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Cannabidiol bei Tumorerkrankungen

Cannabidiol in cancer treatment

Zusammenfassung

Hintergrund

Cannabis wurde bereits vor ca. 2500 Jahren bei Krebspatienten verwendet. Experimentelle Untersuchungen zeigten schon vor mehr als 40 Jahren eine tumorinhibierende Aktivität verschiedener Cannabinoide. In Anbetracht der Stellung von THC als Suchtgift kommt dem nichtpsychotomimetischen CBD eine besondere Bedeutung zu.

Fragestellung

Tumorwirksamkeit von reinem CBD in verschiedenen Tiermodellen sowie erste Ergebnisse (Fallberichte) an Patienten.

Material, Methode

Übersicht der Literatur zu Tierstudien und Fallberichte mit CBD

Ergebnisse

Präklinische Untersuchungen insbesondere während der letzten Jahre, darunter an zahlreichen Tumormodellen am Tier, weisen unisono auf eine therapeutische Wirksamkeit von CBD hin. In vereinzelt durchgeführten Kombinationsstudien zeigten sich in der Regel synergistische Effekte. Darüber hinaus kann CBD möglicherweise in der palliativmedizinischen Versorgung von Patienten insbesondere bei Symptomen wie Schmerzen, Schlaflosigkeit, Angstzuständen und Depression eine Rolle spielen. Weitergehende Humanstudien wären wünschenswert.

Abstract

Background

Cannabis was used for cancer patients as early as about 2500 years ago. Experimental studies demonstrated tumor-inhibiting activities of various cannabinoids more than 40 years ago. In view of the status of tetrahydrocannabinol (THC) as a regulated substance, non-psychotomimetic cannabidiol (CBD) is of particular importance.

Objectives

Efficacy of pure CBD in various animal models as well as initial results (case reports) from patients.

Methods

Review of the literature on animal experiments and observations in humans.

Results

Preclinical studies, particularly recent ones, including numerous animal models of tumors, unanimously suggest the therapeutic efficacy of CBD. In isolated combination studies, synergistic effects were generally observed. In addition, CBD may potentially play a role in the palliative care of patients, especially concerning symptoms such as pain, insomnia, anxiety, and depression. Further human studies are warranted.

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Literatur

  1. 1.

    Abrams DI (2016) Integrating cannabis into clinical cancer care. Curr Oncol 23(S2):S8–S14

  2. 2.

    Armstrong JL, Hill DS, McKee CS, Hernandez-Tiedra S, Lorente M, Lopez-Valero I et al (2015) Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death. J Invest Dermatol 135(6):1629–1637

  3. 3.

    Aviello G, Romano B, Borrelli F, Capasso R, Gallo L, Piscitelli F et al (2012) Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer. J Mol Med 90(8):925–934

  4. 4.

    Calpe-Lopez C, Garcia-Pardo MP, Aguilar MA (2019) Cannabidiol treatment might promote resilience to cocaine and methamphetamine use disorders: a review of possible mechanisms. Molecules 24(14):E2583. https://doi.org/10.3390/molecules24142583

  5. 5.

    Chavez T (2019) New British study on CBD and pediatric tumors. https://cashcbdoil.com/2019/04/21/new-british-study-on-cbd-and-pediatric-tumors/. Zugegriffen: 07.09.2019

  6. 6.

    Casey SL, Atwal N, Vaughan CW (2017) Cannabis constituent synergy in a mouse neuropathic pain model. Pain 158(12):2452–2460

  7. 7.

    Dall’Stella PB, Docema MFL, Maldaun MVC, Feher O, Lancellotti CLP (2019) Case report: clinical outcome and image response of two patients with secondary high-grade glioma treated with chemoradiation, PCV, and cannabidiol. Front Oncol 8:643. https://doi.org/10.3389/fonc.2018.00643

  8. 8.

    De Gregorio D, McLaughlin RJ, Posa L, Ochoa-Sanchez R, Enns J, Lopez-Canul M et al (2019) Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain 160(1):136–150

  9. 9.

    De Petrocellis L, Ligresti A, Schiano Moriello A, Iapelli M, Verde R, Stott CG et al (2013) Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms. Br J Pharmacol 168:79–102

  10. 10.

    Elbaz M, Nasser MW, Ravi J, Wani NA, Ahirwar DK, Zhao H et al (2015) Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: novel anti-tumor mechanisms of cannabidiol in breast cancer. Mol Oncol 9:906–919

  11. 11.

    Ferro R, Adamska A, Lattanzio R, Mavrommati I, Edling CE, Arifin SA et al (2018) GPR55 signalling promotes proliferation of pancreatic cancer cells and tumour growth in mice, and its inhibition increases effects of gemcitabine. Oncogene 37(49):6368–6382

  12. 12.

    Fisher Z, Golan H, Schiby G, PriChen S, Smoum R, Moshe I et al (2016) In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma. Curr Oncol 23(S2):S15–S22

  13. 13.

    Fouad AA, Albuali WH, Al-Mulhim AS, Jresat I (2013) Cardioprotective effect of cannabidiol in rats exposed to doxorubicin toxicity. Environ Toxicol Pharmacol 36(2):347–357

  14. 14.

    Galaj E, Bi GH, Yang HJ, Xi ZX (2019) Cannabidiol attenuates the rewarding effects of cocaine in rats by CB2, 5‑TH1A and TRPV1 receptor mechanisms. Neuropharmacology. https://doi.org/10.1016/j.neuropharm.2019.107740

  15. 15.

    Grauso F, Autiero R, Lannino GR, Zizolfi B, Perone C, Messalli EM (2019) The role of the endocannabinoid system in the gynaecological malignancy. Preprints. https://doi.org/10.20944/preprints201806.0001.v1

  16. 16.

    Hao E, Mukhopadhyay P, Cao Z, Erdelyi K, Holovac E, Liaudet L et al (2015) Cannabidiol protects against doxorubicin-induced cardiomyopathy by modulating mitochondrial function and biogenesis. Mol Med. https://doi.org/10.2119/molmed.2014.00261

  17. 17.

    Harris H, Radwan M, Gul W, ElSohly M, Sufka K (2018) Effects of cannabidiol and a novel cannabidiol analog against tactile allodynia in a murine model of cisplatin-induced neuropathy; synergistic effects of sub-analgesic doses of morphine. Med Cannabis Cannabinoids 1:54–59

  18. 18.

    Hay GL, Baracz SJ, Everett NA, Roberts J, Costa PA, Arnold JC et al (2018) Cannabidiol treatment reduces the motivation to self-administer methamphetamine and methamphetamine-primed relapse in rats. J Psychopharmacol 32(12):1369–1378

  19. 19.

    Katsidoni V, Anagnostou I, Panagis G (2013) Cannabidiol inhibits the reward-facilitating effect of morphine: involvement of 5‑HT 1A receptors in the dorsal raphe nucleus. Addict Biol 18:286–296

  20. 20.

    Kenyon JN, Fuller RJ, Lewis TJ (2018) Report of objective clinical responses of cancer patients to pharmaceutical-grade synthetic cannabidiol. Anticancer Res 38:5831–5835

  21. 21.

    King KM, Myers AM, Soroka-Monzo AJ, Tuma RF, Tallarida RJ, Walker EA et al (2017) Single and combined effects of ∆9-tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain. Br J Pharmacol 174(17):2832–2841

  22. 22.

    Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C et al (2012) Cannabidiol enhances anandamide signalling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry 2:e94. https://doi.org/10.1038/tp.2012.15

  23. 23.

    Ligresti A, Moriello AS, Starowicz K, Matias I, Pisanti S, De Petrocellis L et al (2006) Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther 318(3):1375–1387

  24. 24.

    Likar R, Koestenberger M, Stultschnig M, Nahler G (2019) Concomitant treatment of malignant brain tumours with CBD—a case series and review of the literature. Anticancer Res 39:5797–5801

  25. 25.

    Likar R, Nahler G (2017) The use of cannabis in supportive care and treatment of brain tumor. Neurooncol Pract 4(3):151–160

  26. 26.

    Likar R (2016) Cannabidiol: Schmerzreduktion bei therapieresistenten Fällen

  27. 27.

    Linge R, Jimenez-Sanchez L, Campa L, Pilar-Cuellar F, Vidal R, Pazos A et al (2016) Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5‑HT/glutamate neurotransmission: role of 5‑HT1A receptors. Neuropharmacology 103:16–26

  28. 28.

    Lukhele ST, Motadi LR (2016) Cannabidiol rather than cannabis sativa extracts inhibit cell growth and induce apoptosis in cervical cancer cells. BMC Complement Altern Med 16(1):335

  29. 29.

    Massi P, Solinas M, Cinquina V, Parolaro D (2013) Cannabidiol as potential anticancer drug. Br J Clin Pharmacol 75(2):303–312

  30. 30.

    Massi P, Valenti M, Vaccani A, Gasperi V, Perletti G, Marras E et al (2008) 5‑Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid. J Neurochem 104:1091–1100

  31. 31.

    Massi P, Vaccani A, Ceruti S, Colombo A, Abbracchio MP, Parolaro D (2004) Antitumor effects of cannabidiol, a non-psychoactive cannabinoid, on human glioma cell lines. J Pharmacol Exp Ther 308(3):838–845

  32. 32.

    Munson AE, Harris LS, Friedman MA, Dewey WL, Carchman RA (1975) Antineoplastic activity of cannabinoids. J Natl Cancer Inst 55(3):597–602

  33. 33.

    Pan H, Mukhopadhyay P, Rajesh M, Patel V, Mukhopadhyay B, Gao B et al (2009) Cannabidiol attenuates cisplatin-induced nephrotoxicity by decreasing oxidative/nitrosative stress, inflammation and cell death. J Pharmacol Exp Ther 328(3):708–714

  34. 34.

    Ramer R, Bublitz K, Freimuth N, Merkord J, Rohde H, Haustein M et al (2012) Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule‑1. Faseb J 26(4):1535–1548

  35. 35.

    Rock EM, Bolognini D, Limebeer CL, Cascio MG, Anavi-Goffer S, Fletcher PJ et al (2012) Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5‑HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus. Br J Pharmacol 165(8):2620–2634

  36. 36.

    Romano B (2014) Non-psychotropic phytocannabinoids in intestinal inflammation and colon cancer

  37. 37.

    Scott KA, Dalgleish AG, Liu WM (2014) The combination of cannabidiol and ∆9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model. Mol Cancer Ther 13(12):2955–2967

  38. 38.

    Shannon S, Lewis N, Lee H, Hughes S (2019) Cannabidiol in anxiety and sleep: a large case series. Perm J 23:18–41

  39. 39.

    Sharafi G, He H, Nikfarjam M (2019) Potential use of cannabinoids for the treatment of pancreatic cancer. J Pancreat Cancer 5(1):1–7

  40. 40.

    Simmerman E, Qin X, Yu JC, Baban B (2019) Cannabinoids as a potential new and novel treatment for melanoma: a pilot study in a murine model. J Surg Res 235:210–215

  41. 41.

    Singer E, Judkins J, Salomonis N, Matlaf L, Soteropoulos P, McAllister S et al (2015) Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma. Cell Death Dis 6:e1601. https://doi.org/10.1038/cddis.2014.566

  42. 42.

    Soroceanu L, Murase R, Limbad C, Singer E, Allison J, Adrados I et al (2013) Id‑1 is a key transcriptional regulator of glioblastoma aggressiveness and a novel therapeutic target. Cancer Res 73(5):1559–1569

  43. 43.

    Sulé-Suso J, Watson NA, van Pittius DG, Jegannathen A (2019) Striking lung cancer response to self-administration of cannabidiol: a case report and literature review. SAGE Open Med Case Rep 7:1–4

  44. 44.

    Torres S, Lorente M, Rodriguez-Fornes F, Hernandez-Tiedra S, Salazar M, Garcia-Taboada E et al (2011) A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol Cancer Ther 10(1):90–103

  45. 45.

    Waissengrin B, Urban D, Leshem Y, Garty M, Wolf I (2015) Patterns of use of medical cannabis among Israeli cancer patients: a single institution experience. J Pain Symptom Manage 49(2):223–230

  46. 46.

    Ward SJ, McAllister SD, Kawamura R, Murase R, Neelakantan H, Walker EA (2014) Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5‑HT(1A) receptors without diminishing nervous system function or chemotherapy efficacy. Br J Pharmacol 171:636–645

  47. 47.

    Xu C, Chang T, Du Y, Yu C, Tan X, Li X (2019) Pharmacokinetics of oral and intravenous cannabidiol and its antidepressant-like effects in chronic mild stress mouse model. Environ Toxicol Pharmacol 70:103202

  48. 48.

    Zogopoulos P (2015) Cancer therapy—the role of cannabinoids and endocannabinoids. Cancer Cell Microenviron 2:e583. https://doi.org/10.14800/ccm.583

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Author information

Correspondence to Dr. Markus Köstenberger.

Ethics declarations

Interessenkonflikt

R. Likar, M. Köstenberger und G. Nahler geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Likar, R., Köstenberger, M. & Nahler, G. Cannabidiol bei Tumorerkrankungen. Schmerz (2020) doi:10.1007/s00482-019-00438-9

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Schlüsselwörter

  • Cannabidiol (CBD)
  • Cannabinoide
  • Krebs
  • Maligne Erkrankung
  • Tumor

Keywords

  • Cannabidiol (CBD)
  • Cannabinoids
  • Cancer
  • Malignant disease
  • Tumors