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Harmala alkaloids and opiate withdrawal

just wanted to add this fascinating abstract, I believe it's from the study YBC was originally looking at: Abstract

This study was designed to determine the affinity and binding profile of beta-carbolines for imidazoline I2 receptors and catalytic sites of monoamine oxidase (MAO)-A/B in rat brain and liver. The aim was also directed to assess the in vivo effects of norharman (beta-carboline) and LSL 60101 (I2 ligand) on brain 3,4-dihydroxyphenylalanine (DOPA) synthesis in morphine-dependent rats. Competition experiments against [3H]2-BFI revealed that beta-carbolines recognize the high- and low-affinity components of the brain imidazoline I2 receptor with the rank order of potency (K(iH) in nM): noreleagnine (12)>norharman (20)>harmalol (82)>harmaline (177)>>harmine (630)>harman (700)>>FG-7142 (>100,000). In liver, this rank was different: harmine (51)>harmaline (103)=noreleagnine (103)>>harmalol (1290)>harman (2000)>>norharman (12,382)>>FG-7142 (>100,000). In brain and liver, competition curves for beta-carbolines against [3H]Ro41-1049 (MAO-A) and [3H]Ro19-6327 (MAO-B) were monophasic and resulted in different drug potencies for the two MAO isozymes (higher affinities for MAO-A) and in similar pharmacological profiles in both tissues. In morphine-dependent rats, naloxone (2 mg/kg, 2 h)-precipitated withdrawal increased the synthesis of DOPA in the cerebral cortex and hippocampus (50%). Pretreatment with norharman (20 mg/kg) or LSL 60101 (20 mg/kg) (30 min before naloxone) fully prevented the stimulatory effect of opiate withdrawal on DOPA synthesis. Norharman and LSL 60101 also attenuated the severity of the withdrawal syndrome. The results indicate that beta-carbolines bind with high affinity to imidazoline I2B receptors, and similarly to I2 ligands (LSL 60101) can block the behavioural and biochemical effects of opiate withdrawal.

Pretty rad. reading up on imidazoline receptors. WIDELY expressed throughout the CNS. Fascinating I had never heard them mentioned until this thread.
 
And here is another interesting one on the partial substitution of ibogaine with harmalas in rats trained to discriminate ibogaine.

The effects of β-carbolines in rats trained with ibogaine as a discriminative stimulus

Abstract

The structural features and hallucinogenic properties shared by ibogaine and certain β-carbolines prompted the evaluation of several representative β-carbolines in rats trained with ibogaine as a discriminative stimulus. In a previous report from our laboratory harmaline completely substituted for ibogaine (83.5%). In the present study, only 6-methoxyharmalan completely substituted (86.3%). However, partial substitution was observed with harmine, harmane, harmalol, and tetrahydro-β-carboline (THBC). Norharmane and 6,7-dimethoxy-4-ethyl–carboline-3-carboxylate (DMCM) failed to produce appreciable substitution. These results provide evidence for an ibogaine-like effect of certain β-carbolines. Whether this extends to the previously reported anti-addictive effects of ibogaine remains to be established.
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Open for interpretation, but still the harmalas have been proven to help in a wide variety of addictions, so the compairson with ibogaine is very interesting to say the least.
 
It's the missing piece of a puzzle for me, I came to aya suuuuper late after doing an ibo flood dose and all sorts of other things, largely due to distaste surrounding all the self-righteous hippies involved in it. It's pretty amazing the two SERIOUS teacher plants of africa and south america share this interesting functionality. I'm not surprised, but I am amazed. I am developing a treatment protocol for opioid dependence on a two tier system - long term/high dose addicts for which ibo is recommended, and short term/low dose addicts for whom a course of kratom taper and ayahuasca is less dangerous and often easier to tolerate than an ibo flood dose. Who knew, 3 weeds with the keyes to upending an entire system of suffering.
 
as an update - ive managed to cut my kratom dosage from ~12 - 15g bali daily to ~4 - 5, a 3 fold improvement and I hope to just keep going from there. Truly an amazing set of substances. And I will further say that of things i have been physically habituated to, kratom is BY FAR the most pleasant both in stopping and in actual use.
 
I apologize in advance for any lack of knowledge in this post as I don't usually post in this forum.
I prefer to read & learn as best I can but this thread caught my interest to much.
From what I understand harmala alkaloids & caapi in particular are useful in reducing opiate consumption.
This is something I'm looking into doing, I'm a pain management patient but would like to reduce dosages.
I also am on 6mg clonazepam daily & also diazepam as needed for panic attacks.
Based on research regarding harmala alkaloids being an inverse agonist at the benzo receptors I am curious as to the safety of using harmala alkaloids.
Again I apologize if this question is to basic or I missed something that would answer this question but I want to proceed with extreme caution.
As such I will wait for a response from a knowledgeable member before even considering caapi or other harmala alkaloid containing plants.
Thanks in advance for any help that anyone is able to give me regarding this question & any interactions.

Note that I also have other health issues & take other medications which I can elaborate on in PM or the like.
If anyone takes an interest that is. Again thanks for any assistance in this matter.
 
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woah woah, wait what? Can you please post a link? I haven't seen anything on this. And the MOA gets more and more mysterious - well, i did some of your homework for you accidentally. I am currently on caapi/etizolam/small kratom dose
doing wonderfully. I've also consumed alprazolam and i believe clonazepam to no ill effect. now that you mention it, seems a bit potentiated and like they gel wonderfully.
 
Yes it's indeed an inverse benzodiazepine receptor agonist. I'm not at home so I can't post a reference atm, but I'll post it here later. However, I don't
think it's of great significance interaction wise, I've never felt any interaction either way, and I've combined benzos and harmalas alot.
 
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YBC said:
Yes it's indeed an inverse benzodiazepine receptor agonist. I'm not at home so I can't post a reference atm, but I'll post it here later. However, I don't
think it's of great significance interaction wise, I've never felt any interaction either way, and I've combined benzos and harmalas alot.
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Were you using the benzo's therapeutically or recreationally? It's possible that the Harmalas could impair the anti-anxiety action of a benzo at a regular dose, but the benzo will "push through" and overpower the negative influence of the Harmalas as dose increases.

Or maybe there's really no interaction. I just don't want anyone jumping to the conclusion that there's no interaction, and later finding their anti-anxiety med's are suddenly ineffective.
 
Umm, as an update, i find them tremendously anti-anxiety. I REALLY like caapi. I have worked my krat dose down to 4 - 5 grams, tommorow im gonna go just caapi and see if it works out. I've found i'm using a LOT more than i thought, like 50 - 80g over the course of the day in tea, but it does not upset me or interact poorly with food, quite the contrary i am hungry and have eaten all sorts of shit, though i prefer good fresh shit. I did eat a cheese enchilada with guac and sour cream tonight and was fine, im also chewing tobacco so..... Anyhow, this is a great transition substance, i really like its effects on their own.
 
Were you using the benzo's therapeutically or recreationally? It's possible that the Harmalas could impair the anti-anxiety action of a benzo at a regular dose, but the benzo will "push through" and overpower the negative influence of the Harmalas as dose increases.

Or maybe there's really no interaction. I just don't want anyone jumping to the conclusion that there's no interaction, and later finding their anti-anxiety med's are suddenly ineffective.
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I was self medicating, but I kept within normal prescription rate dose wise. I can't tell for sure that there weren't any decrease or potentitiation in effects, but the magnitude of interaction wasn't enough for me to notice at least. I got the expected anxiety relief, nothing more nothing less.
 
I'm sorry for upping this old thread, but I find it really interesting and I have something to add. I'm concerned by the activity of harmala on the 5HT2B receptor, and the linked risk of valvulopathy with extensive use.
 
Ah, a good point, not something I had considered. There's some questionable stuff going on w/5HT2B and heart problems - I was just reading a thread, can't find it atm, talking about fen/phen, NBOME's and a few other compounds with 5HT2B affinity wondering why some seemed to exhibit this property and others not. To my mind, aya and harmala alkaloids have a pretty reasonable safety profile. Anything that has been used in a consistent manner by humans for tens of thousands of years has gotta be at least marginally safe. then again, those same people use datura and tobacco on the regular too... i'd like to know more about this too!
 
I've started opiate withdrawal using Syrian rue this weekend Will keep everyone updated on progress. So far I hate the taste of the tea so am taking it in 00 capsules. I feel the effects which are on the whole positive.
 
It isn't clear that beta-carbolines like harmine and harmaline produce appreciable 5-HT2B activation in vivo. They do have moderate affinity for 5-HT2 sites but there isn't a lot of indications that they actually interact with 5-HT2 sites at behaviorally active doses. There is a consensus that their psychoactive effects probably do not reflect 5-HT2A activation, suggesting they may not have any effect at 5-HT2B either.
 
PersephonesDream said:
I've started opiate withdrawal using Syrian rue this weekend Will keep everyone updated on progress. So far I hate the taste of the tea so am taking it in 00 capsules. I feel the effects which are on the whole positive.
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Interesting! What are you withdrawing from and at what dose? How much rue seeds are you using? And most importantly, how's it working for you? :)
 
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