Can Psilocybin Increase Optimism Over Time?

Stop me if you’ve heard this before: psilocybin shows potential for treating depression. Even if you haven’t read a word I’ve written previously, you’ve likely heard this somewhere if you’re subscribed to the Psychedelic Pulse. (And if you’re not subscribed, get that fixed after reading, mmkay?)

The Potential of Psilocybin

Diving deeper, psilocybin appears to increase positive mood and decrease pessimism. It may do so by driving engagement in “reward” behavior. Persons with depression sometimes choose to withdraw from the world around them rather than engaging in rewarding activities. Encouraging engagement in rewarding activities, rather than choosing to withdraw, is a primary goal for cognitive behavioral therapy (CBT), a non-medication modality with good evidence for treating depression and certain other mental health conditions.

Thus, it makes sense to explore psilocybin – a substance that drives engagement in reward behaviors – as a treatment for major depressive disorder. But scientists and healthcare professionals are not satisfied simply answering “Does psilocybin work to treat depression?” We want to know why. What, exactly, explains its efficacy (or lack thereof)? Why does it do what it does? How does it do it?

The Study

In this study, researchers divided rats into two groups. One group (n = 12) received psilocybin, and the other group (n = 10) received saline 24 hours before the rats were exposed to an engagement task. Each rat lived in their own cage, and the engagement task was administered in the rat’s home cage.

24 hours prior to the engagement task, psilocybin or saline were administered. The following day, the engagement task was introduced into each cage. The engagement task was a modified “two-armed bandit” – a contraption with two buttons the rat could poke. One button, considered the “active” button, would dispense a sucrose (sugar) pellet when poked. The other button could be poked, but dispensed no reward. Simple enough – poke the correct button, get sugar.

After 10 successful pokes, the “active” button switched – so if the left button originally dispensed sugar pellets, it would become inactive after 10 pokes and now the right button would need to be poked for the rat to receive a sugar pellet.

Thus we have three possible outcomes possible based on how the rat acted:

• Poke the active side, receive the “reward”. This was considered a “positive outcome”, as the rat spent energy and received a reward for doing so.

• Poke the non-active side, receive no reward. This was considered a “negative outcome”, as the rat spent energy but received no reward.

• Do not engage with the task. This was considered a “null outcome” – the rat didn’t receive a reward, but also expended zero energy.

Switching up which “poke” delivers a reward forces the rat to relearn the reward-stimuli association. Broken down, this involves both 1) unlearning or inhibiting the first learned reward association, and 2) learning the new reward association. This allows us to compare the psilocybin group with the saline (placebo) group and compare engagement in learning and reward behavior – including the decision to not engage at all.

This process was repeated over a total of 14 experimental sessions. Numerous computation models were used to analyze the data. I won’t go into detail on these models – you can read the “Methods” section of the study if you’d like to learn more.

The Results

Reviewing their data, the researchers found that rats pre-treated with psilocybin were more likely to receive the coveted sugar pellet by pushing the correct pellet on the two-armed bandit than rats who received saline. They were also more likely to rack up “losses” or negative outcomes (pressing the button but not receiving a pellet) – indicating a level of engagement with the task.

As the study went on, rats who received psilocybin showed less loss aversion, indicating a willingness to engage and fail. Conversely, rats who received saline were significantly more likely to not engage and simply stay in the cage without interacting with the contraption.

So, How Does This Translate to People?

As we discussed in the introduction, current treatments for depression such as CBT aim to promote engagement, rather than withdrawal, with the world. The study shows that rats who received psilocybin were more likely to forget their previous “beliefs” after receiving a reward from the bandit device more so than after a loss. This suggests an optimism bias – learning more from positive than negative outcomes – effect due to psilocybin.