Trends in the Top-Cited Articles on Classic Psychedelics
This review paper (2021) investigates the trends in the top-cited papers on psychedelics and finds more RCT studies on psilocybin being done that get cited more often.
Authors
- Carhart-Harris, R. L.
- Griffiths, R. R.
- Lawrence, D. W.
Published
Abstract
This study was designed to identify trends in the top-cited classic psychedelic publications. The top 50 publications on classic psychedelics with the greatest total of number of citations and annual citation rate were identified and pooled. Unique articles (n = 77) were dichotomized by median year of publication (2010); the differential distribution of study characteristics between the “Recent Cohort” (n = 40) and “Older Cohort” (n = 37) were documented. The Recent Cohort had a greater annual citation rate (median 76.5, IQR 43.8 to 103.3) compared to the Older Cohort (median 8.8, IQR 4.2 to 17.2, p < .001). The Recent Cohort included a greater number of clinical studies (n = 27 [67.5%] vs. n = 10 [27.0%]) while the Older Cohort included more basic science and preclinical studies (n = 22 [59.5%] vs. n = 3 [7.5%], p < .001). Psilocybin was the predominant psychedelic studied in the Recent Cohort (n = 26 [40.6%] vs. n = 8 [17.4%]) while lysergic acid diethylamide (LSD) was predominantly studied in the Older Cohort (n = 26 [56.5%] vs. n = 19 [29.7%], p = .028). The Recent Cohort included more studies examining affective disorders (n = 16 [25.8%] vs. n = 1 [2.7%]) and substance use disorders (n = 6 [9.7%] vs. n = 1 [2.7%]), while the Older Cohort included a greater number of pharmacological outcomes (n = 26 [70.3%] vs. n = 11 [17.7%], p < .001). This study identified and documented trends in the top-cited classic psychedelic publications. The field is continuing to form a foundational understanding of the pharmacological effects of psychedelics and is now advancing with the identification of therapeutic uses within clinical populations.
Research Summary of 'Trends in the Top-Cited Articles on Classic Psychedelics'
Introduction
Lawrence and colleagues situate this study within a period of renewed academic and public interest in classic psychedelics, driven by accumulating evidence that these substances may have therapeutic utility for a range of mental health conditions. Earlier research has established that classic psychedelics are serotonergic 5-HT2A receptor agonists (examples include psilocybin, LSD, DMT, and mescaline) and that investigations have ranged from basic pharmacology to clinical trials. The authors argue that bibliometric analysis—measuring citation counts and citation rates—can map the maturity and influence of subareas within this growing field and help identify which topics and study types are most prominent. Accordingly, the study aimed to perform a systematic bibliometric analysis to identify and document trends among the most highly cited publications on classic psychedelics. The investigators sought to characterise the top-cited articles by publication year, study design, psychedelic compound studied, geographic origin, and principal outcomes, with a particular focus on differences between more recent and older influential papers.
Methods
The researchers constructed two complementary databases. PubMed was used to estimate the annual number of publications on classic psychedelics per year, and Thomson Reuters Web of Science (Clarivate Analytics) was used to extract citation metrics for bibliometric analyses. A classic psychedelic was defined for the search as a 5-HT2A receptor agonist and the search terms included psilocybin, psilocin, LSD, DMT (including 5‑MeO‑DMT), mescaline and natural products such as peyote and ayahuasca. The amphetamine-derived DOI was excluded despite its 5‑HT2A activity because of its classification within the amphetamine derivatives. The Web of Science search returned 8,074 records; the PubMed search identified 8,889 publications. Search dates for citation metrics and total publication counts were current as of October 22, 2020 and January 25, 2020, respectively. From the Web of Science results the authors generated citation reports and rank-ordered articles by two metrics separately: total number of citations (TNC) and annual citation rate (ACR, an estimate of citations per year). Titles and abstracts were screened in descending order of TNC and ACR until 50 articles were identified for each metric (50 for TNC, 50 for ACR). Full-text review of these 50+50 articles was then completed; none were excluded at that stage. For each included article the investigators extracted lead author, title, publication type, journal, year, country of lead author, total citations and annual citation rate. Inclusion criteria required peer-reviewed, English-language articles with accessible full texts; exclusions included non-peer-reviewed items, books, non-English manuscripts, duplicates and inaccessible full texts. Two reviewers applied a grounded theory approach to code study design and outcomes for each publication. Each reviewer independently coded manuscripts into meaningful units which were then grouped into categorical themes; consensus was reached after category development. To examine temporal trends among the highly cited works, the unique articles identified across both cohorts (n = 77) were pooled and dichotomised at the median year of publication (2010) into a Recent Cohort (published 2010 or later) and an Older Cohort (published before 2010). Descriptive statistics described variable distributions across cohorts and comparisons used the Wilcoxon Rank Sum test with continuity correction for continuous measures and Fisher-type tests (Fisher‑Freeman‑Halton) for categorical variables. A significance threshold of α < 0.05 was applied and analyses were conducted in R v3.5.2. The authors state that research ethics board approval was not required because the study analysed existing publications.
Results
Using the PubMed search strategy, 8,889 publications on classic psychedelics were identified. Annual publication rates peaked around 1965–1975, declined during a roughly 25‑year period that followed the UN Schedule 1 classification in 1967, and then rose from about 2010 onward, reaching an all‑time high in 2020. The Web of Science search produced a primary dataset of 8,074 items; from this the investigators screened 69 titles/abstracts to identify the top 50 by total citations and 61 titles/abstracts to identify the top 50 by annual citation rate. Following full‑text review, each cohort comprised 50 publications and no articles were excluded. There was overlap between the two ranked lists: 23 studies (23.0%) appeared in both the TNC and ACR cohorts, giving 77 unique articles for pooled analysis. The pooled set had a median year of publication of 2010 and was split into a Recent Cohort (n = 40; published 2010 or later) and an Older Cohort (n = 37; published before 2010). The extracted text does not clearly report the interquartile range for the Recent Cohort median year. The Recent Cohort had a significantly lower total number of citations (median 24.9, IQR 18.4 to 190.5) than the Older Cohort (median 209, IQR 166.0 to 377.0), p < .001. In contrast, the Recent Cohort had a significantly higher annual citation rate (median 76.5, IQR 43.8 to 103.3) than the Older Cohort (median 8.8, IQR 4.2 to 17.2), p < .001. Geographic origin differed between cohorts (p = .003): 78.4% (n = 29) of Older Cohort studies were led from the USA versus 37.5% (n = 15) of the Recent Cohort, while the Recent Cohort included more studies originating in the UK (32.5%, n = 13) and Brazil (12.5%, n = 5) compared with the Older Cohort (UK 2.7%, n = 1; Brazil 0%). Study design distributions also diverged (p < .001): the Recent Cohort contained more clinical studies (n = 27, 67.5%) and fewer preclinical studies (n = 3, 7.5%) compared with the Older Cohort (clinical n = 10, 27.0%; preclinical n = 22, 59.5%). The class of psychedelic investigated differed between the cohorts (p = .028). Psilocybin appeared most frequently in the Recent Cohort (n = 26, 40.6%) compared with the Older Cohort (n = 8, 17.4%), whereas LSD predominated in the Older Cohort (n = 26, 56.5%) versus the Recent Cohort (n = 19, 29.7%). Regarding outcomes, the Recent Cohort included more studies of therapeutic effects—affective disorders (n = 16, 25.8%) and substance use disorders (n = 6, 9.7%)—while the Older Cohort mainly comprised investigations of pharmacology and pharmacokinetics (n = 26, 70.3% in the Older Cohort vs. n = 11, 17.7% in the Recent Cohort).
Discussion
Lawrence and colleagues interpret these findings as evidence of a shift in highly cited psychedelic research from foundational preclinical pharmacology toward clinical investigations of therapeutic effects. More recent influential articles tend to have higher annual citation rates, are more often clinical in design, focus more frequently on psilocybin, and originate from a broader set of countries than older influential work, which was concentrated in the USA and dominated by LSD and basic pharmacological studies. The observed temporal pattern of publications—an early peak in the 1960s–1970s, stagnation during restrictive regulatory periods, and renewed growth from 2010 onwards—is consistent with prior bibliometric work and with changes in regulatory and institutional access that have facilitated contemporary research activity. The authors note that the progression from preclinical pharmacology to clinical trials mirrors a conventional drug‑development pathway in which mechanisms, receptor targets and pharmacokinetics are characterised prior to clinical safety and efficacy studies. They also highlight differences in funding context compared with typical pharmaceutical development: many classic psychedelics are off‑patent or naturally occurring (for example, LSD and psilocybin), and much research to date has relied on non‑industry funding, including philanthropic support. Several limitations are acknowledged. The bibliometric approach may miss influential recent papers that had not yet accrued enough citations by the search date, and the ACR metric can be affected by the month of publication for newer articles. The study did not perform formal risk‑of‑bias or quality assessments of included articles. Potential biases include omission of relevant papers that used different terminology, unadjusted self‑citation rates, exclusion of non‑English manuscripts which may under‑represent some countries, and the decision not to apply alternative citation indices (for example the g‑index or h‑index) or altmetrics. The authors suggest that future bibliometric work could address these limitations and that continued funding and coordinated efforts will be required to support larger clinical trials to define the therapeutic utility of classic psychedelics. Overall, the investigators conclude that the top‑cited literature reflects a field that established its pharmacological foundations in earlier decades and is now increasingly focused on clinical applications and therapeutic outcomes, with recent publications showing greater citation velocity and broader geographic representation.
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INTRODUCTION
The renewed interest in classic psychedelics and their role in the management of mental health conditions and mental well-being is evident. The increased academic and media attention has been galvanized by the expanding research documenting a largely therapeutic role for these substances in the treatment of a multitude of mental healthrelated conditions. Moreover, research access to these substances is improving as a result of broadening regulatory approval and institutional acceptance. Psychedelics are a broad class of psychoactive agents defined as substances that induce alterations in perception, mood, cognition, sense of self, and consciousness). Psychedelics can be classified by their "(1) pharmacodynamics and molecular structure; (2) the subjective perceptual, psychological, and/or spiritual effect; and (3) the derived source material". Classic psychedelics, also described as serotonergic psychedelics, are serotonin 5-HT 2A receptor agonists and are structurally related to either tryptamine or phenethylamine. Examples of classic psychedelics include psilocybin, lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), and mescaline. Classic psychedelics have shown to be of benefit in the management of major depressive disorder, anxiety, cancer-related existential crisis, and substance use disorders, particularly as an adjuvant to psychotherapy;. Commitments to advancing our understanding of psychedelics are reliant upon continued support and appraisal of research efforts. Systematically examining the state of the field of psychedelic research via a bibliometric analysis can help identify areas that are well established and those that are deficient. Measuring the number of citations that publications have accumulated can aid in assessing the cross-sectional landscape and maturity of subcategories within a particular field. Moreover, publication citation rates act as a proxy for the relative influence of articles within a particular field, with widely cited articles having greater recognition, broader reach and discussion, and greater respective importance. Previous biblometric analyses and annual citation rates have provided clarity on patterns, themes, and trends within a diversity of scientific fields. Therefore, the purpose of this study was to perform a systematic bibliometric analysis in order to identify and document trends in the publications investigating classic psychedelics with the highest citation rates.
SEARCH STRATEGIES AND DATABASE CONSTRUCTION
Two databases were used for the analyses: PubMed and Web of. PubMed was used to identify the total number of publications on classic psychedelics per year, while publications for the bibliometric citation analyses were retrieved Thomson Reuters Web of Science (Clarivate Analytics 2020). Web of Science is an online database that allows inquiry into comprehensive citation data for academic articles across disciplines and has been used frequently for surveying citation indices within an academic field (Clarivate Analytics 2020;. For this study, a classic psychedelic was defined as a serotonin 2A (5-HT2A) receptor agonist and studies discussing any of the following psychedelics were included: psilocybin, psilocin, LSD, mescaline, and DMT (including 5methoxy [5-MeO] DMT)). The psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) exhibits 5-HT2A agonism and has contributed greatly to preclinical studies on psychedelics,, however it was excluded from this search strategy based on its previous recognition within the amphetamine-derivate class. Studies were also included if they discussed the natural product in which a classic psychedelic is found (i.e., peyote and Ayahuasca). The following search strategy of article titles and keywords was applied to Web of Science in order to construct a comprehensive database of published works investigating classic psychedelics: "classic* psychedelic*" OR "psychedelic*" OR "hallucinogen*" OR "psilocybin" OR "psilocin" OR "magic mushroom*" OR "lysergic acid diethylamide" OR "LSD" OR "dimethyltryptamine" OR "DMT" OR "5-MeO-DMT" OR "Ayahuasca" OR "mescaline" OR "peyote." To increase the search specificity for classic psychedelics, the PubMed search strategy, which was solely used to calculate annual citation rates for visual display, excluded the terms hallucinogen, LSD, and DMT, of which the latter terms are frequently used acronyms in other fields. The PubMed search strategy included a search of both titles and MeSH terms of all published articles. The search strategies for the citation metrics and the total number of publications per year were current as of October 22, 2020 and January 25, 2020, respectively. A citation report of all results from the Web of Science search strategy (n = 8074) was completed via the Web of Science "Create Citation Report" function, which provides citation metrics for all identified articles (Clarivate Analytics 2020). The total number of citations for an article reflects the total number of citations within the Web of Science Core Collection, which includes prescreened publications of high quality only. The citation report additionally provides an estimate of the average citation per year for each article identified in the search strategy (Clarivate Analytics 2020). The primary database (n = 8074) was then rank ordered and sorted by descending order with respect to both: (1) total number of citations and (2) annual citation rate (see Figure). The title and abstracts of the publications within each rank ordered database were reviewed consecutively in descending order and the inclusion/exclusion (see below) criteria applied. This procedure was discontinued after n = 50 articles, determined a priori, within each database were identified. Full manuscript review of these publications was then conducted resulting in the two final study cohorts: (1) greatest total number of citations (TNC) cohort (n = 50) and (2) greatest annual citation rate (ACR) cohort (n = 50). The following data were then extracted for each article: lead author, title, type of publication (e.g., peerreviewed article, book, website), journal of publication, year of publication, reported country of the lead author (country of origin), total number of citations, and annual citation rate. Publications were included if they investigated or discussed classic psychedelics, as defined above, were peer-reviewed, and the full-manuscript was accessible. Publications were excluded if they were non peerreviewed, books, non-English language, duplicates, or if the full manuscript was not accessible. All dates of publication and study designs, including primary research articles and reviews, were included in this study.
QUALITATIVE ANALYSES
Two reviewers subsequently conducted a grounded theory approach to extract data on the study design and study outcome(s) for each publication in both cohorts. Each reviewer independently reviewed all full manuscripts and coded the study design and study outcome(s) into meaningful units (MU), from which categorical themes were created for analysis, if required. Consensus was achieved after category development for each MU.
ANALYSIS BY YEAR OF PUBLICATION
In order to evaluate trends in publications on the topcited classic psychedelics by year of publication, all unique articles identified within both the TNC and ACR cohorts (n = 77) were pooled and dichotomized by the median year of publication (2010; see Figure). Thus, two cohorts were created: (1) the Recent Cohort, defined as articles published within and after 2010 (n = 40), and (2) the Older Cohort, defined as articles published prior to 2010 (n = 37). Descriptive statistics were used to describe the distribution of the collected variables among the two cohorts. A Wilcoxon Rank Sum test with continuity correction and Fisher test (Fisher-Freeman-Halton test) were used to compare the distribution of included variables between the two cohorts. A significance level of α < 0.05 was used for all tests and all analyses were conducted using R software v 3.5.2. Research ethics board approval was not required as the analyses were solely on existing publications.
RESULTS
A total of 8,889 publications on classic psychedelics were identified based on the PubMed search strategy. Annual publication rates were initially highest around 1965 to 1975 followed by an approximate 25-year period of low research activity, coinciding the classification of psychedelics under Schedule 1 by the United Nations (UN) Convention on Drugs in 1967 (see Figure). An increasing rate in annual publication was observed from 2010 to 2020, resulting in a all-time high annual publication rate in 2020. The bibliometric search strategies resulted in a primary database (n = 8074) that was rank ordered by descending TNC and ACR, respectively (see Figure). A total of 69 and 61 consecutive titles and abstracts were screened in order to identify the 50 publications with the greatest TNC and ACR, respectively. The 50 articles within each cohort then underwent full manuscript review, of which zero articles were subsequently excluded resulting in the two final cohorts: the TNC cohort and the ACR cohort (see Tablesandfor included articles within both cohorts, respectively).
TRENDS BY YEAR OF PUBLICATION
Twenty-three studies (23.0%) were included within both TNC and ACR cohorts resulting in a total of 77 unique studies with a median year of publication of 2010. A total of 40 studies were published within or after 2010 ("Recent Cohort") while 37 studies were published prior to 2010 ("Older Cohort"). The median year of publication for the Recent Cohort was 2016 (interquartile rangein the Older Cohort. The Recent Cohort had a significantly lower total number of citations (median 24.9, IQR 18.4 to 190.5) compared to the Older Cohort (median 209, IQR 166.0 to 377.0, p < .001) but a significantly higher annual citation rate (median 76.5, IQR 43.8 to 103.3) compared to the Older Cohort (median 8.8, IQR 4.2 to 17.2, p < .001; see Table). There was a significant difference in the distribution of country of origin between the Recent and Older Cohorts (p = .003; see Table). In the Older Cohort, 78.4% (n = 29) of the studies were conducted in the United States of America (USA) compared to 37.5% (n = 15) of the studies in the Recent Cohort. One (2.7%) and zero (0.0%) studies in the Older Cohort were conducted in the United Kingdom (UK) and Brazil compared to 32.5% (n = 13) and 12.5% (n = 5), respectively, in the Recent Cohort.
STUDY DESIGN, PSYCHEDELICS STUDIED, AND STUDY OUTCOMES
A significant difference in the study design was observed between the Recent and Older Cohorts (p < .001; see Table). The Recent Cohort included a greater number of clinical studies (n = 27, 67.5%) and fewer preclinical studies (n = 3, 7.5%) compared to the Older Cohort (n = 10, 27.0% and n = 22, 59.5%, respectively). The distribution of the type of classic psychedelics studied also differed between the two cohorts (p = .028). Psilocybin was the most frequently included psychedelic within the Recent Cohort (n = 26, 40.6% vs. n = 8, 17.4% in the Older Cohort) while LSD was the most frequently included psychedelic within the Older Cohort (n = 26, 56.5% vs. n = 19, 29.7% in the Recent Cohort). A significant difference was observed in the distribution of the study outcomes between the Recent Cohort and Older Cohort (p < .001). The Recent Cohort included a greater number of studies investigating the therapeutic effect of classic psychedelics, predominantly affective disorders, anxiety, and/or depression (n = 16, 25.8%) and substance use disorders (n = 6, 9.7%) compared to the Older Cohort (n = 1, 2.7% and n = 1, 2.7%; respectively). The Older Cohort included predominantly studies investigating the pharmacology and pharmacokinetics of classic psychedelics.7% in the Recent Cohort). Moreover, the Recent Cohort included a greater number of studies using
DISCUSSION
This study identified publications within the field of classic psychedelic research with the greatest total and annual publication rates. Among the publications with highest citation indices, key differences were observed between those published more recently compared to older studies. The Recent Cohort was comprised of studies with a higher annual citation rate and included predominantly clinical studies investigating the therapeutic effects of psychedelics in affective and substance use disorders. Conversely, the Older Cohort was predominantly comprised of preclinical studies investigating the pharmacology and pharmacokinetics of classic psychedelics, largely in animal and in vitro models. Moreover, the distribution of the type(s) of psychedelic studied significantly differed between the two cohorts, with psilocybin most frequently studied in the Recent Cohort while LSD was most frequently studied in the Older Cohort. The trends in annual publication rates are consistent with a similar investigation by Rucker and colleagues who reported annual publication rates (as a proportion of total PubMed publication) up until 2016. The field of psychedelic research, as indicated by the number of publications, was prolific leading up to, and shortly following, the classification of psychedelics under Schedule 1 by the UN Convention on Drugs in 1967. The prohibitive period following the Schedule 1 classification and corresponding national legislative action resulted in academic stagnation through the 1980s and 1990s.observed an emerging increase in publication rates from 2010 to 2016, however, the current study confirms the trend toward renewed academic productivity with increasing annual publication rates observed from 2010 through 2020. The Recent Cohort consists of publications from a broader range of countries and supports the sentiment that the field of classic psychedelic research is expanding. A broadening research base and productivity has facilitated progress in the field of classic psychedelic research. Jurisdictional differences in regulatory restrictions limiting access to psychedelics for academic use significantly impacts the geographic distribution of this research. The analysis involving comparisons between countries therefore mainly reflects the size of the countries allowed to conduct research on this topic. Study findings suggest that classic psychedelic research is advancing, with an increasing focus on the clinical use, and global research centers are increasingly productive, as evident by the highest annual citation rates represented by newer studies from a broader range of countries. The Older Cohort included more preclinical studies, predominantly within animal and in vitro models,and studies examining pharmacological effects of classic psychedelics. Conversely, the Recent Cohort had a greater number of clinical studies examining psychiatric outcomes). This trend is consistent with other fields of study and follows the process of pharmaceutical development. The pharmacology, including molecular structural analysis, mechanism of action (i.e., receptor site targeting), and pharmacokinetics, is predominantly established prior to clinical safety and efficacy studies. It should be noted, however, that differential citations rates of clinical versus preclinical studies have been documented, whereby clinical studies are cited more frequently than basic science studies. This trend might similarly influence the identified manuscripts and psychedelics included within this study. However, the field of classic psychedelic research differs from the development of most pharmaceuticals, whereby the resource intensive studies on pharmaceuticals are conducted by industry during a period patented market exclusivity that follows if a given compound is deemed safe and effective. The patents for LSD and psilocybin have expired and some of the most studied classic psychedelics (psilocybin and DMT) are naturally occurring, therefore, most research has relied on largely nonindustry funded research support, frequently of a philanthropic nature. The observed progression toward clinical studies within the field of classic psychedelics is notable. However, large clinical trials are resource intensive, which are exacerbated by additional logistical barriers imposed by the strict regulatory statutes placed on these substances. Ongoing efforts will be required to establish research funding for the larger trials needed to advance our understanding of the clinical utility of classic psychedelics. Similar to other citation analyses studies, this study was unable to detect potential highly influential novel studies that failed to meet the threshold of number of total citations and annual citation rate). Furthermore, highly cited studies that met citation thresholds after the search date in this study were not included. Additionally, the month of publication relative to the timing of the search could affect the ACR metric, particularly with newer studies, and should be accounted for in future bibliometric analyses. Next, as with previous bibliometric studies, the risk of bias and formal analyses of study quality were not conducted. Objective quality analyses would provide more clarity on the risk of bias among the included studies. For example, the top-cited article in the TNC analysis (i.e.,was the first to discover a separation between serotonin type 1 and type 2 receptors, a landmark in serotonin research but less obviously in psychedelic science. In a similar way,) psychedelic relevant articles may have been overlooked because of less prominence to the relevant search terms. The field of psychedelics is relatively small with few active research centers, largely due to regulatory restrictions described above, likely generating higher numbers of self-citation rates. Self-citation rates were not controlled in this study but may bias results and should be considered in future studies. Next, excluding non-English manuscripts can bias the distribution of country-of-origin of the included studies. Despite the methodology of this study allowing for the inclusion of several studies from non-English speaking countries, recognition is made that non-English speaking countries maybe under-represented. Lastly, alternative citation indices, such as the g-index, h-index, and e-index. are recognized, however, were not incorporated in this study as author or institution specific analyses were not accounted for. We also chose not to assess alternative metrics of article impact, such as the "Altmetric Tracker of Online Interest," which can be considered for future bibliometric analyses. This study documented the top-cited classic psychedelic publications and observed that the field continues to explore a foundational understanding of the physiological and pharmacological effects of psychedelics, initially in preclinical basic science and animal models, but is progressing through the identification of therapeutic uses of psychedelics in clinical populations. More recent publications within the field of classic psychedelics have higher annual citation rates, more frequently study psilocybin compared to LSD, and include a higher-prevalence of clinical study designs examining therapeutic outcomes.
DISCLOSURE STATEMENT
No potential conflict of interest was reported by the authors.
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Study Details
- Study Typemeta
- Populationhumans
- Characteristicsliterature review
- Journal
- Compound