serotonin OVERLOAD and aggression, anyone?

[null24]

I've been experimenting with rue, specificity as an anti depressant. I was curious if the RIMA properties would effect relief from suffering due to severe depression which I've not been able to find pharmacological help for.

When I've taken SSRIs, or even St. John's wort, I've experienced horrible side effects that consist of extreme anger and irritability, to the point of being in a rage. Over something as dumb as my phone being itself or someone owing me five bucks who won't pay. Big deal right?

This same thing began after three or four days of consistent smoking of raw rue seeds continuing for nearly a week after i ceased doing that. It was scary, I'm a very laid back guy normally.

Of course, its very distressing to think I've found something to help that harms, but i honestly think that a more careful administration and perhaps less frequent i use would be more beneficial, but right now, I'm clearing my system of harmalas before, and if, i begin this exp again.

Funny thing, short acting seratonergic tryptamines, ala DMT, seem to have incredible efficacy with depression for me, so my research isn't a total fail, but still, I'd like to incorporate rue.

Does, or has, anyone else had this thing happen to them with the use of seratonin raising substances, SSRIs, MAOIs, etc? How about with St Johns wort, or SAMe, etc??

 

[DreaMTripper]

I think it could be increasing testosterone levels rather than serotonin levels.. no time tro find a study now but a quick google search hinted it may be the case..

 

[pitubo]

What about noradrenaline and other pressor amines?

 

[DesykaLamgeenie]

I don't know anything about it possibly being testosterone, but I am under the impression that extended use of harmalas could allow more neurotransmitters than just serotonin to build to a level of excess - i.e. all amines, which would include dopamine and possibly others - I know very little about neurotransmitters and harmalas' effect on them.

But what I'm getting at is that when working with harmalas, it seems likely to me that you're not just affecting your serotonin levels. I think it may be more complicated than that...and as I saw you say in a different thread, you experienced positive effects before you took it a little too far and then it went downhill. If I understand correctly, depression is mirrored in one's levels of certain neurotransmitters - so let's say prior to experimenting with harmalas some of your neurotransmitter levels were on the low side - serotonin or not, I guess it doesn't really matter. Point is, you smoked a little and it helped to boost them a bit, making you feel better. But then you kept smoking more, and it likely brought the levels up too high - just as they can be too low. So more is not always better.

Another thing that could complicate matters is that if the harmalas are affecting more than just serotonin levels, they could be making the levels of certain neurotransmitters higher that were already at an adequate level.


I'm no doctor and like I said know very little of this subject...so someone else may come along throw everything I've said in the garbage...but I've seen you post a few times about this and hadn't seen much discussion on it so I figured this time I'd chip in with what little I have to offer.

 

[cave paintings]

I think as others mentioned, the potentiation of other neurotransmitter amines is something worth thinking about. Its a very complex coordinated dance in our brain of all these transmitters and neurotrophic factors it seems, so I'm careful running with the more serotonin = more happy hypothesis that is often posited. I don't doubt serotonin has a powerful role, I just wonder sometimes if its more about what synaptic networks are rewarded and building 'healthier' thought patterns (and therefore synaptic connections) that sustainably reward us. But one can speculate all day about neurochemistry. I had a couple week period where I was microdosing caapi by smoking it. I found myself a bit more psychedelic and good at times, but also much more sensitive to my natural dips in mood.

I think harmalas sensitize us to our own emotions via their transmitter interactions, but also to our diets and habits. Diet seems to be pretty strictly adhered to in traditional use of the harmala plants. Heck, food really profoundly affects how one feels anyway without harmalas.
I think you probably have the right idea tapering off your usage for a bit if you're feelin cranky and irritable. Listen to your body and mind. Good food, exercise, sleep, and generating an inner sense of stability and purpose I believe are essentials for working one's way out of depression.

 

[null24]

Thanks for the input y'all, i haven't gone over all your responses yet but I've seen some good points.
Yes, i think i overdid it, in my defense (er,uh,excuse) I really thought the amounts i was getting were negligible. Disregarding the fact that one bowl of raw seeds potentiated a vaped DMT trip to over an hour, so yeah, i was being careless.

The reason i pointed my finger at serotonin as the culprit was frankly ignorance. I'm going on the fact that the symptoms are the same as what I've had from SSRIs and St Johns wort, both of which-i thought-only acted on serotonin. The testosterone is interesting,I'll have to look into that. I didn't know that harmalas affected such a wide spectrum of things.
Anyway, thanks

 

[DesykaLamgeenie]

Thanks for the input y'all

Yup!

I'm going on the fact that the symptoms are the same as what I've had from SSRIs and St Johns wort, both of which-i thought-only acted on serotonin.

Ah well if that's the case then maybe you're not far off base with your thinking. I don't really know much about them, so for all I know it could be primarily a serotonin issue.

 

[skoobysnax]

If you decide to use harmalas again you might try sub-lingual extracted harmalas around 15mg or less to start. It seems to be easier on me that smoking and easy to gauge dose levels accurately. It's may favorite so far before I use DMT. I may like it better than Changa. But I use it alone a lot at about 20mg in the evenings and it definitely puts my in even keel. I did the extraction myself and cleaned it until it was almost white so the nasties are gone. Rue alone has more than harmalas that could be affecting the experience.

 

[obliguhl]

null24, i'm getting the same, everytime i'm slightly out of depression. This is part of the reason i go back to depression because i don't like me as a nasty person. I think that in my case, this anger has more to do with overcompensation and release of pent up anger, self hatred and so forth.

 

[DreaMTripper]

Some say depression can result from anger turned inward..one of my workmates was on SSRI and she wasnt depressed anymore but evry now and again would fly off in fits of rage, medication can only do so much you have to look for the reasons behind the anger and try to reconcile them or let them go, maybe thats what the harmalas are showing you that your depression is rooted in anger?

There could still b biochemical factors involved like someone said before the balance of neurotransmitters is a delicate one, if I were you I would lay off them and have think about what makes you angry while observing whether the anger increases or dissipates. You could start using them again at lower doses I wouldnt rule them out theyve helped me through a tough time before.

I would say harmalas dont raise testosterone, there is only one study that shoed moclo as rasing testosterone. Another study that I couldnt access said peganum harmala reduced tesosterone in rodents.

 

[ManicMongrel]

When it comes to genetics and aggression, research suggest that the 3R variation of the gene that codes for Monoamine-oxidase is more prevalent among agressive and anti-social individuals.

The difference between this 3R variation and the 3.5R and 4R variation, is that 3.5R and 4R is working at a significantly higher rate.

(In individuals with ADHD its also more common to have a fast type of two different enzymes that remove serotonin and dopamine, MAO (3.5 or 4R) and COMT (Catechol-O-methyltransferase))

Now to the point, since there seems to be a link between a slow type of MAO and agression, it might not be too far fetched to suggest that anti-depressants could have anger as a side effect. Although it's important to keep in mind that the body regulate the amounts of MAO so if it has a slow type, it will likely compensate by making more enzymes.

Aggression is obviousoly not a function of serotonin action directly but, likely the balance between dopamine and serotonin. So if something is messing with the serotonin balance then agression might be a side effect in some individuals.

Not sure if any of this helps

 

[steppa]

Here's a good post from dreamer, where he explains some general stuff on maoi. I think this fits here.

 

[dreamer042]

When it comes to genetics and aggression, research suggest that the 3R variation of the gene that codes for Monoamine-oxidase is more prevalent among agressive and anti-social individuals.

The difference between this 3R variation and the 3.5R and 4R variation, is that 3.5R and 4R is working at a significantly higher rate.

(In individuals with ADHD its also more common to have a fast type of two different enzymes that remove serotonin and dopamine, MAO (3.5 or 4R) and COMT (Catechol-O-methyltransferase))

Now to the point, since there seems to be a link between a slow type of MAO and agression, it might not be too far fetched to suggest that anti-depressants could have anger as a side effect. Although it's important to keep in mind that the body regulate the amounts of MAO so if it has a slow type, it will likely compensate by making more enzymes.

Aggression is obviousoly not a function of serotonin action directly but, likely the balance between dopamine and serotonin. So if something is messing with the serotonin balance then agression might be a side effect in some individuals.

Not sure if any of this helps

This is really interesting, I was vaguely familiar with the "warrior gene" idea, but I wasn't aware of the different versions of the MAO gene. This is something I'm going to have to look into more.

I've been aware of the studies linking low levels of MAO-A to aggressive/anti-social behavior for some time, but I've never been quite sure what to make of them because there are also a plethora of studies showing practices like meditation/yoga/pranayama/etc... lower endogenous levels of MAO as well. I'm thinking what's happening, and this purely speculation on my part, is that the aggression is likely related (at least in part) to increased norepinephrine/epinephrine levels and related increases in cortisol/other stress hormones, as well as increased conversion of testosterone to estradiol. I'm thinking the reason this doesn't occur with meditation and the like is that these practices also spur an increase in production of (anxiolytic?) pineal metabolites like melatonin and pinoline (amongst dozens of other tryptamines and beta-carbolines) that inhibit this kind of increased stress response.

This has some interesting implications and would explain a few things. Like why tryptamines like DMT and psilocybin alleviate depressive symptoms and why people can tend to get very anxious on harmalas alone if they don't lay down/relax/meditate. Assuming this hypothesis is correct, this would make a good case for adding tryptamines or engaging in meditative practices when working with harmala alkaloids.

 

[null24]

Wow, a lot to digest here!
Obli you're on to something there...

DreaMTripper-right, right. I've been trying to be as honest with myself as I can (pretty hard sometimes! ) in uncovering the roots of this in my psyche. They say anger is a secondary emotion to fear usually, and i think that they both (anger and sadness ) are based in a fear of abandonment, a deep fear within which I'm pretty much living the realization of. The anger was coming out in response to some things that it was very reasonable to be unhappy about, my over reaction however was the issue. Luckily, i didn't lash out at anyone that i love or vice versa. That's happened before.

M.M.- Fascinating and illuminating info. I really need to educate myself more on the science behind what I'm dealing with, thank you for that though, it makes me feel a little better somehow, maybe I'm not hopelessly broken, lol.

Dreamer042- yes, I've been wondering how a short acting seratonergic tryptamine like psilocybin or DMT could have such positive long lasting effects on mood y that seem to be a pharmacological response, rather than just a euphoric recollection of the event.

 

[RhythmSpring]

I think if you actually do your research, high testosterone is associated with good mood, not aggression. Low serotonin would be associated with aggression.

Y'all wrong.

 

[dreamer042]

Okay, let's bring in some research.

It's important to note I am not suggesting there is any increase in testosterone, I'm suggesting that a higher amount of naturally present testosterone is converted to estradiol when the amount of norepinephrine/epinephrine in the synapse is increased.

This article demonstrates how administration of norepinephrine increased the aromatization of testosterone into estradiol in the pineal glands of rats.
www.sciencedirect.com/science/article/pii/0303720782900326 * Attached

This one demonstrates the link between estradiol and aggression in humans.
OESTRADIOL AND HUMAN MALE ALCOHOL-RELATED AGGRESSION * Full Text

This one demonstrates photoperiod (day length) effects whether or not administration of estradiol will cause aggressive behavior in rats. This lends more support to the idea that certain pineal metabolites (associated with circadian rhythms) may play a role in inhibiting the aggressive tendencies associated with estradiol.
http://www.sciencedirect.com/science/article/pii/S0018506X07002334 * Attached

Chapter 6 of Left in the Dark is also very relevant to this discussion as it provides further evidence for and explanation of the mechanics behind the steroid/hormone inhibiting properties of pineal indoleamines.

Of course this is a very narrow look at a few factors in a highly complex system and emotional/behavioural states cannot be simply attributed to a handful of neurotransmitters. Anyway, regarding the OP, I'd suggest taking some melatonin or engaging in some meditation practice the next time you ingest harmalas and seeing if that helps alleviate the irritability and anger.

 

[universecannon]

I've been aware of the studies linking low levels of MAO-A to aggressive/anti-social behavior for some time, but I've never been quite sure what to make of them because there are also a plethora of studies showing practices like meditation/yoga/pranayama/etc... lower endogenous levels of MAO as well. I'm thinking what's happening, and this purely speculation on my part, is that the aggression is likely related (at least in part) to increased norepinephrine/epinephrine levels and related increases in cortisol/other stress hormones, as well as increased conversion of testosterone to estradiol. I'm thinking the reason this doesn't occur with meditation and the like is that these practices also spur an increase in production of (anxiolytic?) pineal metabolites like melatonin and pinoline (amongst dozens of other tryptamines and beta-carbolines) that inhibit this kind of increased stress response.

This has some interesting implications and would explain a few things. Like why tryptamines like DMT and psilocybin alleviate depressive symptoms and why people can tend to get very anxious on harmalas alone if they don't lay down/relax/meditate. Assuming this hypothesis is correct, this would make a good case for adding tryptamines or engaging in meditative practices when working with harmala alkaloids.

Very interesting dreamer. Seems to make sense to me. Maybe that's one reason why melatonin worked so well with my daily harmala use. And especially so when other techniques like yoga/meditation/tryptamines were engaged in.

Harmalas in general can make people much more emotional, which certainly can be a double edged sword.

high testosterone is associated with good mood, not aggression.

This doesn't seem entirely accurate...it's far too complex to be simplified in this way imo, because you have to take into account it's metabolites as well. But in many cases, there does seem to be a relationship with a lack of empathy (arguably one of the most underrated traits), dominance, and aggression. But maybe we should continue that in PM so to not derail the thread too much.

 

[ManicMongrel]

I have to add a little to what I wrote earlier, first of all it's important to remember that aggression and anti-social behavior are two different aspects. Antisocial is most commonly referred to as the category of personality traits that make up the "dark triad", which is the subcategories narcissism, Machiavellianism and psychopathy.

What is so remarkable is that the 3R version of MAO-A is related to both aggressive and "dark triad" traits.

Even more remarkable is that psychopathic individuals get 4(!) times the dopamine response from amphetamine and stimulants. Although these individuals only have instrumental aggression, as in aggression without any anger aspect (it's a means to and end so to speak). It does suggest that aggression has partly to do with dopamine surges ("cocaine rage" anyone?) since the two personality aspects are influenced by the same genetics. When looking at the neurotransmitter aspect of behavior it's the imbalance between noradrenaline, dopamine and serotonin that tend to be the easiest to observe, the neural anatomy and density of receptors is also very much influenced by the childhood environment.

My impression is that aggression is strongly rooted in early childhood stress, children are very sensitive to emotional distress in other individuals. If the parents are often stressed the first few years of life then that reinforce genetic predispositions to aggression and vulnerability to stress later in life. I think that serotonin's role in balancing the two other (behavior related) transmitters give a strong hit to why the serotonergic psycedelics helps so much with both depression and aggression.

 

[Dead man]

looked into vitamin D3 depletion? there's a connection between mao inhibition and levels of vitamin D in circulation...

Do you have a source for this information? How is vitamin D correlated with agression?

 

[Hyperdimensional Cuttlefish]

it's only anecdotal, but I have messed around with both oral and smoked harmalas over a 6+ month period of daily use and I noticed several things:

-increased activity drive, but increased desire to rest: like an increased "cognitive inertia" where I want to continue on a given process e.g. working out, sleeping etc and not wanting to stop that task. Almost a fixation.

-increased inward thinking and contemplation.

Lack of general illness that I used to get chronically. No more seasonal colds or sinus infections for me, and very little difficulty breathing or exercise induced asthma.


Overall, it has been a very interesting ride and I'm still incorporating stuff from that time, but it was worth it overall.