Psilocybin is a psychedelic compound that is present in over 200 varieties of fungi. Since its isolation in 1958 by Albert Hofmann, a variety of synthetic methods for producing psilocybin have been found. The human body quickly metabolizes psilocybin into psilocin, which is the pharmacologically active agent which interacts with several serotonin receptors in the brain. It is known as a 5-HT2a agonist, meaning it can change serotonin activity in the human brain and disrupt brain connectivity.
Psilocybin Mushroom Science and Research
Things to Know
- Psilocybin impacts the brain’s Default Mode Network (DMN) and Central Executive Network (CEN)
- Psilocybin increases connectivity between many areas of the brain
- Psilocybin is the second most studied psychedelic to date
- The U.S. and Europe are leading the world in research on psilocybin
Psilocybin Chemistry and Neuroscience
Psilocybin was first synthesized in 1958 by Albert Hoffman, a research chemist at the Swiss pharmaceutical company Sandoz who in the previous decade discovered the psychedelic effects of LSD. Hoffmann was provided with samples of Mexican psychedelic mushrooms by R. Gordon Wasson, who had obtained them from the Mazatec curandera, Maria Sabina. Hoffmann identified and synthesized the psychoactive ingredient, which he named psilocybin, after the psilocybe mushroom.1
Recent research suggests that psilocybin’s mechanism of action is a result, at least in part, of a down-regulation of the default mode network (DMN). The DMN refers to a network of brain regions that are typically activated when an individual is not engaged in specific tasks or focused on the external environment. It is often associated with introspection, self-referential thinking, and mind-wandering. In particular, rumination and self-reflection on negative experiences and emotions such as regret, trauma, and loss, along with other negative self-referential processing, take place in the DMN and have been connected to the onset and perpetuation of depression.
fMRI Research
Functional Magnetic Resonance Imaging (or fMRI) measures brain activity by looking at the magnetism of iron in the hemoglobin of blood. This allows neuroscientists to map blood flow and the oxygen levels in the blood using a blood-oxygen level dependent response, or BOLD signal. When an area becomes more active through the use of psilocybin, for example, it uses more glucose but generates energy in rapid chemical reactions that do not use oxygen. Consequently, blood flow increases, but oxygen consumption does not, resulting in a higher concentration of oxygen in blood in the local veins. Scans have shown that psilocybin reduces blood flow and neural activity in several brain regions, including the posterior cingulate cortex and medial prefrontal cortex.
Using fMRI technology, researchers have visually analyzed brain activity during the psilocybin experience. One key findings is that psilocybin downregulates the Default Mode Network while up-regulating and increasing connectivity between all areas of the brain.2 This brain-wide synergy is not present during normal consciousness, and is hard or perhaps impossible to achieve with talk therapy or SSRIs.
Researchers hypothesize that this highly connected brain experience allows for the release and integration of experiences, thoughts, and feelings associated with depression and anxiety. The sudden, brainwide activity and integration of experience could be a partial explanation for how people with treatment-resistant depression can make such significant progress in only one or two psilocybin-assisted therapy sessions, when typical treatments fail to make progress.3
EEG Research
Researchers are using electroencephalography (EEG) to investigate psilocybin. While fMRI uses the BOLD response, EEG detects the electricity in your brain, but only the cortical regions (the top part). While this tool has been available for just about 100 years, it has the ability to detect different oscillations and waves that fMRI cannot detect. EEG has a higher temporal precision than fMRI, but the spatial precision isn’t as accurate as fMRI.
A 2013 study4 using EEG found that psilocybin impaired negative response to fearful faces. Psilocybin’s effect on happy faces was not affected. Researchers believe this means that psilocybin makes the negative response to fearful faces less impactful.
Clinical Trials
Psilocybin is one of the most studied psychedelics to date. There have been over 100 clinical trials to investigate psilocybin of which 28 are Phase II studies. Psilocybin has been studied as a possible treatment for a wide range of mental health disorders. The following is a list of conditions for which psilocybin has potential therapeutic benefits based on clinical trials and academic studies conducted to date:
- Depression (MDD, TRD, postpartum, and bipolar)
- Anxiety and depression in patients with life-threatening disease
- Social anxiety for those with autism
- Substance misuse, including alcohol, opioid and nicotine dependence
- Eating disorders such as anorexia nervosa
- Long-term mindfulness5
- Demoralisation in long-term AIDS survivors
- Pain disorders, including cluster headaches/migraines and fibromyalgia
- Symptoms of obsessive-compulsive disorder (OCD)
- Post-Traumatic Stress Disorder (PTSD)
Traumatic Brain Injury (TBI)
Among the active trials investigating psilocybin are those investigating the compound for the treatment of migraine headaches, the treatment of OCD, and psilocybin-assisted treatment for alcohol dependence. Most of these studies are either taking place in the U.S. or Europe, as is the case for the other key psychedelics.
