• Members of the previous forum can retrieve their temporary password here, (login and check your PM).

Progesterone antagonises the action of DMT

Migrated topic.
Infundibulum

Infundibulum

Kalt und Heiß, Schwarz und Rot, Kürper und Geist,
Moderator
OG Pioneer
Chemical engineer
Another thread prompted me to search in the scientific literature for the latest articles re dmt, and I found this little recent gem:

Johannessen M, Fontanilla D, Mavlyutov T, Ruoho AE, Jackson MB.Antagonist Action of Progesterone at Sigma Receptors in the Modulation of Voltage-Gated Sodium Channels.Am J Physiol Cell Physiol. 2010 Nov 17.

Sigma receptors are integral membrane proteins that have been implicated in a number of biological functions, many of which involve the modulation of ion channels. A wide range of synthetic ligands activate sigma receptors, but endogenous sigma receptor ligands have proven elusive. One endogenous ligand, dimethyltryptamine (DMT), has been shown to act as a sigma receptor agonist. Progesterone and other steroids bind sigma receptors but the functional consequences of these interactions are unclear. Here we investigated progesterone binding to sigma-1 and sigma-2 receptors and evaluated its effect on sigma receptor-mediated modulation of voltage-gated Na+ channels. Progesterone binds both sigma receptor subtypes in liver membranes with comparable affinities and blocks photolabeling of both subtypes in HEK293 cells that stably express the human cardiac Na(+) channel Nav1.5. Patch clamp recording in this cell line tested Na(+) current modulation by the sigma receptor ligands ditolylguanidine, PB28, (+)SKF10047, and DMT. Progesterone inhibited the action of these ligands to varying degrees, and some of these actions were reduced by sigma-1 receptor knock-down with small interfering RNA. Progesterone inhibition of channel modulation by drugs was consistent with stronger antagonism of sigma-2 receptors. By contrast, progesterone inhibition of channel modulation by DMT was consistent with stronger antagonism of sigma-1 receptors. Progesterone binding to sigma receptors blocks sigma receptor mediated modulation of a voltage-gated ion channel, and this novel membrane action of progesterone may be relevant to changes in brain and cardiovascular function during endocrine transitions.
Click to expand...
(I am not going to attach the paper yet since it can only be found in its draft submission format, will do so when it gets properly formatted to publication standards.)

In a nutshell, after the discovery that dmt is a ligand for the intracellular sigma-1 receptor, this paper shows that progesterone antagonises the cellular effects that dmt exerts when it binds to sigma-1 receptor. Progesterone, one of the major reproductive hormones is also a ligand for the sigma-1 receptor. This thickens the plot and it may be relevant to female users of dmt. Insofar, the relevance of dmt acting on the sigma-1 receptor is unclear. We really do not know what this means when it comes to the effects of dmt, especially when we refer to its psychoactive effects. But whatever (psychoactive) effect (if any!) dmt exerts through the sigma-1 receptor, these are abolished by progesterone. It must be mentioned that the study was performed in vitro using cultured human cells, so despite the importance of these results it is essential not to overemphasize.

For me the most striking part (as I specialize in female reproductive endocrinology) is the effect of progesterone. This is where I'd like the input of the ladies of the Nexus on this issue. Progesterone, the prime hormone of pregnancy ("pro-" as in favouring, "-gesterone" as in gestation, pregnancy) is secreted after the day 14 of the menstrual cycle (i.e. after ovulation) and progressively rises till till it drops on the menstrual bleeding. I wonder whether the women of the Nexus get a different experience when they smoke or take orally dmt during the last days of their cycle before their period. By different effects I mean things that may include from poor experience outcomes to elevated/reduced bodily effects(e.g. heartbeating) to mindset( e.g. more/less calm state) etc.

Any input would be greatly appreciated!
 
I hate to bring up the layman's DMT study once again , but I think Strassman did a mesntrual study in 90-95 study, might be worth looking into if you can find a concise paper on it (rather than reading the whole book)

Although without him having knowledge of the info in the above post at the time ,his info may have little relevance.
 
Magicman said:
I hate to bring up the layman's DMT study once again , but I think Strassman did a mesntrual study in 90-95 study, might be worth looking into if you can find a concise paper on it (rather than reading the whole book)

Although without him having knowledge of the info in the above post at the time ,his info may have little relevance.
Click to expand...
Really? I looked at the original papers and it appeared that there was only one woman in his study, who was given dmt on just after her period had finished. Or to quote the papers:

...The one woman subject was studied during the early follicular phase of her cycle...
Click to expand...
(From the part I. Neuroendocrine, Autonomic, and Cardiovascular Effects of the study)

...Sessions were separated by at least 1 week for men, and at least 1 month for the only woman,who always was studied during the early follicular phase of her menstrual cycle...
Click to expand...
(From the partII. Subjective Effects and Preliminary Results of a New Rating Scale of the study)

So basically there's no mention of a menstrual study, at least not a published one.
 
this is from page 152 of the PDF I downloaded( i did pay for a hardcopy to :) )

We began preliminary work in three volunteers for this project. However,
one fellow felt so bad on naltrexone alone that he dropped out after
his first session. In the other two men, we saw little effect one way or the
other, and so we went no further.
Another pilot project was to assess if the phase of the menstrual cycle
in women affected the DMT response. Many women report cyclical variations
in their sensitivity to psychedelics. In addition, animal studies clearly
indicated that sex hormones influenced responses to psychedelic and other
serotonin-active drugs.
We divided the cycle into early, middle, and late in one woman, Willow,
who usually had quite deep and insightful DMT experiences. In this
sole volunteer, no obvious differences in psychological effects emerged.
Since we didn't have funding to pursue this fascinating line of DMT research,
we brought in no more volunteers for it.
Click to expand...

page 236 of the PDF
A few months later, Willow reexperienced another high dose of DMT
in the menstrual phase study. As she stirred, she began speaking:
Click to expand...

besides him standardizing the times the female(s) took the DMT to that sake of congruency, this was all i could find, and it gives no worthy information , but it does more than suggest a specific study on the matter doesn't it ?
 
Thanks for the quotes;

The milieu of hormonal dynamics in women may indeed change their responsiveness to psychedelics so it was a good thing that Strassman standardised it. Yet, even though your quotes suggest a "pilot study" about the effect of menstrual cycle to the dmt experience nothing has been done today AFAIK. One subject is hardly enough to take any conclusions out of it.
 
Wicked find, Infundibulum!

If DMT has anything to do with regulating a sense of well-being, connectedness to life, etc. (I love it for the antidepressant effects), I think it's also worth mentioning I went on the pill for a month (not even for contraceptive reasons), and I felt so horrible. I felt like a whale that wanted to beach itself. I was completely not myself, it made me feel insane, and I felt 1000% better as soon as I was done with it. :? This was maybe a month or two before I learned about Aya, though, so I can't comment on how it relates to tripping.

My quality of Ayahuasca experience definitely changes with the moon cycle, and my body is synced. If I drink on the first day of my cycle (full moon), the experiences are extremely animal, gutteral, primal, basic, instinctual. I go inside my body, have strange visions with "the slime," and any kind of "control"/negotiation I have within the experience disappears. I am a helpless animal ripped apart by the forces of the universe. There have been some powerfully sexual kundalini experiences, and beautiful nights exploring the creative powers within my womb. :D

Compared to times when I am not menstruating, visions are clear, there is more of a mental/intellectual quality, it's much easier for me to interact with what's happening. I am allowed to co-pilot, vs. being strapped to a rocketship and taken for one hell of a ride. Very yang.

Both have always been extremely positive, and they have their place. I like to always try and catch major lunar events because the experiences are more overpowering. I would not choose one or the other. Different doors open on different days.

My sensitivity to smoked DMT is massively heightened on the new moon (ovulation), I will break through on crumbs. The full moon is sensitizing, but not to the same degree as the new moon. I did smoke with a girl on the new moon who is also synced with me, and she needed abnormally low amounts to break through. This would require further experimentation, though, as there are obviously a lot of variables. :p

Maybe menstruating women are banned from ceremonies because men don't want to deal with the totally primal madness that could likely ensue? :p
 
But is it a rising and falling progesterone cycle that behaves the same way?

I thought I should also mention (um, pretty cool), I have a microscope for saliva-based ovulation observation. I can spit on a slide and watch crystals form in my saliva patterns roughly six days before ovulation, and they break apart immediately after ovulation ceases, so I can watch hour by hour what's going on inside my body, if I really want to. :p

So, anyway, I'm not just guessing these things, when there are crystal ferns in my spit, I require less freebase DMT. :twisted:

Physical existence is a fascinating thing!!
 
imPsimon said:
polytrip said:
But all man have progesterone in their bodies two, right?
Click to expand...

It seems like it from this source:

"Adult males have levels similar to those in women during the follicular phase of the menstrual cycle."(Taken from wikipedia)
Progesterone - Wikipedia
Click to expand...
yep, men have progesterone too, albeit in very low basal levels (i.e. similar to the follicular phase of women) and the men's level do not show the dynamic levels typical of the female menstrual cycle. Progesterone peaks massively in women in days 20-24 (7-10 days after ovulation) whereas it goes over the roof in pregnancy.

Manic minxx, very interesting info, thanks for sharing that! It is hard to explain your experiences in the light of progesterone effect on dmt's effect. I was not even expecting to hear that it alters the trip at all! Interestingly, you have lower threshold when you ovulate? this is indeed interesting, during ovulation you're loaded with estrogen and LH (luteinising hormone), one can only wonder how (or if!) these hormones can influence the threshold.

Also, there are better ways to check for ovulation than the saliva test, like vaginal smears (it's really not that hard to do) or even checking at temperature spikes (body temperature rises a degree celsius or so in ovulation)
 
Yeah, I have a special thermometer and awareness of other symptoms, too. :d It's all extremely fascinating to me... especially amplifying the whole birth-life-death mystery with something like DMT. :shock:

Does anyone have any more information about any other related hormones?

This is just a blog, BUT, might provide some kindling to dig deeper into DMT/hormone-related mysteries (uwahaha), I think it's a pretty good summary in plain language:

link :)

Now, IF one is actually more sensitive to DMT while ovulating, AND there are the same and similar hormones in semen that can induce ovulation, AND lots of tryptamines, ______________________________________________.

Time for a SCIENCE PROJECT?!?! :twisted: :idea: :?

(Stepping away from this thread now... :p )
 
Back
Top Bottom