Opioid Kullanım Bozukluklarında İmmünoterapi

Yıl 2021, , 109 - 125, 31.03.2021

Bahadır Geniş , Hakan Aksu , Zehra Arıkan

https://doi.org/10.18863/pgy.738689

Öz

Opioid kullanım bozuklukları dünya çapında ölümcül bir sorundur. Farmakolojik tedaviler yoksunluk için etkilidir, ancak bağımlılığın tedavisinde yetersiz kalmaktadır. İmmünoterapi, opioid kullanım bozukluklarında umut verici bir tedavi yöntemidir. İmmünoterapi, antikorlarla maddeleri tespit etmeyi ve yakalamayı amaçlamaktadır. Maddelere karşı üretilen spesifik antikorlar psikoaktif bir maddeye bağlanır ve kan / beyin bariyerinden geçmelerini önler. Kan beyin bariyerini geçemeyen psikoaktif madde hem öfori etkisini hem de solunum depresyonu gibi yan etkilerini ortaya koyamayacaktır. Klinik öncesi çalışmalar etkinlik ve güvenilirlik açısından kısmen yeterlidir. Bununla birlikte, aşıları takiben kanda uzun süreli yüksek antikor seviyeleri elde edilememiştir. Klinik araştırma düzeyine ulaşmış olan opioid aşıları ile ilgili çalışma sayısı çok düşüktür. Aşıların etkinliğini artırma çabaları devam etmektedir. Bu çalışmalarda olumlu sonuçlar alınmasına rağmen aşılama çalışmalarında bazı zorluklar bulunmaktadır. Aşı gelişiminin mali yükü, opioid bağımlılarında çoklu maddelerin kullanımı, opioidlerin bağışıklık sistemi baskılanması ve opioid saflık derecesindeki değişiklikler bunlardan bazılarıdır. Tüm bu zorluklara rağmen, immünoterapi araştırmacıların ve hastaların umutla bekledikleri tedavidir.

Anahtar Kelimeler

opioid bağımlılığı, morfin, aşı, eroin, immünoterapi, antikor

Immunotherapy in Opioid Use Disorders

Öz

Opioid use disorders are a deadly problem worldwide. Pharmacological therapies are effective for abstinence but remain inadequate in the treatment of addiction. Immunotherapy is a promising treatment modality in opioid use disorders. Immunotherapy aims to detect and capture substances by antibodies. Specific antibodies generated against substances bind a psychoactive substance and prevent them from passing through the blood/brain barrier. The psychoactive substance, which cannot pass through the blood brain barrier, will not be able to reveal both the euphoria effect and its side effects such as respiratory depression. Pre-clinical studies are partially sufficient in terms of effectiveness and reliability. However, long term high antibody levels could not be obtained in the blood following the vaccinations. The number of studies on opioid vaccines that have reached the clinical research level is very low. Thus, the effect of matter in the brain is prevented from occurring. Although effective results were obtained in preclinical studies, long-term high antibody levels could not be achieved in the blood. The number of studies that have reached the level of clinical research is insufficient. Efforts to increase the effectiveness of vaccines are ongoing. Although positive results are obtained in these studies, there are some difficulties vaccination studies. The financial burden of vaccine development, the use of multiple substances in opioid dependents, immune system suppression by the opioids, and changes in the degree of opioid purity are some of them. Despite all these difficulties, immunotherapy is the treatment that the researchers and patients expect with hope.

Anahtar Kelimeler

opioid addiction, morphine, heroin, vaccine, immunotherapy, antibody

Kaynakça

• Abbas A, Lichtman A, Pillai S (2012) B cell activation and antibody production. Cellular and molecular immunology, 7. baskı, Abbas A, Lichtman A, Pillai S (Ed), Philadelphia, Elsevier Saunders, s. 243-68.
• Akbarzadeh A, Norouzian D, Farhangi A, Mehrabi MR, Bakhtiari M, Afshar P ve ark. (2007) Study of human therapeutic morphine vaccine: Safety and immunogenicity. Asain J Biochem 2: 58-65.
• Akbarzadeh A, Norouzian D, Farhangi A, Mehrabi MR, Chiani M, Zare D ve ark. (2009) Immunotherapy of 347 volunteer outpatient morphine addicts by human therapeutic morphine vaccine in Kermanshah province of Iran. J Pharmacol Toxicol 4: 30-5.
• Anton B, Leff P (2006) A novel bivalent morphine/heroin vaccine that prevents relapse to heroin addiction in rodents. Vaccine 24: 3232-40.
• Avrupa Uyuşturucu ve Uyuşturucu Bağımlılığını İzleme Merkezi (2019) Avrupa Uyuşturucu Raporu 2019: Eğilimler ve Gelişmeler. Lüksemburg: Avrupa Toplulukları Resmi Yayınlar Bürosu, s. 24.
• Baruffaldi F, Kelcher AH, Laudenbach M, Gradinati V, Limkar A, Roslawski M ve ark. (2018) Preclinical efficacy and characterization of candidate vaccines for treatment of opioid use disorders using clinically viable carrier proteins. Mol Pharm 15: 4947-62.
• Bell JR, Butler B, Lawrance A, Batey R, Salmelainen P (2009) Comparing overdose mortality associated with methadone and buprenorphine treatment. Drug Alcohol Depend 104: 73-7.
• Berkowitz B, Spector S (1972) Evidence for active immunity to morphine in mice. Science 178: 1290-92.
• Berterame S, Erthal J, Thomas J, Fellner S, Vosse B, Clare P ve ark. (2016) Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study. Lancet 387: 1644-56.
• Bonese KF, Wainer BH, Fitch FW, Rothberg RM, Schuster CR ve ark. (1974) Changes in heroin self-administration by a rhesus monkey after morphine immunisation. Nature 252: 708-10.
• Borg L, Khuri E, Wells A, Melia D, Bergasa NV, Ho A ve ark. (1999) Methadone-maintained former heroin addicts, including those who are anti-HIV-1 seropositive, comply with and respond to hepatitis B vaccination. Addiction 94: 489-93.
• Bremer PT, Kimishima A, Schlosburg JE, Zhou B, Collins KC, Janda KD ve ark. (2016) Combatting synthetic designer opioids: a conjugate vaccine ablates lethal doses of fentanyl class drugs. Angew Chem Int Ed Engl 55: 3772-5.
• Campa A, Martinez SS, Baum M (2017) Drug addiction, relapse and recovery. J Drug Abuse 3: 1-2.
• Center for Behavioral Health Statistics and Quality (2015). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health. 20.12.2019'da https://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf adresinden indirildi.
• Compton WM, Jones CM, Baldwin GT (2016) Relationship between nonmedical prescription-opioid use and heroin use. N Engl 374: 154-63.
• Cornuz J, Zwahlen S, Jungi WF, Osterwalder J, Klingler K, Van Melle G ve ark. (2008) A vaccine against nicotine for smoking cessation: a randomized controlled trial. PLoS One 3: e2547.
• Crowley TJ, Wagner JE, Zerbe G, Macdonald M (1985) Naltrexone-induced dysphoria in former opioid addicts. Am J Psychiatry 142: 1081-4.
• Delves PJ, Roitt IM (2000) The immune system. First of two parts. N Engl 343: 37-49.
• Durmaz EÖ (2013) B hücre aktivasyonu ve antikor üretimi. Türkderm-Deri Hastalıkları ve Frengi Arşivi Dergisi 47: 24-7.
• Evren EC, Tamar D, Babayağmur B, Çakmak D (2000) Opioid bağımlılığının tedavisinde buprenorfin: metadonla karşılaştırma çalışmaları. Klinik Psikofarmakoloji Bülteni 10: 205-12.
• Giglio RE, Li G, DiMaggio CJ (2015) Effectiveness of bystander naloxone administration and overdose education programs: a meta-analysis. Inj Epidemiol 2: 10.
• Hatsukami DK, Jorenby DE, Gonzales D, Rigotti NA, Glover ED, Oncken CA ve ark. (2011) Immunogenicity and smoking-cessation outcomes for a novel nicotine immunotherapeutic. Clin Pharmacol Ther 89: 392-9.
• Inturrisi CE, Schultz M, Shin S, Umans JG, Angel L, Simon EJ (1983) Evidence from opiate binding studies that heroin acts through its metabolites. Life Sciences 33 (Suppl 1): 773-6. Kimishima A, Wenthur CJ, Zhou B, Janda KD (2017) An advance in prescription opioid vaccines: overdose mortality reduction and extraordinary alteration of drug half-life. ACS Chem Biol 12: 36-40.
• Kosten T, Domingo C, Orson F, Kinsey B (2014) Vaccines against stimulants: cocaine and MA. Br J Clin Pharmacol 77: 368-74.
• Kosten T, Owens SM (2005) Immunotherapy for the treatment of drug abuse. Pharmacol Ther 108: 76-85.
• Kosten TR, Domingo CB, Hamon SC, Nielsen DA (2013) DBH gene as predictor of response in a cocaine vaccine clinical trial. Neurosci Lett 541: 29-33.
• Kosten TR, Kreek M-J, Ragunath J, Kleber HD (1986) A preliminary study of beta endorphin during chronic naltrexone maintenance treatment in ex-opiate addicts. Life Sciences 39: 55-9.
• Kosten TR, Rosen M, Bond J, Settles M, Roberts JSC, Shields J ve ark. (2002) Human therapeutic cocaine vaccine: safety and immunogenicity. Vaccine 20: 1196-204.
• Kulaksizoğlu B, Kara H, Özçelik Ö, Kuloğlu M (2019) Opioid bağımlılığının tedavisinde naltrekson implant kullanımı: Geriye dönük bir çalışma. Anadolu Psikiyatri Dergisi 20: 133-8.
• Laudenbach M, Baruffaldi F, Robinson C, Carter P, Seelig D, Baehr C ve ark. (2018) Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose. Sci Rep 8: 5508.
• Laudenbach M, Baruffaldi F, Vervacke JS, Distefano MD, Titcombe PJ, Mueller DL ve ark. (2015) The frequency of naive and early-activated hapten-specific B cell subsets dictates the efficacy of a therapeutic vaccine against prescription opioid abuse. J Immunol 194: 5926-36.
• Li QQ, Sun CY, Luo YX, Xue YX, Zhu WL, Shi HS ve ark. (2014) A conjugate vaccine attenuates morphine- and heroin-induced behavior in rats. Int J Neuropsychopharmacol 18: pyu093.
• Martell BA, Orson FM, Poling J, Mitchell E, Rossen RD, Gardner T ve ark. (2009) Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial. Arch Gen Psychiatry 66: 1116-23.
• Maurer P, Jennings GT, Willers J, Rohner F, Lindman Y, Roubicek K ve ark. (2005) A therapeutic vaccine for nicotine dependence: preclinical efficacy, and Phase I safety and immunogenicity. Eur J Immunol 35: 2031-40.
• Mesquita Júnior D, Araújo JAP, Catelan TTT, Souza AWS, Cruvinel WM, Andrade LEC ve ark. (2010) Immune system - part II: basis of the immunological response mediated by T and B lymphocytes. Rev Bras Reumatol 50: 552-80.
• Mounteney J, Giraudon I, Denissov G, Griffiths P (2015) Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe. Int J Drug Policy 26: 626-31.
• Neuman MD, Bateman BT, Wunsch H (2019) Inappropriate opioid prescription after surgery. Lancet 393: 1547-57.
• Pravetoni M, Keyler D, Pidaparthi R, Carroll FI, Runyon SP, Murtaugh MP ve ark. (2012a) Structurally distinct nicotine immunogens elicit antibodies with non-overlapping specificities. Biochem Pharmacol 83: 543-50.
• Pravetoni M, Le Naour M, Harmon TM, Tucker AM, Portoghese PS, Pentel PR ve ark. (2012b) An oxycodone conjugate vaccine elicits drug-specific antibodies that reduce oxycodone distribution to brain and hot-plate analgesia. J Pharmacol Exp Ther 341: 225-32.
• Pravetoni M, Pentel PR, Potter DN, Chartoff EH, Tally L, LeSage MG (2014) Effects of an oxycodone conjugate vaccine on oxycodone self-administration and oxycodone-induced brain gene expression in rats. PLoS One 9: e101807.
• Pravetoni M, Raleigh M, Le Naour M, Tucker AM, Harmon TM, Jones JM ve ark. (2012c) Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats. Vaccine 30: 4617-24.
• Quaglio G, Talamini G, Lugoboni F, Lechi A, Venturini L, Jarlais DCD ve ark. (2002) Compliance with hepatitis B vaccination in 1175 heroin users and risk factors associated with lack of vaccine response. Addiction 97: 985-92.
• Raleigh MD, Laudenbach M, Baruffaldi F, Peterson SJ, Roslawski MJ, Birnbaum AK ve ark. (2018) Opioid dose and route-dependent efficacy of oxycodone and heroin vaccines in rats. J Pharmacol Exp Ther 365: 346-53.
• Raleigh MD, Peterson SJ, Laudenbach M, Baruffaldi F, Carroll FI, Comer SD ve ark. (2017) Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse. PLoS One 12: e0184876.
• Selley DE, Cao CC, Sexton T, Schwegel JA, Martin TJ, Childers SR (2001) mu Opioid receptor-mediated G-protein activation by heroin metabolites: evidence for greater efficacy of 6-monoacetylmorphine compared with morphine. Biochem Pharmacol 62: 447-55.
• Shen X, Kosten TR (2011) Immunotherapy for drug abuse. CNS Neurol Disord Drug Targets 10: 876-9. Taylor JJ, Laudenbach M, Tucker AM, Jenkins MK, Pravetoni M (2014) Hapten-specific naïve B cells are biomarkers of vaccine efficacy against drugs of abuse. J Immunol Methods 405: 74-86.
• The United Nations Office on Drugs and Crime (UNODC) (2018) World Drug Report 2018. United Nations publication, s. 6.
• Uğurlu TT, Şengül CB, Şengül C (2012) Bağımlılık psikofarmakolojisi. Psikiyatride Güncel Yaklaşımlar 4: 37-50.
• Wainer BH, Fitch FW, Fried J, Rothberg RM (1973) A measurement of the specificities of antibodies to morphine-6-succinyl-BSA by competitive inhibition of 14 C-morphine binding. J Immunol 110: 667-73.
• WHO (2018) World Drug Report 2018. Vienna, United Nations publication.
• Yılmaz A, Can Y, Bozkurt M, Evren C (2014) Alkol ve madde bağımlılığında remisyon ve depreşme. Psikiyatride Güncel Yaklaşımlar 6: 243-56.