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Your Brain on Psilocybin Mushrooms

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Psilocybin and the default mode network (DMN)

Photo credit: Neuro Image Journal

The DMN is a powerful neural network that forms the basis of self-identity. In normal states of consciousness during periods of rest, the default mode network ramps up, leading to internal chatter, mind wandering, future worrying, and self-obsessive thoughts.

People with highly active default mode networks are typically more anxious and depressed, because they’re constantly ruminating on past trauma and mistakes, future fears, and internal criticisms. The same people are also more likely to seek solace in dangerous, addictive substances and harmful behaviors like eating disorders.

Psilocybin’s incredible power comes from its ability to change DMN wiring. Research indicates this classic psychedelic compound decreases connectivity within key components of the DMN, creating novel connections that support sensory and high-level emotional and cognitive processes.

In other words, psilocybin gives people a break from the obsessive thoughts that have defined their sense of self, allowing them to relive repressed memories without the stories attached. And, in that DMN reprieve, with high-level emotional and cognitive regions online, people can reframe trauma from an insurmountable tragedy into a healing opportunity.

Psilocybin and the amygdala

image of amygdala

While magic mushrooms’ DMN-rewiring is essential, emerging research shows the amygdala also plays a crucial role in transformative experiences.

The amygdala is the brain’s center for emotions, emotional behavior, and motivation. It serves an essential evolutionary purpose, helping people detect danger and respond accordingly. But some people have overactive amygdalas when there’s no imminent threat, causing unnecessary aggression and fear.

For example, people with PTSD continue living in fear of traumatic memories that no longer exist in the present, because the amygdala still senses danger. Chronic amygdala overstimulation ultimately makes PTSD, depression, and anxiety symptoms more severe. It can also condition fear in otherwise healthy individuals.

Psilocybin’s therapeutic power lies in its ability to deactivate part of the amygdala by reducing blood flow to the region. This action weakens people’s reactions to triggering stimuli, reducing the emotional intensity that’s trapped them in the past. Free from the fear associated with trauma and conditioning, people can harness psilocybin hallucinations to emotionally process challenging memories for the first time in their lives.

Johns Hopkins University research on healthy subjects showed that psilocybin-induced diminished amygdala response endured one week after the psychedelic experience, eventually returning to baseline one month later. The Johns Hopkins team theorized they could extend this window by providing professional therapeutic support.

In 2022, Johns Hopkins Medicine researchers conducted a follow-up study on some of the same patients. This time they found psilocybin, combined with a supportive psychotherapy container, allowed treatment-resistant depression symptoms to subside for at least a year after their second dose.

Microdosing and the brain

Most psilocybin brain-imaging studies focus on magic mushroom effects at high doses. However, scientists are starting to expand research to psilocybin microdosing as well.

Microdosing, taking sub-perceptual or sub-threshold psychedelics doses, is an increasingly popular practice. People microdose psilocybin and LSD regularly for mood elevation, anxiety reduction, and cognitive enhancement. Many also tout the practice for its antidepressant benefits, as shown in Paul Stamets’s observational psilocybin microdosing study.

In 2020, the Beckley Foundation conducted a placebo-controlled within-subject study investigating the effect of a single low dose of LSD on BDNF (brain-derived neurotrophic factor) levels in healthy volunteers. BDNF is an essential protein that scientists associate with improved mental health, learning, and memory.

Beckley’s blood-sample findings indicated that LSD microdosing caused a dose-proportionate rise in BDNF six hours after administration. The study focused on LSD, not psilocybin. But LSD and psilocybin’s similar neural mechanisms indicate a psilocybin microdosing trial might produce similar results.

Also, the world’s first study protocol for a randomized, double-masked, placebo-controlled trial of microdosing in healthy volunteers confirmed that the practice improves self-reported ratings of connectedness, creativity, happiness, and energy. The study, from the University of Auckland, hasn’t published its complete findings yet. But the research team believes fMRI imaging will reveal greater levels of neuroplasticity and changes in the DMN than with a placebo.

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