Non-Addictive Opioids

[Gaz_hmmmm]

I remember reading on pubmed I think it was about opioids that had been created years ago that in animals (Rats or Apes, I can't remember which one) caused no withdrawl symptoms, but in humans they did.

Does anyone know why this was, what's happened to these opioids?

Also what's the closest opioid we (Science) has came to a non-addictive opioid?

 

[shags2dope78]

To be honest, I do not know of any non-addictive opioid. I have done opoids a lot during, especially on a everyday basis sometimes, I never find myself being addictive to them. I always take breaks for a few months for my tolerance to lower, but never really addictive. The only thing that I ever had cravings for were OCs, but nothing major.

I remember reading or hearing about that somewhere to. But as far as non-addictive, as far as I know, there are none.

 

[rand420]

All opioids which bind to the mu-receptor have the capability of forming dependance. Even tramadol, a non-scheduled opioid, has been shown to have withdrawal symptoms. Dextromethorphan is technically an opioid, but without mu-affinity it is not usually considered addictive.

 

[negrogesic]

Loperamide is an opioid, a piperidine similar to fentanyl, yet it is not addictive in the traditional sense, as it does not permeate the blood brain barrier. Loperamide is also known as immodium....

 

[Tri-nity]

^^^
Yep. what we junkies call OTC methadone around here(southern US).

Is there any way you could easily change loperimide to better cross the BBB. Maybe like drink a soda or grapefruit juice?

 

[malfunkshun]

All opioids which bind to the mu-receptor have the capability of forming dependance. Even tramadol, a non-scheduled opioid, has been shown to have withdrawal symptoms. Dextromethorphan is technically an opioid, but without mu-affinity it is not usually considered addictive.

even tramadol? thats an understatement. i've had worse withdrawals from tramadol than from morphine sulfate

 

[rand420]

Is there any way you could easily change loperimide to better cross the BBB. Maybe like drink a soda or grapefruit juice?

Nope, unless you happened to find a way to bind loperimide to the nanoparticles of polysorbate 80.

 

[malfunkshun]

and what would be the benefit of this bbb crossing? would loperimide become the new hillbilly heroin?

 

[toolazy2think]

even tramadol? thats an understatement. i've had worse withdrawals from tramadol than from morphine sulfate

then you were withdrawing from a much higher relative dose or from a longer druation of tramadol than you were from morphine

 

[rand420]

Tramadol and morphine are completely different molecular structures. Morphine does not have a dosage ceiling for tolerant patients, but Tramadol can be very dangeous in high amounts (seizures, etc...)

 

[who mE?]

Metopon (5-methyl-oxymorphone) was thought to not have a Physical Dependance Capacity (PDC) in the 1950s based upon studies in rats and later, monkeys... Unfortunately during clinical trials in man, it was discovered that it did have a withdrawal syndrome.
See:
Metopon analgesia in the dog.
Am J Vet Res. 1954 Jul;15(56):338-42. No abstract available
http://history.nih.gov/exhibits/opiates/docs/3_newDrugs.htm is an awesome resource on the subject of "THE QUEST FOR THE NON ADDICTIVE OPIOID"
Etorphine has a low physical dependance capacity, and Dihydroetorphine has an extremely low physical dependance capacity, as you can read about here:
http://www.cpdd.vcu.edu/98pdf/aceto.pdf
See also: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9424015

This is some interesting research from 1963 on the search for an opioid with a low (or no) addiction potential:
http://www.unodc.org/unodc/en/bulletin/bulletin_1963-01-01_1_page005.html

Somebody interested in this subject should look into:
Ciramadol - http://www.google.com/search?hl=&cat=&meta=&q=ciramadol (a "non-addictive" tramadol analogue)

Incarvillateine - http://www.google.com/search?hl=&cat=&meta=&q=incarvillateine

Xorphanol
Drug Alcohol Depend. 1985 Feb;14(3-4):373-80.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=4039650&dopt=Abstract
Xorphanol is a new mixed agonist-antagonist from the morphinan class of analgesics. On the basis of animal experiments, the physical dependence liability of xorphanol is predicted to be of a low order in man. Conceptually, xorphanol is of interest since in vitro experiments have revealed anti-naloxone properties and resistance to antagonism by opioid antagonists. At the practical level, xorphanol is a well tolerated, orally active analgesic that provides effective pain relief clinically.



I've also got some references on this subject here: http://hive.dopers.org/tolerance_and_withdrawal.txt

And no discussion of addiction-free opioids could be complete without mentioning the work of Mike Strates in his quest to stay high on Dilaudid forever:
http://www.dilaudid.net/uldntx.shtml (I've got many more references on this subject... somewhere)

 

[shags2dope78]

The user "who me" was prepared for this one, lol. I have actually learned from all those links that he posted.

 

[Dj_TranceMadness]

Try using Kratom Leaf.

Although not an opioid, in high doses (15 grams+) the leaf produces an effect very similar to Opium. Physical dependence is possible, but unlikely.

 

[who mE?]

Just to clarify, one makes a TEA with 15 grams of kratom for a high, not smokes it! Or do you eat it? What dosage of say oxycodone would 10 grams of kratom leaf be equivalant to? Does anybody have any experience with the extract? What is the mg/mg equivalancy of mitragynine?

I've also heard that many vendors received a very large fake shipment of kratom (a different herb - see http://www.erowid.org/plants/kratom/kratom_article1.shtml)... How can one tell if a sample of kratom is the correct herb? Does anybody know if the majority of enthobotanical vendors have replaced their kratom stock with the real thing since this occurred? Did anybody ever figure out what the fake herb was?

Lastly (and least likely to be answered), has anybody who uses buprenorphine daily tried kratom and can explain the effects?

 

[negrogesic]

^^Yes these is a bunch of bogus crap kratom sold by ethnobotanical places online. Im sure some places get the real stuff, but your best bet is buying it in an a herb store in china town, growing it, or actually go to east asia to find it. But i think you can become dependent, at least in some way to almost anything, including things like loperamide.......

 

[Ronald]

So this loperimide stuff (aka lobster) is available otc in Immodium then? I'll have to check that one out this afternoon at bimart. That is a cool trademark secret if it is for real. ^^This plant is worth a look at too. Safe tips brothers, thanks for the advice.

 

[converge]

I've tried Kratom from a couple vendors, it didn't do anything so it was either fake or just doesn't work when it's dried and probably months old. I really wish some chemists would just make truckloads of 7-hydroxymitragynine, as Kratom isn't regulated at all and mitragynine isn't an analogue of anything scheduled.


who me, here are a couple refs I picked up a few months ago when I was trying to get off this stuff, the other forum is down right now but I'll post the whole articles there later-

Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa

Kenjiro Matsumoto, Syunji Horie, Hayato Ishikawa, Hiromitsu Takayama, Norio Aimi, Dhavadee Ponglux, Kazuo Watanabe

Abstract:
Mitragynine is an indole alkaloid isolated from the Thai medicinal plant Mitragyna speciosa. We previously
reported the morphine-like action of mitragynine and its related compounds in the in vitro assays. In the present study,
we investigated the opioid effects of 7-hydroxymitragynine, which is isolated as its novel constituent, on contraction
of isolated ileum, binding of the specific ligands to opioid receptors and nociceptive stimuli in mice. In guinea-pig
ileum, 7-hydroxymitragynine inhibited electrically induced contraction through the opioid receptors. Receptor-binding
assays revealed that 7-hydroxymitragynine has a higher affinity for mu-opioid receptors relative to the other
opioid receptors. Administration of 7-hydroxymitragynine (2.5 –10 mg/kg, s.c.) induced dose-dependent
antinociceptive effects in tail-flick and hot-plate tests in mice. Its effect was more potent than that of morphine in
both tests. When orally administered, 7-hydroxymitragynine (5–10 mg/kg) showed potent antinociceptive activities
in tail-flick and hot-plate tests. In contrast, only weak antinociception was observed in the case of oral administration
of morphine at a dose of 20 mg/kg. It was found that 7-hydroxymitragynine is a novel opioid agonist that is
structurally different from the other opioid agonists, and has potent analgesic activity when orally administered.



Studies on the Synthesis and Opioid Agonistic Activities of Mitragynine-Related Indole Alkaloids: Discovery of Opioid Agonists Structurally Different from Other Opioid Ligands

Hiromitsu Takayama, Hayato Ishikawa, Mika Kurihara, Mariko Kitajima, Norio Aimi, Dhavadee Ponglux, Fumi Koyama, Kenjiro Matsumoto, Tomoyuki Moriyama, Leonard T. Yamamoto, Kazuo Watanabe, Toshihiko Murayama, and Syunji Horie

Abstract:
Mitragynine (1) is a major alkaloidal component in the Thai traditional medicinal herb,
Mitragyna speciosa, and has been proven to exhibit analgesic activity mediated by opioid
receptors. By utilizing this natural product as a lead compound, synthesis of some derivatives,
evaluations of the structure-activity relationship, and surveys of the intrinsic activities and
potencies on opioid receptors were performed with guinea pig ileum. The affinities of some
compounds for mu, delta, and kappa receptors were determined in a receptor binding assay. The essential
structural moieties in the Corynanthe type indole alkaloids for inducing the opioid agonistic
activity were also clarified. The oxidative derivatives of mitragynine, i.e., mitragynine
pseudoindoxyl (2) and 7-hydroxymitragynine (12), were found as opioid agonists with higher
potency than morphine in the experiment with guinea pig ileum. In addition, 2 induced an
analgesic activity in the tail flick test in mice.

 

[toolazy2think]

So this loperimide stuff (aka lobster) is available otc in Immodium then? I'll have to check that one out this afternoon at bimart. That is a cool trademark secret if it is for real. ^^This plant is worth a look at too. Safe tips brothers, thanks for the advice.

"Loperamide is an opioid, a piperidine similar to fentanyl, yet it is not addictive in the traditional sense, as it does not permeate the blood brain barrier. Loperamide is also known as immodium.... "

It does not permeate the BBB, therefore does not get you high.

 

[Ronald]

Yes, that is correct. But I was on sciencedirect.com yesterday and I read that by taking this drug with propylene glycol or quarternary ammonium ions may increase absorption. Propylene glycol is used in baking or something similar. Basically just to coaddminister the Loperamide with a phase-transfer catalyst. I am still a skeptic but it is better than nothing, or is it?

 

[Ronald]

That said, fentanyl just plain laughs in the face of users taking loperamide to get high.