The Biggest Lie About Microdosing

whether it's microdoting.com thousands of online articles touting micro dosing's positive effects or the fact that micro dosing is now a multi-billion dollar industry taking small amounts of psychedelics is now the IT thing to do while you can technically microdose any drugs micro dosing psychedelics like magic mushrooms and LSD are where most of these positive claims are coming from but the scientific results of micro dosing are only really coming in now so is micro dosing actually one of the biggest scams of the 2020s this is psychedelic science to start how does Micro dosing work let's take the popular micro dosing drug magic mushrooms containing the active ingredient psilocybin when ingested the psilocybin is rapidly dephosphorylated under the acidic environment of the stomach or by alkaline phosphatase in the intestine kidney and even the blood the biochemical reaction generates a phenol compound called cylosis This is the active compound that can easily cross the blood-brain barrier and get you high if you have taken a recreational dose as high as 2 000 milligrams the active silosin causes the body to experience Visual and auditory hallucinations heightened senses and emotional sensitivity these feelings usually last three to eight hours and it is thought that the effects are mediated by the fact that the drug prevents the re-uptake of the neurotransmitter serotonin in the brain and also has a similar chemical structure to serotonin meaning it can also bind to receptors in your brain new information on how psychedelics work add to these ideas and think that cylosin can cross cellular membranes bind intracellularly to specific proteins which cause neuroplastic effects essentially making your brain work in new ways either way it causes your brain to biologically perceive and experience things without a real stimulus also known as hallucinating now there is some pretty exciting research showing that this altered Consciousness created by a recreational dose of psilocybin could help with symptoms of major depressive disorder there are also other promising studies explaining how the Drug's ability to alter your brain activity could help neurological Connections in the brain that could mitigate the effects of anxiety disorders depressive disorders and attention deficit disorder as well full doses of LSD might have anti-inflammatory properties that are related to depression and could help with depression but these studies are not about micro dosings these studies involve full doses of the drug microdosing means you take one-tenth to 1 20th the recreational dose so instead of taking 2 000 milligrams you're taking between 100 to 200 milligrams and most often once every three days keeping the doses low enough that you don't feel any of the physiological alterations of Consciousness from the recreational dose but still get the psychological benefits of regular use microdosing Advocates products and websites have claims of increased productivity creativity social ability better sex lives increased focused positive mood increased mindfulness and a better General well-being but I hate to say it a lot of the new scientific research is coming in saying that these companies might be lying to you and the reasons are surprising to start one of the biggest issues is that the claims from these micro dosing websites and Advocates are too broad to study the claims are so wide-ranging that it leads to too many variables when trying to create a scientific study that can stand up to scrutiny claiming that micro dosing will make you more productive creative have better sex or just enjoy life more is extremely Broad and not usually how drugs work but these broad positive claims from Advocates or websites actually lead to the biggest problem with microdosing right now which is that in double-blind controlled studies micro dosing doesn't perform any better than a placebo one double-blind controlled study examined the effects of four LSD microdoses on people aged 18 to 35. one group was given a micro dose of 13 micrograms another given double that at 26 micrograms and a third group given a placebo the participants were asked questionnaires for five hours after each dose and completed cognitive and behavioral tests after the first and final doses there were no significant differences between the three groups those who were microdosing and those who got placebos but thought they were microdosing felt the same another study on 191 participants who gave themselves micro doses of either the real thing or a placebo they didn't know which they got but they did administer the pills themselves at home found that in all cases they had improved psychological outcomes significantly from the Baseline but there was no significant difference between the people taking a real microdose or those taking a placebo the researcher actually said as the results came in when we started this study our vision was that we'll be the heroes to prove that microdosing works our results were somewhat disappointing the micro dosing Community was pretty bummed out another study found that there were changes in brain activity in those who were microdosing psilocybin but it was not a double-blind placebo test they were aware that they were microdosing and although there was altered EEG rhythms there was no evidence to support enhanced well-being creativity or cognitive function and the understanding was that expectation underlied the anecdotal benefits attributed to microdose essentially because people were expecting microdosing to work it did the same way a placebo works this doesn't necessarily mean that micro dosing isn't working because there are amazing studies about how placebos work micro dosing just might be a placebo but the scientific Community is starting to lose hope around the actual physiological mechanisms of micro dosing and think that the popularity of microdosing has outpaced the research so many people I know microdose and have talked to me about it so I find this information fascinating I'm curious how the scientific literature will impact the industry but right now it is a Boomin thank you so much for watching this science video we'll see you soon for a new one ace

Channel: AsapSCIENCE

Views: 527,334

Keywords: asapscience, asap science, asapscience youtube, asap science youtube, asap, science, fun science, Psychedelics, microdosing, micro dosing, the science of microdosing, placebo, does microdosing work, how do psychedelics work, joe rogan, gregory brown, greg brown, best science videos, biochemistry of psychedelics

Id: V6aQ7bpdIIo

Length: 5min 53sec (353 seconds)

Published: Thu Mar 09 2023

Reddit Comments

[u/bonobomaster]

Report that shit for misinformation. I already did.

[u/mousekeeping]

Complete BS lolol.

Psilocybin/psilocin have no ability to block pre-synaptic serotonin reuptake transport (SERT). If that was its main mechanism of action it would just be an antidepressant.

The effects are caused directly by binding to the post-synaptic serotonin receptor family, more specifically the subfamily 2 type A receptor (5-HT2A). Though not all 5-HT2A activating drugs are psychedelic (it has to bind in a particular way) all the classic, widely used psychedelics (AKA tryptamines like psilocin, phenethylamines like mescaline and 2C-X drugs, and lysergamides like LSD) have this as their main mechanism of action.

Agonism of 5-HT2A heterodimers with various glutamate receptors and monodimers on pre-synaptic glutamate neurons dose-dependently increase glutamate activity in neurons associated with in visual perception, neurogenesis, learning, memory, and other higher-order functions that structure conscious perception and thinking. But this is a deeply simplified view and the details of how this occurs is enormously complex.

Psilocybin does lightly touch some other receptors but it’s a pretty selective 5-HT2A agonist, which makes it a good prototypical psychedelic without other actions. There can be benefits to action at other serotonin receptors but it also increases the risk of side effects. Lysergamides are much more complicated and affect a wide array of dopamine, serotonin, and other receptors that make them very stimulating and highly potent; same with psychedelic phenethylamines except that they can also have entactogenic properties like (but weaker than) MDMA.

Serotonin on its own doesn’t cause psychedelia. There aren’t that many 5-HT2A receptors and way before those got stimulated to any significant degree you would get severe serotonin syndrome by overloading the much more numerous receptor subtypes in the thalamus and brain stem that control things like body temperature and blood pressure. So you need something that's decently selective for 2A, or at least avoids the 1 and 2B-2C and probably 3 (bc of the QTC prolongation) though mild stimulation of these can have beneficial effects (3 family agonists reduce nausea). 4-7 are less well-understood.

5-HT2A receptors are unique bc they link the monoamine sytem to always combined with an NMDA receptor, allowing it to cause glutamate and associated things like neurogenesis, spontaneous new pathway. It's a little bit more complex but if you want to really simplify things you can think of 5-HT2A as a way to indirectly increase glutamate activity. Oddly while glutamate receptor antagonists (dissociatives) cause the opposite effect, they have a lot of overlapping qualities - probably because they both lead to radically different glutamate activity than in most conscious states. But the mechanism of psychedelics is more targeted, while dissociatives affect core CNS functions like conscious muscle/motor control and the ability to perceive external stimuli (or even be conscious past a certain point).

Edit: 5-HT2A forms oligodimers with various other receptor types as a comment below explains (not just NMDAR), but the heterodimers involving glutamate receptors and presence of 5-HT2A on glutamatergic neurons, most heavily expressed in layer 5 pyramidal cells of the neocortex as well as “laminae III and V of the frontal, parietal, temporal, occipital, [and] anterogenual cortexes”, are probably the crucial biochemical basis of psychedelia and activity in these neurons/brain regions maps onto brain activity observed during psychedelic drug activity.

5-HT2A agonism is necessary but not sufficient to cause psychedelic effects. While not all strong CNS 5-HT2A agonists are psychedelics, all psychedelics are strong CNS 5-HT2A agonists. There are various hypotheses for this, but afaik so far there is not one universally accepted mechanism or theory that would allow you to predict whether a compound is psychedelic or not without putting it inside an animal.

[u/catecholaminergic]

brb while I rail a 2g microdose of the SSRI psilocin

[u/Zealousideal-Spend50]

Why are you wasting your time watching videos like that. Psilocin binds to SERT but with very low affinity relative to its main target (5-HT2A).

[u/banneryear1868]

Well there's no reliable evidence that psychedelics act as SSRIs afaik, nevermind at a microdose level.

But also I don't know of any evidence that microdosing outperforms placebo for what people think they're taking it for. It's being taken for things like depression or "happiness" primarily in a professional-managerial context.

There's evidence that psychedelics may be doing other things at microdose levels though. Charles Nichols has done animal studies to establish anti-inflammatory effects, hypothesized that correlation of treatment-resistant depression and brain inflammation is a potential mechanism of how psychedelics may retain lasting power of effects.

I think the research is pointing to occasional full doses in a therapeutic setting the most beneficial regardless.

[u/LtHughMann]

2000mg of psilocin? Right...

[u/ksk1222]

Well, if I'm mistaken, isn't that how SSRI works? Serotonin re-up take inhibitors....

[u/Isomorphic_reasoning]

Before we get too upset here. (This chart)[https://en.wikipedia.org/wiki/Monoamine_releasing_agent] does list psilocin as having potency of an ec50 of 561nM at the serotonin transporter. Now thats about an order of magnitude lower than MDMA but it's not that far away from methylone (234) or MDA (100-310 depending on isomer) and it's actually higher than 4-fa (739-939).

​

Now I fully realize that when we combine this lower affinity with the much ower dose for pure psilocin compared to the other drugs I mentioned we do in fact realize that the majority of the effects are coming from the direct receptor agonism and not neurotrasmitter release or reuptake inhibition but I do still beieve that it is important to realize that there is a nonzero effect there in a way that there isn't with drugs like 2c-i, 2c-e or DPT that truly have zero affinity and that especially at heroic doses this is likely to have at least some level of effect on the experience.