https://neo.life/2021/12/the-psychedelic-divide/
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Growing interest in psychedelic therapy reveals two different visions of the future: one of spiritual interconnectedness and one of sober neurochemistry.
Two competing visions of the future of psychedelics reveal much more than a mere debate about drugs—legal or otherwise. They symbolize larger ideas whose evolution reflects how we perceive ourselves at this moment in history, and what societal changes could result.
On one side is a scientific view, where psychedelics are simply chemical compounds affecting the brain which, in itself, determines the emotions, motivations, perceptions, and actions of the person. In this “medical model” worldview, the mind is the brain, and a person is neither more nor less than the sum of their complex biological parts, which we can increasingly map, monitor, and alter with precision.
On the other side is a view of psychedelics that pays homage to the ancient ceremonial significance of these drugs, while also responding to our contemporary era. Under this “healing model” worldview, rules about morals and behavior are no longer imposed from above—not by God, the state, or corporate entities. Instead, they evolve in the same way nature evolves, through dynamic systems of interaction. That non-hierarchical interconnectedness drives decentralized, blockchain-powered concepts like Web 3.0 and cryptocurrency. It’s also the force governing the spread of COVID-19 and the effects of global climate change. Psychedelics bring those hard-to-see forces to light.
Statues of the Buddha line the window ledge of Bryan Roth’s office at the University of North Carolina. The psychiatrist and pharmacology professor invented a biological tool called DREADDs, which is now used in neuroscience labs across the world. “My lab invented it because I wanted to understand how psychedelics work,” Roth says.
The acronym, DREADDs, is short for Designer Receptors Exclusively Activated by Designer Drugs—a name that describes the way the tool works. Essentially, Roth created DREADDs by designing a neural receptor that no chemical in the human body could bind to; he then engineered the sole chemical capable of binding to that receptor. This created a biological switch that Roth could control, allowing him to turn neurons on or off, causing a cascade of reactions. The receptor he targeted was the G protein-coupled receptor (GPCR), a common class of proteins found in the human brain, and the one to which LSD binds.
In effect, Roth’s first DREADD let him precisely map the circuits and cells responsible for LSD’s action.
“A lot of people were trying to make these creatures,” Roth says, referring to DREADDs. He succeeded where others failed because he used a then-new method for drug discovery, called directed evolution. The power of this method is that scientists, not nature, decide which traits should survive through the evolutionary process.
Twenty years after Roth evolved a human protein through directed evolution, scientists are using the method to create everything from biodegradable plastics and clean energy to new medicines. The technique has gotten exponentially more sophisticated with advances in machine learning. The brute-force approach Roth used to create his first DREADD has been streamlined through AI. Instead of generating compounds in yeast, he can do so through his computer platform, called Ultra LSD. “We’re able to access this huge chemical space,” Roth says, since the compounds he’s evolving “don’t exist in the physical universe”—not until he chooses which ones to synthesize.
Roth is choosing LSD-like compounds whose binding actions cause the growth of dendrites—the neuronal spines that reach across the brain, connecting to other neurons—but don’t cause hallucinations.
“The idea of harnessing neural plasticity to rewire neural circuits is a paradigm shift in neural psychiatry.”
This is the nub of the chemical view of psychedelics: that psychedelics are effective at treating mental illness because they induce dendritic growth, not because they initiate the experience of a trip.
Roth readily admits that psychedelics have therapeutic benefit, as shown by recent clinical trials. “It’s a gigantic effect,” he says. “They’re going to revolutionize the treatment of mental illness. No question. But wouldn’t it be great if you could just take a pill and the next day your depression would be gone? I mean, you may miss out on the mystical experience, but you wouldn’t be depressed anymore.”
Through Ultra LSD, Roth sought a drug that could do just that. He examined 11 billion chemical compounds, searching for those that could induce dendritic growth without hallucinations. After choosing a handful of the most promising candidates, he synthesized the drugs and tested them on mice. The results are currently under embargo since publication is pending in a peer-reviewed journal. All Roth can say is that he’s “very pleased” with the outcome.
Non-hallucinogenic psychedelics have been dubbed “psychoplastogens” by professor David Olson, a biochemist at UC Davis and co-founder of Delix Therapeutics, a company developing new drugs in this class for therapeutic use.