{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:55:09Z","timestamp":1790564109135,"version":"4.1.0"},"reference-count":155,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>\n                    The therapeutic use of phytocannabinoids has expanded considerably over the past decade because of their potential application across a wide range of clinical conditions. However, their concomitant use with conventional medications raises important concerns regarding drug interactions and patient safety. This narrative review provides a critical overview of current evidence on the pharmacokinetic (PK), pharmacodynamic, and toxicological interactions of major phytocannabinoids, with particular emphasis on cannabidiol (CBD) and \u0394\n                    <jats:sup>9<\/jats:sup>\n                    -tetrahydrocannabinol (THC), while also discussing emerging evidence related to minor phytocannabinoids and the potential contribution of terpenes. Phytocannabinoids modulate the activity of drug-metabolizing enzymes, particularly cytochrome P450 isoenzymes, and may affect selected drug transporters, thereby altering the systemic exposure and clinical effects of co-administered medications. Conversely, conventional medications that inhibit or induce cannabinoid-metabolizing enzymes may modify phytocannabinoid exposure, efficacy, and tolerability. Documented or potentially clinically relevant interactions have been reported for antiseizure medications, anticoagulants, antidepressants, opioids, alcohol, and other central nervous system depressants. However, the strength of the supporting evidence varies considerably, ranging from\n                    <jats:italic>in vitro<\/jats:italic>\n                    predictions and case reports to controlled PK and clinical studies. The magnitude and clinical relevance of these interactions are influenced by multiple factors, including cannabinoids formulation, dose, route of administration, treatment duration, pharmacogenetic variability, patient-specific characteristics, and polypharmacy. Particular attention should be given to vulnerable populations, such as pregnant women, children, older adults, and patients with hepatic impairment, in whom altered PK and increased susceptibility to adverse effects may further complicate treatment. Although substantial progress has been made in understanding cannabinoid pharmacology, important knowledge gaps remain regarding the clinical significance of many predicted interactions, the interaction profiles of minor phytocannabinoids, full-spectrum preparations, and terpenes and the long-term safety of cannabinoid-based therapies. Careful differentiation between mechanistically plausible and clinically demonstrated interactions, together with consideration of cannabinoid composition, dose, route of administration, patient vulnerability, and concomitant medications, can support safer and more individualized clinical management while guiding future research priorities.\n                  <\/jats:p>","DOI":"10.3389\/ftox.2026.1952599","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:04:06Z","timestamp":1790561046000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Phytocannabinoid-drug interactions: pharmacokinetic and pharmacodynamic mechanisms, clinical relevance and toxicological considerations"],"prefix":"10.3389","volume":"8","author":[{"given":"Diogo Alexandre","family":"Gomes","sequence":"first","affiliation":[{"name":"Behavioral Neuroscience Laboratory, Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL)","place":["Tubar\u00e3o, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wellyngton Vieira","family":"Eufr\u00e1zio","sequence":"additional","affiliation":[{"name":"Behavioral Neuroscience Laboratory, Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL)","place":["Tubar\u00e3o, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella Silva","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Behavioral Neuroscience Laboratory, Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL)","place":["Tubar\u00e3o, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin\u00e9rio","family":"Ribeiro de Novais J\u00fanior","sequence":"additional","affiliation":[{"name":"Behavioral Neuroscience Laboratory, Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL)","place":["Tubar\u00e3o, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via","family":"Rigo","sequence":"additional","affiliation":[{"name":"Medicinal Plant Laboratory (LaPlaM), Postgraduate Program in Health Sciences, University of the Extreme South of Santa Catarina (UNESC)","place":["Crici\u00fama, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"de Aguiar Amaral","sequence":"additional","affiliation":[{"name":"Medicinal Plant Laboratory (LaPlaM), Postgraduate Program in Health Sciences, University of the Extreme South of Santa Catarina (UNESC)","place":["Crici\u00fama, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Campanale","sequence":"additional","affiliation":[{"name":"Behavioral Neuroscience Laboratory, Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL)","place":["Tubar\u00e3o, Brazil"]},{"name":"Canadian Consortium for the Study of Natural Psychedelics and Consciousness (CCNPC)","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f4nio","family":"Inserra","sequence":"additional","affiliation":[{"name":"Behavioral Neuroscience Laboratory, Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL)","place":["Tubar\u00e3o, Brazil"]},{"name":"Canadian Consortium for the Study of Natural Psychedelics and Consciousness (CCNPC)","place":["Montreal, QC, Canada"]},{"name":"Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanit\u00e0 (ISS, Italian National Institute of Health)","place":["Rome, Italy"]},{"name":"Department of Neuroscience, Imaging and Clinical Sciences, G. 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