Skip to main content
SpringerLink
Log in

Licit and Illicit Drug Use in Cluster Headache

  • Trigeminal Autonomic Cephalalgias (M Matharu, Section Editor)
  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Cluster headache patients seem to use more licit and illicit substances than the general population. The epidemiologic data supporting this is growing. We included the licit drugs in this review because their use seems to be driven by the same addiction mechanisms leading to illicit drug abuse. Some drugs may be used in an attempt to treat cluster headache, especially cocaine and hallucinogens. Drug exposure may also play a role in CH pathophysiology, as suggested by interesting data on tobacco use and second-hand smoke exposure. A common factor may contribute both to CH and drug use predisposition. Genetic factors may be at play, and the dopaminergic and orexinergic pathways could be targeted for future studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33:629–808.

    Google Scholar 

  2. Fischera M, Marziniak M, Gralow I, Evers S: The incidence and prevalence of cluster headache: a meta-analysis of population-based studies. Cephalalgia : an international journal of headache 2008;28(6):614–18.

    Google Scholar 

  3. Bahra A, May A, Goadsby PJ: Cluster headache: a prospective clinical study with diagnostic implications. Neurology 2002;58(3):354–61.

    Google Scholar 

  4. Robbins MS, Bronheim R, Lipton RB, Grosberg BM, Vollbracht S, Sheftell FD, et al. Depression and anxiety in episodic and chronic cluster headache: a pilot study. Headache. 2012;52:600–11.

    Article  PubMed  Google Scholar 

  5. May A. Illicit drugs and cluster headache: an inevitable discussion. Cephalalgia. 2012;32:1021–2.

    Article  PubMed  Google Scholar 

  6. Rossi P, Allena M, Tassorelli C, Sances G, Di Lorenzo C, Faroni JV, et al. Illicit drug use in cluster headache patients and in the general population: a comparative cross-sectional survey. Cephalalgia. 2012;32:1031–40. Unique study presenting data on drug use in CH population compared with the Italian general population.

    Article  PubMed  Google Scholar 

  7. Torelli P, Cologno D, Cademartiri C, Manzoni GC. Primary and secondary chronic cluster headache: 2 separate entities? Cephalalgia. 2000;20:826–9.

    Article  CAS  PubMed  Google Scholar 

  8. Evans RW, Schurks M. Alcohol and cluster headaches. Headache. 2009;49:126–9.

    Article  PubMed  Google Scholar 

  9. Schurks M, Kurth T, Knorn P, Pageler L, Diener HC. Predictors of hazardous alcohol consumption among patients with cluster headache. Cephalalgia. 2006;26:623–7.

    Article  CAS  PubMed  Google Scholar 

  10. Case-control study on the epidemiology of cluster headache. I: Etiological factors and associated conditions. Italian Cooperative Study Group on the Epidemiology of Cluster Headache (ICECH). Neuroepidemiology. 1995;14:123–7.

    Google Scholar 

  11. Manzoni GC. Cluster headache and lifestyle: remarks on a population of 374 male patients. Cephalalgia. 1999;19:88–94.

    Article  CAS  PubMed  Google Scholar 

  12. Manzoni GC. Gender ratio of cluster headache over the years: a possible role of changes in lifestyle. Cephalalgia. 1998;18:138–42.

    Article  CAS  PubMed  Google Scholar 

  13. Torelli P, Manzoni GC. What predicts evolution from episodic to chronic cluster headache? Curr Pain Headache Rep. 2002;6:65–70.

    Article  PubMed  Google Scholar 

  14. Torelli P, Cologno D, Cademartiri C, Manzoni GC. Possible predictive factors in the evolution of episodic to chronic cluster headache. Headache. 2000;40:798–808.

    Article  CAS  PubMed  Google Scholar 

  15. Schurks M, Kurth T, de Jesus J, Jonjic M, Rosskopf D, Diener HC. Cluster headache: clinical presentation, lifestyle features, and medical treatment. Headache. 2006;46:1246–54.

    Article  PubMed  Google Scholar 

  16. Sjostrand C, Russell MB, Ekbom K, Waldenlind E. Familial cluster headache: demographic patterns in affected and nonaffected. Headache. 2010;50:374–82.

    Article  PubMed  Google Scholar 

  17. Holtzman SG. Caffeine as a model drug of abuse. Trends Pharmacol Sci. 1990;11:355–6.

    Article  CAS  PubMed  Google Scholar 

  18. Strain EC, Griffiths RR. Caffeine dependence: fact or fiction? J R Soc Med. 1995;88:437–40.

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Xie Q, Huang Q, Wang J, Li N, Tan G, Zhou J. Clinical features of cluster headache: an outpatient clinic study from china. Pain Med. 2013;14:802–7.

    Article  PubMed  Google Scholar 

  20. Leroux E, Taifas I, Valade D, Donnet A, Chagnon M, Ducros A. Use of cannabis among 139 cluster headache sufferers. Cephalalgia. 2013;33:208–13. First study on cannabinoid use in a wide French CH population including patient’s perspective of the effect on CH. The results do not support the use of cannabis to treat CH.

    Article  PubMed  Google Scholar 

  21. Lin KH, Wang PJ, Fuh JL, Lu SR, Chung CT, Tsou HK, et al. Cluster headache in the Taiwanese—a clinic-based study. Cephalalgia. 2004;24:631–8.

    Article  PubMed  Google Scholar 

  22. Rozen TD, Fishman RS. Cluster headache in the United States of America: demographics, clinical characteristics, triggers, suicidality, and personal burden. Headache. 2012;52:99–113. Even if this large survey is not centered on drug use, it provides a global clinical overview on the CH population, confirming high frequency of tobacco use.

    Article  PubMed  Google Scholar 

  23. Ferrari A, Zappaterra M, Righi F, Ciccarese M, Tiraferri I, Pini LA, et al. Impact of continuing or quitting smoking on episodic cluster headache: a pilot survey. J Headache Pain. 2013;14(1):48. A study showing that even if tobacco use is associated with a more severe form of cluster, quitting smoking does not improve the CH condition.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Donnet A, Lanteri-Minet M, Guegan-Massardier E, Mick G, Fabre N, Geraud G, et al. Chronic cluster headache: a French clinical descriptive study. J Neurol Neurosurg Psychiatry. 2007;78:1354–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Beck F, Legleye S, Spilka S, Briffault X, Gautier A, Lamboy B, et al. Les niveaux d'usage des drogues en France. Tendances. 2006;48:1–6.

    Google Scholar 

  26. McGeeney BE. Cannabinoids and hallucinogens for headache. Headache. 2013;53:447–58.

    Article  PubMed  Google Scholar 

  27. Levi R, Edman GV, Ekbom K, Waldenlind E. Episodic cluster headache. II: High tobacco and alcohol consumption in males. Headache. 1992;32:184–7.

    Article  CAS  PubMed  Google Scholar 

  28. Robbins MS, Tarshish S, Solomon S, Grosberg BM. Cluster attacks responsive to recreational cannabis and dronabinol. Headache. 2009;49:914–6.

    Article  PubMed  Google Scholar 

  29. Ogborne AC, Smart RG, Weber T, Birchmore-Timney C. Who is using cannabis as a medicine and why: an exploratory study. J Psychoactive Drugs. 2000;32:435–43.

    Article  CAS  PubMed  Google Scholar 

  30. Greco R, Gasperi V, Maccarrone M, Tassorelli C. The endocannabinoid system and migraine. Exp Neurol. 2010;224:85–91.

    Article  CAS  PubMed  Google Scholar 

  31. Akerman S, Holland PR, Goadsby PJ. Cannabinoid (CB1) receptor activation inhibits trigeminovascular neurons. J Pharmacol Exp Ther. 2007;320:64–71.

    Article  CAS  PubMed  Google Scholar 

  32. Walker JM, Hohmann AG. Cannabinoid mechanisms of pain suppression. Handb Exp Pharmacol. 2005;168:509–54.

    Article  CAS  PubMed  Google Scholar 

  33. Halberstadt AL, Geyer MA. Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology. 2011;61:364–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Abramson HA RA, editor. Comparison of LSD with methysergide and psilocybin on test subjects. 2nd Headache 457 International Conference on the Use of LSD in Psychotherapy and Alcoholism; 1967.

  35. Horita A, Weber LJ. The enzymic dephosphorylation and oxidation of psilocybin and psilocin by mammalian tissue homogenates. Biochem Pharmacol. 1961;7:47–54.

    Article  CAS  PubMed  Google Scholar 

  36. Russell MB. Epidemiology and genetics of cluster headache. Lancet Neurol. 2004;3:279–83.

    Article  PubMed  Google Scholar 

  37. Cremer PD, Halmagyi GM, Goadsby PJ. Secondary cluster headache responsive to sumatriptan. J Neurol Neurosurg Psychiatry. 1995;59:633–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Nichols DE. Hallucinogens. Pharmacol Ther. 2004;101:131–81.

    Article  CAS  PubMed  Google Scholar 

  39. Johnson MW, Sewell RA, Griffiths RR. Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers. Drug Alcohol Depend. 2012;123:132–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Sewell RA, Halpern JH, Pope Jr HG. Response of cluster headache to psilocybin and LSD. Neurology. 2006;66:1920–2.

    Article  PubMed  Google Scholar 

  41. McGeeney BE. Hallucinogens and cannabinoids for headache. Headache. 2012;52 Suppl 2:94–7. Wide review on hallucinogens and cannabinoid use for headache, past and present, including for CH patients.

    Article  PubMed  Google Scholar 

  42. Troxler FHA. Substitutionen am Ringsystem der Lysergsaanure - Sustitutionen am Indol-Stickstoff. Hely Chem Acta. 1957;40:2160–70.

    Article  CAS  Google Scholar 

  43. Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A. The pharmacology of lysergic acid diethylamide: a review. CNS Neurosci Ther. 2008;14:295–314.

    Article  CAS  PubMed  Google Scholar 

  44. Karst M, Halpern JH, Bernateck M, Passie T. The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: an open, non-randomized case series. Cephalalgia. 2010;30:1140–4. A case series of BOL-148 use as a treatment for CH. This preliminary work opens an important research area.

    Article  PubMed  Google Scholar 

  45. Halpern JH. Reply to: 'illicit drugs and cluster headache: an inevitable discussion'. Cephalalgia. 2013;33:496–7.

    Article  PubMed  Google Scholar 

  46. Bertino JR, Klee GD, Weintraub W. Cholinesterase, dlysergic acid diethylamide, and 2-bromolysergic acid diethylamide. J Clin Exp Neuropsychol. 1959;20:218–22.

    CAS  Google Scholar 

  47. Sicuteri F. Prophylactic treatment of migraine by means of lysergic acid derivatives. triangle. Sandoz. J Med Sci. 1963;67:116–25.

    CAS  Google Scholar 

  48. Balestrieri A, Fontanari D. Acquired and crossed tolerance to mescaline, LSD-25, and BOL-148. Arch Gen Psychiatry. 1959;1:279–82.

    Article  CAS  Google Scholar 

  49. Tfelt-Hansen P. Is BOL-148 hallucinogenic? Cephalalgia. 2011;31:634. author reply 5–6.

    Article  PubMed  Google Scholar 

  50. Richards N, Chapman LF, Goodell H, Wolff HG. LSD-like delirium following ingestion of a small amount of its brom analog (BOL-148). Ann Intern Med. 1958;48:1078–82.

    Article  CAS  PubMed  Google Scholar 

  51. Pedersen JL, Barloese M, Jensen RH. Neurostimulation in cluster headache: a review of current progress. Cephalalgia. 2013;33:1179–93.

    Article  PubMed  Google Scholar 

  52. Goadsby PJ, Schoenen J, Ferrari MD, Silberstein SD, Dodick D. Towards a definition of intractable headache for use in clinical practice and trials. Cephalalgia. 2006;26:1168–70.

    Article  CAS  PubMed  Google Scholar 

  53. Sprenger T, Seifert CL, Miederer M, Valet M, Tolle TR. Successful prophylactic treatment of chronic cluster headache with low-dose levomethadone. J Neurol. 2008;255:1832–3.

    Article  CAS  PubMed  Google Scholar 

  54. Franceschini R, Leandri M, Gianelli MV, Cataldi A, Bruno E, Rolandi E, et al. Evaluation of beta-endorphin secretion in patients suffering from episodic cluster headache. Headache. 1996;36:603–7.

    Article  CAS  PubMed  Google Scholar 

  55. Sprenger T, Willoch F, Miederer M, Schindler F, Valet M, Berthele A, et al. Opioidergic changes in the pineal gland and hypothalamus in cluster headache: a ligand PET study. Neurology. 2006;66:1108–10.

    Article  CAS  PubMed  Google Scholar 

  56. Paemeleire K, Evers S, Goadsby PJ. Medication-overuse headache in patients with cluster headache. Curr Pain Headache Rep. 2008;12:122–7.

    Article  PubMed  Google Scholar 

  57. Costa A, Pucci E, Antonaci F, Sances G, Granella F, Broich G, et al. The effect of intranasal cocaine and lidocaine on nitroglycerin-induced attacks in cluster headache. Cephalalgia. 2000;20:85–91.

    Article  CAS  PubMed  Google Scholar 

  58. Markley HG. Topical agents in the treatment of cluster headache. Curr Pain Headache Rep. 2003;7:139–43.

    Article  PubMed  Google Scholar 

  59. Kittrelle JP, Grouse DS, Seybold ME. Cluster headache. Local anesthetic abortive agents. Arch Neurol. 1985;42:496–8.

    Article  CAS  PubMed  Google Scholar 

  60. Horton B. The use of histamine in the treatment of specific types of headaches. JAMA. 1941;116:377–83.

    Article  Google Scholar 

  61. Rozen TD. Cluster headache as the result of secondhand cigarette smoke exposure during childhood. Headache. 2010;50:130–2.

    Article  PubMed  Google Scholar 

  62. Rozen TD. A history of cigarette smoking is associated with the development of cranial autonomic symptoms with migraine headaches. Headache. 2011;51:85–91.

    Article  PubMed  Google Scholar 

  63. Weingarten TN, Moeschler SM, Ptaszynski AE, Hooten WM, Beebe TJ, Warner DO. An assessment of the association between smoking status, pain intensity, and functional interference in patients with chronic pain. Pain Phys. 2008;11:643–53.

    Google Scholar 

  64. U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006.

  65. Cafforio G, Morelli N, Rota E, Piane RM, Mazzoni M. Cocaine-induced cluster-like headache. Neurol Sci. 2014;35:319–21.

    Google Scholar 

  66. Penarrocha M, Bagan JV, Penarrocha MA, Silvestre FJ. Cluster headache and cocaine use. Oral Surg Oral Med Oral Pathol Oral Radiol. 2000;90:271–4.

    Article  CAS  Google Scholar 

  67. Lambru G, Castellini P, Manzoni GC, Torelli P. Mode of occurrence of traumatic head injuries in male patients with cluster headache or migraine: is there a connection with lifestyle? Cephalalgia. 2010;30:1502–8.

    Article  PubMed  Google Scholar 

  68. Agrawal A, Verweij KJ, Gillespie NA, Heath AC, Lessov-Schlaggar CN, Martin NG, et al. The genetics of addiction-a translational perspective. Transl Psychiatr. 2012;2:e140.

    Article  CAS  Google Scholar 

  69. Richter L, Foster SE. The exclusion of nicotine: closing the gap in addiction policy and practice. Am J Public Health. 2013;103:e14–6.

    Article  PubMed  Google Scholar 

  70. Volkow ND, Fowler JS, Wang GJ, Swanson JM, Telang F. Dopamine in drug abuse and addiction: results of imaging studies and treatment implications. Arch Neurol. 2007;64:1575–9.

    Article  PubMed  Google Scholar 

  71. Lynch WJ, Roth ME, Carroll ME. Biological basis of sex differences in drug abuse: preclinical and clinical studies. Psychopharmacology. 2002;164:121–37.

    Article  CAS  PubMed  Google Scholar 

  72. Littlewood JT, Glover V, Sandler M, Petty R, Peatfield R, Clifford RF. Migraine and cluster headache: links between platelet monoamine oxidase activity, smoking and personality. Headache. 1984;24:30–4.

    Article  CAS  PubMed  Google Scholar 

  73. Levi R, Edman GV, Ekbom K, Waldenlind E. Episodic cluster headache. I: Personality and some neuropsychological characteristics in male patients. Headache. 1992;32:119–25.

    Article  CAS  PubMed  Google Scholar 

  74. Buonfiglio M, Di Sabato F. Analytic cognitive style in cluster headache. Neurol Sci. 2011;32:875–81.

    Article  PubMed  Google Scholar 

  75. Italian Cooperative Study Group on the Epidemiology of Cluster H. Case-control study on the epidemiology of cluster headache. II: Anthropometric data and personality profile. Function Neurol. 2000;15:215–23.

    Google Scholar 

  76. Leeman RF, Potenza MN. A targeted review of the neurobiology and genetics of behavioural addictions: an emerging area of research. Can J Psychiatry. 2013;58:260–73.

    PubMed  Google Scholar 

  77. Lader M. Antiparkinsonian medication and pathological gambling. CNS Drugs. 2008;22:407–16.

    Article  CAS  PubMed  Google Scholar 

  78. Levy MJ, Matharu MS, Goadsby PJ. Prolactinomas, dopamine agonists and headache: 2 case reports. Eur J Neurol. 2003;10:169–73.

    Article  CAS  PubMed  Google Scholar 

  79. Ossemann M. Recurrence of cluster headache with pramipexole. Acta Neurol Belg. 2010;110:279–80.

    PubMed  Google Scholar 

  80. Palmieri A. Chronic cluster headache responsive to pramipexole. Cephalalgia. 2006;26:761–2.

    Article  CAS  PubMed  Google Scholar 

  81. Sewell RA. Response of cluster headache to kudzu. Headache. 2009;49:98–105.

    Article  PubMed  Google Scholar 

  82. Schurks M. Genetics of cluster headache. Curr Pain Headache Rep. 2010;14:132–9.

    Article  PubMed  Google Scholar 

  83. Rainero I, Rubino E, Valfre W, Gallone S, De Martino P, Zampella E, et al. Association between the G1246A polymorphism of the hypocretin receptor 2 gene and cluster headache: a meta-analysis. J Headache Pain. 2007;8:152–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Holland PR, Goadsby PJ. Cluster headache, hypothalamus, and orexin. Curr Pain Headache Rep. 2009;13:147–54.

    Article  PubMed  Google Scholar 

  85. Dwivedi S, Aggarwal A, Singh N, Aggarwal S, Sharma V. Role of family milieu in tobacco addiction: a study in a tertiary-care institution in India. J Health Popul Nutr. 2013;31:130–2.

    Article  PubMed Central  PubMed  Google Scholar 

  86. Agrawal A, Lynskey MT, Pergadia ML, Bucholz KK, Heath AC, Martin NG, et al. Early cannabis use and DSM-IV nicotine dependence: a twin study. Addiction. 2008;103:1896–904.

    Article  PubMed Central  PubMed  Google Scholar 

  87. Aston-Jones G, Smith RJ, Sartor GC, Moorman DE, Massi L, Tahsili-Fahadan P, et al. Lateral hypothalamic orexin/hypocretin neurons: a role in reward-seeking and addiction. Brain Res. 2010;1314:74–90.

    Article  CAS  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

ᅟ

Conflict of Interest

Amelie Govare declares no potential conflicts of interest relevant to this article. Elizabeth Leroux is a board member for Electro Core. Ms. Leroux received payment for development of educational presentations including service on speakers' bureaus from Electro Core, Pfizer, and Merck. Ms. Leroux has done Ad Board, Speaker honoraria, research grant, and unrestricted educational grant for Allergan.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Centre hospitalier universitaire de Montréal, Montreal, Canada

    Amelie Govare

  2. Headache Clinic, Centre hospitalier universitaire de Montréal, Montreal, Canada

    Elizabeth Leroux

  3. Hospital Notre-Dame, 1560 Sherbrooke East, Montreal, Quebec, H2L 4M1, Canada

    Elizabeth Leroux

Authors
  1. Amelie Govare
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth Leroux
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elizabeth Leroux.

Additional information

This article is part of the Topical Collection on Trigeminal Autonomic Cephalalgias

Rights and permissions

Reprints and permissions

About this article

Cite this article

Govare, A., Leroux, E. Licit and Illicit Drug Use in Cluster Headache. Curr Pain Headache Rep 18, 413 (2014). https://doi.org/10.1007/s11916-014-0413-8

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11916-014-0413-8

Keywords

Search

Navigation