{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T12:16:13Z","timestamp":1776687373514,"version":"3.51.2"},"reference-count":111,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T00:00:00Z","timestamp":1731801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["10.54499\/UIDP\/04567\/2020"],"award-info":[{"award-number":["10.54499\/UIDP\/04567\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["10.54499\/UIDB\/04567\/2020"],"award-info":[{"award-number":["10.54499\/UIDB\/04567\/2020"]}]},{"name":"SPFITO","award":["10.54499\/UIDP\/04567\/2020"],"award-info":[{"award-number":["10.54499\/UIDP\/04567\/2020"]}]},{"name":"SPFITO","award":["10.54499\/UIDB\/04567\/2020"],"award-info":[{"award-number":["10.54499\/UIDB\/04567\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>This study explores the complementary or synergistic effects of medicinal cannabis constituents, particularly terpenes, concerning their therapeutic potential, known as the entourage effect. A systematic review of the literature on cannabis \u201centourage effects\u201d was conducted using the PRISMA model. Two research questions directed the review: (1) What are the physiological effects of terpenes and terpenoids found in cannabis? (2) What are the proven \u201centourage effects\u201d of terpenes in cannabis? The initial approach involved an exploratory search in electronic databases using predefined keywords and Boolean phrases across PubMed\/MEDLINE, Web of Science, and EBSCO databases using Medical Subject Headings (MeSH). Analysis of published studies shows no evidence of neuroprotective or anti-aggregatory effects of \u03b1-pinene and \u03b2-pinene against \u03b2-amyloid-mediated toxicity; however, modest lipid peroxidation inhibition by \u03b1-pinene, \u03b2 pinene, and terpinolene may contribute to the multifaceted neuroprotection properties of these C. sativa L. prevalent monoterpenes and the triterpene friedelin. Myrcene demonstrated anti-inflammatory proprieties topically; however, in combination with CBD, it did not show significant additional differences. Exploratory evidence suggests various therapeutic benefits of terpenes, such as myrcene for relaxation; linalool as a sleep aid and to relieve exhaustion and mental stress; D-limonene as an analgesic; caryophyllene for cold tolerance and analgesia; valencene for cartilage protection; borneol for antinociceptive and anticonvulsant potential; and eucalyptol for muscle pain. While exploratory research suggests terpenes as influencers in the therapeutic benefits of cannabinoids, the potential for synergistic or additive enhancement of cannabinoid efficacy by terpenes remains unproven. Further clinical trials are needed to confirm any terpenes \u201centourage effects.\u201d<\/jats:p>","DOI":"10.3390\/ph17111543","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T05:36:45Z","timestamp":1731908205000},"page":"1543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The Entourage Effect in Cannabis Medicinal Products: A Comprehensive Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2733-5797","authenticated-orcid":false,"given":"Rebeca","family":"Andr\u00e9","sequence":"first","affiliation":[{"name":"Escola de Ci\u00eancias e Tecnologias da Sa\u00fade (ECTS), CBIOS\u2014Universidade Lus\u00f3fona\u2019s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal"}]},{"given":"Ana Patr\u00edcia","family":"Gomes","sequence":"additional","affiliation":[{"name":"Escola de Ci\u00eancias e Tecnologias da Sa\u00fade (ECTS), CBIOS\u2014Universidade Lus\u00f3fona\u2019s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal"},{"name":"SOMA\u00cd Pharmaceuticals, R. 13 de Maio 52, 2580-507 Carregado, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5407-3983","authenticated-orcid":false,"given":"Catarina","family":"Pereira-Leite","sequence":"additional","affiliation":[{"name":"Escola de Ci\u00eancias e Tecnologias da Sa\u00fade (ECTS), CBIOS\u2014Universidade Lus\u00f3fona\u2019s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal"},{"name":"Laborat\u00f3rio Associado para a Qu\u00edmica Verde, REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Ant\u00f3nio","family":"Marques-da-Costa","sequence":"additional","affiliation":[{"name":"SOMA\u00cd Pharmaceuticals, R. 13 de Maio 52, 2580-507 Carregado, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0198-7671","authenticated-orcid":false,"given":"Luis","family":"Monteiro Rodrigues","sequence":"additional","affiliation":[{"name":"Escola de Ci\u00eancias e Tecnologias da Sa\u00fade (ECTS), CBIOS\u2014Universidade Lus\u00f3fona\u2019s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal"}]},{"given":"Michael","family":"Sassano","sequence":"additional","affiliation":[{"name":"SOMA\u00cd Pharmaceuticals, R. 13 de Maio 52, 2580-507 Carregado, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7992-8343","authenticated-orcid":false,"given":"Patricia","family":"Rijo","sequence":"additional","affiliation":[{"name":"Escola de Ci\u00eancias e Tecnologias da Sa\u00fade (ECTS), CBIOS\u2014Universidade Lus\u00f3fona\u2019s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9887-0973","authenticated-orcid":false,"given":"Maria do C\u00e9u","family":"Costa","sequence":"additional","affiliation":[{"name":"Escola de Ci\u00eancias e Tecnologias da Sa\u00fade (ECTS), CBIOS\u2014Universidade Lus\u00f3fona\u2019s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal"},{"name":"NICiTeS, Polytechnic Institute of Lusophony, ERISA-Escola Superior de Sa\u00fade Ribeiro Sanches, Rua do Telhal aos Olivais 8, 1950-396 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0014-2999(98)00392-6","article-title":"An Entourage Effect: Inactive Endogenous Fatty Acid Glycerol Esters Enhance 2-Arachidonoyl-Glycerol Cannabinoid Activity","volume":"353","author":"Fride","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Christensen, C., Rose, M., Cornett, C., and Alles\u00f8, M. (2023). Decoding the Postulated Entourage Effect of Medicinal Cannabis: What It Is and What It Isn\u2019t. Biomedicines, 11.","DOI":"10.3390\/biomedicines11082323"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"ElSohly, M.A., Radwan, M.M., Gul, W., Chandra, S., and Galal, A. (2017). Phytochemistry of Cannabis sativa L.. Phytocannabinoids, Springer.","DOI":"10.1007\/978-3-319-45541-9_1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1038\/d41586-019-02528-1","article-title":"Unpicking the Entourage Effect","volume":"572","author":"Worth","year":"2019","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1039\/C9NP00011A","article-title":"Synergy and Antagonism in Natural Product Extracts: When 1 + 1 Does Not Equal 2","volume":"36","author":"Caesar","year":"2019","journal-title":"Nat. Prod. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1002\/cpt.1434","article-title":"Pharmacodynamic Drug\u2013Drug Interactions","volume":"105","author":"Niu","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.fitote.2013.10.010","article-title":"Synergy Effects of Herb Extracts: Pharmacokinetics and Pharmacodynamic Basis","volume":"92","author":"Yang","year":"2014","journal-title":"Fitoterapia"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Namdar, D., Anis, O., Poulin, P., and Koltai, H. (2020). Chronological Review and Rational and Future Prospects of Cannabis-Based Drug Development. Molecules, 25.","DOI":"10.3390\/molecules25204821"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.tplants.2020.04.007","article-title":"Cannabis Phytomolecule \u201cEntourage\u201d: From Domestication to Medical Use","volume":"25","author":"Koltai","year":"2020","journal-title":"Trends Plant Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1021\/np50008a001","article-title":"Constituents of Cannabis sativa L. XVII. A Review of the Natural Constituents","volume":"43","author":"Turner","year":"1980","journal-title":"J. Nat. Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jpainsymman.2009.06.008","article-title":"Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of the Efficacy, Safety, and Tolerability of THC:CBD Extract and THC Extract in Patients with Intractable Cancer-Related Pain","volume":"39","author":"Johnson","year":"2010","journal-title":"J. Pain. Symptom Manag."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4236\/pp.2015.62010","article-title":"Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Extract Enriched in Cannabidiol","volume":"6","author":"Gallily","year":"2015","journal-title":"Pharmacol. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1089\/can.2018.0010","article-title":"Identification of Synergistic Interaction Between Cannabis-Derived Compounds for Cytotoxic Activity in Colorectal Cancer Cell Lines and Colon Polyps That Induces Apoptosis-Related Cell Death and Distinct Gene Expression","volume":"3","author":"Nallathambi","year":"2018","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Berman, P., Futoran, K., Lewitus, G.M., Mukha, D., Benami, M., Shlomi, T., and Meiri, D. (2018). A New ESI-LC\/MS Approach for Comprehensive Metabolic Profiling of Phytocannabinoids in Cannabis. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-32651-4"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.bcp.2018.06.025","article-title":"Appraising the \u201cEntourage Effect\u201d: Antitumor Action of a Pure Cannabinoid versus a Botanical Drug Preparation in Preclinical Models of Breast Cancer","volume":"157","author":"Tundidor","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Castillo-Arellano, J., Canseco-Alba, A., Cutler, S.J., and Le\u00f3n, F. (2023). The Polypharmacological Effects of Cannabidiol. Molecules, 28.","DOI":"10.3390\/molecules28073271"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lee, S., Kim, E.J., Kwon, E., Oh, S.J., Cho, M., Kim, C.M., Lee, W., and Hong, J. (2023). Identification of Terpene Compositions in the Leaves and Inflorescences of Hybrid Cannabis Species Using Headspace-Gas Chromatography\/Mass Spectrometry. Molecules, 28.","DOI":"10.3390\/molecules28248082"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1055\/s-0043-124873","article-title":"Quantitative Determination of \u03949-THC, CBG, CBD, Their Acid Precursors and Five Other Neutral Cannabinoids by UHPLC-UV-MS","volume":"84","author":"Wang","year":"2018","journal-title":"Planta Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"595","DOI":"10.2307\/1433419","article-title":"The Great Herbal of Leonhart Fuchs. De Historia Stirpium Commentarii Insignes, 1542","volume":"24","author":"Classen","year":"2001","journal-title":"Ger. Stud. Rev."},{"key":"ref_20","unstructured":"Linnaeus, C. (1753). Species Plantarum, Laurentii Salvii."},{"key":"ref_21","unstructured":"Agasse, H., Agasse, T.-C., and Panckoucke, C.-J. (1783). Encyclop\u00e9die M\u00e9thodique: Botanique, Chez Panckoucke."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1089\/can.2015.29003.ebr","article-title":"The Cannabis sativa Versus Cannabis indica Debate: An Interview with Ethan Russo, MD","volume":"1","author":"Piomelli","year":"2016","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_23","first-page":"337","article-title":"Cannabis: An Example of Taxonomic Neglect","volume":"23","author":"Schultes","year":"1974","journal-title":"Bot. Mus. Leafl. Harv. Univ."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"405","DOI":"10.2307\/1220524","article-title":"A Pratical and Natural Taxonomy for Cannabis","volume":"25","author":"Small","year":"1976","journal-title":"Taxon"},{"key":"ref_25","unstructured":"Usher, G. (1996). The Wordsworth Dictionary of Botany, Wordsworth Edition."},{"key":"ref_26","unstructured":"Brickell, C.D., Alexander, C., Cubey, J.J., David, J.C., Hoffman, M.H.A., Leslie, A.C., Mal\u00e9cot, V., and Jin, X. (2009). Internacional Code for Nomenclature for Cultivated Plants, International Society for Horticultural Science. [9th ed.]."},{"key":"ref_27","unstructured":"Bailey, L.H., and Bailey, E.Z. (1976). Hortus Third: A Concise Dictionary of Plants Cultivated in the United States and Canada, MacMillan Publishing Co."},{"key":"ref_28","unstructured":"Small, E. (2016). Cannabis: A Complete Guide, CRC Press."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1055\/s-0043-122240","article-title":"Pharmacological Foundations of Cannabis Chemovars","volume":"84","author":"Lewis","year":"2018","journal-title":"Planta Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.bse.2004.04.004","article-title":"A Chemotaxonomic Analysis of Terpenoid Variation in Cannabis","volume":"32","author":"Hillig","year":"2004","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_31","first-page":"181","article-title":"Cannabinoids and Terpenes as Chemotaxonomic Markers in Cannabis","volume":"3","author":"Elzinga","year":"2015","journal-title":"Nat. Prod. Chem. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/jps.2600820623","article-title":"Fragrance Compounds and Essential Oils with Sedative Effects upon Inhalation","volume":"82","author":"Buchbauer","year":"1993","journal-title":"J. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1111\/j.1476-5381.2011.01238.x","article-title":"Taming THC: Potential Cannabis Synergy and Phytocannabinoid-terpenoid Entourage Effects","volume":"163","author":"Russo","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/bs.apha.2017.03.004","article-title":"Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads","volume":"80","author":"Russo","year":"2017","journal-title":"Adv. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"McPartland, J.M., and Russo, E.B. (2014). Non-Phytocannabinoid Constituents of Cannabis and Herbal Synergy. Handbook of Cannabis, Oxford University Press.","DOI":"10.1093\/acprof:oso\/9780199662685.003.0015"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhang, J., Yan, J., Huang, S., Pan, G., Chang, L., Li, J., Zhang, C., Tang, H., Chen, A., and Peng, D. (2020). Genetic Diversity and Population Structure of Cannabis Based on the Genome-Wide Development of Simple Sequence Repeat Markers. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00958"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S176","DOI":"10.1111\/1556-4029.12005","article-title":"Analysis of the NMI01 Marker for a Population Database of Cannabis Seeds","volume":"58","author":"Shirley","year":"2013","journal-title":"J. Forensic Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sawler, J., Stout, J.M., Gardner, K.M., Hudson, D., Vidmar, J., Butler, L., Page, J.E., and Myles, S. (2015). The Genetic Structure of Marijuana and Hemp. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133292"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Gao, C., Xin, P., Cheng, C., Tang, Q., Chen, P., Wang, C., Zang, G., and Zhao, L. (2014). Diversity Analysis in Cannabis sativa Based on Large-Scale Development of Expressed Sequence Tag-Derived Simple Sequence Repeat Markers. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110638"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.indcrop.2017.04.043","article-title":"Genetic Structure of Cannabis sativa Var. Indica Cultivars Based on Genomic SSR (GSSR) Markers: Implications for Breeding and Germplasm Management","volume":"104","author":"Soler","year":"2017","journal-title":"Ind. Crop. Prod."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ioannidis, K., Tomprou, I., Mitsis, V., and Koropouli, P. (2022). Genetic Evaluation of In Vitro Micropropagated and Regenerated Plants of Cannabis sativa L. Using SSR Molecular Markers. Plants, 11.","DOI":"10.3390\/plants11192569"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Pereira da Silva Oliveira, A., do C\u00e9u Costa, M., and Pires Bicho, M. (2023). Use of Medicinal Plants: Interindividual Variability of Their Effects from a Genetic and Anthropological Perspective. Medicinal Plants\u2014Chemical, Biochemical, and Pharmacological Approaches [Working Title], IntechOpen.","DOI":"10.5772\/intechopen.113841"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1124\/pharmrev.122.000600","article-title":"Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years","volume":"75","author":"Maccarrone","year":"2023","journal-title":"Pharmacol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Morales, P., Hurst, D.P., and Reggio, P.H. (2017). Molecular Targets of the Phytocannabinoids: A Complex Picture. Phytocannabinoids, Springer.","DOI":"10.1007\/978-3-319-45541-9_4"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Vitale, R.M., Iannotti, F.A., and Amodeo, P. (2021). The (Poly)Pharmacology of Cannabidiol in Neurological and Neuropsychiatric Disorders: Molecular Mechanisms and Targets. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094876"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Zagzoog, A., Mohamed, K.A., Kim, H.J.J., Kim, E.D., Frank, C.S., Black, T., Jadhav, P.D., Holbrook, L.A., and Laprairie, R.B. (2020). In Vitro and in Vivo Pharmacological Activity of Minor Cannabinoids Isolated from Cannabis sativa. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-77175-y"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4790","DOI":"10.1111\/bph.13250","article-title":"Cannabidiol Is a Negative Allosteric Modulator of the Cannabinoid CB1 Receptor","volume":"172","author":"Laprairie","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.mehy.2005.08.026","article-title":"A Tale of Two Cannabinoids: The Therapeutic Rationale for Combining Tetrahydrocannabinol and Cannabidiol","volume":"66","author":"Russo","year":"2006","journal-title":"Med. Hypotheses"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1111\/j.1476-5381.2010.01166.x","article-title":"Effects of Cannabinoids and Cannabinoid-enriched Cannabis Extracts on TRP Channels and Endocannabinoid Metabolic Enzymes","volume":"163","author":"Ligresti","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"87","DOI":"10.2174\/1570159X17666190903103923","article-title":"The \u201cEntourage Effect\u201d: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders","volume":"18","author":"Ferber","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/sj.bjp.0707442","article-title":"The Diverse CB1 and CB2 Receptor Pharmacology of Three Plant Cannabinoids: \u03949-tetrahydrocannabinol, Cannabidiol and \u03949-Tetrahydrocannabivarin","volume":"153","author":"Pertwee","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1089\/can.2022.0257","article-title":"Behavioral Effects of Vaporized Delta-8 Tetrahydrocannabinol, Cannabidiol, and Mixtures in Male Rats","volume":"9","author":"Durbin","year":"2024","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1111\/bph.13000","article-title":"The Phytocannabinoid, \u03949-tetrahydrocannabivarin, Can Act through 5-HT1A Receptors to Produce Antipsychotic Effects","volume":"172","author":"Cascio","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.archoralbio.2019.05.028","article-title":"Cannabidiol, Cannabinol and Their Combinations Act as Peripheral Analgesics in a Rat Model of Myofascial Pain","volume":"104","author":"Wong","year":"2019","journal-title":"Arch. Oral. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1002\/ejp.1085","article-title":"Delta-9-tetrahydrocannabinol Decreases Masticatory Muscle Sensitization in Female Rats through Peripheral Cannabinoid Receptor Activation","volume":"21","author":"Wong","year":"2017","journal-title":"Eur. J. Pain"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.1111\/bph.15185","article-title":"A Systematic Review of Minor Phytocannabinoids with Promising Neuroprotective Potential","volume":"177","author":"Stone","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1089\/can.2019.0016","article-title":"Absence of Entourage: Terpenoids Commonly Found in Cannabis sativa Do Not Modulate the Functional Activity of \u03949-THC at Human CB1 and CB2 Receptors","volume":"4","author":"Santiago","year":"2019","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1089\/can.2019.0099","article-title":"Terpenoids Commonly Found in Cannabis sativa Do Not Modulate the Actions of Phytocannabinoids or Endocannabinoids on TRPA1 and TRPV1 Channels","volume":"5","author":"Heblinski","year":"2020","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5119","DOI":"10.1021\/acsomega.1c00318","article-title":"Flavonoids in Cannabis sativa: Biosynthesis, Bioactivities, and Biotechnology","volume":"6","author":"Bautista","year":"2021","journal-title":"ACS Omega"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1071\/CH21006","article-title":"The Chemistry of Cannabis and Cannabinoids","volume":"74","author":"Duggan","year":"2021","journal-title":"Aust. J. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1021\/np960004a","article-title":"The Volatile Oil Composition of Fresh and Air-Dried Buds of Cannabis sativa","volume":"59","author":"Ross","year":"1996","journal-title":"J. Nat. Prod."},{"key":"ref_62","first-page":"1934578X2092672","article-title":"Chemical Composition of Volatile Oils of Fresh and Air-Dried Buds of Cannabis c Hemovars, Their Insecticidal and Repellent Activities","volume":"15","author":"Wanas","year":"2020","journal-title":"Nat. Prod. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Rice, S., and Koziel, J.A. (2015). Characterizing the Smell of Marijuana by Odor Impact of Volatile Compounds: An Application of Simultaneous Chemical and Sensory Analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144160"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ternelli, M., Brighenti, V., Anceschi, L., Poto, M., Bertelli, D., Licata, M., and Pellati, F. (2020). Innovative Methods for the Preparation of Medical Cannabis Oils with a High Content of Both Cannabinoids and Terpenes. J. Pharm. Biomed. Anal., 186.","DOI":"10.1016\/j.jpba.2020.113296"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"112793","DOI":"10.1016\/j.indcrop.2020.112793","article-title":"Impact of Four Hemp (Cannabis sativa L.) Varieties and Stage of Plant Growth on Yield and Composition of Essential Oils","volume":"155","author":"Abdollahi","year":"2020","journal-title":"Ind. Crop. Prod."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1159\/000509733","article-title":"Terpenes\/Terpenoids in Cannabis: Are They Important?","volume":"3","author":"Hod","year":"2020","journal-title":"Med. Cannabis Cannabinoids"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.molstruc.2014.08.027","article-title":"Novel Insights for Permeant Lead Structures through in Vitro Skin Diffusion Assays of Prunus lusitanica L., the Portugal Laurel","volume":"1079","author":"Costa","year":"2015","journal-title":"J. Mol. Struct."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Peterson, B., Weyers, M., Steenekamp, J.H., Steyn, J.D., Gouws, C., and Hamman, J.H. (2019). Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) That Modulate Drug Membrane Permeation and Pre-Systemic Metabolism. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11010033"},{"key":"ref_69","first-page":"381","article-title":"Herbal Bioenhancers: A Revolutionary Concept in Modern Medicine","volume":"16","author":"Zafar","year":"2017","journal-title":"World J. Pharm. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/npp.2017.209","article-title":"Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and \u03949-Tetrahydrocannabinol","volume":"43","author":"Boggs","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Johnson, A.L., Verbitsky, R., Hudson, J., Dean, R., and Hamilton, T.J. (2023). Cannabinoid Type-2 Receptors Modulate Terpene Induced Anxiety-Reduction in Zebrafish. Biomed. Pharmacother., 168.","DOI":"10.1016\/j.biopha.2023.115760"},{"key":"ref_72","unstructured":"European Scientific Cooperative on Phytotherapy (2009). ESCOP Monographs: The Scientific Foundation for Herbal. Medicinal Products. Second. Edition, Supplement 2009, Thieme Medical Publishers."},{"key":"ref_73","unstructured":"Weiss, R.F., and Fintelmann, V. (2000). Herbal Medicine, Thieme. Complementary Medicine."},{"key":"ref_74","unstructured":"European Medicines Agency (2012). EMA\/HMPC\/143181\/2010 Community Herbal. Monograph on Lavandula Angustifolia Miller, Aetheroleum, European Medicines Agency."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.2174\/1570159X19666210920094504","article-title":"Linalool as a Therapeutic and Medicinal Tool in Depression Treatment: A Review","volume":"20","author":"Maia","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.phymed.2008.08.001","article-title":"Inhaled Linalool-Induced Sedation in Mice","volume":"16","author":"Linck","year":"2009","journal-title":"Phytomedicine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/ffj.2045","article-title":"Actions of Essential Oils on the Central Nervous System: An Updated Review","volume":"26","author":"Dobetsberger","year":"2011","journal-title":"Flavour Fragr. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1078\/094471102321621322","article-title":"Anti-Inflammatory Activity of Linalool and Linalyl Acetate Constituents of Essential Oils","volume":"9","author":"Peana","year":"2002","journal-title":"Phytomedicine"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.neulet.2006.12.063","article-title":"Mechanism of Changes Induced in Plasma Glycerol by Scent Stimulation with Grapefruit and Lavender Essential Oils","volume":"416","author":"Shen","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0944-7113(99)80044-0","article-title":"Anticonvulsant Properties of Linalool in Glutamate-Related Seizure Models","volume":"6","author":"Elisabetsky","year":"1999","journal-title":"Phytomedicine"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1023\/A:1011034409814","article-title":"Effects of Linalool on Glutamate Release and Uptake in Mouse Cortical Synaptosomes","volume":"26","author":"Emanuelli","year":"2001","journal-title":"Neurochem. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.neuro.2023.12.004","article-title":"Characterizing Cannabis-Prevalent Terpenes for Neuroprotection Reveal a Role for \u03b1 and \u03b2-Pinenes in Mitigating Amyloid \u03b2-Evoked Neurotoxicity and Aggregation in Vitro","volume":"100","author":"Laws","year":"2024","journal-title":"Neurotoxicology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6305","DOI":"10.3390\/molecules17066305","article-title":"Biological Activities of A-Pinene and \u03b2-Pinene Enantiomers","volume":"17","author":"Lopes","year":"2012","journal-title":"Molecules"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"McDougall, J.J., and McKenna, M.K. (2022). Anti-Inflammatory and Analgesic Properties of the Cannabis Terpene Myrcene in Rat Adjuvant Monoarthritis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147891"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1089\/can.2023.0083","article-title":"Evaluating Potential Anxiolytic Effects of Minor Cannabinoids and Terpenes After Acute and Chronic Oral Administration in Rats","volume":"8","author":"Jenkins","year":"2023","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1021\/acs.jnatprod.7b00654","article-title":"Biochemometrics to Identify Synergists and Additives from Botanical Medicines: A Case Study with Hydrastis Canadensis (Goldenseal)","volume":"81","author":"Britton","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s42238-022-00170-9","article-title":"Systematic Combinations of Major Cannabinoid and Terpene Contents in Cannabis Flower and Patient Outcomes: A Proof-of-Concept Assessment of the Vigil Index of Cannabis Chemovars","volume":"5","author":"Vigil","year":"2023","journal-title":"J. Cannabis Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1089\/can.2019.29014.dpi","article-title":"Waiting for the Entourage","volume":"4","author":"Piomelli","year":"2019","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Andre, C.M., Hausman, J.-F., and Guerriero, G. (2016). Cannabis sativa: The Plant of the Thousand and One Molecules. Front. Plant Sci., 7.","DOI":"10.3389\/fpls.2016.00019"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1016\/j.phytochem.2010.10.001","article-title":"Metabolic Fingerprinting of Cannabis sativa L., Cannabinoids and Terpenoids for Chemotaxonomic and Drug Standardization Purposes","volume":"71","author":"Fischedick","year":"2010","journal-title":"Phytochemistry"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/dta.407","article-title":"Cannabis\u2014From Cultivar to Chemovar","volume":"4","author":"Hazekamp","year":"2012","journal-title":"Drug Test. Anal."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"115","DOI":"10.17660\/ActaHortic.2011.925.15","article-title":"Variations in Terpene Profiles of Different Strains of Cannabis sativa L.","volume":"925","author":"Casano","year":"2011","journal-title":"Acta Hortic."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Milay, L., Berman, P., Shapira, A., Guberman, O., and Meiri, D. (2020). Metabolic Profiling of Cannabis Secondary Metabolites for Evaluation of Optimal Postharvest Storage Conditions. Front. Plant Sci., 11.","DOI":"10.3389\/fpls.2020.583605"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Russo, E.B. (2019). The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No \u201cStrain\u201d, No Gain. Front. Plant Sci., 9.","DOI":"10.3389\/fpls.2018.01969"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1055\/s-2000-8616","article-title":"Bioavailability and Pharmacokinetics of Natural Volatile Terpenes in Animals and Humans","volume":"66","author":"Kohlert","year":"2000","journal-title":"Planta Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.1002\/jps.22568","article-title":"First-Pass Metabolism via UDP-Glucuronosyltransferase: A Barrier to Oral Bioavailability of Phenolics","volume":"100","author":"Wu","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"ref_97","first-page":"80","article-title":"Essential Oil of Cannabis sativa L. Strains","volume":"4","author":"Mediavilla","year":"1997","journal-title":"J. Int. Hemp Assoc."},{"key":"ref_98","first-page":"519","article-title":"Effect of Beta-Myrcene on Pentobarbital Sleeping Time","volume":"26","author":"Freitas","year":"1993","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.chroma.2014.10.045","article-title":"Multidimensional Analysis of Cannabis Volatile Constituents: Identification of 5,5-Dimethyl-1-Vinylbicyclo[2.1.1]Hexane as a Volatile Marker of Hashish, the Resin of Cannabis sativa L.","volume":"1370","author":"Marchini","year":"2014","journal-title":"J. Chromatogr. A"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"L\u00f3pez, V., Nielsen, B., Solas, M., Ram\u00edrez, M.J., and J\u00e4ger, A.K. (2017). Exploring Pharmacological Mechanisms of Lavender (Lavandula angustifolia) Essential Oil on Central Nervous System Targets. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00280"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1515\/chem-2018-0040","article-title":"\u03b1-Terpineol, a Natural Monoterpene: A Review of Its Biological Properties","volume":"16","author":"Khaleel","year":"2018","journal-title":"Open Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1177\/1535370213520112","article-title":"D-Limonene Suppresses Doxorubicin-Induced Oxidative Stress and Inflammation via Repression of COX-2, INOS, and NF\u03baB in Kidneys of Wistar Rats","volume":"239","author":"Rehman","year":"2014","journal-title":"Exp. Biol. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1124\/mol.116.105080","article-title":"\u03b1-Pinene, a Major Constituent of Pine Tree Oils, Enhances Non-Rapid Eye Movement Sleep in Mice through GABA A-Benzodiazepine Receptors","volume":"90","author":"Yang","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1007\/s10886-008-9515-2","article-title":"Production and Diversity of Volatile Terpenes from Plants on Calcareous and Siliceous Soils: Effect of Soil Nutrients","volume":"34","author":"Baldy","year":"2008","journal-title":"J. Chem. Ecol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9673(02)00376-X","article-title":"Aroma Compound Analysis of Piper Nigrum and Piper Guineense Essential Oils from Cameroon Using Solid-Phase Microextraction\u2013Gas Chromatography, Solid-Phase Microextraction\u2013Gas Chromatography\u2013Mass Spectrometry and Olfactometry","volume":"976","author":"Jirovetz","year":"2002","journal-title":"J. Chromatogr. A"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Ceccarelli, I., Fiorenzani, P., Pessina, F., Pinassi, J., Aglian\u00f2, M., Miragliotta, V., and Aloisi, A.M. (2020). The CB2 Agonist \u03b2-Caryophyllene in Male and Female Rats Exposed to a Model of Persistent Inflammatory Pain. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00850"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Alberti, T., Barbosa, W., Vieira, J., Raposo, N., and Dutra, R. (2017). (\u2212)-\u03b2-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040691"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Hashiesh, H.M., Sharma, C., Goyal, S.N., Sadek, B., Jha, N.K., Al Kaabi, J., and Ojha, S. (2021). A Focused Review on CB2 Receptor-Selective Pharmacological Properties and Therapeutic Potential of \u03b2-Caryophyllene, a Dietary Cannabinoid. Biomed. Pharmacother., 140.","DOI":"10.1016\/j.biopha.2021.111639"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"110726","DOI":"10.1016\/j.intimp.2023.110726","article-title":"An in Vitro and in Vivo Study: Valencene Protects Cartilage and Alleviates the Progression of Osteoarthritis by Anti-Oxidative Stress and Anti-Inflammatory Effects","volume":"123","author":"Chen","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/B978-0-12-819485-0.00017-7","article-title":"Biologically Active Compounds from Lamiaceae Family: Central Nervous System Effects","volume":"68","author":"Abdelhalim","year":"2021","journal-title":"Stud. Nat. Prod. Chem."},{"key":"ref_111","unstructured":"European Medicines Agency (2023). European Union Herbal Monograph on Eucalyptus Globulus Labill; Eucalyptus Polybractea R.T. Baker; Eucalyptus Smithii R.T. Baker, Aetheroleum EMA\/HMPC\/320292\/2023, European Medicines Agency."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/11\/1543\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:34:03Z","timestamp":1760114043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/11\/1543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,17]]},"references-count":111,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ph17111543"],"URL":"https:\/\/doi.org\/10.3390\/ph17111543","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,17]]}}}