Onkolojide Tıbbi Kannabis ve Sentetik Türevlerinin Kullanımı
Özet
Tıbbi kannabis ve sentetik türevlerinin onkoloji alanındaki terapötik potansiyeli ve riskleri, son yıllarda klinik araştırmaların odağında yer almaktadır. Kannabis bitkisinin ana aktif bileşiği olan delta-9-tetrahidrokanabinol (THC) ve psikotropik etkileri modüle edebilen kannabidiol (CBD), vücuttaki CB1 ve CB2 reseptörlerine bağlanarak etki gösterir. Yapılan çalışmalar, bu maddelerin özellikle kemoterapi kaynaklı dirençli bulantı ve kusmanın önlenmesinde ve opioid tedavisine yanıt vermeyen kanser ağrılarının hafifletilmesinde önemli terapötik faydalar sağlayabildiğini ortaya koymaktadır. Ancak, iştah kaybı ve kaşeksi üzerindeki etkilerine dair araştırma sonuçları birbiriyle uyumsuz olup, hormonal preparatlar kadar üstün bir başarı gösteremediğini işaret etmektedir. En kritik bulgu ise kannabinoidlerin bağışıklık sistemini baskılayıcı etkileridir; özellikle anti-PD-L1 antikorları gibi immünoterapi ajanlarıyla birlikte kullanıldığında sitotoksik T lenfositlerinin işlevini bozarak genel sağ kalım sürelerinde ciddi bir düşüşe yol açtığı saptanmıştır. Hücre hatlarında görülen umut verici tümör süpresör etkiler henüz hayvan deneyleriyle tutarlı şekilde desteklenemediğinden ve halüsinasyon, sedasyon gibi ciddi advers etkiler barındırdığından, onkoloji pratiğinde güvenli kullanım için daha fazla klinik çalışmaya ihtiyaç duyulmaktadır.
The therapeutic potential and risks of medical cannabis and its synthetic derivatives in oncology have become a major focus of clinical research in recent years. The primary active compound of the plant, delta-9-tetrahydrocannabinol (THC), and cannabidiol (CBD), which modulates psychotropic properties, exert their effects by binding to CB1 and CB2 receptors in the body. Studies demonstrate that these cannabinoids offer significant therapeutic benefits, particularly in managing refractory chemotherapy-induced nausea and vomiting and alleviating cancer-related pain that remains unresponsive to conventional opioid regimens. However, data regarding their efficacy against appetite loss and cachexia remain inconsistent, indicating that they do not outperform standard hormonal therapies like megestrol acetate. The most critical finding involves their immunosuppressive nature; when combined with immunotherapy agents such as anti-PD-L1 antibodies, cannabinoids impair the function of cytotoxic T lymphocytes, correlating with a substantial reduction in both progression-free and overall survival rates. Although in vitro studies show promising tumor-suppressive activities, these results are not consistently supported by animal models, and given the high incidence of adverse events like sedation and hallucinations, further extensive clinical trials are strictly required before widespread adoption in oncological practice.
Referanslar
Lebel-Hardenack S, Grant SR. Genetics of sex determination in flowering plants. Trends in Plant Science. 1997;2(4):130-136. doi:10.1016/S1360-1385(97)01012-1
Touw M. The religious and medicinal uses of cannabis in China, India and Tibet. J Psychoactive Drugs. 1981;13(1):23-34. doi: 10.1080/02791072.1981.10471447
Pisanti S, Bifulco M. Medical Cannabis: A plurimillennial history of an evergreen. J Cell Physiol. 2019;234(6):8342-8351. doi: 10.1002/jcp.27725
Kalant H. Medicinal use of cannabis: history and current status. Pain Res Manag. 2001;6(2):80-91. doi: 10.1155/2001/469629
Ebbert JO, Scharf EL, Hurt RT. Medical cannabis. Mayo Clin Proc. 2018;93(12):1842-1847. doi: 10.1016/j.mayocp.2018.09.005
Arias S, Leon M, Jaimes D, et al. Clinical evidence of magistral preparations based on medicinal cannabis. Pharmaceuticals (Basel). 2021;14(2):78. doi: 10.3390/ph14020078
T.C. Resmi Gazete. Kenevir yetiştiriciliği ve kontrolü hakkında yönetmelik 2016. (23.02.2023 tarihinde https://www.resmigazete.gov.tr/eskiler/2016/09/20160929-3.htm) adresinden ulaşılmıştır.
Amin MR, Ali DW. Pharmacology of medical cannabis. Adv Exp Med Biol. 2019;1162:151-165. doi: 10.1007/978-3-030-21737-2_8
Crocq MA. History of cannabis and the endocannabinoid system. Dialogues Clin Neurosci. 2020;22(3):223-228. doi: 10.31887/DCNS.2020.22.3/mcrocq
Boggs DL, Nguyen JD, Morgenson D, et al. Clinical and preclinical evidence for functional interactions of cannabidiol and Δ9-tetrahydrocannabinol. Neuropsychopharmacology. 2018;43(1):142-154. doi: 10.1038/npp.2017.209
ElSohly MA, Radwan MM, Gul W, et al. Phytochemistry of cannabis sativa L. Prog Chem Org Nat Prod. 2017;103:1-36. doi: 10.1007/978-3-319-45541-9_1
Schurman LD, Lu D, Kendall DA, et al. Molecular mechanism and cannabinoid pharmacology. Handb Exp Pharmacol. 2020;258:323-353. doi: 10.1007/164_2019_298
Karimi-Haghighi S, Razavi Y, Iezzi D, et al. Cannabidiol and substance use disorder: dream or reality. Neuropharmacology. 2022;207:108948. doi: 10.1016/j.neuropharm.2022.108948
Britch SC, Babalonis S, Walsh SL. Cannabidiol: pharmacology and therapeutic targets. Psychopharmacology (Berl). 2021;238(1):9-28. doi: 10.1007/s00213-020-05712-8
Bodine M, Kemp AK. Medical cannabis use in oncology. Treasure Island (FL): StatPearls Publishing; 2022.
Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol. 2018;84(11):2477-2482. doi: 10.1111/bcp.13710
Briscoe J, Casarett D. Medical marijuana use in older adults. J Am Geriatr Soc. 2018;66(5):859-863. doi: 10.1111/jgs.15346
Cloutier RM, Calhoun BH, Linden-Carmichael AN. Associations of mode of administration on cannabis consumption and subjective intoxication in daily life. Psychol Addict Behav. 2022;36(1):67-77. doi: 10.1037/adb0000726
Bar-Sela G, Cohen I, Campisi-Pinto S, et al. Cannabis consumption used by cancer patients during immunotherapy correlates with poor clinical outcome. Cancers (Basel). 2020;12(9):2447. doi: 10.3390/cancers12092447
Henriquez JE, Bach AP, Matos-Fernandez KM, et al. Δ9-Tetrahydrocannabinol (THC) impairs CD8+ T cell-mediated activation of astrocytes. J Neuroimmune Pharmacol. 2020;15(4):863-874. doi: 10.1007/s11481-020-09912-z
Janelsins MC, Tejani MA, Kamen C, et al. Current pharmacotherapy for chemotherapy-induced nausea and vomiting in cancer patients. Expert Opin Pharmacother. 2013;14(6):757-66. doi: 10.1517/14656566.2013.776541
Aapro M. CINV: still troubling patients after all these years. Support Care Cancer. 2018;26(Suppl 1):5-9. doi: 10.1007/s00520-018-4131-3
Wickham RJ. Revisiting the physiology of nausea and vomiting-challenging the paradigm. Support Care Cancer. 2020;28(1):13-21. doi: 10.1007/s00520-019-05012-8
Shirley M. Netupitant/palonosetron: A review in chemotherapy-induced nausea and vomiting. drugs. 2021;81(11):1331-1342. doi: 10.1007/s40265-021-01558-2
Grimison P, Mersiades A, Kirby A, et al. Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial. Ann Oncol. 2020;31(11):1553-1560. doi: 10.1016/j.annonc.2020.07.020
Polito S, MacDonald T, Romanick M, et al. Safety and efficacy of nabilone for acute chemotherapy-induced vomiting prophylaxis in pediatric patients: a multicenter, retrospective review. Pediatr Blood Cancer. 2018;65(12):e27374. doi: 10.1002/pbc.27374
Boland EG, Bennett MI, Allgar V, et al. Cannabinoids for adult cancer-related pain: systematic review and meta-analysis. BMJ Support Palliat Care. 2020;10(1):14-24. doi: 10.1136/bmjspcare-2019-002032
Johnson JR, Burnell-Nugent M, Lossignol D, et al. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage. 2010;39(2):167-79. doi: 10.1016/j.jpainsymman.2009.06.008
Pawasarat IM, Schultz EM, Frisby JC, et al. The efficacy of medical marijuana in the treatment of cancer-related pain. J Palliat Med. 2020;23(6):809-816. doi: 10.1089/jpm.2019.0374.
Pin F, Barreto R, Couch ME, et al. Cachexia induced by cancer and chemotherapy yield distinct perturbations to energy metabolism. J Cachexia Sarcopenia Muscle. 2019;10(1):140-154. doi: 10.1002/jcsm.12360
Strasser F, Luftner D, Possinger K, et al. Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the cannabis-in-cachexia-study-group. J Clin Oncol. 2006;24(21):3394-400. doi: 10.1200/JCO.2005.05.1847
Jatoi A, Windschitl HE, Loprinzi CL, et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a north central cancer treatment group study. J Clin Oncol. 2002;20(2):567-73. doi: 10.1200/JCO.2002.20.2.567
Wang J, Wang Y, Tong M, et al. Medical cannabinoids for cancer cachexia: a systematic review and meta-analysis. Biomed Res Int. 2019;2019:2864384. doi: 10.1155/2019/2864384
Hinz B, Ramer R. Anti-tumour actions of cannabinoids. Br J Pharmacol. 2019;176(10):1384-1394. doi: 10.1111/bph.14426
Xiong X, Chen S, Shen J, et al. Cannabis suppresses antitumor immunity by inhibiting JAK/STAT signaling in T cells through CNR2. Signal Transduct Target Ther. 2022;7(1):99. doi: 10.1038/s41392-022-00918-y
Baram L, Peled E, Berman P, et al. The heterogeneity and complexity of cannabis extracts as antitumor agents. Oncotarget. 2019;10(41):4091-4106. doi: 10.18632/oncotarget.26983
