Cannabinoids and the endocannabinoid system in the regulation of cytochrome P450 metabolic activity-a review

. 2025 ; 16 () : 1599012. [epub] 20250605

Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic-ecollection

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid40538541

The use of cannabinoids has a history spanning thousands of years, and their pharmacological and toxicological properties, particularly those of THC and CBD, are well-documented. However, their potential to induce drug-drug interactions remains underexplored. This review aims to provide a comprehensive perspective by contextualizing the historical and pharmacological significance of cannabinoids while focusing on their capacity to modulate the metabolic activity of cytochrome P450 isoforms relevant to drug metabolism. Additionally, we look at the impact of cannabinoids in neuronal circuits impacting the hypothalamic-pituitary hormonal axis, such as the locus coeruleus and raphe nuclei and their possible consequences on the cytochrome P450 system. Recognising potential interactions between cannabinoids and other drugs could enhance understanding of their pharmacological effects, improve the efficacy and safety profiles of cannabinoid-based therapies, and encourage further exploration into this under-researched area of psychopharmacology, with implications for both preclinical research and clinical practice.

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Aggarwal S. K., Carter G. T., Sullivan M. D., ZumBrunnen C., Morrill R., Mayer J. D. (2009). Medicinal use of cannabis in the United States: historical perspectives, current trends, and future directions. J. Opioid Manag. 5, 153–168. 10.5055/jom.2009.0016 PubMed DOI

Alzu’bi A., Almahasneh F., Khasawneh R., Abu-El-Rub E., Baker W. B., Al-Zoubi R. M. (2024). The synthetic cannabinoids menace: a review of health risks and toxicity. Eur. J. Med. Res. 29, 49. 10.1186/s40001-023-01443-6 PubMed DOI PMC

Arreaza G., Devane W. A., Omeir R. L., Sajnani G., Kunz J., Cravatt B. F., et al. (1997). The cloned rat hydrolytic enzyme responsible for the breakdown of anandamide also catalyzes its formation via the condensation of arachidonic acid and ethanolamine. Neurosci. Lett. 234, 59–62. 10.1016/s0304-3940(97)00673-3 PubMed DOI

Atalay S., Jarocka-Karpowicz I., Skrzydlewska E. (2019). Antioxidative and anti-inflammatory properties of Cannabidiol. Antioxidants (Basel) 9, 21. 10.3390/antiox9010021 PubMed DOI PMC

Atakan Z. (2012). Cannabis, a complex plant: different compounds and different effects on individuals. Ther. Adv. Psychopharmacol. 2, 241–254. 10.1177/2045125312457586 PubMed DOI PMC

Bansal S., Maharao N., Paine M. F., Unadkat J. D. (2020). Predicting the potential for cannabinoids to precipitate pharmacokinetic drug interactions via reversible inhibition or inactivation of major cytochromes P450. Drug Metab. Dispos. 48, 1008–1017. 10.1124/dmd.120.000073 PubMed DOI PMC

Bansal S., Paine M. F., Unadkat J. D. (2022). Comprehensive predictions of cytochrome P450 (P450)-mediated PubMed DOI PMC

Baratta F., Pignata I., Ravetto Enri L., Brusa P. (2022). Cannabis for medical use: analysis of recent clinical trials in view of current legislation. Front. Pharmacol. 13, 888903. 10.3389/fphar.2022.888903 PubMed DOI PMC

Berglund B. A., Boring D. L., Howlett A. C. (1999). Investigation of structural analogs of prostaglandin amides for binding to and activation of CB1 and CB2 cannabinoid receptors in rat brain and human tonsils. Adv. Exp. Med. Biol. 469, 527–533. 10.1007/978-1-4615-4793-8_77 PubMed DOI

Bisogno T., Hanus L., De Petrocellis L., Tchilibon S., Ponde D. E., Brandi I., et al. (2001). 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. 134, 845–852. 10.1038/sj.bjp.0704327 PubMed DOI PMC

Blanton H., Yin L., Duong J., Benamar K. (2022). Cannabidiol and beta-caryophyllene in combination: a therapeutic functional interaction. Int. J. Mol. Sci. 23, 15470. 10.3390/ijms232415470 PubMed DOI PMC

Breton-Provencher V., Drummond G. T., Sur M. (2021). Locus coeruleus norepinephrine in learned behavior: anatomical modularity and spatiotemporal integration in targets. Front. Neural Circuits 15, 638007. 10.3389/fncir.2021.638007 PubMed DOI PMC

Bromek E., Rysz M., Haduch A., Daniel W. A. (2019). Serotonin receptors of 5-HT2 type in the hypothalamic arcuate nuclei positively regulate liver cytochrome P450 via stimulation of the growth hormone-releasing hormone/growth hormone hormonal pathway. Drug Metab. Dispos. 47, 80–85. 10.1124/dmd.118.083808 PubMed DOI

Bromek E., Rysz M., Haduch A., Wójcikowski J., Daniel W. A. (2018). Activation of 5-ht1a receptors in the hypothalamic paraventricular nuclei negatively regulates cytochrome P450 expression and activity in rat liver. Drug Metab. Dispos. 46, 786–793. 10.1124/dmd.117.079632 PubMed DOI

Bromek E., Wójcikowski J., Daniel W. A. (2013). Involvement of the paraventricular (PVN) and arcuate (ARC) nuclei of the hypothalamus in the central noradrenergic regulation of liver cytochrome P450. Biochem. Pharmacol. 86, 1614–1620. 10.1016/j.bcp.2013.09.006 PubMed DOI

Brown P., Molliver M. E. (2000). Dual serotonin (5-HT) projections to the nucleus accumbens core and shell: relation of the 5-HT transporter to amphetamine-induced neurotoxicity. J. Neurosci. 20, 1952–1963. 10.1523/JNEUROSCI.20-05-01952.2000 PubMed DOI PMC

Carlini E. A., Cunha J. M. (1981). Hypnotic and antiepileptic effects of cannabidiol. J. Clin. Pharmacol. 21, 417S-427S–427S. 10.1002/j.1552-4604.1981.tb02622.x PubMed DOI

Carriba P., Ortiz O., Patkar K., Justinova Z., Stroik J., Themann A., et al. (2007). Striatal adenosine A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids. Neuropsychopharmacology 32, 2249–2259. 10.1038/sj.npp.1301375 PubMed DOI

Casarett L. J., Doull J., Klaassen C. D. (2008). Casarett and Doull’s toxicology: the basic science of poisons. 7th ed. (New York: McGraw-Hill; ).

Cascio M. G., Gauson L. A., Stevenson L. A., Ross R. A., Pertwee R. G. (2010). Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. Br. J. Pharmacol. 159, 129–141. 10.1111/j.1476-5381.2009.00515.x PubMed DOI PMC

Chen J., Varga A., Selvarajah S., Jenes A., Dienes B., Sousa-Valente J., et al. (2016). Spatial distribution of the cannabinoid type 1 and capsaicin receptors may contribute to the complexity of their crosstalk. Sci. Rep. 6, 33307. 10.1038/srep33307 PubMed DOI PMC

Chevaleyre V., Takahashi K. A., Castillo P. E. (2006). Endocannabinoid-mediated synaptic plasticity in the CNS. Annu. Rev. Neurosci. 29, 37–76. 10.1146/annurev.neuro.29.051605.112834 PubMed DOI

Chowdhury K. U., Holden M. E., Wiley M. T., Suppiramaniam V., Reed M. N. (2024). Effects of cannabis on glutamatergic neurotransmission: the interplay between cannabinoids and glutamate. Cells 13, 1130. 10.3390/cells13131130 PubMed DOI PMC

Crocq M.-A. (2020). History of cannabis and the endocannabinoid system. Dialogues Clin. Neurosci. 22, 223–228. 10.31887/DCNS.2020.22.3/mcrocq PubMed DOI PMC

Dauchy S., Miller F., Couraud P.-O., Weaver R. J., Weksler B., Romero I.-A., et al. (2009). Expression and transcriptional regulation of ABC transporters and cytochromes P450 in hCMEC/D3 human cerebral microvascular endothelial cells. Biochem. Pharmacol. 77, 897–909. 10.1016/j.bcp.2008.11.001 PubMed DOI

Daujat M., Peryt B., Lesca P., Fourtanier G., Domergue J., Maurel P. (1992). Omeprazole, an inducer of human PubMed DOI

Deutsch D. G., Chin S. A. (1993). Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist. Biochem. Pharmacol. 46, 791–796. 10.1016/0006-2952(93)90486-G PubMed DOI

Devane W. A., Hanus L., Breuer A., Pertwee R. G., Stevenson L. A., Griffin G., et al. (1992). Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258, 1946–1949. 10.1126/science.1470919 PubMed DOI

Di Giovanni G. (2010). Dopamine interaction with other neurotransmitter systems: relevance in the pathophysiology and treatment of CNS disorders. CNS Neurosci. Ther. 16, 125–126. 10.1111/j.1755-5949.2010.00143.x PubMed DOI PMC

Di Marzo V. (2009). The endocannabinoid system: its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploitation. Pharmacol. Res. 60, 77–84. 10.1016/j.phrs.2009.02.010 PubMed DOI

Di Marzo V. (2018). New approaches and challenges to targeting the endocannabinoid system. Nat. Rev. Drug Discov. 17, 623–639. 10.1038/nrd.2018.115 PubMed DOI

Doohan P. T., Oldfield L. D., Arnold J. C., Anderson L. L. (2021). Cannabinoid interactions with cytochrome P450 drug metabolism: a full-spectrum characterization. AAPS J. 23, 91. 10.1208/s12248-021-00616-7 PubMed DOI

Dvorak Z., Pavek P. (2010). Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids. Drug Metab. Rev. 42, 621–635. 10.3109/03602532.2010.484462 PubMed DOI

El Khoury M.-A., Gorgievski V., Moutsimilli L., Giros B., Tzavara E. T. (2012). Interactions between the cannabinoid and dopaminergic systems: evidence from animal studies. Prog. Neuropsychopharmacol. Biol. Psychiatry 38, 36–50. 10.1016/j.pnpbp.2011.12.005 PubMed DOI

European Medicines Agency (2019). European medicines agency. Available online at: https://www.ema.europa.eu/en/medicines/human/EPAR/epidyolex (Accessed May 5, 2025).

Evagorou A., Anagnostopoulos D., Farmaki E., Siafaka-Kapadai A. (2010). Hydrolysis of 2-arachidonoylglycerol in Tetrahymena thermophila. Identification and partial characterization of a Monoacylglycerol Lipase-like enzyme. Eur. J. Protistol. 46, 289–297. 10.1016/j.ejop.2010.06.001 PubMed DOI

Fernández‐Ruiz J., Hernández M., Ramos J. A. (2010). Cannabinoid–dopamine interaction in the pathophysiology and treatment of CNS disorders. CNS Neurosci. Ther. 16, e72–e91. 10.1111/j.1755-5949.2010.00144.x PubMed DOI PMC

Gaoni Y., Mechoulam R. (1964). Isolation, structure, and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc. 86, 1646–1647. 10.1021/ja01062a046 DOI

Gertsch J., Leonti M., Raduner S., Racz I., Chen J.-Z., Xie X.-Q., et al. (2008). Beta-caryophyllene is a dietary cannabinoid. Proc. Natl. Acad. Sci. U. S. A. 105, 9099–9104. 10.1073/pnas.0803601105 PubMed DOI PMC

Gonsiorek W., Lunn C., Fan X., Narula S., Lundell D., Hipkin R. W. (2000). Endocannabinoid 2-arachidonyl glycerol is a full agonist through human type 2 cannabinoid receptor: antagonism by anandamide. Mol. Pharmacol. 57, 1045–1050. 10.1016/s0026-895x(24)26516-0 PubMed DOI

Gonzalez B., Paz F., Florán L., Aceves J., Erlij D., Florán B. (2009). Cannabinoid agonists stimulate [3H]GABA release in the globus pallidus of the rat when G(i) protein-receptor coupling is restricted: role of dopamine D2 receptors. J. Pharmacol. Exp. Ther. 328, 822–828. 10.1124/jpet.108.145425 PubMed DOI

Granja A. G., Carrillo-Salinas F., Pagani A., Gómez-Cañas M., Negri R., Navarrete C., et al. (2012). A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis. J. Neuroimmune Pharmacol. 7, 1002–1016. 10.1007/s11481-012-9399-3 PubMed DOI

Groce E. (2018). The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. J. Med. Regul. 104, 32. 10.30770/2572-1852-104.4.32 DOI

Grotenhermen F., Russo E. B. (2002). Cannabis and cannabinoids: pharmacology, toxicology, and therapeutic potential. 1st Edn. New York, NY: Routledge.

Haduch A., Bromek E., Kuban W., Basińska-Ziobroń A., Danek P. J., Alenina N., et al. (2023). The effect of brain serotonin deficit (TPH2-KO) on the expression and activity of liver cytochrome P450 enzymes in aging male Dark Agouti rats. Pharmacol. Rep. 75, 1522–1532. 10.1007/s43440-023-00540-x PubMed DOI PMC

Haduch A., Bromek E., Pukło R., Jastrzębska J., Danek P. J., Daniel W. A. (2022). The effect of the selective N-methyl-D-aspartate (NMDA) receptor GluN2B subunit antagonist CP-101,606 on cytochrome P450 2D (CYP2D) expression and activity in the rat liver and brain. Int. J. Mol. Sci. 23, 13746. 10.3390/ijms232213746 PubMed DOI PMC

Halpert J. R. (1995). Structural basis of selective cytochrome P450 inhibition. Annu. Rev. Pharmacol. Toxicol. 35, 29–53. 10.1146/annurev.pa.35.040195.000333 PubMed DOI

Hermann H., Marsicano G., Lutz B. (2002). Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain. Neuroscience 109, 451–460. 10.1016/s0306-4522(01)00509-7 PubMed DOI

Jang Y. su, Jeong S., Kim A.-ram, Mok B. R., Son S. J., Ryu J., et al. (2023). Cannabidiol mediates epidermal terminal differentiation and redox homeostasis through aryl hydrocarbon receptor (AhR)-dependent signaling. J. Dermatological Sci. 109, 61–70. 10.1016/j.jdermsci.2023.01.008 PubMed DOI

Jéquier E., Lovenberg W., Sjoerdsma A. (1967). Tryptophan hydroxylase inhibition: the mechanism by which p-chlorophenylalanine depletes rat brain serotonin. Mol. Pharmacol. 3, 274–278. 10.1016/s0026-895x(25)14792-5 PubMed DOI

Katzung B. G. (2018). Basic and clinical pharmacology. Fourteenth edition (New York Chicago San Francisco Athens London Madrid Mexico City Milan New Delhi Singapore Sydney Toronto: McGraw-Hill Education; ).

Kim D.-K., Kim Y.-H., Jang H.-H., Park J., Kim J. R., Koh M., et al. (2013). Estrogen-related receptor γ controls hepatic CB1 receptor-mediated CYP2E1 expression and oxidative liver injury by alcohol. Gut 62, 1044, 1054. 10.1136/gutjnl-2012-303347 PubMed DOI PMC

Knight T. R., Choudhuri S., Klaassen C. D. (2008). Induction of hepatic glutathione S-transferases in male mice by prototypes of various classes of microsomal enzyme inducers. Toxicol. Sci. 106, 329–338. 10.1093/toxsci/kfn179 PubMed DOI PMC

Kot M., Daniel W. A. (2011). Cytochrome P450 is regulated by noradrenergic and serotonergic systems. Pharmacol. Res. 64, 371–380. 10.1016/j.phrs.2011.06.020 PubMed DOI

Kot M., Pilc A., Daniel W. A. (2012). Simultaneous alterations of brain and plasma serotonin concentrations and liver cytochrome P450 in rats fed on a tryptophan-free diet. Pharmacol. Res. 66, 292–299. 10.1016/j.phrs.2012.06.009 PubMed DOI

Kuban W., Daniel W. A. (2021). Cytochrome P450 expression and regulation in the brain. Drug Metab. Rev. 53, 1–29. 10.1080/03602532.2020.1858856 PubMed DOI

Kuepper R., Morrison P. D., van Os J., Murray R. M., Kenis G., Henquet C. (2010). Does dopamine mediate the psychosis-inducing effects of cannabis? A review and integration of findings across disciplines. Schizophr. Res. 121, 107–117. 10.1016/j.schres.2010.05.031 PubMed DOI

Landa L., Juřica J., Slíva J., Pechacková M., Demlová R. (2018). Medical cannabis in the treatment of cancer pain and spastic conditions and options of drug delivery in clinical practice. Biomed. Pap. 162 (1), 18–25. 10.5507/bp.2018.007 PubMed DOI

Laprairie R. B., Bagher A. M., Kelly M. E. M., Denovan-Wright E. M. (2015). Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br. J. Pharmacol. 172, 4790–4805. 10.1111/bph.13250 PubMed DOI PMC

Lenoir C., Rollason V., Desmeules J. A., Samer C. F. (2021). Influence of inflammation on cytochromes P450 activity in adults: a systematic review of the literature. Front. Pharmacol. 12, 733935. 10.3389/fphar.2021.733935 PubMed DOI PMC

Lin J. H., Lu A. Y. (1998). Inhibition and induction of cytochrome P450 and the clinical implications. Clin. Pharmacokinet. 35, 361–390. 10.2165/00003088-199835050-00003 PubMed DOI

Lněničková K., Svobodová H., Skálová L., Ambrož M., Novák F., Matoušková P. (2018). The impact of sesquiterpenes β-caryophyllene oxide and trans-nerolidol on xenobiotic-metabolizing enzymes in mice PubMed DOI

Manthey J., Freeman T. P., Kilian C., López-Pelayo H., Rehm J. (2021). Public health monitoring of cannabis use in Europe: prevalence of use, cannabis potency, and treatment rates. Lancet Regional Health - Eur. 10, 100227. 10.1016/j.lanepe.2021.100227 PubMed DOI PMC

Marsicano G., Lutz B. (1999). Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain. Eur. J. Neurosci. 11, 4213–4225. 10.1046/j.1460-9568.1999.00847.x PubMed DOI

Matias I., Chen J., Petrocellis L. D., Bisogno T., Ligresti A., Fezza F., et al. (2004). Prostaglandin ethanolamides (prostamides): PubMed DOI

Mechoulam R., Ben-Shabat S., Hanus L., Ligumsky M., Kaminski N. E., Schatz A. R., et al. (1995). Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 50, 83–90. 10.1016/0006-2952(95)00109-D PubMed DOI

Melis M., Pistis M., Perra S., Muntoni A. L., Pillolla G., Gessa G. L. (2004). Endocannabinoids mediate presynaptic inhibition of glutamatergic transmission in rat ventral tegmental area dopamine neurons through activation of CB1 receptors. J. Neurosci. 24, 53–62. 10.1523/JNEUROSCI.4503-03.2004 PubMed DOI PMC

Mendiguren A., Pineda J. (2004). Cannabinoids enhance N-methyl-d-aspartate-induced excitation of locus coeruleus neurons by CB1 receptors in rat brain slices. Neurosci. Lett. 363, 1–5. 10.1016/j.neulet.2004.02.073 PubMed DOI

Mendiguren A., Pineda J. (2006). Systemic effect of cannabinoids on the spontaneous firing rate of locus coeruleus neurons in rats. Eur. J. Pharmacol. 534, 83–88. 10.1016/j.ejphar.2006.01.002 PubMed DOI

Menezes M. C. de. (2024). Canábis: Maldita e Maravilhosa. Alfragide: Oficina do Livro.

Michelsen K. A., Prickaerts J., Steinbusch H. W. M. (2008). The dorsal raphe nucleus and serotonin: implications for neuroplasticity linked to major depression and Alzheimer’s disease. Prog. Brain Res. 172, 233–264. 10.1016/S0079-6123(08)00912-6 PubMed DOI

Mitrano D. A., Schroeder J. P., Smith Y., Cortright J. J., Bubula N., Vezina P., et al. (2012). α-1 Adrenergic receptors are localized on presynaptic elements in the nucleus accumbens and regulate mesolimbic dopamine transmission. Neuropsychopharmacology 37, 2161–2172. 10.1038/npp.2012.68 PubMed DOI PMC

Nagao M., Nakano Y., Tajima M., Sugiyama E., Sato V. H., Inada M., et al. (2020). Nonlinear disposition and metabolic interactions of cannabidiol through CYP3A inhibition PubMed DOI PMC

Navarro G., Varani K., Reyes-Resina I., Sánchez de Medina V., Rivas-Santisteban R., Sánchez-Carnerero Callado C., et al. (2018). Cannabigerol action at cannabinoid CB1 and CB2 receptors and at CB1–CB2 heteroreceptor complexes. Front. Pharmacol. 9, 632. 10.3389/fphar.2018.00632 PubMed DOI PMC

Nebert D. W., Wikvall K., Miller W. L. (2013). Human cytochromes P450 in health and disease. Philos. Trans. R. Soc. Lond B Biol. Sci. 368, 20120431. 10.1098/rstb.2012.0431 PubMed DOI PMC

Nguyen L. T., Myslivečková Z., Szotáková B., Špičáková A., Lněničková K., Ambrož M., et al. (2017). The inhibitory effects of β-caryophyllene, β-caryophyllene oxide and α-humulene on the activities of the main drug-metabolizing enzymes in rat and human liver PubMed DOI

Niederhoffer N., Schmid K., Szabo B. (2003). The peripheral sympathetic nervous system is the major target of cannabinoids in eliciting cardiovascular depression. Schmiedeb. Arch. Pharmacol. 367, 434–443. 10.1007/s00210-003-0755-y PubMed DOI

Nyíri G., Cserép C., Szabadits E., MacKie K., Freund T. F. (2005). CB1 cannabinoid receptors are enriched in the perisynaptic annulus and on preterminal segments of hippocampal GABAergic axons. Neuroscience 136, 811–822. 10.1016/j.neuroscience.2005.01.026 PubMed DOI

Pavek P. (2016). Pregnane X receptor (PXR)-Mediated gene repression and cross-talk of PXR with other nuclear receptors via coactivator interactions. Front. Pharmacol. 7, 456. 10.3389/fphar.2016.00456 PubMed DOI PMC

Pelkonen O., Turpeinen M., Hakkola J., Honkakoski P., Hukkanen J., Raunio H. (2008). Inhibition and induction of human cytochrome P450 enzymes: current status. Arch. Toxicol. 82, 667–715. 10.1007/s00204-008-0332-8 PubMed DOI

Pertwee R. G. (2008). Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond. Addict. Biol. 13, 147–159. 10.1111/j.1369-1600.2008.00108.x PubMed DOI

Pukło R., Bromek E., Haduch A., Basińska-Ziobroń A., Kuban W., Daniel W. A. (2023). Molecular mechanisms of the regulation of liver cytochrome P450 by brain NMDA receptors and via the neuroendocrine pathway—a significance for new psychotropic therapies. Int. J. Mol. Sci. 24, 16840. 10.3390/ijms242316840 PubMed DOI PMC

Raz N., Eyal A. M., Zeitouni D. B., Hen-Shoval D., Davidson E. M., Danieli A., et al. (2023). Selected cannabis terpenes synergize with THC to produce increased CB1 receptor activation. Biochem. Pharmacol. 212, 115548. 10.1016/j.bcp.2023.115548 PubMed DOI

Resstel L. B., Tavares R. F., Lisboa S. F., Joca S. R., Corrêa F. M., Guimarães F. S. (2009). 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br. J. Pharmacol. 156, 181–188. 10.1111/j.1476-5381.2008.00046.x PubMed DOI PMC

Rockwell C. E., Kaminski N. E. (2004). A cyclooxygenase metabolite of anandamide causes inhibition of interleukin-2 secretion in murine splenocytes. J. Pharmacol. Exp. Ther. 311, 683–690. 10.1124/jpet.104.065524 PubMed DOI

Rodríguez de Fonseca F., Del Arco I., Bermudez-Silva F., Bilbao A., Cippitelli A., Navarro M. (2005). The endocannabinoid system: physiology and pharmacology. Alcohol Alcohol. 40, 2–14. 10.1093/alcalc/agh110 PubMed DOI

Roque-Bravo R., Silva R. S., Malheiro R. F., Carmo H., Carvalho F., da Silva D. D., et al. (2023). Synthetic cannabinoids: a pharmacological and toxicological overview. Annu. Rev. Pharmacol. Toxicol. 63, 187–209. 10.1146/annurev-pharmtox-031122-113758 PubMed DOI

Ross S. B. (1976). Long-term effects of N-2-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurones in the rat brain and heart. Br. J. Pharmacol. 58, 521–527. 10.1111/j.1476-5381.1976.tb08619.x PubMed DOI PMC

Ross S. B., Johansson J. G., Lindborg B., Dahlbom R. (1973). Cyclizing compounds. I. Tertiary N-(2-bromobenzyl)-N-haloalkylamines with adrenergic blocking action. Acta Pharm. Suec. 10, 29–42. PubMed

Roth M. D., Marques-Magallanes J. A., Yuan M., Sun W., Tashkin D. P., Hankinson O. (2001). Induction and regulation of the carcinogen-metabolizing enzyme CYP1A1 by marijuana smoke and delta (9)-tetrahydrocannabinol. Am. J. Respir. Cell Mol. Biol. 24, 339–344. 10.1165/ajrcmb.24.3.4252 PubMed DOI

Roy P., Dennis D. G., Eschbach M. D., Anand S. D., Xu F., Maturano J., et al. (2022). Metabolites of cannabigerol generated by human cytochrome P450s are bioactive. Biochemistry 61, 2398–2408. 10.1021/acs.biochem.2c00383 PubMed DOI PMC

Russo E. B. (2017). Cannabidiol claims and misconceptions. Trends Pharmacol. Sci. 38, 198–201. 10.1016/j.tips.2016.12.004 PubMed DOI

Russo E. B., Burnett A., Hall B., Parker K. K. (2005). Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem. Res. 30, 1037–1043. 10.1007/s11064-005-6978-1 PubMed DOI

Rysz M., Bromek E., Haduch A., Liskova B., Wójcikowski J., Daniel W. A. (2016). The reverse role of the hypothalamic paraventricular (PVN) and arcuate (ARC) nuclei in the central serotonergic regulation of the liver cytochrome P450 isoform CYP2C11. Biochem. Pharmacol. 112, 82–89. 10.1016/j.bcp.2016.04.017 PubMed DOI

Šadibolová M., Zárybnický T., Smutný T., Pávek P., Šubrt Z., Matoušková P., et al. (2019). Sesquiterpenes are agonists of the pregnane X receptor but do not induce the expression of phase I drug-metabolizing enzymes in the human liver. Int. J. Mol. Sci. 20, 4562. 10.3390/ijms20184562 PubMed DOI PMC

Sanders-Bush E., Bushing J. A., Sulser F. (1975). Long-term effects of p-chloroamphetamine and related drugs on central serotonergic mechanisms. J. Pharmacol. Exp. Ther. 192, 33–41. 10.1016/s0022-3565(25)30027-3 PubMed DOI

Schlicker E., Kathmann M. (2001). Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol. Sci. 22, 565–572. 10.1016/s0165-6147(00)01805-8 PubMed DOI

Simard M., Archambault A.-S., Lavoie J.-P. C., Dumais É., Di Marzo V., Flamand N. (2022). Biosynthesis and metabolism of endocannabinoids and their congeners from the monoacylglycerol and N-acyl-ethanolamine families. Biochem. Pharmacol. 205, 115261. 10.1016/j.bcp.2022.115261 PubMed DOI

Soliño M., Larrayoz I. M., López E. M., Rey-Funes M., Bareiro M., Loidl C. F., et al. (2022). CB1 cannabinoid receptor is a target for neuroprotection in light induced retinal degeneration. Adv. Drug Alcohol Res. 2, 10734. 10.3389/adar.2022.10734 PubMed DOI PMC

Sperlágh B., Windisch K., Andó R. D., Sylvester Vizi E. (2009). Neurochemical evidence that stimulation of CB1 cannabinoid receptors on GABAergic nerve terminals activates the dopaminergic reward system by increasing dopamine release in the rat nucleus accumbens. Neurochem. Int. 54, 452–457. 10.1016/j.neuint.2009.01.017 PubMed DOI

Suriaga A., Tappen R. M., Aston E. R., Chiang-Hanisko L., Newman D. (2023). Cannabinoids and synthetic cannabinoids as a cause of death: trends and their healthcare implications. J. Nurs. Scholarsh. 55, 623–636. 10.1111/jnu.12817 PubMed DOI PMC

Szabadi E. (2013). Functional neuroanatomy of the central noradrenergic system. J. Psychopharmacol. 27, 659–693. 10.1177/0269881113490326 PubMed DOI

Treyer A., Reinhardt J. K., Eigenmann D. E., Oufir M., Hamburger M. (2023). Phytochemical comparison of medicinal cannabis extracts and study of their CYP-mediated interactions with coumarinic oral anticoagulants. Med. Cannabis Cannabinoids 6, 21–31. 10.1159/000528465 PubMed DOI PMC

U.S. Food and Drug Administration (2020). FDA. Available online at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms (Accessed May 5, 2025).

U.S. Food and Drug Administration (2023). FDA. Available online at: https://www.fda.gov/news-events/public-health-focus/fda-and-cannabis-research-and-drug-approval-process (Accessed May 5, 2025).

Wójcikowski J., Daniel W. A. (2008). Identification of factors mediating the effect of the brain dopaminergic system on the expression of cytochrome P450 in the liver. Pharmacol. Rep. 60, 966–971. PubMed

Wójcikowski J., Daniel W. A. (2009). The brain dopaminergic system as an important center regulating liver cytochrome P450 in the rat. Expert Opin. drug metabolism and Toxicol. 5, 631–645. 10.1517/17425250902973703 PubMed DOI

Wójcikowski J., Daniel W. A. (2011). The role of the nervous system in the regulation of liver cytochrome p450. Curr. Drug Metab. 12, 124–138. 10.2174/138920011795016908 PubMed DOI

Wójcikowski J., Gołembiowska K., Daniel W. A. (2007). The regulation of liver cytochrome P450 by the brain dopaminergic system. CDM 8, 631–638. 10.2174/138920007781368872 PubMed DOI

Wójcikowski J., Gołembiowska K., Daniel W. A. (2008). Regulation of liver cytochrome P450 by activation of brain dopaminergic system: physiological and pharmacological implications. Biochem. Pharmacol. 76, 258–267. 10.1016/j.bcp.2008.04.016 PubMed DOI

Yamaori S., Kinugasa Y., Jiang R., Takeda S., Yamamoto I., Watanabe K. (2015). Cannabidiol induces expression of human cytochrome P450 1A1 that is possibly mediated through aryl hydrocarbon receptor signaling in HepG2 cells. Life Sci. 136, 87–93. 10.1016/j.lfs.2015.07.007 PubMed DOI

Yamaori S., Koeda K., Kushihara M., Hada Y., Yamamoto I., Watanabe K. (2012). Comparison in the PubMed DOI

Yamaori S., Kushihara M., Yamamoto I., Watanabe K. (2010). Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochem. Pharmacol. 79, 1691–1698. 10.1016/j.bcp.2010.01.028 PubMed DOI

Yamaori S., Maeda C., Yamamoto I., Watanabe K. (2011a). Differential inhibition of human cytochrome P450 2A6 and 2B6 by major phytocannabinoids. Forensic Toxicol. 29, 117–124. 10.1007/s11419-011-0112-7 DOI

Yamaori S., Okamoto Y., Yamamoto I., Watanabe K. (2011b). Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab. Dispos. 39, 2049–2056. 10.1124/dmd.111.041384 PubMed DOI

Zendulka O., Dovrtělová G., Nosková K., Turjap M., Šulcová A., Hanuš L., et al. (2016). Cannabinoids and cytochrome P450 interactions. Curr. Drug Metab. 17, 206–226. 10.2174/1389200217666151210142051 PubMed DOI

Zhang Y., Kim D.-K., Lee J.-M., Park S. B., Jeong W.-I., Kim S. H., et al. (2015). Orphan nuclear receptor oestrogen-related receptor γ (ERRγ) plays a key role in hepatic cannabinoid receptor type 1-mediated induction of CYP7A1 gene expression. Biochem. J. 470, 181–193. 10.1042/BJ20141494 PubMed DOI PMC

Zuardi A. W. (2006). History of cannabis as a medicine: a review. Braz J. Psychiatry 28, 153–157. 10.1590/s1516-44462006000200015 PubMed DOI

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