This list was made in cooperation, and co-published, with Blossom.
The number of publications in the psychedelic research field has been steadily growing in the year 2020. While the majority of the outside world was dealing with a global pandemic, research on psychedelics continued its march forward. This list of top 10 articles will present some of the most impactful publications of the year.
The papers have been selected from the 2.000 (PubMed) to 39.000 (Google Scholar) articles published last year on psychedelics. Most of the publications listed below have already been featured in Blossom’s monthly round-ups of psychedelic research and the MIND’s ASC Study Monitor. Although the top-cited paper on the list has ‘only’ 27 citations as of early 2021, we expect many of these to become future classics.
Read our list of Top 10 Articles of 2020 to learn about a ground-breaking trial with psilocybin for major depressive disorder, long-term outcomes of MDMA-assisted psychotherapy for PTSD, how psychedelics work in the brain, and how to produce psychedelics at a larger scale.
Psilocybin has been studied, in combination with psychotherapy, for its potential in helping those with treatment-resistant depression (TRD, e.g., Carhart-Harris et al., 2017). Patients suffering from major depressive disorder (with moderate to severe scores on the Hamilton Depression Rating Scale) qualify as treatment-resistant when showing no improvements after two treatments with antidepressants of different classes, each lasting at least 6 weeks.
Those suffering from TRD represent 10 to 30% of patients suffering from depression (Al-Harbi, 2012). Davis and colleagues’ study provided evidence that psilocybin-assisted therapy may be a suitable option for the treatment of major depressive disorder.
This study used two sessions with a high dose of psilocybin and found a clinically significant response (>50% lower score on depression score) in 71% of patients four weeks later. Although the study was open-label and done with no more than 24 participants, it offers hope that psychedelic-assisted therapy will become a viable option to improve symptoms of depression in patients who do not respond to conventional psychiatric treatments.
Jerome and colleagues conducted a long-term follow-up study on the results across six phase 2 trials led by Multidisciplinary Association for Psychedelic Studies (MAPS). The trials were all double-blind, open-label, and included a long-term follow-up. At the end of the treatment, 56% of the patients did not meet the criteria for PTSD, and at the long-term follow-up (at least 12 months later), 67%. More than half of the study participants indicated that they experienced considerable benefits that persisted or increased over time.
These results contributed another piece of evidence to the hypothesis that psychedelics and entactogens may become a feasible treatment option for those suffering from mental health disorders. An analysis of the costs of this medical approach by Marseille and colleagues modeled that MDMA-assisted psychotherapy for PTSD can add quality-adjusted life years (QALY) at lower costs than conventional treatments.
Psychedelic-assisted therapy sessions are usually done with individual patients. In their pilot study (n=18), Anderson and colleagues showed that psilocybin can be useful in treating demoralization and that it also has the potential to be used in a group setting. Although more data is needed, offering the preparation and follow-up sessions (or in the future, even the session with the administration of psychedelics) in a group setting showcased a potential to improve the therapy’s costs side even further.
Psychedelics may offer a novel alternative in the treatment of PTSD, depression (TRD, MDD), addiction, and several other mental disorders. Schindler and colleagues expanded the reach of psychedelics with the first double-blind, placebo-controlled study (n=10) and the use of psilocybin for migraines.
The study used a medium dose of psilocybin and found a significant reduction in migraine frequency up to two weeks later. The exact mechanisms behind this phenomenon are still not fully understood, but a recent review of psychedelics for cluster headaches identified functional connectivity changes as a possible route.
The acute psychedelic experience is often defined as an altered state of consciousness. In the treatment of mental disorders, psychedelic substances can achieve long-term beneficial effects in the patients, but the acute experience may not always be desired. The possibility of eliminating the acute psychedelic effects while preserving long-term outcomes was explored by Cameron et al. In their study, the administration of tabernanthalog, a non-psychoactive analog to ibogaine, led to similar structural neural plasticity (something seen with other psychedelics too, e.g., Ly et al., 2018 or Barrett et al., 2020), reduction in addiction-like behavior, and antidepressant-like effects in mice. This phenomenon still needs to be explored in humans, but it suggested that analogs to psychedelic substances could offer therapeutic value without the acute effect and lower to no toxicity.
Mason and colleagues undertook a closer inspection of brain activity during a psychedelic experience. This study investigated changes in the levels of the neurotransmitter glutamate in different brain areas. The authors concluded that psychedelics might increase neuroplasticity via glutamatergic activity. In the double-blind, placebo-controlled brain imaging study, lower hippocampal glutamate levels were associated with a positively experienced ego dissolution.
Several other studies in 2020 investigated neuronal changes at the peak of a psychedelic experience. Alamia and colleagues provided further evidence of changed cortical waves under DMT, while Varley and colleagues found that psilocybin and LSD increase fractal dimensions in brain areas related to spatial and temporal domains.
Salvia Divinorum is a sage species found in Mexico with longstanding traditions in religious and healing practices. Salvinorin A is a hallucinogen and a k-opioid receptor agonist found in Salvia Divinorum. In the study by Doss et al., participants were given Salvinorin A, and their brain activity was assessed with fMRI. Interestingly, the data showed a decrease in static functional connectivity of the default mode network (DMN), which is an effect comparable to the action of classic psychedelics. Although the sample size was relatively small (n=12) and the participants were already experienced with psychedelics (on average more than 250 previous experiences!), the results suggested that the k-opioid receptor signaling pathways may elicit effects comparable to those triggered by classic psychedelics, which target serotonin receptors. Müller and colleagues have already observed this phenomenon and found similar neuronal changes induced by MDMA.
The mechanisms of action of psychedelics can be studied at various levels. The studies above mostly looked at changes in and between networks of brain areas. This study, published by Roth and colleagues, investigated the molecular properties of the 5-HT2A serotonin receptor.
This article, just like the one on tabernanthalog, contributes to our understanding of how to separate the brain-plasticity (therapeutic) effects from the acute effects of psychedelics. It also aimed at explaining how psychedelics bind to the serotonin receptor and subsequently trigger its conformational change.
To get a better overview of the recent research on 5HT2A receptors, visit our list of recommended readings in the Psychedelic Compendium.
One large area of research on psychedelics in the year 2020 was the manufacturing of psychedelic substances. In order to make psychedelics available for therapy in patients, the production (and administration) of psychedelics needs to be realized at an industrial scale and at lower costs. Kargbo and colleagues (primarily at Usona Institute) published a method to produce psilocybin on a large scale (1kg, or >33.000 high dosages).
This study is just one among many to investigate novel ways of producing psychedelics. Milne and colleagues were able to use brewer’s yeast to produce not only psilocybin but also norbaeocystin, baeocystin, and aeruginascin. And co-authors on the paper of this section, Cozzi and Daley also synthesized DMT for clinical trials.
To dive deeper into the psilocybin production in microorganisms, read the interview that Nick Milne gave in the MIND Blog.
The studies above provided a glimpse into the future of psychedelics research. They showcased ways in which psychedelics can be beneficial, how they work in the brain, and even how they can be produced on a large scale. Looking back at the research and publications between the years 2007 and 2019, Reiff and colleagues reviewed the current state of insights on psychedelics for psychedelic-assisted psychotherapy.
They identified and discussed studies with MDMA for PTSD and the psilocybin trials for depression and cancer-related anxiety, and that studies like the ones above have offered more evidence for psychedelics as therapeutics. Another review by Goldberg and colleagues comes to a similar conclusion, finding significant positive effects on various mental diseases symptoms in their across 24 unique samples with almost 550 subjects total.
New to the topic of psychedelic research? Read the Recommended Readings for Psychedelic Novices
Images by Paweł Czerwiński on Unsplash.