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Two different psychedelic medicines have achieved breakthrough drug status with the United States Food and Drug Administration. The FDA is the agency that reviews and approves medicines for legal use based on their safety and effectiveness. Psilocybin and MDMA have been found to be amazingly effective as adjunctive treatment for depression (psilocybin) and post-traumatic stress disorder (MDMA). They are used to make psychotherapy or coaching sessions more effective and only require a dose or two to produce an effect much more successful that achieved by standard antidepressants given daily for weeks or months at a time. Researchers believe that these psychedelic medicines produce longer lasting or even permanent changes in how the brain works. As these medicines move toward approval researchers have begun looking into how psychedelics affect the brain on a more complete basis than simply how they work for the treatments they are being tested for.

Flattening of the Brain’s Dynamic Landscape with Psychedelics

Researchers at Weill Cornell Medical College of Cornell University studied the effects of both psilocybin and LSD on the brain. Their conclusions can be summarized as this. These psychedelics reduce the “energy” needed by the brain to switch between activity states by activating serotonin receptors. The researchers used non-invasive tests such as functional MRI testing and PET scanning to identify activation patterns in the brain when test subjects were given psychedelics versus a placebo. They were able to create receptor density maps of serotonin receptors showing that after taking a psychedelic medicine less energy is required for the brain to adjust or switch between states like anxiety, depression, joy, fear, anticipation, happiness, etc.

Flattening of the Brain’s Dynamic Landscape with Psychedelics
Flattening of the Brain’s Dynamic Landscape with Psychedelics

Psychedelic Effects on Brain Measured by PET and MRI Scanning

The researchers’ explanation of testing results is extremely “dense” reading with discussions of temporal sequences of brain states and temporal dynamics of brain states with both LSD and psilocybin. They looked at specific brain networks to see which were activated and which were suppressed. These included the DAT (dorsal attention network), DMN (default mode network), FPN (frontoparietal network), LIM (limbic network), SOM (somatomotor network), VAT (ventral attention network), and VIS (visual network). Each of these is a specific part of the brain which carries out specific functions. The scanning tests used allowed researchers to see changes in activity in each region in real time.

Brain States Affected by Psychedelics

The human brain goes through various “states” as it processes information and emotions, engages in physical activity or solves problems. Each state is associated with a different pattern of activation of the various brain networks. The researchers studied the various brain states after subjects received LSD, psilocybin, or a placebo. Both medicines had the effect of dampening or reducing the “energy” or degree of stimulus required to move from state to state and there were some differences in timing which related to how the two psychedelics are processed by the body and how they work in the brain. Again, the reading is pretty dense but the bottom line is that both psychedelics tested allowed the brain to transition more easily between brain states using less energy (stimulus).

Brain States Affected by Psychedelics
Brain States Affected by Psychedelics

Psychedelics and the 5-HT2a Serotonin Receptor

The 5-HT2a serotonin receptor is believed to be critical in brain functions and the researchers were able to map activity in relation to known density of these receptors which are not located uniformly throughout the brain. Their findings showed that this receptor was the one most responsible for the effect of lowering the “energy” needed to easily transition from one brain state to the other. This receptor is likely the one most important in treating depression with psilocybin and psychotherapy.

Dose and Effect of Psychedelics on the Brain

Within the ranges of doses given for both LSD and psilocybin, higher doses caused more rapid, longer lasting, and more profound effects, which effects are consistent with how medicines commonly work. The researchers point out that when they refer to “energy” in this study they are not referring to physical energy but rather the magnitude of input in terms of emotion or external stimulus experienced by the person and thus applied to the brain.

Understanding How Psychedelics Affect the Brain

When a potential treatment is being considered by the FDA the first concern is that it does not cause harm. The second is that it works and that it works better than a placebo. In the case of psilocybin and MDMA, they are used with psychotherapy. To pass FDA testing they need to produce a statistically better result than psychotherapy alone. The work done by researchers in this study is much more basic but no less important. By understanding the very basics of how psychedelics affect the brain, we will be able to envision new therapies and avoid problems along the way. We will also very likely better understand how the brain works!

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