Psychedelic medications were outlawed almost fifty years ago, but they are re-emerging as extremely promising therapeutic solutions for mental health conditions. Since it was outlawed, many individuals have used it clandestinely to enhance their mental health, and many of them have experienced significant improvement. In light of these results, scientists have initiated clinical trials to determine whether psychedelic-assisted therapy can be reintroduced in the treatment of mental health diseases, specifically clinical depression. “The psychedelic experience has been described by some participants as being among the most meaningful or spiritually significant experiences of their lives”(Artin et al., 2021) ‘Charles Raison, a psychiatrist at the University of Wisconsin–Madison was amazed by his observation that a single treatment (of psychadelic drug) produced a long-term change in emotional state. He contrasts this with conventional antidepressants such as selective serotonin reuptake inhibitors (SSRIs), which require daily administration and trial-and-error matching of patient and drug — and where halting treatment too abruptly can lead to a brutal relapse. The US Food and Drug Administration has even granted psilocybin a ‘breakthrough therapy’ designation as a potential treatment for severe depression.’ (Eisenstein, 2022) In this blog, I will examine if psychedelic-assisted therapy can aid patients suffering from clinical depression more than psychotherapy alone and faster than other antidepressants.
Psychedelic drugs have shown to assist patients in gaining a more profound perspective on life, typically through mystical experiences of various kinds. This helps patients find considerable happiness in their lives, hence lowering their depression symptoms. “Fortunately, a growing database from prior large-scale survey-based studies have provided insight into a wide range of associations either unexplored or only hinted at in clinical trials conducted to date. Taken as a whole, these studies provide convergent support for findings from clinical trials, including that psychedelic use is associated with increased emotional well-being, reduced harmful substance use/misuse (i.e., illicit drugs/tobacco/alcohol), a tendency toward liberal political views and an enhanced sense of connection with nature. These effects are reliably associated with the occurrence of various types of transformative mental states (e.g., mystical, emotional breakthrough, insight-type) during the acute psychedelic experience that have also predicted outcomes in clinical trials” (Raison et al., 2022) ‘In several studies in patients and in healthy volunteers, the intensity of mystical-type experiences reported after psilocybin sessions was associated with favourable outcomes. Furthermore, cross-sectional studies have suggested that mystical-type and psychologically insightful experiences during a psychedelic session predict positive therapeutic effects. Consistent with these previous studies, the current trial showed that psilocybin-occasioned mystical-type, personally meaningful, and insightful experiences were associated with decreases in depression at 4 weeks.’ (Davis et al., 2020) In a research study conducted by Charles Raison and his colleagues, they found that “the majority of respondents (81.7%) identified either psilocybin or LSD as the agent they felt had been most beneficial for them; in addition to mental health benefits, most participants reported sustained increases in transformative/pivotal states of mind/attitudes often observed during dosing sessions in clinical trials (e.g., mystical, emotional breakthrough, insight-type), as well as increases in self-perceived altruism and prosocial behaviour.” (Raison et al., 2022)
In 2019, ‘Silvia Muttoni and her colleagues conducted clinical trials, and after analysing 130 patients- suffering from depression and anxiety- over seven studies, they observed that ayahuasca, psilocybin, and LSD consistently produced immediate and significant anti-depressant and anxiolytic effects that were endured for several months. Psychedelics appeared to be effective in significantly reducing symptoms of depression and anxiety and were well-tolerated.’ (S et al., 2019) In august 2022, Damien Prouzeau and his colleagues studied the efficacy of psilocybin in the treatment of depression. They found that ‘Psilocybin has a large, rapid, and persistent clinical effect in the treatment of resistant or end-of-life depression and tolerance is good, with mild side effects limited to a few hours after dosing.’ (Prouzeau et al., 2022) In spite of the 1970 ban on psychedelic drugs, it has proven to be extremely effective in current research with some scientists suggesting that it is even more effective than antidepressants such as SSRIs. “A double-blind trial published by Carhart-Harris and his colleagues showed that two doses of psilocybin benefited people with major depression about as much as a six-week course of the SSRI antidepressant escitalopram” (Eisenstein, 2022). ‘Recent interest into the use of psychedelic-assisted therapy using ayahuasca, psilocybin or lysergic acid diethylamide (LSD) may also be a promising alternative for patients unresponsive to traditional treatments.’ (S et al., 2019) Overall, these findings show that ‘psilocybin administered in the context of supportive psychotherapy produce large, rapid, and sustained antidepressant effects among patients with major depressive disorder.’ (Davis et al., 2020)
There are, however, some disadvantages to utilizing psychedelic substances in treatment. Despite the fact that the majority of patients benefited after undergoing psychedelic-assisted therapy, a minority of patients experienced unfavorable effects if any at all, including nausea, a sudden increase in anxiety, blood pressure, and heart rate. ‘In the research study conducted by Silvia Muttoni, as discussed above, the most common adverse effects were transient anxiety, short-lived headaches, nausea and mild increases in heart rate and blood pressure.’ (S et al., 2019) However, these concerns can be resolved by conducting more clinically controlled research with a bigger sample size. Another downside of psychedelic therapy is that psychedelic experiences are more abstract in nature and are experienced differently by each individual, making it harder to determine the causal relationship between psychedelic drugs and depression symptom reduction. However, many scientists have tried to identify the cause; one such proposal is that ‘classic psychedelics acutely reduce activity and internal functional connectivity within the DMN, potentially reducing abstracted and self-referential rumination, a hallmark of depressotypic thinking. Additionally, decreased functional connectivity between the amygdala and ventromedial prefrontal cortex have been found post-psilocybin consumption. Taken together, these preliminary findings have been speculated to suggest that psilocybin may encourage increased emotional sensitivity and acceptance post-treatment’ (Johansen et al., 2022)
As stated previously, psychedelic medications have disadvantages, as do most treatments for MDD. However, given the encouraging results of using psychadelic assisted treatment in numerous clinical investigations, it is puzzling why psychadelic is still not used as part of MDD treatment processes in most countries. The stunning outcomes of such clinical trials are compelling enough to inspire other psychological researchers to perform more experiments to see whether this treatment is efficacious and safe enough to employ for individuals suffering from clinical depression.
Works Cited
Eisenstein, M. (2022). The psychedelic escape from depression. Nature, 609(7929), S87–S89. https://doi.org/10.1038/d41586-022-02872-9
Artin, H., Zisook, S., & Ramanathan, D. (2021). How do serotonergic psychedelics treat depression: The potential role of neuroplasticity. World Journal of Psychiatry, 11(6), 201–214. https://doi.org/10.5498/wjp.v11.i6.201
S, M., M, A., & C, J. (2019, November 1). Classical Psychedelics for the Treatment of Depression and Anxiety: A Systematic Review. Journal of Affective Disorders. https://pubmed.ncbi.nlm.nih.gov/31382100/
Prouzeau, D., Conejero, I., Voyvodic, P. L., Becamel, C., Abbar, M., & Lopez-Castroman, J. (2022). Psilocybin Efficacy and Mechanisms of Action in Major Depressive Disorder: a Review. Current Psychiatry Reports. https://doi.org/10.1007/s11920-022-01361-0
Raison, Charles, et al. "Effects of Naturalistic Psychedelic Use on Depression, Anxiety, and Well-Being: Associations With Patterns of Use, Reported Harms, and Transformative Mental States." Frontiers in Psychiatry, 2022, https://doi.org/10.3389/fpsyt.2022.831092.
Johansen, L., Liknaitzky, P., Nedeljkovic, M., Mastin-Purcell, L., & Murray, G. (2022). The psychological processes of classic psychedelics in the treatment of depression: a systematic review protocol. Systematic Reviews, 11(1). https://doi.org/10.1186/s13643-022-01930-7
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