resorcinol
08-25-2009, 11:53 PM
a 5HT reuptake inhibitor?
Does anybody know how concrete the information on how tramadol effects the serotonergic system is? I ask because of my trip report that includes some tramadol:
http://forum.opiophile.org/showthread.php?p=411603
I felt effects including empathy, increased tactile sensitivity, increased appreciation of everything around me physically and psychologically, and a feeling of peace that was different than the opioid feeling of peace alone ... along with pressure on my head and a strange feeling in my jaws that I definitely associate with serotonergic activity.
I never felt any effects that I know are associated with MDMA from ANY SSRI at ALL, ever. These effects were mild, but definitely there, and different from the SSRI feeling. SSRIs only have the weird head feeling and jaw feeling for a few days, but NONE of the empathetic and tactile sensations. I felt such sensations from tramadol.
I feel that perhaps tramadol is a weak 5-HT releaser rather than a 5-HT reuptake inhibitor. I suppose it could be a reuptake inhibitor of the other monoamines but a releaser of 5-HT, but I even suspect that it may be a general monoamine releaser, albeit a weak one, rather than a reuptake inhibitor. Alternatively, perhaps it is both (which would explain why one cannot get full blown empathogenic effects by just taking a higher dose, as 5-HT transporter blockade would cap how much 5-HT release could occur ... same at the other transporters). It could be a very weak reuptake inhibitor of the monoamines and a weak (but stronger than its actions as a reuptake inhibitor) monoamine releaser. This would cause the effects of monoamine release to dominate, but be severely limited and capped at mild effects by the NET, SERT, and DAT substrate reuptake inhibition. I think this latter possibility is what is going on with tramadol. I'm curious what you folks think about this. It would explain also how even quite opioid tolerant people can get mild euphoria from tramadol when it makes no sense if tramadol was merely a mu agonist as it's a weak mu agonist. It's good for potentiating the mu agonism of stronger dope (excellent for that in fact), but alone, it's very mediocre. I'd still take it over dextropropoxyphene anyday, though. D-propoxyphene is stronger as a mu agonist but hits the WRONG MU RECEPTOR (mu2) for analgesia and euphoria! Tramadol and even its M1 metabolite are quite weak mu agonists but they hit the correct (mu1) mu receptor for analgesia and euphoria. The mu2 receptor only contributes to physical dependence, sedation, and respiratory depression. Darvocet really DOES suck! It's affinity for mu1 is absolutely pathetic, but most equivalencies are calculated based on its average mu affinity between mu1 and mu2, giving it the appearance of being a decent weak opioid, when in reality, it royally sucks. NSAIDS relieve pain better than darvocet, and euphoria is not achievable for many people even with NO TOLERANCE due to pathetic mu1 affinity. It might be decent if that oxygen bridge was removed (that would boost mu1 affinity nicely), but then it would be CIII like vicodin when combined with APAP. It would be more structurally similar to methadone without that oxygen bridge, but still much weaker due to the offset phenyl ring.
I'd take codeine over both tramadol AND darvocet, but unfortunately you're more likely to get handed trams or darvocet by docs nowadays than tylenol #3 or #4 w/ codeine. This is really fucking sad. Most countries sell codeine OTC. The UK and several others even sell preparations with small amounts of morphine OTC. In the US, you get handed tramadol or darvocet when you're in tears from the pain. It's disgusting how opiophobic the drug war has made doctors. Even getting codeine is like pulling teeth now. And getting Vicodin or Percocet from a PC physician is near impossible. If you want anything stronger than codeine, you need a PM doc, since the strongest most PC docs will hand out now is T3 or MAYBE if they're being "GENEROUS WITH YOU" (seriously, they say shit like that) T4 with one refill. The only way that you MIGHT get hydrocodone more easily from a PC doc is by faking a nonproductive cough that keeps you awake and is putting your job in jeopardy due to sleep deprivation in this unstable economy or something like that ... might land you tussionex (XR hydrocodone / XR chlorpheniramine) syrup from a PC doc. I have FAR TOO MANY family members that have been in extremely severe pain (brought them to tears) and docs STILL refused to give anything stronger than tramadol, codeine T3, or darvocet with zanaflex or skelaxin (but NOT Soma because "Soma is highly addictive and causes a recreational euphoric high, so even though Soma would probably work better to ease this pain, I can't write you a prescription for that one" --- exact quote from a doc to a 73 yr old family member with severe upper back pain that had her in tears ... this doc would only upgrade her to T3 after darvocet was totally useless and refused to give Soma instead of zanaflex or skelaxin). The T3 was the only one that helped A LITTLE when combined with 2 otc aleve tablets and 3 skelaxin.
When the pain got REALLY bad one night, I gave her 90 mg of my oxazepam to take along with 3 T3 (doc said MAX two, more was "dangerous" but I assured her that three was fine) so 90 mg codeine, and two aleve otc tabs. The high dose of oxazepam was b/c she was having extreme insomnia and anxiety from the pain also, and I wanted to ensure the skeletal muscle relaxant effects of the benzo came on full force. 45 minutes later she hugged me and thanked me and said it reduced the pain 80 percent and made her sleepy (90 mg codeine, 1 g apap [in the T3], 500 mg naproxen sodium, and 90 mg oxazepam ... this was the combo). Adding an extra codeine tablet and the benzo dramatically helped her, and I could easily spare those 3 x 30 mg oxazepam capsules to bring her some relief. She took a few more during the days after that at just 30 mg oxazepam, 120 mg codeine, and one aleve (codeine boosted because she felt she could tolerate even more than 90 mg) and was nearly pain free and just stopped when the pain went away after a week (it was a temporary but very painful muscle injury in the upper back and shoulder region). Docs just don't give a SHIT how much you're hurting anymore. She's a 73 year old woman and they're holding back even some friggin 10 mg percs that would have abolished her pain because "it's insidiously addictive"... and wouldn't even consider 5/500 Vic because "it's too habit forming" or carisoprodol / diazepam / oxazepam / clonazepam in a very low dose because those muscle relaxers are "very addictive downer street drugs and cause very addictive highs when taken with alcohol". All this they said in a lecture-like tone to a 73 yr old woman in pain so bad she was crying at times, all the while she is so confused and doesn't understand why they're being so stern and harsh with her. It's FUCKED UP. I've witnessed the same happen to my sister, father, mom, grandfather, uncle, and aunt. It's so fucked up. Sickening.
Fuck 'em. They wouldn't give her enough relief ... I got relief to her by upping her T3 from 2 MAX to three or four and my oxazepam PRN for muscle relaxant effects far better than those of skelaxin or zanaflex along with the potent nsaid aleve all until the pain resolved. She felt much much better (could see it right from her facial expression) 45 minutes after swallowing the 90 mg oxazepam, 90 mg codeine, and 500 mg naproxen and the pain was reduced enough, along with the oxazepam sedation, for her to sleep. Fuck the doctor, when they don't treat you, there are other ways to get the meds you need. Assholes. And did she get addicted? Of course not. She's never even mentioned the meds again after the painful condition passed.
Tangent, but one hell of an important one. The only thing more under-treated than chronic pain is semi-acute (a few weeks to a few months) pain. Only post op or post severe injury pain is (USUALLY) treated sufficiently (for opioid non-tolerant people). If you're opioid tolerant, don't expect the er doc to care and to boost your PCA delivery rate, IV dose frequency or dose, or anything like that. You'll just have to cry it out.
Does anybody know how concrete the information on how tramadol effects the serotonergic system is? I ask because of my trip report that includes some tramadol:
http://forum.opiophile.org/showthread.php?p=411603
I felt effects including empathy, increased tactile sensitivity, increased appreciation of everything around me physically and psychologically, and a feeling of peace that was different than the opioid feeling of peace alone ... along with pressure on my head and a strange feeling in my jaws that I definitely associate with serotonergic activity.
I never felt any effects that I know are associated with MDMA from ANY SSRI at ALL, ever. These effects were mild, but definitely there, and different from the SSRI feeling. SSRIs only have the weird head feeling and jaw feeling for a few days, but NONE of the empathetic and tactile sensations. I felt such sensations from tramadol.
I feel that perhaps tramadol is a weak 5-HT releaser rather than a 5-HT reuptake inhibitor. I suppose it could be a reuptake inhibitor of the other monoamines but a releaser of 5-HT, but I even suspect that it may be a general monoamine releaser, albeit a weak one, rather than a reuptake inhibitor. Alternatively, perhaps it is both (which would explain why one cannot get full blown empathogenic effects by just taking a higher dose, as 5-HT transporter blockade would cap how much 5-HT release could occur ... same at the other transporters). It could be a very weak reuptake inhibitor of the monoamines and a weak (but stronger than its actions as a reuptake inhibitor) monoamine releaser. This would cause the effects of monoamine release to dominate, but be severely limited and capped at mild effects by the NET, SERT, and DAT substrate reuptake inhibition. I think this latter possibility is what is going on with tramadol. I'm curious what you folks think about this. It would explain also how even quite opioid tolerant people can get mild euphoria from tramadol when it makes no sense if tramadol was merely a mu agonist as it's a weak mu agonist. It's good for potentiating the mu agonism of stronger dope (excellent for that in fact), but alone, it's very mediocre. I'd still take it over dextropropoxyphene anyday, though. D-propoxyphene is stronger as a mu agonist but hits the WRONG MU RECEPTOR (mu2) for analgesia and euphoria! Tramadol and even its M1 metabolite are quite weak mu agonists but they hit the correct (mu1) mu receptor for analgesia and euphoria. The mu2 receptor only contributes to physical dependence, sedation, and respiratory depression. Darvocet really DOES suck! It's affinity for mu1 is absolutely pathetic, but most equivalencies are calculated based on its average mu affinity between mu1 and mu2, giving it the appearance of being a decent weak opioid, when in reality, it royally sucks. NSAIDS relieve pain better than darvocet, and euphoria is not achievable for many people even with NO TOLERANCE due to pathetic mu1 affinity. It might be decent if that oxygen bridge was removed (that would boost mu1 affinity nicely), but then it would be CIII like vicodin when combined with APAP. It would be more structurally similar to methadone without that oxygen bridge, but still much weaker due to the offset phenyl ring.
I'd take codeine over both tramadol AND darvocet, but unfortunately you're more likely to get handed trams or darvocet by docs nowadays than tylenol #3 or #4 w/ codeine. This is really fucking sad. Most countries sell codeine OTC. The UK and several others even sell preparations with small amounts of morphine OTC. In the US, you get handed tramadol or darvocet when you're in tears from the pain. It's disgusting how opiophobic the drug war has made doctors. Even getting codeine is like pulling teeth now. And getting Vicodin or Percocet from a PC physician is near impossible. If you want anything stronger than codeine, you need a PM doc, since the strongest most PC docs will hand out now is T3 or MAYBE if they're being "GENEROUS WITH YOU" (seriously, they say shit like that) T4 with one refill. The only way that you MIGHT get hydrocodone more easily from a PC doc is by faking a nonproductive cough that keeps you awake and is putting your job in jeopardy due to sleep deprivation in this unstable economy or something like that ... might land you tussionex (XR hydrocodone / XR chlorpheniramine) syrup from a PC doc. I have FAR TOO MANY family members that have been in extremely severe pain (brought them to tears) and docs STILL refused to give anything stronger than tramadol, codeine T3, or darvocet with zanaflex or skelaxin (but NOT Soma because "Soma is highly addictive and causes a recreational euphoric high, so even though Soma would probably work better to ease this pain, I can't write you a prescription for that one" --- exact quote from a doc to a 73 yr old family member with severe upper back pain that had her in tears ... this doc would only upgrade her to T3 after darvocet was totally useless and refused to give Soma instead of zanaflex or skelaxin). The T3 was the only one that helped A LITTLE when combined with 2 otc aleve tablets and 3 skelaxin.
When the pain got REALLY bad one night, I gave her 90 mg of my oxazepam to take along with 3 T3 (doc said MAX two, more was "dangerous" but I assured her that three was fine) so 90 mg codeine, and two aleve otc tabs. The high dose of oxazepam was b/c she was having extreme insomnia and anxiety from the pain also, and I wanted to ensure the skeletal muscle relaxant effects of the benzo came on full force. 45 minutes later she hugged me and thanked me and said it reduced the pain 80 percent and made her sleepy (90 mg codeine, 1 g apap [in the T3], 500 mg naproxen sodium, and 90 mg oxazepam ... this was the combo). Adding an extra codeine tablet and the benzo dramatically helped her, and I could easily spare those 3 x 30 mg oxazepam capsules to bring her some relief. She took a few more during the days after that at just 30 mg oxazepam, 120 mg codeine, and one aleve (codeine boosted because she felt she could tolerate even more than 90 mg) and was nearly pain free and just stopped when the pain went away after a week (it was a temporary but very painful muscle injury in the upper back and shoulder region). Docs just don't give a SHIT how much you're hurting anymore. She's a 73 year old woman and they're holding back even some friggin 10 mg percs that would have abolished her pain because "it's insidiously addictive"... and wouldn't even consider 5/500 Vic because "it's too habit forming" or carisoprodol / diazepam / oxazepam / clonazepam in a very low dose because those muscle relaxers are "very addictive downer street drugs and cause very addictive highs when taken with alcohol". All this they said in a lecture-like tone to a 73 yr old woman in pain so bad she was crying at times, all the while she is so confused and doesn't understand why they're being so stern and harsh with her. It's FUCKED UP. I've witnessed the same happen to my sister, father, mom, grandfather, uncle, and aunt. It's so fucked up. Sickening.
Fuck 'em. They wouldn't give her enough relief ... I got relief to her by upping her T3 from 2 MAX to three or four and my oxazepam PRN for muscle relaxant effects far better than those of skelaxin or zanaflex along with the potent nsaid aleve all until the pain resolved. She felt much much better (could see it right from her facial expression) 45 minutes after swallowing the 90 mg oxazepam, 90 mg codeine, and 500 mg naproxen and the pain was reduced enough, along with the oxazepam sedation, for her to sleep. Fuck the doctor, when they don't treat you, there are other ways to get the meds you need. Assholes. And did she get addicted? Of course not. She's never even mentioned the meds again after the painful condition passed.
Tangent, but one hell of an important one. The only thing more under-treated than chronic pain is semi-acute (a few weeks to a few months) pain. Only post op or post severe injury pain is (USUALLY) treated sufficiently (for opioid non-tolerant people). If you're opioid tolerant, don't expect the er doc to care and to boost your PCA delivery rate, IV dose frequency or dose, or anything like that. You'll just have to cry it out.