A very, very reputable source told me:

"There is the possibility that there is a rebound effect from DMT use; it promotes release/uptake, etc. of serotonin and other compounds.
When you stop using it, the brain attempts to readjust its normal “balance” but usually does not attain the same state. Withdrawal may be similar to, yet milder
than, stopping a prescription anti-depressant.

I think DMT shows us the complexity of our own minds and that we should work to open those areas of the brain ourselves."


My response:

"Yeah, I did some more and felt once again like a newborn child, I feel great and normal again. But it seems like around every 2-3 weeks I start to feel down and melancholy, I do some more, just a low to medium dose, and then I am great. Starting to wonder lately if there is a causal relation, if one is causing the other.

Thanks for the good response, maybe I should do less, or space it out a lot more. Thing is, the longer I get away from it, the more scared out of my fucking wits I am to do it, paha. Then once I do it, I am glad, haha"


Sort of confirms my suspicion of a brain chemical dependence for well-being.

The section that I have put in bold is unlikely in the extreme. Unless your very, very reputable source has some serious citations, I would take it with a boulder of salt. DMT is not an effective serotonin reputake inhibitor (it does not have anything like the affinity for SERT proteins that a pharmaceutical antidepressant does), nor is it a serotonin releasing agent (you're thinking of MDMA). The ONLY study I could find of DMT's affinity for the 5-HT transporter concludes that tryptamines are unlikely to be re-uptake blockers (interestingly, that same study suggests that tryptamines may be transporter substrates instead of blockers, so maybe your brain is recycling tryptamines along with endogenous 5-HT?)

Here's another study that found that regular exposure to DMT in the form of Ayahuasca increased 5-HT transporter expression (in platelet cells), which would actually DECREASE the amount of synaptic 5-HT available, doing the exact opposite of what you'd expect DMT to do if it really was a SSRI.

As for DMT addiction, it has never been observed in any animal or human models. Even organizations like NIDA and the DEA have (grudgingly) admitted that psychedelic drugs are unlikely to be addictive.

It sounds to me like you're coming to rely on DMT too much. Not that you are 'addicted,' in the clinical sense, but rather, you're using it instead of doing some serious examining of your life that you really should be doing.

Blessings
~ND

Reputable source is Dr. Steven Barker, no reason why I cannot say who he is.

I think that you should take it seriously, use it as medicinal—it is good psychotherapy if needed.

...Then take that knowledge back to become, as you already are, one with nature. Eternity in every moment. Ya know?

No, but seriously... Melancholy is a fact of life, imho. I wouldn't call it "withdrawal." I'd call it sober everyday life.

But this doesn't address any of the points made by Nathaniel.Dread and appears to be an appeal to authority

I would indeed love to see the points of Nathaniel.Dread addressed as well.

And also I have questions like what is this hypothesis of Steven Barker based on? What sources did he use to come to this conclusion? Questions like those linger in my mind and we need some substantiation on this hypothesis.


Kind regards,

The Traveler

And "possibility" ranges from not-so to whatever. Impossible to be wrong with such a witty disclaimer.

"Usually" also ranges from not-at-all to whatever, right, another of that sort.

And what does that mean: "When you stop using it.."?
From what kind of "use" start his targeted effects become an issue that we should take into account?


Usually it's possible that Doctors estimate with logic at hand.

" Melancholy is a fact of life, imho. I wouldn't call it "withdrawal." I'd call it sober everyday life."

I like that.


I sent him Nathaniel's response and am waiting.

Personally I'd say that DMT/Harmala gives an updrawal instead of a withdrawal ..

These were my thoughts as well. Perhaps a psychological dependence has formed. I know I certainly have created a positive association with everything DMT so maybe there's some underlying psychological that's unresolved which gives you the urge to want to return to that place.

There are infinite possibilities.. so the statement starts with admittance to uncertainty about what is to be said after..




In any case, regarding DMT


I have taken SSRIs and dmt gives me the ssri effect for about 5-6 days. So it likely hightens Serotonin levels for a few days.

Maybe DMT heightens serotonin levels for a while, a few days, weeks, whatever, and once those heightened levels go away, things seem much more mundane, in comparison, to what one felt during those heightened levels.

I'm just curious how one would explain the orgasmic feelings exploding in my brain when I smoke dmt?

Dopamine is probably much more likely to be responsible for that than serotonin. Dopamine is the feel good chemical...this is an issue that comes up with some of the RCs that cause serotonin dumps that aren't accompanied by dopamine (and their subsequent lack of popularity).

Now correct me if I'm wrong here. (ND I'm looking at you )

We know that exogenously administered DMT is taken up by neurons and stored in the vesicles and then slowly released over the course of about a week (Source). This being the case, is it possible that the DMT is displacing or functioning in a similar manner to serotonin over that week? Could this (perhaps paired with some receptor upregulation) be what is responsible for the SSRI-like effect people report in the days after using DMT?

The downstream effects of 5-HT receptor agonism are not entirely well understood, but I'm going to echo Snozz on this one. I have a study here that shows that 5-HT2A antagonists inhibit release of dopamine in the striatum, and while that's not direct evidence that an angonist like N,N-DMT might *trigger* release, it's certainly compelling.

Another study has found that 5-HT2A receptors tend to co-localize with an enzyme that helps turn tyrosine into dopamine. The presence of this enzyme is usually considered a good indicator as to whether a cell is dopaminergic or not. The presence of 5-HT2Ars on dopaminergic neurons suggests that a psychedelic agonist might trigger dopamine release.

The big questions is: why doesn't that orgasmic feeling happen all the time? If I shoot up a bunch of heroin, I'm going to get that dopamine release (and the consequent euphoria/analgesia) every time. That doesn't happen all the time with psychedelics (sometimes you can get the opposite), which makes me think that the phamacological activity of DMT is a few steps removed from the release of dopamine, which allows for other things to have some input into what release looks like.

DMT also acts at pretty much every other 5-HT receptor, and a few receptors that are not serotonergic at all, so this is just a tiny, tiny piece of the puzzle.

Blessings
~ND

RhythmSpring I like that. Your statements have what I see as a necessary rhythm. In the 60's they used to say that a person became, if they did, dependent upon the psychedelic experience and not the drug.

A short-lived 5HT agonist such as DMT appears to stimulate an efflorescence of excitatory and inhibitory effects in both the Central and Enteric Nervous systems and that in turn produces cascading effects through other neurotransmitter systems. (citations needed here)

We might call such short lived agonists as give acute effects an acute drug. Acute drugs are not prone to chronic effect. Unless used chronically. And even then we lack the studies I think. Perhaps because it makes no sense rationally to take an acute drug at acute levels for an extended period of time?

SSRIs we might call plateau drugs that depend upon a chronic blood plasma level that give less acute effects and have much longer half lives in the nervous systems.

https://en.wikipedia.org...discontinuation_syndrome The SSRI syndrome you refer to is most evident in plateau drugs with a long enough half-life but not too long. A very long half-life SSRI is not as likely to cause discontinuation syndrome.

The prototypical agonist https://en.wikipedia.org/wiki/Agonist for 5HT is serotonin itself. A SSRI or reuptake inhibitor is not an agonist and as it were, hangs around, never producing an acute effect, but moderating a overall systemic flow over long periods.

MAOI on the other hand when used to treat depression and administered chronically have had record of some discontinuation syndrome.

Post psychedelic depression is often reported and sometimes attributed to the existence of an already existing depression, to depressing facts of life outside the "trip", or to the aforementioned or hinted at despair generated by a greedy need for an "experience"?

Most SSRIs have affinities for receptors other than the serotonin transporter, so it's impossible to be certain that SSRI discontinuation syndrome is specifically related to 5-HT or not. My hunch is that 5-HT is involved, but that there are other elements to the experience (including psychological ones associated with going off one's meds).
Ex. Sertraline is an 5-HT reuptake inhibitor, a DA reuptake inhibitor, an agonist of the sigma-1 receptor, and an a1 receptor antagonist.
Fluoxetine is SSRI, but also a positive allosteric modulator of the GABA A receptor, (again) a sigma-1 agonist, and possible have some inhibitory action as nicotinic acetylcholine receptors.

For reasons that are (imho) largely political and economic, we spend a lot of time looking at 5-HT activity exclusively when talking about these drugs, forgetting that there are 4 other major neurotransmitters, and literally thousands of more minor ones that all also help give rise to consciousness.

Blessings
~ND

I haven't received a response from the Nathaniel questions, but I asked him after that first post:

"I wonder if the rebound effect is similar to MDMA?, can the same be said for other psychedelics as well?
Maybe that is why one should not take them for years..."

and he said:

"Yeah. Any drug that elevates serotonin can cause a depressive “withdrawal”. They’re usually brief.
Repeated dosing of DMT does not cause tolerance but the brain does adapt!

Psychedelic drugs don't raise synaptic levels of serotonin, unless we're talking mescaline, which is a different thread altogether. DMT does not possess any aspects of addiction potential in humans or animals insofar as modern science is aware.*

*I suspend citation due to the late hour and my general malaise at the current time. If necessary I can cite sources later