The healing power of psychedelics
Science is one step closer to reverse the damage of chronic stress
Stress is inevitable and suffering is universal, but victimhood is optional. The choice is yours, says Dr.Eger, who survived a concentration camp during World War II and reflected on life in her book. However, it is not easy to change the brain by using the brain itself. Stress causes maladaptive plasticity within the brain’s reward circuit. The mood and anxiety disorders affect one out of every six people in their lifetime and cost the United States economy an excess of $50 billion per year.
The recent good news stemmed from new studies attempting to tune the brain’s plasticity back to normal and undoing the damaging effects of a stressful life. By undoing the harm of the stress on brain signaling and functioning, the symptoms of anhedonia (inability to feel pleasure) and social avoidance (prevalent in depressed individuals) may resolve.
Learning from animal studies
First, to understand and measure chronic stress, scientists introduced an animal model of social defeat stress. The protocol is simple, and it takes 3–4 weeks and a couple of mice to complete. You need at least two mice — one is repeatedly subjected to bouts of social defeat by a larger aggressive mouse. After a while, the first mouse tries to avoid the second one. And if the test is repeated, the stressed mouse will develop a depression-like phenotype marked by anhedonia, anxiety, and social-avoidance behaviors.
Stress induces synaptic plasticity within several different brain regions is causally linked to depression-like behaviors in animals. That means that the brain is altered by chronic stress. Neurobiological changes underlying mood and anxiety disorders are directly related to different brain areas like the hippocampus and prefrontal cortex. Compared to a stress-free mouse, in a chronically stressed mouse, the expression of presynaptic proteins and structural neuroplasticity was significantly altered.
The next step is to figure out if the altered state could be dialed back to normal. And the study with pigs may have provided some additional clues to that. According to a fascinating recent publication, brain alterations induced by stress appear to be reversed in pigs after a single dose of psilocybin. The international team of researchers from Harvard Medical School and Faculty of Health and Medical Sciences at the University of Copenhagen, measured synaptic density and 5-HT2A receptor density in pigs’ brains after only one dose of psilocybin ( 0.08 mg/kg). That dose was chosen as an equivalent to a mild amount for humans.
Structural shifts in animal’s brain
They observed that the plasma level of psilocybin was undetectable one day after injection, meaning the psilocybin doesn't have lingering toxicity. However, certain brain areas responsible for emotional processing were significantly different in the psilocybin receiving pigs than pigs receiving a saline injection.
“A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT2AR) agonist, may be associated with long-duration antidepressant effects”, assumed the research team. The effect of a single dose was gradual, and the depression score continuously got lower over at least seven days that followed the single injection. Intriguingly, findings suggest that psilocybin causes increased persistent synaptogenesis (formation of new synapses in the brain). An acute decrease in 5-HT2AR density seems to play a role in psilocybin’s antidepressive effects.
It emerges transient down-regulation of 5-HT2AR is essential for boosting the formation of new synapses. By day seven, the 5-HT2AR returned to the baseline. But seven days of downregulated the 5-HT2AR provided an opportunity for new synapses to grow in two relevant key brain regions responsible for mood.
These intriguing and encouraging results are just the beginning of our understanding of how psilocybin, the active ingredient of certain fungus (mushrooms), could facilitate new brain synapses in humans and reverse the physical changes in brain areas caused by chronic stress.
Anna Deveaux, M.Sc. is a learner, writer, biotech investor who is interested in research translation, drug development, genetics.