Three takeaways to tell your friends:

• Magic mushrooms, or psilocybin, was granted breakthrough therapy status for depression by the FDA in 2018.
• Psilocybin treatment resulted in significantly more mice recovering from a depressed behavioral state than ketamine or saline.¹
• Psilocybin treatment improved neuronal structures essential in neuronal communication that were long-lasting.¹

Are you starting to wonder what the fuss is about with psychedelics? Are more people telling you about how a psychedelic experience changed their lives? Maybe it’s about time you started believing them. The evidence is piling up in support of psychedelics for treating depression, specifically, magic mushrooms aka. psilocybin. So much so the Food and Drug Administration (FDA) granted psilocybin as a Breakthrough Therapy for depression in 2018. This major recognition by the FDA promotes research studying the impact of psilocybin on mental health while imparting to you, the reader, how much scientific support psilocybin has in the mental health research community.

This post highlights an article by Shao et al,¹ showing molecular evidence that psilocybin could function as a treatment for depression. To begin, the authors tested multiple doses of psilocybin on mice and assessed a behavioral response known as the “head-twitch response.” The head-twitch response is a typical rodent behavior used to assess hallucinogenic drug activity. These authors found the lowest dose of psilocybin that caused a spike in head-twitch responses and used that dose for their experiments.¹

To test the effect of psilocybin on depression, the authors needed a behavioral test that represented a depressed state. For this, they chose the learned helplessness model. Even by rodent behavioral depression models, it’s pretty brutal. Look it up if you like, but I’ll explain. Researchers administer inescapable electric shocks to mice for two days. Then they administer escapable shocks for two days while recording if and how quickly they escape to the safe side of the box. You expect some will give up trying to escape (learned helplessness/depression) because at one point they learned the shocks were inescapable. After learning the shocks were inescapable, three groups of mice were treated with control, psilocybin, and ketamine, a known antidepressant.¹ However, in this study, the only treatment that significantly decreased the percentage of escape failures or total depression was psilocybin.¹ Ketamine did slightly decrease escape failures but not significantly.¹

To discuss the molecular evidence from this study supporting psilocybin as a quick and lasting treatment for depression, I must introduce background information. Throughout the brain, neurons communicate by signaling with one another. This occurs at points where neurons are connected or extremely close, called synapses. These synapses contain a neuron that is sending the signals, the axon, and a neuron receiving the signals, the dendrite. The specific region of the dendrite that forms the synapse with the axon is typically the dendritic spine. The spines are tiny ever-changing outgrowths from the dendrite that carry meaning behind their shapes and numbers. The shapes signify whether the spines are strong, weak, lasting, or faint. The thicker the distant part of the spine, the stronger the spine,² and the greater number of spines present, the greater the capacity to form synapses,³ except in chromosomal disorders with abnormal spine growths, like Fragile X Syndrome.⁴

So to recap, the axons of one neuron send signals across synapses to spines of dendrites from another neuron (while this is the most common type of synapse, there are other forms). As the destination for neuron signals, these spines are essential for communication between neurons.

A recent study found a relationship between depression and having a lower number of synapses throughout the brain.⁵ Given psilocybin’s ability to improve depression symptoms in a learned helplessness behavioral model (and lots of anecdotal evidence, have you been to California?), the researchers wanted to know if any changes were occurring at the molecular level, specifically dendritic spine number and shape.

Taking that into consideration, spine numbers were measured in combination with psilocybin administration.¹ Using mice that are expressing a green fluorescent protein within their neurons (to visualize spines), combined with a high-tech imaging technique, the researchers can image specific spines on dendrites in these live mice repeatedly over periods of days. This allows for the first-ever molecular analysis of psilocybin on dendritic spine modifications over time in live animals.

They found that with the addition of psilocybin, there were more spines present, and the spines had thicker heads.¹ These results signify the ability to form more synapses and the presence of strong spines for healthy signaling, respectfully. Importantly, the new spines that formed following psilocybin addition were tracked, and one month later, large percentages of those spines remained in females (34%) and males (37%).¹ Thus, psilocybin provides rapid and lasting alterations at the molecular level that may have a persisting effect on the symptoms of depression.

Additionally, along with the increase in spines, there was no change in the number of spines that were disappearing following psilocybin.¹ If that were the case, the increase would be seen as a failure to eliminate existing spines. Therefore, the increased number of spines is not due to a failure in the natural elimination of some of the newly formed spines following psilocybin administration, but rather a significant increase in spines as a result of psilocybin treatment.¹

So it seems, your friends tripping on mushrooms aren’t preaching nonsense, I mean, at least not entirely; just wait until you’re prepared to lose control of your perceptions before partaking. Plus with its breakthrough therapy status, we will continue to unravel the natural health benefits of controlled psilocybin use.

Experimental factors to consider…

In this study, the dose of psilocybin used was 1mg/kg, which to a human who weighs 165lbs/75kgs would equate to around 75mg dose of psilocybin.¹ Let me explain that when people take magic mushrooms, they consume the dried mushroom, which based on the table below should give you an understanding of how much psilocybin there is per gram of mushroom. Taking that into consideration, I would like to see this experiment done with a lower dose that wouldn’t have these mice thinking they were competing in Hell’s Kitchen. Thank you for your service, mice.

1.         Shao LX, Liao C, Gregg I, Davoudian PA, Savalia NK, Delagarza K, et al. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron. 2021;109(16):2535-44 e4.

2.         Alimohamadi H, Bell MK, Halpain S, Rangamani P. Mechanical Principles Governing the Shapes of Dendritic Spines. Front Physiol. 2021;12:657074.

3.         Yuste R, Bonhoeffer T. Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu Rev Neurosci. 2001;24:1071-89.

4.         Wisniewski KE, Segan SM, Miezejeski CM, Sersen EA, Rudelli RD. The Fra(X) syndrome: neurological, electrophysiological, and neuropathological abnormalities. Am J Med Genet. 1991;38(2-3):476-80.

5.         Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, et al. Lower synaptic density is associated with depression severity and network alterations. Nat Commun. 2019;10(1):1529.