The psychoactive cannabinoids fromCannabis sativaL. and the arachidonic acid-derived endocannabinoids are nonselective natural ligands for cannabinoid receptor type 1 (CB₁) and CB₂receptors. Although the CB₁receptor is responsible for the psychomodulatory effects, activation of the CB₂receptor is a potential therapeutic strategy for the treatment of inflammation, pain, atherosclerosis, and osteoporosis. Here, we report that the widespread plant volatile (E)-β-caryophyllene [(E)-BCP] selectively binds to the CB₂receptor (K_i= 155 ± 4 nM) and that it is a functional CB₂agonist. Intriguingly, (E)-BCP is a common constituent of the essential oils of numerous spice and food plants and a major component inCannabis. Molecular docking simulations have identified a putative binding site of (E)-BCP in the CB₂receptor, showing ligand π–π stacking interactions with residues F117 and W258. Upon binding to the CB₂receptor, (E)-BCP inhibits adenylate cylcase, leads to intracellular calcium transients and weakly activates the mitogen-activated kinases Erk1/2 and p38 in primary human monocytes. (E)-BCP (500 nM) inhibits lipopolysaccharide (LPS)-induced proinflammatory cytokine expression in peripheral blood and attenuates LPS-stimulated Erk1/2 and JNK1/2 phosphorylation in monocytes. Furthermore, peroral (E)-BCP at 5 mg/kg strongly reduces the carrageenan-induced inflammatory response in wild-type mice but not in mice lacking CB₂receptors, providing evidence that this natural product exerts cannabimimetic effectsin vivo. These results identify (E)-BCP as a functional nonpsychoactive CB₂receptor ligand in foodstuff and as a macrocyclic antiinflammatory cannabinoid inCannabis.

The ethnopharmacological approach toward the understanding and appraisal of traditional and herbal medicines is characterized by the inclusions of the social as well as the natural sciences. Anthropological field-observations describing the local use of nature-derived medicines are the basis for ethnopharmacological enquiries. The multidisciplinary scientific validation of indigenous drugs is of relevance to modern societies at large and helps to sustain local health care practices. Especially with respect to therapies related to aging related, chronic and infectious diseases traditional medicines offer promising alternatives to biomedicine. Bioassays applied in ethnopharmacology represent the molecular characteristics and complexities of the disease or symptoms for which an indigenous drug is used in “traditional” medicine to variable depth and extent. One-dimensional in vitro approaches rarely cope with the complexity of human diseases and ignore the concept of polypharmacological synergies. The recent focus on holistic approaches and systems biology in medicinal plant research represents the trend toward the description and the understanding of complex multi-parameter systems. Ethnopharmacopoeias are non-static cultural constructs shaped by belief and knowledge systems. Intensified globalization and economic liberalism currently accelerates the interchange between local and global pharmacopoeias via international trade, television, the World Wide Web and print media. The increased infiltration of newly generated biomedical knowledge and introduction of “foreign” medicines into local pharmacopoeias leads to syncretic developments and generates a feedback loop. While modern and post-modern cultures and knowledge systems adapt and transform the global impact, they become more relevant for ethnopharmacology. Moreover, what is traditional, alternative or complementary medicine depends on the adopted historic-cultural perspective.

Ethnopharmacology focuses on the understanding of local and indigenous use of medicines and therefore an emic approach is inevitable. Often, however, standard biomedical disease classifications are used to describe and analyse local diseases and remedies. Standard classifications might be a valid tool for cross-cultural comparisons and bioprospecting purposes but are not suitable to understand the local perception of disease and use of remedies. Different standard disease classification systems exist but their suitability for cross-cultural comparisons of ethnomedical data has never been assessed. Depending on the research focus, (I) ethnomedical, (II) cross-cultural, and (III) bioprospecting, we provide suggestions for the use of specific classification systems. We analyse three different standard biomedical classification systems (the International Classification of Diseases (ICD); the Economic Botany Data Collection Standard (EBDCS); and the International Classification of Primary Care (ICPC)), and discuss their value for categorizing diseases of ethnomedical systems and their suitability for cross-cultural research in ethnopharmacology. Moreover, based on the biomedical uses of all approved plant derived biomedical drugs, we propose a biomedical therapy-based classification system as a guide for the discovery of drugs from ethnopharmacological sources. Widely used standards, such as the International Classification of Diseases (ICD) by the WHO and the Economic Botany Data Collection Standard (EBDCS) are either technically challenging due to a categorisation system based on clinical examinations, which are usually not possible during field research (ICD) or lack clear biomedical criteria combining disorders and medical effects in an imprecise and confusing way (EBDCS). The International Classification of Primary Care (ICPC), also accepted by the WHO, has more in common with ethnomedical reality than the ICD or the EBDCS, as the categories are designed according to patient's perceptions and are less influenced by clinical medicine. Since diagnostic tools are not required, medical ethnobotanists and ethnopharmacologists can easily classify reported symptoms and complaints with the ICPC in one of the "chapters" based on 17 body systems, psychological and social problems. Also the biomedical uses of plant-derived drugs are classifiable into 17 broad organ- and therapy-based use-categories but can easily be divided into more specific subcategories. Depending on the research focus (I-III) we propose the following classification systems: I. Ethnomedicine: Ethnomedicine is culture-bound and local classifications have to be understood from an emic perspective. Consequently, the application of prefabricated, "one-size fits all" biomedical classification schemes is of limited value. II. Cross-cultural analysis: The ICPC is a suitable standard that can be applied but modified as required. III. Bioprospecting: We suggest a biomedical therapy-driven classification system with currently 17 use-categories based on biomedical uses of all approved plant derived natural product drugs.

What are the minimum methodological and conceptual requirements for an ethnopharmacological field study? How can the results of ethnopharmacological field studies be reported so that researchers with different backgrounds can draw on the results and develop new research questions and projects? And how should these field data be presented to get accepted in a scientific journal such as the Journal of Ethnopharmacology? The objective of this commentary is to create a reference that covers the basic standards necessary during planning, conducting and reporting of field research. We focus on conducting and reporting ethnopharmacological field studies on medicinal plants or materia medica and associated knowledge of a specific people or region. The article highlights the most frequent problems and pitfalls, and draws on published literature, fieldwork experience, and extensive insights from peer-review of field studies. Research needs to be ethical and legal, and follow local and national regulations. Primary ethnopharmacological field data need to be collected and presented in a transparent and comprehensible way. In short this includes: 1) Relevant and concise research questions, 2) Thorough literature study encompassing all available information on the study site from different disciplines, 3) Appropriate methods to answer the research questions, 4) Proper plant use documentation, unambiguously linked to voucher specimens, and 5) Qualitative and quantitative analyses of the collected data, the latter relying on use-reports as basic units. Although not exhaustive, we provide an overview of the necessary main issues to consider for field research and data reporting including a list of minimal standards and recommendations for best practices. For methodological details and how to correctly apply specific methods, we refer to further reading of suggested textbooks and methods manuals.