Psilocybin vs TMS: Do They Treat the Brain in Similar Ways?

Welcome to Brandywine Valley TMS, a leading mental health clinic in Wilmington Delaware, offering TMS therapy as an effective depression treatment. In this article, we will explore psilocybin and how it might correlate to TMS in order to treat depression.

Psilocybin In Magic Mushrooms

Psilocybin & TMS effects on the Default Mode Network (DMN)

5HT2A receptors are found in various brain regions, but they are highly concentrated on the neo-cortex or prefrontal cortex (this is the region that, by the way, we stimulate with TMS). This makes perfect sense since a depressed brain tends to have decreased activity and metabolism at the level of the prefrontal cortex. Another brain region that is rich in 5HT2A receptors is the visual cortex and this also makes a lot of sense, given that psychedelic mushrooms are often recreationally consumed with the intention of experiencing visual hallucinations.

Psilocybin and TMS are known to exert their therapeutic effects by altering so-called default mode network (DMN). Without getting too technical, suffice it say that this network of brain structures is most active when we are in a resting state or idling, so to speak, with no specific demands on our attention, without engaging in any specific mental tasks. This is where our minds go to wander. The DMN is where our sense of self is headquartered, it allows us to develop an individual identity, providing us with the means to become aware that we are separate from everything else. It’s not until late in a child’s development that the DMN establishes itself. Neuroscientists have a nickname for the DMN: “the me-network”.

Whereas the DMN functions as an orchestra director that allows for introspection and intellectual achievement, it can also become diseased with damaging forms of self-regard, unhappiness and low self-esteem. Anxiety, depression, OCD & addiction all have a tendency for rumination and negative self-talk. An unhealthy-hyperactive-rigid DMN is allowed to gain flexibility when exposed to psilocybin – or when the prefrontal cortex is strengthened with the magnetic pulses TMS delivers.

Studies commonly refer to doses of 25-30 Mg psilocybin as the most effective in treating depression, compared to lower doses of 1-10 Mg. Adverse events were more common at higher doses. Studies show that the chances of having a therapeutically beneficial psilocybin journey are increased by controlling several factors. For example, covering the eyes with an eye mask is recommended. This is in order to re-focus the individual’s experience away from visual hallucinations and more towards the more transcendental and psychological effects we are looking to achieve in psychiatry. Studies also show certain types of music are more conducive to a transformative effect. Studies have been performed in adults only, with ages ranging from 25 to 70. To avoid serious complications, studies have excluded subjects prone to experience psychosis such as those with schizophrenia or bipolar disorder, or even individuals who had a close relative with such conditions.

A word of caution is in order for mushroom foragers: when I was training in psychosomatic medicine in Montefiore Medical Center, we had a 20 y/o male patient who consumed mushrooms with the intention of enjoying a trip with his friends - “recreational” drug use, as they say. He developed a severe case of acute hepatitis and was facing a liver transplant. This young man was severely jaundiced (yellow discoloration of skin). He also had track marks from heroin abuse and tested positive for Hepatitis C and it wasn’t clear if his hepatitis was due to consuming the wrong kind of mushrooms, hepatitis C or both. The bottom line for my reader that pertains to psilocybin is: do not attempt to go into the woods to pick up mushrooms as there is considerable risk in ingesting the wrong kind of mushrooms. Many types of mushrooms are poisonous.

Most magic mushrooms have a 1% psilocybin concentration, but it can vary from 0.5% to 2%. So 1 gram of mushrooms will contain about 10 Mg of psilocybin. Concentration varies from batch to batch, region of origin, storage and other factors. Source is key and studies use synthetic psilocybin which makes it more standard. Studies use a dosage of about 25-30 Mg, given as a single dose or twice.

According to various clinical trials, prerequisites for an effective therapeutic psilocybin journey include not being predisposed to psychosis and not having a family history of psychotic disorders; being between the ages 25-70; lying down with eyes covered and listening to music with no vocalization, such as classical. Food should be avoided 4 hrs prior, as the stomach acidity converts psylocibin to psilocyn. The effects become noticeable within 30 minutes, and experiencing anxiety due to “ego dissolution” is common.  The typical psilocybin journey lasts 4-6 hrs.

Pyramidal neurons in the brain have ramifications, or apical dendrites, which are rich on 5HT2A receptors. These apical dendrites connect upwardly and laterally to other neurons in different regions, increasing communication to various parts of the brain and blurring the typical segmentation of brain functions. In other words, causing integration of brain regions.

Psilocybin also broadens the input of information at the level of the thalamus (the thalamus functions as a telephone switch board allowing for the input of information) by activation of 5HT2A receptors, allowing for a blending of interoceptions and other sensory inputs, so that for example breathing deeply may result in a subjective sensation of bending or stretching one’s visual field. This blending of perception is referred to as synesthesia, which is caused by an alteration in the process of “thalamic gating” - the mechanism by which a complex cortico-subcortical network of neurons filters, organizes and collates sensory information in the brain and then selectively relays it to the frontal lobes.

Brain MRIs of psilocybin study subjects have shown extensive lateral connectivity, less hierarchical organization and more interconnection between different brain areas. This suggests the brain has rewired in different ways.

Whereas recreational users of psilocybin often describe a journey as otherworldly, the long-term beneficial effects are due to changes in neuroplasticity. The formation of new neurons, or neurogenesis, happens in the dentate gyrus and other subregions of the hippocampus, which is involved in learning and memory. Neurogenesis may happen in other parts of the brain, but neuroscientists don’t think that neurogenesis happens in any significant way in areas like the neocortex, striatum or cerebellum.

Moreover, psilocybin’s effects on neuroplasticity don’t seem to be related neurogenesis (adding new neurons) per se, but to the addition and strengthening of new neural connections, and the elimination or weakening of others. Psilocybin seems to play a role in the addition of novel connections between pyramidal neurons of the frontal cortex, visual cortex and other cortical regions, and probably subcortical regions as well, such as the thalamus and brain stem. This process involves the growth of apical dendrites on pyramidal neurons that connect laterally with other neurons, as well as dendrites that come out of the base of these pyramidal neurons. These processes are enhanced in response to psilocybin.

Dendritic spines, which are protrusions on the dendrites that mediate connectivity between cells, also proliferate and strengthen communications with each other. Of note, it is known from postmortem tissue studies that depressed individuals have lower concentrations of dendritic spines and that both CBT (cognitive behavioral therapy) and antidepressants increase the expression of dendritic spines in the brain.

In conclusion, whereas psilocybin has been used for a long time as a way to access different levels of consciousness, in recent years a body of research has developed evidence that this drug can effectively treat depression, anxious states and addiction. Psilocybin is found in naturally occurring “magic mushrooms” of the genus Psilocybe, but identifying and collecting these mushrooms on your own poses significant health risks as many mushrooms are toxic. Psilocybin seems to improve brain connectivity in similar ways to TMS, modulating the DMN. In addition, possessing the actual Psilocybe mushrooms is illegal. We must be patient while research continues to evolve. Hopefully, in a few years the FDA may approve the use of psilocybin for certain psychiatric disorders.

Note: The purpose of this article is educational only and does not constitute a recommendation to ingest psilocybin. In the US, psilocybin is classified as a schedule 1 Drug, which is illegal in most states.

Are you local to Wilmington Delaware? If so, contact our local TMS clinic to schedule a consultation for the treatment of depression with psychiatrist, Dr. Jack Castro, to learn more about TMS therapy as an effective treatment option.

For more information on how psilocybin and other psychedelics are being used in mental health, I strongly recommend the book "How to Change your Mind" by Michael Pollan.