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Are Psychedelics the New Mental Health Revolution?

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Are Psychedelics the New Mental Health Revolution? 

Author: Mashiyat Ahmed

Editor: Riyaa Sri Ramanathan



The psychoactive class of drugs known as psychedelics or serotonergic hallucinogens occupies a unique place in the cultural history of the psychological sciences. In recent memory, psychedelics have been associated with the vibrant and politically charged counterculture of the 1960s; they have also been known to garner substantial scientific skepticism due to the historical lack of research dedicated to their function and influence. The active ingredient in psychedelics, known as psilocybin, is a key aspect of many Indigenous cultural rituals and spiritualistic practices, and historically, the adoption of psychedelic science to Western empirical methods has failed to acknowledge their rich cultural significance to Indigenous communities or the perspectives of holistic Indigenous medicine (Nichols, 2016). However, in the last 30 years, scientific research has seen an explosion in both interest and success in understanding psychedelics, and in particular, their therapeutic significance in psychiatric disorders such as treatment-resistant depression (TRD), substance abuse, and generalized anxiety (Nichols, 2016).  


Psychedelics (with the principal ingredient being psilocybin) are psychoactive drugs that operate on the central nervous system producing significant and sustained alterations in perception, cognition, attitude, behavior, and states of consciousness (Nichols, 2016). The neurobiological or neurochemical activity supporting psychedelic mechanisms is poorly understood, but scientists are slowly uncovering how certain global brain networks and neuroplasticity (i.e., structural and functional malleability of the brain in response to new stimuli) may explain how psychedelics work. The rebirth of public and scientific interest in psychedelics is conveniently situated in the timeline of psychological research because the world is currently experiencing a resurgence of psychological distress/disorders. Globalization, social media, urbanicity, technology, and more, have all fundamentally shifted how we interact with ourselves and others. With this shift comes new mental health challenges that require novel and innovative solutions. Psychedelics have shown significant success in controlled experiments relating to psychiatric disorders. There is also vehement anecdotal evidence as to the spiritually stimulative effects of psychedelics and how they positively influence the personal and philosophical lives of individuals. For these reasons, and more, psychedelics have been cited as the new “mental health revolution.” This article will explore the recent clinical studies involving psychedelics, their proposed mechanism(s) of function, and the ethical considerations relevant to their administration.  

1.0 An Overview of Major Clinical Findings 


The clinical relevance of psychedelics comes in the form of sustained symptom relief and treatment potential for many psychiatric illnesses. According to the World Health Organization (WHO, 2022), one in eight individuals lives with a mental health disorder. Common disorders include depression, anxiety, substance abuse, and more. Controlled studies involving psychedelics have shown promising results in symptom relief and severity alleviation for treatment-resistant depression, existential crises for terminally ill patients, and substance abuse disorders.  

1.1 Depression and Emotional Disorders 


According to a study by Griffiths (2016), 80% of participants in a clinical study investigating one-time psychedelic administration (n = 51) and depression relief in terminally ill cancer patients responded positively to the drug, citing that “psilocybin produced large and significant decreases in clinician-rated and self-rated measures of depression, anxiety, or mood disturbances, and increases in measures of quality of life, life meaning, death acceptance, and optimism.” Multiple other studies have corroborated these findings, suggesting that safe and controlled use of psychedelics can have significant antidepressant effects without the debilitating side effects of classical antidepressants, which include compromised oral and sexual health, headaches, and emotional numbness (Griffiths et al, 2016).  

1.2 Substance Abuse Disorders (Alcohol and Nicotine) 


Addiction is another challenging problem that psychedelics have shown incredible promise in. Substance abuse disorders are often multifactorial, meaning straightforward pharmacological interventions are ineffective in providing long-term abstinence. Both clinical and naturalistic studies continue to illustrate the potential anti-addiction effects of lysergic acid diethylamide (LSD). In a clinical study surveying 343 respondents (n = 343) with 7+ years of alcohol consumption, 83% reported dramatic reductions in alcohol craving, in which they no longer met the Alcohol Use Disorder (AUD) criteria, after an LSD experience (Garcia-Romeu, 2019). As a testament to the prolonged effects of psychedelics, respondents also observed improvements in personal relationships, exercise, diet, mindset, and work or career performance (Garcia-Romeu, 2019). Similar results have been obtained in the context of nicotine addiction. Johnson (2017) conducted a naturalistic study on smoking addiction and psychedelics, in which he and his research team hypothesized that greater spiritual significance or personal meaning of the psychedelic experiences would produce more successful anti-addiction effects. Indeed, 88.5% of participants in the study who attributed great personal meaning, rediscovering of values, and a renewed orientation about life to their psychedelic experience reported successful quitting attempts (Johnson, 2017). In addition to these remarkable results, “such [anti-addiction] effects are likely to lead to a substantially higher probability of persisting behavior change (i.e., abstinence when smoking cessation is the a priori goal of the psychedelic experience, and when combined with effective behavior therapy” (Johnson, 2017). Despite all these promising results, it is still unclear why or how psychedelics work the way they do, both naturally and in the context of mental disorders. Like most questions in science, the answer is likely to be complex and unexpected.  

2.0 Neurobiological Basis of Psychedelics 


Scientists have taken a key interest in investigating the neurobiological mechanisms of psychedelics. Two primary theories emerge in order to potentially explain the incredibly varied and dramatic effects of psychedelics: serotonin receptor signaling and neuroplasticity. Common psychedelics (i.e., psilocybin, magic mushrooms, mescaline, and LSD) bind to the serotonin 5-HT2A receptor site due to them having a similar chemical structure to serotonin itself. Affective disorders (e.g., depression and generalized anxiety) correspond with more 2A receptors in the prefrontal cortex, while antidepressant treatments typically aim to reduce receptor density (Banks, 2021). Neuropsychology has yet to discover the precise ways in which 2A receptors and other neurobiological chemicals interact to produce psychedelic action and their long-term behavioral and cognitive effects, however, possible theories strongly suggest that psychedelics decrease serotonin receptor density in key brain regions (e.g., prefrontal cortex) and encourage the release of extracellular glutamate (excitatory neurotransmitter) that promotes neuroplastic changes in the brain. Scientists suspect that neuroplasticity and connectivity following psychedelic use are central to the drugs’ cognitive and behavioral manifestations!

2.1 Neuroplasticity and Connectivity 


Neuroplasticity is the phenomenal capacity of the brain’s physical and functional pathways to reorient (i.e., change) themselves in response to stimuli, and in the case of psychedelics, novel experiences (Banks, 2021). Connectivity, broadly speaking, refers to the patterns of anatomical links in the brain between different regions (Lang, 2012). In mood disorders, the amygdala, involved in emotional reactivity, is consistently overstimulated, and its communication with other key brain areas for emotional processing (e.g., frontal cortex) is similarly disrupted in the form of overactivation. Studies have shown that “psychedelics alter connectivity between the amygdala and key brain regions during emotional stimulus processing, effects that may contribute to altered behavioral and neural responses to these stimuli characteristic of mood disorders” (Banks, 2021). Reducing pathological connectivity could be a possible explanation for the therapeutic success of psychedelics in treating depression, anxiety, and other disorders involving emotional disturbances.  


Have you ever heard of the default mode network (DMN)? The default mode network is a collection of structures in the brain associated with self-referential mental activity and wakeful resting (e.g., daydreaming and mental idleness) in healthy individuals. Functional Magnetic Resonance Imaging (fMRI) studies suggest that “psychedelics acutely reduce connectivity within the default mode network” but the exact “mechanism of changes and whether these changes persist post acutely remain areas of active inquiry” (Banks, 2021).  


Psychedelics are also thought to enhance or promote morphological (physical form) aspects of structural plasticity. Structural plasticity is fascinating because it directly links physical changes in the brain to diverse behavioral/cognitive changes. A type of structural change, the growth of neurites (i.e., arms of neurons that receive electrochemical information; dendrites) in excitatory synaptic activity are said to be the building blocks of neuroplasticity. According to Banks (2021), “studies of cultured cortical neurons indicate that psychedelics act on 5-HT2A receptors to increase dendritic spine diameter.” The central idea is that the perceptual, cognitive, and affective (emotional) changes that follow and persist after psychedelic use is a result of alterations in neuroplasticity. 


2.2 Behavioral Plasticity 


Behavioral plasticity broadly means behavioral flexibility or the ability to adapt quickly to new mental and behavioral modes, particularly in regard to learning and memory (Lang, 2012). A key aspect of the psychedelic experience is the ability to absorb and easily adapt to new ways of thinking, new philosophical perspectives, and new behavioral tendencies. For example, “psychedelics enhance both the acquisition and extinction of fear conditioning in rodents”, meaning that the drug's potential behavioral power lies in its ability to “support the learning of new behaviors, while also facilitating the extinction of older learned behaviors” (Banks, 2021). The majority of psychedelic users, both recreational and clinical, report having experienced ego death. Ego death or ego dissolution is when individuals experience an unselfing; in psychoanalysis, it refers to the disappearance of an individual’s sense of self or the removal of one’s perception of one’s self as fundamentally different from the social and physical world. The conscious and unconscious openness to behavioral plasticity that psychedelics allow could be a possible explanation for ego death.  




In summary, the last few decades of neuroscience and psychology have experienced a revival in scientific and public interest in psychedelics, a remarkable and mysterious class of hallucinogenic drugs that, through neuroplasticity and psychological experiential novelty, have had positive effects on treating mental health disorders. Psychedelics also spur important conversations about ethics, such as the need to enhance informed consent or re-evaluate religious and cultural sensitivities. How do standard consent procedures need to be changed in order to modify the unique nature of psychedelics? What language should be used to talk about psychedelics in the mainstream with different audiences? How should scientists and medical professionals use the benefits of psychedelics while respecting cultural and religious boundaries? There is a substantial amount of research to be done in psychedelic science, and education about their potential therapeutic potential should be a part of mainstream discourse. Historically, psychedelics have been a politically sensitive topic, but research, education, and a collective mentality toward openness can establish psychedelics as the new mental health revolution.  



Banks, M. I., Zahid, Z., Jones, N. T., Sultan, Z. W., & Wenthur, C. J. (2021). Catalysts for change: the cellular neurobiology of psychedelics. Molecular biology of the cell, 32(12), 1135–1144. 


Garcia-Romeu, A., Davis, A. K., Erowid, F., Erowid, E., Griffiths, R. R., & Johnson, M. W. (2019). Cessation and reduction in alcohol consumption and misuse after psychedelic use. Journal of psychopharmacology (Oxford, England), 33(9), 1088–1101. 


Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., & Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of psychopharmacology (Oxford, England), 30(12), 1181–1197. 


Johnson, M. W., Garcia-Romeu, A., Johnson, P. S., & Griffiths, R. R. (2017). An online survey of tobacco smoking cessation associated with naturalistic psychedelic use. Journal of psychopharmacology (Oxford, England), 31(7), 841–850. 


Lang, E. W., Tomé, A. M., Keck, I. R., Górriz-Sáez, J. M., & Puntonet, C. G. (2012). Brain connectivity analysis: a short survey. Computational intelligence and neuroscience, 2012, 412512. 


Nichols D. E. (2016). Psychedelics. Pharmacological reviews, 68(2), 264–355. 


World Health Organization. (2022, June 8). Mental disorders. 

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