The Drugnerd Combo: An Exploration Into Mimicking the Effects of Drinking Alcohol
Ah alcohol, man’s true best friend: the first invention of settled humanity*, the social lubricant, the spark in cupid’s arrow, the maker of babies, the trigger of wars, and the ultimate muse of artists. It’s undeniable that humanity has had a long and storied history with the world’s first known psychoactive substance, and until the discovery of caffeine, the most widely used psychoactive compound on earth.
*some historians have posited that settling down into cities was done with the precise intention of brewing beer
The First Agricultural Revolution. Some even posit that settling into cities was done out of a need of organized manpower to brew beer“Drinking Alcohol” aka “Ethanol”, has had its hand in almost every single major event in world history, helping us prevent water born infections in the ancient era, encouraging interpersonal bonds and the creation of tighter knit tribes and societies as we settled into societies, but also taking the lives of countless millions through its relatively intense toxicity and addictiveness.
Albeit being one of the most sacred chemicals in our species’ collective culture, it is also ironically one of the most dangerous drugs readily available.
EthanolLuckily, with modern science, we can postulate potential mixtures of other compound that can work together to achieve the complex set of pharmacological effects of Ethanol while minimizing its toxic organ damaging effects.
In other words,
The Drugnerd Alcohol Combo, or “Look at What They Need to Mimic a Fraction of our Power!”
Before we get started, we first need to establish the major goals of this hypothetical combo: Achieving the pharmacodynamic effects of ethanol and minimizing its heptotoxicity (liver damage).
Alcohol Pharmacodynamics
As discussed previously in the drug categories blog entry, we know that Alcohol is primarily a Gabanergic depressant, but its full psychoactive effects are a bit more interesting than that.
When ingested, alcohol tends to produce 3 primarily distinct but interspersed categories of effects: Gabanergic disinhibition / sedation, dissociation, and paradoxical stimulation. We can break these 3 parts down separately to discuss:
Gabanergic Effects
(See this blog entry for more details: https://www.drugnerd.net/blog/the-various-drugs-that-affect-the)
We already know that Alcohol binds to a disputed allosteric site on the Gaba A receptor that has a very similar impact on the operation of Gaba A receptor as that of benzos (drugs such as xanax). In other words, ethanol binds to a site on the side of the standard Gaba A receptor binding site and works to enable more frequent openings of the Gaba A ion channel. This essentially “multiplies” the effects of endogenous Gaba, and leads to a very disinhibited, talkative, and sleepy effect.
This effect is what contributes to the sociability enhancement, anxiety relief, euphoria, disinhibition (dgaf “I can do anything” energy), and sleepiness of drinking alcohol.
Dissociative Effects
As a secondary effect, alcohol also acts as a dissociative by inhibiting the effects of glutamatergic neurotransmission at NMDA receptors. This works very similar to standard arylcyclohexylamine dissociatives such as PCP and Ketamine.
This effect is what contributes to the mild anesthesia / analgesia (numbness / pain relief), euphoria, tunnel vision, and room spinning effects of drinking alcohol.
Stimulating Effects
Perhaps least understood and most paradoxical of alcohol’s effects is its counterintuitive stimulating effect. This is well known by many alcohol enthusiasts as a few drinks can easily get one into the mood to dance and shout at the top of their lungs. There’s the least amount of info available around the potential pharmacodynamic cause of this phenomenon and indeed most of alcohol’s known effects are strictly sedating (both increased gaba and inhibited glutamate act in an inhibitory manner).
https://pubmed.ncbi.nlm.nih.gov/21560041/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826822/
[While some papers about ethanol mention its stimulating effect, most do not point to any particular system that might be a root cause]
A few hypotheses exist for this, but they all fall short under scrutiny:
Downregulation of Gaba: Long term usage of gabanergic alcohol leads the brain to downregulate endogenous Gaba levels, leading a subject to have a higher than usual excitatory state. This hypothesis falls short because the stimulating effects of alcohol are more common in the first half of a drinking experience and does not require chronic alcoholism to be felt. Even first time drinkers frequently experience the stimulation.
Disinhibition of Dopamine: There are loads of Gabanergic neuroprojections from the frontal cortex into the mesolimbic dopamine pathway. These serve to slow down the production of dopamine into the nucleus accumbens. By increasing the effects of Gaba, the Gaba receptors on these Gaba producing neurons are hit, leading to less dopamine inhibition, which means more dopamine is released.
Since mesolimbic dopamine is involved in motivation, reward, and pleasure (indirectly), this effect could explain the hype ethanol can provide a drinker. A lot of other downers operate on similar effects (such as gabapentinoids and gaba B agonists), so this hypothesis potentially carries some weight.
Disinhibition of Mesolimbic Dopamine is frequently cited as the reason behind Phenibut’s own paradoxical stimulating / pro-motivation effectsDisinhibition of dopamine release doesn’t explain the whole picture though, considering the existence of gabanergic but non-stimulating ethanol analogs such as 2m2b.
Upregulation of Glutamate: Similar to how ketamine leads to downstream upregulation of Glutamate (which explains ketamine’s pro-neuroplasticity and anti-depressive effects), ethanol’s inhibition of NMDA receptors might lead to upregulation of glutamate. However, this effect should be heavily countered by the much stronger Gabanergic effects. Still, this hypothesis could potentially hold a bit of water.
Harms of Alcohol
The liver damage of alcohol comes due to its primary metabolite: acetaldehyde, a heptotoxin and carcinogen. Most alcohol induced liver damage and cancer risk are due to the effects of accumulated acetaldehyde.
Luckily in most humans, the liver enzyme alcohol dehydrogenase serves to further metabolize acetaldehyde away into the more harmless acetic acid and acetyl-CoA. However, in either those with genetic variations that reduce alcohol dehydrogenase (common in Asians) or in those who drink excess amounts of alcohol, acetaldehyde can accumulate and cause severe organ damage or death.
Asian Glow or Asian Flush is caused by a genetic variation (common in asians) that leads to inhibited levels of alcohol dehydrogenase. Various symptoms arise due to an accumulation of acetaldehyde. Severe forms of this phenomenon could be termed as an alcohol allergy.Attribution: https://en.wikipedia.org/wiki/Alcohol_flush_reaction#/media/File:The_Alcohol_Flushing_Response.pngSimulating Alcohol
The first thing we should do is try to find an analog of Ethanol that does not contain the acetaldehyde byproduct in the metabolism chain. Luckily, one phenomenon can help us: more complex chained alcohols tend to be harder to metabolize into acetaldehyde. From here, a clear winner pops up, the previously mentioned 2-methyl-2-butanol or 2m2b.
2m2b
2m2b is a branched pentanol and has almost identical gabanergic pharmacodynamic pathway as that of the simpler Ethanol, but does NOT get metabolized into acetaldehyde. 2m2b is almost completely devoid of either organ damage nor nasty hangovers. The one notable downside, however, is the fact that it tends to last a very long time (5-10 hours of peak drunkeness) due to your body’s difficulty in processing it.
Since your body can’t get rid of it by making it into a deadly toxin, you’re stuck with just getting drunk for far longer.
So now we’re close, but 2m2b famous lacks the dissociating effects of ethanol and the stimulating edge. Thats where the following two come in:
2m2b2-fma and O-PCE.
2-FMA is a flurosubstituted amphetamine (2-floromethamphetamine) that provides very clean and functional dopaminergic and norepi stimulation and wakefulness without much serotonergic activity. It is a relatively “simple” stimulant that will provide just the small stimulating kick needed.
O-PCE is a stimulating dissociative that can help contribute to the manic “litness” of alcohol while also helping with inducing the tunnel vision and “everything else may as well not exist” dissociative feeling of alcohol. It will also help make the room spin when you’ve had a bit too much for some full authentic experience 😙👌
Final Result
So there you have it, the Drugnerd Ethanol Combo:
2M2B + 2-FMA + O-PCE
Note: This is for educational / entertainment purposes only. We do not recommend anyone to seek out this combo without extensive independent research.
