{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:37:22Z","timestamp":1791859042715,"version":"4.3.4"},"reference-count":103,"publisher":"Georg Thieme Verlag KG","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacopsychiatry"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Medical cannabis, nabiximols, dronabinol and nabilone are used for various\n                    medical conditions. Despite their pronounced pharmacokinetic variability and\n                    complex concentration\u2013effect relationships, therapeutic drug monitoring\n                    recommendations are lacking. We aimed to identify therapeutic reference ranges\n                    based on blood concentration\u2013clinical effect relationships. Studies reporting\n                    blood concentrations and clinical effects\/adverse effects or assessing\n                    cannabinoid receptors 1 and 2 occupancy were selected through a systematic\n                    literature search in the MEDLINE database via PubMed. Twenty-three articles were\n                    selected for vaporized\/smoked medical cannabis, three for nabiximols, nine for\n                    dronabinol and one for nabilone. No article was identified for\n                    delta-9-tetrahydrocannabinol-dominant cannabis extracts. For vaporized\/smoked\n                    medical cannabis, an orienting therapeutic reference range of 15\u201330\u2009ng\/mL\n                    delta-9-tetrahydrocannabinol was identified for pain reduction in diabetic\n                    peripheral neuropathy, while concentrations of &lt;20\u2009ng\/mL\n                    delta-9-tetrahydrocannabinol were significantly correlated with intraocular\n                    pressure reduction and 7.5\u201310\u2009ng\/mL with improvement of tic symptoms.\n                    Half-maximum effective concentrations of 7\u201329 ng\/mL delta-9-tetrahydrocannabinol\n                    were reported for \u201chigh\u201d effects. For nabiximols, a preliminary therapeutic\n                    reference range of 1\u201310 ng\/mL delta-9-tetrahydrocannabinol was determined for\n                    treating neuropathic pain and spasticity in adults with multiple sclerosis. For\n                    chemotherapy-induced nausea and vomiting, a preliminary therapeutic reference\n                    range of 1\u20135 ng\/mL for nabilone and 5\u201315 ng\/mL delta-9-tetrahydrocannabinol for\n                    dronabinol was assessed. In conclusion, relatively low concentrations may be\n                    sufficient to achieve therapeutic effects across all substances studied, with\n                    medical cannabis demonstrating these effects at lower concentrations than\n                    typically observed in recreational use. Nevertheless, adverse effects at\n                    therapeutic reference ranges cannot be excluded.<\/jats:p>","DOI":"10.1055\/a-2853-4984","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T23:16:28Z","timestamp":1781133388000},"source":"Crossref","is-referenced-by-count":1,"title":["Therapeutic Drug Monitoring of Cannabinoids: Therapeutic Reference\n                    Ranges for Delta-9-tetrahydrocannabinol in Medical Cannabis, Nabiximols,\n                    Dronabinol and Nabilone"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7653-3746","authenticated-orcid":false,"given":"Friederike","family":"Amann","sequence":"additional","affiliation":[{"name":"Central Institute of Mental Health, Department of\n                    Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg,\n                    Mannheim, Germany"},{"name":"German Center for Mental Health (DZPG)\u2014partner site\n                    Mannheim\u2014Heidelberg\u2014Ulm, Mannheim, Germany"},{"name":"Society for Neuropsychopharmacology and Pharmacopsychiatry (AGNP),\n                    Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Hefner","sequence":"additional","affiliation":[{"name":"Society for Neuropsychopharmacology and Pharmacopsychiatry (AGNP),\n                    Mannheim, Germany"},{"name":"Psychiatric Hospital, Vitos Clinic for Forensic\n                    Psychiatry, Eltville, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Cremer-Schaeffer","sequence":"additional","affiliation":[{"name":"Bundesopiumstelle, Bundesinstitut f\u00fcr Arzneimittel und\n                    Medizinprodukte, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7868-3903","authenticated-orcid":false,"given":"Gerhard","family":"Gr\u00fcnder","sequence":"additional","affiliation":[{"name":"Central Institute of Mental Health, Department of\n                    Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg,\n                    Mannheim, Germany"},{"name":"German Center for Mental Health (DZPG)\u2014partner site\n                    Mannheim\u2014Heidelberg\u2014Ulm, Mannheim, Germany"},{"name":"Society for Neuropsychopharmacology and Pharmacopsychiatry (AGNP),\n                    Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"H\u00e4user","sequence":"additional","affiliation":[{"name":"Medical Center Pain Medicine and Mental Health Saarbruecken,\n                    Saarbruecken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xenia M.","family":"Hart","sequence":"additional","affiliation":[{"name":"Central Institute of Mental Health, Department of\n                    Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg,\n                    Mannheim, Germany"},{"name":"Society for Neuropsychopharmacology and Pharmacopsychiatry (AGNP),\n                    Mannheim, Germany"},{"name":"Department of Neuropsychiatry, Keio University School\n                    of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Petzke","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine, University Medical Center\n                    G\u00f6ttingen (UMG), G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Zernig","sequence":"additional","affiliation":[{"name":"Society for Neuropsychopharmacology and Pharmacopsychiatry (AGNP),\n                    Mannheim, Germany"},{"name":"Private Practice for Psychotherapy and Court-Certified Expert Witness,\n                    Hall in Tirol, Austria"},{"name":"Department of Pharmacology, Medizinische Universit\u00e4t\n                    Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Havemann-Reinecke","sequence":"additional","affiliation":[{"name":"Society for Neuropsychopharmacology and Pharmacopsychiatry (AGNP),\n                    Mannheim, Germany"},{"name":"Department of Psychiatry and Psychotherapy, University\n                    Medical Center G\u00f6ttingen (UMG), G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00406-019-00983-5","article-title":"New trends in cannabis potency in USA and Europe during the last decade\n                    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(DAC\/NRF)","author":"DAC\/NRF-Kommission, Bundesvereinigung Deutscher\n                            Apothekerverb\u00e4nde (ABDA)","year":"2023"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2165\/00003088-200342040-00003","article-title":"Pharmacokinetics and pharmacodynamics of cannabinoids","volume":"42","author":"F Grotenhermen","year":"2003","journal-title":"Clin Pharmacokinet"},{"key":"ref9","first-page":"Cd014915","article-title":"Cannabis-based medicines and medical cannabis\n                    for adults with cancer pain","volume":"6","author":"W H\u00e4user","year":"2023","journal-title":"Cochrane Database Syst\n                    Rev"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s40263-021-00879-w","article-title":"Cannabis-based medicines and medical cannabis for chronic neuropathic pain","volume":"36","author":"F Petzke","year":"2022","journal-title":"CNS Drugs"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1186\/s12916-022-02459-1","article-title":"Medical cannabinoids: A pharmacology-based systematic review and meta-analysis\n                    for all relevant medical indications","volume":"20","author":"A Bilbao","year":"2022","journal-title":"BMC Med"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1055\/a-2256-0098","article-title":"Cannabinoids in the treatment of selected mental illnesses: Practical approach\n                    and overview of the literature","volume":"57","author":"K R M\u00fcller-Vahl","year":"2024","journal-title":"Pharmacopsychiatry"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"974","DOI":"10.2174\/1570159X17666190603171901","article-title":"Cannabidiol adverse effects and toxicity","volume":"17","author":"M A Huestis","year":"2019","journal-title":"Curr Neuropharmacol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1038\/s41386-020-0667-2","article-title":"Adverse effects of cannabidiol: A systematic review and meta-analysis of\n                    randomized clinical trials","volume":"45","author":"E Chesney","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1111\/bcp.14038","article-title":"A systematic review of cannabidiol dosing in clinical populations","volume":"85","author":"S A Millar","year":"2019","journal-title":"Br J Clin Pharmacol"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18284","article-title":"Pharmacokinetic variability and use of therapeutic drug monitoring of\n                    cannabidiol in patients with refractory epilepsy","author":"C Landmark Johannessen","year":"2025","journal-title":"Epilepsia"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00280-017-3387-5","article-title":"A review of oral cannabinoids and medical marijuana for the treatment of\n                    chemotherapy-induced nausea and vomiting: A focus on pharmacokinetic variability\n                    and pharmacodynamics","volume":"80","author":"M E Badowski","year":"2017","journal-title":"Cancer Chemother Pharmacol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1517\/13543784.9.7.1553","article-title":"Cannabinoid receptor ligands: Clinical and neuropharmacological considerations,\n                    relevant to future drug discovery and development","volume":"9","author":"R G Pertwee","year":"2000","journal-title":"Expert Opin Invest Drugs"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"173059","DOI":"10.1016\/j.pbb.2020.173059","article-title":"Therapeutic potential and safety considerations for the clinical use of\n                    synthetic cannabinoids","volume":"199","author":"D J Sholler","year":"2020","journal-title":"Pharmacol Biochem Behav"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.1007\/s00018-016-2300-4","article-title":"The CB(2) receptor and its role as a regulator of inflammation","volume":"73","author":"C Turcotte","year":"2016","journal-title":"Cell Mol Life Sci"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.1017\/S1462399409000957","article-title":"Emerging role of the cannabinoid receptor CB2 in immune regulation: Therapeutic\n                    prospects for neuroinflammation","volume":"11","author":"G A Cabral","year":"2009","journal-title":"Expert Rev Mol Med"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.lfs.2006.12.032","article-title":"Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and\n                    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reference range for a psychotropic drug\n                    systematically? Recommendations of the TDM task force of the AGNP","volume":"47","author":"X M Hart","year":"2025","journal-title":"Ther Drug Monit"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/j.1600-0773.1980.tb03660.x","article-title":"Plasma and brain levels of delta 6-THC and seven monooxygenated metabolites\n                    correlated to the cataleptic effect in the mouse","volume":"47","author":"A Ohlsson","year":"1980","journal-title":"Acta Pharmacol Toxicol (Copenh)"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"208s","DOI":"10.1002\/j.1552-4604.1981.tb02597.x","article-title":"The kinetics of cannabinoid distribution and storage with special reference to\n                    the brain and testis","volume":"21","author":"G Nahas","year":"1981","journal-title":"J Clin Pharmacol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/BF00432179","article-title":"Relationship between plasma delta-9-tetrahydrocannabinol 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