Psychedelics vs. Traditional Treatments —How Do They Stack Up for Mental Health Disorders? – Part 1
The treatment landscape for mental health conditions has evolved significantly over the past decades, with selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, and cognitive-behavioral therapy (CBT) being the primary therapeutic interventions. While these conventional approaches have demonstrated considerable efficacy and improved countless lives, clinical data indicates that a substantial portion of patients exhibit treatment resistance or experience relapse over time.
This therapeutic gap has prompted researchers to investigate novel approaches, leading to renewed scientific interest in psychedelic-assisted therapy (PAT). The potential therapeutic applications of classical psychedelics such as psilocybin and LSD, as well as entactogens like MDMA, have garnered attention in contemporary psychiatric research. As clinical trials advance and mechanistic studies deepen our understanding of these compounds, the field moves forward in balancing hope with caution.
This review examines the distinct mechanisms, therapeutic potentials, and limitations of both conventional and psychedelic-assisted treatments, providing a comprehensive analysis of their roles in modern psychiatric care.
Psychedelic-Assisted Therapy vs traditional treatments – In a nutshell
Traditional Treatments | Psychedelic-Assisted Therapy (PAT) | |
---|---|---|
Primary Approaches | SSRIs, benzodiazepines, cognitive-behavioral therapy (CBT) | Psilocybin, LSD, MDMA, often combined with psychological support |
Mechanism of Action | Targets neurotransmitter systems (e.g., serotonin for SSRIs, GABA for benzodiazepines) | Primarily acts on serotonin 5-HT2A receptors; impacts the default mode network (DMN) |
Duration of Treatment | Long-term, often months to years | Short-term, typically involves 2-3 sessions over a few months |
Therapeutic Effects | Effective for symptom management, but may not address underlying trauma | Facilitates neuroplasticity, may lead to psychological breakthroughs and sustained improvements |
Side Effects | Physical and emotional side effects (e.g., nausea, insomnia); potential dependency risks for benzodiazepines | Low toxicity, but may cause psychological distress; requires controlled settings |
Limitations | Treatment resistance, relapse risk, and long wait times for psychotherapy | Potential for adverse effects in vulnerable individuals, lack of long-term data |
Implementation | Widely available in healthcare systems, often requires ongoing adherence | Requires structured setting and trained facilitators; typically includes preparation and integration phases |
Mechanisms of Action: Different Pathways, Different Potentials
Traditional psychiatric interventions and emerging psychedelic therapies operate through distinct neurobiological pathways. Conventional treatments primarily target specific neurotransmitter systems: SSRIs treat depression by blocking serotonin reuptake in the brain, allowing more serotonin to remain active in neural synapses (IQWiG, 2024). Benzodiazepines reduce anxiety by enhancing GABA activity, which decreases overall brain cell excitability (Benzodiazepine Information Coalition, 2022). These pharmacological mechanisms typically require sustained administration to maintain therapeutic effects (Donald et al., 2021). CBT complements these approaches by promoting neuroplasticity through systematic modification of thought patterns and behaviors, leading to structural and functional changes in regions associated with emotional regulation (Nakao et al., 2021).
Psychedelic compounds exert their effects primarily through serotonin 5-HT2A receptor agonism (Vargas et al., 2023). This mechanism induces rapid alterations in neural connectivity and information processing (Smausz et al., 2022). Of particular interest is their impact on the default mode network (DMN), where overactivity correlates with various psychiatric conditions (Chou et al., 2023). Research indicates that psychedelics may temporarily disrupt DMN connectivity, potentially facilitating the formation of novel neural pathways. This neuroplastic effect, combined with the compounds’ ability to enhance emotional processing, provides a neurobiological basis for the acute and sustained therapeutic effects observed in clinical trials (Gattuso et al., 2022).
The distinct mechanisms of action between conventional treatments and psychedelic interventions present both advantages and limitations. Traditional approaches effectively target symptom management but may overlook underlying psychological trauma (IQWiG, 2024). PAT shows potential for deep neurobiological restructuring, yet the intensity of these interventions can be difficult and result in lasting negative effects for some individuals (Evans et al., 2023).
Treatment Protocols: Contrasting Continuous Care with Rapid-Acting Interventions
Building on the neurobiological foundations, treatment duration and efficacy present notable distinctions between conventional and psychedelic-assisted approaches. While traditional pharmacotherapy has proven effective for many individuals, it typically requires extended periods of administration, with patients maintaining antidepressant regimens for months to years (Hu et al., 2024). This prolonged treatment course often accompanies various side effects (NHS, 2021b). Additionally, resource limitations in mental health services frequently result in extended wait times for traditional psychotherapeutic interventions like CBT (PricewaterhouseCoopers, n.d.).
Emerging clinical evidence suggests that PAT may achieve therapeutic outcomes through significantly fewer interventions. Research with psilocybin in major depressive disorder demonstrates that a single 25mg dose, combined with psychological support, can produce substantial and sustained reductions in depressive symptoms (Raison et al., 2023). Similarly, MDMA-assisted therapy for PTSD has shown remarkable efficacy, with over 50% of participants no longer meeting diagnostic criteria after two sessions (van der Kolk et al., 2024). The treatment typically involves 2-3 guided sessions integrated with psychotherapy over several months (Mitchell et al., 2023).
The intensity of psychedelic experiences may pose challenges for some individuals, potentially inducing anxiety or distress, particularly when compared to conventional treatments like SSRIs or talk therapy which typically have more predictable response patterns. While the shorter treatment duration offers an attractive alternative to traditional long-term therapeutic approaches, the long-term implications of PAT require more thorough investigation.
Emotional Breakthroughs and Psychotherapeutic Integration
The therapeutic mechanisms of conventional and psychedelic treatments further diverge in their capacity to facilitate psychological breakthroughs. Psychedelic compounds can induce altered states of consciousness that enable patients to access and process repressed emotional content and trauma (Roseman et al., 2019). These experiences, when conducted in controlled therapeutic environments, often represent critical junctures in the treatment process.
Conventional therapeutic approaches primarily emphasize symptom management and gradual cognitive and behavioral modification (Stein et al., 2022). While traditional psychotherapy facilitates emotional understanding, it rarely produces the acute psychological insights characteristic of psychedelic experiences. MDMA-assisted therapy demonstrates this distinction, with patients reporting to process traumatic memories with reduced emotional activation (Morgan, 2020), potentially achieving therapeutic outcomes that conventional methods find challenging to replicate.
PAT functions not as a standalone treatment but as a catalyst within a comprehensive therapeutic framework (Brennan & Belser, 2022). The process involves three key phases: preparation, the psychedelic experience, and integration therapy (Mitchell et al., 2023). This structured approach, combined with careful consideration of patients’ psychosocial resources and support systems, is essential for optimizing therapeutic outcomes and minimizing risks.
Side Effects and Safety Concerns
Treatment modalities demonstrate distinct safety profiles and contraindications. SSRIs commonly induce physiological and emotional side effects, including nausea, insomnia, and sexual dysfunction (NHS, 2021). Long-term benzodiazepine use presents risks of dependency and cognitive impairment (NHS, 2024). While CBT exhibits minimal adverse effects, accessibility limitations and duration requirements pose practical constraints (NHS, 2022).
Psychedelic compounds demonstrate favorable physiological tolerability, with substances like psilocybin showing low toxicity and minimal addictive potential (National Institute on Drug Abuse, 2024). However, psychological risks emerge particularly in non-controlled settings (Barber et al., 2023). Adverse psychological reactions require careful therapeutic management to maintain safety parameters (Brooks, 2018).
Research indicates specific risk factors in PAT, including potential psychotic episodes in vulnerable individuals (Simonsson et al., 2023). Recent data suggests 16% of participants experience decreased psychological well-being four weeks post-treatment, with elevated rates among those with personality disorder diagnoses (Marrocu et al., 2024). Personality traits, particularly neuroticism, further influence treatment outcomes in both conventional and psychedelic interventions. While high neuroticism correlates with increased acute adverse effects in PAT, these individuals often report enhanced long-term outcomes (Mason et al., 2020). Similarly, conventional treatments consistently demonstrate reduced efficacy in individuals with high neuroticism scores (Mulder, 2011).
Implementation of PAT requires comprehensive screening protocols to identify contraindications and optimize patient selection. Clinical settings provide essential safeguards, resulting in predominantly positive therapeutic outcomes with minimal adverse effects (Williams et al., 2021). Further research is needed to better understand how individual differences, particularly personality traits, influence treatment responses. This knowledge would enable more precise patient selection and personalized treatment approaches, ultimately enhancing safety and therapeutic efficacy.
Durability of Therapeutic Effects: Comparing Long-Term Outcomes Across Treatment Modalities
Potential long-term therapeutic efficacy represents a significant advantage of PAT. Clinical trials demonstrate sustained symptom reduction across multiple conditions: psilocybin for depression (Gukasyan et al., 2022), MDMA for PTSD (van der Kolk et al., 2024), and ketamine for treatment-resistant depression (Murrough et al., 2013). These outcomes contrast with conventional treatments’ requirement for continuous medication administration without addressing underlying pathological mechanisms.
The potential for achieving substantial therapeutic change within limited sessions warrants methodological consideration. While preliminary data indicates promising results, psychedelic research in psychopharmacology is still in its beginning. Current limitations include a lack of longitudinal and follow-up studies, resulting in an incomplete understanding of delayed adverse effects and individual response variations.
Where Do We Go from Here?
Current evidence necessitates a balanced evaluation of PAT. While contraindications and methodological challenges persist, clinical trial data demonstrates significant therapeutic potential, particularly for treatment-resistant conditions including PTSD, depression, and substance use disorders (Belouin & Henningfield, 2018). These novel interventions may address limitations inherent in conventional treatment approaches.
The evolution of psychiatric medicine suggests an integrative framework incorporating both established and emerging therapeutic modalities. Psychedelic compounds, when administered within structured clinical settings, represent a promising pharmacological class that may complement existing treatment paradigms (Yaden et al., 2024). This integration has the potential to advance therapeutic mechanisms beyond symptom management toward sustained psychological transformation, directly addressing underlying trauma and promoting long-term healing.
The successful implementation of psychedelic-assisted therapy (PAT) requires a multi-faceted approach encompassing patient screening, preparation protocols, and integrated aftercare support. Critical research priorities include understanding neurobiological mechanisms, identifying reliable biomarkers for treatment response, and examining interactions with concurrent therapies. While current evidence supports PAT’s potential, limitations in longitudinal data and study population diversity constrain its broader clinical application. Ko et al. (2022) highlight the need for expanded research across diverse demographic groups to establish standardized safety protocols and treatment guidelines. Future studies should focus on systematic outcome assessment, monitoring of adverse effects, and analysis of population-specific treatment responses to optimize clinical effectiveness and safety standards.
The emerging evidence base supporting PAT’s therapeutic potential, combined with increasing institutional support and methodological refinement, indicates a promising direction for psychiatric medicine. As research continues and treatment guidelines evolve, these interventions may significantly expand the therapeutic options available to clinicians and patients, potentially transforming the landscape of mental health treatment.
References
- Barber, G. S., & Dike, C. C. (2023). Ethical and practical considerations for the use of psychedelics in psychiatry. Psychiatric Services, 74(8), 838–846. https://doi.org/10.1176/appi.ps.20220525
- Belouin, S. J. & Henningfield, J. E. (2018). Psychedelics: Where we are now, why we got here, what we must do. Neuropharmacology, 142, 7-19. https://doi.org/10.1016/j.neuropharm.2018.02.018
- Benzodiazepine Information Coalition. (2022, July 27). Mechanism of action – Benzodiazepine Information Coalition. https://www.benzoinfo.com/mechanism-of-action/
- Brennan, W. & Belser, A. B. (2022). Models of Psychedelic-Assisted Psychotherapy: A Contemporary Assessment and an Introduction to EMBARK, a Transdiagnostic, Trans-Drug Model. Frontiers in Psychology, 13. https://doi.org/10.3389/fpsyg.2022.866018
- Brooks, M. (2018, July 20). Psilocybin “Bad trips” underscore need for research safeguards. Medscape. https://www.medscape.com/viewarticle/874136?form=fpf
- Chou, T., Deckersbach, T., Dougherty, D. D., & Hooley, J. M. (2023). The default mode network and rumination in individuals at risk for depression. Social Cognitive and Affective Neuroscience, 18(1). https://doi.org/10.1093/scan/nsad032
- Donald, M., Partanen, R., Sharman, L., Lynch, J., Dingle, G. A., Haslam, C., & van Driel, M. (2021). Long-term antidepressant use in general practice: a qualitative study of GP’s views on discontinuation. Br J Gen Pract., 71(708), e508-e516. https://doi.org/10.3399/BJGP.2020.0913
- Evans, J., Robinson, O. C., Ketzitzidou Argyri, E., Suseelan, S., Murphy-Beiner, A., McAlpine, R., Luke, D., Michelle, K., & Prideaux, E. (2023). Extended difficulties following the use of psychedelic drugs: A mixed methods study. PLOS ONE, 18(10). https://doi.org/10.1371/journal.pone.0293349
- Gattuso, J. J., Perkins, D., Ruffell, S., Lawrence, A. J., Hoyer, D., Jacobson, L. H., Timmermann, C., Castle, D., Rossell, S. L., Downey, L. A., Pagni, B. A., Galvao-Coelho, N. L., Nutt, D., & Sarris, J. (2023). Default Mode Network Modulation by Psychedelics: A Systematic Review. Int J. Neuropsychopharmacol., 26(3): 155-188. https://doi.org/10.1093/ijnp/pyac074
- Gukasyan, N., Davis, A. K., Barrett, F. S., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., & Griffiths, R. R. (2022). Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Journal of Psychopharmacology, 36(2). https://doi.org/10.1177/02698811211073759
- Hu, Y., Xue, H., Ni, X., Guo, Z., Fan, L., & Du, W. (2024). Association between duration of antidepressant treatment for major depressive disorder and relapse rate after discontinuation: A meta-analysis. Psychiatry Research, 337, 115926. https://doi.org/10.1016/j.psychres.2024.115926
- Institute for Quality and Efficiency in Health Care (IQWiG). (2024, April 15). Depression: Learn More – How effective are antidepressants? InformedHealth.org – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK361016/
- Ko, K., Knight, G., Rucker, J. J., & Cleare, A. J. (2022). Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic review. Frontiers in Psychiatry, 13. https://doi.org/10.3389/fpsyt.2022.917199
- Mason, N. L., Dolder, P. C., & Kuypers, K. P. (2020). Reported effects of psychedelic use on those with low well-being given various emotional states and social contexts. Drug Science Policy and Law, 6, 205032451990006. https://doi.org/10.1177/2050324519900068
- Mitchell, J. M., Ot’alora G., M., van der Kolk, B. et al. (2023). MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med, 29, 2473–2480. https://doi.org/10.1038/s41591-023-02565-4
- Morgan, L. (2020). MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD: what it is and what it isn’t. Annals of General Psychiatry, 19(33). https://doi.org/10.1186/s12991-020-00283-6
- Marrocu, A., Kettner, H., Weiss, B., Zeifman, R. J., Erritzoe, D., & Carhart-Harris, R. L. (2024). Psychiatric risks for worsened mental health after psychedelic use. Journal of Psychopharmacology, 38(3), 225–235. https://doi.org/10.1177/02698811241232548
- Mulder, R. T. (2011). The influence of personality on the treatment outcome of psychopathology. Word Psychiatry, 10(2), 115-116. PMID: 21633687
- Murrough, J. W., Perez, A. M., Pillemer, S., Stern, J., Parides, M. K., aan het Rot, M., Collins, K. A., Mathew, S. J., Charney, D. S., Iosifescu, D. V. (2013). Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biological Psychiatry, 74(4), 250-6. https://doi.org/10.1016/j.biopsych.2012.06.022
- Nakao, M., Shirotsuki, K., & Sugaya, N. (2021). Cognitive-behavioral therapy for management of mental health and stress-related disorders: Recent advances in techniques and technologies. Biopsychosocial Medicine, 15(1), 16. https://doi.org/10.1186/s13030-021-00219-w
- National Institute on Drug Abuse (2024, June 24). Psilocybin (Magic Mushrooms) | National Institute on Drug Abuse. https://nida.nih.gov/research-topics/psilocybin-magic-mushrooms
- NHS (2021, December 8). Side effects – Selective serotonin reuptake inhibitors (SSRIs). https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/ssri-antidepressants/side-effects/
- NHS (2022, November 10). Overview – Cognitive behavioural therapy (CBT). https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/talking-therapies-and-counselling/cognitive-behavioural-therapy-cbt/overview/
- NHS (2024, September 30). Side effects of diazepam. https://www.nhs.uk/medicines/diazepam/side-effects-of-diazepam/
- PricewaterhouseCoopers. (n.d.). “Waiting times” in mental healthcare. https://www.pwc.nl/en/insights-and-publications/services-and-industries/public-sector/social-determinants-of-health/waiting-times-in-mental-healthcare.html
- Simonsson, O., Goldberg, S. B., Chambers, R., Osika, W., Simonsson, C., & Hendricks, P. S. (2023). Psychedelic use and psychiatric risks. Psychopharmacology. https://doi.org/10.1007/s00213-023-06478-5
- Stein, D. J., Shoptaw, S. J., Vigo, D. V., Lund, C., Cuijpers, P., Bantjes, J., Sartorius, N., & Maj, M. (2022). Psychiatric diagnosis and treatment in the 21st century: paradigm shifts versus incremental integration. World Psychiatry, 21(3), 393-414. https://doi.org/10.1002/wps.20998
- Raison, C. L., Sanacora, G., Woolley, J., …, & Griffiths, R. R. (2023). Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial. JAMA, 330(9), 843-853. https://doi.org/10.1001/jama.2023.14530
- Roseman, L., Haijen, E., Idialu-Ikato, K., Kaelen, M., Watts, R., & Carhart-Harris, R. (2019). Emotional breakthrough and psychedelics: Validation of the Emotional Breakthrough Inventory. Journal of Psychopharmacology, 33(9). https://doi.org/10.1177/0269881119855974
- Smausz, R., Neill, J., & Gigg, J. (2022). Neural mechanisms underlying psilocybin’s therapeutic potential – the need for preclinical in vivo electrophysiology. Journal of Psychopharmacology, 36(7), 781-793. https://doi.org/10.1177/02698811221092508
- van der Kolk, B. A., Wang, J. B., Yehuda, R., Bedrosian, L., Coker, A. R., Harrison, C., Mithoefer, M., Yazar-Klosinki, B., Emerson, A., & Doblin, R. (2024). Effects of MDMA-assisted therapy for PTSD on self-experience. PLoS ONE 19(1). https://doi.org/10.1371/journal.pone.0295926
- Vargas, M. V., Dunlap, L. E., Dong, C., Carter, S. J., Tombari, R. J., Jami, S. A., Cameron, L. P., Patel, S. D., Hennessey, J. J., Saeger, H. N., Mccorvy, J. D., Gray, J. A., Tian, L., & Olson, D. E. (2023). Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors. Neuroscience, 379, 6633. https://doi.org/10.1126/science.adf0435
- Williams, M. L., Korevaar, D., Harvey, R., Fitzgerald, P. B., Liknaitzky, P., O’Carroll, S., Puspanathan, P., Ross, M., Strauss, N., & Bennett-Levy, J. (2021). Translating psychedelic therapies from clinical trials to community clinics: building bridges and addressing potential challenges ahead. Frontiers in Psychiatry, 12. https://doi.org/10.3389/fpsyt.2021.737738
- Yaden, D. B., Berghella, A. P., Hendricks, P. S., Yaden, M. E., Levine, M., Rohde, J. S., Nayak, S., Johnson, M. W., & Garcia-Romeu, A. (2024). IUPHAR-review: The integration of classic psychedelics into current substance use disorder treatment models. Pharmacological Research, 199, 106998. https://doi.org/10.1016/j.phrs.2023.106998