In episode 129, Jesse interviews Dr. Robin Carhart-Harris, Research Fellow at Imperial College London, about lysergic acid diethylamide, more widely known as LSD.
From counterculture symbol, to possibly solving climate change… LSD is political in a way that few other substances are. Turn on and tune into the episode, but don’t drop out just yet.
The Birth of LSD
LSD is the “prototypical” psychedelic. It’s not the oldest psychedelic substance, but the term “psychedelic” was coined to describe the LSD experience. It’s what catalyzed the systematic study of psychedelics.
Albert Hofmann, a Swiss chemist, was the first person to synthesize and take LSD. While working in Basel for a pharmaceutical company searching for novel pharmaceuticals, he synthesized LSD on November 16, 1938. However, it wasn’t until 1943 that Hofmann revisited the compound.
He accidentally (or maybe not…) ingested some — definitely not through his fingertips as you might have heard, since that would be impossible — and experienced the world’s first acid trip. He described it as “dreamlike” with “intense, kaleidoscopic play of colors.” This first trip lasted about two hours.
The first intentional acid trip happened three days later, on April 19, 1943, when Hofmann took a massive dose of 250 micrograms — most people take 100 micrograms — rode home on his bicycle, and had a pretty rough trip. Highlights (lowlights?) include thinking his neighbor was a malevolent witch.
A friend once told Jesse, “talking about psychedelics is like dancing about architecture.” Well, it’s not quite thaaat hard to describe an LSD trip, although it is certainly a profound and conscious-altering experience. But what’s more interesting is what happens after the trip. Steve Jobs called taking LSD “one of the most important things in my life,” and it wasn’t because of the cool colors.
People feel and behave differently after taking LSD. Research has found a change in personality post-trip. People become more open, more community-minded, and feel more connected to nature.
Here’s something weird: despite Hofmann’s bad bicycle trip, the next day he woke up feeling fantastic.
It’s what Dr. Carhart-Harris calls the “paradoxical psychological effects of LSD.” While tripping, people can experience symptoms approaching psychosis. But in the days and weeks after dosing, people experience high levels of well-being, increased optimism, and greater cognitive flexibility. Food even tastes better. So what’s going on?
How Does LSD Work?
LSD stimulates a particular aspect of our serotonin systems. Serotonin performs many roles, depending on which of 14 serotonin receptors are in play. Serotonin 2A receptors are important for regulating mood, cognition, and plasticity — including memory, learning, flexibility of thinking. LSD shows a high affinity for 2A receptors, which seems to explain its emotion and creativity-enhancing effects.
LSD changes your brain not only during a trip, but in long-lasting ways. In studies on animals, researchers have seen markers of neuronal growth, including increased brain-derived neurotrophic factor (BDNF). These effects are strongest in the cortex, the area of the brain responsible for cognition, suggesting that LSD can promote new, permanent connections in the brain. New research shows increased neuronal connections in humans, too.
- Dr. Carhart-Harris’s recent TEDx talk on the treatment possibilities of psychedelics
- Neural correlates of the LSD experience revealed by multimodal neuroimaging
- Dr. Carhart-Harris also studies psilocybin: Psilocybin with psychological support for treatment-resistant depression
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