• N&PD Moderators: Skorpio | someguyontheinternet

Opiate anti-depressent properties

i have in mind that tramadol is more neurotoxic than most opiates. i know people that have gone through grams of it in one day claiming they never noticed any neurotoxic effects.
on the other hand there are many who got tramadol prescribed as a pain med on a regular basis and reported of a reduced ability to think afterwards.
 
^just because a drug is interfering with your cognition, that doesnt mean damage is taking place. i don't know if tramadol is neurotoxic, but your reasoning that it is neurotoxic is invalid
 
qwe: you should also accept then that your logic here is invalid -
"opiates resemble endogenous molecules so much they're effectively nontoxic..."
I mean, methamphetamine resembles dopamine/NE, but it is neurotoxic. In fact, most neurotoxins are neurotoxic because they resemble endogenous ligands enough to bind to a receptor and screw it up. So, no matter whether or not opiates are neurotoxic or not (I'm sure they aren't), your logic is just as much shite.

Also, traditional opiates do not structurally resemble the most common endogenous ligands of opioid receptors, which are peptides. They fit the pharmacophore obviously, but overall they don't look similar.
 
Even within the opioid group they don't look the same; just compare etonitazene with dimethylthiambutene - what the fuck do they have in common (or with morphine?) other than mu agonism.

Neurotoxic compouds come in many guises, but some of the most potent/severe look quite similar to the neuroreceptor eg 6-hydroxydopamine (and others not, like MPTP)
 
right, such examples are no indication for tramadols neurotoxity.
i thought i read about it in a german medical magazine some time ago but i did'nt find any valuable references for my statement when searching today.
i found one paper stating tramadol and morphine are on the same level when it comes to red neuron degeneration in rat brains.
 
izo said:
i have in mind that tramadol is more neurotoxic than most opiates. i know people that have gone through grams of it in one day claiming they never noticed any neurotoxic effects.
on the other hand there are many who got tramadol prescribed as a pain med on a regular basis and reported of a reduced ability to think afterwards.


I am seeing way much more hogwash from all sides than I am used to. Almost every statement brought up by anyone (in this thread) really opens up a can of worms, and needs several paragraphs to reconcile it. Fact is, comformationally, be it a protein or long peptide chain, in comparison to all different organic narcotics, certain shapes and electrical charges between the two must be in common in order to activate opioid receptors. Its similar to an enzyme and an active site.

On your side: tramadol has been EXTENSIVELY studied in many countries over many years over a long period of time with many millions of people taking it. From a quick reading of the literature, both skeptics and endorsers of the drug seem to agree it is very safe, albeit somewhat addictive. Tramadol is in fact a narcotic opiate, and is quite typical in so many ways. It is funny how it could have ever been classified differently. Perhaps, because it looks chemically like Effexor’s API (structurally), combined with the fact of extremely low (parent) mu agonistic potency, and also the re-uptake properties (which may be looked at in with knowledge of an Effexor type looking molecule.) Whatever the case, FDA got it all wrong. For many, tramadol is just like hydrocodone, same nod, same buzz, longer lasting, and effects due to primarily opioid activation. Worldwide, with such wide, long term usage, if there were anything out of the ordinary especially significant with regards to safety and(or) brain damage, I believe it is more likely (vs less likely) that someone, somewhere, at some time, in some country, would have reported this. There are many reasons that tramadol doesn't seem to cause MDMA like damage. And there are other reasons why, although (red neuronal) degen. has been seen, this model (link above) is the exception. There is much evidence that tramadol can be used long term, with minimal permanent effects. If someone wants me to put all the shit together, its going to be very lengthy, but from the data available, and in the spirit of correctly interpreting the studies at hand, tramadol seems to be safer than even aspirin in some ways. Tramadol may even have a built in neuro-protective effect similar to mechanisms with which PCP can protect neurons from amphetamine toxicity. Anyway, I’m not going to get anymore into it on such a crappy, jerry springer type level. VERY DISAPPOINTED with this thread  I expect much higher standards here. Even my paragraph here is one of my worst. I have been brought down.
____________________________________________________________

Tramadol - present and future

Abstract
The atypical opioid, tramadol, has recently been introduced into Australia and New Zealand. Tramadol’s efficacy in a wide range of acute and chronic pain states, its multi-formulation availability, and its low serious side-effect potential at high doses and in prolonged therapy, combine to bestow on it a user-friendly profile, for short- and long-term use in hospitals and communities. This paper reviews the following: its formulation and routes of administration; its unique enantiomeric biochemistry and metabolism; its triple mechanisms of action; its pharmacokinetics and pharmacodynamics; its analgesic efficacy compared with other opioids; the indications for its clinical use in a variety of acute and chronic (including cancer) painful states; its specific use in the elderly, in paediatric and in obstetric patients; its adverse event (including drug interaction) and safety profile; its advantages in terms of its relative lack of respiratory depression, major organ toxicity and histamine release, and dependence and abuse potential. The review looks at new uses for this drug and what can be expected in this area in the future.
 
Possibly we should slowly steer this conversation away from tramadol otherwise thats another thread down the drain devoted to FOR and AGAINST tramadol. haha. 8)

Tramadol has to be the most subjectively discussed opioid (ignoring practical discussions like "how can I get high with opioid X"). 8(
 
DadeMurphy said:
qwe: you should also accept then that your logic here is invalid -
"opiates resemble endogenous molecules so much they're effectively nontoxic..."
I mean, methamphetamine resembles dopamine/NE, but it is neurotoxic. In fact, most neurotoxins are neurotoxic because they resemble endogenous ligands enough to bind to a receptor and screw it up. So, no matter whether or not opiates are neurotoxic or not (I'm sure they aren't), your logic is just as much shite.
Also, traditional opiates do not structurally resemble the most common endogenous ligands of opioid receptors, which are peptides. They fit the pharmacophore obviously, but overall they don't look similar.
you're right, i shouldn't have said it like that
 
Reminisant B said:
Possibly we should slowly steer this conversation away from tramadol otherwise thats another thread down the drain devoted to FOR and AGAINST tramadol. haha. 8)
i think the thread is supposed to be about opioid agonism helping with depression.

bringing tramadol up changes everything because it has SNRI properties, so if tramadol helps someone's depression that doesn't prove anything in the first three pages of the debate here
 
I'm sure F&B pointed to a new antidepressent thats related to tramadol. Tramadol has 2 isomers. The M1 metabolite of one is a mu agonist, the other gets the old cathecolamine system rumbling (SNRI action).
 
The SERT activity lies in both isomers though, ie it's an intrinsic property of the molecule that cannot be 'cut out'.
 
Back on topic please....
The fact is opiates/opioids have been used for centuries as anti-depressants with much efficacy--much more so than our new ssri's and snri's. The only point that has been made against the fact that opioids could be used effectively as an ad is that they are addictive and will only make the problem worse in the long-run. Also, the fact that they cause euphoria does not negate their AD properties, as what AD have you ever known not to cause "euphoria' on some level?? That is the sole purpose--to stabalize mood and uplift one's self-esteem or state of mind. Yes, opioids have a greater abuse liability issue than the new AD's but that is not an issue if one uses them as directed and are actually looking to cure one's depression, as opposed to getting high (which is usually the case, sadly). People who are depressed tend to rather escape their "pathetic reality" than enjoy the reality as it is, and, thus, they are very likely to abuse an opioid medication, which is the main reason most don't get them for their problem. But as one person mentioned earlier in the thread, he has managed to obtain a script for oxycodone for his bi-polar disorder (? I believe that's what it was) with much success as he uses it as intended and doesn't abuse it. This is exactly what I am trying to point out--opioids have great anti-depressant properties for those who want to use them to treat their condition (if they are even truly depressed and not just causing themselves depression or going through difficult times. Opioids are great for people who have severe clinical depression, not just a depressive episode, and have tried other medications without success. It is just bullshit to say that they have no AD properties because they cause euphoria and tolerance, as all AD's commonly used today possess the same exact side-effects. The issue here, again, is those who just want opioids because they like them i.e. want to get high or are trying to escape their reality through medication rather than trying to assess their issues and solve them. Opioids should only be used in patients who will use them properly and actually benefit from them--I know, you all are going to say you could benefit from them, but think long and hard and maybe, just maybe, you will come to the conclusion that you just have an addiction to opioids and probably don't even suffer from depression or do because of your addiction. It angers me when some of the more prominent people on this board make posts saying that opioids should not be used in any case as AD's, as there are journal articles which say the complete opposite and have the results to prove their efficacy in refractory clinical depression of all kinds. Doctors are so unwilling to provide such a prescription due to the addicts who are just down in life, trying to escape reality trhough opioid abuse, which tends to be much more common than those who actually would benefit from it, and they obviously know this. Maybe if people were honest with themselves and their doctors about their issues and tried other possibilities (including non-medication solutions) they would recieve opiods if they truly need them, but like I said, this is not the typical case.... I could go on and on but that should be sufficient grounds for further discussion for now.
 
I find most Opiates make depression worse on the long-term (esp. all the Morphine close relatives: Oxy, Hydro, Heroin... and Methadone too)

But there are 2 kinds of VERY promising antidepressant Opioids:

- Tramadol-like compound. Opioids with mu agonist properties and Serotonin and/or Norepinephrine and/or Dopamine reuptake inhibiting properties.

- Kappa antagonists. There are more and more papers showing that kappa antagonists have efficacy as antidepressants.
http://opioids.com/norbinaltorphimine/antidepressant.html
http://opioids.com/kappa/kappa-antagonist.html
http://opioids.com/norbinaltorphimine/index.html

-----

Problem is: the only mixed SNRI+mu agonist commonly available is Tramadol; and the only kappa antagonist commonly available is Buprenorphine...

Are there people suffering from depression who got relief from tramadol? (without being on another antidepressant)?

Concerning Buprenorphine, I can say that it's a strong, effective, fast acting antidepressant.
And it's not due to its mu partial agonist effects, because I switched to Morphine during a few months, and quickly became very depressed, went back to Bupe and felt the antidepressant effect again; then later switched to Methadone, which made me depressed after a month...
And again, switching back to Buprenorphine supressed my depression.

So it has to be caused by kappa antagonism.
 
suprise suprise, my opiate usage turned into full blown addiction, I rent to rehab, cleaned up, and have been sober since January 1st 2007, (That was the day I got out of detox and sent to rehab, pure coincidence!).

So now im doing well, stopped my amphetamines for ADHD (which I miss sometimes) and am on no psychotropic drugs.

Opiates for depression = big no no.

I still love what opiates do for my mood. Eases my anxiety, mood lift, sense of comfort and well being. I love how opiates allow me to function when I used them for the anti-depressent properties. Sure I could get totally smacked and be falling over, nodding off, sloppy as shit and generally fucked up from an opiate high, but I could also take a modest dose, feel pretty high and be very functional. Unlike alcohol or marijuana, the side effects were too great when I tried to achieve anti-depressent effects............

I still think it would be great if a drug was invented that had the same anti-depressent properties that opiates have. I realise that the anti-depressent properties that I experience is subjective, but I believe alot of people share my feelings about opiates.


Are there any similar drugs out there that feel similar to the anti-depressent effects of most opiates? The drugs don't have to be chemically similar.

Like some people might say the anti-depressent effects of prozac feels pretty smiliar to the anti-depressent effects of opiates. So, yeh, can anyone think of a few?

For me, possibly a low dose of ghb feels the closest to the anti-depressent properties of opiates. Sucks that ghb is way up there for highly addictiing and probably even more dangerous to use than opiates.

remember, i'm only comparing the anti-depressent properties of opiates, not the body high or side-effects or anything.
 
jasoncrest said:
So it has to be caused by kappa antagonism.

i dunno about that, depends on the person.

I use opium or morphine and it is actually very like an antidepressant. it is motivating, energizing, makes me do more things then i normally do as oppose to jus nod out.

dont all opiates have an effect on the limibic system or emotional part of the brain to some degree. thats how they depersonalize pain. i feel for my anxiety they do the exact same thing - it depersonalizes it. like i can think an anxious thought but it doesnt make me anxious. its very interesting.

so ya we can argue over and over but i think its very subjective and it wouldnt be a good antidepressant for everyone. the fact remains it can be used to alleviate a depressive state. and it can effect our emotions in complex ways.
 
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