Il “last mile” della sospensione metadonica: utilizzo della Passiflora incarnata 600 mg/die in tre pazienti con terapia sostitutiva di lunga durata

Journal title MISSION
Author/s Giovanni Crespi
Publishing Year 2026 Issue 2026/74
Language Italian Pages 5 P. 39-43 File size 0 KB
DOI 10.3280/mis74-2026oa23184
DOI is like a bar code for intellectual property: to have more infomation click here

View article Download Open Access article

FrancoAngeli is member of Publishers International Linking Association, Inc (PILA), a not-for-profit association which run the CrossRef service enabling links to and from online scholarly content.

Complete discontinuation of methadone maintenance therapy in patients with opioid use disorder undergoing long-term substitution treatment represents one of the most challenging phases of the therapeutic pathway.
In clinical practice, progressive methadone tapering is often well tolerated down to very low dosages, whereas the final phase of complete discontinuation is frequently characterized by the emergence of residual subjective symptoms preventing treatment completion, thus configuring the so-called “last mile” of methadone discontinuation.
The aim of the present study is to describe three patients followed at the Monza Addiction Service (SerD), who had been receiving methadone treatment for many years and in whom progressive dose reduction had substantially stalled at extremely low dosages, making complete discontinuation impossible despite repeated attempts.
In all cases, patients showed clinical and toxicological stability, absence of relapse, and good tolerability of progressive dose reductions.
Difficulties emerged exclusively during the terminal phase of tapering and were mainly characterized by subjective symptoms such as inner restlessness, agitation, insomnia, psychophysical discomfort, and emotional instability, in the absence of a major opioid withdrawal syndrome.
During the final tapering phase, Passiflora incarnata dry extract was introduced at a dosage of 600 mg/day for three months.
In the observed cases, this intervention appeared to be associated with successful completion of methadone discontinuation, good clinical tolerability, and six-month negative toxicological follow-up on keratin matrix analysis.
In light of the GABAergic modulatory properties of Passiflora incarnata, the observed findings suggest a possible role for phytotherapy in the management of residual symptoms characterizing the terminal phase of long-term methadone discontinuation.

Keywords: Methadone;Tapering;Passiflora incarnata;Opioid use disorder;Replacement therapy;Craving,;GABA;Herbal medicine

  1. Akhondzadeh S., Naghavi H.R., Vazirian M., Shayeganpour A., Rashidi H., & Khani M. (2001). Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther., 26(5): 363-367.
  2. American Psychiatric Association (2022). Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR). Washington DC: APA Publishing.
  3. Appel K., Rose T., Fiebich B., Kammler T., Hoffmann C., & Weiss G. (2011). Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L. Phytother Res., 25(6): 838-843.
  4. Brett J., & Murnion B. (2015). Management of benzodiazepine misuse and dependence. Aust Prescr., 38(5): 152-155.
  5. Carminati M., Tondello M., Zappia M., & Zanardi R. (2024). Passiflora incarnata L., herba, in benzodiazepine tapering: long-term safety and efficacy in a real-world setting. Front Psychiatry.
  6. Crespi G., Moretti F., Giampieri E., Galimberti G.L., & Zanalda E. (2024). Use of Passiflora incarnata L. Herba in the Treatment of Cocaine Use Disorders: The Experience of an Addiction Center in Monza, Italy. Journal of Psychiatry Research.
  7. Dole V.P., & Nyswander M.E. (1965). A medical treatment for diacetylmorphine (heroin) addiction. JAMA, 193: 646-650.
  8. Dhawan K., Kumar S., & Sharma A. (2001). Anti-anxiety studies on extracts of Passiflora incarnata Linneaus. J Ethnopharmacol., 78(2-3): 165-170.
  9. Elsas S.M., Rossi D.J., Raber J., & White G. (2010). Passiflora incarnata extracts elicit GABA currents in hippocampal neurons. Phytomedicine, 17(12): 940-949.
  10. EMCDDA (2025). European Drug Report 2025: Trends and Developments. Luxembourg: Publications Office of the European Union.
  11. Jawna-Zboin´ska K., Blecharz-Klin K., Joniec-Maciejak I. et al. (2022). Passiflora incarnata in neuropsychiatric disorders: a systematic review. Nutrients., 14(23), 4987.
  12. Koob G.F., & Volkow N.D. (2016). Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry, 3(8): 760-773.
  13. Kosten T.R., & Baxter L.E. (2019). Effective management of opioid withdrawal symptoms: a gateway to opioid dependence treatment. Am J Addict., 28(2): 55-62.
  14. Kreek M.J. (2000). Methadone-related opioid agonist pharmacotherapy for heroin addiction. JAMA, 283(10): 1335-1336.
  15. Lader M. (2014). Benzodiazepine harm: how can it be reduced? Br J Clin Pharmacol., 77(2): 295-301.
  16. Miyasaka L.S., Atallah A.N., & Soares B.G.O. (2007). Passiflora for anxiety disorder. Cochrane Database Syst Rev., (1), CD004518.
  17. Zanalda E. (2021). Uso cronico di benzodiazepine e demenza senile. Rivista Società Italiana di Medicina Generale, 28(4): 22-27.
  18. Zanardi R., Carminati M., Fazio V., Maccario M., Verri G., & Colombo C. (2023). Add-On Treatment with Passiflora incarnata L., herba, during Benzodiazepine Tapering in Patients with Depression and Anxiety: A Real-World Study. Pharmaceuticals (Basel), 16(3): 426.
  19. World Health Organization (2009). Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence. Geneva: WHO.

Giovanni Crespi, Il “last mile” della sospensione metadonica: utilizzo della Passiflora incarnata 600 mg/die in tre pazienti con terapia sostitutiva di lunga durata in "MISSION" 74/2026, pp 39-43, DOI: 10.3280/mis74-2026oa23184