Demystifying Microdosing

We’re at an interesting juncture in the world of alternative medicine nowadays aren’t we?

On one hand, we've got unlicensed hippies flagrantly touting the virtues of (and leading) life-changing ayahuasca ceremonies, filled with rich tech Bros vomiting their way into transcendental clarity. And on the other hand we’ve got creepy billionaires t-bagging the proverbial ballsack of psychedelia, hoarding Intellectual Property, to tragically restrict patient access in this traditionally pluralistic space.

But fret not - there are still options available to us normies out there, which don't require shelling out 400 bucks to your aunty's dog’s hairdresser-come-spiritual guide to reap the benefits of psychedelic medicine.

Let’s take a look at the world of psychedelic medicine and start with demystifying the world of “microdosing”.

Fun Fact: A friend of mine wrote their Master’s thesis almost entirely while microdosing and absolutely smashed it.

BUT HOW DID TINY AMOUNTS OF ACTUALLY ACID HELP WITH WRITING A THESIS?


Firstly, let's ask - what equates to micro-dosing?

In the case of my friend, it was ALD-52. Because of the nomenclature - it’s name sounds nothing like Lysergic acid diethylamide, (LSD) but - like almost all legal-modern derivatives its simply a pro-drug to LSD. Normally, this means that something is consumed in an inactive form but becomes active in vivo (in the body). In the case of LSD derivatives, it’s consumed in a legal form and get’s converted into something, which could otherwise not be sold lawfully.

ALD-52 has an inactive moiety (drug bit) that is connected to the LSD molecule with a notoriously weak amide bond. But since you are only as strong as your weakest link - this law-deceiving disguise breaks off almost immediately leaving you with the active form.

For those interested - the parts highlighted in blue are particularly vulnerable to amide hydrolysis under extremely acidic conditions (like in the stomach) or through the action of enzymes called amidases (found mostly in the liver).

At this point in Germany they have made about 6 subsequent iterations illegal starting with ALD-52, then P1-LSD, then 1V-LSD, then 1D-LSD and the rest. But in this endless game of cat and mouse - chemists simply alter the inactive moiety and have a brand-new exception to the law sold openly in places like https://lsd-legal.de/shop/ - Wahnsinn, oder!!?????

People microdose with a multitude of substances reflecting a diverse range of shapes, sizes, charges, sources, both natural and synthetic but my maxim is - for it to count as true microdosing it must have the capacity to interact with the 5-HT-2A receptor. This is the most widely acknowledged commonality of all psychedelics. And while a little shot of schnapps, a tiny bump of coke or even a baby dab of ket might induce an altered state of consciousness, I’d say for our current purposes, this falls outside the definition of microdosing.

I’m in! How Does it Work?

To oversimplify, we could say that the agonism (activation) of the 5HT-2A receptor triggers a subtle alteration in consciousness, which falls short of the profound experiences people report from taking higher doses and thus allows you to remain clear headed but from a different emotional perspective. Your take on things is more nuanced, you see connections that you missed before with a more rigid, baseline consciousness.

Let’s dig a little deeper… Serotonin (aka 5HT) in its endogenous (freshly produced by the body) form helps to modulate numerous cognitive processes, including mood, perception, and cognition.

As a potent agonist of serotonin receptors, (in particular 5HT-2A) LSD can lead to elevation of mood and crucially, trigger the release of Brain Derived Neurotrophic Factor (BDNF). BDNF facilitates increased connectivity within the brain - neuroplasticity - leading to increased growth of dendritic spines (pictured below). Spines are tiny cell ‘arms’ that reach out and touch other cells to communicate electronically. More spines, more connections, more communication, more thinking outside the box?

Exercise, as well as SSRI antidepressant medication (like Prozac & Sertraline) also indirectly trigger the release of BNDF, which is a central theory as to why all three interventions might be effective against depression. But that’s a story for another day.

On the point of connectivity - microdosing might also affect the Default Mode Network (DMN). I’ve written about this before but, in a nutshell - the region responsible for all that internal chatter, that rumination and fixation over the past and future can be silenced, through various means, providing one with respite to focus purely on the present. This, for many helps improve concentration or at least interest in tasks in the current moment.

Take too much though, and you my friend, will transform temporarily into a giggling, dribbling, space-case incapable of cooking an omelette, let alone writing a thesis. I’m guessing.

Next, I'll take a look at the so-called 'Thalamic Filter' model of psychedelics, which relates to the absolute compromise of sensory-gating to explain what is widely known as tripping balls.