Skip to main content

The effects of cannabis use on salience attribution: a systematic review

  • Surapi Bhairavi Wijayendran (a1), Aisling O’Neill (a1) and Sagnik Bhattacharyya (a1)

The relationship between cannabis use and the onset of psychosis is well established. Aberrant salience processing is widely thought to underpin many of these symptoms. Literature explicitly investigating the relationship between aberrant salience processing and cannabis use is scarce; with those few studies finding that acute tetrahydrocannabinol (THC) administration (the main psychoactive component of cannabis) can result in abnormal salience processing in healthy cohorts, mirroring that observed in psychosis. Nevertheless, the extent of and mechanisms through which cannabis has a modulatory effect on aberrant salience, following both acute and chronic use, remain unclear.


Here, we systematically review recent findings on the effects of cannabis use – either through acute THC administration or in chronic users – on brain regions associated with salience processing (through functional MRI data); and performance in cognitive tasks that could be used as either direct or indirect measures of salience processing. We identified 13 studies either directly or indirectly exploring salience processing. Three types of salience were identified and discussed – incentive/motivational, emotional/affective, and attentional salience.


The results demonstrated an impairment of immediate salience processing, following acute THC administration. Amongst the long-term cannabis users, normal salience performance appeared to be underpinned by abnormal neural processes.


Overall, the lack of research specifically exploring the effects of cannabis use on salience processing, weaken any conclusions drawn. Additional research explicitly focussed on salience processing and cannabis use is required to advance our understanding of the neurocognitive mechanisms underlying the association between cannabis use and development of psychosis.

Corresponding author
Dr. Sagnik Bhattacharyya, M6.01.04, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, 16 De Crespigny Park, London SE5 8AF, UK. Tel: +44 20 7848 0955 Fax: +44 20 7848 0976 E-mail:
Hide All

These two authors contributed equally to this work.

Hide All
1. Burns L. World drug report 2013 by United Nations office on drugs and crime. Drug Alcohol Rev 2013;33:216.
2. Di Forti M, Marconi A, Carra E et al. Proportion of patients in South London with first-episode psychosis attributable to use of high potency cannabis: a case-control study. Lancet Psychiatry 2015;2:233238.
3. Moore TH, Zammit S, Lingford-Hughes A et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007;370:319328.
4. Schoeler T, Monk A, Sami MB et al. Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis. Lancet Psychiatry 2016;3:215225.
5. Patel R, Wilson R, Jackson R et al. Association of cannabis use with hospital admission and antipsychotic treatment failure in first episode psychosis: an observational study. BMJ Open 2016;6:e009888.
6. Schoeler T, Petros N, Di Forti M et al. Effects of continuation, frequency, and type of cannabis use on relapse in the first 2 years after onset of psychosis: an observational study. Lancet Psychiatry 2016;3:947953.
7. Schoeler T, Petros N, Di Forti M et al. Examining the association between continued cannabis use and risk of relapse in first episode psychosis: a quasi-experimental investigation within an observational study. JAMA Psychiatry 2016;doi:10.1001/jamapsychiatry.2016.2427.
8. Pamplona FA, Takahashi RN. Psychopharmacology of the endocannabinoids: far beyond anandamide. J Psychopharmacol 2012;26:722.
9. Mechoulam R, Parker LA. The endocannabinoid system and the brain. Annu Rev Psychol 2013;64:2147.
10. Leweke FM, Giuffrida A, Wurster U, Emrich HM, Piomelli D. Elevated endogenous cannabinoids in schizophrenia. Neuroreport 1999;10:16651669.
11. Appiah-Kusi E, Leyden E, Parmar S, Mondelli V, McGuire P, Bhattacharyya S. Abnormalities in neuroendocrine stress response in psychosis: the role of endocannabinoids. Psychol Med 2016;46:2745.
12. Bossong MG, Jansma JM, Bhattacharyya S, Ramsey NF. Role of the endocannabinoid system in brain functions relevant for schizophrenia: an overview of human challenge studies with cannabis or 9-tetrahydrocannabinol (THC). Prog Neuropsychopharmacol Biol Psychiatry 2014;52:5369.
13. Stefanis NC, Delespaul P, Henquet C, Bakoula C, Stefanis CN, Van Os J. Early adolescent cannabis exposure and positive and negative dimensions of psychosis. Addiction 2004;99:13331341.
14. D’Souza DC, Perry E, MacDougall L et al. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 2004;29:15581572.
15. Bhattacharyya S, Crippa JA, Allen P et al. Induction of psychosis by delta9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing. Arch Gen Psychiatry 2012;69:2736.
16. Bhattacharyya S, Fusar-Poli P, Borgwardt S et al. Modulation of mediotemporal and ventrostriatal function in humans by delta9-tetrahydrocannabinol: a neural basis for the effects of cannabis sativa on learning and psychosis. Arch Gen Psychiatry 2009;66:442451.
17. Bhattacharyya S, Atakan Z, Martin-Santos R et al. Impairment of inhibitory control processing related to acute psychotomimetic effects of cannabis. Eur Neuropsychopharmacol 2015;25:2637.
18. Bhattacharyya S, Falkenberg I, Martin-Santos R et al. Cannabinoid modulation of functional connectivity within regions processing attentional salience. Neuropsychopharmacology 2015;40:13431352.
19. Kapur S. Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry 2003;160:1323.
20. Charboneau EJ, Dietrich MS, Park S et al. Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: preliminary results. Psychiatry Res 2013;214:122131.
21. Filbey FM, Schacht JP, Myers US, Chavez RS, Hutchison KE. Marijuana craving in the brain. Proc Natl Acad Sci U S A 2009;106:1301613021.
22. Wolfling K, Flor H, Grusser SM. Psychophysiological responses to drug-associated stimuli in chronic heavy cannabis use. Eur J Neurosci 2008;27:976983.
23. Berridge KC. From prediction error to incentive salience: mesolimbic computation of reward motivation. Eur J Neurosci 2012;35:11241143.
24. Metrik J, Aston ER, Kahler CW, Rohsenow DJ, McGeary JE, Knopik VS. Marijuana’s acute effects on cognitive bias for affective and marijuana cues. Experimental Clin Psychopharmacol 2015;23:339350.
25. Ballard ME, Bedi G, de Wit H. Effects of delta-9-tetrahydrocannabinol on evaluation of emotional images. J Psychopharmacol 2012;26:12891298.
26. Phan KL, Angstadt M, Golden J, Onyewuenyi I, Popovska A, de Wit H. Cannabinoid modulation of amygdala reactivity to social signals of threat in humans. J Neurosci 2008;28:23132319.
27. Somaini L, Manfredini M, Amore M et al. Psychobiological responses to unpleasant emotions in cannabis users. Eur Arch Psychiatry Clin Neurosci 2012;262:4757.
28. Niu Y, Todd RM, Anderson AK. Affective salience can reverse the effects of stimulus-driven salience on eye movements in complex scenes. Front Psychol 2012;3:336.
29. Hooker WD, Jones RT. Increased susceptibility to memory intrusions and the Stroop interference effect during acute marijuana intoxication. Psychopharmacology 1987;91:2024.
30. Grant JE, Chamberlain SR, Schreiber L, Odlaug BL. Neuropsychological deficits associated with cannabis use in young adults. Drug Alcohol Depend 2012;121:159162.
31. Gruber SA, Yurgelun-Todd DA. Neuroimaging of marijuana smokers during inhibitory processing: a pilot investigation. Brain Res Cogn Brain Res 2005;23:107118.
32. Kober H, DeVito EE, DeLeone CM, Carroll KM, Potenza MN. Cannabis abstinence during treatment and one-year follow-up: relationship to neural activity in men. Neuropsychopharmacology 2014;39:22882298.
33. Eldreth DA, Matochik JA, Cadet JL, Bolla KI. Abnormal brain activity in prefrontal brain regions in abstinent marijuana users. NeuroImage 2004;23:914920.
34. Shinn-Cunningham BG. Object-based auditory and visual attention. Trends Cogn Sci 2008;12:182186.
35. Bowman H, Su L, Wyble B, Barnard PJ. Salience sensitive control, temporal attention and stimulus-rich reactive interfaces. In: Roda C editor Human attention in digital environments. Cambridge: Cambridge University Press, 2011; p. 114146.
36. Singer T, Seymour B, O’Doherty J, Kaube H, Dolan RJ, Frith CD. Empathy for pain involves the affective but not sensory components of pain. Science 2004;303:11571162.
37. Peyron R, Laurent B, Garcia-Larrea L. Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiol Clin 2000;30:263288.
38. Craig AD. How do you feel? Interoception: the sense of the physiological condition of the body. Nat Rev Neurosci 2002;3:655666.
39. Bartels A, Zeki S. The neural correlates of maternal and romantic love. Neuroimage 2004;21:11551166.
40. Eisenberger NI, Lieberman MD, Williams KD. Does rejection hurt? An FMRI study of social exclusion. Science 2003;302:290292.
41. Jensen J, Kapur S. Salience and psychosis: moving from theory to practise. Psychol Med 2009;39:197198.
42. Wylie KP, Tregellas JR. The role of the insula in schizophrenia. Schizophr Res 2010;123:93104.
43. Menon V. Salience network. In: Toga AW editor Brain mapping: an encyclopedic reference. 2. Cambridge: Academic Press: Elsevier, 2015; p. 597611.
44. Seeley WW, Menon V, Schatzberg AF et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 2007;27:23492356.
45. Winton-Brown TT, Fusar-Poli P, Ungless MA, Howes OD. Dopaminergic basis of salience dysregulation in psychosis. Trends Neurosci 2014;37:8594.
46. Pertwee RG. Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond. Addict Biol 2008;13:147159.
47. Beaulieu JM, Gainetdinov RR. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 2011;63:182217.
48. White TP, Joseph V, Francis ST, Liddle PF. Aberrant salience network (bilateral insula and anterior cingulate cortex) connectivity during information processing in schizophrenia. Schizophr Res 2010;123:105115.
49. Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci 2011;15:483506.
50. Manoliu A, Riedl V, Zherdin A et al. Aberrant dependence of default mode/central executive network interactions on anterior insular salience network activity in schizophrenia. Schizophr Bull 2014;40:428437.
51. Bossong MG, van Berckel BN, Boellaard R et al. Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum. Neuropsychopharmacology 2009;34:759766.
52. Boehme R, Deserno L, Gleich T et al. Aberrant salience is related to reduced reinforcement learning signals and elevated dopamine synthesis capacity in healthy adults. J Neurosci 2015;35:1010310111.
53. Gardner EL, Vorel SR. Cannabinoid transmission and reward-related events. Neurobiol Dis 1998;5(6 Pt B):502533.
54. Chen JP, Paredes W, Li J, Smith D, Lowinson J, Gardner EL. Delta 9-tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis. Psychopharmacology 1990;102:156162.
55. Sami MB, Rabiner EA, Bhattacharyya S. Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date. Eur Neuropsychopharmacol 2015;25:12011224.
56. Boudin F, Nie J-Y, Dawes M. editor. Clinical information retrieval using document and PICO structure. Human Language Technologies: The 2010 Annual Conference of the North American Chapter of the ACL, Association for Computational Linguistics, Los Angeles, CA, 2010.
57. Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration 2011. Available at
58. West S, King V, Carey TS et al. Systems to rate the strength of scientific evidence. Evid Rep Technol Assess 2002;47:111.
59. D’Souza DC, Ranganathan M, Braley G et al. Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology 2008;33:25052516.
60. Bossong MG, Jager G, Bhattacharyya S, Allen P. Acute and non-acute effects of cannabis on human memory function: a critical review of neuroimaging studies. Curr Pharm Des 2014;20:21142125.
61. Jung WH, Jang JH, Park JW et al. Unravelling the intrinsic functional organization of the human striatum: a parcellation and connectivity study based on resting-state FMRI. PLoS One 2014;9:e106768.
62. Liberzon I, Phan KL, Decker LR, Taylor SF. Extended amygdala and emotional salience: a PET activation study of positive and negative affect. Neuropsychopharmacology 2003;28:726733.
63. Santos A, Mier D, Kirsch P, Meyer-Lindenberg A. Evidence for a general face salience signal in human amygdala. Neuroimage 2011;54:31113116.
64. Smith SM, Vale WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci 2006;8:383395.
65. Epstein DH, Willner-Reid J, Vahabzadeh M, Mezghanni M, Lin JL, Preston KL. Real-time electronic diary reports of cue exposure and mood in the hours before cocaine and heroin craving and use. Arch Gen Psychiatry 2009;66:8894.
66. Cheer JF, Wassum KM, Heien ML, Phillips PE, Wightman RM. Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats. J Neurosci 2004;24:43934400.
67. Malone DT, Taylor DA. Modulation by fluoxetine of striatal dopamine release following delta 9-tetrahydrocannabinol: a microdialysis study in conscious rats. Br J Pharmacol 1999;128:2126.
68. Bloomfield MA, Morgan CJ, Egerton A, Kapur S, Curran HV, Howes OD. Dopaminergic function in cannabis users and its relationship to cannabis-induced psychotic symptoms. Biol Psychiatry 2014;75:470478.
69. Mizrahi R, Kenk M, Suridjan I et al. Stress-induced dopamine response in subjects at clinical high risk for schizophrenia with and without concurrent cannabis use. Neuropsychopharmacology 2014;39:14791489.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Acta Neuropsychiatrica
  • ISSN: 0924-2708
  • EISSN: 1601-5215
  • URL: /core/journals/acta-neuropsychiatrica
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 22
Total number of PDF views: 100 *
Loading metrics...

Abstract views

Total abstract views: 712 *
Loading metrics...

* Views captured on Cambridge Core between 21st November 2016 - 22nd February 2018. This data will be updated every 24 hours.