{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:31:49Z","timestamp":1790188309618,"version":"4.1.0"},"reference-count":100,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2012,5,21]],"date-time":"2012-05-21T00:00:00Z","timestamp":1337558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients. A systematic search was performed in the electronic databases PubMed and EMBASE using the key word \u201ccannabidiol\u201d. Both monotherapy and combination studies (e.g., CBD + \u22069-THC) were included. A total of 34 studies were identified: 16 of these were experimental studies, conducted in healthy subjects, and 18 were conducted in clinical populations, including multiple sclerosis (six studies), schizophrenia and bipolar mania (four studies), social anxiety disorder (two studies), neuropathic and cancer pain (two studies), cancer anorexia (one study), Huntington\u2019s disease (one study), insomnia (one study), and epilepsy (one study). Experimental studies indicate that a high-dose of inhaled\/intravenous CBD is required to inhibit the effects of a lower dose of \u22069-THC. Moreover, some experimental and clinical studies suggest that oral\/oromucosal CBD may prolong and\/or intensify \u22069-THC-induced effects, whereas others suggest that it may inhibit \u22069-THC-induced effects. Finally, preliminary clinical trials suggest that high-dose oral CBD (150\u2013600 mg\/d) may exert a therapeutic effect for social anxiety disorder, insomnia and epilepsy, but also that it may cause mental sedation. Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed.<\/jats:p>","DOI":"10.3390\/ph5050529","type":"journal-article","created":{"date-parts":[[2012,5,21]],"date-time":"2012-05-21T11:24:56Z","timestamp":1337599496000},"page":"529-552","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":163,"title":["Cannabidiol in Humans\u2014The Quest for Therapeutic Targets"],"prefix":"10.3390","volume":"5","author":[{"given":"Simon","family":"Zhornitsky","sequence":"first","affiliation":[{"name":"Multiple Sclerosis Clinic, Foothills Medical Centre, Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Potvin","sequence":"additional","affiliation":[{"name":"Fernand-Seguin Research Centre, Department of Psychiatry, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec H1N 3V2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2012,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1590\/S1516-44462006000200015","article-title":"History of cannabis as a medicine: A review","volume":"28","author":"Zuardi","year":"2006","journal-title":"Rev. Bras. Psiquiatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.lfs.2005.09.011","article-title":"Chemical constituents of marijuana: The complex mixture of natural cannabinoids","volume":"78","author":"Elsohly","year":"2005","journal-title":"Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0301-0082(98)00087-2","article-title":"The effects of cannabinoids on the brain","volume":"58","author":"Ameri","year":"1999","journal-title":"Prog. Neurobiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.3390\/ph3103101","article-title":"Endocannabinoids and schizophrenia","volume":"3","author":"Desfosses","year":"2010","journal-title":"Pharmaceuticals"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1124\/jpet.109.159145","article-title":"Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo","volume":"332","author":"Jones","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3109\/15622970801908047","article-title":"Potential antipsychotic properties of central cannabinoid (CB1) receptor antagonists","volume":"11","author":"Roser","year":"2010","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.freeradbiomed.2011.01.007","article-title":"Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress","volume":"51","author":"Booz","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s00213-010-2157-4","article-title":"Interaction between non-psychotropic cannabinoids in marihuana: Effect of cannabigerol (CBG) on the anti-nausea or anti-emetic effects of cannabidiol (CBD) in rats and shrews","volume":"215","author":"Rock","year":"2011","journal-title":"Psychopharmacology (Berl.)"},{"key":"ref_9","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: delta9-Tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin","volume":"153","author":"Pertwee","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1185\/030079906X158066","article-title":"Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain","volume":"23","author":"Iskedjian","year":"2007","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1590\/S1516-44462008000300015","article-title":"Cannabidiol: From an inactive cannabinoid to a drug with wide spectrum of action","volume":"30","author":"Zuardi","year":"2008","journal-title":"Rev. Bras. Psiquiatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1755-5949.2008.00065.x","article-title":"Cannabidiol: A promising drug for neurodegenerative disorders?","volume":"15","author":"Iuvone","year":"2009","journal-title":"CNS Neurosci. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0031-6997(25)06861-9","article-title":"Pharmacokinetics and metabolism of delta 1-tetrahydrocannabinol and other cannabinoids with emphasis on man","volume":"38","author":"Agurell","year":"1986","journal-title":"Pharmacol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3109\/00498259009046849","article-title":"Metabolites of cannabidiol identified in human urine","volume":"20","author":"Harvey","year":"1990","journal-title":"Xenobiotica"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/0091-3057(91)90386-G","article-title":"Controlled clinical trial of cannabidiol in Huntington\u2019s disease","volume":"40","author":"Consroe","year":"1991","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/bms.1200130206","article-title":"Single-dose kinetics of deuterium-labelled cannabidiol in man after smoking and intravenous administration","volume":"13","author":"Ohlsson","year":"1986","journal-title":"Biomed. Environ. Mass Spectrom."},{"key":"ref_17","unstructured":"Guy, G.W., Whittle, B.A., and Robson, P. (2004). The Medicinal Uses of Cannabis and Cannabinoids, TJ International."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1097\/01.ftd.0000177223.19294.5c","article-title":"Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of delta-9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract","volume":"27","author":"Nadulski","year":"2005","journal-title":"Ther. Drug Monit."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1093\/jat\/29.8.782","article-title":"Simultaneous and sensitive analysis of THC, 11-OH-THC, THC-COOH, CBD, and CBN by GC-MS in plasma after oral application of small doses of THC and cannabis extract","volume":"29","author":"Nadulski","year":"2005","journal-title":"J. Anal. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1016\/j.bcp.2010.01.028","article-title":"Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes","volume":"79","author":"Yamaori","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.lfs.2011.02.017","article-title":"Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: Role of phenolic hydroxyl groups in the resorcinol moiety","volume":"88","author":"Yamaori","year":"2011","journal-title":"Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1124\/dmd.111.041384","article-title":"Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6","volume":"39","author":"Yamaori","year":"2011","journal-title":"Drug Metab. Dispos."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yamaori, S., Koeda, K., Kushihara, M., Hada, Y., Yamamoto, I., and Watanabe, K. (2011). Comparison in the in vitro inhibitory effects of major phytocannabinoids and polycyclic aromatic hydrocarbons contained in marijuana smoke on cytochrome P450 2C9 activity. Drug Metab. Pharmacokinet.","DOI":"10.2133\/dmpk.DMPK-11-RG-107"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/BF01059266","article-title":"Evidence that cannabidiol does not significantly alter the pharmacokinetics of tetrahydrocannabinol in man","volume":"9","author":"Hunt","year":"1981","journal-title":"J. Pharmacokinet. Biopharm."},{"key":"ref_25","first-page":"231","article-title":"Anticonvulsant properties of cannabidiol","volume":"8","author":"Turkanis","year":"1974","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/S0022-3565(25)30824-4","article-title":"Cannabidiol-antiepileptic drug comparisons and interactions in experimentally induced seizures in rats","volume":"201","author":"Consroe","year":"1977","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1038\/sj.bjp.0707460","article-title":"The orphan receptor GPR55 is a novel cannabinoid receptor","volume":"152","author":"Ryberg","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14136","DOI":"10.1073\/pnas.96.24.14136","article-title":"Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors","volume":"96","author":"Wagner","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s11064-005-6978-1","article-title":"Agonistic properties of cannabidiol at 5-HT1a receptors","volume":"30","author":"Russo","year":"2005","journal-title":"Neurochem. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0014-2999(02)02624-9","article-title":"(\u2212)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens","volume":"456","author":"Pertwee","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/sj.bjp.0704327","article-title":"Molecular targets for cannabidiol and its synthetic analogues: Effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide","volume":"134","author":"Bisogno","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"16124","DOI":"10.1074\/jbc.M707104200","article-title":"Inhibition of recombinant human T-type calcium channels by Delta9-tetrahydrocannabinol and cannabidiol","volume":"283","author":"Ross","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1159\/000201556","article-title":"The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-beta glycine receptor function","volume":"83","author":"Ahrens","year":"2009","journal-title":"Pharmacology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/S0024-3205(98)00052-6","article-title":"Distribution and characterization of anandamide amidohydrolase in mouse brain and liver","volume":"62","author":"Watanabe","year":"1998","journal-title":"Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1111\/j.1471-4159.2007.05073.x","article-title":"5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid","volume":"104","author":"Massi","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s11481-009-9177-z","article-title":"Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: Focus on G-protein-coupled receptors and transient receptor potential channels","volume":"5","year":"2010","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/BF01946311","article-title":"Cannabidiol and cannabinol in man","volume":"29","author":"Hollister","year":"1973","journal-title":"Experientia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/BF00431988","article-title":"Interaction of cannabidiol and alcohol in humans","volume":"66","author":"Consroe","year":"1979","journal-title":"Psychopharmacology (Berl.)"},{"key":"ref_40","first-page":"213","article-title":"Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human volunteers","volume":"26","author":"Zuardi","year":"1993","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1177\/026988119300700112","article-title":"Effects of ipsapirone and cannabidiol on human experimental anxiety","volume":"7","author":"Zuardi","year":"1993","journal-title":"J. Psychopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/sj.npp.1300340","article-title":"Effects of cannabidiol (CBD) on regional cerebral blood flow","volume":"29","author":"Crippa","year":"2004","journal-title":"Neuropsychopharmacology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.biopsych.2008.05.011","article-title":"Neural basis of delta-9-tetrahydrocannabinol and cannabidiol: Effects during response inhibition","volume":"64","author":"Borgwardt","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1038\/npp.2011.17","article-title":"Modulation of auditory and visual processing by delta-9-tetrahydrocannabinol and cannabidiol: An FMRI study","volume":"36","author":"Allen","year":"2011","journal-title":"Neuropsychopharmacology."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1001\/archgenpsychiatry.2008.519","article-title":"Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing","volume":"66","author":"Crippa","year":"2009","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1017\/S1461145709990617","article-title":"Modulation of effective connectivity during emotional processing by delta-9-tetrahydrocannabinol and cannabidiol","volume":"13","author":"Allen","year":"2010","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.pnpbp.2010.11.002","article-title":"The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects","volume":"35","author":"Hallak","year":"2011","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0091-3057(00)00201-X","article-title":"Different effects of nabilone and cannabidiol on binocular depth inversion in man","volume":"66","author":"Leweke","year":"2000","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/0014-2999(74)90129-0","article-title":"Cannabidiol interferes with the effects of delta 9-tetrahydrocannabinol in man","volume":"28","author":"Karniol","year":"1974","journal-title":"Eur. J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/cpt197518180","article-title":"Interactions in man of delta-9-tetrahydrocannabinol. II. Cannabinol and cannabidiol","volume":"18","author":"Hollister","year":"1975","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/BF00432554","article-title":"Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects","volume":"76","author":"Zuardi","year":"1982","journal-title":"Psychopharmacology (Berl.)"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.schres.2007.08.015","article-title":"Acute effects of Delta9-tetrahydrocannabinol and standardized cannabis extract on the auditory evoked mismatch negativity","volume":"97","author":"Juckel","year":"2007","journal-title":"Schizophr. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.euroneuro.2008.04.008","article-title":"Effects of acute oral delta-9-tetrahydrocannabinol and standardized cannabis extract on the auditory P300 event-related potential in healthy volunteers","volume":"18","author":"Roser","year":"2008","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s00406-009-0868-5","article-title":"Psychomotor performance in relation to acute oral administration of delta-9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects","volume":"259","author":"Roser","year":"2009","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/01.jcp.0000125688.05091.8f","article-title":"Effect of delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults","volume":"24","author":"Nicholson","year":"2004","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/cpt1976193300","article-title":"Influence of cannabidiol on delta-9-tetrahydrocannabinol effects","volume":"19","author":"Dalton","year":"1976","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/00008877-200509000-00023","article-title":"Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids","volume":"16","author":"Ilan","year":"2005","journal-title":"Behav. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/npp.2009.184","article-title":"Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology","volume":"35","author":"Bhattacharyya","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"ref_59","first-page":"315","article-title":"Possvel efeito hipnotico do cannabidiol no ser humano. Estudo preliminar","volume":"31","author":"Carlini","year":"1979","journal-title":"Cienc. Cult."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"417S","DOI":"10.1002\/j.1552-4604.1981.tb02622.x","article-title":"Hypnotic and antiepileptic effects of cannabidiol","volume":"21","author":"Carlini","year":"1981","journal-title":"J. Clin. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1159\/000137430","article-title":"Chronic administration of cannabidiol to healthy volunteers and epileptic patients","volume":"21","author":"Cunha","year":"1980","journal-title":"Pharmacology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1177\/0269881110379283","article-title":"Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report","volume":"25","author":"Crippa","year":"2011","journal-title":"J. Psychopharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/npp.2011.6","article-title":"Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients","volume":"36","author":"Bergamaschi","year":"2011","journal-title":"Neuropsychopharmacology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"S207","DOI":"10.1016\/S0924-9338(09)70440-7","article-title":"S39-02 Antipsychotic effects of cannabidiol","volume":"24","author":"Leweke","year":"2009","journal-title":"Eur. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1177\/0269881106060967","article-title":"Cannabidiol monotherapy for treatment-resistant schizophrenia","volume":"20","author":"Zuardi","year":"2006","journal-title":"J. Psychopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1177\/0269881108096521","article-title":"Cannabidiol was ineffective for manic episode of bipolar affective disorder","volume":"24","author":"Zuardi","year":"2010","journal-title":"J. Psychopharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1590\/S1516-44462010000100011","article-title":"Performance of schizophrenic patients in the Stroop Color Word Test and electrodermal responsiveness after acute administration of cannabidiol (CBD)","volume":"32","author":"Hallak","year":"2010","journal-title":"Rev. Bras. Psiquiatr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1212\/WNL.58.9.1404","article-title":"Safety, tolerability, and efficacy of orally administered cannabinoids in MS","volume":"58","author":"Killestein","year":"2002","journal-title":"Neurology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/S0165-5728(03)00045-6","article-title":"Immunomodulatory effects of orally administered cannabinoids in multiple sclerosis","volume":"137","author":"Killestein","year":"2003","journal-title":"J. Neuroimmunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/S0140-6736(03)14738-1","article-title":"Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): Multicentre randomised placebo-controlled trial","volume":"362","author":"Zajicek","year":"2003","journal-title":"Lancet"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1007\/s00192-006-0086-x","article-title":"The effect of cannabis on urge incontinence in patients with multiple sclerosis: A multicentre, randomised placebo-controlled trial (CAMS-LUTS)","volume":"17","author":"Freeman","year":"2006","journal-title":"Int. Urogynecol. J. Pelvic Floor Dysfunct."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1200\/JCO.2005.05.1847","article-title":"Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: A multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group","volume":"24","author":"Strasser","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_73","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 Manage."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1191\/1352458504ms1063oa","article-title":"An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis","volume":"10","author":"Brady","year":"2004","journal-title":"Mult. Scler."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1191\/0269215503cr581oa","article-title":"A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms","volume":"17","author":"Wade","year":"2003","journal-title":"Clin. Rehabil."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1365-2044.2004.03674.x","article-title":"Initial experiences with medicinal extracts of cannabis for chronic pain: Results from 34 'N of 1' studies","volume":"59","author":"Notcutt","year":"2004","journal-title":"Anaesthesia"},{"key":"ref_77","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_78","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00213-010-2036-z","article-title":"The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors","volume":"213","author":"Gomes","year":"2011","journal-title":"Psychopharmacology (Berl.)"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1177\/0269881110389095","article-title":"Cannabidiol injected into the bed nucleus of the stria terminalis reduces the expression of contextual fear conditioning via 5-HT1A receptors","volume":"26","author":"Gomes","year":"2012","journal-title":"J. Psychopharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.bbr.2010.05.004","article-title":"Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors","volume":"213","author":"Campos","year":"2010","journal-title":"Behav. Brain Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.1476-5381.2008.00046.x","article-title":"5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats","volume":"156","author":"Resstel","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/j.pnpbp.2009.08.017","article-title":"Evidence for a potential role for TRPV1 receptors in the dorsolateral periaqueductal gray in the attenuation of the anxiolytic effects of cannabinoids","volume":"33","author":"Campos","year":"2009","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_83","first-page":"113","article-title":"Effects of the cannabinoid receptor ligands on anxiety-related effects of d-amphetamine and nicotine in the mouse elevated plus maze test","volume":"60","author":"Biala","year":"2009","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.euroneuro.2008.07.001","article-title":"Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats","volume":"18","author":"Bitencourt","year":"2008","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1527-3458.2006.00021.x","article-title":"Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597)","volume":"12","author":"Piomelli","year":"2006","journal-title":"CNS Drug Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.neuropharm.2007.08.011","article-title":"The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition","volume":"54","author":"Scherma","year":"2008","journal-title":"Neuropharmacology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pbb.2010.12.002","article-title":"Inhibition of endocannabinoid catabolic enzymes elicits anxiolytic-like effects in the marble burying assay","volume":"98","author":"Kinsey","year":"2011","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/BF00421553","article-title":"Effect of cannabinoids on the abdominal constriction response in mice: Within cannabinoid interactions","volume":"46","author":"Welburn","year":"1976","journal-title":"Psychopharmacologia"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1111\/j.1476-5381.1973.tb08534.x","article-title":"The effect of cannabinoids on intestinal motility and their antinociceptive effect in mice","volume":"49","author":"Chesher","year":"1973","journal-title":"Br. J. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"9561","DOI":"10.1073\/pnas.160105897","article-title":"The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis","volume":"97","author":"Malfait","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1002\/art.20050","article-title":"A novel synthetic, non-psychoactive cannabinoid acid (HU-320) with anti-inflammatory properties in murine collagen-induced arthritis","volume":"50","author":"Sumariwalla","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.neulet.2011.06.004","article-title":"The abnormal cannabidiol analogue O-1602 reduces nociception in a rat model of acute arthritis via the putative cannabinoid receptor GPR55","volume":"500","author":"Schuelert","year":"2011","journal-title":"Neurosci. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0014-2999(01)01243-2","article-title":"Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects","volume":"428","author":"Wallace","year":"2001","journal-title":"Eur. J. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1176\/appi.ajp.161.6.975","article-title":"Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder","volume":"161","author":"Meltzer","year":"2004","journal-title":"Am. J. Psychiatry."},{"key":"ref_95","first-page":"386","article-title":"Pharmacological interaction between 9-tetrahydrocannabinol and cannabidiol, two active constituents of Cannabis sativa","volume":"36","author":"Zuardi","year":"1984","journal-title":"Ci\u00eanc. Cult."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00213-011-2495-x","article-title":"Interaction between cannabidiol (CBD) and \u0394(9)-tetrahydrocannabinol (THC): Influence of administration interval and dose ratio between the cannabinoids","volume":"219","author":"Zuardi","year":"2012","journal-title":"Psychopharmacology (Berl.)"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s00213-011-2342-0","article-title":"Cannabidiol potentiates \u03949-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats","volume":"218","author":"Klein","year":"2011","journal-title":"Psychopharmacology (Berl.)"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1300\/J175v03n03_03","article-title":"A single centre, placebo-controlled, four period, crossover, tolerability study assessing, pharmacodynamic effects, pharmacokinetic characteristics and cognitive profiles of a single dose of three formulations of Cannabis Based Medicine Extracts (CBMEs) (GWPD9901), plus a two period tolerability study comparing pharmacodynamic effects and pharmacokinetic characteristics of a single dose of a cannabis based medicine extract given via two administration routes (GWPD9901 EXT)","volume":"3","author":"Guy","year":"2004","journal-title":"J. Cannabis Ther."},{"key":"ref_99","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 (GWPK02125)","volume":"3","author":"Guy","year":"2003","journal-title":"J. Cannabis Ther."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pbb.2010.12.002","article-title":"Inhibition of endocannabinoid catabolic enzymes elicits anxiolytic-like effects in the marble burying assay","volume":"98","author":"Kinsey","year":"2011","journal-title":"Pharmacol. Biochem. Behav."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/5\/5\/529\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:50:23Z","timestamp":1760219423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/5\/5\/529"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,21]]},"references-count":100,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2012,5]]}},"alternative-id":["ph5050529"],"URL":"https:\/\/doi.org\/10.3390\/ph5050529","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,21]]}}}