A Trip to Better Health

Although clinical research involving psychedelics showed great promise over 60 years ago when it began, false information peddled by the media and throughout popular culture framed many of these plant-based chemicals as drugs of abuse or even as the cause of rebellions. As a result, the clinical studies evaluating their potential for good dried up as the drugs became tightly regulated and funding for research became increasingly scarce.

Fortunately, studies began to re-emerge around the 1990’s and this time the potential of these substances could no longer be ignored. Part of what is great about these unique substances is that they can be administered in animal models, allowing us to not only gain greater insight into their efficacy as a method of treatment, but they also help us to learn more about the mechanisms that may be underlying these various mental/emotional disorders.

For example, repeated administration of LSD activates feel-good receptors in the front of our brains, which eventually leads to their down-regulation—making us more sensitive to future feel-good moments (Buckholtz et al., 1990). Post-mortem brain samples of people with major depression showed an increase in these same receptors (Shelton et al., 2008), and mice genetically engineered to have a low amount of these receptors showed a significant decrease in anxiety-like behavior (Weisstaub et al., 2006). This research along with many other studies suggests that LSD could really help people with depression and anxiety disorders!

Currently, the theory is that these receptors may normally play a role in modulating the activity of other brain structures like the amygdala (Weisstaub et al., 2006), which is known for its function in fearful memory-associations (this part of the brain tends to be enlarged in people with PTSD for example (Kuo et al., 2012)), so if down-regulating these receptors can cause a decrease in the bad mojo feelings that come from the amygdala, this could lead to some promising avenues for treating a disorder that we still don’t really understand.

Right now the goal of this research is to break the stigma that these drugs currently hold so that we can finally pursue some novel (and promising!) approaches to the many mental/emotional disorders that are currently plaguing our society. Also by deepening our understanding of the underlying mechanisms of these disorders, we can seek to develop other effective treatments that have less psychoactive symptoms, potentially allowing us to treat even more people.

References:

Buckholtz NS, Zhou DF, Freedman DX, Potter WZ. (1990) Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain. Journal of Neuropsychopharmacology. 137-148

Kuo JR, Kaloupek DG, Woodward SH. (2012). Amygdala Volume in Combat-Exposed Veterans With and Without Posttraumatic Stress Disorder: A Cross-sectional Study. Archive of General Psychiatry. 69(10),1080–1086. doi:10.1001/archgenpsychiatry.2012.73

Shelton, R.C., Sanders-Bush, E., Manier, D.H., & Lewis, D.A. (2008). Elevated 5-HT 2A receptors in postmortem prefrontal cortex in major depression is associated with reduced activity of protein kinase, A. Journal of Neuroscience. 158,1406-1415

Weisstaub, N.V. et al. (2006). Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice. Journal of Science. 313, 536-540