have not been studied. There is evidence suggesting that morphine induces apoptotic cell death in neuronal and glial cells, whereas controversial studies support a neuroprotective role for morphine. The exact mechanisms for both protective and destructive pathways are not clear and are still under investigation. Improved understanding of morphine neuroprotection and neurotoxicity will be helpful to control morphine side effects in medical applications and to identify new targets for potential therapies and prevention strategies to opioid addiction. NEUROSCIENTIST 14(6):561-570, 2008. DOI:

Thanks for the link! I do wish that I had a subscription so that I could read the full extent of the paper, but I saved the link in case I happen to decide to do just that.

Weird question. If the dosage is pushed far enough, a pretty vast array of substances are neurotoxic, but why ask? Even water is toxic, at least harmful at the right dose.

It makes little sense to nitpick over definitions if we have a fairly clear line drawn already. There will always be SOME blurring, but as oatmeel kindly pointed out there is a keen difference between determining whether or not a recreational dose of a particular drug will have significant neurological repercussions and the potential for an electrolyte disturbance to cause harm due to an extremely excessive intake of water. I do appreciate the input, though.

There's a difference between taking obscene and lethal levels of a compounds, including water, and ingesting sane, recreational or medicinal levels of a drug. Yes enough of anything will kill you, but that doesn't help the discussion very much.

It's a matter of X amount of Y opiate will do Z neurotoxic effects, to try to discern whether or not it's reasonable and/or safe to take a specific drug. There's a big difference between taking a theurapeutic dose of a drug to achieve optimial effects and taking vast quantities of potentially dangerous compounds.

I agree that assembling a list of drugs that are not "neurotoxic" might be a bit myopic, but I think it's a good basis for assembling a list of drugs that are not inherently, or realistically, neurotoxic.

Personally, though I am obviously biased, I wouldn't even stray to label it as myopic. I don't see any basis as to why we shouldn't at least attempt to define which drugs have the least potential to do significant, quantifiable harm to neurological processes.

 

[MurphyClox]

Thanks for the link! I do wish that I had a subscription so that I could read the full extent of the paper, but I saved the link in case I happen to decide to do just that.

PM me your email adress! Full article is available. - Murphy