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  • BDD Moderators: Keif’ Richards

Opioids Dyphenhydramine works as good as promethazine for potentiating opiates ?

I’ve previously enjoyed using DPH to enhance, but I wouldn’t bother nowadays, I’ve just become to scared about all the dementia risk stuff and also it perhaps competing with the enzymes..

Both DPH and Promethazine are so pharmacologically dirty I’m just put off. I didn’t use either in my last run to potentate as I was to afraid lol.

I don’t know enough about Hydroxyzine to say if it’s any safer or more effective, but anecdotally from memory I’ve always seen people say it’s very good for what it is.

For pure itching a newer antihistamine is properly the “safer” choice but I can’t comment enough to say if that’s really true beyond being just more targeted to only histamine.

But recreationally seems like only Hydroxyzine..
 
notsmokeymcpot42088 said:
Yes you are onto something. I (sigh) take 4 benadryls a day with my sub. I remember having one very insistent rather ignorant friend that would get "Lean" prometh/codeine/sprite/jolly rangers 2 cups (Yea that kinda guy) "Liquid H right here man you having a cup" -' it'd be a waste' Than I'll pour you a double (which there was a fancy name for but I don't speak lean) "Man its just gunna be the prometh that hits me" So I do it but I throw a few benzos down with it.

"oh man you nodding hard told ya that ish was strong" -- nah man I admit the prometh be knocking me out but believe me the codeine ain't gettting through -- which angered him. Silly situation no longer talk to that bald be flat earth in trumpy

Now Benadryl has been linked to Alzheimer's/dementia recently so uh I'm fucked. opi's benzos pot booze and dyph --- when you find me wandering in a field check my back pocket for a bullet or loaded rig lmao

ACTUALLY -- Our chemistry folk -- Benadryl is an anticholinergic medication, meaning it blocks the action of the neurotransmitter acetylcholine, which plays a role in memory and learning. --

ANYTHING that can be done to stimulate action of acetylcholine? Suggestions or theories appreciated dementia is a pretty big fear.
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Seems lots of stuff about nicotine demonstrating decent effects on retaining memory etc or preventing dementia, but it’s still new stuff, and only a patch really seems to be the sensible way.

There’s Alpha GPC and CDP choline but I’ve seen lots of people say they get nasty sides if overdoing it.

Due to my diet and stimulant use, I take a conservative 600mg of CDP once a week due to the half life.
 
Yes, they are going to be pretty much indistinguishable to anyone other than a true connoisseur of antihistamines. The notion that Promethazine (Phenergan) is somehow much better/worse (depending on who you're talking to) than Diphenhydramine (Benadryl) is mostly due to socio-cultural issues. Promethazine/Codeine became very popular as a recreational drug about a decade ago when hip-hop began talking about it incessantly. Being perennially starved for originality, Hip Hop artists just began all talking about Lean in unison. This lead to a backlash against both Codeine and Promethazine. This backlash is not rooted in pharmacology or medicine but in public discontent/hysteria.
 
Maybe I'm the odd one out but I honestly haven't noted any of the first-generation antihistamines making the slightest difference to my medication. I tend not to mess with anything I don't NEED because by definition there is no such thing as a 'safe' drug.

In another thread I mentioned that a moderately large study of people undertaking opiate replacement therapy showed almost half were also consuming promethazine.

Both cyclizine and promethazine appear to have a specific effect on the psychoactivity of methadone and it's homologues (dipipanone, phenadoxone and so on). In the UK we suffered a very British drug epidemic in which people were injecting Diconal (dipipanine + cyclizine) tablets until the drug was virtually banned. Then we saw people smurfing pharmacies to buy cyclizine tablets in bulk so people could inject them after consuming methadone orally.

The rules around cyclizine sales have got a little bit tougher but in spite of that one person (in Liverpool) caught (twice) doing just that. I mean, In bulk it's only about 10p a pill and she was selling them for £1 each. She got caught because dozens of skallies were turning up at her home every day but I suggest that the US idiom 'nickel and dime' fits perfectly into her business model.
 
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'nickel and dime' is some crazy shit that = Penny wise pound stupid. In a hypothetical world when I got mdpv (for like 15 a g -- smoke shops selling it 75% cut at 60 a qg) hand to guy tell him you bring back x amount (lets say roughly 100 a g) I hand you another one --- no communication just here ya go, 150 and I'll hand ya another one. (Of course this was all when mdpv was legal, even in the hypothetical world)


In this hypothetical world I had plenty of C-lam but ppl doubted its legitimacy --- had an associate "We could get the whole town addicted" --- Than what happens when this connect dries up? You think they stay loyal --- no fuckin way man can't have this anywhere near the market.
 
notsmokeymcpot42088 said:
...had an associate "We could get the whole town addicted" --- Than what happens when this connect dries up?
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Yeah, just one reason I stick to my prescribed medications consumed exactly as prescribed.

Gosh, I was sent a sample of MDPV a couple of decades ago. I didn't like it. I've mentioned elsewhere that pure dopamagenics induce dysphoria in me so after one line I gave the rest away. Plain pyrovalerone was better but still not my thing and now we are seeing pyrophenidone turning up as are homologues that appear to demonstrate both dopamagenic AND MOR activity. Only heard a couple of reports on that last one and some marketing genius had decided to call it 'Crystal'. All very shady.

Honestly, if you want to be put of RCs for life, check the instrumental data for a lot of samples. For some classes of RC almost half (48%) of the samples showed dangerous impurities.

I would be prepared to bet £1 that in the decades to come we will see an association between the use of some RCs with very serious illnesses.

But yeah, it was mental to read that the same person just sat there day after day racking up those £1 coins. since cyclizine is technically a [P] medication rather than a [POM] or [CD], both times they were found innocent but the magistrate made it clear that at the scale involved, technically the seller was selling a [P] medicine without the appropriate 'Medicines Counter Assistant' course. Maybe that individual did just that and carried on.
 
Sometimes I’ll take a few certirazine to get to sleep. It’s milder than diphenhydramine, but one of the most selective antihistamines out there (and it’s otc unlike the parent compound hydroxyzine, although it lacks some of the smoothness that hydroxyzine has).
 
Skorpio said:
Sometimes I’ll take a few certirazine to get to sleep. It’s milder than diphenhydramine, but one of the most selective antihistamines out there (and it’s otc unlike the parent compound hydroxyzine, although it lacks some of the smoothness that hydroxyzine ha
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This one (if you mean cetirizine) is absolutely fab for the itches. I’ll never forget taking about 300mg of Codeine as a teenager and getting terrible itches, had to run down to the village shop and buy this. The lady behind the counter looked bewildered 🤣.

Not noticed much more but it is a second generation so makes sense.
 
4DQSAR said:
Honestly, if you want to be put of RCs for life, check the instrumental data for a lot of samples. For some classes of RC almost half (48%) of the samples showed dangerous impurities.

I would be prepared to bet £1 that in the decades to come we will see an association between the use of some RCs with very serious illnesses.
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Ive always made sure to get lab reports on anything that was a large batch -- really just had the one trusted source. Than for a bit labs were doing custom synth's and of course those also came with assays and whatnot.

Almost more importantly than that you better look hard into any compound you are going to be using long terms safety and toxicity profile -- preferably choose something that's been around A LONG TIME AND IS THOROUGHLY RESEARCHED. (Old patents are good for this)

EVEN SO --- no way would I bet against you there. The person I know that took the most 25i-nbome died at 36 of pancreatic cancer. obviously I don't know if there is any corre-or causation.

MDPV always felt toxic AF took me at 99% purity -- stuff was nasty but at the time I had a friend that really liked it - and so did the rest of the speed ppl I hear.

I remember hearing 3-meo-pcp was liver or kidney toxic (I forget)

Even Dimethocaine 1/3 potency of cocaine 3x cardiovascular toxicity -- slim margins.

Ech had a buddy come back with a festival with "Acid and DOx but forgot which ones were which" -- weekend of tripping is too long!

I hope I am not making it sound like research chemicals are safe and to be played with
 
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In my experience, it increases the sedation but doesn't seem to do anything for pain relief. It may even blunt the euphoria but you said you aren't just getting high anyway.
 
I think this has about played its course clyizine -- promethazine -- Benadryl. Dramamine? There are Alot of anti histimants I suppose what do I know
 
@notsmokeymcpot42088 It was the synthetic CB1 ligands that were the worst. I think something like 68% of them contained dimers and trimers (I just counted the MW of the active and the impuries and what do you know, exactly the right MW FOR dimers and trimers).

Ihe problem is that having much higher MWs, they won't vapourize ahead of the flame-front. Instead they pyrolize into lovely things like nitrosamines. So all those kids smoking Spice today are quite likely to be the subject of cancer studies in a couple of decades.

MDPV in particular is a perverse example. It was in the original patent for pyrovalerone but wasn't used clinically. I think that highlights the fact that more potent does not mean better. I would GUESS that pyrovalerone was chosen because that para methyl moiety is going to ensure a simple metabolic pathway. We KNOW that if that MD bridge breaks, the results are not pretty.
 
4DQSAR said:
@notsmokeymcpot42088 It was the synthetic CB1 ligands that were the worst. I think something like 68% of them contained dimers and trimers (I just counted the MW of the active and the impuries and what do you know, exactly the right MW FOR dimers and trimers).

Ihe problem is that having much higher MWs, they won't vapourize ahead of the flame-front. Instead they pyrolize into lovely things like nitrosamines. So all those kids smoking Spice today are quite likely to be the subject of cancer studies in a couple of decades.

MDPV in particular is a perverse example. It was in the original patent for pyrovalerone but wasn't used clinically. I think that highlights the fact that more potent does not mean better. I would GUESS that pyrovalerone was chosen because that para methyl moiety is going to ensure a simple metabolic pathway. We KNOW that if that MD bridge breaks, the results are not pretty.
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Ooh Yea spice was some sketch stuff. Jwh - 018? I remember smoking it while on probation -- than I think I was still failing from that as if I recall the line got darker than it was previous to smoking it. *Protip, you need drug tests buy em in bulk for like .89 cents a piece, Do not get taken by Walmart or w/e --- I had like 300 and 100 of the strips to check dilution, ph, specific gravity, creatinine etc and it was like an 80 dollar order. Still handing the dilution creatinine strips out lol

For awhile I had a guy that had oz's of bubble hash for 180 but pot was 200 -- I suspect something may have been up there but it did not feel any different than THC so I rolled with it.
 
notsmokeymcpot42088 said:
For awhile I had a guy that had oz's of bubble hash for 180 but pot was 200 -- I suspect something may have been up there but it did not feel any different than THC so I rolled with it.
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As each class of CB1 ligand came under legal control via the use of Markush structures, vendors ended up having to produce unselective (CB1/C2B) ligands. I mean, CB2 receptors are found throughout the body so who knows what dangers they pose.

In the UK at least we got to see the societal damage Spice was causing. In US people talk about people nodding out on city streets. But we got exactly those behaviors with people using whatever was being sold as Spice. But possible even more bizarre as some would nod out, some would become psychotic, some became violent. It was really unpredictable. I'm glad I don't live anywhere that Spice is an issue.
 
Agmatine is a good cheap OTC opiate potentiator thats also naturally occuring (sometimes considered a neurotransmitter).
It reduces tolerance build-up for most drugs and reduces withdrawals (reported for benzos, stimulants, opiates).
Agmatine shares similar MOA to ketamine (NMDA antagonist, AMPA, mTOR) with additional pro 5-HT2A, imidazoline, sigma-1 activity and alpha-2 adrenergic antagonism.

When exogenously administered to rodents, agmatine enhances morphine analgesia, blocks tolerance to opioids and attenuates withdrawal syndrome in morphine.
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annals-general-psychiatry.biomedcentral.com

Agmatine synthesis in morphine dependence - Annals of General Psychiatry

annals-general-psychiatry.biomedcentral.com annals-general-psychiatry.biomedcentral.com

We conclude that agmatine reduces the development of dependence to morphine and that this effect is probably mediated by the inhibition of cAMP signaling pathway during chronic morphine exposure.
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Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system - PMC

Agmatine is an endogenous amine derived from arginine that potentiates morphine analgesia and blocks symptoms of naloxone-precipitated morphine withdrawal in rats. In this study, we sought to determine whether treatment with agmatine during the ...
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Our results indicate that pretreatment of animals with agmatine enhances the rewarding properties of morphine via a mechanism which may involve α2-adrenergic receptors.
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www.nature.com

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors - Neuropsychopharmacology

The effects of agmatine, an endogenous polyamine metabolite formed by decarboxylation of L-arginine, and its combination with morphine on conditioned place preference (CPP) has been investigated in male mice. Our data show that subcutaneous administration of morphine (1–7.5 mg/kg) significantly...
www.nature.com www.nature.com

General Agmatine overview:
Agmatine, a naturally occurring polyamine derived from arginine via arginine decarboxylase, has been shown to play multifaceted roles in the mammalian body, impacting a wide range of physiological and pathological processes.
This comprehensive review delineates the significant insights into agmatine's pharmacological profile, emphasizing its structure and metabolism, neurotransmission and regulation, and pharmacokinetics and function.
...
In the brain, comparable to established neurotransmitters, agmatine acts as a neuromodulator, influencing the regulation, metabolism, and reabsorption of neurotransmitters that are key to mood disorders, learning, cognition, and the management of anxiety and depression. Beyond its neuromodulatory functions, agmatine exhibits protective effects across various cellular and systemic contexts, including neuroprotection, nephroprotection, cardioprotection, and cytoprotection, suggesting a broad therapeutic potential.
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I have pointed out many times how just how badly animal models fail in modelling psychoactive compounds.

I will just give you the best example I know of. For decades and decades people believed that the opiate analgesic viminol was a mixed agonist/antagonist. Of the six stereoisomers, four were thought inactive (based on animal tests), one was an agonist (Straub test in animal models) and the last was defined as an antagonist (Wei test AKA jumping test in animal models).

It turned out that the isomer that for decades was repeatedly referred to as an antagonist... isn't. It just makes rodents jump. It has no affinity for any of the opiate receptors.

It astounds me that as recently as 2022 there are still researchers who repeat that mistake.

I spent a whole day reading every paper I could find. I might be wrong but I think doi:10.1016/0960-894X(95)00077-7 was the article that disclosed the truth and that's three decades old!!!

Now it's not unreasonable to think that the original inventors of viminol in the 1960s may not have had access to affinity data BUT I find it hard to believe that they didn't at least test all six stereoisomers seperately but as far as I can tell, the jumping test wasn't adopted until the early 1970s so how they tested activity I don't know. I SUSPECT that Zambon saw how much money the Stirling Drug Company were making from pentazocine and a mixed-agonist may have seemed a better bet than yet another potent agonist.

Zambon opened a drug discovery laboratory in Brazil in the late 1950s and who knows - maybe the board of directors needed to see their investment having a yield but that is entiely guesswork.

FYI the reaon I spend so long researching viminol was because I have a hypothesis that for a MOR ligand to demonstrate antagonist activity, the A-ring requires the presence a phenol or bioisostere thereof. Viminol appeared to violate my hypothesis and I really wanted to understand why that sould be. Well, MAYBE in a couple of decades my hypothesis might become a theory... but I'm not confident of that. But I hope it shows that a mistake (or sales pitch) becomes a fact simply because everyone assumes all previous research to be accurate.
 
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