The profoundly hierarchical body and mind (soul) dichotomy is one of the most persistent models in Western philosophy and history (Taylor, 1989). It posits that human beings are composed of two distinct, unequal parts: a material body and an immaterial soul, with the soul holding a superior position. In the context of mental health, depression has been seen as a biological phenomenon, arising from the imbalance of four bodily ‘humors’; or attributed to satanic influence and moral sins, and therefore perceived as pertaining to mind or soul (Foucault, 2013, Jackson 1986).
This understanding of depression may be seen today as persistent, long-term, cultural (mis)understandings, such as stigma (negative labels) and self-stigma (internalized negative label). These frequently discredited social beliefs might interfere with the contemporary understanding of (treatment-resistant) depression as a multifactorial disease and the development and adoption of effective treatments for depression.
Treatment-resistant) depression (TRD), defined as a form of major depressive disorder (MDD) that fails to improve after at least two adequate trials of different antidepressant medications or psychotherapy treatment options, has deep biological/ neurological roots.
One of the most common predictors or risk factors of depression, including TRD, is biological sex (O’Connor et al 2024). Women are considerably more likely to be affected by (major) depression (Bromet et al. 2011, Moderie et al. 2022), even in cross-cultural perspectives, though the proportion of affected women and men might differ substantially (Bromet et al. 2011). Sex might affect onset, development and treatment outcomes of (treatment-resistant) depression (Da Silva et al., 2025) and treatment response (Ponton et al., 2022, Freeman et al., 2017). Differences in prevalence are driven by biological factors (da Silva et al., 2025), psychosocial factors, and hormonal imbalances, especially fluctuations in hormones such as estrogen and progesterone (Huang et al., 2008, da Silva et al., 2025) .
Historically, whereas depression in women is believed to correlate strongly with hormonal fluctuations, men’s depression is often stigmatized as weakness of the mind, or as moral or religious weakness. Esposito et al. (2024) argue that the stigma of depression as ‘weakness’ in general, and ‘weakness of will’ in particular, are some of the most common misconceptions about depression, especially among men themselves (e.g., Yokoya et al., 2018). Moreover, the concept of depression as ‘laziness’ when an affected person is seen as not wanting to exert control over their mood and participate in the society (Esposito et al., 2024) echoes religious notions of depression as moral and religious failure. This is reflected in some of the world’s largest religions: or example, in Roman Catholicism ‘sloth’ is considered one of the seven deadly sins (Lyman, 1989).
The belief that depression is a consequence of the weakness of the mind or will presents a barrier in seeking treatment for depression among men in particular (Shi et al., 2021, Gough and Novikova (2020)). Gender differences are the most consistent finding in studies which examined socio-demographic factors in relation to health behavior (Mahalik et al., 2007). There are also other factors at play. Shi et al., (2021) and Gough and Novikova (2020) argue that men experience a number of depressive symptoms, different than women.
Women tend to experience somatic depressive symptoms, related to the body, such as irritability and sleep disturbance. In contrast, men are more likely to express symptoms of the mind and engage in avoidant, numbing, and escapist behavior, conducive to substance abuse, aggression, violence, and suicide (Shi et al., 2021, Gough and Novikova (2020)). As male symptoms of depression are often not captured in the diagnostic manuals and tools, men are consequently less likely to engage in seeking help for their symptoms and healthcare professionals are less likely to promptly and correctly diagnose them (Gough and Novikova (2020).
The gender paradox
This may explain the so-called ‘the gender paradox in suicide’, a phenomenon which has been observed in many (Western) societies that while women more often consider committing suicide, the actual suicide rates among the men are higher (in Mallon et al. 2016, Shi et al., 2021; Gough and Novikova 2020). It could be argued that whereas women’s depression is perceived as a (somatic) distress of the body, men’s persistent depression is at least partly expressed as culturally desirable personality traits and behaviors, corresponding to hegemonic masculinity ideal (e.g., self-reliance, avoiding vulnerability, engagement in risky behaviors, emotional control, toughness, independence and action orientation).
However, it is precisely this adherence to normative masculinity that is a risk factor in depression in men, also because it increases self-stigma (Kilian et al., 2020, Levant et al., 2013). Men are therefore in a ‘contradiction of male depression’; if they comply with hegemonic masculinity, they might be at risk of depression. However, if they do not adhere to the dominant cultural model of masculinity, then their risk of depression is lower but many of the traits of hegemonic masculinity, for example emotional flatness, low social engagement and tendency to risky behaviors, may also appear as the symptoms of depression and overlooked by both the affected men themselves and healthcare professionals. This might explain observations of Yokoya (2018) who argue that many Japanese do not recognize depression in others, irrespective of gender (though they might recognize that the person is in distress).They argue (Yokoya et al. 2018), that the Japanese appreciate some of these facets, e.g., emotional restraint, especially in public settings.
Distress in men might also not be readily recognized as it might be seen as a part of their maladaptive coping strategies (Gough and Novikova (2020) in relation to intersectionality, which takes into account that all people are positioned at the intersection of multiple, often mutually reinforcing and constitutive, intertwined social categories (in Salk et al., 2017). The stigma associated with gender might therefore be further compounded by the stigma of gender identity, social class, ethnicity and race, etc. For example, depression in a particular man might be missed because it is seen as a symptom of alcohol abuse,. Some men seek help for their depression only after they have experienced somatic symptoms of depression, such as panic attacks (in Gough and Novikova, 2020), suggesting that depressive symptoms are taken seriously only when they are not experienced ‘only in the mind’.
Psychedelic treatments and depression in men
A promising treatment for TRD is psychedelic-assisted therapy (PAT), a therapeutic approach that combines the use of psychedelics and psychotherapy. Psychedelics are potent mind-altering compounds that induce profound changes in a range of cognitive processes that affect perception, mood, and sense of self. The empirical evidence suggest that psychedelics are a promising treatment for TRD (in Norman 2025). Though they are physiologically relatively safe and not addictive (Nichols, 2016, Schlag et al. 2022), they are not without risks (Holze et al., 2024). Though patients might undergo negative experiences during psychedelic administration, these might be beneficial after being processed and integrated over a period of time (Gaughan et al., 2025, Nygart et al. 2022).
Psychedelic treatments could be particularly suitable for men because they challenge stigmas that many gender, racial and ethnic, and sexual minorities are still subjected to. This is due to the fact that psychedelic treatments, among others, increase neuroplasticity and relax internalized rigid beliefs, such as homophobia, which has been evidenced as an important driver of anxiety, depression and suicidality in sexual minority populations (Hanshaw et al. 2024). During psychedelic-assisted therapy, patients may reduce self-focus, rumination, hypervigilance, self-monitoring and negative self-beliefs, including those imposed by the dominant society, expand scope of attention, increase range of emotions and promote hyper-associative thinking (Carlisle et al. 2023, Hanshaw et al. 2024). PATs therefore promote greater self-acceptance and resilience (Hanshaw et al. 2024).
In this way, those undergoing psychedelic-assisted therapy might address traumas related to stigmatized identities and internalized chronic shame resulting from marginalization (Lancelotta et al. 2025, Carlslie et al. 2023). For example, Mehtani et al. (2024) argue that reducing shame of HIV and abuse among the older, gay men with HIV infection also result in greater treatment adherence. As shame is one of the contributing factors to risk-taking, the researchers concluded that PATs might also contribute to more productive, healthier behaviors (Mehtani et al., 2024).
Whereas accumulating evidence (Carlisle et al. 2023, Hanshaw et al. 2024, Lancelotta et al. 2025, Mehtani et al., 2024) points out that psychedelics help in reducing stigma in minority populations, and consequently, lead to better mental health outcomes, it is important to point out that psychedelics reduce self-stigma, rather than negative labels, given to minority populations by e.g., dominant society. During PAT, the individuals’ consciousness expands so that they can gain new insights and perceive novel perspectives and connections in order to question previous, perhaps inflexible beliefs. Because of this characteristic, psychedelics might not only be particularly suited for gender, sexual and other minorities, but also for those cisgendered men who are at risk of depression because they believe that they have failed to comply with normative models of masculinity. For example, by questioning how healthy and realistic many of the traits of hegemonic masculinity are and what would be a healthier and more productive model, the men might experience reduced stress and shame, resulting in better mental health outcomes.
Stigma of legality and legitimacy
While psychedelics are a promising treatment for TRD, especially among stigmatized communities, the psychedelic treatments themselves are also stigmatized. A major source of stigma concerns the legal status of psychedelic drugs. Psychedelics for recreational use are still illegal and might also be associated with counter-culture and drug use of the 1960s. In addition to the issue of legality but psychedelics also introduce novel stigma, the stigma of legitimacy. Because of the question of legitimate use, psychedelic treatments might be less acceptable to a number of those affected. For example, Handy (2021) observed that the scientists working on clinical trials on ±3,4-methylenedioxymethamphetamine (MDMA) never referred to the substance with its street name, Ecstasy, because patients perceived them as two different compounds. While MDMA was believed to be ‘pure’, Ecstasy was perceived by the researchers as ‘unsafe’ because in addition to MDMA, it might have contained a number of potentially dangerous adulterants. In contrast, Handy (2021) contends that the main difference was the ‘safety’ of MDMA, codified via careful documentation of research practices and drug effects.
A growing number of studies focusing on the psychedelic use in naturalistic, real-life settings (Lancelotta et al., 2025, Aday et al., 2024, Nygart al., 2022, Perkins et al., 2022, Raison et al. 2022) confirmed the positive therapeutic effects on users, though more research among non self-selected populations is needed for conclusive findings. This is important because patients may themselves might prefer ‘street’, naturalistic use if it eradicates or lessens stigma. For example, Viña (2024) argues that those users who perceived utilizing mental health services as stigmatizing were less likely to use them and preferred self-medicating in a situation where psychedelics were more widely available and accepted.
Conclusion
Even though the contemporary understanding of depression, including treatment-resistant depression, is that it is a multifactorial disease, those affected might still be stigmatized, also due to persistent Western cultural models of understanding of the relationship between body and mind or soul. In this model, depression in women is related to imbalance of hormones and is expressed as somatic symptoms, and in men as the weakness of the mind, expressed through behavior, some of which correspond to desirable traits of normative masculinity. One of the unique characteristics of psychedelic treatments is that they are conductive to questioning long held, perhaps inflexible beliefs and thus reduce self-stigma in minority populations, and in those cisgendered men who adhere to normative models of masculinity. Psychedelic treatments also introduce new stigma, related to their legal and legitimacy aspects. Greater understanding of stigma in different populations, related to mental health and depression in general, and treatment-resistant depression in particular, is necessary for proper integrative care.
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About the Author
Judy Lytle, Executive Director of Evidence Development Study Solutions
Judy Lytle serves as the Executive Director of Evidence Development Study Solutions for UBC. Dr. Lytle joined UBC in 2023, bringing more than 15 years of experience in life science and healthcare strategy development, implementation, and execution. With a background in medical affairs and real-world evidence, she brings together differentiated study design and evidence generation solutions for value demonstration. She also has oversight of epidemiology, patient and physician services, scientific/clinical strategy, and medical writing teams.
Dr. Lytle holds a PhD in Neuroscience from Georgetown University as well as a Master of Biotechnology Enterprise & Entrepreneurship (MBEE) from Johns Hopkins University. A fellow of the American Association for the Advancement of Science (AAAS), and certified Project Management Professional (PMP), her approach is systematic and grounded in science.
Barbara Potrata, Manager Clinical Outcome Assessment (COA)
Barbara Potrata is a skilled consultant with more than 15 years experience in the qualitative/ mixed methods, patient- centred outcomes (PCO/ COA) and patient engagement research in both the commercial sector and academia. Highly experienced in all stages of research cycle design and implementation, including in the education or training/ mentoring of employees/ researchers.
