Understanding Hallucinogens as Fast-acting Antidepressants

Category Science

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Hallucinogens such as LSD, psilocybin, and DMT, are being used in clinical trials as fast-acting antidepressants. Unlike Prozac, these drugs need to be carefully administered in a doctor's office and have to be taken under supervision to get the best therapeutic results. A new study shows that it is possible to strip the trip away from psychedelics, but leave its mood-boosting magic. The study found that psychedelics work in a different way than traditional antidepressants, by connecting to TrkB receptors instead of serotonin receptors.

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Everyone is raving about hallucinogens as the future of antidepressants.

LSD (better known as acid), psilocybin (the active ingredient in magic mushrooms), and the "spirit molecule" DMT are all being tested in clinical trials as fast-acting antidepressants. And I mean fast: when carefully administered by a doctor, they can uplift mood in just one session, with the results lasting for months. Meanwhile, traditional antidepressants such as Prozac often take weeks to see any improvement—if they work at all. But tripping all day is hardly a practical solution. Unlike Prozac, hallucinogens need to be carefully administered in a doctor’s office, under supervision, and in a comfortable setting for best therapeutic results. It’s a tough sale for busy individuals.

Hallucinogen research for mental health has been going on for decades

Then there’s the elephant in the room: psychedelics are still classified as Schedule I drugs at the federal level, meaning that similar to heroin, their possession and consumption is illegal.

What if we could strip the trip out of psychedelics, but leave their mood-boosting magic? This week, a new study in Nature Neuroscience suggests it’s possible. Led by Dr. Eero Castrén, a long-time champion of psychedelic research for mental health, the Finnish team dug deep into the molecular machinery that either lifts mood or gives you a trippy head rush.

In December of 2020, the FDA accepted a new Depression Drug application using the hallucinogen psilocybin

The results came as a surprise: similar to traditional antidepressants, psychedelics spurred new growth in both baby and mature neurons. But the mind-bending substances were 1,000 times more efficient than Prozac at grabbing onto a key molecular hub, TrkB. With just a single dose, the drugs elevated mood in mice under chronic stress and reduced a previously-established fear. However, when genetically stripped of a critical protein site, LSD lost its magic.

Scientists are still researching the long-term effects of hallucinogens on mental health

It’s still early days for re-configuring psychedelics as antidepressants. But the results "open an avenue for structure-based design" that can skirt unwanted hallucinations while developing fast and long-lasting antidepressants, the team said.

Meet the Players .

Think of neurons as a fast-growing basil plant. It starts as a tiny sprout. With nutrition it blooms into a bushy wonder. Pruning the plant along the way helps its health and survival. In neurons the main nutrient is BDNF, or brain-derived neurotrophic factor. It’s the all-star of rejuvenating the brain. In the hippocampus—a brain region critical for memory and mood— it helps nurture new neurons through life, cradling neural stem cell "seeds" into maturity. The protein is also essential for rewiring neural networks by pruning connections—a process called neuroplasticity. It’s a fundamental process in the brain that allows us to learn, adapt, and reason in an ever-changing world. Neuroplasticity is especially important for battling depression, as the condition often "locks" people into negative mindsets.

Research has indicated that when psychedelics are consumed in a psychologically safe setting, there is a reduced risk of adverse experiences

BDNF doesn’t act alone. It floats outside of neurons. Grabbing onto it is TrkB, a protein that usually lies low inside neurons until it’s time to rise to the top—literally. Once on the surface of neurons, it captures floating BDNF. The union then triggers a cascade of molecules that help the neuron braid and spell its dendritic trees, and encourages the sprouting of new neurons.

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