The best antidepressant for nerds

So, I finished ordering my new microphone and once I get to pick it up we will have a new golden age. Billionairophobia episode 4 will be finished and I should even be able to plug it into my smartphone so it’s almost obligatory to have a new livestream too.

But I first want to bring up something else. There’s a really effective antidepressant, that you never really hear about. It’s scopolamine. Scopolamine has a bad reputation, because you see a lot of stories about people who have bad experiences with it. But that’s what happens in high doses. You only need very low doses, to have an antidepressant effect. Scopolamine is regularly given to people who suffer car sickness. An effective antidepressant dose in mice is 0.03mg/kg. The dose that kills half of mice, is 1880mg/kg.

When teenagers take Benadryl, they’re generally self-medicating depression. Benadryl hits the same receptor as scopolamine: The m1 Muscarinic acetylcholine receptor. But Benadryl, is a cold medicine, you need very high doses to get the anticholinergic effect, the active ingredient in Benadryl is far more inclined to bind to histamine receptors, its intended target.

Scopolamine has been often found to be an effective antidepressant, particularly in women. We know why. There’s a balance between cholinergic neurotransmission and catecholaminergic neurotransmission in the brain. More of one, means less of the other.

Catecholaminergic neurotransmission is Dopamine, Adrenaline and Noradrenaline. Cholinergic neurotransmission is mostly acetylcholine. Acetylcholine is important in learning, attention and concentration. The brain loses acetylcholine receptors and transporters as it ages, but it’s quite good at compensating for that, by simply increasing acetylcholine.

A lot of drugs raise cholinergic neurotransmission. Nicotine from tobacco basically activates the same receptors as acetylcholine. Caffeine from coffee slows down the natural breakdown of acetylcholine in the brain.

As we get older, our brains start to rely more on cholinergic neurotransmission. You see this in how our personality changes. Our interests become more narrow, we become less assertive and extraverted, we start to base our behavior more on reason and acquired knowledge. When this is excessively the case, we become depressed.

When the brain is injured, for example, through psychological trauma, you know what it does? There’s a sudden burst of acetylcholine in the brain during acute stress. That then leads to new neuronal connections in the brain, which can then be regularly recalled. But when they give the animals scopolamine before the stress, the traumatic memory can’t be formed.

There seems to be a certain sort of depressive phenotype, where neurotransmission has shifted excessively from catecholaminergic neurotransmission, towards cholinergic neurotransmission. You see it a lot, with anxious depressed people, who are just stuck ruminating on their own trauma and who are stuck worrying about big abstract problems most other people seem unaffected by. It also results in anhedonia: The inability to find things pleasurable that used to please you. This is just the type of depression I notice in smart nerdy people: Their joy for life has been overshadowed by knowledge.

With scopolamine, you just temporarily make some cholinergic pathways in the brain unavailable to your mind. As a result, the brain is forced to rely on other routes, strengthening those alternative connections. That’s what you see in the brain after a small dose of scopolamine: A rapid increase in synapses in the prefrontal cortex. The brain is forced to reroute. NDMA antagonists like Ketamine do this too.

There is a synergistic effect seen, when animals receive a small dose of scopolamine and ketamine. I’m not really encouraging people to hurry and try that, rather, I’m explaining it as a solution for when other solutions don’t work or are not an option. I think for the vast majority of people, it’s best to first try Psilocybe mushrooms.

We used to have nightshade plants with scopolamine in the beer that people drink. Before the use of hops in beer, medieval people used gruit. What’s gruit? A mixture of all sorts of plants people traditionally used. But included among the list was henbane, the main nightshade plant that was known to medieval Europeans.

My own recommendation, if you want to try scopolamine, is as following. First, you need to get yourself some Datura seeds. My recommendation is either Datura Innoxia, that I have, or Datura Wrightii, known as Sacred Datura.

Datura Stramonium or Datura Metel can be used, but these two species are not preferable, as they have atropine in addition to scopolamine in their seeds. The atropine has a more stimulating effect, whereas scopolamine is sedative and just helps you fall asleep.

Note: A seedpod, is not the same as a seed! The seedpod is spiky and contains numerous very small seeds within it. You need just a tiny amount of plant material, do NOT eat a whole seedpod!

Next, you start out by chewing and swallowing two of the seeds, about an hour or two before you go to bed. Then about an hour later, you drink a glass of beer. It’s my observation that a bit of beer just goes really well together with the effect of Datura. After finishing your beer, take a piss, so you won’t have to get out of bed to empty your bladder in the middle of the night.

Most likely, you will notice no effects from the Datura at all when you take just two seeds and you will just fall asleep. The first clear effect you may expect to notice when you experience the effects of a nightshade plant, is a dry mouth. When you notice no effect, you can increase the dose by one or two seeds the next time you take it. Be sure to keep at least 72 hours between doses, because scopolamine sticks around for a pretty long time in the body.

Please always make sure to check secondary sources, don’t just blindly believe what I say. There is a guide on Reddit.

Also be sure to use common sense. Datura innoxia seeds weigh about 13 milligram on average. The scopolamine content of a seed is around 0.17%, the atropine content is 0.023%. So, one seed is 0.0221 milligram of scopolamine. The scopolamine dose in a motion sickness patch is 1.5 milligram.

This means the dose in one motion sickness patch, is equivalent to the dose found in about 67 Datura innoxia seeds. Of course the dose in a motion sickness patch is released over a period of about 72 hours, but it illustrates that you really shouldn’t expect to lose your mind from eating one or two Datura seeds.

In fact, if you take less than ten seeds, you probably don’t notice anything at all. Again, I recommend starting with two seeds before you go to bed and increasing the dose by one or two seeds every time you take it, with 72 hours in between.

For me, there is nothing that quite works the way scopolamine works. The next day I just feel like I have more energy, more desire to do stuff, more lust for life and all the misery in the world affects me less. While I experience the direct effects of the datura seeds, music just sounds amazing, it’s like I hear a song I like again for the first or second time.