This post was authored by Sam Woolfe, an Odyssey writer covering mental health, psychedelics, and philosophy.‍

‍

Psychedelic researchers are trying to better understand how psilocybin helps various mental health conditions by examining the brain changes that occur both during and after the experience. Many are particularly interested in neuroplasticity, or the brain’s ability to change and rewire itself. Indeed, there is a growing body of research showing that psilocybin promotes neuroplasticity, and this appears to play a crucial role in why psychedelic experiences can lead to rapid, significant, and long-lasting benefits.

‍

The links between psilocybin, neuroplasticity, and mental health are complex. And every year, many important new studies are published that further clarify these links. In this article, we describe the most groundbreaking research in this area, including the most recent studies. This will enable you to get a better sense of not only how psilocybin can improve your mental health but also how to maximize these benefits.

‍

What is Psilocybin?

Psilocybin is the main psychedelic compound found in ‘magic mushrooms’. There are over 300 species of psychedelic mushrooms that we know about (with more being discovered). They are also known as ‘psilocybin mushrooms’ because psilocybin is their most abundant alkaloid. Other alkaloids present in these mushrooms include psilocin, norpsilocin, baeocystin, norbaeocystin, and aeruginascin.

‍

Some researchers believe that the combination of these alkaloids can create an ‘entourage effect’ when consumed. This means that the alkaloids, in combination, modulate or enhance psychedelic effects and benefits. It is not clear exactly if, how, or to what extent consuming whole mushrooms produces an entourage effect in humans. But if it does occur, then consuming whole mushrooms may provide additional benefits over synthetic psilocybin.

‍

Psilocybin is a tryptamine psychedelic. This means, chemically, that it is built around an indole ring structure and a two-carbon side chain. Other tryptamine psychedelics include DMT and 5-MeO-DMT. Psilocybin, like DMT, is a classic serotonergic psychedelic. This means it causes classic psychedelic effects, primarily mediated by action at the serotonin 5-HT2A receptors in the brain.

‍

However, unlike other classic psychedelics (e.g. DMT, LSD, and mescaline), psilocybin is a pro-drug. This means it is not psychoactive itself. When you consume psilocybin (either in mushrooms or in synthetic form), the body metabolizes it into the active compound psilocin. So technically speaking, while taking psilocybin leads to psychedelic effects, it is psilocin that actually causes them. And, of course, other alkaloids present in mushrooms may change the quality of the experience somewhat and contribute to therapeutic benefits.

‍

What is Neuroplasticity?

Neuroplasticity (also known as neural plasticity or brain plasticity) refers to the brain’s ability to strengthen, form, and reorganize synaptic connections, which are the connections between neurons. New synaptic connections and patterns of connection occur throughout our lives, in response to new information and life experiences. This rewiring allows the brain to function in a different way from how it previously functioned.

‍

Yet in conditions like depression, neuroplasticity is disrupted. This disruption of neural plasticity occurs in important brain regions, including the hippocampus (which is involved in memory) and the prefrontal cortex (which helps to regulate emotions). Stress and other negative events can induce these changes in neuroplasticity, which plays a significant role in the onset of depression. A 2021 paper published in Experimental and Therapeutic Medicine outlines some evidence suggesting that depression treatments – including SSRI antidepressants and ketamine – can help alleviate symptoms by reversing the effects on neuroplasticity seen in depression. This can lead to improvements in mood, energy, motivation, and sleep.

‍

While researchers stress that an effective antidepressant will enhance neuroplasticity, this is only part of the picture in tackling psychological stress. As the authors of the 2021 paper state, “Special attention must be drawn to non-pharmacological methods that can enhance the antidepressant effects [of antidepressant therapy] and provide psychological means to overcome other stressful situations in life.” This is precisely what psychedelic-assisted psychotherapy aims to achieve. Psilocybin therapy for depression can be effective because it combines the neuroplasticity effects of psilocybin with talk therapy, a positive intervention that can help to strengthen new synaptic connections.

‍

Research on the Ability of Psilocybin to Enhance Neuroplasticity

The atrophy of neurons in the prefrontal cortex plays a key role in the development of depression. Through this atrophy, the prefrontal cortex becomes underactive, losing control of the amygdala (which is involved in the processing of emotions). As a result, the amygdala becomes overactive. This is associated with rumination, intrusive thoughts, negative thinking about the future, and impaired concentration. However, there is research showing that psychedelics promote neuroplasticity, which is associated with rapid and sustained antidepressant effects.

‍

A 2023 study published in Nature Neuroscience found that psychedelics, including psilocin, promote neural plasticity by binding to receptors for the molecule brain-derived neurotrophic factor (BDNF). This is an important agent of neuroplasticity. Yet it seems there is not a single mechanism involved in the formation of new connections in the brain. As another 2023 study revealed, psilocin promotes neuroplasticity through the activation of intracellular 5-HT2A receptors (the receptors inside the neurons). The researchers found that activation of the same receptor on the surface of the neurons did not promote the growth of new connections.

‍

A study published this July in Nature revealed that psilocybin desynchronizes the human brain. At the level of neurons, brain regions, and the brain as a whole, there is less synchronized activity. This means the activity is occurring at different times – a departure from typical synchronized patterns of co-activity. This desynchronization of neural activity has been referred to as increased entropy (disorder, disorganization, or randomness) in the brain. Researchers suggest that these changes underpin not only acute subjective effects but also increased neuroplasticity.

‍

Potential Benefits of Psilocybin-Induced Neuroplasticity

We’ve already touched on how psilocybin-induced neuroplasticity could benefit depression. For example, by increasing neuroplasticity in the hippocampus and prefrontal cortex, their functions can return to normal. These functions include memory, focus, attention, and regulation of mood. But we also know that psilocybin therapy for OCD may be effective, which researchers believe is partly related to the brain changes that occur following treatment. An Imperial College London study is investigating the effects of psilocybin on neural plasticity in OCD patients.

‍

The ability of psilocybin to improve mental health through neuroplasticity effects can apply to other hard-to-treat or treatment-resistant versions of conditions such as addiction, anxiety, anorexia, and PTSD. Psilocybin may help alleviate all of these conditions because one thing they share in common is ingrained negative thought patterns. By increasing neuroplasticity, psilocybin can disrupt these states of mind, allowing other ways of thinking and feeling to emerge.

‍

Robin Carhart-Harris and colleagues have proposed an entropic brain model of conscious states, as a way of explaining how psychedelics like psilocybin benefit so many types of psychological distress. According to these researchers, conditions like depression, anxiety, anorexia, and OCD are marked by rigid, inflexible thought patterns (e.g. rumination), which they call low entropy states. ‘Entropy’, a term borrowed from physics, refers to the level of chaos or disorder in a system.

‍

A condition like depression or OCD is a highly ordered brain state, but biased towards negative thoughts and emotions. Psilocybin, in contrast, creates a much more flexible (or entropic) brain state. This more disordered brain activity helps to ‘unstick’ people from their mental prisons, allowing them to adopt other perspectives on themselves, others, and the world.

‍

Yet enhanced neuroplasticity outlasts the acute effects of psilocybin. In his latest book, The Psychedelic Handbook (2022), DMT research pioneer Rick Strassman writes that “these [neuroplasticity] effects continue over time – a couple of weeks to a month – and may correspond in humans to the afterglow or “critical period” during which milder but real benefit continues to accrue after one’s drug session. Remember, too, that this critical period is one in which the effects of psychotherapy may be especially powerful”.

‍

This is why psilocybin-assisted therapy can be more powerful than taking psilocybin on its own. There are many forms of psychotherapy that could be applied after the drug session, with popular forms including cognitive-behavioral, person-centered, somatic, transpersonal, and Internal Family Systems (IFS) approaches. Whatever approach is applied, the aim is to solidify healthier ways of relating to self, others, and the world. Psychotherapy sessions in the days and weeks following the psilocybin sessions is a way of making the most of the ‘critical period’, in which neuroplasticity is still enhanced. This presents an opportunity to integrate the experiences and insights elicited by psilocybin.

‍

Nonetheless, psychotherapy is not the only way to maximize the neuroplasticity effects of psilocybin. Psychedelic retreats also work with this knowledge in mind. In countries and states that have legalized or decriminalized psilocybin mushrooms, many retreat centers offer post-psilocybin integration sessions for participants. Sharing your experiences, insights, and reflections in a group setting – and hearing about others’ experiences – can help you better make sense of what attitudes and behavior changes you want to adopt moving forward. Odyssey offers both group psilocybin retreats and private sessions to support individuals on their journey towards better mental health and wellbeing.

‍

The nature-based setting of these retreats might also synergize with increases in neuroplasticity. For example, we know that classic psychedelics like psilocybin can enhance a trait called nature relatedness, or how connected one feels to the natural world. Many people report that this feeling is particularly strong when one has a psychedelic experience in nature. A Colorado psilocybin retreat is a great option for experiencing psilocybin in this way, as it takes place in a quiet, comfortable retreat center, surrounded by nature.

‍

In this kind of setting, many participants feel strongly connected to nature both during and after their psilocybin experiences. Indeed, researchers have found this feeling is influenced by natural surroundings during the acute effects of a psychedelic. Psilocybin-induced neuroplasticity, occurring when people experience contact with nature, may prove to be a highly effective way of promoting nature relatedness. This would have important implications not only for mental health but also for planetary health.

‍

In conclusion, the exploration of psilocybin's ability to enhance neuroplasticity represents a significant frontier in mental health research. As our understanding deepens, it becomes increasingly clear that psilocybin-induced neuroplasticity offers unique therapeutic potential across a wide range of mental health conditions, from depression and OCD to anxiety and addiction. The ongoing studies are not only unraveling the complex mechanisms behind these effects but also highlighting the importance of integrating these insights into therapeutic practices. Whether through psilocybin-assisted therapy or retreat-based experiences, the combination of enhanced neuroplasticity with supportive environments and interventions holds the promise of profound, lasting improvements in mental wellbeing. As we continue to unlock the mysteries of psilocybin, we stand on the cusp of new, more effective ways to heal and grow, both individually and collectively.

‍