Psychedelics-assisted therapy — a literature review
I am currently studying to earn a Master of Science in Applied Psychology. Within the framework of the first module “Scientific Work in Psychology”, I concluded my first ever literature research. Here is an edit in a little lesser academic language.
For this review, seven scientific and non-scientific papers have been examined, which are listed and briefly summarised below.
Introduction.
The interest in psychedelics has been exploding. Scientists worldwide are exploring different psychedelic substances, their effects on the brain, and how they might help improve health. Psychedelics can alter perception and affect numerous cognitive processes (Nichols, 2016).
The idea to heal trauma and enhance cognitive functioning is not new. But lately, psychedelic retreat centres are growing in popularity, and even mainstream media has been picking up the trend of psychedelic-assisted therapy. Hypotheses describe the physiological changes underlying altered states of consciousness, how LSD and related compounds could be used to benefit humankind to enhance cognitive functioning.
The research area in general.
Cutting-edge research has demonstrated the value of psychedelics. Phase 3 clinical trials are on the horizon. People are being treated with psychedelics in several clinical trials, and the possibility of turning these compounds into licensed medicines looks well within reach.
Franz X Vollenweider and Katrin H. Preller address the renewed interest in psychedelics. State-of-the-art studies have recently begun to close essential knowledge gaps by elucidating the mechanisms of action of psychedelics concerning their effects on receptor subsystems, systems-level brain activity and connectivity, and cognitive and emotional processing (Vollenweider & Preller, 2020).
A new understanding has been developed on the relevance of psychedelics as deep curative medications. Research is finding that these compounds reduce the centerline controlling part of the specific human mechanism, called the ego, or in modern era scientific terminology, the default mode network.
Psychedelics can remove or weaken the defensive mechanisms of the ego and allow the individual to dive deeper into his or her consciousness.
Data from several clinical trials approved by the proper regulatory agencies suggest safety and potentially profound efficacy for therapeutic use. Typical methodological operationalization for data collection has been among other things: the assessment of study participants for eligibility the randomization with psychedelic drugs and placebos experiments to be carried out in controlled clinical environments the presence of a trained therapist the assessment of data by a centralized pool of blinded, independent diagnostic assessors.
Context.
Nearly every culture throughout history has used chemicals that alter consciousness for spiritual exploration. In the 20th century, these drugs caught the attention of scientists. Psychedelics proved effective at treating intractable illnesses like depression and addiction. Furthermore, they became a tool for studying the mind. Soon after LSD escaped the labs, psychedelics have been associated with counterculture and declared as dangerous. (Pollan, 2018).
Over time, there has been a slow paradigm shift in regards to psychedelic-assisted psychotherapy and research is further conducted into possible first applications for disorders such as PTSD, Alzheimer's, anxiety disorders, and relief for the terminally ill.
Prominent theories build on the dissolution of the ego and the possible healing of root cause rather than treating symptoms with common antidepressants (Pollan, 2018). Studies go as far as suggesting that psychedelics “may influence the future of brain injury treatment in both the acute and chronic phases through a variety of mechanisms including modulation of neuroinflammation, neuroplasticity, hippocampal neurogenesis, and increases in brain complexity” (Khan et al., 2021, para. 6).
Future research will be asking questions regarding the long-term effects, the frequency, the dosage, personalization of the experience, area of application, and time intervals in between treatments. Science is only at the beginning of understanding how electrical signalling from some brain areas takes precedence over others and how the Default Mode Network (DMN) reigns on top of this hierarchy. Pollan (2018) writes about the role of the default mode network, as what we commonly call the self or ego.
The literature.
Book — How to Change Your Mind. By Michael Pollan.
Michael Pollan’s book has been a trailblazer in arguing the transformative experiences and positive impacts of psychedelic-assisted therapy. It is composed of six themed chapters, and “it is a very personal as well as public history “(Pollan, 2018, p.11). Author Michael Pollan first gives an overview of the recent rise of psychedelic research and then continues by looking into a) the history, b) the effects, and c) giving cultural and political context. He introduces critical personalities such as Roland Griffiths, Bob Jesse, Rick Doblin, Stephen Ross, Abram Hoffer, Leo Zeff, and Al Hubbard.
The New York Times wrote that “nothing in Pollan’s book argues for the recreational use or abuse of psychedelic drugs “but “that psychedelic-aided therapy, conducted properly conducted by professionals can be personally transformative “(Bissel, 2018, para. 5). Pollan (2018) talks in detail about his personal experiences and of what he calls “the dissolution of his ego “(p. 240). He leaves the reader with the hope for psychedelics to allow humans to reboot the brain and breakthrough thought and behaviour patterns that are limiting or anything but noble.
Book Chapter — Changing Our Minds: Psychedelic Sacraments and the New Psychotherapy. Chapter 7. By Don Lattin.
In chapter 7 of his book Changing Our Minds: Psychedelic Sacraments and the New Psychotherapy, Lattin provides insights about the consequences of an FDA approval of psychedelics and opposing critical players in the field.
Lattin (2017) examines the extent to which a federal policy in the US allows companies to capitalize on data exclusivity that is granted by the FDA for the first one “to make a drug into a medicine that has not been made into a medicine before” (p. 226).
As Rick Doblin, the founder of the Multidisciplinary Association for Psychedelic Studies (MAPS), who is focusing on the MDMA market, points out to Lattin: “MAPS could raise upwards of $30 million over the six years that it had a marketing monopoly “(Lattin, 2017, p.227).
Dave Nichols, president of the Heffter Research Institute, focuses on psilocybin and openly questions Rick Doblin’s methods, qualifications, and motivations (Lattin, 2017). Lattin concludes the chapter by publishing statements supposedly taken from Email exchanges between Doblin and Nichols, which draws attention to the tension around the commercialization of psychedelics.
Lifestyle media picked up the topic of psychedelics after Nature published the MDMA-assisted therapy for severe PTSD in May 2021.
Article — Psychedelic Medicine Is About To Blow Up. By Ruth Readers. Published by FastCompany.
In her article for FastCompany, Ruth Readers elaborates on the potentially significant impact of psychedelic-assisted therapy and its commercialization. Readers draw on a report by the journal Nature that published “the phase-III clinical trial results on MDMA-assisted psychotherapy as a treatment for PTSD, operated by the Multidisciplinary Association of Psychedelic Studies (MAPS) “(2021, para. 2).
Readers (2021) points out that while therapy can help with PTSD symptoms, the healing process can be accelerated when adding psychedelics, which is especially significant because of the high dropout rates of trauma patience of therapy.
The article refers to the clinical studies operated by the Multidisciplinary Association of Psychedelic Studies (MAPS) and an interview with Amy Emerson, CEO of MAPS. Readers are also referring to Yaron Conforti, CEO of Novamind, a network of psychiatry clinics and research sites specializing in psychedelic medicine, talking about scalability and commercial growth, based on the FDA’s anticipated approvals of MDMA and psilocybin.
The article is evidence of the commercial rise of the research topic.
Article — The Psychedelic revolution is coming. Psychiatry may never be the same. By Andrew Jacobs. Published by The New York Times.
Jacobs suggests in his article, that psychedelic drugs are on the threshold of commercialization for therapeutic use. He is referencing results published by Nature Medicine, being “the first Phase 3 clinical trial conducted with psychedelic-assisted therapy, found that MDMA paired with counselling brought marked relief to patients with severe post-traumatic stress disorder “(2021, para. 2).
Jacobs (2021) mentions the importance of rigorous oversights due to suggestions of psychedelics prompting psychosis when underlying mental disorders exist.
The article educates by giving an overview of the topic, revealing the steep rise of start-ups, the increase of psychedelic research divisions in universities, and treatment centres, and the interest of investors. With the potential FDA approval on the horizon, numbers are only going up.
Jacob addresses some concerns of industry professionals, which regard the dangers of profit-focused motivations behind the commercialization of psychedelics. A growing body of literature recognizes an increase in clinical studies into the use of psychedelic therapeutics for treatment.
Scientific Review — Psychedelics for Brain Injury. By Khan et al. Published by Frontiers in Neurology.
In their review Psychedelics for Brain Injury, the authors aim to “summarize the current state of the science’s relevance to neurorehabilitation and may act as a resource for those seeking to understand the precedence for these ongoing clinical trials” in their review (Khan et al., 2021, para. 1). Studies were selected for their relevance in implying neuroprotective potential in preference to their therapeutic properties, as proposed by Khan et al. (2021).
Khan et al. (2021) state that they conducted a “literature search of articles relevant to psychedelic therapeutics for brain injury using PubMed”, with a clear focus on a variety of psychedelic drugs “with regards to its effects on neuroinflammation and reperfusion injury” (para. 7).
The authors conclude that the effects of psychedelics on neuroplasticity have not been tested with subjects suffering from a stroke (Khan et al., 2021). However, “recent reports demonstrate that psychedelics promote both structural and functional neuroplasticity in non-injured brains” (Khan et al., 2021, para. 20).
A meta-analysis — A meta-analysis of placebo-controlled trials of psychedelic-assisted therapy. By Luoma et al. Published by PubMed.
This meta-analysis provides support for their efficacy across four mental health conditions. To the authors’ knowledge, their study was “the first meta-analysis of modern placebo-controlled clinical trials of psychedelic-assisted therapy” (Luoma et al., 2020, p.2).
The Meta-analysis compared nine identified randomized and placebo-controlled clinical trials that have been published since 1994, exploring the effect sizes of psilocybin, LSD, ayahuasca, versus MDMA, which according to the examiners, has “a differing biological and phenomenological effect” (Luoma et al., 2020, p.3).
The methodological approach taken in this analysis was based on a mixed methodology based on literature searches, data extraction, risk of bias assessment, computation, and moderator analyses.
All studies reviewed had a) similar study designs, b) patience received comparable psychotherapeutic support, and c) the context of psychotherapeutic support was established.
The summary concludes that “despite these limitations, large effect sizes are rare in psychiatry and psychology, and our findings suggest that psychedelic-assisted therapy presents a promising new direction in mental health treatment” (Luoma et al., 2020, p.10).
Scientific Research Paper — MDMA-assisted therapy for severe PTSD: A randomized, double-blind, placebo-controlled phase 3 study. By Mitchell et al. Published by Nature Medicine.
“This study was designed to assess “the efficacy and safety of MDMA-assisted therapy in individuals with severe PTSD” and “report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial” (Mitchell et al., 2021, para. 1).
This paper examines MDMA given in conjunction with therapy. PTSD is a common condition with immense social costs, and treatment outcomes are associated with several related conditions. The authors are raising questions as to the potential benefit of MDMA-assisted therapy.
However, head-to-head comparison with antidepressants, such as SSRI (Selective Serotonin Reuptake Inhibitor), currently the most common medications used for treating the depression and anxiety associated with PTSD, make sense to explore in future research.
Methods extraction
The FDA granted the MDMA-assisted therapy an FDA Breakthrough Therapy designation, and “the protocol and statistical analysis plan (SAP) were developed in conjunction with the FDA” (Mitchell et al., 2021, para. 5).
Three hundred forty-five participants were assessed for eligibility, of which 131 were enrolled, 91 confirmed for randomization, and 46 were randomized to MDMA, with 44 to placebo. They have been recruited over a time period of 19 months (Mitchell et al., 2021).
The study participants were given three doses of MDMA or placebo in a controlled clinical environment and in the presence of a trained therapy team. Primary and secondary outcome measures (CAPS-5 and SDS, respectively) were assessed by a centralized pool of blinded, independent diagnostic assessors. (Mitchell et al., 2021, para.5)
Primary results
The primary study endpoint was 18 weeks after baseline. The authors highlight clinically significant improvement, loss of diagnosis, and remission (Mitchell et al., 2021).
This result is significant with “28 of 42 (67%) of the participants in the MDMA group no longer met the diagnostic criteria for PTSD, compared with 12 of 37 (32%) of those in the placebo group after three sessions” (Mitchell et al., 2021, para 14). The current findings support the relevance of the benefits of MDMA-assisted therapy. This study lays the groundwork for future research into psychedelic-assisted therapy.
Potential improvement
The generalisability of these results is subject to certain limitations when looking at the statistical characteristics. For instance, further experiments could be using a broader range of demographics. Unfortunately, 76.7% of the total participants have been of white background. The authors acknowledge that in the conclusions.
Additionally, due to the COVID-19 pandemic, the number of participants was smaller than initially planned (Mitchell et al., 2021). Future research questions could include investigations also in regards to the differences in male versus female participants.
Discussions.
The main aim was to create a very high level, holistic overview of the research area: a) the current state of psychedelic research, b) a manageable understanding of history, and c) touching on exploring future potential.
Future research and studies will fill the gaps in understanding physiological changes in neurons and changes in brain network connectivity. Biases in demographics need to be addressed. More research is needed on possible side effects. Clinical studies have been conducted with relatively small numbers of people.
Conclusion.
To conclude, based on the current evidence, psychedelic-assisted therapy can increase the positive characteristics of humanity, such as compassion, empathy, openness, and creativity. Therefore, psychedelics open questions around Artificial Intelligence versus Human Intelligence, allowing speculations regarding testing medication on artificial neural networks and the expansion of human cognition.
I am personally now interested in further research into cognition, ethically use of psychedelics, and explorations in context with technologies such as AI and nanobots.
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Bissell, T. (4. June 2018). Michael Pollan drops acid — and comes back from his trip convinced. The New York Times. https://www.nytimes.com/2018/06/04/books/review/michael-pollan-how-to-change-your-mind.html
Jacobs, A. (9. May 2021). The Psychedelic revolution is coming. Psychiatry may never be the same. The New York Times. https://www.nytimes.com/2021/05/09/health/psychedelics-mdma-psilocybin-molly-mental-health.html
Khan, S. M., Carter, G. T., Aggarwal, S. K., & Holland J. (2021). Psychedelics for brain injury: A mini-review. Frontiers in Neurology, 12(685085), 1260. https://doi.org/10.3389/fneur.2021.685085
Lattin, D. (2017). Psychedelic medicine. In K. Goffman & L. Sperling (Eds.), Changing our minds: Psychedelic sacraments and the new psychotherapy (pp. 223–251). Synergetic Press. https://www.scribd.com/read/354011144/Changing-Our-Minds-Psychedelic-Sacraments-and-the-New-Psychotherapy
Luoma, J. B., Chwyl, C., Bathje, G.J., Davis, A.K., Lancelotta, R. (12. June 2020). A meta-analysis of placebo-controlled trials of psychedelic-assisted therapy. PubMed. https://doi:10.1080/02791072.2020.1769878
Mitchell, J.M., Bogenschutz, M., Lilienstein, Harrison, C., Kleiman, S., Parker-Guilbert, K., Ot’alora, M., Garas, W., Paleos, C., Gorman, I., Nicholas, C., Mithoefer, M., Carlin, S., Poulter, B., Mihoefer, A., Quevedo, S., Wells, G., Klaire, S., Van der Kolk, B., … Doblin, R. (2021). MDMA-assisted therapy for severe PTSD: A randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine, 27(1025–1033). https://doi.org/10.1038/s41591-021-01336-3
Nichols, D. E. (1. April 2016). Psychedelics. Pharmacological Reviews. https://doi.org/10.1124/pr.115.011478
Pollan, M. (2018). How to change your mind: What the new science of psychedelics teaches us about consciousness, dying, addiction, depression, and transcendence. Penguin Random House.
Readers, R. (11. May 2021). Psychedelic medicine is about to blow up. FastCompany. https://www.fastcompany.com/90634925/psychedelic-medicine-mdma-ptsd-study
Schenberg, E. E. (2018). Psychedelic-assisted psychotherapy: A paradigm shift in psychiatric research and development. Frontiers in Pharmacology, 9(733). https://doi.org/10.3389/fphar.2018.00733
Vollenweider, F. X., & Preller, K. H. (2020). Psychedelic drugs: neurobiology and potential for the treatment of psychiatric disorders. Nature Reviews Neuroscience, 21(11), 611–624. https://www.nature.com/articles/s41583-020-0367-2
