{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:49:07Z","timestamp":1790131747890,"version":"4.0.1"},"reference-count":82,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cultural Bureau and Ministry of Education PhD Scholarship, Kingdom of Saudi Arabia","award":["SPR-73707"],"award-info":[{"award-number":["SPR-73707"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Neuropathic pain is a chronic disorder that arises from damaged or malfunctioning nerves. Hypersensitivity to stimuli, also known as hyperalgesia, can cause a person to experience pain from non-painful stimuli, termed allodynia. Cannabis-based medicines (CBMs) may provide new treatment options to manage neuropathic pain. A review of the relevant studies was conducted to evaluate the effectiveness of CBMs in treating neuropathic pain. Scientific literature was systematically searched from January 2003 to December 2024 using the Web of Science Core Collection, PubMed, and MEDLINE. A total of 22 randomized controlled trials (RCTs) were identified that considered the use of 1\u2032,1\u2032-dimethylheptyl-\u03948-tetrahydrocannabinol-11-oic acid (CT-3), \u03949-tetrahydrocannabinol (\u03949-THC), cannabidiol (CBD), combinations of \u03949-THC with CBD, and cannabidivarin for treatment of neuropathic pain. Significant reductions in pain were reported in 15 studies focused on the treatment of multiple sclerosis, spinal cord injuries, diabetic neuropathy, postherpetic neuralgia, HIV-associated sensory neuropathy, peripheral neuropathic pain, complex regional pain syndrome, chronic radicular neuropathic pain, and peripheral neuropathy of the lower extremities. These positive outcomes often adopted personalized and adjusted dosing strategies. By contrast, seven RCTs observed no significant pain relief compared to placebo, although some had minor improvements in secondary outcomes, such as mood and sleep. Collectively, CBM treatments may improve pain scores, but study limitations such as small sample sizes and study durations, high placebo response rates, and trial unblinding because of the psychoactive effects of cannabinoids all hinder data interpretation and the extrapolation to chronic pain conditions. Hence, future RCTs will need to have larger numbers and be more extended studies that explore optimal dosing and delivery methods and identify patient subgroups that are most likely to benefit. While CBMs show potential, their current use balances modest benefits against possible adverse effects and variable outcomes.<\/jats:p>","DOI":"10.3390\/biom15060816","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T08:51:04Z","timestamp":1749027064000},"page":"816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Are Cannabis-Based Medicines a Useful Treatment for Neuropathic Pain? A Systematic Review"],"prefix":"10.3390","volume":"15","author":[{"given":"Nawaf","family":"Almuntashiri","sequence":"first","affiliation":[{"name":"Clinical Toxicology Research Group, School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby DE22 3DT, UK"},{"name":"Forensic Toxicology Services Administration, Ministry of Health, P.O. Box 290, Makkah 25315, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2126-6185","authenticated-orcid":false,"given":"Basma M.","family":"El Sharazly","sequence":"additional","affiliation":[{"name":"Clinical Toxicology Research Group, School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby DE22 3DT, UK"},{"name":"Parasitology Department, Faculty of Medicine, Tanta University, Tanta 31111, Gharbia Governorate, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1475-2476","authenticated-orcid":false,"given":"Wayne G.","family":"Carter","sequence":"additional","affiliation":[{"name":"Clinical Toxicology Research Group, School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby DE22 3DT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1097\/j.pain.0000000000001939","article-title":"The revised International Association for the Study of Pain definition of pain: Concepts, challenges, and compromises","volume":"161","author":"Raja","year":"2020","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.neuron.2007.07.016","article-title":"Nociceptors-Noxious Stimulus Detectors","volume":"55","author":"Woolf","year":"2007","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.pain.2007.08.013","article-title":"Prevalence of chronic pain with neuropathic characteristics in the general population","volume":"136","author":"Bouhassira","year":"2008","journal-title":"Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/bja\/87.1.3","article-title":"Mechanisms of inflammatory pain","volume":"87","author":"Kidd","year":"2001","journal-title":"Br. J. Anaesth."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.pain.2013.11.013","article-title":"Neuropathic pain in the general population: A systematic review of epidemiological studies","volume":"155","author":"Austin","year":"2014","journal-title":"Pain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17002","DOI":"10.1038\/nrdp.2017.2","article-title":"Neuropathic pain","volume":"3","author":"Colloca","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/j.pain.0000000000001365","article-title":"The IASP classification of chronic pain for ICD-11, Chronic neuropathic pain","volume":"160","author":"Scholz","year":"2019","journal-title":"Pain"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cavalli, E., Mammana, S., Nicoletti, F., Bramanti, P., and Mazzon, E. (2019). The neuropathic pain: An overview of the current treatment and future therapeutic approaches. Int. J. Immunopathol. Pharmacol., 33.","DOI":"10.1177\/2058738419838383"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.pharep.2018.01.006","article-title":"The importance of chemokines in neuropathic pain development and opioid analgesic potency","volume":"70","author":"Kwiatkowski","year":"2018","journal-title":"Pharmacol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3390\/clinpract13010015","article-title":"The Diagnostic Odyssey of Patients with Chronic Neuropathic Pain\u2014Expert Opinion of Greek Pain Specialists","volume":"13","author":"Kritikou","year":"2023","journal-title":"Clin. Pr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1097\/j.pain.0000000000001122","article-title":"Inflammation in the pathophysiology of neuropathic pain","volume":"159","author":"Sommer","year":"2018","journal-title":"Pain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1124\/pr.117.014399","article-title":"Etiology and pharmacology of neuropathic pain","volume":"70","author":"Alles","year":"2018","journal-title":"Pharmacol. Rev."},{"key":"ref_13","unstructured":"Cohen, S.P., Vase, L., and Hooten, W.M. (2025, April 14). Chronic Pain 1 Chronic Pain: An Update on Burden, Best Practices, and New Advances. Available online: www.thelancet.com."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Obata, H. (2017). Analgesic mechanisms of antidepressants for neuropathic pain. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112483"},{"key":"ref_15","first-page":"CD005454","article-title":"Antidepressants for neuropathic pain","volume":"2007","author":"Saarto","year":"2007","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1097\/WCO.0000000000000980","article-title":"Advances in the treatment of neuropathic pain","volume":"34","author":"Attal","year":"2021","journal-title":"Curr. Opin. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.neurol.2020.01.361","article-title":"Pharmacological and non-pharmacological treatments for neuropathic pain: Systematic review and French recommendations","volume":"176","author":"Moisset","year":"2020","journal-title":"Rev. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.neuroscience.2016.06.057","article-title":"Antidepressants and gabapentinoids in neuropathic pain: Mechanistic insights","volume":"338","author":"Kremer","year":"2016","journal-title":"Neuroscience"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1177\/1756285613501576","article-title":"Capsaicinoids in the treatment of neuropathic pain: A review","volume":"7","author":"Peppin","year":"2014","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S2-12","DOI":"10.1093\/pm\/pnz075","article-title":"A Comprehensive Algorithm for Management of Neuropathic Pain","volume":"20","author":"Bates","year":"2019","journal-title":"Pain Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(14)70251-0","article-title":"Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis","volume":"14","author":"Finnerup","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_22","first-page":"CD010902","article-title":"Oral nonsteroidal anti-inflammatory drugs for neuropathic pain","volume":"2017","author":"Moore","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.pain.2009.03.013","article-title":"Non-steroidal anti-inflammatory drugs for neuropathic pain: How do we explain continued widespread use?","volume":"143","author":"Vo","year":"2009","journal-title":"Pain"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Petroianu, G.A., Aloum, L., and Adem, A. (2023). Neuropathic pain: Mechanisms and therapeutic strategies. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1072629"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Vu\u010dkovic, S., Srebro, D., Vujovic, K.S., Vu\u010detic, \u010c., and Prostran, M. (2018). Cannabinoids and pain: New insights from old molecules. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01259"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11916-020-00873-9","article-title":"The Role of the Cannabinoid System in Pain Control: Basic and Clinical Implications","volume":"24","author":"Wolf","year":"2020","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.aat.2013.10.004","article-title":"Targeting the cannabinoid system for pain relief?","volume":"51","author":"Chiou","year":"2013","journal-title":"Acta Anaesthesiol. Taiwanica"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Xu, K., Wu, Y., Tian, Z., Xu, Y., Wu, C., and Wang, Z. (2023). Microglial Cannabinoid CB2 Receptors in Pain Modulation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032348"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/sj.bjp.0707442","article-title":"The diverse CB 1 and CB 2 receptor pharmacology of three plant cannabinoids: \u0394 9-tetrahydrocannabinol, cannabidiol and \u0394 9-tetrahydrocannabivarin","volume":"153","author":"Pertwee","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1021\/cn5000524","article-title":"Nonpsychotropic plant cannabinoids, Cannabidivarin (CBDV) and Cannabidiol (CBD), activate and desensitize Transient Receptor Potential Vanilloid 1 (TRPV1) channels in vitro: Potential for the treatment of neuronal hyperexcitability","volume":"5","author":"Iannotti","year":"2014","journal-title":"ACS Chem. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, X., Lin, C., Wu, S., Zhang, T., Wang, Y., Jiang, Y., and Wang, X. (2022). Cannabidivarin alleviates neuroinflammation by targeting TLR4 co-receptor MD2 and improves morphine-mediated analgesia. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.929222"},{"key":"ref_32","first-page":"142","article-title":"Cannabis and pain: A scoping review","volume":"72","author":"Rosselli","year":"2022","journal-title":"Braz. J. Anesthesiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s11916-018-0658-8","article-title":"Medical Cannabis for Neuropathic Pain","volume":"22","author":"Lee","year":"2018","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_34","first-page":"CD012182","article-title":"Cannabis-based medicines for chronic neuropathic pain in adults","volume":"2018","author":"Phillips","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1136\/bmj.b2535","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"339","author":"Moher","year":"2009","journal-title":"BMJ"},{"key":"ref_36","unstructured":"Huang, X., Lin, J., and Demner-Fushman, D. (2025, March 13). Evaluation of PICO as a Knowledge Representation for Clinical Questions. Available online: http:\/\/www.fpin.org\/."},{"key":"ref_37","unstructured":"Karst, M., Salim, K., Burstein, S., Conrad, I., Hoy, L., and Schneider, U. (2025, April 14). Analgesic Effect of the Synthetic Cannabinoid CT-3 on Chronic Neuropathic Pain A Randomized Controlled Trial [Internet]. Available online: https:\/\/jamanetwork.com\/journals\/jama\/fullarticle\/197396."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.pain.2004.09.013","article-title":"Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: Results of a randomised controlled trial","volume":"112","author":"Berman","year":"2004","journal-title":"Pain"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1136\/bmj.38149.566979.AE","article-title":"Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial","volume":"329","author":"Svendsen","year":"2004","journal-title":"BMJ"},{"key":"ref_40","unstructured":"Rog, D.J., Nurmikko, T.J., Friede, T., and Young, C.A. (2025, March 13). Randomized, Controlled Trial of Cannabis-Based Medicine in Central Pain in Multiple Sclerosis. Available online: www.neurology.org."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.pain.2007.08.028","article-title":"Sativex successfully treats neuropathic pain characterised by allodynia: A randomised, double-blind, placebo-controlled clinical trial","volume":"133","author":"Nurmikko","year":"2007","journal-title":"Pain"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1212\/01.wnl.0000253187.66183.9c","article-title":"Cannabis in painful HIV-associated sensory neuropathy A randomized placebo-controlled trial","volume":"68","author":"Abrams","year":"2007","journal-title":"Neurology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.jpain.2007.12.010","article-title":"A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain","volume":"9","author":"Wilsey","year":"2008","journal-title":"J. Pain"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/npp.2008.120","article-title":"Smoked medicinal cannabis for neuropathic pain in HIV: A randomized, crossover clinical trial","volume":"34","author":"Ellis","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"128","DOI":"10.2337\/dc09-1029","article-title":"Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: Depression is a major confounding factor","volume":"33","author":"Selvarajah","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"E694","DOI":"10.1503\/cmaj.091414","article-title":"Smoked cannabis for chronic neuropathic pain: A randomized controlled trial","volume":"182","author":"Ware","year":"2010","journal-title":"CMAJ. Can. Med. Assoc. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jpain.2012.10.009","article-title":"Low-dose vaporized cannabis significantly improves neuropathic pain","volume":"14","author":"Wilsey","year":"2013","journal-title":"J. Pain"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jpainsymman.2013.02.018","article-title":"A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain","volume":"47","author":"Lynch","year":"2014","journal-title":"J. Pain Symptom Manag."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.jpain.2015.03.008","article-title":"Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy","volume":"16","author":"Wallace","year":"2015","journal-title":"J. Pain"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"587","DOI":"10.2147\/JPR.S113138","article-title":"A preliminary evaluation of the relationship of cannabinoid blood concentrations with the analgesic response to vaporized cannabis","volume":"9","author":"Wilsey","year":"2016","journal-title":"J. Pain Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"E1285-94","DOI":"10.1212\/WNL.0000000000006293","article-title":"Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity","volume":"91","author":"Weizman","year":"2018","journal-title":"Neurology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"390","DOI":"10.2174\/1389201020666191202111534","article-title":"The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities","volume":"21","author":"Xu","year":"2019","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1002\/cpt.2016","article-title":"Cannabidivarin for HIV-Associated Neuropathic Pain: A Randomized, Blinded, Controlled Clinical Trial","volume":"109","author":"Eibach","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hansen, J.S., Hansen, R.M., Petersen, T., Gustavsen, S., Oturai, A.B., Sellebjerg, F., S\u00e6dder, E.A., Kasch, H., Rasmussen, P.V., and Finnerup, N.B. (2021). The effect of cannabis-based medicine on neuropathic pain and spasticity in patients with multiple sclerosis and spinal cord injury: Study protocol of a national multicenter double-blinded, placebo-controlled trial. Brain Sci., 11.","DOI":"10.3390\/brainsci11091212"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Hansen, J.S., Gustavsen, S., Roshanisefat, H., Kant, M., Biering-S\u00f8rensen, F., Andersen, C., Olsson, A., Chow, H.H., Asgari, N., and Hansen, J.R. (2023). Cannabis-Based Medicine for Neuropathic Pain and Spasticity\u2014A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial. Pharmaceuticals, 16.","DOI":"10.3390\/ph16081079"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/ejp.2072","article-title":"Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment","volume":"27","author":"Zubcevic","year":"2023","journal-title":"Eur. J. Pain"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s40263-024-01085-0","article-title":"Oral Delta-9-Tetrahydrocannabinol (THC) Increases Parasympathetic Activity and Supraspinal Conditioned Pain Modulation in Chronic Neuropathic Pain Male Patients: A Crossover, Double-Blind, Placebo-Controlled Trial","volume":"38","author":"Weizman","year":"2024","journal-title":"CNS Drugs"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e1556","DOI":"10.1089\/can.2023.0253","article-title":"Topical Cannabidiol for Established Chemotherapy-Induced Neuropathy: A Pilot Randomized Placebo-Controlled Trial","volume":"9","author":"Novotny","year":"2024","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1097\/CORR.0000000000003221","article-title":"Does Cannabis-based Medicine Improve Pain and Sleep Quality in Patients With Traumatic Brachial Plexus Injuries? A Triple-blind, Crossover, Randomized Controlled Trial","volume":"483","author":"Kittithamvongs","year":"2024","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/S0140-6736(15)60742-5","article-title":"The history and fate of the gold standard","volume":"385","author":"Jones","year":"2015","journal-title":"Lancet"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.jpain.2007.10.018","article-title":"Efficacy of Dronabinol as an Adjuvant Treatment for Chronic Pain Patients on Opioid Therapy","volume":"9","author":"Narang","year":"2008","journal-title":"J. Pain"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2165\/00003088-200342040-00003","article-title":"Pharmacokinetics and Pharmacodynamics of Cannabinoids","volume":"42","author":"Grotenhermen","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/FTD.0b013e3182a5c446","article-title":"Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence","volume":"36","author":"Milman","year":"2014","journal-title":"Ther. Drug Monit."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1002\/cbdv.200790152","article-title":"Human cannabinoid pharmacokinetics","volume":"4","author":"Huestis","year":"2007","journal-title":"Chem. Biodivers."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1111\/bcp.13710","article-title":"The pharmacokinetics and the pharmacodynamics of cannabinoids","volume":"84","author":"Lucas","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1373\/clinchem.2010.152439","article-title":"Plasma cannabinoid pharmacokinetics following controlled oral \u0394 9-tetrahydrocannabinol and oromucosal cannabis extract administration","volume":"57","author":"Karschner","year":"2011","journal-title":"Clin. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1192\/bjp.178.2.101","article-title":"Pharmacology and effects of cannabis: A brief review","volume":"178","author":"Ashton","year":"2001","journal-title":"Br. J. Psychiatry"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Baglot, S.L., Hume, C., Petrie, G.N., Aukema, R.J., Lightfoot, S.H.M., Grace, L.M., Zhou, R., Parker, L., Rho, J.M., and Borgland, S.L. (2021). Pharmacokinetics and central accumulation of delta-9-tetrahydrocannabinol (THC) and its bioactive metabolites are influenced by route of administration and sex in rats. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-03242-7"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1300\/J175v03n04_02","article-title":"A phase I, double blind, three-way crossover study to assess the pharmacokinetic profile of Cannabis Based Medicine Extract (CBME) administered sublingually in variant cannabinoid ratios in normal healthy male volunteers (GWPK0215)","volume":"3","author":"Guy","year":"2003","journal-title":"J. Cannabis Ther."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Scheidweiler, K., Russo, E.B., Henderson-Redmond, A., Kessler, C.S., and M\u00fcller-Vahl, K.R. (2022). Implications for blinding in clinical trials with THC-containing cannabinoids based on the CANNA-TICS trial. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.793703"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Farrar, J.T., Young, J.P.B., Lamoreaux, L., Werth, J.L., and Poole, R.M. (2025, March 13). Clinical Importance of Changes in Chronic Pain Intensity Measured on an 11-Point Numerical Pain Rating Scale. Available online: https:\/\/journals.lww.com\/pain\/abstract\/2001\/11000\/clinical_importance_of_changes_in_chronic_pain.6.aspx.","DOI":"10.1016\/S0304-3959(01)00349-9"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s40122-017-0087-0","article-title":"A review of Neuropathic Pain: From Guidelines to Clinical Practice","volume":"6","author":"Cruccu","year":"2017","journal-title":"Pain Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.mayocp.2016.01.017","article-title":"Central Neuropathic Pain Syndromes","volume":"91","author":"Watson","year":"2016","journal-title":"Mayo Clin. Proc."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Doneddu, P.E., Pensato, U., Iorfida, A., Alberti, C., Nobile-Orazio, E., Fabbri, A., and Voza, A. (2023). Neuropathic Pain in the Emergency Setting: Diagnosis and Management. J. Clin. Med., 12.","DOI":"10.3390\/jcm12186028"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/sj.bjp.0705920","article-title":"Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation","volume":"143","author":"Costa","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_77","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_78","doi-asserted-by":"crossref","unstructured":"IASP (2021). International Association for the Study of Pain Presidential Task Force on Cannabis and Cannabinoid Analgesia position statement. Pain, 162, S1\u2013S2.","DOI":"10.1097\/j.pain.0000000000002265"},{"key":"ref_79","unstructured":"FDA (2025, March 13). FDA and Cannabis: Research and Drug Approval Process, Available online: https:\/\/www.fda.gov\/news-events\/public-health-focus\/fda-and-cannabis-research-and-drug-approval-process."},{"key":"ref_80","unstructured":"Home Office (2025, March 13). Rescheduling of Cannabis-Based Products for Medicinal Use in Humans (Accessible Version), Available online: http:\/\/www.legislation.gov.uk\/uksi\/2018\/1055\/contents\/made."},{"key":"ref_81","unstructured":"NICE, and NG144 (2025, March 13). Cannabis-Based Medicinal Products NICE Guideline. Available online: www.nice.org.uk\/guidance\/ng144."},{"key":"ref_82","unstructured":"British Pain Society (2025). Position Statement on the Medicinal Use of Cannabinoids in Pain Management, John Wiley and Sons Ltd.. Available online: https:\/\/www.britishpainsociety.org."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/6\/816\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:46:34Z","timestamp":1760031994000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/6\/816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,4]]},"references-count":82,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["biom15060816"],"URL":"https:\/\/doi.org\/10.3390\/biom15060816","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,4]]}}}