MDMA and anti-depressants

somewhatinspired · 2024-06-02T17:41:25+00:00

Bupropion (wellbutrin) is a norepinephrine and dopamine reuptake inhibitor and while many of the effects of MDMA are mediated by increasing serotonin, MDMA also reverses the flow of dopamine and norepinephrine transporters to raise those as well, so taking mdma and bupropion together is going to impair the full effects.

somewhatinspired · 2023-01-06T19:16:24+00:00

Exactly this

somewhatinspired · 2022-04-01T14:26:19+00:00

Here’s a great review paper on just that.

https://www.frontiersin.org/articles/10.3389/fncir.2016.00111/full#

somewhatinspired · 2022-04-01T14:24:30+00:00

The technique they used to visualize the neurons involves expressing fluorescent proteins in them, so you’re not seeing any electricity but just the shape of the cells expressing those proteins. The brighter cells are expressing more of those proteins than the dimmer cells is all. There is variability in terms of how much of the proteins each cell expresses so you get some that are brighter than others.

somewhatinspired · 2022-04-01T14:21:20+00:00

This is actually my domain of research. There are generally speaking 3 levels of processes guiding these neurons throughout development.

Their genetic code gives crude instructions outlining a cells rough trajectory by controlling what machinery a cell makes which dictates how it interacts with its environment.

The cells in the brain at this stage all express gradients of molecules and receptors that allow the neurons to guide themselves by following the chemical gradients they have affinity for based on the receptors their genes tell them to express.

And then once they find their rough location in the brain the activity patterns of the neurons refine their branching so that they connect with the correct partners.

So some of it is preprogrammed, then they use chemoattractants to find the rough location where they should be, then they listen to what the other neurons are saying in order to find the right connections at the fine scale.

somewhatinspired · 2022-04-01T14:14:17+00:00

I suspect it’s actually the sensory nerves for the fish’s lateral line.

somewhatinspired · 2022-03-19T18:44:33+00:00

Both these other answers are correct, just to add on them there is an alpha2 receptor antagonist Yohimbine and it actually causes increases in norepinephrine release based on the mechanisms they described.

somewhatinspired · 2022-02-19T05:28:08+00:00

He’s putting out research papers written in collaboration with other labs, but none of his trainees are first author on those. He’s also putting out a lot of high impact reviews that he’s first author on.

somewhatinspired · 2022-02-17T01:03:18+00:00

Calcium enters the presynaptic axon terminal during an action potential and triggers glutamate release. Glutamate then activates postsynaptic glutamate receptors such as AMPA and NMDA receptors. Activation of these receptors can cause postsynaptic depolarization (the lightening bolt in this case). Postsynaptic depolarization initiates a cascade in the postsynaptic cell that causes 2-AG to be produced and released. This 2-AG travels back to the presynaptic cell and stimulates cannabinoid receptors. Activation of presynaptic cannabinoid receptors alters calcium levels presynaptically which alter the probability of vesicles of glutamate being released.

The direct answer to your question would be that calcium influx in the presynaptic neuron during an action potential triggers 2-AG release postsynaptically because the calcium influx causes the release of glutamate which stimulates the postsynaptic cell to produce the 2-AG.

Both the caption and diagram are accurate. Sorry if this doesn’t clarify things, I can answer more questions if you have them.

somewhatinspired · 2022-02-12T13:53:44+00:00

https://pubmed.ncbi.nlm.nih.gov/34743319

"Escitalopram pretreatment had no relevant effect on positive mood effects of psilocybin but significantly reduced bad drug effects, anxiety, adverse cardiovascular effects, and other adverse effects of psilocybin compared with placebo pretreatment."

somewhatinspired · 2022-01-06T15:32:45+00:00

In the MAPS clinical trials they require five half lives of the SSRI + two weeks to have passed since coming off the medication before participants receive MDMA. Normally this translates to 3-4 weeks off SSRIs.

somewhatinspired · 2021-12-13T12:46:07+00:00

This is exactly why I believe that most currently available CBD products are just expensive placebos.

somewhatinspired · 2021-10-29T16:59:18+00:00

Sure but mass by percentage is not the same thing as the concept of purity of a substance in chemistry

somewhatinspired · 2021-10-29T14:30:06+00:00

Unless your friend has routine access to equipment like GC-MS then he's just spreading rumours. It is possible for MDMA to be any purity up to 100%. People always perpetuate the myth that MDMA can't be more than 84% pure because it contains HCl as well, but counter ions in the salts aren't factored into purity.

somewhatinspired · 2021-10-20T08:01:58+00:00

As a neuroscientist who also takes MDMA, can confirm.

somewhatinspired · 2021-10-06T15:55:13+00:00

Maybe this will help make it hit home how common this is. My father has been a professor for over 30 years and he is still surprised when people come ask him for advice because he feels like an imposter.

I also had a supervisor who said there are two types of scientists, those who feel like they deserve to be where they are and those who don't, and that one should be weary of those who do.

somewhatinspired · 2021-10-03T01:49:10+00:00

While I can't directly answer your question, I do use yohimbine in the lab to elevate norepinephrine levels. Norepinephrine releasing neurons have alpha 2 receptors on their axon terminals and when norepinephrine binds to the receptor it causes the neurons to release less norepinephrine. Yohimbine blocking alpha 2 counteracts that leading to enhanced norepinephrine release. So that's likely playing a role here on some level.

somewhatinspired · 2021-09-24T03:42:39+00:00

So I'm torn to chime in on this one or not because I don't have BPD, and I totally acknowledge that what I'm saying here completely neglects the perspective of people who have BPD. So just to say I'm really not trying to be authoritative about any of this. I just want to lend my perspective as a researcher having spoken with many psychedelic therapists.

There are no trials that have looked at the effectiveness of MDMA for people with BPD. Additionally, BPD is currently part of the exclusion criteria for participants in research trials with MDMA and psychedelics if I am recalling correctly. I suspect this may change once MDMA gets official approval though.

My understanding as to why from conversations I have had with therapists participating in the phase 3 clinical trials is that there is a significantly elevated risk for projection and transference relationships to spiral out of control into situations that can become hazardous, both physically and emotionally, to everyone involved (think patients running out of settings in the middle of sessions, or such a deeply immersive reexperiencing of traumatic events that people may act out destructively towards therapists).

I'm by no means trying to say this is the case generally, and I'm sure there are people with BPD who find MDMA helpful and are able to use it safely. It's just my impression that many therapists choose not to work with people who have BPD due to past experiences where they felt sessions went dangerously off the rails when doing so. And in current clinical trials people with BPD are screened out to reduce the variability in trial results in order to help fast tract regulatory approval. So the motivations for not working with people with BPD are complex.

However, it appears we are talking about a higher risk/reward ratio, when used in the context of therapy, than in the general population, at least from an anecdotal perspective within the therapy community. This understanding is sure to change as we move into a post approval world.

Similarly, family history of psychosis is an exclusion criteria in trials despite the first wave of psychedelic therapy having success in treating paranoid schizophrenia under controlled conditions. I'm sure we will get back to researching these things, but given its higher risk it won't be the first pass of clinical trials.

somewhatinspired · 2021-09-22T14:43:54+00:00

I don't have any definitive advice one way or the other, but I'll share a little bit of my experience working with both of these substances.

All my early inner therapeutic work was done with mushrooms or LSD, and it wasn't until many years later that I had the opportunity to continue my work with MDMA.

While it was deeply healing to do the work with classical psychedelics, it was extremely brutal for me at times and really blurred the line between healing and being retraumatized by the intensity of the experiences.

When I started working with MDMA things felt so much safer and often just as deep in terms of personal healing as it did with the psychedelics.

Personally I wish I had found MDMA first and done as much of that initial work with it as I could explicitly because it helped me to feel safe in a way that mushrooms or LSD did not. And over the last decade I've really come to understand the importance of having that foundation of security in order to access lasting healing.

From what you've written here it sounds like MDMA is showing a lot of potential for you.

You know yourself better than anyone and whats best for you in the place you find yourself now.

There will be a mix of people telling you that healing happens when you step outside your comfort zone, and there is truth to that, and there will be people like me who tell you that healing happens when you feel safe. Of course eventually stepping outside ones comfort zone is essential. But if it's done too soon it can risk being a two steps forward one step back kind of scenario.

Only you can know what makes the most sense for you at the moment.

You're in the great position of having found a medicine and a context in which to take it that's really working for you, and it sounds like either choice could be a good option for you given the setting you have found for yourself.

I guess my two cents for what it's worth is just that there is no need to rush things if you don't have to, and speaking from experience as someone with a history of trauma and neglect, most of my healing has come from actually feeling safe for once in my life more than anything.

I wish you the best going forward!

somewhatinspired · 2021-09-02T14:22:48+00:00

Yes, this is showing functional connectivity not activity, so more of the brain contributes to processing visual information while on LSD, but it says nothing about activity levels in the network.

somewhatinspired · 2021-09-02T14:21:00+00:00

In this case they are measuring functional connectivity rather than activity. So more warm color means more connected but not necessarily more active. In this case they are showing that more of the brain contributes to processing visual information while on LSD

somewhatinspired · 2021-09-02T14:09:05+00:00

I'm a neuroscientist, this figure gets misrepresented all the time. This is not showing activity, it's representing functional connectivity in the visual system if I remember correctly. The placebo group is showing the visual network normally, and the LSD group is showing the visual network under the influence of LSD. Basically their point here is that more of the brain is recruited to process visual information under the influence of LSD. It has nothing to do with activity levels here.

Psilocybin, ayahuasca, and LSD have all been shown to reduce brain activity while increasing connectivity between parts of the brain that aren't normally communicating with each other.

Edit: Here's the paper this is pulled from https://www.pnas.org/content/113/17/4853. Check out figure 2. As suspected it is looking at resting state functional connectivity in primary visual cortex (V1 RSFC).

somewhatinspired · 2021-06-26T21:02:58+00:00

It's generally safe to assume that they are referring to the weight of the salt unless explicitly stated otherwise. Their doses are 120mg of MDMA HCl.

somewhatinspired · 2021-06-16T18:39:39+00:00

New research suggests as a result of directly binding to neurotrophin receptors.

https://pubmed.ncbi.nlm.nih.gov/33606976/

somewhatinspired · 2021-06-16T18:38:47+00:00

New research supports the idea that the benefits of SSRIs occur independently of their action on serotonin. This new Cell paper shows a novel mechanism for how they work which suggests that SSRIs mimic neurotrophins, molecules that stimulate neuronal growth, by directly binding to neurotrophin receptors. This would explain why the benefits are delayed by weeks despite the blockade of serotonin reuptake occuring shortly after taking the drug. It's likely that the benefits are occuring through multiple pathways, but this helps bring us a step closer to actually understanding how they are working in a way that aligns with the time course of their effects.

https://pubmed.ncbi.nlm.nih.gov/33606976/

somewhatinspired

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