Research with psychedelics is progressing on two fronts. Treatment of individuals with conditions like depression, PTSD, and substance abuse disorders with psychedelics is effective. This is progressing to the point where psilocybin and MDMA have been made legal for therapy outside of the research setting in Australia. We can expect the same to be true in the US within a year or so. At the same time basic research is helping us understand the physiological effects of drugs like psilocybin on a molecular level. A recent study has shed light on how psilocybin reduces anxiety.
Effects of Psilocybin on Stress Hormone Levels
When psilocybin is administered it alters perception, consciousness, and mood causing a psychedelic experience. In addition, psilocybin reduces anxiety for as long as a week after use. Animal research published in ACS Pharmacology and Translational Science showed a short term elevation of plasma glucocorticoids after subjects were given psilocybin. Glucocorticoids are stress hormones. While the increase in these hormones was temporary the reduction in anxiety lasted for seven to ten days.
What Happens When Psilocybin is Given and Stress Hormones Are Blocked?
An obvious question arises. Was it really the stress hormones that were causing less anxiety? To answer this question the researchers premedicated test subjects with the drug mifepristone. This medicine antagonizes (blocks) the effects of stress hormones (glucocorticoids). When this was done test subjects did not experience the same reduction in anxiety that they did when given psilocybin alone.
Another interesting finding was than when psilocybin was given to test subjects with chronically elevated cortisol levels they did not get the expected reduction in anxiety as did the other test subjects. When stress levels were allowed to go up and come back down subjects experienced less anxiety. When stress levels stayed up, there was never any reduction in anxiety.
Glucocorticoid Release and Anxiety Reduction
Researchers wanted to know to what degree stress hormone reduction as responsible for less anxiety versus what was caused only by psilocybin. They gave test subjects lisuride. This is a compound which blocks serotonin 2A like psilocybin does but does not produce the same psychedelic effects. What they found was the test subjects experienced reduced anxiety but not the psychedelic experience.
What Does This Research About Psilocybin and Anxiety Reduction Tell Us?
A major problem for patients with conditions like post-traumatic stress disorder and major depression is anxiety. The person is troubled by old memories such as with military veterans and memories of combat situations. Unfortunately, whenever they try to recall those old memories and sort out their painful feelings they experience a surge of anxiety and are unable to do so. Thus the reduction of anxiety that comes with taking a psychedelic medicine like psilocybin appears to be an important part of why this psychedelic medicine works to treat depression and why MDMA works to treat PTSD. The point of doing this type of basic research is to sort out the various types of basic physiological effects of psychedelics. Which are useful for treatment? Which are critical for getting good results? Which are unnecessary for successful treatment?
What Are Glucocorticoids?
Glucocorticoids are steroid hormones. They are produced in the cortex of the adrenal glands. These hormones are critical for metabolism of fats, proteins, and glucose in the body. Medically these substances are important because of how they suppress inflammation, allergies, and immunological reactions. These are not the steroids that bodybuilders use to increase muscle mass. Rather when used in excess they cause muscle breakdown. The glucocorticoid cortisol varies in the human body with highest levels around 8 am and lowest levels around 4 am.
These compounds are called stress hormones because the body increases secretion of them during periods of stress. The secretion of these hormones provides temporary help in coping with stressful and dangerous situations. This is why on an evolutionary basis the stress response exists. However, when a person is under chronic stress the continual secretion of these hormones and their continual high levels essentially wears out the body and the mind as well. We see just a snapshot of this in the current study where test subjects that were constantly under stress did not get the anxiety reduction from a temporary boost in cortisol because the level did not drop back down again.