Issue 002: LSD Afters
This issue’s theme is AFTERS.
Dispatching in the days after Bicycle Day—the official psychedelic high holy day.
takes a beat in After Bicycle Day to look carefully at what Albert Hofmann did in the days after his fateful dose, and what lessons we should carry into today asks why plants and people make medicine in Bicycle Day was Just a Mutation Event. He also offers some answers…but is he right?Let’s dig in 👽
1. After Bicycle Day
By Reilly Capps
On April 20, 1943, Albert Hofmann woke up refreshed. War raged in Europe. Bombs fell on Berlin. But in the riverside town of Basel, Switzerland, things were neutral and calm. The chemist had a clear head and a “sensation of well-being and renewed life.” In fact, “everything glistened and sparkled in a fresh light,” he wrote, and “the world was as if newly created.”
Yes, Hofmann had a kind of reverse hangover. The opposite of how you’d feel after a bender.
In his story, there’s a lesson about how we should approach scientific inquiry and discovery, and what the benefits of curiosity and open-mindedness might be.
There has been, in the decades after Bicycle Day, extensive psychedelic research, with a notable resurgence in formal scientific investigations beginning in the early 2000s. We've definitely gained momentum, not lost it. Still, there's so much more to learn, so much knowledge to be acquired. And the last thing we want is for that knowledge to be locked away—either because people don't have safe spaces to share it, or because companies want to "own" it.
Even Albert Hofmann had much more to learn, even after Bicycle Day.
Of course, on April 20, 1943, Hofmann felt renewed because, on the day before, Hofmann took 250 micrograms of LSD. It might seem strange, but it’s common to feel better after an LSD trip than before, even if it’s a bad trip. (Not always; your mileage may vary.)
Hofmann, famously, took his LSD in his lab. And, at first, he felt "a desire to laugh"—but then he spent hours worried he was going to die. He biked home through the streets of Basel and, as Hofmann wrote in his book, “LSD: My Problem Child”: "I half-crazily cried or muttered indistinctly … my field of vision fluctuated and swam like an image in a distorted mirror." Hofmann found his experience "terrifying" and "threatening." The woman next door turned into "a malevolent, insidious witch," and Hofmann felt like "a demon had invaded me, had taken possession of my body, mind and soul." “I was seized by the dreadful fear of going insane.”
Hofmann, prudent man that he was, never again took a dose as high as 250 micrograms, which he considered an overdose. When he got his co-workers to try LSD, they took about 85 mics, according to one source.
We can ask why, if Hofmann felt so good the day after taking 250 mics, did he tell his friends to take less?
And why, upon telling his friends to take what we’d now call a standard dose, did Hofmann start to take mini-doses?
On Hofmann's second, third, and fourth experiments with LSD, which have only recently been reported on, he took mini-doses—20 or 30 micrograms. One night, for example, he drank coffee and grappa with buddies, and felt "warm comfortable feelings". His mini-doses weren't all successful: two other nights Hofmann dosed late and had uncomfortable visions and disturbing dreams.
For the rest of his life, Hofmann took these mini-doses and lived normally. He kept these small experiences to himself. He never again took a dose as high as his first one.
Another question: if he liked the very small doses, why didn’t he tell more people about them?
In fact, he rarely told the world of psychedelic users that he liked taking 20 or 30 mics. Instead, he and the pharmaceutical company he worked for shipped out thousands of doses of LSD with no great instructions on how to use it. Most of the tests used bigger doses.
Researchers gave their subjects the LSD in controlled, lab settings, with an eye toward patenting a use for the LSD. “Public mini-doses with friends,” as a new invention, will not impress a patent clerk.
So, what are researchers keeping to themselves now about new psychedelics? What are we not hearing?
Hofmann did share his mini-dosing approach with his buddy Robert Forte, who wrote the book “Entheogens and the Future of Religion” and “Tim Leary: Outside Looking In.” Forte ran Hofmann's foundation decades ago, Hofmann confided to Forte that he took LSD in small doses to help him write and to focus. Hofmann suggested microdosing could replace Ritalin. Hofmann told Forte he thought microdosing was one of the most valuable and unexplored uses of LSD. One day a long time ago, Forte decided to experiment by taking a "wee bit" of LSD before playing golf, and ended up shooting 74 on one of California's toughest courses during windy conditions.
In the years that followed, Forte would microdose from time to time. He noticed that some mini-dose days were awesome, while others fell flat. Despite these experiences, Forte continued to advocate for full-dose, intentional, guided journeys rather than casual microdosing.
One answer to the question of why Hofmann kept his love of mini-doses to himself? According to Forte, Hofmann thought psychedelics don't fare well in the general public. Microdosing or mini-doses might have led to people using psychedelics too often and too publicly, and who knew what could happen.
Forte still agrees. The public is likely to misuse the drugs.
Forte believes psychedelics are best used discretely, in secret, sort of like sex. Sex in public, Forte says, is "sort of gross." Same with psychedelics.
Because of that secrecy, mini-dosing or microdosing remained a semi-secret until this century, when Forte told his friend Jim Fadiman, who told the world. Microdosing is now more popular than mega-dosing, and may be the most common way people use LSD. And yet no one thought to use LSD in smaller doses for 70 years, except Hofmann and a few friends.
And all that to say: what are the chances we’re not overlooking something super important and useful today?
Unlike alcohol, which is one drug that feels the same no matter how you drink it, whether merlot, zinfandel, or an old fashioned, psychedelics are often wildly different from one another. Like the old song about Alice, one makes you tall, the other makes you small. One turns the lights up bright, another dims them. One makes you feel love, another makes you feel just … weird.
A macro dose of LSD can make the neighbor lady look like a witch, and a mini-dose is more likely to bring “warm comfortable feelings,” as Hofmann wrote. Add molly to a psychedelic and you get one of the best feelings on Earth. Smoke DMT and a possible side effect is “death by astonishment.”
We have momentum now, but there's still so much work to be done. We need to make sure that valuable knowledge doesn't get locked away—like it was in Hofmann's mind—either because of lack of safe spaces or because companies want to "own" knowledge for profit. Maybe if Hofmann had lived in our world of changing policy, he'd have shared his personal knowledge on the power of small doses. We need a psychedelic IP commons where insights can be freely shared, where the next breakthrough isn't just discovered but also made available to benefit everyone.
We should build that for the next Albert Hofmann, which could be any one of us.
So that, in more places, more people can wake up feeling refreshed.
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2. Bicycle Day Was Just a Mutation Event
By Tyler Quigley
Plant medicine. Medicine…made by plants.
A painkiller in an Aspen tree. Psilocybin in a mushroom. DMT in a leaf.
Why do plants make medicine?
It’s a good question that maybe you’ve asked yourself, or asked others, or asked the plants themselves.
There are many ways to answer. God. Aliens. Kismet. Science, at this point, can't disprove the alien or God hypothesis. Personally, if I am going to gaze for long into an abyss, I want it to gaze back in a way that tells me something more about myself and the world I aim to survive in.
A good quality abyss for that kind of staring is evolution (by natural selection, of course). Five stars on NietzchYelp. Natural selection is a reliable lens to have in one’s arsenal of perspective because, using only simple evolutionary principles, one can see how strange, beautiful, and wildly different lifeforms are connected to one another by the ancestral tendrils of time and adaptation.
So why do plants make medicine? It’s the same motivation behind human medicine-making.
MUST GET GENES INTO NEXT GENERATION.
[Critic stands]
☝️”Akchyually, Tyler, the gene-as-unit-of-selection concept is an outdated oversimplification of the more nuanced, systems-level view of evolution we now recognize post-Dawkins…”
Yeah sure sure sure.
Evolution is insanely complex. But this six-word law of biology will do just fine to guide our exploration of the Why’s in biology.
To know why, we must know how:
“Plant medicines” are produced through biosynthetic pathways, a chain of enzymatic reactions that turn ordinary molecules into wildly useful compounds. Enzymes are helper molecules that do everything from break down food to create energy. These enzymes are encoded by genes.
Sometimes, genes mutate as they’re passed down into their offspring. And sometimes, that mutated gene produces an enzyme that’s functionally different from their parent’s—maybe slightly, maybe significantly. In certain cases, that difference ends up being useful. It might make a biosynthetic pathway more efficient, or cause the pathway to produce a new compound.It might make the offspring more effective at deterring predators. For example, by tasting worse or disrupting digestion or just making things weird.
If these subtle molecular changes help the organism survive and reproduce, even just a little, then the mutated gene becomes more likely to get passed on. Generation by generation, small advantages enable the gene to become common, or even universal, in the population.
This cycle—mutation, variation, selection, inheritance—has played out again and again across every gene in every species for as long as life has existed. It’s how evolution works. As near as we can tell, using the tools of science, this cycle works not by planning, not by design, but by endless iteration.
Plants don’t make “medicine”
They make defensive molecules—bitter, numbing, disorienting—to keep themselves alive.
We call some of these “medicine” because they just so happen to do things to us that we like. They taste good, sometimes. They ease pain. They grant us access to non-ordinary states of consciousness. Or they simply remind us that we are animals with nervous systems, embedded in environments we only partly understand.
But they work on us because they were naturally selected to work on something else. These molecules exist because they interact the physiology of other animals—grazers, insects, predators—by targeting the same neurotransmitters, ion channels, and sensory pathways that shape behavior and perception across the tree of life.
And defense might be where it starts—but it’s not always where it ends.
Sometimes, an animal eats a plant for more than food. Chimps self-medicate with bitter herbs that kill parasites. Starlings line their nests with aromatic plants that enhance antimicrobial protection of their offspring. Maybe it feels good. Maybe it works. Maybe the animal spreads the seeds.
Eventually, that interaction starts to shape the future of the plant.
Humans also make medicine.
LSD was one of many derivatives of ergot, a fungus, that Albert Hofmann was studying at Sandoz in the 1940s when he was accidentally exposed to LSD. Maybe there was some kismet involved there. But look at this event through our evolutionary lens:
If Bicycle Day was the mutation event, then the ways in which LSD altered the human’s interaction with its environment - cultural, psychological, and spiritual - after Bicycle Day was its selective advantage.
LSD is a defensive molecule slightly tweaked conferring something adaptive to the species through which it emerged.
How does LSD feed into our biological programming for MUST GET GENE INTO NEXT GENERATION?
Do LSD-doers get more genes into the next generation? Did LSD help create Love-Ins, sites of conception of thousands of kids? Does LSD now fuel festivals and raves and long stares into the eyes of sparkly humans? Does LSD help you love your spouse? Did LSD help Elon Musk open his mind, create vast wealth, and father 12 children? (Albert Hofmann had four kids, which is not too shabby.) All those spawnings required someone, somewhere, to grow some ergot.
Or maybe LSD offers a different kind of advantage—less about libido, more about alignment. Not a fertility drug, but a cognitive mutagen. Something that softens rigid patterns, quiets stress, increases harmony within inner and outer worlds.
Maybe the adaptive benefit LSD offers isn’t working at the individual level, but at the society level. Not by making individuals more fertile, but by making groups more flexible, more cohesive, and more resilient. LSD has been shown to increase empathy, reduce fear, and disrupt rigid thinking—traits that, at scale, can strengthen social bonds, improve conflict resolution, and support collective problem-solving. In evolutionary terms, a group that communicates better, adapts faster, and tolerates difference is more likely to survive environmental and cultural stressors. The benefit isn’t just who reproduces, but which groups hold together, innovate, and persist.
Plants make medicine to survive in the conditions they’re dealt. So do we.
🔮 From Around the Psychosphere
📑 Must read: Contemplative Wisdom for Superalignment, Laukonnen et al. accompanying thread.
🎨 Emotions, Visible — DMXE is for scientists and artists
🥽 60-Hour Dance Sessions, Simulated Sex, and Ketamine: Inside the World of Hardcore VR Ravers
🤯 Keep an eye on psilocybin for cluster headaches, fascinating work ahead
👀 University College London recruiting for their next study
🍯 Tunes for your next flow state
This issue’s playlist provided by Brittney Scott. Few tracks below, full playlist here.
🤟🏽 Have a swell weekend friends 👽
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 | A guest post by
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Are the effects of LSD on age, sex, or race specific, different?