Abstract
Cannabis use for cancer symptom management is increasing and is becoming part of polypharmacy that patients with advanced cancer are often subjected to. Drug-drug interactions depend in part on the schedule of administration, absorption, method of administration, the capacity of either the drug and cannabinoids to inhibit CYP enzymes (inhibitory constant) or the ability to upregulate CYP enzymes. Phytocannabinoids and endocannabinoids are both metabolized by CYP450 enzymes, though endocannabinoids also have their own specific metabolic pathways. In general, endocannabinoids influence responses to various drug classes such as antiseizure medications, antidepressants, and opioids. Both tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations in blood are dependent on dose, diet(fat), route of administration, vehicle, and disease state. The more important cannabis-induced drug interactions are largely inhibitory in nature and encountered through the CYP2C family. Other drug interactions via immunomodulatory mechanisms have been shown to reduce efficacy of check-point inhibitors and are a reminder that cannabis use should be closely monitored in cancer patients.
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References
Drug interactions with cannabis. Prescrire Int. 2011;20(115):100.
Adamczyk P, Golda A, McCreary AC, Filip M, Przegalinski E. Activation of endocannabinoid transmission induces antidepressant-like effects in rats. J Physiol Pharmacol. 2008;59(2):217–28.
Agurell S, Halldin M, Lindgren JE, Ohlsson A, Widman M, Gillespie H, Hollister L. Pharmacokinetics and metabolism of delta 1-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacol Rev. 1986;38(1):21–43.
Al Saabi A, Allorge D, Sauvage FL, Tournel G, Gaulier JM, Marquet P, Picard N. Involvement of UDP-glucuronosyltransferases UGT1A9 and UGT2B7 in ethanol glucuronidation, and interactions with common drugs of abuse. Drug Metab Dispos. 2013;41(3):568–74.
Alhouayek M, Muccioli GG. COX-2-derived endocannabinoid metabolites as novel inflammatory mediators. Trends Pharmacol Sci. 2014;35(6):284–92.
Allen KV, McGregor IS, Hunt GE, Singh ME, Mallet PE. Regional differences in naloxone modulation of Delta(9)-THC induced Fos expression in rat brain. Neuropharmacology. 2003;44(2):264–74.
Alonso R, Voutsinos B, Fournier M, Labie C, Steinberg R, Souilhac J, Le Fur G, Soubrie P. Blockade of cannabinoid receptors by SR141716 selectively increases Fos expression in rat mesocorticolimbic areas via reduced dopamine D2 function. Neuroscience. 1999;91(2):607–20.
Alvheim AR, Malde MK, Osei-Hyiaman D, Lin YH, Pawlosky RJ, Madsen L, Kristiansen K, Froyland L, Hibbeln JR. Dietary linoleic acid elevates endogenous 2-AG and anandamide and induces obesity. Obesity (Silver Spring). 2012;20(10):1984–94.
Anderson GD, Chan LN. Pharmacokinetic drug interactions with tobacco, cannabinoids and smoking cessation products. Clin Pharmacokinet. 2016;55(11):1353–68.
Andrianova EL, Genrikhs EE, Bobrov MY, Lizhin AA, Gretskaya NM, Frumkina LE, Khaspekov LG, Bezuglov VV. In vitro effects of anandamide and prostamide e2 on normal and transformed nerve cells. Bull Exp Biol Med. 2011;151(1):30–2.
Anzenbacher P, Anzenbacherova E. Cytochromes P450 and metabolism of xenobiotics. Cell Mol Life Sci. 2001;58(5–6):737–47.
Apaya MK, Hsiao PW, Yang YC, Shyur LF. Deregulating the CYP2C19/epoxy-Eicosatrienoic acid-associated FABP4/FABP5 Signaling network as a therapeutic approach for metastatic triple-negative breast cancer. Cancers (Basel). 2020;12(1):199.
Arnold JC, Boucher AA, Karl T. The yin and yang of cannabis-induced psychosis: the actions of Delta(9)-tetrahydrocannabinol and cannabidiol in rodent models of schizophrenia. Curr Pharm Des. 2012a;18(32):5113–30.
Arnold JC, Hone P, Holland ML, Allen JD. CB2 and TRPV1 receptors mediate cannabinoid actions on MDR1 expression in multidrug resistant cells. Pharmacol Rep. 2012b;64(3):751–7.
Aso E, Ozaita A, Valdizan EM, Ledent C, Pazos A, Maldonado R, Valverde O. BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice. J Neurochem. 2008;105(2):565–72.
Atone J, Wagner K, Hashimoto K, Hammock BD. Cytochrome P450 derived epoxidized fatty acids as a therapeutic tool against neuroinflammatory diseases. Prostaglandins Other Lipid Mediat. 2020;147:106385.
Atwal N, Casey SL, Mitchell VA, Vaughan CW. THC and gabapentin interactions in a mouse neuropathic pain model. Neuropharmacology. 2019;144:115–21.
Auzmendi J, Palestro P, Blachman A, Gavernet L, Merelli A, Talevi A, Calabrese GC, Ramos AJ, Lazarowski A. Cannabidiol (CBD) inhibited Rhodamine-123 efflux in cultured vascular endothelial cells and astrocytes under hypoxic conditions. Front Behav Neurosci. 2020;14:32.
Avraham Y, Grigoriadis N, Poutahidis T, Vorobiev L, Magen I, Ilan Y, Mechoulam R, Berry E. Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice. Br J Pharmacol. 2011;162(7):1650–8.
Bambico FR, Katz N, Debonnel G, Gobbi G. Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex. J Neurosci. 2007;27(43):11700–11.
Banni S, Carta G, Murru E, Cordeddu L, Giordano E, Sirigu AR, Berge K, Vik H, Maki KC, Di Marzo V, Griinari M. Krill oil significantly decreases 2-arachidonoylglycerol plasma levels in obese subjects. Nutr Metab (Lond). 2011;8(1):7.
Bansal S, Maharao N, Paine MF, Unadkat JD. Predicting the potential for cannabinoids to precipitate pharmacokinetic drug interactions via reversible inhibition or inactivation of major cytochromes P450. Drug Metab Dispos. 2020;48(10):1008–17.
Bar-Sela G, Cohen I, Campisi-Pinto S, Lewitus GM, Oz-Ari L, Jehassi A, Peer A, Turgeman I, Vernicova O, Berman P, Wollner M, Moskovitz M, Meiri D. Cannabis consumption used by cancer patients during immunotherapy correlates with poor clinical outcome. Cancers (Basel). 2020;12(9):2447.
Baracos VE, Mazurak VC, Bhullar AS. Cancer cachexia is defined by an ongoing loss of skeletal muscle mass. Ann Palliat Med. 2019;8(1):3–12.
Barco S, Fucile C, Manfredini L, De Grandis E, Gherzi M, Martelli A, Tripodi G, Mattioli F, Cangemi G. A UHPLC-MS/MS method for the quantification of Delta9-tetrahydrocannabinol and cannabidiol in decoctions and in plasma samples for therapeutic monitoring of medical cannabis. Bioanalysis. 2018;10(24):2003–14.
Beardsley PM, Balster RL, Harris LS. Dependence on tetrahydrocannabinol in rhesus monkeys. J Pharmacol Exp Ther. 1986;239(2):311–9.
Benyamina A, Bonhomme-Faivre L, Picard V, Sabbagh A, Richard D, Blecha L, Rahioui H, Karila L, Lukasiewicz M, Farinotti R, Picard V, Marill C, Reynaud M. Association between ABCB1 C3435T polymorphism and increased risk of cannabis dependence. Prog Neuro-Psychopharmacol Biol Psychiatry. 2009;33(7):1270–4.
Bergamaschi MM, Karschner EL, Goodwin RS, Scheidweiler KB, Hirvonen J, Queiroz RH, Huestis MA. Impact of prolonged cannabinoid excretion in chronic daily cannabis smokers’ blood on per se drugged driving laws. Clin Chem. 2013;59(3):519–26.
Berger C, Schmid PC, Schabitz WR, Wolf M, Schwab S, Schmid HH. Massive accumulation of N-acylethanolamines after stroke. Cell signalling in acute cerebral ischemia? J Neurochem. 2004;88(5):1159–67.
Berrendero F, Maldonado R. Involvement of the opioid system in the anxiolytic-like effects induced by Delta(9)-tetrahydrocannabinol. Psychopharmacology. 2002;163(1):111–7.
Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther. 2002;302(2):645–50.
Bhattacharyya S, Wilson R, Appiah-Kusi E, O'Neill A, Brammer M, Perez J, Murray R, Allen P, Bossong MG, McGuire P. Effect of Cannabidiol on medial temporal, midbrain, and striatal dysfunction in people at clinical high risk of psychosis: a randomized clinical trial. JAMA Psychiat. 2018;75(11):1107–17.
Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, Moriello AS, Davis JB, Mechoulam R, Di Marzo V. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 2001;134(4):845–52.
Boehnke KF, Scott JR, Litinas E, Sisley S, Williams DA, Clauw DJ. Pills to pot: observational analyses of cannabis substitution among medical cannabis users with chronic pain. J Pain. 2019;20(7):830–41.
Boggs DL, Surti T, Gupta A, Gupta S, Niciu M, Pittman B, Schnakenberg Martin AM, Thurnauer H, Davies A, D'Souza DC, Ranganathan M. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacology. 2018;235(7):1923–32.
Bonhomme-Faivre L, Benyamina A, Reynaud M, Farinotti R, Abbara C. Disposition of Delta tetrahydrocannabinol in CF1 mice deficient in mdr1a P-glycoprotein. Addict Biol. 2008;13(3–4):295–300.
Bornheim LM, Kim KY, Li J, Perotti BY, Benet LZ. Effect of cannabidiol pretreatment on the kinetics of tetrahydrocannabinol metabolites in mouse brain. Drug Metab Dispos. 1995;23(8):825–31.
Bouquie R, Deslandes G, Mazare H, Cogne M, Mahe J, Gregoire M, Jolliet P. Cannabis and anticancer drugs: societal usage and expected pharmacological interactions - a review. Fundam Clin Pharmacol. 2018;32(5):462–84.
Bovasso G. The long-term treatment outcomes of depression and anxiety comorbid with substance abuse. J Behav Health Serv Res. 2001a;28(1):42–57.
Bovasso GB. Cannabis abuse as a risk factor for depressive symptoms. Am J Psychiatry. 2001b;158(12):2033–7.
Bowles NP, Hill MN, Bhagat SM, Karatsoreos IN, Hillard CJ, McEwen BS. Chronic, noninvasive glucocorticoid administration suppresses limbic endocannabinoid signaling in mice. Neuroscience. 2012;204:83–9.
Braida D, Iosue S, Pegorini S, Sala M. Delta9-tetrahydrocannabinol-induced conditioned place preference and intracerebroventricular self-administration in rats. Eur J Pharmacol. 2004;506(1):63–9.
Brenneman DE, Petkanas D, Kinney WA. Pharmacological comparisons between Cannabidiol and KLS-13019. J Mol Neurosci. 2018;66(1):121–34.
Brown GW, Bellnier TJ, Janda M, Miskowitz K. Delta-9-tetrahydrocannabinol dose increase leads to warfarin drug interaction and elevated INR. J Am Pharm Assoc (2003). 2020;61(1):e57–60.
Brown JD. Potential adverse drug events with tetrahydrocannabinol (THC) due to drug-drug interactions. J Clin Med. 2020;9(4):919.
Brown NK, Harvey DJ. In vivo metabolism of the ethyl homologues of delta-8-tetrahydrocannabinol and delta-9-tetrahydrocannabinol in the mouse. Biol Mass Spectrom. 1991;20(5):324–8.
Bruni N, Della Pepa C, Oliaro-Bosso S, Pessione E, Gastaldi D, Dosio F. Cannabinoid delivery systems for pain and inflammation treatment. Molecules. 2018;23(10):2478.
Brzozowska N, Li KM, Wang XS, Booth J, Stuart J, McGregor IS, Arnold JC. ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice. PeerJ. 2016;4:e2081.
Brzozowska NI, de Tonnerre EJ, Li KM, Wang XS, Boucher AA, Callaghan PD, Kuligowski M, Wong A, Arnold JC. The differential binding of antipsychotic drugs to the ABC transporter P-glycoprotein predicts cannabinoid-antipsychotic drug interactions. Neuropsychopharmacology. 2017;42(11):2222–31.
Budney AJ, Bickel WK, Amass L. Marijuana use and treatment outcome among opioid-dependent patients. Addiction. 1998;93(4):493–503.
Buoite Stella A, Gortan Cappellari G, Barazzoni R, Zanetti M. Update on the impact of omega 3 fatty acids on inflammation, insulin resistance and sarcopenia: a review. Int J Mol Sci. 2018;19(1):218.
Carlini EA, Mechoulam R, Lander N. Anticonvulsant activity of four oxygenated cannabidiol derivatives. Res Commun Chem Pathol Pharmacol. 1975;12(1):1–15.
Chavarria-Siles I, Contreras-Rojas J, Hare E, Walss-Bass C, Quezada P, Dassori A, Contreras S, Medina R, Ramirez M, Salazar R, Raventos H, Escamilla MA. Cannabinoid receptor 1 gene (CNR1) and susceptibility to a quantitative phenotype for hebephrenic schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2008;147(3):279–84.
Chen C, Bazan NG. Lipid signaling: sleep, synaptic plasticity, and neuroprotection. Prostaglandins Other Lipid Mediat. 2005;77(1–4):65–76.
Chen J, Chen JK, Falck JR, Guthi JS, Anjaiah S, Capdevila JH, Harris RC. Mitogenic activity and signaling mechanism of 2-(14,15- epoxyeicosatrienoyl)glycerol, a novel cytochrome p450 arachidonate metabolite. Mol Cell Biol. 2007;27(8):3023–34.
Chen P, Hu S, Yao J, Moore SA, Spector AA, Fang X. Induction of cyclooxygenase-2 by anandamide in cerebral microvascular endothelium. Microvasc Res. 2005;69(1–2):28–35.
Chidambaran V, Pilipenko V, Spruance K, Venkatasubramanian R, Niu J, Fukuda T, Mizuno T, Zhang K, Kaufman K, Vinks AA, Martin LJ, Sadhasivam S. Fatty acid amide hydrolase-morphine interaction influences ventilatory response to hypercapnia and postoperative opioid outcomes in children. Pharmacogenomics. 2017;18(2):143–56.
Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet. 2007;370(9600):1706–13.
Chu J, Zheng H, Zhang Y, Loh HH, Law PY. Agonist-dependent mu-opioid receptor signaling can lead to heterologous desensitization. Cell Signal. 2010;22(4):684–96.
Church SH, Rothenberg JL, Sullivan MA, Bornstein G, Nunes EV. Concurrent substance use and outcome in combined behavioral and naltrexone therapy for opiate dependence. Am J Drug Alcohol Abuse. 2001;27(3):441–52.
Cichewicz DL. Synergistic interactions between cannabinoid and opioid analgesics. Life Sci. 2004;74(11):1317–24.
Cichewicz DL, Haller VL, Welch SP. Changes in opioid and cannabinoid receptor protein following short-term combination treatment with delta(9)-tetrahydrocannabinol and morphine. J Pharmacol Exp Ther. 2001;297(1):121–7.
Cichewicz DL, Martin ZL, Smith FL, Welch SP. Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification. J Pharmacol Exp Ther. 1999;289(2):859–67.
Cichewicz DL, Welch SP. Modulation of oral morphine antinociceptive tolerance and naloxone-precipitated withdrawal signs by oral Delta 9-tetrahydrocannabinol. J Pharmacol Exp Ther. 2003;305(3):812–7.
Cipriano M, Bjorklund E, Wilson AA, Congiu C, Onnis V, Fowler CJ. Inhibition of fatty acid amide hydrolase and cyclooxygenase by the N-(3-methylpyridin-2-yl)amide derivatives of flurbiprofen and naproxen. Eur J Pharmacol. 2013;720(1–3):383–90.
Clem SN, Bigand TL, Wilson M. Cannabis use motivations among adults prescribed opioids for pain versus opioid addiction. Pain Manag Nurs. 2020;21(1):43–7.
Cocco MT, Congiu C, Onnis V, Morelli M, Cauli O. Synthesis of ibuprofen heterocyclic amides and investigation of their analgesic and toxicological properties. Eur J Med Chem. 2003;38(5):513–8.
Colombero C, Cardenas S, Venara M, Martin A, Pennisi P, Barontini M, Nowicki S. Cytochrome 450 metabolites of arachidonic acid (20-HETE, 11,12-EET and 14,15-EET) promote pheochromocytoma cell growth and tumor associated angiogenesis. Biochimie. 2020;171–172:147–57.
Consroe P, Kennedy K, Schram K. Assay of plasma cannabidiol by capillary gas chromatography/ion trap mass spectroscopy following high-dose repeated daily oral administration in humans. Pharmacol Biochem Behav. 1991;40(3):517–22.
Cooper ZD, Bedi G, Ramesh D, Balter R, Comer SD, Haney M. Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. Neuropsychopharmacology. 2018;43(10):2046–55.
Cooper ZD, Haney M. Opioid antagonism enhances marijuana's effects in heavy marijuana smokers. Psychopharmacology. 2010;211(2):141–8.
Cox EJ, Maharao N, Patilea-Vrana G, Unadkat JD, Rettie AE, McCune JS, Paine MF. A marijuana-drug interaction primer: precipitants, pharmacology, and pharmacokinetics. Pharmacol Ther. 2019;201:25–38.
Crockett J, Critchley D, Tayo B, Berwaerts J, Morrison G. A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. Epilepsia. 2020;61(2):267–77.
Crupi R, Paterniti I, Ahmad A, Campolo M, Esposito E, Cuzzocrea S. Effects of palmitoylethanolamide and luteolin in an animal model of anxiety/depression. CNS Neurol Disord Drug Targets. 2013;12(7):989–1001.
Czikora A, Lizanecz E, Boczan J, Darago A, Papp Z, Edes I, Toth A. Vascular metabolism of anandamide to arachidonic acid affects myogenic constriction in response to intraluminal pressure elevation. Life Sci. 2012;90(11–12):407–15.
D'Souza DC, Pittman B, Perry E, Simen A. Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans. Psychopharmacology. 2009;202(4):569–78.
Dalton VS, Long LE, Weickert CS, Zavitsanou K. Paranoid schizophrenia is characterized by increased CB1 receptor binding in the dorsolateral prefrontal cortex. Neuropsychopharmacology. 2011;36(8):1620–30.
Damkier P, Lassen D, Christensen MMH, Madsen KG, Hellfritzsch M, Pottegard A. Interaction between warfarin and cannabis. Basic Clin Pharmacol Toxicol. 2019;124(1):28–31.
De Gregorio D, Manchia M, Carpiniello B, Valtorta F, Nobile M, Gobbi G, Comai S. Role of palmitoylethanolamide (PEA) in depression: Translational evidence: Special Section on “Translational and Neuroscience Studies in Affective Disorders”. Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders. J Affect Disord. 2019;255:195–200.
De Marchi N, De Petrocellis L, Orlando P, Daniele F, Fezza F, Di Marzo V. Endocannabinoid signalling in the blood of patients with schizophrenia. Lipids Health Dis. 2003;2:5.
De Petrocellis L, Ligresti A, Moriello AS, Allara M, Bisogno T, Petrosino S, Stott CG, Di Marzo V. Effects of cannabinoids and cannabinoid-enriched cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol. 2011;163(7):1479–94.
Dean B, Sundram S, Bradbury R, Scarr E, Copolov D. Studies on [3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use. Neuroscience. 2001;103(1):9–15.
Dean C, Hillard CJ, Seagard JL, Hopp FA, Hogan QH. Upregulation of fatty acid amide hydrolase in the dorsal periaqueductal gray is associated with neuropathic pain and reduced heart rate in rats. Am J Physiol Regul Integr Comp Physiol. 2017;312(4):R585–96.
Delis F, Rosko L, Shroff A, Leonard KE, Thanos PK. Oral haloperidol or olanzapine intake produces distinct and region-specific increase in cannabinoid receptor levels that is prevented by high fat diet. Prog Neuropsychopharmacol Biol Psychiatry. 2017;79(Pt B):268–80.
Devinsky O, Patel AD, Thiele EA, Wong MH, Appleton R, Harden CL, Greenwood S, Morrison G, Sommerville K, G. P. A. S. Group. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 2018;90(14):e1204–11.
Di Girolamo FG, Situlin R, Mazzucco S, Valentini R, Toigo G, Biolo G. Omega-3 fatty acids and protein metabolism: enhancement of anabolic interventions for sarcopenia. Curr Opin Clin Nutr Metab Care. 2014;17(2):145–50.
Di S, Malcher-Lopes R, Halmos KC, Tasker JG. Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism. J Neurosci. 2003;23(12):4850–7.
Di S, Malcher-Lopes R, Marcheselli VL, Bazan NG, Tasker JG. Rapid glucocorticoid-mediated endocannabinoid release and opposing regulation of glutamate and gamma-aminobutyric acid inputs to hypothalamic magnocellular neurons. Endocrinology. 2005;146(10):4292–301.
Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi SL, Kathuria S, Piomelli D. Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci U S A. 2002;99(16):10819–24.
Eggan SM, Hashimoto T, Lewis DA. Reduced cortical cannabinoid 1 receptor messenger RNA and protein expression in schizophrenia. Arch Gen Psychiatry. 2008;65(7):772–84.
Eggan SM, Stoyak SR, Verrico CD, Lewis DA. Cannabinoid CB1 receptor immunoreactivity in the prefrontal cortex: comparison of schizophrenia and major depressive disorder. Neuropsychopharmacology. 2010;35(10):2060–71.
Elkhayat HA, Aly RH, Elagouza IA, El-Kabarity RH, Galal YI. Role of P-glycoprotein inhibitors in children with drug-resistant epilepsy. Acta Neurol Scand. 2017;136(6):639–44.
Ellgren M, Spano SM, Hurd YL. Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats. Neuropsychopharmacology. 2007;32(3):607–15.
Endo T, Takeuchi T, Maehara S. Pharmacological characterization of a novel, potent, selective, and orally active fatty acid amide hydrolase inhibitor, PKM-833 [(R)-N-(pyridazin-3-yl)-4-(7-(trifluoromethyl)chroman-4-yl)piperazine-1-carboxami de] in rats: potential for the treatment of inflammatory pain. Pharmacol Res Perspect. 2020;8(2):e00569.
Endocannabinoid Research, G, De Filippis D, D’Amico A, Cipriano M, Petrosino S, Orlando P, Di Marzo V, Iuvone T. Levels of endocannabinoids and palmitoylethanolamide and their pharmacological manipulation in chronic granulomatous inflammation in rats. Pharmacol Res. 2010;61(4):321–8.
Engels FK, de Jong FA, Sparreboom A, Mathot RA, Loos WJ, Kitzen JJ, de Bruijn P, Verweij J, Mathijssen RH. Medicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel. Oncologist. 2007;12(3):291–300.
Epstein DH, Preston KL. Does cannabis use predict poor outcome for heroin-dependent patients on maintenance treatment? Past findings and more evidence against. Addiction. 2003;98(3):269–79.
Fattore L, Vigano D, Fadda P, Rubino T, Fratta W, Parolaro D. Bidirectional regulation of mu-opioid and CB1-cannabinoid receptor in rats self-administering heroin or WIN 55,212-2. Eur J Neurosci. 2007;25(7):2191–200.
Fawley JA, Hofmann ME, Andresen MC. Cannabinoid 1 and transient receptor potential vanilloid 1 receptors discretely modulate evoked glutamate separately from spontaneous glutamate transmission. J Neurosci. 2014;34(24):8324–32.
Fechtner S, Singh AK, Ahmed S. Role of cannabinoid receptor 2 in mediating interleukin-1beta-induced inflammation in rheumatoid arthritis synovial fibroblasts. Clin Exp Rheumatol. 2019;37(6):1026–35.
Feinshtein V, Erez O, Ben-Zvi Z, Erez N, Eshkoli T, Sheizaf B, Sheiner E, Huleihel M, Holcberg G. Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines. PeerJ. 2013b;1:e153.
Feinshtein V, Erez O, Ben-Zvi Z, Eshkoli T, Sheizaf B, Sheiner E, Holcberg G. Cannabidiol enhances xenobiotic permeability through the human placental barrier by direct inhibition of breast cancer resistance protein: an ex vivo study. Am J Obstet Gynecol. 2013a;209(6):573.e571–15.
Fezza F, Bari M, Florio R, Talamonti E, Feole M, Maccarrone M. Endocannabinoids, related compounds and their metabolic routes. Molecules. 2014;19(11):17078–106.
Fidelman S, Mizrachi Zer-Aviv T, Lange R, Hillard CJ, Akirav I. Chronic treatment with URB597 ameliorates post-stress symptoms in a rat model of PTSD. Eur Neuropsychopharmacol. 2018;28(5):630–42.
Finn K. Why marijuana won’t fix the opioid epidemic. Mo Med. 2019;116(5):363.
Fonseca BM, Costa MA, Almada M, Correia-da-Silva G, Teixeira NA. Endogenous cannabinoids revisited: a biochemistry perspective. Prostaglandins Other Lipid Mediat. 2013;102–103:13–30.
Foster BC, Abramovici H, Harris CS. Cannabis and cannabinoids: kinetics and interactions. Am J Med. 2019;132(11):1266–70.
Fowler CJ, Naidu PS, Lichtman A, Onnis V. The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1. Br J Pharmacol. 2009;156(3):412–9.
Fraser GA. The use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD). CNS Neurosci Ther. 2009;15(1):84–8.
Garcia-Gutierrez MS, Manzanares J. The cannabinoid CB1 receptor is involved in the anxiolytic, sedative and amnesic actions of benzodiazepines. J Psychopharmacol. 2010;24(5):757–65.
Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP, Program UC. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017;58(9):1586–92.
Ghabrash MF, Coronado-Montoya S, Aoun J, Gagne AA, Mansour F, Ouellet-Plamondon C, Trepanier A, Jutras-Aswad D. Cannabidiol for the treatment of psychosis among patients with schizophrenia and other primary psychotic disorders: a systematic review with a risk of bias assessment. Psychiatry Res. 2020;286:112890.
Ghazizadeh-Hashemi M, Ghajar A, Shalbafan MR, Ghazizadeh-Hashemi F, Afarideh M, Malekpour F, Ghaleiha A, Ardebili ME, Akhondzadeh S. Palmitoylethanolamide as adjunctive therapy in major depressive disorder: a double-blind, randomized and placebo-controlled trial. J Affect Disord. 2018;232:127–33.
Ghodke-Puranik Y, Thorn CF, Lamba JK, Leeder JS, Song W, Birnbaum AK, Altman RB, Klein TE. Valproic acid pathway: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2013;23(4):236–41.
Giang DK, Cravatt BF. Molecular characterization of human and mouse fatty acid amide hydrolases. Proc Natl Acad Sci U S A. 1997;94(6):2238–42.
Giuffrida A, Leweke FM, Gerth CW, Schreiber D, Koethe D, Faulhaber J, Klosterkotter J, Piomelli D. Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology. 2004;29(11):2108–14.
Glass M, Hong J, Sato TA, Mitchell MD. Misidentification of prostamides as prostaglandins. J Lipid Res. 2005;46(7):1364–8.
Gobbi G, Bambico FR, Mangieri R, Bortolato M, Campolongo P, Solinas M, Cassano T, Morgese MG, Debonnel G, Duranti A, Tontini A, Tarzia G, Mor M, Trezza V, Goldberg SR, Cuomo V, Piomelli D. Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis. Proc Natl Acad Sci U S A. 2005;102(51):18620–5.
Gonzalez S, Fernandez-Ruiz J, Sparpaglione V, Parolaro D, Ramos JA. Chronic exposure to morphine, cocaine or ethanol in rats produced different effects in brain cannabinoid CB(1) receptor binding and mRNA levels. Drug Alcohol Depend. 2002;66(1):77–84.
Goparaju SK, Ueda N, Yamaguchi H, Yamamoto S. Anandamide amidohydrolase reacting with 2-arachidonoylglycerol, another cannabinoid receptor ligand. FEBS Lett. 1998;422(1):69–73.
Green AI, Burgess ES, Dawson R, Zimmet SV, Strous RD. Alcohol and cannabis use in schizophrenia: effects of clozapine vs. risperidone. Schizophr Res. 2003;60(1):81–5.
Greenblatt DJ, Divoll M, Abernethy DR, Ochs HR, Shader RI. Clinical pharmacokinetics of the newer benzodiazepines. Clin Pharmacokinet. 1983a;8(3):233–52.
Greenblatt DJ, Divoll M, Puri SK, Ho I, Zinny MA, Shader RI. Clobazam kinetics in the elderly. Br J Clin Pharmacol. 1981;12(5):631–6.
Greenblatt DJ, Divoll M, Puri SK, Ho I, Zinny MA, Shader RI. Reduced single-dose clearance of clobazam in elderly men predicts increased multiple-dose accumulation. Clin Pharmacokinet. 1983b;8(1):83–94.
Greger J, Bates V, Mechtler L, Gengo F. A review of cannabis and interactions with anticoagulant and antiplatelet agents. J Clin Pharmacol. 2020;60(4):432–8.
Griebel G, Stemmelin J, Scatton B. Effects of the cannabinoid CB1 receptor antagonist rimonabant in models of emotional reactivity in rodents. Biol Psychiatry. 2005;57(3):261–7.
Gronewold A, Skopp G. A preliminary investigation on the distribution of cannabinoids in man. Forensic Sci Int. 2011;210(1–3):e7–e11.
Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003;42(4):327–60.
Guindon J, De Lean A, Beaulieu P. Local interactions between anandamide, an endocannabinoid, and ibuprofen, a nonsteroidal anti-inflammatory drug, in acute and inflammatory pain. Pain. 2006a;121(1–2):85–93.
Guindon J, LoVerme J, De Lean A, Piomelli D, Beaulieu P. Synergistic antinociceptive effects of anandamide, an endocannabinoid, and nonsteroidal anti-inflammatory drugs in peripheral tissue: a role for endogenous fatty-acid ethanolamides? Eur J Pharmacol. 2006b;550(1–3):68–77.
Guo Z, Johnson V, Barrera J, Porras M, Hinojosa D, Hernandez I, McGarrah P, Potter DA. Targeting cytochrome P450-dependent cancer cell mitochondria: cancer associated CYPs and where to find them. Cancer Metastasis Rev. 2018;37(2–3):409–23.
Hallak JE, Dursun SM, Bosi DC, de Macedo LR, Machado-de-Sousa JP, Abrao J, Crippa JA, McGuire P, Krystal JH, Baker GB, Zuardi AW. The interplay of cannabinoid and NMDA glutamate receptor systems in humans: preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects. Prog Neuro-Psychopharmacol Biol Psychiatry. 2011;35(1):198–202.
Hallak JE, Machado-de-Sousa JP, Crippa JA, Sanches RF, Trzesniak C, Chaves C, Bernardo SA, Regalo SC, Zuardi AW. Performance of schizophrenic patients in the Stroop Color Word Test and electrodermal responsiveness after acute administration of cannabidiol (CBD). Braz J Psychiatry. 2010;32(1):56–61.
Halldin MM, Isaac H, Widman M, Nilsson E, Ryrfeldt A. A comparison between the metabolism of delta 1-tetrahydrocannabinol by perfused lung and liver of rat and Guinea-pig. Xenobiotica. 1984;14(3):277–82.
Hallinan R, Crettol S, Agho K, Attia J, Besson J, Croquette-Krokar M, Hammig R, Deglon JJ, Byrne A, Ray J, Somogyi AA, Eap CB. Cannabis and benzodiazepines as determinants of methadone trough plasma concentration variability in maintenance treatment: a transnational study. Eur J Clin Pharmacol. 2009;65(11):1113–20.
Hamdani N, Tabeze JP, Ramoz N, Ades J, Hamon M, Sarfati Y, Boni C, Gorwood P. The CNR1 gene as a pharmacogenetic factor for antipsychotics rather than a susceptibility gene for schizophrenia. Eur Neuropsychopharmacol. 2008;18(1):34–40.
Haney M. Opioid antagonism of cannabinoid effects: differences between marijuana smokers and nonmarijuana smokers. Neuropsychopharmacology. 2007;32(6):1391–403.
Haney M, Bisaga A, Foltin RW. Interaction between naltrexone and oral THC in heavy marijuana smokers. Psychopharmacology. 2003;166(1):77–85.
Hansen HS. Palmitoylethanolamide and other anandamide congeners. Proposed role in the diseased brain. Exp Neurol. 2010;224(1):48–55.
Hartman RL, Brown TL, Milavetz G, Spurgin A, Gorelick DA, Gaffney G, Huestis MA. Controlled cannabis vaporizer administration: blood and plasma cannabinoids with and without alcohol. Clin Chem. 2015;61(6):850–69.
Harvey DJ, Brown NK. In vitro metabolism of the equatorial C11-methyl isomer of hexahydrocannabinol in several mammalian species. Drug Metab Dispos. 1991;19(3):714–6.
Hauer D, Schelling G, Gola H, Campolongo P, Morath J, Roozendaal B, Hamuni G, Karabatsiakis A, Atsak P, Vogeser M, Kolassa IT. Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder. PLoS One. 2013;8(5):e62741.
Hesketh SA, Brennan AK, Jessop DS, Finn DP. Effects of chronic treatment with citalopram on cannabinoid and opioid receptor-mediated G-protein coupling in discrete rat brain regions. Psychopharmacology. 2008;198(1):29–36.
Hill MN, Barr AM, Ho WS, Carrier EJ, Gorzalka BB, Hillard CJ. Electroconvulsive shock treatment differentially modulates cortical and subcortical endocannabinoid activity. J Neurochem. 2007;103(1):47–56.
Hill MN, Bierer LM, Makotkine I, Golier JA, Galea S, McEwen BS, Hillard CJ, Yehuda R. Reductions in circulating endocannabinoid levels in individuals with post-traumatic stress disorder following exposure to the World Trade Center attacks. Psychoneuroendocrinology. 2013;38(12):2952–61.
Hill MN, Carrier EJ, Ho WS, Shi L, Patel S, Gorzalka BB, Hillard CJ. Prolonged glucocorticoid treatment decreases cannabinoid CB1 receptor density in the hippocampus. Hippocampus. 2008c;18(2):221–6.
Hill MN, Carrier EJ, McLaughlin RJ, Morrish AC, Meier SE, Hillard CJ, Gorzalka BB. Regional alterations in the endocannabinoid system in an animal model of depression: effects of concurrent antidepressant treatment. J Neurochem. 2008a;106(6):2322–36.
Hill MN, Gorzalka BB. Enhancement of anxiety-like responsiveness to the cannabinoid CB(1) receptor agonist HU-210 following chronic stress. Eur J Pharmacol. 2004;499(3):291–5.
Hill MN, Gorzalka BB. Is there a role for the endocannabinoid system in the etiology and treatment of melancholic depression? Behav Pharmacol. 2005a;16(5–6):333–52.
Hill MN, Gorzalka BB. Pharmacological enhancement of cannabinoid CB1 receptor activity elicits an antidepressant-like response in the rat forced swim test. Eur Neuropsychopharmacol. 2005b;15(6):593–9.
Hill MN, Ho WS, Hillard CJ, Gorzalka BB. Differential effects of the antidepressants tranylcypromine and fluoxetine on limbic cannabinoid receptor binding and endocannabinoid contents. J Neural Transm (Vienna). 2008b;115(12):1673–9.
Hill MN, Ho WS, Sinopoli KJ, Viau V, Hillard CJ, Gorzalka BB. Involvement of the endocannabinoid system in the ability of long-term tricyclic antidepressant treatment to suppress stress-induced activation of the hypothalamic-pituitary-adrenal axis. Neuropsychopharmacology. 2006;31(12):2591–9.
Hill MN, Miller GE, Carrier EJ, Gorzalka BB, Hillard CJ. Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress. Psychoneuroendocrinology. 2009;34(8):1257–62.
Hill MN, Miller GE, Ho WS, Gorzalka BB, Hillard CJ. Serum endocannabinoid content is altered in females with depressive disorders: a preliminary report. Pharmacopsychiatry. 2008d;41(2):48–53.
Hill MN, Patel S, Carrier EJ, Rademacher DJ, Ormerod BK, Hillard CJ, Gorzalka BB. Downregulation of endocannabinoid signaling in the hippocampus following chronic unpredictable stress. Neuropsychopharmacology. 2005;30(3):508–15.
Hindocha C, Cousijn J, Rall M, Bloomfield MAP. The effectiveness of cannabinoids in the treatment of Posttraumatic Stress Disorder (PTSD): a systematic review. J Dual Diagn. 2020;16(1):120–39.
Hlozek T, Uttl L, Kaderabek L, Balikova M, Lhotkova E, Horsley RR, Novakova P, Sichova K, Stefkova K, Tyls F, Kuchar M, Palenicek T. Pharmacokinetic and behavioural profile of THC, CBD, and THC+CBD combination after pulmonary, oral, and subcutaneous administration in rats and confirmation of conversion in vivo of CBD to THC. Eur Neuropsychopharmacol. 2017;27(12):1223–37.
Holland ML, Lau DT, Allen JD, Arnold JC. The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids. Br J Pharmacol. 2007;152(5):815–24.
Holland ML, Panetta JA, Hoskins JM, Bebawy M, Roufogalis BD, Allen JD, Arnold JC. The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells. Biochem Pharmacol. 2006;71(8):1146–54.
Holt S, Paylor B, Boldrup L, Alajakku K, Vandevoorde S, Sundstrom A, Cocco MT, Onnis V, Fowler CJ. Inhibition of fatty acid amide hydrolase, a key endocannabinoid metabolizing enzyme, by analogues of ibuprofen and indomethacin. Eur J Pharmacol. 2007;565(1–3):26–36.
Hong S, Fan J, Kemmerer ES, Evans S, Li Y, Wiley JW. Reciprocal changes in vanilloid (TRPV1) and endocannabinoid (CB1) receptors contribute to visceral hyperalgesia in the water avoidance stressed rat. Gut. 2009;58(2):202–10.
Huestis MA, Cone EJ. Relationship of Delta 9-tetrahydrocannabinol concentrations in oral fluid and plasma after controlled administration of smoked cannabis. J Anal Toxicol. 2004;28(6):394–9.
Huestis MA, Scheidweiler KB, Saito T, Fortner N, Abraham T, Gustafson RA, Smith ML. Excretion of Delta9-tetrahydrocannabinol in sweat. Forensic Sci Int. 2008;174(2–3):173–7.
Hungund BL, Vinod KY, Kassir SA, Basavarajappa BS, Yalamanchili R, Cooper TB, Mann JJ, Arango V. Upregulation of CB1 receptors and agonist-stimulated [35S]GTPgammaS binding in the prefrontal cortex of depressed suicide victims. Mol Psychiatry. 2004;9(2):184–90.
Hutchins-Wiese HL, Li Y, Hannon K, Watkins BA. Hind limb suspension and long-chain omega-3 PUFA increase mRNA endocannabinoid system levels in skeletal muscle. J Nutr Biochem. 2012;23(8):986–93.
Ibeas Bih C, Chen T, Nunn AV, Bazelot M, Dallas M, Whalley BJ. Molecular targets of Cannabidiol in neurological disorders. Neurotherapeutics. 2015;12(4):699–730.
Imig JD. Epoxide hydrolase and epoxygenase metabolites as therapeutic targets for renal diseases. Am J Physiol Renal Physiol. 2005;289(3):F496–503.
Izgelov D, Domb AJ, Hoffman A. The effect of piperine on oral absorption of cannabidiol following acute vs. chronic administration. Eur J Pharm Sci. 2020;148:105313.
Jetly R, Heber A, Fraser G, Boisvert D. The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: a preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology. 2015;51:585–8.
Jhaveri MD, Richardson D, Robinson I, Garle MJ, Patel A, Sun Y, Sagar DR, Bennett AJ, Alexander SP, Kendall DA, Barrett DA, Chapman V. Inhibition of fatty acid amide hydrolase and cyclooxygenase-2 increases levels of endocannabinoid related molecules and produces analgesia via peroxisome proliferator-activated receptor-alpha in a model of inflammatory pain. Neuropharmacology. 2008;55(1):85–93.
Jiang R, Yamaori S, Takeda S, Yamamoto I, Watanabe K. Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes. Life Sci. 2011;89(5–6):165–70.
Jusko WJ, Gardner MJ, Mangione A, Schentag JJ, Koup JR, Vance JW. Factors affecting theophylline clearances: age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates, and ethanol. J Pharm Sci. 1979;68(11):1358–66.
Jusko WJ, Schentag JJ, Clark JH, Gardner M, Yurchak AM. Enhanced biotransformation of theophylline in marihuana and tobacco smokers. Clin Pharmacol Ther. 1978;24(4):405–10.
Justinova Z, Munzar P, Panlilio LV, Yasar S, Redhi GH, Tanda G, Goldberg SR. Blockade of THC-seeking behavior and relapse in monkeys by the cannabinoid CB(1)-receptor antagonist rimonabant. Neuropsychopharmacology. 2008;33(12):2870–7.
Kalichman SC, Washington C, Kegler C, Grebler T, Kalichman MO, Cherry C, Eaton L. Continued substance use among people living with HIV-hepatitis-C co-infection and receiving antiretroviral therapy. Subst Use Misuse. 2015;50(12):1536–43.
Karschner EL, Darwin WD, Goodwin RS, Wright S, Huestis MA. Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clin Chem. 2011;57(1):66–75.
Karschner EL, Schwilke EW, Lowe RH, Darwin WD, Pope HG, Herning R, Cadet JL, Huestis MA. Do Delta9-tetrahydrocannabinol concentrations indicate recent use in chronic cannabis users? Addiction. 2009;104(12):2041–8.
Karschner EL, Schwope DM, Schwilke EW, Goodwin RS, Kelly DL, Gorelick DA, Huestis MA. Predictive model accuracy in estimating last Delta9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC. Drug Alcohol Depend. 2012;125(3):313–9.
Karschner EL, Swortwood MJ, Hirvonen J, Goodwin RS, Bosker WM, Ramaekers JG, Huestis MA. Extended plasma cannabinoid excretion in chronic frequent cannabis smokers during sustained abstinence and correlation with psychomotor performance. Drug Test Anal. 2016;8(7):682–9.
Kathuria S, Gaetani S, Fegley D, Valino F, Duranti A, Tontini A, Mor M, Tarzia G, La Rana G, Calignano A, Giustino A, Tattoli M, Palmery M, Cuomo V, Piomelli D. Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med. 2003;9(1):76–81.
Kebir O, Lafaye G, Blecha L, Chaumette B, Mouaffak F, Laqueille X, Benyamina A. ABCB1 C3435T polymorphism is associated with tetrahydrocannabinol blood levels in heavy cannabis users. Psychiatry Res. 2018;262:357–8.
Kelly DL, Gorelick DA, Conley RR, Boggs DL, Linthicum J, Liu F, Feldman S, Ball MP, Wehring HJ, McMahon RP, Huestis MA, Heishman SJ, Warren KR, Buchanan RW. Effects of the cannabinoid-1 receptor antagonist rimonabant on psychiatric symptoms in overweight people with schizophrenia: a randomized, double-blind, pilot study. J Clin Psychopharmacol. 2011;31(1):86–91.
Kim J, Alger BE. Inhibition of cyclooxygenase-2 potentiates retrograde endocannabinoid effects in hippocampus. Nat Neurosci. 2004;7(7):697–8.
Kiso T, Watabiki T, Sekizawa T. ASP8477, a fatty acid amide hydrolase inhibitor, exerts analgesic effects in rat models of neuropathic and dysfunctional pain. Eur J Pharmacol. 2020;881:173194.
Klotz KA, Hirsch M, Heers M, Schulze-Bonhage A, Jacobs J. Effects of cannabidiol on brivaracetam plasma levels. Epilepsia. 2019;60(7):e74–7.
Ko JY, Wu RW, Kuo SJ, Chen MW, Yeh DW, Ke HC, Wu SL, Wang FS. Cannabinoid receptor 1 mediates glucocorticoid-induced bone loss in rats by perturbing bone mineral acquisition and marrow adipogenesis. Arthritis Rheum. 2012;64(4):1204–14.
Koethe D, Giuffrida A, Schreiber D, Hellmich M, Schultze-Lutter F, Ruhrmann S, Klosterkotter J, Piomelli D, Leweke FM. Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis. Br J Psychiatry. 2009;194(4):371–2.
Koethe D, Llenos IC, Dulay JR, Hoyer C, Torrey EF, Leweke FM, Weis S. Expression of CB1 cannabinoid receptor in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression. J Neural Transm (Vienna). 2007;114(8):1055–63.
Kola B, Farkas I, Christ-Crain M, Wittmann G, Lolli F, Amin F, Harvey-White J, Liposits Z, Kunos G, Grossman AB, Fekete C, Korbonits M. The orexigenic effect of ghrelin is mediated through central activation of the endogenous cannabinoid system. PLoS One. 2008;3(3):e1797.
Kong TY, Kim JH, Kim DK, Lee HS. Synthetic cannabinoids are substrates and inhibitors of multiple drug-metabolizing enzymes. Arch Pharm Res. 2018;41(7):691–710.
Kopelli E, Samara M, Siargkas A, Goulas A, Papazisis G, Chourdakis M. The role of cannabidiol oil in schizophrenia treatment. A systematic review and meta-analysis. Psychiatry Res. 2020;291:113246.
Kosel BW, Aweeka FT, Benowitz NL, Shade SB, Hilton JF, Lizak PS, Abrams DI. The effects of cannabinoids on the pharmacokinetics of indinavir and nelfinavir. AIDS. 2002;16(4):543–50.
Kozak KR, Crews BC, Ray JL, Tai HH, Morrow JD, Marnett LJ. Metabolism of prostaglandin glycerol esters and prostaglandin ethanolamides in vitro and in vivo. J Biol Chem. 2001;276(40):36993–8.
Kozak KR, Marnett LJ. Oxidative metabolism of endocannabinoids. Prostaglandins Leukot Essent Fatty Acids. 2002;66(2–3):211–20.
Kozak KR, Prusakiewicz JJ, Rowlinson SW, Prudhomme DR, Marnett LJ. Amino acid determinants in cyclooxygenase-2 oxygenation of the endocannabinoid anandamide. Biochemistry. 2003;42(30):9041–9.
Kozak KR, Rowlinson SW, Marnett LJ. Oxygenation of the endocannabinoid, 2-arachidonylglycerol, to glyceryl prostaglandins by cyclooxygenase-2. J Biol Chem. 2000;275(43):33744–9.
Kozak PP Jr. Factors that influence theophylline metabolism. West J Med. 1979;131(4):319–20.
Kreyenbuhl J, Nossel IR, Dixon LB. Disengagement from mental health treatment among individuals with schizophrenia and strategies for facilitating connections to care: a review of the literature. Schizophr Bull. 2009;35(4):696–703.
Lafourcade M, Larrieu T, Mato S, Duffaud A, Sepers M, Matias I, De Smedt-Peyrusse V, Labrousse VF, Bretillon L, Matute C, Rodriguez-Puertas R, Laye S, Manzoni OJ. Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. Nat Neurosci. 2011;14(3):345–50.
Lai JCL, Lee DYH, Leung MOY, Lam YW. Daily hassles, loneliness, and diurnal salivary cortisol in emerging adults. Horm Behav. 2019;115:104558.
Landmark CJ, Brandl U. Pharmacology and drug interactions of cannabinoids. Epileptic Disord. 2020;22(S1):16–22.
Larrieu T, Madore C, Joffre C, Laye S. Nutritional n-3 polyunsaturated fatty acids deficiency alters cannabinoid receptor signaling pathway in the brain and associated anxiety-like behavior in mice. J Physiol Biochem. 2012;68(4):671–81.
Lee CR, Goldstein JA, Pieper JA. Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. Pharmacogenetics. 2002;12(3):251–63.
Lee D, Bergamaschi MM, Milman G, Barnes AJ, Queiroz RH, Vandrey R, Huestis MA. Plasma cannabinoid pharmacokinetics after controlled smoking and ad libitum cannabis smoking in chronic frequent users. J Anal Toxicol. 2015;39(8):580–7.
Leineweber CG, Pietzner A, Zhang IW, Blessin UB, Rothe M, Schott E, Schebb NH, Weylandt KH. Assessment of the effect of Sorafenib on Omega-6 and Omega-3 Epoxyeicosanoid formation in patients with hepatocellular carcinoma. Int J Mol Sci. 2020;21(5):1875.
Leweke FM, Giuffrida A, Koethe D, Schreiber D, Nolden BM, Kranaster L, Neatby MA, Schneider M, Gerth CW, Hellmich M, Klosterkotter J, Piomelli D. Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: impact of cannabis use. Schizophr Res. 2007;94(1–3):29–36.
Leweke FM, Giuffrida A, Wurster U, Emrich HM, Piomelli D. Elevated endogenous cannabinoids in schizophrenia. Neuroreport. 1999;10(8):1665–9.
Leweke FM, Mueller JK, Lange B, Fritze S, Topor CE, Koethe D, Rohleder C. Role of the endocannabinoid system in the pathophysiology of schizophrenia: implications for pharmacological intervention. CNS Drugs. 2018;32(7):605–19.
Leweke FM, Mueller JK, Lange B, Rohleder C. Therapeutic potential of cannabinoids in psychosis. Biol Psychiatry. 2016;79(7):604–12.
Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, Klosterkotter J, Hellmich M, Koethe D. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;2:e94.
Lichtman AH, Sheikh SM, Loh HH, Martin BR. Opioid and cannabinoid modulation of precipitated withdrawal in delta(9)-tetrahydrocannabinol and morphine-dependent mice. J Pharmacol Exp Ther. 2001;298(3):1007–14.
Lies B, Martens S, Schmidt S, Boll M, Wenzel U. Flavone potently stimulates an apical transporter for flavonoids in human intestinal Caco-2 cells. Mol Nutr Food Res. 2012;56(11):1627–35.
Ligresti A, Moriello AS, Starowicz K, Matias I, Pisanti S, De Petrocellis L, Laezza C, Portella G, Bifulco M, Di Marzo V. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther. 2006;318(3):1375–87.
Lile JA, Kelly TH, Pinsky DJ, Hays LR. Substitution profile of Delta9-tetrahydrocannabinol, triazolam, hydromorphone, and methylphenidate in humans discriminating Delta9-tetrahydrocannabinol. Psychopharmacology. 2009;203(2):241–50.
Lin F, Abraham NG, Schwartzman ML. Cytochrome P450 arachidonic acid omega-hydroxylation in the proximal tubule of the rat kidney. Ann N Y Acad Sci. 1994;744:11–24.
Liu J, Tawa GJ, Wallqvist A. Identifying cytochrome p450 functional networks and their allosteric regulatory elements. PLoS One. 2013;8(12):e81980.
Liu S, Baracos VE, Quinney HA, Clandinin MT. Dietary omega-3 and polyunsaturated fatty acids modify fatty acyl composition and insulin binding in skeletal-muscle sarcolemma. Biochem J. 1994;299(Pt 3):831–7.
Liu Z, Martin JH. Gaps in predicting clinical doses for cannabinoids therapy: overview of issues for pharmacokinetics and pharmacodynamics modelling. Br J Clin Pharmacol. 2018;84(11):2483–7.
Locci A, Geoffroy P, Miesch M, Mensah-Nyagan AG, Pinna G. Social isolation in early versus late adolescent mice is associated with persistent Behavioral deficits that can be improved by Neurosteroid-based treatment. Front Cell Neurosci. 2017;11:208.
Lopez-Moreno JA, Lopez-Jimenez A, Gorriti MA, de Fonseca FR. Functional interactions between endogenous cannabinoid and opioid systems: focus on alcohol, genetics and drug-addicted behaviors. Curr Drug Targets. 2010;11(4):406–28.
Lopez JF, Chalmers DT, Little KY, Watson SJ. A.E. Bennett Research Award. Regulation of serotonin1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for the neurobiology of depression. Biol Psychiatry. 1998;43(8):547–73.
Lowe RH, Karschner EL, Schwilke EW, Barnes AJ, Huestis MA. Simultaneous quantification of Delta9-tetrahydrocannabinol, 11-hydroxy-Delta9-tetrahydrocannabinol, and 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid in human plasma using two-dimensional gas chromatography, cryofocusing, and electron impact-mass spectrometry. J Chromatogr A. 2007;1163(1–2):318–27.
Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol. 2018b;84(11):2477–82.
Lucas CJ, Galettis P, Song S, Solowij N, Reuter SE, Schneider J, Martin JH. Cannabinoid disposition after human intraperitoneal use: AnInsight into intraperitoneal pharmacokinetic properties in metastatic cancer. Clin Ther. 2018a;40(9):1442–7.
Lucas P, Baron EP, Jikomes N. Medical cannabis patterns of use and substitution for opioids & other pharmaceutical drugs, alcohol, tobacco, and illicit substances; results from a cross-sectional survey of authorized patients. Harm Reduct J. 2019;16(1):9.
Lynskey MT, Glowinski AL, Todorov AA, Bucholz KK, Madden PA, Nelson EC, Statham DJ, Martin NG, Heath AC. Major depressive disorder, suicidal ideation, and suicide attempt in twins discordant for cannabis dependence and early-onset cannabis use. Arch Gen Psychiatry. 2004;61(10):1026–32.
Madras BK. Are THC levels in oral fluids and blood plasma comparable after oral ingestion of edibles containing cannabis or THC? Clin Chem. 2017;63(3):629–31.
Maia J, Fonseca BM, Cunha SC, Braga J, Goncalves D, Teixeira N, Correia-da-Silva G. Impact of tetrahydrocannabinol on the endocannabinoid 2-arachidonoylglycerol metabolism: ABHD6 and ABHD12 as novel players in human placenta. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865:158807.
Malcher-Lopes R, Di S, Marcheselli VS, Weng FJ, Stuart CT, Bazan NG, Tasker JG. Opposing crosstalk between leptin and glucocorticoids rapidly modulates synaptic excitation via endocannabinoid release. J Neurosci. 2006;26(24):6643–50.
Maldonado R, Valverde O. Participation of the opioid system in cannabinoid-induced antinociception and emotional-like responses. Eur Neuropsychopharmacol. 2003;13(6):401–10.
Manini AF, Yiannoulos G, Bergamaschi MM, Hernandez S, Olmedo R, Barnes AJ, Winkel G, Sinha R, Jutras-Aswad D, Huestis MA, Hurd YL. Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans. J Addict Med. 2015;9(3):204–10.
Manzanares J, Corchero J, Romero J, Fernandez-Ruiz JJ, Ramos JA, Fuentes JA. Pharmacological and biochemical interactions between opioids and cannabinoids. Trends Pharmacol Sci. 1999;20(7):287–94.
Mato S, Aso E, Castro E, Martin M, Valverde O, Maldonado R, Pazos A. CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptors. J Neurochem. 2007;103(5):2111–20.
Mato S, Vidal R, Castro E, Diaz A, Pazos A, Valdizan EM. Long-term fluoxetine treatment modulates cannabinoid type 1 receptor-mediated inhibition of adenylyl cyclase in the rat prefrontal cortex through 5-hydroxytryptamine 1A receptor-dependent mechanisms. Mol Pharmacol. 2010;77(3):424–34.
Matricon J, Seillier A, Giuffrida A. Distinct neuronal activation patterns are associated with PCP-induced social withdrawal and its reversal by the endocannabinoid-enhancing drug URB597. Neurosci Res. 2016;110:49–58.
Mazur A, Lichti CF, Prather PL, Zielinska AK, Bratton SM, Gallus-Zawada A, Finel M, Miller GP, Radominska-Pandya A, Moran JH. Characterization of human hepatic and extrahepatic UDP-glucuronosyltransferase enzymes involved in the metabolism of classic cannabinoids. Drug Metab Dispos. 2009;37(7):1496–504.
McGuire P, Robson P, Cubala WJ, Vasile D, Morrison PD, Barron R, Taylor A, Wright S. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. Am J Psychiatry. 2018;175(3):225–31.
McIntosh AL, Martin GG, Huang H, Landrock D, Kier AB, Schroeder F. Delta(9)-tetrahydrocannabinol induces endocannabinoid accumulation in mouse hepatocytes: antagonism by Fabp1 gene ablation. J Lipid Res. 2018;59(4):646–57.
McLaughlin RJ, Hill MN, Morrish AC, Gorzalka BB. Local enhancement of cannabinoid CB1 receptor signalling in the dorsal hippocampus elicits an antidepressant-like effect. Behav Pharmacol. 2007;18(5–6):431–8.
McPartland JM, Guy GW, Di Marzo V. Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system. PLoS One. 2014;9(3):e89566.
Medeiros P, de Freitas RL, Silva MO, Coimbra NC, Melo-Thomas L. CB1 cannabinoid receptor-mediated anandamide signaling mechanisms of the inferior colliculus modulate the haloperidol-induced catalepsy. Neuroscience. 2016;337:17–26.
Meltzer HY, Arvanitis L, Bauer D, Rein W, G. Meta-Trial Study. Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am J Psychiatry. 2004;161(6):975–84.
Menzies JR, Ludwig M, Leng G. Direct and indirect effects of cannabinoids on in vitro GABA release in the rat arcuate nucleus. J Neuroendocrinol. 2010;22(6):585–92.
Micale V, Cristino L, Tamburella A, Petrosino S, Leggio GM, Drago F, Di Marzo V. Anxiolytic effects in mice of a dual blocker of fatty acid amide hydrolase and transient receptor potential vanilloid type-1 channels. Neuropsychopharmacology. 2009;34(3):593–606.
Millar SA, Stone NL, Bellman ZD, Yates AS, England TJ, O'Sullivan SE. A systematic review of cannabidiol dosing in clinical populations. Br J Clin Pharmacol. 2019;85(9):1888–900.
Millar SA, Stone NL, Yates AS, O’Sullivan SE. A systematic review on the pharmacokinetics of Cannabidiol in humans. Front Pharmacol. 2018;9:1365.
Mitchell MD, Sato TA, Wang A, Keelan JA, Ponnampalam AP, Glass M. Cannabinoids stimulate prostaglandin production by human gestational tissues through a tissue- and CB1-receptor-specific mechanism. Am J Physiol Endocrinol Metab. 2008;294(2):E352–6.
Mitra R, Guo Z, Milani M, Mesaros C, Rodriguez M, Nguyen J, Luo X, Clarke D, Lamba J, Schuetz E, Donner DB, Puli N, Falck JR, Capdevila J, Gupta K, Blair IA, Potter DA. CYP3A4 mediates growth of estrogen receptor-positive breast cancer cells in part by inducing nuclear translocation of phospho-Stat3 through biosynthesis of (+/−)-14,15-epoxyeicosatrienoic acid (EET). J Biol Chem. 2011;286(20):17543–59.
Miyata N, Seki T, Tanaka Y, Omura T, Taniguchi K, Doi M, Bandou K, Kametani S, Sato M, Okuyama S, Cambj-Sapunar L, Harder DR, Roman RJ. Beneficial effects of a new 20-hydroxyeicosatetraenoic acid synthesis inhibitor, TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide], on hemorrhagic and ischemic stroke. J Pharmacol Exp Ther. 2005;314(1):77–85.
Mizrachi Zer-Aviv T, Segev A, Akirav I. Cannabinoids and post-traumatic stress disorder: clinical and preclinical evidence for treatment and prevention. Behav Pharmacol. 2016;27(7):561–9.
Morano A, Fanella M, Albini M, Cifelli P, Palma E, Giallonardo AT, Di Bonaventura C. Cannabinoids in the treatment of epilepsy: current status and future prospects. Neuropsychiatr Dis Treat. 2020;16:381–96.
Morrison G, Crockett J, Blakey G, Sommerville K. A phase 1, open-label, pharmacokinetic trial to investigate possible drug-drug interactions between Clobazam, Stiripentol, or valproate and Cannabidiol in healthy subjects. Clin Pharmacol Drug Dev. 2019;8(8):1009–31.
Murphy N, Cowley TR, Blau CW, Dempsey CN, Noonan J, Gowran A, Tanveer R, Olango WM, Finn DP, Campbell VA, Lynch MA. The fatty acid amide hydrolase inhibitor URB597 exerts anti-inflammatory effects in hippocampus of aged rats and restores an age-related deficit in long-term potentiation. J Neuroinflammation. 2012;9:79.
Nadulski T, Pragst F, Weinberg G, Roser P, Schnelle M, Fronk EM, Stadelmann AM. Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract. Ther Drug Monit. 2005;27(6):799–810.
Nahler G, Grotenhermen F, Zuardi AW, Crippa JAS. A conversion of oral Cannabidiol to Delta9-tetrahydrocannabinol seems not to occur in humans. Cannabis Cannabinoid Res. 2017;2(1):81–6.
Nakazawa K, Costa E. Metabolism of delta 9 -tetrahydrocannabinol by lung and liver homogenates of rats treated with methylcholanthrene. Nature. 1971;234(5323):48–9.
Nava F, Manzato E, Lucchini A. Chronic cannabis use does not affect the normalization of hypothalamic-pituitary-adrenal (HPA) axis induced by methadone in heroin addicts. Prog Neuro-Psychopharmacol Biol Psychiatry. 2007;31(5):1089–94.
Navarro M, Carrera MR, Fratta W, Valverde O, Cossu G, Fattore L, Chowen JA, Gomez R, del Arco I, Villanua MA, Maldonado R, Koob GF, Rodriguez de Fonseca F. Functional interaction between opioid and cannabinoid receptors in drug self-administration. J Neurosci. 2001;21(14):5344–50.
Newell KA, Deng C, Huang XF. Increased cannabinoid receptor density in the posterior cingulate cortex in schizophrenia. Exp Brain Res. 2006;172(4):556–60.
Ney LJ, Matthews A, Bruno R, Felmingham KL. Cannabinoid interventions for PTSD: where to next? Prog Neuro-Psychopharmacol Biol Psychiatry. 2019;93:124–40.
Nielsen S, Sabioni P, Trigo JM, Ware MA, Betz-Stablein BD, Murnion B, Lintzeris N, Khor KE, Farrell M, Smith A, Le Foll B. Opioid-sparing effect of cannabinoids: a systematic review and meta-analysis. Neuropsychopharmacology. 2017;42(9):1752–65.
Nomura DK, Morrison BE, Blankman JL, Long JZ, Kinsey SG, Marcondes MC, Ward AM, Hahn YK, Lichtman AH, Conti B, Cravatt BF. Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation. Science. 2011;334(6057):809–13.
O’Sullivan SE, Kendall DA. Cannabinoid activation of peroxisome proliferator-activated receptors: potential for modulation of inflammatory disease. Immunobiology. 2010;215(8):611–6.
O’Sullivan SE, Sun Y, Bennett AJ, Randall MD, Kendall DA. Time-dependent vascular actions of cannabidiol in the rat aorta. Eur J Pharmacol. 2009;612(1–3):61–8.
Oh DA, Parikh N, Khurana V, Cognata Smith C, Vetticaden S. Effect of food on the pharmacokinetics of dronabinol oral solution versus dronabinol capsules in healthy volunteers. Clin Pharmacol. 2017;9:9–17.
Ohlsson A, Lindgren JE, Andersson S, Agurell S, Gillespie H, Hollister LE. Single-dose kinetics of deuterium-labelled cannabidiol in man after smoking and intravenous administration. Biomed Environ Mass Spectrom. 1986;13(2):77–83.
Ohlsson A, Lindgren JE, Wahlen A, Agurell S, Hollister LE, Gillespie HK. Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin Pharmacol Ther. 1980a;28(3):409–16.
Ohlsson A, Widman M, Carlsson S, Ryman T, Strid C. Plasma and brain levels of delta 6-THC and seven monooxygenated metabolites correlated to the cataleptic effect in the mouse. Acta Pharmacol Toxicol (Copenh). 1980b;47(4):308–17.
Okusanya BO, Asaolu IO, Ehiri JE, Kimaru LJ, Okechukwu A, Rosales C. Medical cannabis for the reduction of opioid dosage in the treatment of non-cancer chronic pain: a systematic review. Syst Rev. 2020;9(1):167.
Olatinsu AO, Sihag J, Jones PJH. Relationship between circulating fatty acids and fatty acid Ethanolamide levels after a single 2-h dietary fat feeding in male Sprague-Dawley rats : elevated levels of oleoylethanolamide, palmitoylethanolamide, linoleoylethanolamide, arachidonoylethanolamide and docosahexanoylethanolamide after a single 2 h dietary fat feeding in male Sprague Dawley rats. Lipids. 2017;52(11):901–6.
Olfson M, Wall MM, Liu SM, Blanco C. Cannabis use and risk of prescription opioid use disorder in the United States. Am J Psychiatry. 2018;175(1):47–53.
Patel S, Gerrits R, Muthian S, Greene AS, Hillard CJ. The CB1 receptor antagonist SR141716 enhances stimulus-induced activation of the primary somatosensory cortex of the rat. Neurosci Lett. 2002;335(2):95–8.
Patilea-Vrana GI, Anoshchenko O, Unadkat JD. Hepatic enzymes relevant to the disposition of (−)-(9)-tetrahydrocannabinol (THC) and its psychoactive metabolite, 11-OH-THC. Drug Metab Dispos. 2019;47(3):249–56.
Patsalos PN, Szaflarski JP, Gidal B, VanLandingham K, Critchley D, Morrison G. Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs. Epilepsia. 2020;61:1854–68.
Paudel KS, Hammell DC, Agu RU, Valiveti S, Stinchcomb AL. Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers. Drug Dev Ind Pharm. 2010;36(9):1088–97.
Perez J. Combined cannabinoid therapy via an oromucosal spray. Drugs Today (Barc). 2006;42(8):495–503.
Perkins D, Butler J, Ong K, Nguyen TH, Cox S, Francis B, McIntosh M, Lilley B. A phase 1, randomised, placebo-controlled, dose escalation study to investigate the safety, tolerability and pharmacokinetics of Cannabidiol in fed healthy volunteers. Eur J Drug Metab Pharmacokinet. 2020a;45(5):575–86.
Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol. 2006;147(Suppl 1):S163–71.
Perucca E, Bialer M. Critical aspects affecting Cannabidiol oral bioavailability and metabolic elimination, and related clinical implications. CNS Drugs. 2020;34(8):795–800.
Piomelli D, Tarzia G, Duranti A, Tontini A, Mor M, Compton TR, Dasse O, Monaghan EP, Parrott JA, Putman D. Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). CNS Drug Rev. 2006;12(1):21–38.
Pratt-Hyatt M, Zhang H, Snider NT, Hollenberg PF. Effects of a commonly occurring genetic polymorphism of human CYP3A4 (I118V) on the metabolism of anandamide. Drug Metab Dispos. 2010;38(11):2075–82.
Pugh G Jr, Smith PB, Dombrowski DS, Welch SP. The role of endogenous opioids in enhancing the antinociception produced by the combination of delta 9-tetrahydrocannabinol and morphine in the spinal cord. J Pharmacol Exp Ther. 1996;279(2):608–16.
Qian Y, Gurley BJ, Markowitz JS. The potential for pharmacokinetic interactions between cannabis products and conventional medications. J Clin Psychopharmacol. 2019;39(5):462–71.
Raby WN, Carpenter KM, Rothenberg J, Brooks AC, Jiang H, Sullivan M, Bisaga A, Comer S, Nunes EV. Intermittent marijuana use is associated with improved retention in naltrexone treatment for opiate-dependence. Am J Addict. 2009;18(4):301–8.
Rakhshan F, Day TA, Blakely RD, Barker EL. Carrier-mediated uptake of the endogenous cannabinoid anandamide in RBL-2H3 cells. J Pharmacol Exp Ther. 2000;292(3):960–7.
Rector JL, Tay L, Wiese CW, Friedman EM. Relative sensitivity of cortisol indices to psychosocial and physical health factors. PLoS One. 2019;14(4):e0213513.
Reid S, Bhattacharyya S. Antipsychotic treatment failure in patients with psychosis and co-morbid cannabis use: a systematic review. Psychiatry Res. 2019;280:112523.
Rios C, Gomes I, Devi LA. mu opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis. Br J Pharmacol. 2006;148(4):387–95.
Ritter JK, Li C, Xia M, Poklis JL, Lichtman AH, Abdullah RA, Dewey WL, Li PL. Production and actions of the anandamide metabolite prostamide E2 in the renal medulla. J Pharmacol Exp Ther. 2012;342(3):770–9.
Roberts JD, Gennings C, Shih M. Synergistic affective analgesic interaction between delta-9-tetrahydrocannabinol and morphine. Eur J Pharmacol. 2006;530(1–2):54–8.
Rohleder C, Muller JK, Lange B, Leweke FM. Cannabidiol as a potential new type of an antipsychotic. A critical review of the evidence. Front Pharmacol. 2016;7:422.
Ronen A, Chassidim HS, Gershon P, Parmet Y, Rabinovich A, Bar-Hamburger R, Cassuto Y, Shinar D. The effect of alcohol, THC and their combination on perceived effects, willingness to drive and performance of driving and non-driving tasks. Accid Anal Prev. 2010;42(6):1855–65.
Ropke J, Busanello A, Leal CQ, de Moraes Reis E, de Freitas CM, Villarinho JG, Figueira FH, Mello CF, Ferreira J, Fachinetto R. Anandamide attenuates haloperidol-induced vacuous chewing movements in rats. Prog Neuro-Psychopharmacol Biol Psychiatry. 2014;54:195–9.
Roser P, Haussleiter IS. Antipsychotic-like effects of cannabidiol and rimonabant: systematic review of animal and human studies. Curr Pharm Des. 2012;18(32):5141–55.
Roser P, Vollenweider FX, Kawohl W. Potential antipsychotic properties of central cannabinoid (CB1) receptor antagonists. World J Biol Psychiatry. 2010;11(2 Pt 2):208–19.
Ross RA, Craib SJ, Stevenson LA, Pertwee RG, Henderson A, Toole J, Ellington HC. Pharmacological characterization of the anandamide cyclooxygenase metabolite: prostaglandin E2 ethanolamide. J Pharmacol Exp Ther. 2002;301(3):900–7.
Rouzer CA, Marnett LJ. Endocannabinoid oxygenation by cyclooxygenases, lipoxygenases, and cytochromes P450: cross-talk between the eicosanoid and endocannabinoid signaling pathways. Chem Rev. 2011;111(10):5899–921.
Rubin K, Ewing P, Backstrom E, Abrahamsson A, Bonn B, Kamata S, Grime K. Pulmonary metabolism of substrates for key drug-metabolizing enzymes by human alveolar type II cells, human and rat lung Microsomes, and the isolated perfused rat lung model. Pharmaceutics. 2020;12(2):117.
Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 2005;30(8):1037–43.
Rutkowska M, Jachimczuk O. Antidepressant--like properties of ACEA (arachidonyl-2-chloroethylamide), the selective agonist of CB1 receptors. Acta Pol Pharm. 2004;61(2):165–7.
Sadhasivam S, Zhang X, Chidambaran V, Mavi J, Pilipenko V, Mersha TB, Meller J, Kaufman KM, Martin LJ, McAuliffe J. Novel associations between FAAH genetic variants and postoperative central opioid-related adverse effects. Pharmacogenomics J. 2015;15(5):436–42.
Sanchis-Segura C, Cline BH, Marsicano G, Lutz B, Spanagel R. Reduced sensitivity to reward in CB1 knockout mice. Psychopharmacology. 2004;176(2):223–32.
Sang N, Chen C. Lipid signaling and synaptic plasticity. Neuroscientist. 2006;12(5):425–34.
Sang N, Zhang J, Chen C. PGE2 glycerol ester, a COX-2 oxidative metabolite of 2-arachidonoyl glycerol, modulates inhibitory synaptic transmission in mouse hippocampal neurons. J Physiol. 2006;572(Pt 3):735–45.
Sarris J, Sinclair J, Karamacoska D, Davidson M, Firth J. Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review. BMC Psychiatry. 2020;20(1):24.
Scarpelli R, Sasso O, Piomelli D. A double whammy: targeting both fatty acid amide hydrolase (FAAH) and cyclooxygenase (COX) to treat pain and inflammation. ChemMedChem. 2016;11(12):1242–51.
Scavone JL, Sterling RC, Van Bockstaele EJ. Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal. Neuroscience. 2013b;248:637–54.
Scavone JL, Sterling RC, Weinstein SP, Van Bockstaele EJ. Impact of cannabis use during stabilization on methadone maintenance treatment. Am J Addict. 2013a;22(4):344–51.
Schoedel KA, Szeto I, Setnik B, Sellers EM, Levy-Cooperman N, Mills C, Etges T, Sommerville K. Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: a randomized, double-blind, controlled trial. Epilepsy Behav. 2018;88:162–71.
Schoevers J, Leweke JE, Leweke FM. Cannabidiol as a treatment option for schizophrenia: recent evidence and current studies. Curr Opin Psychiatry. 2020;33(3):185–91.
Schubart CD, Sommer IE, Fusar-Poli P, de Witte L, Kahn RS, Boks MP. Cannabidiol as a potential treatment for psychosis. Eur Neuropsychopharmacol. 2014;24(1):51–64.
Schuchardt JP, Schneider I, Meyer H, Neubronner J, von Schacky C, Hahn A. Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations–a comparative bioavailability study of fish oil vs. krill oil. Lipids Health Dis. 2011;10:145.
Schwope DM, Karschner EL, Gorelick DA, Huestis MA. Identification of recent cannabis use: whole-blood and plasma free and glucuronidated cannabinoid pharmacokinetics following controlled smoked cannabis administration. Clin Chem. 2011;57(10):1406–14.
Secher A, Husum H, Holst B, Egerod KL, Mellerup E. Risperidone treatment increases CB1 receptor binding in rat brain. Neuroendocrinology. 2010;91(2):155–68.
Seillier A, Giuffrida A. Disruption of social cognition in the sub-chronic PCP rat model of schizophrenia: possible involvement of the endocannabinoid system. Eur Neuropsychopharmacol. 2016;26(2):298–309.
Seillier A, Martinez AA, Giuffrida A. Phencyclidine-induced social withdrawal results from deficient stimulation of cannabinoid CB(1) receptors: implications for schizophrenia. Neuropsychopharmacology. 2013;38(9):1816–24.
Sellers EM, Schoedel K, Bartlett C, Romach M, Russo EB, Stott CG, Wright S, White L, Duncombe P, Chen CF. A multiple-dose, randomized, double-blind, placebo-controlled, parallel-group QT/QTc study to evaluate the Electrophysiologic effects of THC/CBD spray. Clin Pharmacol Drug Dev. 2013;2(3):285–94.
Shang VC, O'Sullivan SE, Kendall DA, Roberts RE. The endogenous cannabinoid anandamide increases human airway epithelial cell permeability through an arachidonic acid metabolite. Pharmacol Res. 2016;105:152–63.
Shearman LP, Rosko KM, Fleischer R, Wang J, Xu S, Tong XS, Rocha BA. Antidepressant-like and anorectic effects of the cannabinoid CB1 receptor inverse agonist AM251 in mice. Behav Pharmacol. 2003;14(8):573–82.
Slawson G, Milloy MJ, Balneaves L, Simo A, Guillemi S, Hogg R, Montaner J, Wood E, Kerr T. High-intensity cannabis use and adherence to antiretroviral therapy among people who use illicit drugs in a Canadian setting. AIDS Behav. 2015;19(1):120–7.
Smaga I, Bystrowska B, Gawlinski D, Pomierny B, Stankowicz P, Filip M. Antidepressants and changes in concentration of endocannabinoids and N-acylethanolamines in rat brain structures. Neurotox Res. 2014;26(2):190–206.
Smaga I, Gawlinski D, Brodowicz J, Filip M. Brain region-dependent changes in the expression of endocannabinoid-metabolizing enzymes in rats following antidepressant drugs. J Physiol Pharmacol. 2019;70(5) https://doi.org/10.26402/jpp.2019.5.06.
Smaga I, Jastrzebska J, Zaniewska M, Bystrowska B, Gawlinski D, Faron-Gorecka A, Broniowska Z, Miszkiel J, Filip M. Changes in the brain endocannabinoid system in rat models of depression. Neurotox Res. 2017;31(3):421–35.
Smart R, Pacula RL. Early evidence of the impact of cannabis legalization on cannabis use, cannabis use disorder, and the use of other substances: findings from state policy evaluations. Am J Drug Alcohol Abuse. 2019;45(6):644–63.
Snider NT, Walker VJ, Hollenberg PF. Oxidation of the endogenous cannabinoid arachidonoyl ethanolamide by the cytochrome P450 monooxygenases: physiological and pharmacological implications. Pharmacol Rev. 2010;62(1):136–54.
Solinas M, Goldberg SR. Motivational effects of cannabinoids and opioids on food reinforcement depend on simultaneous activation of cannabinoid and opioid systems. Neuropsychopharmacology. 2005;30(11):2035–45.
Solinas M, Panlilio LV, Goldberg SR. Exposure to delta-9-tetrahydrocannabinol (THC) increases subsequent heroin taking but not heroin's reinforcing efficacy: a self-administration study in rats. Neuropsychopharmacology. 2004;29(7):1301–11.
Spano MS, Fattore L, Cossu G, Deiana S, Fadda P, Fratta W. CB1 receptor agonist and heroin, but not cocaine, reinstate cannabinoid-seeking behaviour in the rat. Br J Pharmacol. 2004;143(3):343–50.
Spector AA. Arachidonic acid cytochrome P450 epoxygenase pathway. J Lipid Res. 2009;50(Suppl):S52–6.
Spiro AS, Wong A, Boucher AA, Arnold JC. Enhanced brain disposition and effects of Delta9-tetrahydrocannabinol in P-glycoprotein and breast cancer resistance protein knockout mice. PLoS One. 2012;7(4):e35937.
Steiner MA, Marsicano G, Nestler EJ, Holsboer F, Lutz B, Wotjak CT. Antidepressant-like behavioral effects of impaired cannabinoid receptor type 1 signaling coincide with exaggerated corticosterone secretion in mice. Psychoneuroendocrinology. 2008;33(1):54–67.
Stinchcomb AL, Valiveti S, Hammell DC, Ramsey DR. Human skin permeation of Delta8-tetrahydrocannabinol, cannabidiol and cannabinol. J Pharm Pharmacol. 2004;56(3):291–7.
Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014;46(1):86–95.
Sugiura T, Kobayashi Y, Oka S, Waku K. Biosynthesis and degradation of anandamide and 2-arachidonoylglycerol and their possible physiological significance. Prostaglandins Leukot Essent Fatty Acids. 2002;66(2–3):173–92.
Sundram S, Copolov D, Dean B. Clozapine decreases [3H] CP 55940 binding to the cannabinoid 1 receptor in the rat nucleus accumbens. Naunyn Schmiedeberg's Arch Pharmacol. 2005;371(5):428–33.
Tai S, Fantegrossi WE. Pharmacological and toxicological effects of synthetic cannabinoids and their metabolites. Curr Top Behav Neurosci. 2017;32:249–62.
Takeuchi K, Renic M, Bohman QC, Harder DR, Miyata N, Roman RJ. Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE. Am J Physiol Heart Circ Physiol. 2005;289(5):H2203–11.
Tang SM, Ansarian A, Courtney DB. Clozapine treatment and cannabis use in adolescents with psychotic disorders – a retrospective cohort chart review. J Can Acad Child Adolesc Psychiatry. 2017;26(1):51–8.
Taylor L, Crockett J, Tayo B, Morrison G. A phase 1, open-label, parallel-group, single-dose trial of the pharmacokinetics and safety of Cannabidiol (CBD) in subjects with mild to severe hepatic impairment. J Clin Pharmacol. 2019;59(8):1110–9.
Taylor L, Gidal B, Blakey G, Tayo B, Morrison G. A phase I, randomized, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect trial of the safety, tolerability and pharmacokinetics of highly purified Cannabidiol in healthy subjects. CNS Drugs. 2018;32(11):1053–67.
Tayo B, Taylor L, Sahebkar F, Morrison G. A phase I, open-label, parallel-group, single-dose trial of the pharmacokinetics, safety, and tolerability of Cannabidiol in subjects with mild to severe renal impairment. Clin Pharmacokinet. 2020;59(6):747–55.
Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. 2007;150(5):613–23.
Thuy Phuong NT, Kim JW, Kim JA, Jeon JS, Lee JY, Xu WJ, Yang JW, Kim SK, Kang KW. Role of the CYP3A4-mediated 11,12-epoxyeicosatrienoic acid pathway in the development of tamoxifen-resistant breast cancer. Oncotarget. 2017;8(41):71054–69.
Tiwari AK, Zai CC, Likhodi O, Lisker A, Singh D, Souza RP, Batra P, Zaidi SH, Chen S, Liu F, Puls I, Meltzer HY, Lieberman JA, Kennedy JL, Muller DJ. A common polymorphism in the cannabinoid receptor 1 (CNR1) gene is associated with antipsychotic-induced weight gain in schizophrenia. Neuropsychopharmacology. 2010;35(6):1315–24.
Tiwari AK, Zai CC, Likhodi O, Voineskos AN, Meltzer HY, Lieberman JA, Potkin SG, Remington G, Muller DJ, Kennedy JL. Association study of cannabinoid receptor 1 (CNR1) gene in tardive dyskinesia. Pharmacogenomics J. 2012;12(3):260–6.
Toczek M, Malinowska B. Enhanced endocannabinoid tone as a potential target of pharmacotherapy. Life Sci. 2018;204:20–45.
Toennes SW, Schneider K, Kauert GF, Wunder C, Moeller MR, Theunissen EL, Ramaekers JG. Influence of ethanol on cannabinoid pharmacokinetic parameters in chronic users. Anal Bioanal Chem. 2011;400(1):145–52.
Tournier N, Chevillard L, Megarbane B, Pirnay S, Scherrmann JM, Decleves X. Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). Int J Neuropsychopharmacol. 2010;13(7):905–15.
Tran A, Rey E, Pons G, Rousseau M, d’Athis P, Olive G, Mather GG, Bishop FE, Wurden CJ, Labroo R, Trager WF, Kunze KL, Thummel KE, Vincent JC, Gillardin JM, Lepage F, Levy RH. Influence of stiripentol on cytochrome P450-mediated metabolic pathways in humans: in vitro and in vivo comparison and calculation of in vivo inhibition constants. Clin Pharmacol Ther. 1997;62(5):490–504.
Tucci SA, Rogers EK, Korbonits M, Kirkham TC. The cannabinoid CB1 receptor antagonist SR141716 blocks the orexigenic effects of intrahypothalamic ghrelin. Br J Pharmacol. 2004;143(5):520–3.
Turna J, Syan SK, Frey BN, Rush B, Costello MJ, Weiss M, MacKillop J. Cannabidiol as a novel candidate alcohol use disorder pharmacotherapy: a systematic review. Alcohol Clin Exp Res. 2019;43(4):550–63.
Tzavara ET, Li DL, Moutsimilli L, Bisogno T, Di Marzo V, Phebus LA, Nomikos GG, Giros B. Endocannabinoids activate transient receptor potential vanilloid 1 receptors to reduce hyperdopaminergia-related hyperactivity: therapeutic implications. Biol Psychiatry. 2006;59(6):508–15.
Uriguen L, Garcia-Fuster MJ, Callado LF, Morentin B, La Harpe R, Casado V, Lluis C, Franco R, Garcia-Sevilla JA, Meana JJ. Immunodensity and mRNA expression of A2A adenosine, D2 dopamine, and CB1 cannabinoid receptors in postmortem frontal cortex of subjects with schizophrenia: effect of antipsychotic treatment. Psychopharmacology. 2009;206(2):313–24.
Vandrey R, Herrmann ES, Mitchell JM, Bigelow GE, Flegel R, LoDico C, Cone EJ. Pharmacokinetic profile of oral cannabis in humans: blood and oral fluid disposition and relation to Pharmacodynamic outcomes. J Anal Toxicol. 2017;41(2):83–99.
VanLandingham KE, Crockett J, Taylor L, Morrison G. A phase 2, double-blind, placebo-controlled trial to investigate potential drug-drug interactions between Cannabidiol and Clobazam. J Clin Pharmacol. 2020;60(10):1304–13.
Vazquez SR. Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Hematology Am Soc Hematol Educ Program. 2018;2018(1):339–47.
Vega OM, Abkenari S, Tong Z, Tedman A, Huerta-Yepez S. Omega-3 polyunsaturated fatty acids and lung cancer: nutrition or pharmacology? Nutr Cancer. 2020;73(4):541–61.
Vigano D, Rubino T, Parolaro D. Molecular and cellular basis of cannabinoid and opioid interactions. Pharmacol Biochem Behav. 2005b;81(2):360–8.
Vigano D, Rubino T, Vaccani A, Bianchessi S, Marmorato P, Castiglioni C, Parolaro D. Molecular mechanisms involved in the asymmetric interaction between cannabinoid and opioid systems. Psychopharmacology. 2005a;182(4):527–36.
Vigano D, Valenti M, Cascio MG, Di Marzo V, Parolaro D, Rubino T. Changes in endocannabinoid levels in a rat model of behavioural sensitization to morphine. Eur J Neurosci. 2004;20(7):1849–57.
Vimalanathan A, Gidyk DC, Diwan M, Gouveia FV, Lipsman N, Giacobbe P, Nobrega JN, Hamani C. Endocannabinoid modulating drugs improve anxiety but not the expression of conditioned fear in a rodent model of post-traumatic stress disorder. Neuropharmacology. 2020;166:107965.
Vinod KY, Arango V, Xie S, Kassir SA, Mann JJ, Cooper TB, Hungund BL. Elevated levels of endocannabinoids and CB1 receptor-mediated G-protein signaling in the prefrontal cortex of alcoholic suicide victims. Biol Psychiatry. 2005;57(5):480–6.
Volk DW, Eggan SM, Horti AG, Wong DF, Lewis DA. Reciprocal alterations in cortical cannabinoid receptor 1 binding relative to protein immunoreactivity and transcript levels in schizophrenia. Schizophr Res. 2014;159(1):124–9.
Vozella V, Zibardi C, Ahmed F, Piomelli D. Fast and sensitive quantification of Delta(9)-tetrahydrocannabinol and its Main oxidative metabolites by liquid chromatography/tandem mass spectrometry. Cannabis Cannabinoid Res. 2019;4(2):110–23.
Vyas MB, LeBaron VT, Gilson AM. The use of cannabis in response to the opioid crisis: a review of the literature. Nurs Outlook. 2018;66(1):56–65.
Wahn H, Wolf J, Kram F, Frantz S, Wagner JA. The endocannabinoid arachidonyl ethanolamide (anandamide) increases pulmonary arterial pressure via cyclooxygenase-2 products in isolated rabbit lungs. Am J Physiol Heart Circ Physiol. 2005;289(6):H2491–6.
Wall ME, Sadler BM, Brine D, Taylor H, Perez-Reyes M. Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clin Pharmacol Ther. 1983;34(3):352–63.
Wang B, Wang J, Huang SQ, Su HH, Zhou SF. Genetic polymorphism of the human cytochrome P450 2C9 gene and its clinical significance. Curr Drug Metab. 2009;10(7):781–834.
Wang J, Shen RY, Haj-Dahmane S. Endocannabinoids mediate the glucocorticoid-induced inhibition of excitatory synaptic transmission to dorsal raphe serotonin neurons. J Physiol. 2012;590(22):5795–808.
Wang S, Lim G, Mao J, Sung B, Yang L, Mao J. Central glucocorticoid receptors regulate the upregulation of spinal cannabinoid-1 receptors after peripheral nerve injury in rats. Pain. 2007;131(1–2):96–105.
Watanabe K, Kayano Y, Matsunaga T, Yamamoto I, Yoshimura H. Inhibition of anandamide amidase activity in mouse brain microsomes by cannabinoids. Biol Pharm Bull. 1996;19(8):1109–11.
Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci. 2007;80(15):1415–9.
Weston-Green K, Huang XF, Deng C. Alterations to melanocortinergic, GABAergic and cannabinoid neurotransmission associated with olanzapine-induced weight gain. PLoS One. 2012;7(3):e33548.
Wheeler CW, Wrighton SA, Guenthner TM. Detection of human lung cytochromes P450 that are immunochemically related to cytochrome P450IIE1 and cytochrome P450IIIA. Biochem Pharmacol. 1992;44(1):183–7.
Wilkerson JL, Ghosh S, Mustafa M, Abdullah RA, Niphakis MJ, Cabrera R, Maldonado RL, Cravatt BF, Lichtman AH. The endocannabinoid hydrolysis inhibitor SA-57: intrinsic antinociceptive effects, augmented morphine-induced antinociception, and attenuated heroin seeking behavior in mice. Neuropharmacology. 2017;114:156–67.
Willoughby KA, Moore SF, Martin BR, Ellis EF. The biodisposition and metabolism of anandamide in mice. J Pharmacol Exp Ther. 1997;282(1):243–7.
Wills KL, Parker LA. Effect of pharmacological modulation of the Endocannabinoid system on opiate withdrawal: a review of the preclinical animal literature. Front Pharmacol. 2016;7:187.
Wilson-Morkeh H, Al-Abdulla A, Sien L, Mohamed H, Youngstein T. Important drug interactions exist between cannabidiol oil and commonly prescribed drugs in rheumatology practice. Rheumatology (Oxford). 2020;59(1):249–51.
Wilson R, Bossong MG, Appiah-Kusi E, Petros N, Brammer M, Perez J, Allen P, McGuire P, Bhattacharyya S. Cannabidiol attenuates insular dysfunction during motivational salience processing in subjects at clinical high risk for psychosis. Transl Psychiatry. 2019;9(1):203.
Wilson RI, Nicoll RA. Endocannabinoid signaling in the brain. Science. 2002;296(5568):678–82.
Wilson RP, Bhattacharyya S. Antipsychotic efficacy in psychosis with co-morbid cannabis misuse: a systematic review. J Psychopharmacol. 2016;30(2):99–111.
Withey SL, Bergman J, Huestis MA, George SR, Madras BK. THC and CBD blood and brain concentrations following daily administration to adolescent primates. Drug Alcohol Depend. 2020;213:108129.
Wolowich WR, Greif R, Kleine-Brueggeney M, Bernhard W, Theiler L. Minimal physiologically based pharmacokinetic model of intravenously and orally Administered Delta-9-tetrahydrocannabinol in healthy volunteers. Eur J Drug Metab Pharmacokinet. 2019;44(5):691–711.
Wood JT, Williams JS, Pandarinathan L, Janero DR, Lammi-Keefe CJ, Makriyannis A. Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma. J Lipid Res. 2010;51(6):1416–23.
Woodward DF, Liang Y, Krauss AH. Prostamides (prostaglandin-ethanolamides) and their pharmacology. Br J Pharmacol. 2008;153(3):410–9.
Wray L, Stott C, Jones N, Wright S. Cannabidiol Does Not Convert to Delta(9)-Tetrahydrocannabinol in an In Vivo Animal Model. Cannabis Cannabinoid Res. 2017;2(1):282–7.
Yamaguchi T, Hagiwara Y, Tanaka H, Sugiura T, Waku K, Shoyama Y, Watanabe S, Yamamoto T. Endogenous cannabinoid, 2-arachidonoylglycerol, attenuates naloxone-precipitated withdrawal signs in morphine-dependent mice. Brain Res. 2001;909(1–2):121–6.
Yamaori S, Ebisawa J, Okushima Y, Yamamoto I, Watanabe K. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci. 2011a;88(15–16):730–6.
Yamaori S, Ishii H, Chiba K, Yamamoto I, Watanabe K. Delta-tetrahydrocannabinol induces cytotoxicity in macrophage J774-1 cells: involvement of cannabinoid receptor 2 and p38 MAPK. Toxicology. 2013;314(2–3):254–61.
Yamaori S, Kinugasa Y, Jiang R, Takeda S, Yamamoto I, Watanabe K. Cannabidiol induces expression of human cytochrome P450 1A1 that is possibly mediated through aryl hydrocarbon receptor signaling in HepG2 cells. Life Sci. 2015;136:87–93.
Yamaori S, Koeda K, Kushihara M, Hada Y, Yamamoto I, Watanabe K. 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. 2012;27(3):294–300.
Yamaori S, Kushihara M, Yamamoto I, Watanabe K. Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochem Pharmacol. 2010;79(11):1691–8.
Yamaori S, Okamoto Y, Yamamoto I, Watanabe K. Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos. 2011b;39(11):2049–56.
Yang W, Ni J, Woodward DF, Tang-Liu DD, Ling KH. Enzymatic formation of prostamide F2alpha from anandamide involves a newly identified intermediate metabolite, prostamide H2. J Lipid Res. 2005;46(12):2745–51.
Yu HL, Deng XQ, Li YJ, Li YC, Quan ZS, Sun XY. N-palmitoylethanolamide, an endocannabinoid, exhibits antidepressant effects in the forced swim test and the tail suspension test in mice. Pharmacol Rep. 2011;63(3):834–9.
Yu M, Ives D, Ramesha CS. Synthesis of prostaglandin E2 ethanolamide from anandamide by cyclooxygenase-2. J Biol Chem. 1997;272(34):21181–6.
Zanger UM, Klein K, Thomas M, Rieger JK, Tremmel R, Kandel BA, Klein M, Magdy T. Genetics, epigenetics, and regulation of drug-metabolizing cytochrome p450 enzymes. Clin Pharmacol Ther. 2014;95(3):258–61.
Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013;138(1):103–41.
Zavitsanou K, Garrick T, Huang XF. Selective antagonist [3H]SR141716A binding to cannabinoid CB1 receptors is increased in the anterior cingulate cortex in schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry. 2004;28(2):355–60.
Zendulka O, Dovrtelova G, Noskova K, Turjap M, Sulcova A, Hanus L, Jurica J. Cannabinoids and cytochrome P450 interactions. Curr Drug Metab. 2016;17(3):206–26.
Zhang JY, Wang Y, Prakash C. Xenobiotic-metabolizing enzymes in human lung. Curr Drug Metab. 2006;7(8):939–48.
Zhang Y, Hu L, Mori TA, Barden A, Croft KD, Whitworth JA. Arachidonic acid metabolism in glucocorticoid-induced hypertension. Clin Exp Pharmacol Physiol. 2008;35(5–6):557–62.
Zhang Z, Wang W, Zhong P, Liu SJ, Long JZ, Zhao L, Gao HQ, Cravatt BF, Liu QS. Blockade of 2-arachidonoylglycerol hydrolysis produces antidepressant-like effects and enhances adult hippocampal neurogenesis and synaptic plasticity. Hippocampus. 2015;25(1):16–26.
Zhong P, Wang W, Pan B, Liu X, Zhang Z, Long JZ, Zhang HT, Cravatt BF, Liu QS. Monoacylglycerol lipase inhibition blocks chronic stress-induced depressive-like behaviors via activation of mTOR signaling. Neuropsychopharmacology. 2014;39(7):1763–76.
Zhu HJ, Wang JS, Markowitz JS, Donovan JL, Gibson BB, Gefroh HA, Devane CL. Characterization of P-glycoprotein inhibition by major cannabinoids from marijuana. J Pharmacol Exp Ther. 2006;317(2):850–7.
Zuardi AW, Hallak JE, Dursun SM, Morais SL, Sanches RF, Musty RE, Crippa JA. Cannabidiol monotherapy for treatment-resistant schizophrenia. J Psychopharmacol. 2006;20(5):683–6.
Zuardi AW, Morais SL, Guimaraes FS, Mechoulam R. Antipsychotic effect of cannabidiol. J Clin Psychiatry. 1995;56(10):485–6.
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Davis, M.P. (2022). Cannabinoid-Based Medicine: Pharmacology and Drug Interactions. In: Cannabis and Cannabinoid-Based Medicines in Cancer Care. Springer, Cham. https://doi.org/10.1007/978-3-030-89918-9_2
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