5 ways psychedelics may affect the brain has been discussed in this blog and should be of great value to you. In the last decade, discussions around psychedelics have exploded, driven in part by research. This shows their safety and efficacy in treating a number of mental health conditions ranging from depression to anxiety. Psychedelic molecules have obvious, dramatic effects on our thinking and mood. But when it comes to understanding exactly how they exert these effects, things are a little less clear. Though the mechanisms of each psychedelic may differ, researchers have noted several overarching themes. Here are five of the top ways that psychedelic molecules may influence our brain function.
1. Affecting neurotransmitters and their receptors
Perhaps the most commonly cited effect of psychedelic drugs relates to their influence on neurotransmitters. That is chemical signaling molecules in the brain. Many psychedelics are thought to work by acting on a site for the neurotransmitter serotonin called the 2A receptor. Psychedelic binds to the 2A receptor on neurons in the brain’s cortex. This seems to be a major driver of their mind-altering effects.
While the 2A serotonin receptor is key, there’s more to the neurotransmitter story. Other additional neurotransmitters and their receptors (including GABA, dopamine, norepinephrine, and glutamate) also appear to play a role.
2. Changing brain activation patterns
Measuring changes in brain activation patterns has become a popular way to examine the biological effects of psychedelics. In this research, much focus has been on a part of the brain called the “default mode network” (DMN). Activation of the DMN is linked to mind wandering and thinking about the past and future. Psychedelics have repeatedly been shown to change activity and connectivity of this network in the brain. This finding has been proposed to the reorganization of thoughts and opportunity for more insight that accompanies psychedelic use.
A number of other brain activation changes have also been linked to the use of psychedelics. Among the more prominent of these changes are alterations in the connectivity between the prefrontal cortex and the amygdala.
3. Helping the brain rewire itself
The brain is always rewiring itself in response to its environment, a process known as neuroplasticity. One of the ways it does so is by changing the connections between neurons. Issues with neuroplasticity have been linked to worse mental health, especially depression. Interestingly, new research in psychedelics suggests that they might help to reverse this deficit.
Some of the most remarkable evidence for the effect of psychedelics on neuroplasticity relates to ketamine. Though the work is primarily based on animal research, ketamine is thought to help enhance connections between neurons. Further, albeit more limited, research suggests that other psychedelics may also facilitate new and stronger connections between neurons. This includes MDMA, LSD (lysergic acid diethylamide), and psilocybin
4. Influencing the brain’s immune system
The connection between immune function and mental health has been the subject of considerable research over the last several decades. Elevated inflammation (a form of imbalanced immunity) has been linked to depression and anxiety. It’s also thought that some of the most commonly prescribed antidepressants may work in part through the immune system. When it comes to psychedelics, researchers are now suggesting there may be a similar effect at play.
As previously described, serotonin and its receptors are thought to play a major role in the psychedelic response. Serotonin itself is involved in multiple aspects of the immune system. And there may be receptors for this neurotransmitter on immune cells. As well as tissues throughout the body and brain. This indicates a potential for widespread immune effects after psychedelic use. Other studies in cells and animals show that psychedelics may have an anti-inflammatory effect. Finally, it has been proposed that psychedelics could directly affect the brain’s own immune cells.
5. Altering gene expression in the brain
One of the most powerful reframes in modern science has to do with the way our genes are expressed. Genes are stretches of DNA that code for proteins and RNA. They influence every aspect of who we are. But though the DNA in our genes is relatively rigid, it has now been shown that our environment. Our choices, and even the food we eat can change our genetic expression for the better or the worse. This fascinating discovery helps explaining some of the benefits of psychedelics, as they may change gene expression in the brain.
Research connecting psychedelics and gene expression has been ongoing for several decades. For example, in 2003, scientists showed a rapid change in gene expression after administration of LSD to rats. In an animal study from 2020, a single dose of the psychedelic psilocybin appeared to alter expression of 19 genes. This is in the brain’s prefrontal cortex, especially those related to the immune system. A subsequent animal study found similar brain effects on genes related to neuroplasticity. Finally, very recent (preprint) research suggests a potential effect on thousands of genes after DMT administration. Despite these data points, the overall effect of psychedelics on gene expression remains somewhat unclear.
What comes next:
As interest in psychedelics continues to grow, scientists will continue to investigate. The myriad ways in which these potent molecules influence our bodies and brains should be known further. Like conventional antidepressants, it seems likely that psychedelics act on a range of biological pathways. This is so as to achieve their effects on mood. Not leaving out cognition, and that different psychedelics may have distinctive effects on the brain.
The climate around psychedelics has changed dramatically over the last several decades. There’s still much to learn about exactly how psychedelics work and how best to leverage them to improve mental health. However, even a slightly richer appreciation for their biological effects could promote understanding of where they might be of value in treatment. As well as helping providers and patients to better anticipate the effects of their use.