Insomnia after Ibogaine use caused by chronic microglia activation?

[Amml]

Hey,
I'm member in an Ibogaine group and a lot of people complain about insomnia after receiving a large dose of ibogaine (mostly for addiction treatment). The insomnia seems to last about 4-6 months depended on the dose, but is permanent in some cases.

My theory:
Ibogaine itself causes microglia activation, which is similar to inflammation (not sure about this, please correct if wrong).

If this is true, the slow release from ibogaine and it's metabolites from fatty tissues such as the brain itself could cause a chronic inflammatory state of the brain, which then affects the mood and sleep. Also some people reported about severe lethargy and depression weeks and months after ibogaine use, which could also be caused by inflammation.

The microglia activation may not cause noticeably effects in some people because they may have a healthy lifestyle that prevents negative effects, but especially former drug users in the most cases have a disturbed brain chemistry and altered metabolism/general health, which then may be further destabilized by the microglia activation.

It fits somehow because ibogaine respectively noribogaine is present in fatty tissues for months after a large dose and this laps with the symptoms that are described. (non confirmed, but ibogaine itself accumulates about 100x more in fat than in plasma and is metabolized quickly to noribogaine, therefore such a long release is thinkable)

In this case, NSAID's or other anti-inflammatory substances such as turmeric extracts or cannabinoids may bring release to the symptoms.

Another reason may just be the increased levels of different neurotransmitters by the active metabolite noribogaine, which is the main metabolite of ibogaine stored in fatty tissues. Then the reason would be non-inflammatory and the mentioned substances would not bring relieve (CBD maybe, but not because of the anti-inflammatory effects).

Any ideas to that?

Links:
http://www.bluelight.org/vb/threads/765945-Half-Life-of-Noribogaine
https://www.ncbi.nlm.nih.gov/pubmed/11085338
https://books.google.at/books?id=jP...page&q=ibogaine storage fatty tissues&f=false

 

[Cotcha Yankinov]

Ibogaine unfortunately has many mechanisms at play so there are many possible causes of persistent insomnia.

As an example, ibogaine blocks alpha3beta4 nicotinic acetylcholine receptors in the habenula - the habenula normally is a source of input to the VTA which is intimately involved in addiction, and sleep. The persisting effects on addiction are thought to be due to modulation of this addiction related circuitry via alpha3beta4 blockade (while the acute withdrawal-relieving effects are a bit different).

In some cases these anti-addictive effects may only last around 6 months to a year according to some providers, and then wear off, while in others the anti-addictive effect is fairly permanent. If the insomnia wears off in a good couple months for some, as do the anti-addictive effects for some, then I wouldn't be surprised if both of the effects are both due to VTA/basal ganglia modulation.

As a specific example, lesions of particular cell bodies in the basal ganglia increase wakefulness in animals by 25 to 45% depending on the region https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928571/

Some of these neurons in globus pallidus are inhibiting pyramidal cells in cortex and thus promoting sleep. So one theory could be that ibogaine decreases VTA/basal ganglia excitability via blocking the excitatory habenula input, and then decreased VTA/basal ganglia excitability causes decreased inhibition of cortex because the basal ganglia would normally modulate the cortex.

 

[Amml]

I just read on wikipedia that most neurons in the VTA use dopamine as neurotransmitter, a small part are GABAergic neurons. Ibogaine increases the expression of GDNF which leads to higher dopamine levels. Maybe this plays a role too.
But for further information I'll read some papers

Something interesting I mentioned was that some people report that they feel very energetic and good after small doses of Ibogaine, while I experienced that repeatedly taken low doses of iboga root bark (maybe that is the point) make me feel high similar to cannabis at first, but after 2-3 doses I feel extremely lethargic and this feeling stays for at least 1-2 days even after.
Maybe it's the age, I used it at the age of 18 several times, but never at high doses (max. 0,5g root bark).
But as you said the mechanism are very complex

 

[DotChem]

Hey,
My theory:...

..ibogaine respectively noribogaine is present in fatty tissues for months after a large dose..

Source?

 

[Amml]

As I said I have no source for that, only on a few websites this fact is mentioned but not confirmed

The two points that could support this theory are that Ibogaine/Noribogaine are highly lipophilic and accumulate in fatty tissues.
Source: (https://books.google.at/books?id=jP...page&q=ibogaine storage fatty tissues&f=false)

And the second point is that most of the long term effects after larger doses - the good ones such as reduced depression and addictive behavior, such as the bad ones like insomnia - wear off after about 6 months average (reported by treatment centers and users)

But this could also be a result of the acute effect itself and not the stored an der slowly released substance