Psychedelics: Yes Even Once?

We’ve broadly covered psychedelics before, in one of our mythbusting editions, which was necessarily a little broad and non-specific, because as we noted:

There are some moderately-well established [usually moderate] clinical benefits from some psychedelics for some people.

If that sounds like a very guarded statement, it is. Part of this is because “psychedelics” is an umbrella term.

Read in full: Taking A Trip Through The Evidence On Psychedelics

And to give some examples of those benefits being evidenced:

• Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases—A Systematic Review and Meta-Analysis of Clinical Trials
• Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials
• Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin
• Changes in self-rumination and self-compassion mediate the effect of psychedelic experiences on decreases in depression, anxiety, and stress.
• Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies
• Repeated lysergic acid diethylamide (LSD) reverses stress-induced anxiety-like behavior, cortical synaptogenesis deficits and serotonergic neurotransmission decline

Today we’re going to talk about the potential of psychedelics to improve…

*drumroll please*

Cognitive flexibility

So first we’ll mention what that actually is: cognitive flexibility is the ability of the brain to adapt to changing circumstances—which is not only a potential measure of general intelligence, but also, cognitive inflexibility is commonly seen as a harbinger of age-related cognitive decline.

In short, that scenario of an older person who “can’t be doing with all these new-fangled things” but the new-fangled things have been the norm for a long time now.

Fun fact: first-generation iPhones are now old enough to vote, having been initially released in January 2007, making them a little over 18 years old now.

Chances are quite high that you’re reading this on on iPhone or similar device, but chances alos are that there are other more recent changes in the world that baffle you. And maybe sometimes it really is the world (there sure are things that baffle this writer, too); sometimes, however, it would be good to at least have the option of jumping on the latest bandwagon, rather than always trying to live in decades past.

That’s where cognitive flexibility comes in; the ability to say “you know what, I can roll with this”, or the ability to switch tracks if new information comes to light contradicting some previously-held belief, things like that.

And as for where psychedelics come in?

A recent study by Dr. Elizabeth Brouns et al. has shown that a single dose of a psychedelic compound can significantly enhance cognitive flexibility in mice for weeks after treatment.

Yes, it’s just a mouse study so far, but generally squeaking, mammalian brains are mammalian brains, so we can expect this to carry over to humans when human trials are conducted next.

They (the researchers, not the mice) found that the psychedelic compound 25CN-NBOH, a selective serotonin 2A receptor agonist that honestly does not have a snappier name than that or else we’d use it, led to improved performance in tasks that required mice to rapidly adapt to changing rules, and that these benefits persisted for 20 days* after administration. This suggests long-lasting changes in brain function, with potential implications for treating conditions like depression, PTSD, and neurodegenerative diseases.

*About that “20 days”, though…

Do you remember the whole “the brain doesn’t finishing maturing until the age of 25” debacle? If not: the short version is that researchers measured brain development at various ages, from childhood until the age of 25, and found that it didn’t stop developing. Importantly, the age of 25 was simply the cut-off for the experiment, because at some point they have to publish results. It wasn’t that the brains stopped developing at 25, but when the popular press got hold of the headlines, they reported it as though that were the case, and 25 is the great landmark age at which the brain is finished developing. Now, we know from other more recent studies that the brain continues changing throughout life, and indeed even neurogenesis continues into old age, with no known stopping point (during life, anyway).

We did a mythbusting edition about that, by the way: The Brain As A Work-In-Progress

And for further reading about that neurogenesis in old age, see: How To Grow New Brain Cells (At Any Age)

The reason we’re mentioning this because in this experiment with the psychedelics, the claim of “the benefits persisted for 20 days after administration” can make it sound a lot like “and on day 21, the benefits vanished”.

The reality is, there was no day 21; the experiment ran for 20 days and that was that. It is not known how long the benefits would have persisted, only that in the first 20 days, they showed no signs of disappearing.

You can read the paper in full (and see graphs!) here:

Single-dose psychedelic enhances cognitive flexibility and reversal learning in mice weeks after administration

Nevertheless, the most well-researched popular psychedelic recently isn’t 25CN-NBOH, but rather, psilocybin, the psychedelic compound that gives “magic mushrooms” their psychoactive properties.

And when we say “popular”: Psilocybin use surges across all age groups since 2019

Not a fan of drugs?

If for whatever reason, psychedelics aren’t your cup of tea, there are other ways to improve cognitive flexibility.

See for example: How (And Why) To Train Your Pre-Frontal Cortex

Take care!