Can Psychedelics & Biotech Help Address Mental Health?

Psilocybin and Serotonin

After you consume psilocybin, your body turns it into psilocin. Psilocin binds (connects) to the 5-HT2a serotonin receptors found on your neurons (brain cells), and “activates” the receptor. When the 5-HT2a receptor is activated, a cascade of chemical signals are triggered inside your brain, resulting in the hallucinogenic “trip” and profound emotional experiences.

For some people with treatment-resistant depression, the actions of psilocin on symptoms can be immediate and last for months. However, other people have a “bad trip” which can worsen depressive symptoms, or even trigger psychosis or suicidal behaviors.

Because of this risk, using psilocybin at scale may simply be hard to do. For example, psilocybin use for treatment-resistant depression occurs under supervision of a trained professional, and typically involves multiple pre- and post-session appointments.

Psilocybin and SSRIs

Selective serotonin reuptake inhibitors (SSRIs) are drugs developed to treat major depressive disorder. SSRIs affect serotonin, but not in the same way as psilocin. SSRIs have been shown to increase serotonin levels in cells outside the brain. This may be why why SSRIs cause such a wide range of effects, including effects on libido, bones, and the gut.

It also typically takes weeks of treatment before the effects of an SSRI are noted – if a person experiences any positive effect at all.

So:

From a drug development perspective, the thought is: can we create a drug which specifically targets the 5-HT2A receptor in a way which:

• still treats depressive symptoms in a manner that is immediate and long-lasting, and

• avoids triggering the “trip” signaling pathway to avoid inducing hallucinogenic effects, and

• doesn’t raise serotonin levels in cells throughout the body, a theory behind why SSRIs cause such a wide range of bothersome side effects.

Implications and Limitations

Years of collaboration between various research institutions, funded by a grant from the Defense Advanced Research Projects Agency (DARPA) in the Department of Defense, resulted in a molecule that binds the 5-HT2A receptor and induces an antidepressant effect, without triggering a hallucinogenic effect, when given to mice. Importantly, these effects were noted to be immediate and long-lasting in mice after just one dose.

There’s still a long way to go before this or a similar compound will be used and consumed by people. Some people believe “the trip” is what leads to long-lasting therapeutic effects psychedelics can cause. But others think it’s possible to have similar effects without hallucinations or a profound emotional experience. We won’t know for certain until we’re able to test these new compounds in people.

Sadly, there’s a dark side to the reality of how drug development and the pharmaceutical industry works which must be addressed here. It’s possible that this research could be used by the pharmaceutical industry to keep natural psilocybin and other psychedelics illegal, forcing all patients to use their patent-protected synthetic compounds.

For example – the synthetic cannabinoid dronabinol (Marinol) was approved for use by the U.S. Food and Drug Administration (FDA) in 1985. I recall a particular professor of mine pointing to dronabinol’s limited effectiveness/utility in clinical practice and saying, “see, we’ve seen that THC doesn’t work well for pain, so I don’t understand why some people are still pushing for medical marijuana” – completely ignoring the differences in synthetically-derived THC and full-spectrum cannabis products. He is not alone in this opinion. Cannabis is still classified as a Schedule I substance at the federal level. Millions of Americans remain in jail over cannabis-related “crimes” while pharmaceutical companies are allowed to profit off synthetically-derived cannabis products. The same companies which lobby keep natural cannabis illegal. It will not shock me to see psychedelics go down the same path.

Conclusion

Researchers have developed a new compound which binds the 5-HT2A receptor – the same target as psilocybin – and induces an antidepressant effect, without triggering a hallucinogenic effect, when given to mice. The compound is able to produce an immediate and long-lasting antidepressant effect, but hasn’t been tested in people yet. Past examples in cannabis research show there’s a risk that this research could be used by the pharmaceutical industry to continue advocating for ineffective and harmful prohibition of natural psychedelics.