Mental Health Blog

Clinical Depression and Psychedelic Medication: A Novel Treatment Avenue

Hello, and I hope everyone has been having a good week (and if not, know that there are good weeks to come).

Today I wanted to write a blog post about a topic of personal interest: the use of psychedelic medication in the treatment of clinical depression.

I first learned that psychedelics constitute a potential treatment avenue for depression back when I took a neuroscience course in the second year of my undergraduate degree. At the time, I found this mind-blowing and intriguing, as I had never considered the possibility that psychedelics (in controlled doses, prescribed by a professional) could have the potential to treat psychopathology. My views on the topic may have been skewed by widespread societal conceptions of psychedelics, resulting from a marked deficit in early research on the topic. Notably, research on psychedelic medication for the treatment of mental disorders constitutes a relatively recent phenomenon. Various factors may have contributed to the early abandonment of research on psychedelic medications. According to an analysis of historical scholarship by Hall (2022), early research on the therapeutic use of psychedelic medication was abandoned as a result of tighter regulations on pharmaceutical drug research, a failure of controlled clinical trials to fulfill the claims of those who advocated psychedelic medication, and a lack of interest by the pharmaceutical industry to fund clinical trials on these medications.

Despite this previous absence of research, there has been a recent surge of interest within the field regarding psychedelics as a potential treatment for mental illnesses, such as depression. 

According to an article by Moliner et al. (2023), psychedelics may produce quick and longstanding antidepressant effects that resemble those of clinically approved antidepressants. Interestingly, these drugs may also induce a phenomenon known as “neuroplasticity”, which also constitutes an effect of clinically approved antidepressant medication.

Neuroplasticity, or neural plasticity, has been defined as the nervous system’s ability to change in response to experience or environmental stimulation (American Psychological Association, n.d.). For instance, after injury to the nervous system, functioning neurons may overtake the roles of damaged neurons.

Building onto this concept, recent studies reveal that impaired neuroplasticity in certain areas of the central nervous system may be key markers of the pathophysiology of depression (Masi & Brovedani, 2011). In turn, abnormalities in neuroplasticity may implicate levels of certain neurotrophic factors, such as brain-derived neurotrophic factor (also known as BDNF), which constitute key players in plasticity. Neurotrophic factors, or neurotrophins, are proteins that aid the development and survival of certain neurons (American Psychological Association, n.d.). BDNF is a neurotrophic factor that is key to cognition, learning, and memory formation, in addition to brain plasticity. This research has led to the formulation of the “neuroplasticity hypothesis of depression”, which posits that decreased expression of neurotrophic factors plays a key role in depression, while effective antidepressant treatments reverse these attenuated neurotrophic effects (Yang et al., 2020). The aforementioned review article by Yang et al. includes diagrams to better understand and conceptualize this theory, and may be of interest to anyone who wants to learn more about this topic.

With the crucial role of BDNF in mind, neuroscience studies indicate that fluoxetine (also known by the brand-name Prozac, a commonly prescribed antidepressant medication), as well as ketamine (a psychedelic drug), display a mechanism of action that involves binding to TrkB, which is a receptor for the neurotrophic factor BDNF (Moliner et al., 2023). Other psychedelic drugs, constituting lysergic acid diethylamide (LSD) and psilocin, have been shown to bind to TrkB with a higher affinity as compared to other antidepressants. Additionally, Moliner et al. (2023) revealed that the effects of these psychedelics on neurotrophic signalling depend on BDNF and TrkB but do not require the activation of 5-HT2A receptors (which constitute a part of the serotonin receptor family). This is important, as the activation of these 5-HT2A receptors has been associated with a head-twitch response in rats and hallucinogenic effects in humans (Halberstadt et al., 2020). However, recent reports, such as one by Hesselgrave et al. (2021) indicate that these hallucinogenic effects may be separate from the antidepressant-like and plasticity-inducing effects, implying that it may be possible to discover psychedelic treatments retaining strong antidepressant effects without rendering individuals vulnerable to hallucinations. 

In sum, recent research points to the potential usefulness of psychedelic medications for the treatment of clinical depression. In my view, this constitutes a novel and interesting treatment avenue, which I chose to discuss in this blog post. 

I hope anyone reading this has learned something new, or learned more about a topic of interest. If you want to read more about neurotrophic factors, psychedelic medication, or the neuroplasticity hypothesis of depression, I highly recommend accessing the references cited in this blog’s bibliography.

I hope you enjoyed this blog post, and I wish everyone a happy, fulfilling, but also restful week!

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Note: The Free Your Mind Mental Health Society is an independent youth-led organization. The contents of this blog are not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. In the event of a medical emergency, please call your doctor or 911 or other local emergency numbers immediately.


American Psychological Association. (n.d.-a). Neural plasticity. APA Dictionary of Psychology

Retrieved February 19, 2024, from 

American Psychological Association. (n.d.-b). Neurotrophin. APA Dictionary of Psychology

Retrieved February 19, 2024, from 

Halberstadt, A. L., Chatha, M., Klein, A. K., Wallach, J., & Brandt, S. D. (2020). Correlation 

between the potency of hallucinogens in the mouse head-twitch response assay and their 

behavioral and subjective effects in other species. Neuropharmacology, 167, 107933–107933. 

Hall, W. (2022). Why was early therapeutic research on psychedelic drugs abandoned?

Psychological Medicine, 52(1), 26–31. 

Hesselgrave, N., Troppoli, T. A., Wulff, A. B., Cole, A. B., & Thompson, S. M. (2021). 

Harnessing psilocybin: Antidepressant-like behavioral and synaptic actions of psilocybin 

are independent of 5-HT2R activation in mice. Proceedings of the National Academy of 

Sciences – PNAS, 118(17). 

Masi, G., & Brovedani, P. (2011). The hippocampus, neurotrophic factors and depression: 

Possible implications for the pharmacotherapy of depression. CNS Drugs, 25(11), 


Moliner, R., Girych, M., Brunello, C. A., Kovaleva, V., Biojone, C., Enkavi, G., Antenucci, L., 

Kot, E. F., Goncharuk, S. A., Kaurinkoski, K., Kuutti, M., Fred, S. M., Elsilä, L. V., 

Sakson, S., Cannarozzo, C., Diniz, C. R. A. F., Seiffert, N., Rubiolo, A., Haapaniemi, H., 

… Castrén, E. (2023). Psychedelics promote plasticity by directly binding to BDNF 

receptor TrkB. Nature Neuroscience, 26(6), 1032–1041.

Yang, T., Nie, Z., Shu, H., Kuang, Y., Chen, X., Cheng, J., Yu, S., & Liu, H. (2020). The role of 

BDNF on neural plasticity in depression. Frontiers in Cellular Neuroscience, 14, 82–82.