So I want to start this thread becasue I heard others say that harmaline is apparently neurotoxic. After a quick google search I came up with everything from harmaline is an anti-tumor medicine to harmaline is toxic in large doses similar to how ibogaine is toxic in large doses..doses beyond what most take here I am sure. Also I read that harmaline is "twice as toxic as harmine"..which really isnt saying much other than that harmine is toxic as well, and we dont see people drinking ayahuasca and ending up with brain damage, so the toxic dose of harmine must be well beyond what ayahuasca users take as well.

Everything is toxic at some level and alot of these animal studies where they pump them full of some chemical until they die I just cant take seriousily. Just becasue rats die from harmine toxicity at 200mg/kg doesnt mean much in relation to a full grown human taking just 200mg of harmine..I dunno what the circumstances are surrounding these apparnt harmaline studies, but I wouldnt doubt its a similar case.

I want opinions from both science people and people who have lots of experience with pure harmaline? Do you think it is toxic in the doses we would take in rue/pharma?..and do users of harmaline actaul feel that it is toxic personally from taking it in the doses they are using?

Here is the paper:

Degeneration of purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline
E. O'Hearn, M.E. Mollivera
Neuroscience Volume 55, Issue 2, 1993, Pages 303-310

You are right everything is toxic at certain dosage/usage, I find it hard to think that harmaline in any reasonable dosage for humans is neurotoxic, considering both rue as well as ayahuasca (some of which may have more harmaline) have been used for very long and yet no sign of any damage. But maybe a special care with high harmaline dosages should be taken?

The study above was done by injecting harmaline in rats, but now we have to find just how much they injected and how often (and if we can generalize any of the findings to human brain).

Can anybody get that paper? My subscription to neuroscience is only starting 1995...

The paper is attached.

For the harmaline experiments a single injection of 40mg/kg in rats (=3 grams in humans!) or 3 x 25mg/kg spread over 3 days had very visible neurotoxic effects.

So the poison is in the dose.

^^
Quite likely, plus it must be mentioned that in contrast to harmine and THH, harmaline appears to have a recognised toxic effect at abnormally high doses. Even though it is hard to extrapolate conclusions from rat experiments to humans, the data suggest that very high doses of harmaline are best avoided. SWIM would have no problem eating a whole gram of harmine (as it often happens with strong caapi aya brews) but he would think twice before gulping a gram of harmaline.

I think a specific mention about the neurotoxicity of harmaline should be made so that people can make wiser decisions.

Harmaline is defo a rougher ride then other harmaloids for me. Also the fact it's more potent by near enough 50% makees it easier to consume more than one would actually need.

A lot of the time with rue extractions the natural balance of alkaloids is quite good and I don't bother refining, though with some that are more harmaline heavy in effect, I find it very necassary to seperate in order to get a good balanced experience.

To put that in to perspective, 40m/kg is a dose of 3 grams of harmaline for a 75kg person (165 pounds). If we assume, on the high end, that syrian rue contains 7% alkaloids (assuming ALL of those alkaloids are harmaline, which they aren't), then 3g of alkaloids would be found in about 42 grams of Syrian Rue. No one should consume that much rue. They certainly wouldn't take it for 3 consecutive days. Also, pretty much anyone who intakes rue, or harmaline takes it orally, giving the body a chance to throw up the overdose of the substance, which they would certainly be doing much of. I've never heard of anyone injecting harmaline.

Anyway, 3g of harmaline is about 30 times larger than a typical dose of harmaline for mao inhibition, typical being 100mg. A strong dose of harmaline for a harmaline only session would about 200mg, or 15 times less than 3g. An overkill, sickening dose of harmaline would be 500mg, or 5 times less than 3g. Or, still 2.5 times less than a 25mg/kg dose (1.5g dose) in a 75 kg person.

Still, these amounts are physically fairly small. It's important that individuals make sure they measure their dose and don't take more than 250mg or so, which would be overkill for most people..... if one happens to be in possession of pure harmaline. Typical dose of Syrian Rue for mao inhibition is 3g. 6g is nauseating. 10g will have you throwing up like you've never thrown up before. Note: theorhetically, 3g of Syrian Rue would contain 210mg of harmala alkaloids if we assume that Syrian Rue contains 7% alkaloids. These are the high estimates.

I wonder though, when the study says, "very visible neurotoxic effects", I wonder how severe those effects are? In in comparison to what? We know that alcohol is toxic. I wonder what the neurotoxic effects are compared to the universal biological destroyer, alcohol.

We have some published reports of people consuming up to 150g syrian rue (!!!) after eating 1kg sheep testicles (go figure), and while the person had convulsions and signs of acute intoxication, after a few hours the person regained health and went home, no sign of lasting effects. A few of the publications are here:

https://www.dmt-nexus.me...&m=158195#post158195

Im not at all suggesting people eat ridiculously high amount of harmaline/rue, please dont do that! All im saying is that because a certain experiment with rats showed a damage after a very high injected dose, it might call for prudency in human use, but doesnt in any way have to say that people are at risk consuming any reasonable, even relatively high doses.

At this point we dont have a single report of anybody ever displaying neurological damage from harmalas and/or harmala-containing plants such as rue or caapi

OMG! Well, I do not condone such actions. I don't know what their motivations were. They surely would have known it was going to make them very sick. Sometimes people just take too much for whatever reason they had to take that much rue with goat testicles. But for the average person, they should know that taking anything over 10g of Syrian Rue, or over 500mg of harmaline is going to make them feel extremely ill. No reason for an average person to take quantities larger than that for any usual purpose. Not neccessary.



agree

A lot of the hard body load I've experienced with harmalas has always accompanied massive detoxing of some kind, physical, emotional, or more. I wonder how much of these effects are the body cleansing itself?

It is also interesting to note, like Dagger said, continued exposure over time results in less body load. It's the difference between crawling and walking a straight line... hmmmmmmm.

Can Harmalas cause cumulative damage from taking low doses for long periods of time?

I ask this because I would like to explore the depression treatment and psychic enhancement I've been hearing about with daily low doses. Possibly even use it post-methadone for opiate addiction.

Long term regular ayahuasca users have been studied and there was no sign of any damage, even after decades of use. B. caapi rarely (if ever) has harmaline, so to be on the safe side you could try using caapi or if extracting from rue, separating harmine and harmaline and using harmine.

Its possible harmaline long term usage presents no damage either but we dont know that for sure, so if you're planning on doing this for long, maybe go for harmine / THH / caapi

Forgive my stupidity, but I'm confused. Are you saying the harmaline isn't necessarily needed to get the anti-depressant properties from Caapi? I was under the assumption that it was the synergistic effect of the three of them (harmine, harmaline, and THH) that treats depression.

No stupidity there, it's an honest question

Well harmaline is present in B. Caapi usually in small to trace amounts. The two main alkaloids are harmine and tetrahydroharmine. There are other trace alkaloids which may or may not play a significant part in terms of beneficial effects, in their synergy with harmine and tetrahydroharmine. (check the attached papers 1 and 2 for more info)

Harmaline is way more present in Rue, where it can vary in amount quite a lot, from, IME, 25% to 75% of the harmala alkaloids in peganum harmala seeds, the rest being harmine.

Caapi/Ayahuasca/Harmala's anti-depressant properties come from at least 4 levels:

1- MAOI effects. MAO enzymes also break down serotonin, and therefore taking a MAOI increases the amount of serotonin in the synapsis. In fact, some of the older anti-depressant medicines were MAOIs (irbocaboxazid, selegiline, and the newer and less dangerous moclobemide). This beneficial MAOI effect will be present with all the harmalas, alone or in synergy. On a side note, the fact that these substances are MAOIs also add risks while the substance is still active in a person's system, specially refering to drug interactions (with pharmaceutical SSRIs, stimulants, etc)

2- SSRI effects of tetrahydroharmine. (McKenna et al., 1998; Frecska et al., 2004). Tetrahydroharmine has shown some mild action in preventing reuptake of serotonin back into the neurons. This means when serotonin is released in the synaptic cleft between neurons, part attaches to the neuroreceptors, and the part that doesnt 'attach' to the neuroreceptors usually gets reabsorbed by the previous neuron. This is the reuptake. So THH mildly prevents this from happening, so there's a bit more serotonin in the synaptic cleft that isnt absorbed back, and this increased amount of serotonin can be a help against depression

3- Upregulation of serotonin neuroreceptors (Callaway et al., 1994). Usually when there's an increased amount of a certain neurotransmitter in the synapsis, there is a downregulation of the neuroreceptors, like a natural compensation of the body to not get overwhelmed by that neurotransmitter. Think about people taking MDMA in large/regular doses, the excess serotonin release will be compensated the next days with both lower serotonin levels as well as a downregulation of serotonin receptors, so people can feel really down. With ayahuasca, this seems to be the inverse, and it actually makes you more sensitive to serotonin afterwards, so it also helps fighting depression. This is known to be caused by THH (check callaway's self experiments), but it might or might not be the case with the other harmalas. Callaway seems to think its specific to THH.

4- Psychological insights. Being in another state of mind can help you see yourself from a different vantage point, think about the causes of your negative state of mind, reassess your life plans, etc. This certainly adds a very important level to the cure of depression, because these insights can be long-lasting and not just based on a pharmacological "clutch". This can be there because of any and all of the harmalas, as well as dmt if its taken in ayahuasca (or even other psychedelics too)

5- Contextual support. Very often, ayahuasca is taken in a supportive context. There are very tight-knit groups which help integrating and dealing with the experiences, whether it is in traditional amazonian indigenous rituals, or in Santo Daime / UDV urban ceremonies, or in a psychonautic careful context with close people involved/aware. Sharing the experience, expressing, communicating and getting feedback, receiving support in different levels, this can all be essential to help one make sense of one's path. This will be independent to the substances themselves.

I just get frustrated because sometimes it seems like the more research I do, the more confused I get.
Thank you for that information, it does help clear some things up.

Everything is toxic in large doses, even water. The poison is in the dosage, not in the substance. I've heard something about oral harmalas have a bioavailability of only around 2%. Injection should have close to 100%. If 40mg/kg in rats by injection is neurotoxic, that would mean 3g for a 75kg human. But that is by injection, so if we assume my numbers on bioavailability is correct, the equivalent for oral use should be 150 grams (!) of pure harmaline. Would be great if someone could back these claims up, or reject them.