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Wile E. Peyote

Nutt interviews Nichols Drug Science Podcast

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What a fantastic episode. Some highlights - Nichols burns Strassman on endogenous DMT, suggests some concerns about the 5ht2b receptor and microdosing LSD, and talks about the background of the Heffter institute.

https://drugscience.org.uk/podcast/27-pharmacology-of-drugs/

If anyone has more information to share about 5ht2b and microdosing risks, please share them. I'm going to do some more research on this topic and will share anything I find here. LSD seems often to be the substance of choice for microdosing as many people find psilocybin tiring and mescaline nausea inducing, so I think it is important to find the harm reduction message here.

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I think Fadiman's protocol is a good point of departure with microdosing mushrooms. I personal feel it is important to have a day or two between doses to enable a more conscious integration of subjective effects, particularly given effects may not be noticed until some time into a microdosing regime.

 

It is also very important that users acknowledge the massive variations in potency between species of mushroom and adjust their dose accordingly. Still I would agree that LSD does offer a somewhat more accurate mode of microdosing as the dose can be a lot more easily calibrated for consistency as opposed to dried mushrooms.

Edited by Responsible Choice
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Interesting (to me) in this podcast was the mention of MDMA's potential for psychoanalytic therapy.

I'd be astonished if micro-dosing mescaline would induce nausea -- or if there were any published data on its use in this context. I think by definition the microdose precludes any noticeable effects (or side effects).

5ht2b apparently unmentioned (?) in Paul Austin's book on microdosing LSD:  https://book4you.org/book/5222947/1098b9

Further critique of Strassman's hypothesis:  https://www.samwoolfe.com/2017/09/is-dmt-really-produced-in-pineal-gland.html

 

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I think the phase 3 clinical trials of MDMA assisted psychotherapy will be a critical piece of evidence in the current consideration of MDMA rescheduling  with the TGA. It is an exciting area and a pity there is not more evidence concerning this therapy for other conditions. If the new schedule is made I suspect access will be for PTSD sufferers alone.

 

Microdosing psychedelics is a bit of a tricky concept. Pharmacologically, microdosing would imply there is no pharmacological effect. With psychedelic microdosing, there is a pharmacological effect but the psychoactive effects are subperceptual. I have read anecdotal reports of nausea with mescaline microdosing. Perhaps some people are less susceptible to this. I also think this nausea might reduce once a bit of a tolerance has built up. Very little research has been done in this area unfortunately.

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The definition of PTSD may be expanded, eventually, to include traumas that occur during early childhood -- the root of so-called "borderline personality disorder" e.g.. It's sad that sufferers "self-medicate" (fall into patterns of substance abuse), all because of the way in which our dualistic western civilisation segregates permissible from illicit substances. In the age of Big Pharma/DSM, the situation has become intolerably worse (not to mention ironic), with routinely prescribed, ineffectual cures pharmacologically blocking routes to genuine (psychedelic) self-healing. Mescaline is such a gentle healer, it seems counter-intuitive to micro-dose. With much stronger psychedelics, such as LSD, I can see the appeal of fractional doses. 

 

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Ok, so drug activity at the 5ht2b receptor has been linked to cardiovascular issues:
https://www.ahajournals.org/doi/10.1161/01.CIR.102.23.2836

https://www.nejm.org/doi/full/10.1056/NEJMp068265

 

People with high blood pressure are often excluded from clinical studies with LSD due to the association with increased cardiovascular activity:

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1755-5949.2008.00059.x

 

As I understand it, there is still some lesser affinity of psilocybin/psilocin for 5ht2b. I haven't been able to find any info on mescaline affinity 5ht2b. I'd be interested to compare the affinity of mescaline and psilocybin, as you might be able to infer that the substance with the least affinity would have the least cardiovascular risk.

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