Kratom and Loperamide seem to have no cross tolerance.

[pcass89]

So I have a lot of experience with both of these drugs. I've actually become addicted to loperamide in the past, taking upwards of 96mg in a day. It has it's own horrible methadone-like withdrawal timeline. I had been using tons of kratom recently, over the course of maybe a year and half. Huge doses I wasn't weighing but it was like a heaping spoonful. Towards the end I was taking it like every 4 or 5 hours. It was bad. Had awfull problems with dehydration and constant urination. Decided to use lope to quit.

From my xperience with the lope I was 100% sure it had a cross tolerance, I was just hoping that it was incomplete. To my amazement there seemed to be no cross tolerance at all. As little as 16mg of lope was making feel great, almost high. Gave me motivation and I was content. No withdrawal or bowl movements in sight. Even 12mg was enough. After like a week or so I came off the lope expecting the "real withdrawal" to come. To my amazement there was literally none besides maybe jusy a tiny bit of of restless leg. Kratom withdrawal isn't like dope or pills obviously, but for some reason the restless leg is one symptom that's right up there with them.

I'm now a week out from the the lope and feel fine. I have the usual paws lack of energy and depression but that's to be expected. I got through this with virtually no acute withdrawal which I thought was crazy. I know people don't take krarom seriously but it really can come with some awful withdrawals, especially if you're taking doses like I was. One caveat I will add is that lope is by no means safe and can cause life threatening cardiac events. It basicly causes too much calcium build up in your blood and can cause your heart to beat irregularly and even stop. It's happened to tons of people. Doctors and medical journals still haven't really caught on. Some have.

16mg is the max dose per day, which I didn't go past. I can tell you when i was taking 48-96mg a day I 100% starting to notice some heart issues and I stopped. 48-96mg is a super low dose for someone who abuses lope too. Usually people take in the 100's. It's certainly dangerous. You don't ever want to get addicted to it, but in small doses it really can help with withdrawal. Just make sure you take laxatives with it or you will literally stop shitting and probably explode.

 

[Snafu in the Void]

So I have a lot of experience with both of these drugs. I've actually become addicted to loperamide in the past, taking upwards of 96mg in a day. It has it's own horrible methadone-like withdrawal timeline. I had been using tons of kratom recently, over the course of maybe a year and half. Huge doses I wasn't weighing but it was like a heaping spoonful. Towards the end I was taking it like every 4 or 5 hours. It was bad. Had awfull problems with dehydration and constant urination. Decided to use lope to quit.

From my xperience with the lope I was 100% sure it had a cross tolerance, I was just hoping that it was incomplete. To my amazement there seemed to be no cross tolerance at all. As little as 16mg of lope was making feel great, almost high. Gave me motivation and I was content. No withdrawal or bowl movements in sight. Even 12mg was enough. After like a week or so I came off the lope expecting the "real withdrawal" to come. To my amazement there was literally none besides maybe jusy a tiny bit of of restless leg. Kratom withdrawal isn't like dope or pills obviously, but for some reason the restless leg is one symptom that's right up there with them.

I'm now a week out from the the lope and feel fine. I have the usual paws lack of energy and depression but that's to be expected. I got through this with virtually no acute withdrawal which I thought was crazy. I know people don't take krarom seriously but it really can come with some awful withdrawals, especially if you're taking doses like I was. One caveat I will add is that lope is by no means safe and can cause life threatening cardiac events. It basicly causes too much calcium build up in your blood and can cause your heart to beat irregularly and even stop. It's happened to tons of people. Doctors and medical journals still haven't really caught on. Some have.

16mg is the max dose per day, which I didn't go past. I can tell you when i was taking 48-96mg a day I 100% starting to notice some heart issues and I stopped. 48-96mg is a super low dose for someone who abuses lope too. Usually people take in the 100's. It's certainly dangerous. You don't ever want to get addicted to it, but in small doses it really can help with withdrawal. Just make sure you take laxatives with it or you will literally stop shitting and probably explode.

Kratom does work differently on the mu opioid receptors to other opioids. There are some anecdotal reports that it increases tolerance to other opioids if taken before, but science suggests otherwise and that it can actually help prevent tolerance development. ( https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.2021.35.S1.05506 )

I have been very curious about using lope because I'm trying to quit kratom, but I don't want to take high doses, so I'm very interested to see you report <16mg can help.

You had no major withdrawal symptoms at all during the acutes while taking 12-16mg lope per day? Were you able to sleep? I can handle some mild RLS as long as I can get sleep. The last time I went through cold turkey kratom I didn't get even an hour of sleep for 4+ days which was the most difficult part for me.

 

[Keif' Richards]

I can't really comment, so I probably shouldn't be posting, but here we go. I definitely defer to @Snafu in the Void in this situation. I was under the impression for a long time now that Kratom and its constituents, the Mitragynine(s) were straight up Opioid agonists. There always seems to have been suspicion that there was something more complex going on in regard to tolerance, especially cross-tolerance. I really don't know personally, buy I'd be willing to follow Snafu's lead.

At the end of the day, we do know that there are Opioid agonists within Kratom. We also know that Loperamide is an Opioid agonist, however you want to define that term. Even if Loperamide has very limited central nervous system activity. we do know that folks have died from overdose at the hands of Loperamide, so do with that information what you will. I'm sure there is cross-tolerance there to some extent.

We have seen a lot less Loperamide-related material in the past couple of years. I just want to perform due diligence here. Loperamide is known to be quite dangerous when used in higher-than-recommended dosages (the standard dosage is ~2mg TID). It has killed through respiratory depression. It also carries potential hazard to the heart. Folks have been found dead from heart failure following the usage of Loperamide for either recreational/maintenance purposes.

I'm not preaching. I've used Loperamide myself and if I was sick, hell, I'd probably do it again. You're stronger than me though, so do better than me!

 

[Snafu in the Void]

I was under the impression for a long time now that Kratom and its constituents, the Mitragynine(s) were straight up Opioid agonists.

They are partial agonists, and antagonists.

There always seems to have been suspicion that there was something more complex going on in regard to tolerance, especially cross-tolerance.

Indeed, this study shows that kratom alkaloids do not downregulate MOR like other opioids do. As to why is less clear, but the kratom alkaloids appear to be less toxic to the receptors.

Unlike Morphine, Long-Term Exposure to Analgesic Mitragynine, 7-Hydroxymitragynine, Paynantheine, and Speciociliatine Alkaloids Does Not Contribute to Antinociceptive Tolerance of μ-Opioid Receptors

Background: Opioids are the most well known antinociceptive alkaloids all over the world, but tolerance and physical dependence are their dominant concerns in clinical applications. In contrast, monoterpene alkaloids are newly considered for their roles in pain management....

www.researchsquare.com

I also made a thread which touches on this subject and a hypothesis on kratom tolerance. I've recently discovered that NAC is able to immediately reduce kratom tolerance when used within a specific time. My hypothesis is that kratom tolerance is mostly due to accumulation of the MOR antagonists, or that chronic use causes the alkaloids to prefer binding as an antagonist vs agonist.

Kratom - Kratom tolerance theory & method to quickly reduce it

Kratom has been shown not to downregulate opioid receptors with long term use like other opioids do. In another study, kratom was shown to reduce both tolerance and withdrawal from morphine in rats when administered together. https://www.researchsquare.com/article/rs-39727/v1...

bluelight.org

 

[Keif' Richards]

@Snafu in the Void oid that's all really interesting. We definitely don't have enough information on the subject. I'm sure everyone really appreciates you doing the leg work with the research.

 

[pcass89]

Kratom does work differently on the mu opioid receptors to other opioids. There are some anecdotal reports that it increases tolerance to other opioids if taken before, but science suggests otherwise and that it can actually help prevent tolerance development. ( https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.2021.35.S1.05506 )

I have been very curious about using lope because I'm trying to quit kratom, but I don't want to take high doses, so I'm very interested to see you report <16mg can help.

You had no major withdrawal symptoms at all during the acutes while taking 12-16mg lope per day? Were you able to sleep? I can handle some mild RLS as long as I can get sleep. The last time I went through cold turkey kratom I didn't get even an hour of sleep for 4+ days which was the most difficult part for me.

Sorry for the late reply. But I had some very mild rls and mild anxiety. I have anxiety whether I'm sober or using. I'm also super sensitive to rls. Like I can't even take benadryl. Maybe my frame of reference is off because I've been through some agonizing withdrawals but this felt like nothing. Sleep will probably be an issue. If you can get your hands on some clonodine it knocks you out even if you're withdrawing. I didn't have any this time. Clonodine is honestly a god send for opiate withdrawal.

 

[pcass89]

I can't really comment, so I probably shouldn't be posting, but here we go. I definitely defer to @Snafu in the Void in this situation. I was under the impression for a long time now that Kratom and its constituents, the Mitragynine(s) were straight up Opioid agonists. There always seems to have been suspicion that there was something more complex going on in regard to tolerance, especially cross-tolerance. I really don't know personally, buy I'd be willing to follow Snafu's lead.

At the end of the day, we do know that there are Opioid agonists within Kratom. We also know that Loperamide is an Opioid agonist, however you want to define that term. Even if Loperamide has very limited central nervous system activity. we do know that folks have died from overdose at the hands of Loperamide, so do with that information what you will. I'm sure there is cross-tolerance there to some extent.

We have seen a lot less Loperamide-related material in the past couple of years. I just want to perform due diligence here. Loperamide is known to be quite dangerous when used in higher-than-recommended dosages (the standard dosage is ~2mg TID). It has killed through respiratory depression. It also carries potential hazard to the heart. Folks have been found dead from heart failure following the usage of Loperamide for either recreational/maintenance purposes.

I'm not preaching. I've used Loperamide myself and if I was sick, hell, I'd probably do it again. You're stronger than me though, so do better than me!

Don't know where you found that but it stops people's hearts through QTC prolongation that stems from elevated calcium levels. This always happens before any type of CNS depression can kill you. I never found any evidence of CNS depression period, let alone deaths from it.

I can't really comment, so I probably shouldn't be posting, but here we go. I definitely defer to @Snafu in the Void in this situation. I was under the impression for a long time now that Kratom and its constituents, the Mitragynine(s) were straight up Opioid agonists. There always seems to have been suspicion that there was something more complex going on in regard to tolerance, especially cross-tolerance. I really don't know personally, buy I'd be willing to follow Snafu's lead.

At the end of the day, we do know that there are Opioid agonists within Kratom. We also know that Loperamide is an Opioid agonist, however you want to define that term. Even if Loperamide has very limited central nervous system activity. we do know that folks have died from overdose at the hands of Loperamide, so do with that information what you will. I'm sure there is cross-tolerance there to some extent.

We have seen a lot less Loperamide-related material in the past couple of years. I just want to perform due diligence here. Loperamide is known to be quite dangerous when used in higher-than-recommended dosages (the standard dosage is ~2mg TID). It has killed through respiratory depression. It also carries potential hazard to the heart. Folks have been found dead from heart failure following the usage of Loperamide for either recreational/maintenance purposes.

I'm not preaching. I've used Loperamide myself and if I was sick, hell, I'd probably do it again. You're stronger than me though, so do better than me!

I honestly can't find a single case of CNS depression deaths. Not one. Every single death has been a cardiac event caused by QTC prolongation. It stems from elevated calcium levels. Every death I've seen had been from the QTC prolongation.

 

[Keif' Richards]

Hey @pcass89

I totally respect what you have to say. You likely know more than I do on the subject. I'll agree that it's easy to confuse the material regarding what actually caused the person's death. Thanks for the information!

 

[Snafu in the Void]

So I've been trying this out. It does indeed help a lot. I was concerned it wouldn't help much with kratom's dopaminergic withdrawal, but it does. I tend to fiend for nicotine like crazy in kratom withdrawal, but that is absent.

I took 16mg the first day and 12mg the second day. Both days 40mg omeprazole as well. It's bearable. Mild RLS and anxiety.

I thought loperamide heart danger was speculated to be from sodium or chloride channel blocking effect? If it's via calcium blocking that is concerning as kratom alkaloids act as calcium channel blockers themself, and due to kratom's unpredictable and long half life (24hr +-8hr), this could present additive danger.

However, from the only case reports available of loperamide heart issues, the lowest I can find was from 20mg daily use, and that person already had a genetic heart defect which the loperamide unmasked. I can't find any reports of cardiac events from under 20mg of daily use, though this obviously doesn't mean it can't or hasn't occurred.

I think 12-16mg is reasonably safe if taken for a few days. OTC max therapeutic dose is 8mg daily, RX max is 16mg daily.

I sure do hate being constipated, though. I rather enjoy my morning bowel movements.