Export file:


  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text


  • Citation Only
  • Citation and Abstract

Marijuana use among adolescents is associated with deleterious alterations in mature BDNF

1 School of Integrated Science and Humanity, Florida International University, Miami, USA
2 Department of Biostatistics and Data Science, University of Texas, Houston, USA
3 Department of Medicine, University of Miami, Miami, USA
4 Center for Education and Drug Abuse Research, University of Pittsburgh, Pittsburgh, USA

Background: With increases in marijuana use and legalization efforts, it is imperative to establish its impact on the developing brain. Therefore, we investigated whether exposure to marijuana alters brain derived neurotropic-factor (BDNF), given its critical role in brain development and plasticity. We then examined whether onset age of cannabis use was associated with more severe changes. A single site, cohort study following 500 urban healthy American adolescents. Changes in plasma m-BDNF levels were longitudinally assessed, and a multi-method approach was implemented to ascertain marijuana use. Multivariate and general linear model (GLM) regression modeling were utilized to test the main hypothesis, controlling for confounders. Results: Group-based trajectory modeling identified four distinct groups, characterized by naive (60% control), starters (14%), chronic users (20%), and experimenting/quitters (6%). Compared to controls, those initiating marijuana use had similar pre-existent m-BDNF (1939.2 ± 221 vs. 2640.7 ± 1309 ng/ml, p=0.4) After adjusting for confounding factors, GLM analyses revealed that, compared to controls, younger adolescents increased BDNF levels when experimenting and during moderate marijuana use. Older adolescents had a steeper increase in endogenous BDNF levels, particularly when escalating use. Multivariate analyses confirmed marijuana use as a predictor of m-BDNF (p = 0.001). Conclusions: This is the first study demonstrating BDNF alterations were not a precondition. Rather, BDNF alteration was secondary to marijuana use, serving as cautionary evidence of marijuana’s deleterious effects. Findings suggest that when marijuana use escalates, the BDNF pathway becomes more deregulated. Analyses confirm that age of marijuana use onset influences the magnitude of these changes.
  Article Metrics

Keywords Marijuana; adolescent; Brain Derived Neurotrophic Factor (BDNF); brain development; smoking

Citation: Maria Jose Miguez, Wenyaw Chan, Luis Espinoza, Ralph Tarter, Caroline Perez. Marijuana use among adolescents is associated with deleterious alterations in mature BDNF. AIMS Public Health , 2019, 6(1): 4-14. doi: 10.3934/publichealth.2019.1.4


  • 1. World Health Organization. Substance Abuse: Facts and Figures, 2015. Available from: http://www.who.int/substance_abuse/facts/cannabis/en/.
  • 2. Jacobus J, Tapert SF (2014) Effects of Cannabis on the Adolescent Brain. Curr Pharm Des 20: 2186–2193.    
  • 3. World Drug Report 2014. United Nations publication, Sales No. E.14.XI.7. Available from: http://www.unodc.org/documents/wdr2014/World_Drug_Report_2014_web.pdf
  • 4. Sevigny EL (2013) Is today's marijuana more potent simply because it's fresher? Drug Test Anal 5: 62–67.    
  • 5. D'Souza DC, Pittman B, Perry E (2009) Simen A Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans. Psychopharmacology 202: 569.    
  • 6. Jockers-Scherübl MC, Danker-Hopfe H, Mahlberg R, et al. (2004) Brain-derived neurotrophic factor serum concentrations are increased in drug-naive schizophrenic patients with chronic cannabis abuse and multiple substance abuse. Neurosci Lett 371: 79–83.    
  • 7. Arseneault L, Cannon M, Poulton R, et al. (2002) Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 7374: 1212–1213.
  • 8. Karege F, Perret G, Bondolfi G, et al. (2002) Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 109: 143–148.    
  • 9. NIDA Marijuana National Institute on Drug Abuse, 2017. Available from: https://www.drugabuse.gov/publications/research-reports/marijuana.
  • 10. Freedland CS, Whitlow CT, Miller MD, et al. (2002) Dose‐dependent effects of Δ9‐tetrahydrocannabinol on rates of local cerebral glucose utilization in rat. Synapse 45: 134–142.    
  • 11. Atakan Z (2012) Cannabis, a complex plant: different compounds and different effects on individuals. Ther Adv Psychopharmacol 2: 241–254.    
  • 12. Berghuis P, Dobszay MB, Wang X, et al. (2005) Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor. Proc Natl Acad Sci U S A 102: 19115–19120.    
  • 13. Angelucci F, Ricci V, Spalletta G, et al. (2008) Reduced serum concentrations of nerve growth factor, but not brain-derived neurotrophic factor, in chronic cannabis abusers. Eur Neuropsychopharmacol 18: 882–887.    
  • 14. Klug M, Maarten VDB (2013) An investigation into "two hit" effects of BDNF deficiency and young-adult cannabinoid receptor stimulation on prepulse inhibition regulation and memory in mice. Front Behav Neurosci 7: 149.
  • 15. Boulle F, Van Den Hove DL, Jakob SB et al. (2012) Epigenetic regulation of the BDNF gene: implications for psychiatric disorders. Mol Psychiatry 17: 584.    
  • 16. Jones S, Bonci A (2005) Synaptic plasticity and drug addiction. Curr Opin Pharmacol 5: 20–25.    
  • 17. Jacobus J, Tapert SF (2014) Effects of Cannabis on the Adolescent Brain. Curr Pharm Des 20: 2186–2193.    
  • 18. Weiland BJ, Thayer RE, Depue BE, et al. (2015) Daily marijuana use is not associated with brain morphometric measures in adolescents or adults. J Neurosci 35: 1505–1512.
  • 19. Gilman JM, Kuster JK, Lee S, et al. (2014) Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users. J Neurosci 34: 5529–5538.    
  • 20. National Institute on Drug Abuse. The NIDA Quick Screen. Screening for Drug Use in General Medical Settings: Resource Guide, March, 2012. Available from: https://www.drugabuse.gov/drugs-abuse/opioids
  • 21. Levy S, Weiss R, Sherritt L, et al. (2014) An Electronic Screen for Triaging Adolescent Substance Use by Risk Levels. JAMA Pediatr 168: 822–828.    
  • 22. Lu B (2003) Pro-region of neurotrophins: role in synaptic modulation. Neuron 39: 735–738.    
  • 23. Klein AB, Williamson R, Santini MA, et al. (2011) Blood BDNF concentrations reflect brain-tissue BDNF levels across species. Int J Neuropsychopharmacol 14: 347–353.    
  • 24. Richardson MT, Ainsworth BE, Jacobs DR, et al. (2001) Validation of the Stanford 7-day recall to assess habitual physical activity. Ann Epidemiol 11: 145–153.    
  • 25. Koh HK, Blakey CR, Roper AY (2014) Healthy People 2020: a report card on the health of the nation. JAMA 311: 2475–2476.    
  • 26. Konings M, Henquet C, Maharajh HD, et al. (2008) Early exposure to cannabis and risk for psychosis in young adolescents in Trinidad. Acta Psychiatr Scand 118: 209–213.    
  • 27. Jessor R, Chase JA, Donovan JE (1980) Psychosocial correlates of marijuana use and problem drinking in a national sample of adolescents. Am J Public Health 6: 604–613.
  • 28. Stefanis NC, Delespaul P, Henquet C, et al. (2004) Early adolescent cannabis exposure and positive and negative dimensions of psychosis. Addiction 99: 1333–1341.    
  • 29. Decoster J, van Os J, Kenis G, et al. (2011) Age at onset of psychotic disorder: Cannabis, BDNF Val66Met, and sex‐specific models of gene–environment interaction. Am J Med Genet B Neuropsychiatr Genet 156: 363–369.    
  • 30. Hill AB (1965) The Environment and Disease: Association or Causation? Proc R Soc Med 58: 295–300.
  • 31. Yücel M, Lorenzetti V, Suo C, et al. (2016) Hippocampal harms, protection and recovery following regular cannabis use. Transl Psychiatry 6: e710.    
  • 32. Shieh PB, Ghosh A (1999) Molecular mechanisms underlying activity-dependent regulation of BDNF expression. J Neurobiol 1: 127–134.
  • 33. Butovsky E, Juknat A, Goncharov I, et al. (2005) In vivo up‐regulation of brain‐derived neurotrophic factor in specific brain areas by chronic exposure to Δ9‐tetrahydrocannabinol. J neurochemistry 93: 802–811.    
  • 34. Murray PS, Holmes PV (2011) An Overview of Brain-Derived Neurotrophic Factor and Implications for Excitotoxic Vulnerability in the Hippocampus. Int J Pept 654085.
  • 35. Monteggia LM, Barrot M, Powell CM, et al. (2004) Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Natl Acad Sci U S A 101: 10827–10832.    
  • 36. Kleim JA, Chan S, Pringle E, et al. (2006) BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nat Neurosci 9: 735–737.    
  • 37. Beste C, Kolev V, Yordanova J, et al. (2010) The role of the BDNF Val66Met polymorphism for the synchronization of error-specific neural networks. J Neurosci 30: 10727–10733.    
  • 38. Li X, Wolf ME (2015) Multiple faces of BDNF in cocaine addiction. Behav Brain Res 279: 240–254.    
  • 39. Vargas-Perez H, Ting-A Kee R, Walton CH, et al. (2009) Ventral tegmental area BDNF induces an opiate-dependent-like reward state in naïve rats. Science 324:1732–1734.    
  • 40. Verheij MM, Vendruscolo LF, Caffino L, et al. (2016) Systemic delivery of a brain-penetrant TrkB antagonist reduces cocaine self-administration and normalizes TrkB signaling in the nucleus accumbens and prefrontal cortex. J Neurosci 36: 8149–8159.    
  • 41. McGinty JF, Whitfield TW, Berglind WJ (2010) Brain-derived neurotrophic factor and cocaine addiction. Brain Res 1314C: 183.
  • 42. Fujimura H, Altar CA, Chen R, et al. (2002) Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 87: 728–734.    
  • 43. Pan W, Banks WA, Fasold MB, et al. (1998) Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 37: 1553–1561.    
  • 44. Radka SF, Holst PA, Fritsche M, et al. (1996) Presence of brain-derived neurotrophic factor in brain and human and rat but not mouse serum detected by a sensitive and specific immunoassay. Brain Res 709: 122–301.    


This article has been cited by

  • 1. Susan H. Adkins, Kayla N. Anderson, Alyson B. Goodman, Evelyn Twentyman, Melissa L. Danielson, Anne Kimball, Eleanor S. Click, Jean Y. Ko, Mary E. Evans, David N. Weissman, Paul Melstrom, Emily Kiernan, Vikram Krishnasamy, Dale A. Rose, Christopher M. Jones, Brian A. King, Sacha R. Ellington, Lori A. Pollack, Jennifer L. Wiltz, Demographics, Substance Use Behaviors, and Clinical Characteristics of Adolescents With e-Cigarette, or Vaping, Product Use–Associated Lung Injury (EVALI) in the United States in 2019, JAMA Pediatrics, 2020, e200756, 10.1001/jamapediatrics.2020.0756

Reader Comments

your name: *   your email: *  

© 2019 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Copyright © AIMS Press All Rights Reserved