Botanical Empress

Psilocybin, the Brain, and Mental Health

Magic mushrooms are making a comeback. If you’ve paid attention to the news in the mental health space over the last several years, odds are you may have noticed growing buzz over Psilocybin – the psychoactive component of magic mushrooms. Psychedelic research first peaked in the 1960s with the Harvard Psilocybin Project, but then quickly became a casualty of the War on Drugs toward the end of the decade. This paused scientific investigation into the drug for many years.

Breakthrough Status

Now, it seems that resistance to the possible medical and scientific benefits of psychedelic drugs has finally begun to fade. In the early 21st century, there was a renewal of psychedelic research as regulations became more relaxed alongside the groundswell in popular support for medical marijuana. In 2018, psilocybin received the FDA’s breakthrough therapy designation for the treatment of major depressive disorder (MDD). “Breakthrough status” is meant to speed the path to market and is granted to therapies that represent a potentially significant leap in therapeutic benefit over currently available treatments. Usually, these types of therapies are products of a shift in the approach or mechanism used to treat a disease or condition, and such is the case with psilocybin.

Revolutionary Treatment

To grasp just how magic mushrooms may eventually revolutionize the treatment of many common mental health conditions, it is useful to first understand a little of the brain science involved. Psilocybin belongs to the so-called “classical” psychedelics group alongside LSD, DMT, and mescaline. All substances in this group share an ability to activate a particular receptor in the brain, called the serotonin 2A receptor or 5HT2A. The serotonin 2A receptor responds to, unsurprisingly, a neurotransmitter called serotonin. This same receptor is targeted by many existing antidepressant drugs, most commonly the selective serotonin reuptake inhibitors (SSRIs). SSRIs work by making more serotonin available to bind to receptors.

Mental Effect 

The brain has all kinds of different receptors, which sit on the surface of neurons and when activated give those neurons instructions to do things. Each receptor type responds to a specific chemical messenger type – like a key fitting into a lock. In addition to naturally produced neurotransmitters and other chemical messengers, sometimes substances from outside our bodies also have the right molecular shape to activate a given receptor. We call these substances drugs. The physiological or mental effect of a certain type of receptor’s activation depends on its location in the nervous system (e.g. in a particular part of the brain or in the gut) and on the particular neurons receiving the instructions. When ingested, the psilocybin found in magic mushrooms is converted by the body into another molecule called psilocin, and it is psilocin that has the direct ability to activate the serotonin 2A receptor in the brain.

Effects of Psilocin

In the short term, while the drug is active in the body, the effects of psilocin are broad and can include euphoria, hallucinations and visual distortions, increased self-reflection, increased heart rate, reduced fear response, creativity, previously inaccessible perspectives, connection with nature, and many others. In certain cases, effects can also include persistent states of fear and paranoia, an experience commonly referred to as a “bad trip”. As with other psychedelics, the subjective experience of psilocin is broadly understood to depend heavily on “set and setting”. Set and setting refer to one’s mental state and physical surroundings at the time the drug is taken. It is generally accepted that it is sensitivity these factors that are responsible for the wide variety of emotional reactions psychedelics can produce.

Greater Interconnectivity

Because serotonin 2A receptors are found all over the brain, most of how what is happening physiologically relates to the subjective short-term experience of a mushroom trip are unknown. One observation that has been made, however, is that psilocin can cause changes in patterns of brain activity that result in “less constrained” thought and experience. It can increase interaction between areas of the brain that do not normally “talk” to each other, and reduce the level of interaction between others that do. This finding may support some of the documented subjective experiences that magic mushrooms enable new ways of thinking about familiar concepts, memories, or experiences of one’s life. Greater interconnectivity may also make the brain more sensitive to stimulation, which could at least in part explain the critical role setting plays in determining the nature of psychedelic experiences.

Behavioral Effects

Research is being published on the long-term effects of psilocin, as well. In recent years, studies have found long-term benefits from one to several doses of psilocin-based treatment for a number of disorders, including cancer-related distress, depression, and addiction. While the research is still in its early phases for disorders beyond depression, there is little doubt that psilocin produces positive and lasting behavioral effects for a number of disorders from just one or a few doses.

How is it doing this exactly? That question is also up in the air, but there are some theories emerging that make sense in light of the drug’s short-term effects. One potential explanation has to do with the prefrontal cortex (PFC), which is a part of the brain that acts as the main control center for things like social behavior, planning and organization, attention, mood regulation, and other “big picture” processing jobs. This part of the brain deteriorates in many diseases, including depression. This may be due to declines in brain-derived neurotrophic factor (BDNF), a protein responsible for helping the brain form new connections and adapt to experience. The ability of the brain to adapt in this way is known as “neuroplasticity”. Notably, prior research has found that LSD increases BDNF, though this research has not been repeated with psilocybin.

Animal studies have also directly suggested that psilocin creates new connections between neurons, perhaps resulting in new pathways that allow us to behave and feel differently. In other words, psilocin may help a brain that is stuck in one way of responding remember how to reengage with mental states to which it has lost or never had access. Early human studies looking at psilocin’s effects on brain connectivity are not quite so far along as the studies on animals, but that research will move quickly.

We won’t have to wait, however, for a certain explanation of exactly how psilocybin works before we see it being used to treat those in need. Given its excellent safety profile, low potential for abuse, staggering effectiveness relative to alternatives, and its breakthrough designation from the FDA, it won’t be long before psilocybin-assisted therapy is available to patients in the United States.

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