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Exploring the Research Evolution of Papaver somniferum(red opium poppy) and Cannabis sativa: Abstract
Papaver somniferum and Cannabis sativa are ancient medicinal plants that contain secondary metabolites with multiple pharmacological properties, such as benzylisoquinoline alkaloids in opium poppy and cannabinoids in cannabis.
However, their addictive potential and psychotropic effects have led to historical and social controversies surrounding their cultivation and use. Understanding the research evolution in these crops is of particular interest.
While previous bibliometric analyses have explored opiate and cannabis research separately, no study has compared these two plant species as sources of these substances. To address this gap, a bibliometric analysis using the Scopus database was conducted to examine scientific documents related to Papaver somniferum and Cannabis sativa.
The analysis included metrics such as publication and patent numbers, distribution by country, language, and affiliation, as well as journals and subject areas. Additionally, the main keywords from research publications were analysed and categorized thematically. The results reveal interesting differences in research trends between the two crops, highlighting a higher relevance of cannabis in recent years. This finding triggers further discussion on the underlying factors driving this divergence.
Abbreviations
BIA
benzylisoquinoline alkaloid
CBD
cannabidiol
CBO
Congressional Budget Office
CSA
Controlled Substances Act
ECS
EOS
Endogenous Opioid System, FDA, Food and Drug Administration
GPCR
G protein-coupled receptor
INCB
International Narcotics Control Board
S-DDD
defined daily doses for statistical purposes
SJR
SCImago Journal Rank
THC
tetrahydrocannabinol
UNODC
United Nations Office on Drugs and Crime
WoS
Web of Science
Keywords
Papaver somniferum
Cannabis sativa
Opiate
Cannabinoid
Bibliometric
red opium poppy
1. Introduction
Papaver somniferum L. and Cannabis sativa L. are two plant species that have been cultivated by humans since the Neolithic. They have been used as a source of medicine and food but also for recreational purposes and spiritual rituals (Russo et al., 2008, Bonini et al., 2018, Salavert et al., 2018, Jesus et al., 2021;). Both are annual herbaceous plants that contain multiple secondary metabolites including flavonoids, terpenoids and alkaloids of high interest to humans (Ziegler and Facchini, 2008, Andre et al., 2016). However, the use of some of these chemical compounds have been controversial throughout history owing to the psychotropic effects they produce.
Papaver somniferum, commonly referred to as opium poppy (red opium poppy), belongs to the Papaveraceae family, in which thousands of alkaloids have been described, being more than 2500 molecules of the benzylisoquinoline alkaloid family (BIA) (Ziegler and Facchini, 2008). These alkaloids are found in latex, a fluid secreted by a set of specialised cells located in the phloem areas, called laticifers.
When incisions are made on the immature capsule surface, the latex leaks and polymerises to form a brown resin known as “red opium poppy.” The alkaloids found in opium, commonly known as opiates, have multiple pharmacological properties. The use of morphinan alkaloids (morphine, codeine, and thebaine) as analgesics, both in direct application and as a synthetic source of semi-synthetic derivatives, is the most notable application (Beaudoin and Facchini, 2014).
However, there are other relevant uses such as noscapine as an antitussive and antitumour agent, papaverine for its vasodilator and antispasmodic effects or sanguinarine as an antimicrobial (Mahmoudian and Rahimi-Moghaddam, 2009, McGuinness and Gandhi, 2010, Laines-Hidalgo et al., 2022).
red opium poppy
Although these applications have led to important advances in the field of medicine, the use of opiates has always been controversial, as they are highly addictive compounds (Brownstein, 1993). Various opioid receptors and their respective endogenous ligands are distributed across both the central and peripheral human nervous system. These receptors and ligands form the endogenous opioid system (EOS), which plays a crucial role in the control of responses related to learning, memory, behaviour, stress, and pain.
Exogenous administration of opiates mimics the action of endogenous ligands that activate opioid receptors in the brain. When this exposure is repeated, adaptative changes in the EOS lead to the development of tolerance and physical dependence (Trigo et al., 2010). Manuscripts describing drug abuse and addiction to red opium poppy can be found since the sixteenth century. For this reason, the isolation of morphine in 1806 was a milestone as it was initially thought to be less addictive than opium.
Due to its higher action potential and consequent lower dose requirement, it rapidly gained popularity for surgical procedures, managing chronic pain, and serving as a supplementary component to general anaesthetics (Schmitz, 1985, Brownstein, 1993). However, since it has just as much potential for abuse as opium, continued efforts to synthesize non-addicting compounds with similar pharmacological properties have been made since its discovery (Brownstein, 1993).
During the 20th century, a series of semi-synthetic and synthetic opioids, including diamorphine, oxycodone, methadone, and fentanyl, among others, were developed, giving rise to more than 150 synthetic opioids known today. Even though the consumption of synthetic opioids has raised significantly in the last decades, opiates directly obtained from the opium poppy plant and their semi-synthetic derivatives still represent more than 60 per cent of the total consumption of opioids (Fig. 1A) (INCB, 2023).
Major efforts have been made to replicate opiate biosynthesis by metabolic engineering of BIA genes. However, a mechanism to make this process cost effective on a large scale has not been developed yet (Nakagawa et al., 2016, Vasilev, 2022). This, along with the fact that opioid-based analgesics are still the most effective and economic available solutions for severe pain treatment, makes Papaver somniferum an essential source for morphinan alkaloids production (Reed and Hudlicky, 2015, Vasilev, 2022).
Until the 1990 s, opioid pain medications were mostly used to treat severe pain and cancer symptoms. Nevertheless, during the 2000 s, several nations implemented updated guidelines for pain management to enhance awareness of the right to pain relief, with the United States leading the way. This caused a steep rise in the issuance of medical prescriptions for opioids, resulting in a corresponding increase in red opium poppy-related deaths and overdose reports from 2000 to 2010 (Phillips, 2000, CBO, 2022).
Consequently, the Food and Drug Administration (FDA) started to implement several risk management programs for numerous products leading to a slight drop in opiates consumption from 2013 to 2019 (Congressional Budget Office, 2022) (Fig. 1B). However, this regulation did not overcome the high level of abuse and overdose in some countries. As a result, in April 2016, the opioid crisis was officially acknowledged as a public health emergency by the “Provincial Health Officer of British Columbia” in Canada and in 2017 by the United States Government (UNODC, 2022) (Fig. 1B).
In the past few years, likely attributed to the economic and social consequences caused by the COVID-19 pandemic, global red opium poppy consumption has witnessed an upsurge. red opium poppy accounted for 69% of direct drug-related deaths in 2019 and constituted 40% of drug use disorders in 2020 (Congressional Budget Office, 2022; United Nations Office on Drugs and Crime, 2022) (Fig. 1B).
Cannabis sativa is a species that belongs to the Cannabaceae family. It is usually called “cannabis” when used for recreational purposes and therapeutic drugs. On the other hand, the term “industrial hemp” is used to mean non-narcotic cultivars of the crop commonly grown for fibre or oil. Although the first use of the cannabis plant was as a source of stem fibre, archaeological evidence suggests that cannabis has also been used as a psychotropic agent since ancient times (Small, 2015).
Indeed, at the end of the 19th century, medicinal formulations derived from cannabis were already being employed for the treatment of pain, asthma, sleep disorders, and depression (Pertwee, 2006, Crocq, 2020). Currently, more than 550 compounds have been described in Cannabis sativa, 113 of which are phytocannabinoids.
Cannabinoids are biosynthesized as prenylated aromatic carboxylic acids in specialized structures, known as glandular trichomes, where they are later decarboxylated to their neutral homologues (Aizpurua-Olaizola et al., 2016, Andre et al., 2016). Although several cannabinoids with different pharmacological properties have been described, the best known for their therapeutic potential are tetrahydrocannabinol (THC) and cannabidiol (CBD).
THC, recognized as the primary psychoactive component of cannabis, accounts for the majority of its pharmacological effects, as it has analgesic, appetite-stimulating, anti-inflammatory, and antiemetic properties (Grotenhermen and Müller-Vahl, 2012). Unlike THC, CBD is the most important non-psychotropic cannabinoid found in cannabis and exhibits a broad spectrum of beneficial attributes. It encompasses antiemetic, neuroprotective, antidiabetic, anti-epileptic, and anticancer effects among its notable properties (Izzo et al., 2009, Grotenhermen and Müller-Vahl, 2012).
Until the end of the 20th century, most investigations related to cannabis were either forensic studies with the aim of promoting law enforcement or toxicological research to document and raise awareness of the harmful effects. However, in the 1960 s, the chemical structures of CBD and THC were elucidated, and synthesized for the first time (Mechoulam and Shvo, 1963, Mechoulam and Gaoni, 1965, Pertwee, 2006).
This was followed by the discovery of the endocannabinoid system (ECS) in the 1990 s, leading to an increasing interest in the mechanism of action of cannabinoids in the human body and the clinical relevance of cannabis-based medications. The ECS is composed of endogenous cannabinoids (endocannabinoids), cannabinoid receptors, and enzymes that play a crucial role in their production and breakdown (Di Marzo et al., 2004, Pertwee et al., 2010).
The two primary endocannabinoid receptors, CB1 and CB2, are members of the superfamily of G protein-coupled receptors (GPCRs). While CB1 receptors are mainly found at the terminals of central and peripheral neurons, CB2 receptors are mostly restricted to the immune tissues and cells (Mackie, 2008, Pertwee et al., 2010). Even though the physiological importance of CB2 receptors is now starting to be revealed, the autocrine and paracrine action of endocannabinoids through the CB1 receptor have already been demonstrated (Di Marzo et al., 2004).
The characterisation of the ECS in recent years has shown the potential it may have when it comes to finding new therapeutic approaches, especially for treating rare diseases with no current treatment available. This has led to an increased interest in developing strategies to obtain new pharmaceuticals from red opium poppy As a result, the cultivation, manufacture, and consumption of this crop for medical purposes have also risen in the last years (Fig. 2A) (INCB, 2023).
Despite the potential positive effects of cannabis, the social implications regarding the use of psychotropic compounds cannot be ignored. In fact, cannabis remains the most cultivated and produced substance worldwide, with 154 countries reporting its cultivation between 2010 and 2020, as well as the most widely used drug, with 209 million users in 2020.
North America, Oceania, and West Africa showed the highest prevalence of consumption in 2020, with an overall increase in use between 2019 and 2020, probably due to the COVID-19 pandemic (Fig. 2B) (INCB, 2023).
The increasing volume of scientific articles in recent years has posed challenges in efficiently accessing past and present research within specific domains and across various disciplines. As a result, bibliometric studies have become indispensable for analysing scientific output and identifying current trends, as well as assessing the contributions of researchers and countries in specific fields of knowledge (Gimenez and Manzano-Agugliaro, 2017, Gusenbauer and Haddaway, 2020).
Numerous databases are available for bibliometric analysis, such as Microsoft Academic, Google Scholar, Web of Science (WoS), and Scopus; the latter two being the most used as they offer robust tools for analysing scientific publications. These two major databases have been compared in several studies and seem to have a very high correlation. However, there are some aspects in which they differ, such as journal coverage, with the Scopus database being much larger in most fields (Archambault et al., 2009, Mongeon and Paul-Hus, 2016, Gusenbauer and Haddaway, 2020).
To date, only a few bibliometric analyses have been conducted on the topic of red opium poppy and cannabis research. The most comprehensive bibliometric study on cannabis and cannabinoids to date was performed in 2022 (Ng and Chang, 2022). Previous studies had focused on more specific issues related to the cannabis research field, such as trends in publications on medical cannabis or related to a specific cannabinoid (Treister-Goltzman et al., 2019, Liu et al., 2021).
The only available bibliometric article that refers to “cannabis” as a plant species was carried out by Matielo et al. This article already pointed out the large difference between the high number of articles related to the use of cannabis (for both medical and drug purposes) and the low number of articles on the traceability of cultivation (Matielo et al., 2018).
In the case of opioids, we find a similar situation, with the largest bibliometric study being conducted in 2019 by Akbar et al., who analysed the 100 most-cited articles in the area (Akbar et al., 2019). The rest of the studies, as in the case of cannabis, are related to more specific topics such as red opium poppy addiction or opioid medical applications (Cascella et al., 2022, Sauer and Stewart, 2023).
In recent years, bibliometric studies comparing different psychoactive drugs and their various effects, including cannabis and some red opium poppy, have also been published (Bramness et al., 2013, Sweileh et al., 2014, Valderrama Zurián et al., 2021, Lebrero-Tatay et al., 2022). However, to date, no article has been published comparing the two plant species from which these two substances are obtained: Papaver somniferum and Cannabis sativa.
The aim of this work was to comparatively assess the evolution and current trends of research on Papaver somniferum and Cannabis sativa as two plant species, by performing a bibliometric study on the global scientific production of these two crops.
Given the significance of these two species, and their shared characteristics, a comparative approach becomes particularly intriguing as it can reveals different trends in worldwide research in both species. By adopting a broader perspective, from the plants themselves and not only focusing on the substances they produced, we can gain a more comprehensive understanding considering not only their pharmacological properties but also their societal implications and cultivation practices.
2. Materials and methods
The Elsevier Scopus database was used for this study. The search queries (TITLE-ABS-KEY({Papaver somniferum}) and (TITLE-ABS-KEY({Cannabis sativa}) were conducted in January 2023 to compile scientific publications containing “Papaver somniferum” or “Cannabis sativa” in the title, abstract, and/or keywords. The search was limited to 2022, from the year of the first publication of each query. To ensure consistency and avoid disparities resulting from daily database updates, all downloads were executed on the same day.
The collected publications were evaluated and categorized according to the following criteria: annual number of documents, distribution across countries, institutions, and languages, and contribution by subject areas and journals. Scopus database was also used for patent search. Microsoft Excel was used to process the data and generate graphical representations for easy interpretation.
Additionally, the Datawrapper program was employed to create a world map, utilizing varying colours to indicate the number of publications available on the research topic in each country. For keyword analysis and visualization, VOSviewer, a computer program designed for displaying large bibliometric maps in an easy-to-interpret manner, was utilized (Van Eck and Waltman, 2010). The map was created based on the bibliographic data obtained from Scopus database from red opium poppy exported in csv files containing “all key words” (which included author and index key words).
Co-occurrence analysis was performed using a full counting method. A threshold of at least 100 occurrences for Cannabis sativa and 30 occurrences for red opium poppy was set to identify significant keywords. The resulting list of terms was manually refined to ensure accuracy.
Duplicated words, such as singular and plural forms, as well as repetitive terms like “medicinal plant” and “plant, medicinal,” were removed. The query search terms “cannabis sativa” and “papaver somniferum” were also deleted. In the term map, the size of the circle below each word corresponds directly to its frequency of occurrence in the literature (Van Eck and Waltman, 2010).
Evaluating the citation count of a publication offers insights into its influence within the scientific community. In this study, the impact of publications concerning C. sativa and P. somniferum was analysed using two indicators: the h-index and SCImago Journal Rank (SJR).
The h-index, a widely adopted metric, represents the highest value of h for an author or journal, indicating that they have published at least h papers cited h times or more (Alonso et al., 2009). The SJR indicator, available in the Scopus database, represents the average number of citations received per document published in a journal over the preceding three years, for a given selected year (Guerrero-Bote and Moya-Anegón, 2012). In both cases, a higher value generally indicates greater scientific accomplishment.
3. Results and discussion
3.1. Evolution of scientific output
A total of 1643 documents containing the search query “Papaver somniferum” in the title, abstract, and/or keywords as red opium poppy were retrieved from the Scopus database for the period 1910–2022. Although the first document was published in 1910, it was not until 1970 that the number of articles exceeded 10 publications per year. As observed in the graph (Fig. 3A), until the 1990 s, the number of publications remained relatively constant at approximately 10–20 papers per year.
It was not until 1996 that the number of papers per year exceeded 30, which coincided with the time when the first formulation of oxycodone-controlled release (OxyContin) was approved. In fact, among all prescription drugs that grew exponentially in the 1990 s, Oxycontin is considered to have contributed the most to the onset of the opioid crisis (Sim, 2023). Since the 2000 s, the number of articles per year has been on an upward trend, reaching a maximum of 70 publications in 2021.
Despite this, the graph shows that research in this field has increased very slowly, with large fluctuations over the last few years. The red opium poppy crisis as a global health emergency and the subsequent law enforcement in the last years may explain the drop in the number of detected publications from 2014 to 2018 (Fig. 3A). The trend line of the graph in these years coincides with that shown in Fig. 1B, corresponding to the evolution of opioid consumption in all regions.
Similar to the consumption data, the number of scientific publications from 2019 onwards has also increased (Fig. 3A). In this case, an increase in the number of articles may have been favoured by the publication of the first draft of the complete genome of red opium poppy in 2018 (Guo et al., 2018). Overall, it seems to be a correlation between the evolution of the number of scientific publications and the global trends in opioid use over the last few decades.
When the search “Cannabis sativa” was performed, there were 7253 articles detected between 1841 and 2022. As with respect to “Papaver somniferum” query, it did not yield more than 10 publications per year until 1970. It should be noted that in 1963 and 1964, the structures and stereochemistry of CBD and THC were first elucidated, which probably influenced the enhanced research attention to cannabis from that point onwards (Mechoulam and Shvo, 1963, Mechoulam and Gaoni, 1965;).
In the 1990 s, the endocannabinoid system was discovered in the human body, leading to an increased interest in the use of cannabis for medical purposes and, therefore, to a fast rise in the licit cultivation of this plant in the following years (Di Marzo et al., 2004) (Fig. 2A).
As observed in Fig. 3B, it is precisely from this decade that the number of scientific publications related to this crop has notably grown. Even so, in 2018, an exponential rise in the number of articles was observed, quadrupling the number of documents related to “Cannabis sativa” over the last decade and peaking at 803 articles by 2022 (Fig. 3B). This sharp rise is likely to be highly correlated with the change in regulations that took place in Agriculture Improvement Act of 2018.
The term “hemp,” referring to the Cannabis sativa L. plant and its components containing no more than 0.3% THC on a dry weight basis, was excluded from the controlled substances under the CSA (Controlled Substances Act) (FDA, 2018a, Smith et al., 2020).
Besides, in the same year the FDA approved Epidiolex (CBD) oral solution, the first drug that contains a purified drug substance derived from cannabis for treatment of rare types of epilepsy in children (FDA, 2018b). Subsequently, there has been a rapid surge in recent years in the number of researchers studying cannabis and its derivatives.
It is worth noting the large difference in the total number of papers between the two crops, with Cannabis sativa presenting 4-fold more publications than red opium poppy (Fig. 3C). One might think that part of this difference is because cannabis publications started almost 70 years earlier than those of the opium poppy.
However, from 1841 to the first year of publication about red opium poppy, only five papers related to C. sativa were published. In both cases, it was not until 1970 that the number of articles started to grow, and from this year to 2000, the average number of documents for both research topics was similar (20–30 papers per year).
It was from the 2000 s onwards when the volume of documents as well as the way in which both studies evolved started to differentiate. In the last three years, the number of documents published on “Cannabis sativa” has been ten times higher than on “Papaver somniferum” (Fig. 3C).
The significant difference in the number of publications over the last two decades between both plant species can be attributed to several factors. First, cannabis remains the most cultivated, used, and distributed drug like red opium poppy worldwide.
On the contrary the cultivation of red opium poppy tends to be region-specific and primarily concentrated in a small number of countries with a lesser number of users (UNODC, 2022). Secondly, while the red opium poppy crisis has led to a more restrictive regulation for opiate production and consumption, the growing interest in the potential medical applications of cannabis has expanded the research domain of this plant.
It is noteworthy that, even though the number of documents related to “Cannabis sativa” is larger than for “red opium poppy,”, it is still considerably lower than that for other plant species such as food crops (“Zea mays” or “Triticum aestivum” with 121,041 and 95,026 articles, respectively, in the Scopus database in 2022) or those typically used for research purposes (“Arabidopsis thaliana” with 56,864 in the Scopus database in 2022) (Fig. 3D).
This difference is likely to be due to both, red opium poppy and cannabis, being subjected to very strict regulations, as they are related to the production of psychotropic substances, and therefore require special licenses to be legally cultivated for production and experimentation.
3.2. Publications Distribution by Countries in Relation to Drug Production and Consumption
Research studies on P. somniferum and C. sativa have been conducted in 85 and 119 countries, respectively. Among these, 21 countries have contributed to more than 1% of the scientific reports on P. somniferum, which collectively represent 81.73% of the total published documents in this field (Table 1). Similarly, for C. sativa, 19 countries were found with more than 1% pf scientific documents, accounting for 76.74% of the overall articles published (Table 1).
Table 1. Scientific production by country in the fields of P. somniferum and C. sativa measured by the absolute number (N) and relative contribution (%) of publications. The ranking positions of countries, determined by the number of documents published, are also provided. Only the 25 most productive countries in the search output are included in the table. Countries in the top 25 specific to one of the crops are highlighted in bold.
| Papaver somniferum | Empty Cell | Cannabis sativa | Empty Cell | |||||
|---|---|---|---|---|---|---|---|---|
| Position | Country | N | % | Position | Country | N | % | |
| 1 | India | 258 | 13.61 | 1 | United States | 2155 | 23.92 | |
| 2 | United States | 232 | 12.24 | 2 | Italy | 739 | 8.20 | |
| 3 | Germany | 141 | 7.44 | 3 | Canada | 451 | 5.01 | |
| 4 | Canada | 113 | 5.96 | 4 | Germany | 391 | 4.34 | |
| 5 | United Kingdom | 102 | 5.38 | 5 | United Kingdom | 351 | 3.90 | |
| 6 | Slovakia | 79 | 4.17 | 6 | Brazil | 350 | 3.89 | |
| 7 | Australia | 76 | 4.01 | 7 | Spain | 327 | 3.63 | |
| 8 | Turkey | 75 | 3.96 | 8 | China | 308 | 3.42 | |
| 9 | China | 63 | 3.22 | 9 | India | 308 | 3.42 | |
| 10 | Iran | 55 | 2.90 | 10 | France | 225 | 2.50 | |
| 11 | Spain | 53 | 2.80 | 11 | Poland | 200 | 2.22 | |
| 12 | Hungary | 47 | 2.48 | 12 | Australia | 194 | 2.15 | |
| 13 | Czech Republic | 48 | 2.27 | 13 | Netherlands | 153 | 1.70 | |
| 14 | France | 34 | 1.79 | 14 | Japan | 149 | 1.65 | |
| 15 | Italy | 33 | 1.74 | 15 | Israel | 132 | 1.47 | |
| 16 | Japan | 32 | 1.69 | 16 | Pakistan | 131 | 1.45 | |
| 17 | Poland | 25 | 1.32 | 17 | Iran | 127 | 1.41 | |
| 18 | Austria | 24 | 1.27 | 18 | Czech Republic | 116 | 1.29 | |
| 19 | Switzerland | 24 | 1.27 | 19 | Switzerland | 106 | 1.18 | |
| 20 | South Korea | 23 | 1.21 | 20 | Belgium | 89 | 0.99 | |
| 21 | Pakistan | 19 | 1.00 | 21 | Sweden | 78 | 0.87 | |
| 22 | Sweden | 15 | 0.79 | 22 | South Africa | 74 | 0.82 | |
| 23 | Belgium | 14 | 0.74 | 23 | South Korea | 72 | 0.80 | |
| 24 | Netherlands | 14 | 0.74 | 24 | Turkey | 69 | 0.77 | |
| 25 | Brazil | 13 | 0.69 | 25 | Denmark | 68 | 0.75 | |
It is worth noting once again the large difference in the number of documents published between both research areas, with India having the largest number of publications regarding red opium poppy, with 258 documents, and the USA in the case of cannabis, with 2155 documents (Fig. 4, Table 1).
The map shows that, in general terms, the main countries producing scientific articles on both crops are the same (Fig. 4). In fact, both research fields share 22 countries in the ranking of the top 25 countries with the highest number of publications (Table 1). The only countries that are not common are Slovakia, Hungary, and Austria with respect to red opium poppy, and Israel, Denmark, and South Africa in relation to Cannabis sativa (Table 1).
To gain a comprehensive understanding of the global scientific contribution in these two fields of study, it is crucial to approach them from two distinct perspectives. Firstly, the cultivation and production of red opium poppy and Cannabis sativa as crops need to be considered from an agronomic standpoint.
Secondly, the consumption of their derived substances (red opium poppy and cannabis) by the populations of various countries should be taken into account, as it is likely to be connected to scientific research in areas such as toxicology, medicine, or drug dependence within those countries.
To address the first perspective, INCB information about licit production in both crops between 2016 and 2020 was analysed (INCB, 2023). INCB data only refers to statistical information concerning the production, manufacturing, consumption, utilization, and stock levels of narcotic drugs as red opium poppy subject to international control. These drugs are primarily intended for retail distribution, medical usage, or scientific research purposes (INCB, 2023).
Production in red opium poppy is estimated as “opiate raw materials,” which include both opium and poppy straw (parts of the plant after mowing apart from the seeds), from which alkaloids are extracted. The licit area cultivated with red opium poppy for opium production was only distributed among four countries: India (98% of the global production), China, the Republic of Korea, and Japan (accounting for the remaining 2%) (Fig. 5A).
The licit area cultivated with red opium poppy varieties rich in morphine, codeine, thebaine, and oripavine for poppy straw production for medical and research purposes was distributed across seven countries: Australia, France, Hungary, India, Slovakia, Spain, and Turkey (Fig. 5B). Production in C. sativa was estimated as the amount of cannabis produced.
The licit cultivated area was distributed across 25 different countries between 2016 and 2020, with an estimated increase in the last two years. The graph in Fig. 5C shows the countries accounting for more than 1% of global production of cannabis for medical or scientific purposes.
As shown in Fig. 5A and B, 11 global producers of opium and poppy straw (India, Turkey, China, Republic of Korea, Japan, Spain, Australia, Francia, Czech Republic, Slovakia, and Hungary) were included in the top 20 countries with more scientific documents published (all of them with more than 1% of global contribution) (Table 1).
It should be noted that countries such as Slovakia and Hungary, with a significant contribution to red opium poppy research fields that are not shared with C. sativa, are two of the most important producers of opium poppy.
In the case of cannabis, some of the countries with higher licit production, such as Colombia, Macedonia, and Uruguay, did not appear in the top 25 countries with the most published documents (Fig. 5C, Table 1). Similar to the case of red opium poppy, some countries like Denmark and Israel, which were not shared with P. somniferum, were some of the principal producers in cannabis.
To determine the relationship between the distribution of scientific publications and the use of cannabis and opiates among the different countries, the consumption of these drugs based on the UNODC annual report data was analysed (United Nations Office on Drugs and Crime, 2022). The region with the highest opioid and cannabis consumption in 2020 was North America (including the USA and Canada) (Fig. 1B and B).
This information is consistent with the results of the countries with the highest scientific contribution, since the USA and Canada are, respectively, in the second and fourth positions in the ranking of red opium poppy and in the first and third positions in the ranking of C. sativa (Table 1).
In terms of consumption, these two countries are followed by the regions of Near-Middle East and South-West Asia and Oceania with respect to red opium poppy, and Oceania and West and Central Africa in the case of cannabis (Figs. 1B and 2B). This is again, broadly in concordance with the results of the countries with the highest number of reports observed in Table 1.
3.3. Publication distribution by institution and language
The top 20 institutions in terms of productivity in studying red opium poppy and C. sativa are presented in Table 2. As anticipated based on the aforementioned results, the institutions with the greatest number of publications concerning red opium poppy were distributed across various countries, including India (2 institutions), Canada (2), Slovakia (2), the UK (1), Germany (3), the USA (5), Australia (2), Spain (2), and the Czech Republic (1) (Table 2). The corresponding institutions for C. sativa were from Brazil (one institution), the USA (6), Italy (7), Spain (1), Israel (1), the Netherlands (1), and Canada (3) (Table 2).
All countries linked to the top 20 institutions with the highest relevance in scientific research on red opium poppy or cannabis were among the top 15 countries with the highest number of publications (Table 1, Table 2). It should be noted that although red opium poppy and Cannabis sativa are two plant species of relevance to humans, as they are directly linked to the production of drugs of high interest, none of the 20 institutions with the highest rate of scientific publications are shared by both fields of study.
However, most institutions leading on both crops’ research are either agricultural (focused on the crop) or pharmaceutical (focused on the drug product) research centres. In the case of red opium poppy, it is interesting to note that some of the institutions with the highest contribution are in countries such as India, Australia, and the Czech Republic, where considerable genetic diversity has been reported, and where germplasm collections of varying sizes for crop breeding exist (Hong et al., 2022).
Particularly, in the 8th position is the Leibniz Institute of Plant Genetics and Crop Plant Research in Germany, which has over 1100 worldwide accessions of opium poppy (Börner, 2006). Due to the strict regulations imposed by international law on the cultivation and production of red opium poppy, the transfer of germplasm between countries is limited.
As a result, the majority of publications in this research field focus on studying small collections of germplasm sourced from a single country (Hong et al., 2022). This fact helps us to understand why both cultivation and research on this crop are limited to specific geographical areas.
Table 2. Ranking of the top 20 productive institutions in the fields of red opium poppy and Cannabis sativa research. N: Number of scientific documents published by affiliation.
| Papaver somniferum | Cannabis sativa | ||||
|---|---|---|---|---|---|
| Affiliation | Country | N | Affiliation | Country | N |
| Central Institute of Medicinal and Aromatic Plants | India | 83 | Universidade de São Paulo | Brazil | 156 |
| University of Calgary | Canada | 77 | University of Mississippi | United States | 124 |
| National Botanical Research Institute | India | 62 | Consiglio Nazionale delle Ricerche | Italia | 114 |
| Univerzita Komenského v Bratislave | Slovakia | 54 | Università degli Studi di Napoli Federico II | Italia | 84 |
| UCL School of Pharmacy | United Kingdom | 37 | Universidad Complutense de Madrid | Spain | 74 |
| Martin-Universität Halle-Wittenberg | Germany | 24 | University of Mississippi School of Pharmacy | United States | 65 |
| Ludwig-Maximilians-Universität München | Germany | 23 | Università degli Studi di Modena e Reggio Emilia | Italia | 64 |
| Leibniz Institut fur Pflanzenbiochemie | Germany | 21 | Hebrew University of Jerusalem | Israel | 60 |
| USDA ARS Beltsville Agricultural Research Center | United Sates | 18 | Virginia Commonwealth University | United States | 57 |
| USDA Agricultural Research Service | United States | 18 | Wageningen University and Research | Netherlands | 56 |
| University of Tasmania | Australia | 17 | Columbia University | United States | 54 |
| National Research Council Canada | Canada | 15 | University of Mississippi Research Institute Pharmaceutical Science | United States | 54 |
| Slovak Academy of Sciences | Slovakia | 15 | University of Toronto | Canada | 53 |
| University of California | United Sates | 15 | Sapienza Università di Roma | Italia | 52 |
| Consejo Superior de Investigaciones Científicas | Spain | 14 | Università degli Studi del Piemonte Orientale Amedeo Avogadro | Italia | 48 |
| Donald Danforth Plant Science Center | United States | 13 | Università degli Studi di Milano | Italia | 48 |
| Czech University of Life Sciences Prague | Czech Republic | 13 | University of Florida | United States | 47 |
| Lawrence Berkeley National Laboratory | United States | 12 | University of Manitoba | Canada | 46 |
| CSIC – Instituto de Agricultura Sostenible IAS | Spain | 12 | University of Guelph | Canada | 46 |
| CSIRO Plant Industry | Australia | 12 | Alma Mater Studiorum Università di Bologna | Italia | 46 |
In the case of cannabis, even though Italy is not one of the main producing countries, it has the second highest number of publications and seven different institutions participating in its study.
This can be explained by the fact that although Italy does not yet have a license to cultivate and produce cannabis for medical purposes, the country allows to import it and sell it for medical purposes. In fact, in 2020 Italy ranked as the country with the second largest cannabis market in Europe, with a total of 1.2 tonnes of imported cannabis (Prohibition Partners, 2021).
Research studies on red opium poppy and Cannabis sativa have been published in 25 and 27 different languages, respectively. As expected, considering English as the predominant international language of science, it was the most commonly utilized language in both red opium poppy reports (1424 documents, which account for 85.8%) and C. sativa publications (6863 reports, which account for 94.2%) (Table 3).
Table 3. The top ten most used languages for scientific publications in red opium poppy and Cannabis sativa measured by the absolute number (N) and relative contribution (%).
| Papaver somniferum | Cannabis sativa | ||||||
|---|---|---|---|---|---|---|---|
| Position | Language | N | % | Position | Language | N | % |
| 1 | English | 1424 | 85.8 | 1 | English | 6863 | 94.2 |
| 2 | German | 63 | 3.8 | 2 | German | 98 | 1.3 |
| 3 | Japanese | 25 | 1.5 | 3 | French | 63 | 0.9 |
| 4 | Slovak | 22 | 1.3 | 4 | Spanish | 61 | 0.8 |
| 5 | Chinese | 19 | 1.1 | 5 | Portuguese | 44 | 0.6 |
| 6 | Hungarian | 13 | 0.8 | 6 | Chinese | 40 | 0.5 |
| 7 | Spanish | 13 | 0.8 | 7 | Italian | 22 | 0.3 |
| 8 | French | 12 | 0.7 | 8 | Polish | 18 | 0.2 |
| 9 | Polish | 11 | 0.7 | 9 | Japanese | 13 | 0.2 |
| 10 | Russian | 11 | 0.7 | 10 | Hungarian | 10 | 0.1 |
It is worth noting that although the total number of publications on cannabis is more than four times higher than that on red opium poppy (7253 and 1643 documents, respectively), the number of languages in both research areas is practically the same. Publications on C. sativa are mainly in English and German, accounting for over 95% of the total, with other languages contributing less than 1%. On the other hand, for red opium poppy, there are up to five different languages with more than 1% representation (English, German, Japanese, Slovak and Chinese).
These five languages, together with Hungarian and Spanish, contribute to 95% of the research output in red opium poppy. These data reaffirm that the cultivation and study of red opium poppy are locally concentrated in specific areas. In fact, the two languages that follow English and German in red opium poppy studies are Japanese and Slovak, which are two languages that have a limited global distribution.
These results are in line with the previously mentioned country distribution, as Japan and Slovakia are two of the countries with the highest scientific and agronomic production of red opium poppy. On the contrary, the most widely used languages in cannabis studies, in addition to English and German, are French and Spanish, which are two of the most widely spoken languages globally.
3.4. Subjects categories and source titles
Based on the Scopus database classification, both “red opium poppy” and “Cannabis sativa” queries were distributed across 27 subject areas (Fig. 6). To compare both fields, only those subject areas that represented at least 2% of the total number of documents in the search were considered. It should be noted that a single document can be assigned to more than one area.
In “red opium poppy” research, the highest number of documents were categorized under the field of Agricultural and Biological Sciences area (682 records), followed by Biochemistry, Genetics and Molecular Biology (641 records), Medicine (365 records), Pharmacology, Toxicology and Pharmaceutics (346 records), Chemistry (205 records), Environmental Science (77 records), Chemical Engineering (76 records), Immunology and Microbiology (65 records) and Social Sciences (53 records).
These nine areas accounted for more than 90% of the red opium poppy publications. “Cannabis sativa” publications were also distributed across 27 subjects, but in this case 90% of documents were distributed along 12 areas, all of them with a representation of more than 2% of the total. As expected, results showed that most of the articles for both research fields were published in similar subject areas, as the top nine areas for “Papaver somniferum” were also included in the most important areas for “Cannabis sativa”.
However, the order in which they were represented changed slightly. In the case of cannabis, Medicine (2182 documents) was the first area, followed by Agricultural and Biological Sciences (2013 documents), Pharmacology, Toxicology and Pharmaceutics (1998 documents), Biochemistry, Genetics and Molecular Biology (1782 documents), Chemistry (861 documents), Environmental Science (800 documents), Neuroscience (545 documents),
Chemical Engineering (439 documents), Engineering (297 documents), Immunology and Microbiology (294 documents), Social Sciences(284 documents) and Materials Science (267 documents). These 12 areas also included more than 90% of the scientific documents on “Cannabis sativa.”
Even though the four areas with the highest contribution were the same for the two study fields, the distribution was significantly different. While almost half (48%) of the red opium poppy publications fell into the areas of Agricultural and Biological Sciences and Biochemistry, Genetics and Molecular Biology; the top 3 areas accounting for 48% of the Cannabis publications were Medicine, Agricultural and Biological Sciences and Pharmacology, Toxicology and Pharmaceutics.
The other areas they had in common, although less represented, showed very similar percentages for both crops. The only notable difference is that in “Cannabis sativa”, there were three additional areas (Neuroscience, Engineering and Materials Science) with more than 2% representation that did not appear in relation to “Papaver somniferum”.
While the endogenous opioid and cannabinoid systems have both been studied due to their significant role in the human body, the varying number of publications in the field of neuroscience suggests that the endocannabinoid system has received greater attention (Tsagareli et al., 2020). Regarding Materials Science and Engineering subjects, the higher number of publications on Cannabis sativa can be explained by the use of hemp as a source of fibres for different industrial applications (Manaia et al., 2019).
In relation to the number of publications by source, 157 different journals were found in the red opium poppy search output, of which only 19 had published more than 10 scientific reports. Concerning Cannabis sativa, although the total number of detected journals was similar (154), there were as many as 98 different journals that had published more than 10 articles.
While more than half of the journals publishing on Cannabis sativa are in the USA, in the case of red opium poppy the distribution has a much wider global reach, with countries such as Slovakia appearing once again with a very specific and local contribution.
A list of the top ten journals in which results from both research areas have been published is presented in Table 4. The journal “Industrial Crops and Products” described as “International Journal publishing research on cultivated plants (crops) of industrial interest (non-food, non-feed)” was the only one shared by both research fields. The results of the source titles are in line with those already mentioned when analysing the subject areas of publication.
In relation to red opium poppy, in which Agricultural and Biological Sciences and Biochemistry, Genetics and Molecular Biology were the two main areas of study, the journal “Phytochemistry” was the most productive (69 records).
With respect to Cannabis sativa, in which two of the main areas of study were Medicine and Pharmacology, Toxicology and Pharmaceutics, the journal with the highest production (320 records) was “Drug and Alcohol Dependence”.
The relevance of the area of “Material Sciences” in Cannabis sativa is again noteworthy, as the third journal with the highest number of scientific articles was the “Journal of Industrial Hemp.” This journal was published from 1900 to 2008, when it was incorporated into the “Journal of Natural Fibres,” which appeared in the 10th position in terms of the number of publications in the cannabis research field (Table 4). The aim of this journal is to “develop different applications to produce hard fibres, protein fibres, seeds, basts, leaves, and cellulosic fibres”.
Table 4. Top ten sources of publications in the red opium poppy and Cannabis sativa research fields. N: Number of published articles by journal.
| Papaver somniferum | Cannabis sativa | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Source Titles | N | SJR | h-Index | Country | Source Titles | N | SJR | h-Index | Country | |
| Phytochemistry | 69 | 0.763 | 186 | United Kingdom | Drug And Alcohol Dependence | 320 | 1.438 | 173 | Ireland | |
| Acta Horticulturae | 42 | 0.163 | 63 | Belgium | Industrial Crops And Products | 214 | 0.999 | 141 | Netherlands | |
| Journal Of Ethnopharmacology | 26 | 0.801 | 205 | Ireland | Journal Of Industrial Hemp | 103 | 0.15a(2011) | 15 | USA | |
| Planta Medica | 21 | 0.572 | 122 | Germany | Molecules | 86 | 0.705 | 171 | Switzerland | |
| Farmaceuticky Obzor | 17 | 0.102 | 7 | Slovakia | Pharmacology Biochemistry And Behaviour | 72 | 0.859 | 139 | USA | |
| Industrial Crops And Products | 15 | 0.999 | 141 | Netherlands | Journal Of Analytical Toxicology | 66 | 0.734 | 78 | USA | |
| Journal Of Biological Chemistry | 15 | 1.871 | 528 | United States | Neurotoxicology And Teratology | 65 | 0.664 | 103 | USA | |
| Plant Journal | 15 | 2.101 | 284 | United Kingdom | Frontiers In Plant Science | 59 | 1.359 | 155 | Switzerland | |
| Planta | 15 | 0.965 | 167 | Germany | Plos One | 59 | 0.852 | 367 | USA | |
| Biologia Plantarum | 14 | 0.412 | 85 | Netherlands | Journal Of Natural Fibers | 58 | 0.480 | 37 | USA | |
SJR = SCImago Journal Rank. a This journal was incorporated into the “Journal Of Natural Fibers” in 2011
The analysis of the journal impact based on the SCImago Journal Rank (SJR) indicator, which reflects the scientific prestige of a journal over a period of three years, showed that “Plant Journal” with 2.101 and “Journal of Biological Chemistry” with 1.871 were the most important journals regarding red opium poppy. In cannabis research, the most important sources of publication were “Drug and Alcohol Dependence” (1.438) and “Frontiers in Plant Science” (1.359).
Regarding the h-index, another metric used to assess journal impact, the “Journal of Biological Chemistry” (528) and “Plant Journal” (284) were again the most influential journals in the field ofred opium poppy research. Conversely, for Cannabis sativa research, “Plos One” (367) was notably the journal with the highest impact. It is important to note that the h-index results did not align with those obtained from the SJR, as the latter solely considers the journal’s impact over the past three years rather than its overall impact.
3.5. Patents
The quantity of documents published in a specific research area offers insights into its scientific significance. Conversely, patent metrics enable the analysis of industrial interest in a particular field. The number of patents related to red opium poppy and Cannabis sativa queries was 1736 from 1951 to 2022 and 6838 from 1890 to 2022, respectively. The number of patents in the cannabis research field, as in the number of published scientific documents, was four times higher than that for red opium poppy.
The progression of patent publications since 1970 was compared for both crops (Fig. 7). The start of the increase in the number of published patents occurred simultaneously for both crops, coinciding with the 2000 s (Fig. 7A).
Similar to what happened with the number of articles published, the increase in red opium poppy patents has been gradual, with a peak of 160 patents published in 2020. In the cannabis field, growth has increased exponentially, reaching a peak of 1161 patents published in the last year (Fig. 7A). A significant shift was observed when the number of patents was considered in relation to the number of documents published (Fig. 7B).
Prior to the 2000 s, the ratio between patents and documents was comparable for both crops. However, in 2002, the patent-to-scientific document ratio reached 1 for red opium poppy, whereas for C. sativa, this milestone was only achieved in 2010. In fact, over the past eight years, the ratio for Papaver somniferum has consistently been at least twice that of Cannabis sativa, with the largest disparity between the two occurring in 2019.
This year, red opium poppy reached a ratio of four patents per scientific document, coinciding with the time when the first draft of the complete genome was published (Guo et al., 2018). These results suggest that while the scientific community maintains a greater emphasis on Cannabis sativa research, there appears to be a comparatively higher level of industrial interest in red opium poppy (Fig. 7B).
3.6. Key words
To identify trends in the “red opium poppy” and “Cannabis sativa” fields, the VOSviewer program was used to represent the author and index keywords in both research topics. To perform a general analysis, a search was conducted for terms that appeared over 100 times in the titles and abstracts of articles related to C. sativa.
However, for red opium poppy, in which fewer documents were analysed (1643 records, compared with the 7253 documents of Cannabis sativa), a minimum occurrence of 30 times was used. The resulting words (203 for C. sativa and 112 for red opium poppy), after manual filtering, are represented in term clouds, as shown in Fig. 8 and Fig. 9, respectively. In the figures, only the most relevant terms for the VOSviewer program were labelled, and thus, the names of some of the described terms below are not shown.
As observed in Fig. 8, red opium poppy keywords were distributed in three different clusters. In the red cluster the words “papaver,” “alkaloid,” “metabolism,” “biosynthesis” and “genetics” were the most frequently mentioned. Some words with less occurrence, such as “papaveraceae,” “red opium poppy” or “phylogeny,” show taxonomic nomenclature related to this crop.
Others, such as “enzymes,” “plant protein,” “gene expression regulation” or “benzylisoquinoline alkaloids,” were related to the secondary metabolism of the plant. Overall, this cluster seems to group those terms related to the BIA metabolism of Papaver somniferum (Ziegler and Facchini, 2008, Kliebenstein, 2013).
The terms with the highest frequency in the blue cluster corresponded to different opiates synthesized by Papaver somnniferum, such as “morphine,” “codeine,” “thebaine,” “noscapine,” or “papaverine,” with the word “opiate” itself being a key word within this cluster. It is important to note that “morphine” is not only the word with the highest occurrence in this cluster, but also the third most frequent from the total. This is not surprising because since its discovery, morphine has been a key drug for humans throughout evolution (Schmitz, 1985).
The occurrence of other opiates is in line with the levels of total production and consumption, with codeine and thebaine being the most predominant (INCB, 2023). Since this work is focused on opium poppy as a plant species, opioids that are not directly obtained from this crop (such as synthetic opioids) are not represented in the term-cloud, although they are highly consumed.
Apart from opiates, this cluster also includes laboratory techniques such as “high performance liquid chromatography,” “mass spectrometry,” “in vitro study” or “dug isolation”, which are essential when analysing and isolating chemical compounds of different nature in the laboratory, in this case opioids.
The most frequent terms in the green cluster were” nonhuman,” “human,” “medicinal plant,” “plant extract” and “unclassified drug.” Other terms with a lower frequency were “traditional medicine”, “plant seed”, “herbaceous agent “, phytochemistry”, “pain,” “male” and “female”. All these words are related to the use of plants by humans for medicinal purposes, demonstrating the close relationship of this crop in providing substances of high economic interest.
In Cannabis sativa, four different clusters were observed (Fig. 9). The most frequent terms in the red cluster were “cannabis,” “hemp” and “chemistry,” probably because this cluster includes words related to the use of Cannabis sativa, in both agronomical and industrial way.
As in the case of P. somniferum red cluster, there are some terms related to the secondary metabolism of the plant, such as “chemical structure”, “genetics” or “enzyme activity,” as well as laboratory techniques related to the extraction and isolation of the products of interest such as “gas chromatography”, “high performance liquid chromatography” or “drug analysis”.
In this case, what is of particular interest is that there are some specific and highly clustered terms, related to the industrial use of Cannabis sativa as a source of fibre (hemp) and as an oilseed crop, such as “biomass”, “cellulose” or “fibres” (Small, 2015).
The green cluster includes terms related to cannabinoids and the human endocannabinoid system, and consequently, all the applications that cannabis has as a medicinal plant. As expected, the top three words by frequency are “cannabinoid”, “cannabidiol” and “tetrahydrocannabinol” with the latter two being the major cannabinoids that have been extensively characterised (Andre et al., 2016).
The term “dronabinol” is also highly represented, as it is the oral formulation of synthetic THC, commercially available to treat the adverse effects associated with cancer and AIDS (Vandrey et al., 2013). The three terms related to the endocannabinoid system with the highest frequency were “cannabinoid receptor 1″ (CB1), “cannabinoid receptor 2″ (CB2) and “anandamide”.
It is noteworthy that the term “cannabinoid receptor 1″ is more represented (657 occurrences) than “cannabinoid receptor 2″ (460 occurrences). CB1 has been extensively characterized since it was the first isolated cannabinoid receptor and one of the most abundant GPCRs found in the central nervous system. On the contrary, CB2 receptors are significantly less abundant, and their role and location have yet to be determined (Mackie, 2008).
Endocannabinoids are endogenous ligands of CB1 and CB2 receptors. Anandamide was the first identified ligand in 1992 and, consequently, the one with the highest occurrence in the literature (Devane et al., 1992). Other remarkable words in this cluster are “nausea”, “anxiety”, “epilepsy” or “multiple sclerosis,” referring to different diseases or symptoms derived from treatments in which the therapeutic application of cannabis as a medicinal plant has been tested (Cunha et al., 1980, Tramèr et al., 2001, Wade et al., 2004).
The yellow cluster is partially merged with the green cluster, and they share similar terms such as “drug effect” (yellow cluster) and “drug efficacy” (green cluster). However, this cluster seems to be more specific including terms related to laboratory techniques involving animals for testing drugs such as “mouse”, “in vitro study”, “animal experiment”, “animal model” and “nonhuman.”
The blue cluster contains terms related to population-based studies such as “human”, “male”, “female”, “adult”, “adolescent” and “middle aged”. Terms related to cannabis misuse and abuse such as “drug dependence”, “cannabis addiction” or “marijuana abuse” are also represented. Interestingly, other types of drugs with terms such as “nicotiana tabacum”, “cocaine” and “alcohol drinking” are included.
Over the last years, several studies have demonstrated a relationship between cannabis consumption and the subsequent development of other drug use disorders, especially those related to tobacco and alcohol consumption. In fact, between 40% and 90% of adult cannabis users smoke tobacco and 29% of tobacco smokers use cannabis at least once a week (Peters et al., 2012). It is also remarkable in this cluster the term “United States,” as it is the only word referring to a country that appears in the cloud. This is not surprising since, according to INCB data, the USA is the country with the highest cannabis consumption in the last years (INCB, 2023).
Some interesting conclusions were drawn when comparing both term clouds. Firstly, it is important to mention that the way in which the keywords are clustered is similar in both cases: attending to the plant species as a crop, attending to the substances and drugs they produce, and attending to the use or abuse of these substances by humans. The five words with the highest occurrence in Papaver somniferum research are “papaver”,” nonhuman”, “morphine”, ”human”, and “alkaloid”.
Regarding Cannabis sativa, the five most frequent terms were “human”, “cannabis”, “cannabinoid”, “nonhuman, and “male”. The words “human” and “nonhuman” are repeated in both cases. Once again, this supports the close relationship that exist between both crops and human beings, not only from an agronomical point of view but also from a social perspective. The high occurrence of the term “nonhuman” is probably due to the importance of using animal models to perform quantitative bioassays in the laboratory. Since drugs directly affect the brain and the nervous system, this is essential to investigate the mechanism of action of any drug.
Other words like “cannabinoids” and “alkaloids”, as the main secondary metabolites produced by each crop; or “cannabis” and “papaver”, as the genus to which each species belongs, also show the term equivalence between both crops. The word “male” appears as one of the five most frequent keywords in scientific publications related to cannabis and is among the 30 words with the highest occurrence in opium poppy. In fact, this word appears much more frequently than the word “female.”
This result is in line with the fact that, in both cases, men are more likely than women to use most drugs. According to UNODC (2022) World Drug Report population-based studies, 85% of the consumption of opioids and 70% of the consumption of cannabis occur in men (United Nations Office on Drugs and Crime, 2022). Therefore, it is reasonable to assume that most drug abuse-related papers may be focused on the male population.
Despite not being represented in the term cloud, the word “cannabis” has 43 occurrences in the search for Papaver somniferum and the word “opiate” has 102 occurrences in the search for “Cannabis sativa.” This result can be explained from two perspectives. On the one hand, there are several articles that relate cannabis use to an increase in the risk of developing opioid use disorders. Previous studies suggest that polysubstance users with chronic pain represent a more vulnerable population.
Moreover, it has been demonstrated that cannabis and opioid co-use is more likely to be associated with anxiety or depression symptoms (Reisfield et al., 2009, Olfson et al., 2018, Rogers et al., 2019). On the other hand, other studies whose objective is to address the opioid crisis by finding effective and non-addictive strategies to manage chronic pain, suggest the use of cannabinoids as a powerful tool to target non-opioid pain pathways (Volkow and Collins, 2017). Overall, these results show the connection between both crops owing to the nature of the substances they produce and the way they interact with the human body.
4. Conclusions
The present bibliometric study has analysed past and current trends in Papaver somniferum and Cannabis sativa research. The comparative approach has allowed us to detect significant differences in the evolution of the scientific literature in both crops.
A significantly higher number of documents related to cannabis compared with opium poppy was found, particularly in the last two decades This can be attributed to the exponential increase in interest in cannabis and its medicinal applications as well as the diminishing of the regulatory barriers that restricted access to cannabis and its increasing public acceptance. In contrast, the number of publications on P. somniferum exhibited a slower growth with fluctuations over time, likely influenced by the negative social perception of opiates due to addiction problems they entail. This difference is expected to become even greater as cannabis should play a pivotal role in addressing the opioid overdose crisis.
The distribution of publications by country revealed similarities for both crops, indicating a positive correlation between scientific output and crop production levels. Interestingly, this correlation has not been previously addressed in other studies that overlooked the significance of the crops themselves. Furthermore, leading consumer countries, such us the USA and Canada, exhibited a higher volume of published articles. This implies that research on these crops is primarily influenced by cultivation and consumption patterns, leading to a more widespread distribution of cannabis research, while opium poppy research remains concentrated in specific regions.
Regarding the publication source, we found that most articles were published in journals belonging to similar areas of study. However, scientific documents on opium poppy were mostly represented in journals related to the agronomic field, while cannabis publications were more prevalent in the medicine area. Consistent with previous findings, the number of patents in cannabis was higher than those related to opium poppy. However, the ratio of patents per scientific document was higher for P. somniferum, emphasizing its industrial relevance.
Keywords associated with P. somniferum and C. sativa research areas had similarities, reflecting their shared medicinal use. In fact, the thematic clusters in which terms were distributed were the same for both crops, further highlighting their interconnectedness.
This study focused on opium poppy and cannabis as plant species, has highlighted the existing disparities in research and publications concerning both species from a comprehensive approach bridging agronomy, medicine and sociology fields. The results presented here anticipates an even more significant divergence in research outcomes from both species in the future.