Therapeutic Potential of Herbalism for Opioid Use Disorder
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Abstract
Introduction: the opioid crisis continues to claim many lives, approximately one hundred thousand annually in the United States of America, motivating solutions. Currently, these focus on synthetic opioids and are helpful in some circumstances, but their adoption has not stymied opioid deaths. Possible solutions for opioid use disorder exist in substances known to herbal medicine, and these may be attractive treatment options.
Objective:: this review aims to provide a comprehensive overview of the integrative therapies available to current opioid users to help in the cessation, through decreasing withdrawal symptoms. We identified several herbal and nutraceutical therapies which require further investigation for their therapeutic potential in opioid use disorder.
Method: we performed a literature search using three databases: Google Scholar, China/Asia on Demand, and China National Knowledge Infrastructure. A protocol was designed that incorporates the PRISMA guidelines, which was applied during the stages of searching and selecting articles.
Discussion and conclusions: tseveral herbal and nutraceutical treatments, including Sophora alopecuroides, crocin, and Berberis vulgaris extracts, and Hab-o-shefa, Tai-Kang Ning, and Fu-Yuan Pellet formulations, demonstrate promise for the treatment of opioid use disorder, motivating their further study in larger scale trials. If the results from previous smaller trials hold, herbal medicines may function as effective therapeutics as part of an opiate cessation regimen.
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References
Abbaszadeh-Mashkani, S., Hoque, S. S., Banafshe, H. R., & Ghaderi, A. (2021). The Effect of Crocin (The Main Active Saffron Constituent) on the Cognitive Functions, Craving, and Withdrawal Syndrome in Opioid Patients under Methadone Maintenance Treatment. Phytotherapy Research, 35(3), 1486-1494. https://doi.org/10.1002/ptr.6913
Alper, K. R., Stajić, M., & Gill, J. R. (2012). Fatalities Temporally Associated with the Ingestion of Ibogaine. Journal of Forensic Sciences, 57(2), 398–412. https://doi.org/10.1111/j.1556-4029.2011.02008.x
Antonio, T., Childers, S. R., Rothman, R. B., Dersch, C. M., King, C., Kuehne, M., Bornmann, W. G., Eshleman, A. J., Janowsky, A., Simon, E. R., Reith, M.E.A., & Alper, K. (2013). Effect of Iboga Alkaloids on μ-Opioid Receptor-Coupled G Protein Activation. PLOS ONE, 8(10). https://doi.org/10.1371/journal.pone.0077262
Arenson, A., Campbell, C. I., & Remler, I. (2024). Psychoactive Plant Derivatives (Ayahuasca, Ibogaine, Kratom) and their Application in Opioid Withdrawal and Use Disorder - a Narrative Review. Journal of Addictive Diseases, 42(3), 253–263. https://doi.org/10.1080/10550887.2023.2195777
Bawa, G., Mahajan, R., Mehta, M., Satija, S., Vyas, M., Sharma, N., & Khurana, N. (2019). Herbal Drugs for the Treatment of Opioid Withdrawal Syndrome: a Mini Review. Plant Archives, 19(2), 1005–1011. https://www.plantarchives.org/SPL%20ISSUE%20SUPP%202,2019/181%20(1005-1011).pdf
Brown, T. K., & Alper, K. (2018). Treatment of Opioid Use Disorder with Ibogaine: Detoxification and Drug Use Outcomes. The American Journal of Drug and Alcohol Abuse, 44(1), 24–36. https://doi.org/10.1080/00952990.2017.1320802
Burma, N. E., Kwok, C. H., & Trang, T. (2017). Therapies and Mechanisms of Opioid Withdrawal. Pain Management, 7(6), 455–459. https://doi.org/10.2217/pmt-2017-0028
Cabral, A., Ruggiero, R. N., Nobre, M. J., Brandão, M. L., & Castilho, V. M. (2009). GABA and Opioid Mechanisms of the Central Amygdala Underlie the Withdrawal-Potentiated Startle from Acute Morphine. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 33(2), 334–344. https://doi.org/10.1016/j.pnpbp.2008.12.012
Cantor, J., Powell, D., Kofner, A., & Stein, B. D. (2021). Population-Based Estimates of Geographic Accessibility of Medication for Opioid Use Disorder by Substance Use Disorder Treatment Facilities from 2014 to 2020. Drug and Alcohol Dependence, 229. https://doi.org/10.1016/j.drugalcdep.2021.109107
Chilcoat, H. D., Amick, H. R., Sherwood, M. R., & Dunn, K. E. (2019). Buprenorphine in the United States: Motives for Abuse, Misuse, and Diversion. Journal of Substance Abuse Treatment, 104, 148–157. https://doi.org/10.1016/j.jsat.2019.07.005
Compton, W. M., & Volkow, N. D. (2006). Major Increases in Opioid Analgesic Abuse in the United States: Concerns and Strategies. Drug and Alcohol Dependence, 81(2), 103–107. https://doi.org/10.1016/j.drugalcdep.2005.05.009
Dabaghzadeh, F., Sharififar, F., Ahmadzadeh, A.-M., & Karami-Mohajeri, S. (2021). The Effects of Berberis Vulgaris L. Root Extract on the Opiate Withdrawal Syndrome and Psychological Factors: a Randomized Double-Blind Clinical Trial.Journal of Basic and Clinical Physiology and Pharmacology, 34(4), 465--472. https://doi.org/10.1515/jbcpp-2020-0327
Deji, C., Yan, P., Ji, Y., Yan, X., Feng, Y., Liu, J., Liu, Y., Wei, S., Zhu, Y., & Lai, J. (2022). The Basolateral Amygdala to Ventral Hippocampus Circuit Controls Anxiety-Like Behaviors Induced by Morphine Withdrawal. Frontiers in Cellular Neuroscience, 16. https://doi.org/10.3389/fncel.2022.894886
Doosti, F., Dashti, S., Tabatabai, S. M., & Hosseinzadeh, H. (2013). Traditional Chinese and Indian Medicine in the Treatment of Opioid-Dependence: A Review. Avicenna Journal of Phytomedicine, 3(3), 205–215. https://pmc.ncbi.nlm.nih.gov/articles/PMC4075718/pdf/ajp-3-205.pdf
Eastwood, B., Strang, J., & Marsden, J. (2017). Effectiveness of Treatment for Opioid Use Disorder: a National, Five-Year, Prospective, Observational Study in England. Drug and Alcohol Dependence, 176, 139–147. https://doi.org/10.1016/j.drugalcdep.2017.03.013
Ebrahimie, M., Bahmani, M., Shirzad, H., Rafieian-Kopaei, M., & Saki, K. (2015). A Review Study on the Effect of Iranian Herbal Medicines on Opioid Withdrawal Syndrome. Journal of Evidence-Based Complementary & Alternative Medicine, 20(4), 302–309. https://doi.org/10.1177/2156587215577896
Fernandez, J. W. (1982). Bwiti: An Ethnography of the Religious Imagination in Africa. Princeton University Press.
García-Pérez, D., López-Bellido, R., Rodríguez, R. E., Laorden, M. L., Núñez, C., & Milanés, M. V. (2015). Dysregulation of Dopaminergic Regulatory Mechanisms in the Mesolimbic Pathway Induced by Morphine and Morphine Withdrawal. Brain Structure and Function, 220(4), 1901–1919. https://doi.org/10.1007/s00429-014-0761-5
Glick, S. D., & Maisonneuve, I. S. (1998). Mechanisms of Antiaddictive Actions of Ibogaine. Annals of the New York Academy of Sciences, 844, 214–226. https://doi.org/10.1111/j.1749-6632.1998.tb08237.x
Govender, D., Moloko, L., Papathanasopoulos, M., Tumba, N., Owen, G., & Calvey, T. (2024). Ibogaine Administration Following Repeated Morphine Administration Upregulates Myelination Markers 2′, 3′-Cyclic Nucleotide 3′-phosphodiesterase (CNP) and Myelin Basic Protein (MBP) mRNA and Protein Expression in the Internal Capsule of Sprague Dawley Rats. Frontiers in Neuroscience, 18. https://doi.org/10.3389/fnins.2024.1378841
Haddaway, N. R., Page, M. J., Pritchard, C. C., & McGuinness, L. A. (2022). PRISMA2020: An R package and Shiny app for Producing PRISMA 2020-Compliant Flow Diagrams, with Interactivity for Optimised Digital Transparency and Open Synthesis. Campbell Systematic Reviews, 18(2), e1230. https://doi.org/10.1002/cl2.1230
Hall, N. Y., Le, L., Majmudar, I., & Mihalopoulos, C. (2021). Barriers to Accessing Opioid Substitution Treatment for Opioid Use Disorder: a Systematic Review from the Client Perspective. Drug and Alcohol Dependence, 221. https://doi.org/10.1016/j.drugalcdep.2021.108651
Hao, W., & Zhao, M. (2000). A Comparative Clinical Study of the Effect of Weinicom, a Chinese Herbal Compound, on Alleviation of Withdrawal Symptoms and Craving for Heroin in Detoxification Treatment. Journal of Psychoactive Drugs, 32(3), 277--284. https://doi.org/10.1080/02791072.2000.10400450
Hashem-Dabaghian, F., & Kianbakht, S. (2023). A Randomized Controlled Trial on the Seeds of Sophora Alopecuroides Var. Alopecuroides for the Treatment of Acute Heroin Withdrawal Syndrome. Complementary Therapies in Clinical Practice, 51, 101740. https://doi.org/10.1016/j.ctcp.2023.101740
Jhanjee, S. (2014). Evidence Based Psychosocial Interventions in Substance Use. Indian Journal of Psychological Medicine, 36(2), 112–118. https://doi.org/10.4103/0253-7176.130960
Johnson, R. E., Strain, E. C., & Amass, L. (2003). Buprenorphine: How to Use it Right. Drug and Alcohol Dependence, 70(2), S59–S77. https://doi.org/10.1016/S0376-8716(03)00060-7
Jones, R. T. (1980). Dependence in Non-Addict Humans after a Single Dose of Morphine. In E. L. Way (Ed.), Endogenous and exogenous opiate agonists and antagonists (pp. 557–560). Pergamon.
Kang, J. H., Lee, K. H., Huh, S. J., Shin, S.-H., Kim, I. H., Hwang, I. G., Koo, D.-H., Lee, D., Koh, S.-J., Seo, S., Lee, G. J., Chun, S. H., Ji, J. H., Oh, S. Y., Choi, J. W., & Go, S.-I. (2024). Efficacy of Transdermal Buprenorphine Patch for Managing Withdrawal Symptoms in Patients with Cancer Physically Dependent on Prescription Opioids. The Oncologist, 29(11), e1593–e1603. https://doi.org/10.1093/oncolo/oyae176
Kang, L., Li, B., Gao, L., Li, S., Wang, D., Hu, M., & Li, J. (2008). Tai-Kang-Ning, a Chinese Herbal Medicine Formula, Alleviates acute Heroin Withdrawal. The American Journal of Drug and Alcohol Abuse, 34(3), 269–276. https://doi.org/10.1080/00952990802013409
Keefe, P. R. (2017, October 23). The Family that Built an Empire of Pain. The New Yorker. https://www.newyorker.com/magazine/2017/10/30/the-family-that-built-an-empire-of-pain
Kenan, K., Mack, K., & Paulozzi, L. (2012). Trends in Prescriptions for Oxycodone and Other Commonly Used Opioids in the United States, 2000–2010. Open Medicine, 6(2), e41-e47. https://pmc.ncbi.nlm.nih.gov/articles/PMC3659213/pdf/OpenMed-06-e41.pdf
Kenny, P. J., Chen, S. A., Kitamura, O., Markou, A., & Koob, G. F. (2006). Conditioned Withdrawal Drives Heroin Consumption and Decreases Reward Sensitivity. Journal of Neuroscience, 26(22), 5894–5900. https://doi.org/10.1523/JNEUROSCI.0740-06.2006
Kianbakht, S., Hajiaghaee, R., & Akhondzadeh, S. (2020). Efficacy and Safety of Sophora Alopecuroides Var. Alopecuroides Seed Extract for Opioid Detoxification: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial. Phytotherapy Research, 34(5), 1108–1113. https://doi.org/10.1002/ptr.6578
Kosten, T. R., & Baxter, L. E. (2019). Effective Management of Opioid Withdrawal Symptoms: A Gateway to Opioid Dependence Treatment. The American Journal on Addictions, 28(2), 55–62. https://doi.org/10.1111/ajad.12862
Krupitsky, E., Nunes, E. V., Ling, W., Illeperuma, A., Gastfriend, D. R., & Silverman, B. L. (2011). Injectable Extended-Release Naltrexone for Opioid Dependence: A Double-Blind, Placebo-Controlled, Multicentre Randomised Trial. The Lancet, 377(9776), 1506–1513. https://doi.org/10.1016/S0140-6736(11)60358-9
Kruszecki, C., Cameron, C. R., Hume, A. L., & Ward, K. E. (2021). A Systematic Review of Integrative Medicine for Opioid Withdrawal. Journal of Substance Abuse Treatment, 125. https://doi.org/10.1016/j.jsat.2021.108279
Lekas, C. (2014). Is the Use of the Drug Buprenorphine and Naloxone (Suboxone) as Effective in Suppressing Opioid Dependency and its Withdrawal Symptoms, or is it Simply a Surrogate for the Opiate with the Addictive Results? PCOM Physician Assistant Studies Student Scholarship. 170. https://digitalcommons.pcom.edu/pa_systematic_reviews/170
Li, J., Kang, L., Wang, X., & Huang, M. (2007). Clinical Efficacy of Six Traditional Chinese Medicines for Opioid Withdrawal Syndrome. Chinese Journal of Drug Dependence, 15(3), 198–202. https://doi.org/10.13936/j.cnki.cjdd1992.2007.03.001
Li, L., Bryant, B. M., Cenczyk, C., & Gawronski, B. (2020). Characteristics Associated with Success for Opioid Use Disorder Treatment in Court-involved Patients. Archives of Clinical and Biomedical Research, 4(6), 749–759. https://doi.org/10.26502/acbr.50170140
Liu, T., Shi, J., Epstein, D. H., Bao, Y.-P., & Lu, L. (2009). A Meta-Analysis of Chinese Herbal Medicine in Treatment of Managed Withdrawal from Heroin. Cellular and Molecular Neurobiology, 29(1), 17–25. https://doi.org/10.1007/s10571-008-9290-1
Maldonado, R., Stinus, L., Gold, L. H., & Koob, G. F. (1992). Role of Different Brain Structures in the Expression of the Physical Morphine Withdrawal Syndrome. The Journal of Pharmacology and Experimental Therapeutics, 261(2), 669–677. https://doi.org/10.1016/S0022-3565(25)11090-2
Mash, D. C. (2018). Breaking the Cycle of Opioid Use Disorder with Ibogaine. The American Journal of Drug and Alcohol Abuse, 44(1), 1–3. https://doi.org/10.1080/00952990.2017.1357184
Mattson, C. L., Tanz, L.J., Quinn, K., Kariisa, M., Patel, P., & Davis, N.D. (2021). Trends and Geographic Patterns in Drug and Synthetic Opioid Overdose Deaths — United States, 2013–2019. Morbidity and Mortality Weekly Report, 70(6), 202–207. https://doi.org/10.15585/mmwr.mm7006a4
Momeni, H., Sadeghi, H., & Salehi, A. (2018). Comparison of Matricaria hamomilla oil, Trachyspermum copticum oil and Clonidin on Withdrawal syndrome in Narcotics Anonymous. Journal of Sabzevar University of Medical Sciences, 25(2). https://jsums.medsab.ac.ir/article_1047_fa3e4d948846cb8e531ac2e7b9599250.pdf?lang=en
Monroe, S. C., & Radke, A. K. (2023). Opioid Withdrawal: Role in Addiction and Neural Mechanisms. Psychopharmacology, 240(7), 1417–1433. https://doi.org/10.1007/s00213-023-06370-2
Moosavyzadeh, A., Mokri, A., Ghaffari, F., Faghihzadeh, S., Azizi, H., Jafari Hajati, R., & Naseri, M. (2020). Hab-o Shefa, a Persian Medicine Compound for Maintenance Treatment of Opioid Dependence: Randomized Placebo-Controlled Clinical Trial. The Journal of Alternative and Complementary Medicine, 26(5), 376–383. https://doi.org/10.1089/acm.2019.0390
Navarro-Zaragoza, J., Martínez-Laorden, E., Teruel-Fernández, F. J., Gómez-Murcia, V., Cánovas, A., Milanés, M.-V., Laorden, M.-L., & Almela, P. (2021). Naloxone-Induced Conditioned Place Aversion Score and Extinction Period are Higher in C57BL/6J Morphine-Dependent Mice than in Swiss: Role of HPA Axis. Pharmacology Biochemistry and Behavior, 201. https://doi.org/10.1016/j.pbb.2021.173106
Nazari, S. M., Naseri, M., Mokri, A., Davati, A., & Kamalinejad, M. (2013). Hab-o Shefa (an Iranian Traditional Medicine Compound) in Withdrawal Syndrome and its Effects in acute Detoxification of Opiates Addict: A Randomized, Double Blind, Clinical Trials. Journal of Medicinal Plants Research, 7(22), 1628–1635. https://doi.org/10.5897/JMPR12.1016
Pergolizzi, J. V., Annabi, H., Gharibo, C., & LeQuang, J. A. (2019). The Role of Lofexidine in Management of Opioid Withdrawal. Pain and Therapy, 8(1), 67–78. https://doi.org/10.1007/s40122-018-0108-7
Pergolizzi, J. V., Raffa, R. B., & Rosenblatt, M. H. (2020). Opioid Withdrawal Symptoms, a Consequence of Chronic Opioid Use and Opioid Use Disorder: Current Understanding and Approaches to Management. Journal of Clinical Pharmacy and Therapeutics, 45(5), 892–903. https://doi.org/10.1111/jcpt.13114
Rodríguez-Cano, B. J., Kohek, M., Ona, G., Alcázar-Córcoles, M. Á., dos Santos, R. G., Hallak, J. E. C., & Bouso, J. C. (2022). Underground Ibogaine Use for the Treatment of Substance Use Disorders: A Qualitative Analysis of Subjective Experiences. Drug and Alcohol Review, 42(2), 401–414. https://doi.org/10.1111/dar.13587
Sangi, S., Ahmed, S. P., Channa, M. A., Ashfaq, M., & Mastoi, S. M. (2008). A New and Novel Treatment of Opioid Dependence: Nigella sativa 500 mg. Journal of Ayub Medical College, Abbottabad: JAMC, 20(2), 118–124. https://ayubmed.edu.pk/JAMC/PAST/20-2/Sangi.pdf
Sayyah, M., Siahpoush, A., & Rahim, F. (2017). The Role of Alcoholic Extract of Zataria multiflora Boiss in Controlling Opium Withdrawal Symptoms: a Randomized, Double-Blind Study. Archives of Psychiatry and Psychotherapy, 19(3), 27–33. https://doi.org/10.12740/APP/74385
Song, Y., Meng, Q.-X., Wu, K., Hua, R., Song, Z.-J., Song, Y., Qin, X., Cao, J.-L., & Zhang, Y.-M. (2020). Disinhibition of PVN-projecting GABAergic Neurons in AV Region in BNST Participates in Visceral Hypersensitivity in Rats. Psychoneuroendocrinology, 117. https://doi.org/10.1016/j.psyneuen.2020.104690
Sterne, J. A. C., Savović, J., Page, M. J., Elbers, R. G., Blencowe, N. S., Boutron, I., Cates, C. J., Cheng, H.-Y., Corbett, M. S., Eldridge, S. M., Emberson, J. R., Hernán, M. A., Hopewell, S., Hróbjartsson, A., Junqueira, D. R., Jüni, P., Kirkham, J. J., Lasserson, T., Li, T. Higgins, J. P. T. (2019). RoB 2: A revised Tool for Assessing Risk of Bias in Randomised Trials. BMJ, 366, l4898. https://doi.org/10.1136/bmj.l4898
Substance Abuse and Mental Health Services Administration (SAMHSA). (2024). Results From the 2023 National Survey on Drug Use and Health. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/data/report/2023-nsduh-annual-national-report
Tabatabai, S. M., Dashti, S., Doosti, F., & Hosseinzadeh, H. (2013). Phytotherapy of Opioid Dependence and Withdrawal Syndrome: A Review. Phytotherapy Research, 28(6), 811–830. https://doi.org/10.1002/ptr.5073
Tang, Y., Zhao, D., Zhao, C., & Cubells, J. F. (2006). Opiate Addiction in China: Current Situation and Treatments. Addiction, 101(5), 657–665. https://doi.org/10.1111/j.1360-0443.2006.01367.x
The Controlled Substances Act, Schedule 1(c) § 812(c) (1978). https://www.dea.gov/drug-information/csa
Von Korff, M., Saunders, K., Ray, G. T., Boudreau, D., Campbell, C., Merrill, J., Sullivan, M. D., Rutter, C. M., Silverberg, M. J., & Banta-Green, C. (2008). De facto Long-Term Opioid Therapy for Noncancer Pain. The Clinical Journal of Pain, 24(6), 521–527. DOI: 10.1097/AJP.0b013e318169d03b
Wang, X., Li, J., Huang, M., Kang, L., & Hu, M. (2009). A study on Fu-Yuan Pellet, a Traditional Chinese Medicine Formula for detoxification of heroin addictions. The American Journal of Drug and Alcohol Abuse, 35(6), 408–411. https://doi.org/10.3109/00952990903377146
Ward, J., Rosenbaum, C., Hernon, C., McCurdy, C. R., & Boyer, E. W. (2011). Herbal Medicines for the Management of Opioid Addiction. CNS Drugs, 25(12), 999–1007. https://doi.org/10.2165/11596830-000000000-00000
Wilson, C., Millar, T., & Matieschyn, Z. (2020). Novel Treatment of Opioid Use Disorder Using Ibogaine and Iboga in Two Adults. Journal of Psychedelic Studies, 4(3), 149–155. https://doi.org/10.1556/2054.2020.00133
Yu, J., & Guo, X. (2013). Trial of Highly Cross-Linked Macroporous Adsorbents for Clinical Use in Heroin-Dependent Persons. Ion Exchange and Adsorption, 29(5). https://doi.org/10.16026/j.cnki.iea.2013.05.002
Zhu, W., Zhang, Y., Huang, Y., & Lu, L. (2017). Chinese Herbal Medicine for the Treatment of Drug Addiction. International Review of Neurobiology, 135, 279–295. https://doi.org/10.1016/bs.irn.2017.02.013