Harmala as anti-depressent?

[apothecary]

Hello fishies!

I'm sitting in my room, a wilting brug flower the size of my arm is next to me...overpowering me with its smell. Feel like I'm about to start seeing shit!

:D

Anyways, my question for today.

One can take P.harmala/B.caapi and it will increase their 5HT uptake, sort of like a natural anti depressant.

Could one take small doses of this, that wouldn't do any MAO inhibition, but would increase 5HT uptake?

What dose would you be looking at for an anti depressant quality, sans trip? Is that dose possible without any MAOI? If it isn't possible, I'm curious anyway.

[Torsten]

yep, basically the same as taking the antidepressant aurorix (moclobemide). The dose would depend on the individual and is best found by trying it out.

I'd avoid regular use of rue seeds though. Fresh caapi bark is really yummy though.

[apothecary]

Why avoid regular use of the seed? Bad taste, bad for your insides, toxins in there?

[Torsten]

check the peganum page for more info on toxic alkaloid content.

[bsm2wr]

Hey apothecary,

Here's a starter on the pharmacology:

Some anti-depressants and many herbals work by "5-HT re-uptake inhibition". ie, the serotonin is re-uptaken by nerves less quickly and in 'circulation' longer.

Antidepressants are effective after continual use for months at a time. The use of herbals in single or recreational doses in order to effect a medical outcome vs depression should be not be considered.

Hope this helps

bsm2wr

[Torsten]

bsm - MAO inhibitors do not work along the uptake inhibition path!

[mescalito]

I reckon it has huge potential but dose and individual reaction have a big part to play.

Don't know much on caapi though...

[bsm2wr]

No... MAO's and 5-HT reuptake inhibitors are different pathways. Sry for the bogus thread guys!

[khanes]

Hi Apothecary,

An interesting question. As far as I'm aware,harmine and harmaline are beta-carbolines and very effective inhibitors of MAOI enzymes, predominantly of MAO type A. As Torsten suggests, this would put them in a similar category to MAOI antidepressants such as moclobemide (Aurorix and others). Unfortunately, as well as psychotropic effects, which some would consider undesirable (others may value such effects), the limitations of MAOI antidepressants, and one of the reasons they have largely fallen out of favour in recent times, has to do with safety. Even with the reversible MAOI's such as moclobemide, dietary restrictions, including avoiding tyramine rich foods such as aged cheeses, chocolate, red wine, yeast products, etc, are highly recommended.

[Torsten]

khanes- the vast majority of people don't have ANY reaction to MAOa and tyramine combinations and do not need any diet restrictions at all. I think much of their loss of favour has to do with the negative hype and the mere possibility of such interactions. If GPs did their job and actually educated and monitored their patients rather than wanting to send them home with the first available safe pill, moclobemide would be much more widely used.

The combination of moclobemide and tryptophan supplementation produces astounding results (both in speed and effect) even in people who have come off SSRIs for various reasons. However it is not without danger and requires more care and education than the PBS is designed to do.

Good antidepressant effects can be had from MAO inhibitors without inhibiting the enzyme fully. ie, if 3g of peganum is a full inhibition dose for an individual (worked out by the minimum required for oral activity of tryptamines), then 1g will produce good antidepressant effects without any significant psychoactive effects (no more than say 100mg of moclobemide). The same applies to the respective caapi or moclobemide dosages too.

The whole concept of SSRIs has naver made much sense to me. By their own design they work the best if the amine levels are already high. ie, because they work on a 'stretching the available resources' principle, if there is little to start then there is not much else to finish off with. The SSRI however deprives the natural recycling system of its input and actually allow the MAO to eliminate more of the resource. It is like the re-use system for resources, with all its limitations.

The MAOI concept however works on preventing the waste of the resource. So no matter how much you have, you are always going to increase it. It is like the recycling concept of a resource.

In essence, the re-use (SSRI) system treats the symptom, but not the underlying problem. This might be very important and I always believed that SSRIs have a place in healing, especially where an immediate 'window' is required.

In contrast you have the recycle system which does not interfere with the normal flow except at the point of 'waste elimination'.

I have yet to meet a single person who had to discontinue MAOI's because of psychosis or anxiety problems - two issues commonly arising from extended SSRI use. I really wish MAOI's were used more widely.

[bsm2wr]

I have been educated that the concept behind SSRIs are that they are a more precisely acting drug than MOA inhibitors, acting on specific locations. This preciseness of effect is clinically desirable. Where SSRIs can be said to 'act as a scalpel cuts', MAOs 'cut like a kitchen knife' and herbs with several active agents all interacting 'cut swathes through entire neurotransmitter systems'.

We must remember there is no single effect on a system of nuerotransmitters- they all interact with eachother.

Before anyone overreacts sceptically, remember I am just trying to share relevant info and personally I would prefer to grow my own St Johns Wort than take Prozac.

[woof woof woof]

SSRI - P R O Z A C info! http://www.ch.ic.ac.uk/local/projects/veit...itch/index.html

[khanes]

 

quote:

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If GPs did their job and actually educated and monitored their patients rather than wanting to send them home with the first available safe pill, moclobemide would be much more widely used.

 

---

Torsten, this is probably true. Having refreshed my own knowledge of the use of MAOI's in depression, moclobemide does seem to be quite an effective treatment. As you suggest, the reasons why it is no longer in vogue may well be quite complex and, at the level of General Practice, may include such considerations as time constraints or a desire to avoid legal complications.

Personally,I'm one of these fusspots who happens to prefer organic foods and would only introduce prescription medicines into my body as an absolute last resort. As a result, I do think natural therapies,such as the combinations you suggest, are worth considering.

Education is very important. If one has a condition that severely compromises one's enjoyment of life, it would be in one's best interests to learn everything about its possible management,and, given the side-effects of many prescription medicines, seeking a natural approach, with reference to compounds that have a rich heritage on the earth, such as St John's Wort, peganum, etc, can certainly be worthwile.

[ 13. April 2005, 15:02: Message edited by: khanes ]

[AndyAmine.]

While not an MAO-I Ive read Sceletium is a good Anti-depressant.

http://www.sceletium.org/

[Torsten]

khanes - In the early/mid 90's my neighbour was prescribed moclobemide, but it had no effect. His anxiety and rage got so out of control he tried to kill his little toddlers one day by swinging an axe at them. SSRI's had previously failed him, so in desperation he went to a naturopath who told him to stop moclobemide and to start on tryptophan. I suggested he get his doc and his naturopath talking to each other and to try a combo of both. They started very carefully at low moclobemide and 100mg of tryptophan. After 3 days he went to 200mg of tryptophan. The improvement was immediate and amazing. From full blown anxiety and rage attacks several times a day he went to just a bit of jaw clenching and some general anxiety WITHIN A WEEK! A good 90% of his symptoms had disappeared within a week. Since then I have recommended that combo to dozens of people and all who have used it had good success with it. The most important thing I found is that this combo is immediate, ie, you don't have to keep taking it when you are feeling better. This means you can chose the timing of your medication yourself rather than a doc saying that you have to take 1 pill per day for the next 12 months.

So far I have only come across one person who had persistent side effects from taking moclobemide. These sideeffects were diet related and a proof that some food interactions with MAO-A are possible, albeit very rare.

Some others also had minor sideeffects like lethargy when initially trying moclobemide until they had their dosage right.

I think the combo of MAO-A inhibitors and tryptophan is the most effective and immediate antidepressant and is terribly undervalued due to its diminished profitability. I would like to see a study into this combo done because it may well turn out to be much safer than SSRI's when things like suicide risk and SSRI long term complications are taken into account.

[Torsten]

bsm - interesting analogy. However, as you said, the system is pretty intertwined and we really know bugger all about it. We also know very little about the actual mode of action of SSRI's. So what's the point of aiming a scalpel if you don't know what you are targeting at?

It is becoming more and more clear that dopamine is implicated in at least half of all severe depression cases. Yet dopamine selective drugs are rarely used because most are poorly tolerated. Wouldn't it be beneficial then to have a 'kitchen knife' that affects all implicated areas, rather than a scalpel being wielded in the dark?

[mescalito]

I know people that have proven unresponsive to the new generation A/D's,and in fact were actually 'happier' before they took them

This is interesting...got a few observations and Q's for yas !

Torsten

quote:

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then 1g will produce good antidepressant effects without any significant psychoactive effects

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in this case would one be required to watch their intake of home fermented beverages etc?

 

quote:

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The whole concept of SSRIs has naver made much sense to me. By their own design they work the best if the amin

 

e levels are already high.

---

so would having to keep dietary amines to a minimum due to amine sensitivity reduce the efficacy of SSRI's for this person?

Also are all amines created equal?

ie. tryptamines v common protein food amines.

exp. would say no but amines do need to build-up before they trigger sesitive reactions...so I'm not sure???

--------------------------------------------------

bsm

quote:

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I have been educated that the concept behind SSRIs are that they are a more precisely acting drug than MOA inhibitors, acting on specific locations. This preciseness of effect is clinically desirable.

---

Yep unless seretonin is not directly involved in the patients illness

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Khanes

quote:

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Personally,I'm one of these fusspots who happens to prefer organic foods and would only introduce prescription medicines into my body as an absolute last resort. As a result, I do think natural therapies,such as the combinations you suggest, are worth considering.

---

I agree and this is why I became interested in ethnobotany in the first place.

Khanes

quote:

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If one has a condition that severely compromises one's enjoyment of life, it would be in one's best interests to learn everything about its possible management,and, given the side-effects of many prescription medicines, seeking a natural approach, with reference to compounds that have a rich heritage on the earth, such as St John's Wort, peganum, etc, can certainly be worthwile.

---

Couldn't agree more but as you have noticed most of the useful remedies are one-by-one coming under the control of those who supposedly provide so-called "health care"

Got more things to ask but I feel like I'm hogging the thread

[mescalito]

sorry

Torsten

quote:

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It is becoming more and more clear that dopamine is implicated in at least half of all severe depression cases.

---

Is this why tobacco use is highest in people with depressive illness?

[Benzito]

Gambling addicts even have unnaturaly low dopamine levels, and see an abnormal spike in dopamine levels when they 'have a win' on the pokies, etc. When they win, they feel better than you or I do, when we have a win.

People with ADD have low dopamine levels, and a high number of ADD adolescents end up self-medicating (probably without even knowing it) their condition with cannabis. As Cannabis causes a short-term increase in dopamine levels. Long-term they become lower, but at the time of ingestion, you have increased dopamine levels.

I think Torsten hit the nail on the head:

It is fast becoming apparent that many mental conditions actually relate back to dopamine.

[Torsten]

Originally posted by mescalito:

in this case would one be required to watch their intake of home fermented beverages etc?

The whole 'food interaction' stuff with MAO-A inhibitors is grossly exaggerated and mostly irrelevant. I would be surprised if one in 100 people has any significant reaction to MAO-A foodinteractions, and one in 1000 or more who might have a reaction that requires intervention. Basically, if you are sensitive to tyramine build up while MAO-A inhibited then you will need to watch what you eat, but the vast majority of us could drink beer or wine, eat yoghurt or salami, or do any of the other prohibited things wihtout any ill effect.

There is only one serious danger with MAO-A inhibitors and that is serotonin syndrome. This can happen if you combine a serotonergic drug or food with a MAOA inhibitor. Hence the caution about combining tryptophan and MAOI. The very fact that serotonin syndrome exists is testament to the drugs efficacy. ie, when treating serotonin related depression with MAOI you want to create a tiny fraction of the effect that ultimately causes serotonin syndrome.

so would having to keep dietary amines to a minimum due to amine sensitivity reduce the efficacy of SSRI's for this person?

SSRI's are selective for serotonin and hence the other dietary amines would not be affected.

Also are all amines created equal?

Not at all. MAO-A is quite selective for serotonin. eg, in my younger years I did a series of experiments trying to work out the safety of foods and drugs while on moclobemide of harmala alkaloids. There were no food interactions EVER, even though i consumed huge quantities of all the wrong foods (note, there is actually an article on medline about an experiment where individuals took large doses of pure tyramine to find out if there was ANY interaction with moclobemide. There was none!!).

There was very little amplification for ephedrine (60mg felt quite normal and safe), and even less for methamphetamine. Tyrosine and phenylalanine were also very safe. I had a whale of a time on 25mg MDMA, but in restrospect that was a very silly thing to do. 25mg felt like several good pills taken at once and left me totally incapacitated. It is quite obvious that MAOAI has strong effects on serotonergic drugs such as MDMA.

The other drug that caused problems was yohimbine. It was the only time ever in all my drug taking that I thought I was going to die, even though I wasn't really out of it.

Ibogaine on the other hand was amplified somewhat, but pleasant enough (as far as ibogaine goes).

ie. tryptamines v common protein food amines.

exp. would say no but amines do need to build-up before they trigger sesitive reactions...so I'm not sure???

Tyramine is the only one of theoretical concern in terms of food. However in reality the 3-4 hours of full MAO inhibition are simply not enough to build up enough to be problematic. If you were to take ayahuasca for a 20 hour continuous session then you might have aproblem. Ditto if you took 300mg moclobemide every 4 hours. But these are simply not realistic values and hence quite irrelevant.

Re smoking - yes, I am certain that the short term gratification caused by the amplification of the dopamine effect via nicotine is what makes it so addictive especially to people who have strong dopamine dependence. There certainly appears to be a correlation between smoking and either a lack of dopamine or a drive for more dopamine.

You see, we are not all created equal. Some of us are happy with low dopamine levels, while other carve more vene if they have high dopamine. It's kinda like biogenic habituation

[mr toodly]

Benzito:

...a high number of ADD adolescents end up self-medicating (probably without even knowing it) their condition with cannabis

A scary thought. I have heard that this is one confoundation for causally linking long-term erratic behavior with marijuana use.

[planthelper]

i heard that some h users, take parkinsons medication (madopar, spell?), somehow the increased dopa must be benefical to them.

reading this topic, it seems many drugs deplete l-dopa, so i ask are ther an natural sources fot dopamin?

i hate pharma people, but in the case of artifical dopamin, i say well done!

btw, there was rumor in my family that a college mate of my father, invented dopamin medication, and by doing so extended my fathers (and the popes)live tremendosly.

as i am a shaman and not a sientist so i say,

the increased dopa levels caused by cannabis are proly the reason for the occurence of psychotic behavior caused by cannabis.

but the view that cannabis can trigger schizophrenia are wrong, i would rather give this symptoms another name, because drug induced psychosis and non drug related psychosis are two differnt pairs of shoes.

damm you stupid shrinks, get it right.

you doctor dungheads,

go ahead and study and teach the wrong conclusions you previous colleges came up with.

as a shaman i can become something else, without beeing crazy, because i return to my personality at will and without any negative side effects.

if i recieve visuals or audios, i know that they are guidance and not meaningless mumbo jumbo, like for schizos.

i believe i can treat schizophrenia, better than doctors, because i have the insight, but doctor dunghead has only studied pieces of papers and people.

sorry for sidetracking...

[Torsten]

l-tyrosine is a good precursor for increasing dopamine.

l-dopa is poorly tolerated, but for some reason the same amount of l-dopa if taken as Mucuna extract is not. We are finally getting a nice crop of Mucuna this year so I will be able to report on the effects of the beans.

[bsm2wr]

 

quote:

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i would rather give this symptoms another name, because drug induced psychosis and non drug related psychosis are two differnt pairs of shoes.

 

damm you stupid shrinks, get it right.

 

you doctor dungheads,

 

go ahead and study and teach the wrong conclusions you previous colleges came up with.

---

Fair enough, but as we are using scientific terms and concepts here then its a little unavoidable that we stray into the cold and dry world of medicine.

When in Rome.

[AndyAmine.]

Just to clarify what PH was saying about opiates, it has less to do with Dopamine and more to do with the activity of the specific cytochrome P450 enzyme 2D6 (CYP2D6)

If you inhibit it, you can greatly increase the effects and vice versa.

For those interested in this, check out http://opioids.com/opiates/

AA.