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Cannabis effects on brain structure, function, and cognition: considerations for medical uses of cannabis and its derivatives

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Pages 563-579 | Received 02 Jan 2019, Accepted 17 Jun 2019, Published online: 31 Jul 2019

References

  • Piluzza G, Delogu G, Cabras A, Marceddu S, Bullitta S. Differentiation between fiber and drug types of hemp (Cannabis sativa L.) from a collection of wild and domesticated accessions. Genet Resour Crop Evol. 2013;60:2331–42. doi:10.1007/s10722-013-0001-5.
  • Andre CM, Hausman J-F, Guerriero G. Cannabis sativa: the Plant of the thousand and one molecules. Front Plant Sci. 2016;7:19. doi:10.3389/fpls.2016.00019.
  • Pellati F, Brighenti V, Sperlea J, et al. New methods for the comprehensive analysis of bioactive compounds in Cannabis sativa L. (hemp) . Mol Basel Switz. 2018;23.
  • U.S. Department of Health and Human Services. National survey on drug use and health [Internet]. Rockville, MD: Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality; 2018. Available from: https://datafiles.samhsa.gov/.
  • Djeungoue-Petga M-A, Hebert-Chatelain E. Linking mitochondria and synaptic transmission: the CB1 receptor. BioEssays News Rev Mol Cell Dev Biol. 2017;39.
  • Mackie K. Cannabinoid receptors: where they are and what they do. J Neuroendocrinol. 2008;20:10–14. doi:10.1111/j.1365-2826.2008.01671.x.
  • Straiker AJ, Maguire G, Mackie K, et al. Localization of cannabinoid CB1 receptors in the human anterior eye and retina. Invest Ophthalmol Vis Sci. 1999;40:2442–48.
  • Bilkei-Gorzo A. The endocannabinoid system in normal and pathological brain ageing. Philos Trans R Soc Lond B Biol Sci. 2012;367:3326–41. doi:10.1098/rstb.2011.0388.
  • Freund TF, Katona I, Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev. 2003;83:1017–66. doi:10.1152/physrev.00004.2003.
  • Regehr WG, Carey MR, Best AR. Activity-dependent regulation of synapses by retrograde messengers. Neuron. 2009;63:154–70. doi:10.1016/j.neuron.2009.06.021.
  • Glass M, Dragunow M, Faull RL. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience. 1997;77:299–318. doi:10.1016/S0306-4522(96)00428-9.
  • Befort K. Interactions of the opioid and cannabinoid systems in reward: insights from knockout studies. Front Pharmacol. 2015;6:6.
  • Egerton A, Allison C, Brett RR, Pratt JA. Cannabinoids and prefrontal cortical function: insights from preclinical studies. Neurosci Biobehav Rev. 2006;30:680–95. doi:10.1016/j.neubiorev.2005.12.002.
  • Katona I, Freund TF. Multiple functions of endocannabinoid signaling in the brain. Annu Rev Neurosci. 2012;35:529–58. doi:10.1146/annurev-neuro-062111-150420.
  • Hill MN, McEwen BS. Involvement of the endocannabinoid system in the neurobehavioural effects of stress and glucocorticoids. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:791–97. doi:10.1016/j.pnpbp.2009.11.001.
  • Diao X, Huestis MA. New synthetic cannabinoids metabolism and strategies to best identify optimal marker metabolites. Front Chem. 2019;7:109. doi:10.3389/fchem.2019.00109.
  • Bloomfield MAP, Hindocha C, Green SF, Wall MB, Lees R, Petrilli K, Costello H, Ogunbiyi MO, Bossong MG, Freeman TP. The neuropsychopharmacology of cannabis: A review of human imaging studies. Pharmacol Ther. 2019;195:132–61. doi:10.1016/j.pharmthera.2018.10.006.
  • Burns HD, Van Laere K, Sanabria-Bohórquez S, Hamill TG, Bormans G, Eng W-S, Gibson R, Ryan C, Connolly B, Patel S, et al. [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proc Natl Acad Sci USA. 2007;104:9800–05. doi:10.1073/pnas.0703472104.
  • Zhang H-Y, Gao M, Liu Q-R, Bi G-H, Li X, Yang H-J, Gardner EL, Wu J, Xi Z-X. Cannabinoid CB2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice. Proc Natl Acad Sci USA. 2014;111:E5007–5015. doi:10.1073/pnas.1413210111.
  • Rodriguez JJ, Mackie K, Pickel VM. Ultrastructural localization of the CB1 cannabinoid receptor in mu-opioid receptor patches of the rat Caudate putamen nucleus. J Neurosci Off J Soc Neurosci. 2001;21:823–33. doi:10.1523/JNEUROSCI.21-03-00823.2001.
  • Díaz-Alonso J, Guzmán M, Galve-Roperh I. Endocannabinoids via CB₁ receptors act as neurogenic niche cues during cortical development. Philos Trans R Soc Lond B Biol Sci. 2012;367:3229–41. doi:10.1098/rstb.2011.0385.
  • Friedrich J, Khatib D, Parsa K, Santopietro A, Gallicano GI. The grass isn’t always greener: the effects of cannabis on embryological development. BMC Pharmacol Toxicol. 2016;17:45. doi:10.1186/s40360-016-0085-6.
  • Huizink AC. Prenatal cannabis exposure and infant outcomes: overview of studies. Prog Neuropsychopharmacol Biol Psychiatry. 2014;52:45–52. doi:10.1016/j.pnpbp.2013.09.014.
  • Crews F, He J, Hodge C. Adolescent cortical development: a critical period of vulnerability for addiction. Pharmacol Biochem Behav. 2007;86:189–99. doi:10.1016/j.pbb.2006.12.020.
  • Giedd JN. Structural magnetic resonance imaging of the adolescent brain. Ann N Y Acad Sci. 2004;1021:77–85. doi:10.1196/annals.1308.009.
  • Wakeford AGP, Wetzell BB, Pomfrey RL, Clasen MM, Taylor WW, Hempel BJ, Riley AL. The effects of cannabidiol (CBD) on Δ9-tetrahydrocannabinol (THC) self-administration in male and female Long-Evans rats. Exp Clin Psychopharmacol. 2017;25:242–48. doi:10.1037/pha0000135.
  • Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153:199–215. doi:10.1038/bjp.2008.22.
  • Martínez-Pinilla E, Varani K, Reyes-Resina I, Angelats E, Vincenzi F, Ferreiro-Vera C, Oyarzabal J, Canela EI, Lanciego JL, Nadal X, et al. Binding and signaling studies disclose a potential allosteric site for cannabidiol in cannabinoid CB2 receptors. Front Pharmacol. 2017;8:744. doi:10.3389/fphar.2017.00744.
  • Morales P, Reggio PH, Jagerovic N. An overview on medicinal chemistry of synthetic and natural derivatives of cannabidiol. Front Pharmacol. 2017;8:422. doi:10.3389/fphar.2017.00422.
  • Navarro G, Reyes-Resina I, Rivas-Santisteban R, Sánchez de Medina V, Morales P, Casano S, Ferreiro-Vera C, Lillo A, Aguinaga D, Jagerovic N, et al. Cannabidiol skews biased agonism at cannabinoid CB1 and CB2 receptors with smaller effect in CB1-CB2 heteroreceptor complexes. Biochem Pharmacol. 2018;157:148–58. doi:10.1016/j.bcp.2018.08.046.
  • Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. 2007;150:613–23. doi:10.1038/sj.bjp.0707133.
  • Tham M, Yilmaz O, Alaverdashvili M, Kelly MEM, Denovan-Wright EM, Laprairie RB. Allosteric and orthosteric pharmacology of cannabidiol and cannabidiol-dimethylheptyl at the type 1 and type 2 cannabinoid receptors. Br J Pharmacol. 2019;176:1455–69. doi:10.1111/bph.14440.
  • Kathmann M, Flau K, Redmer A, Tränkle C, Schlicker E. Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn. Schmiedebergs Arch. Pharmacol. 2006;372:354–61. doi:10.1007/s00210-006-0033-x.
  • Dornbush RL, Freedman AM. Chronic cannabis use: introduction. Ann N Y Acad Sci. 1976;282:vii–viii. doi:10.1111/nyas.1976.282.issue-1.
  • Hollister LE. Health aspects of cannabis. Pharmacol Rev. 1986;38:1–20.
  • Hollister LE. Health aspects of cannabis: revisited. Int J Neuropsychopharmacol. 1998;1:71–80. doi:10.1017/S1461145798001060.
  • Iversen L. Cannabis and the brain. Brain J Neurol. 2003;126:1252–70. doi:10.1093/brain/awg143.
  • Batalla A, Bhattacharyya S, Yücel M, Fusar-Poli P, Crippa JA, Nogué S, Torrens M, Pujol J, Farré M, Martin-Santos R, et al. Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings. PLoS One. 2013;8:e55821. doi:10.1371/journal.pone.0055821.
  • Lorenzetti V, Chye Y, Silva P, Solowij N, Roberts CA. Does regular cannabis use affect neuroanatomy? An updated systematic review and meta-analysis of structural neuroimaging studies. Eur Arch Psychiatry Clin Neurosci. 2019;269:59–71. doi:10.1007/s00406-019-00979-1.
  • Egertová M, Elphick MR. Localisation of cannabinoid receptors in the rat brain using antibodies to the intracellular C-terminal tail of CB. J Comp Neurol. 2000;422:159–71. doi:10.1002/(SICI)1096-9861(20000626)422:2<159::AID-CNE1>3.0.CO;2-1.
  • Katona I, Rancz EA, Acsady L, Ledent C, Mackie K, Hájos N, Freund TF. Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission. J Neurosci Off J Soc Neurosci. 2001;21:9506–18. doi:10.1523/JNEUROSCI.21-23-09506.2001.
  • Nader DA, Sanchez ZM. Effects of regular cannabis use on neurocognition, brain structure, and function: a systematic review of findings in adults. Am J Drug Alcohol Abuse. 2018;44:4–18. doi:10.1080/00952990.2017.1306746.
  • Ashtari M, Avants B, Cyckowski L, Cervellione KL, Roofeh D, Cook P, Gee J, Sevy S, Kumra S. Medial temporal structures and memory functions in adolescents with heavy cannabis use. J Psychiatr Res. 2011;45:1055–66. doi:10.1016/j.jpsychires.2011.01.004.
  • Battistella G, Fornari E, Annoni J-M, Chtioui H, Dao K, Fabritius M, Favrat B, Mall J-F, Maeder P, Giroud C. Long-term effects of cannabis on brain structure. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2014;39:2041–48. doi:10.1038/npp.2014.67.
  • Burggren AC, Siddarth P, Mahmood Z, London ED, Harrison TM, Merrill DA, Small GW, Bookheimer SY. Subregional hippocampal thickness abnormalities in older adults with a history of heavy cannabis use. Cannabis Cannabinoid Res. 2018;3:242–51. doi:10.1089/can.2018.0035.
  • Yücel M, Lorenzetti V, Suo C, Zalesky A, Fornito A, Takagi MJ, Lubman DI, Solowij N. Hippocampal harms, protection and recovery following regular cannabis use. Transl Psychiatry. 2016;6:e710. doi:10.1038/tp.2015.201.
  • Yücel M, Solowij N, Respondek C, et al. Regional brain abnormalities associated with long-term heavy cannabis use. Arch Gen Psychiatry. 2008;65:694–701.
  • Demirakca T, Sartorius A, Ende G, et al. Diminished gray matter in the hippocampus of cannabis users: possible protective effects of cannabidiol. Drug Alcohol Depend. 2011;114:242–45.
  • Matochik JA, Eldreth DA, Cadet J-L, Bolla KI. Altered brain tissue composition in heavy marijuana users. Drug Alcohol Depend. 2005;77:23–30. doi:10.1016/j.drugalcdep.2004.06.011.
  • Tzilos GK, Cintron CB, Wood JBR, Simpson NS, Young AD, Pope HG, Yurgelun-Todd DA. Lack of hippocampal volume change in long-term heavy cannabis users. Am J Addict. 2005;14:64–72. doi:10.1080/10550490590899862.
  • Koenders L, Lorenzetti V, de Haan L, Suo C, Vingerhoets W, van Den Brink W, Wiers RW, Meijer CJ, Machielsen M, Goudriaan AE, et al. Longitudinal study of hippocampal volumes in heavy cannabis users. J Psychopharmacol Oxf Engl. 2017;31:1027–34. doi:10.1177/0269881117718380.
  • Chye Y, Lorenzetti V, Suo C, Batalla A, Cousijn J, Goudriaan AE, Jenkinson M, Martin‐Santos R, Whittle S, Yücel M, et al. Alteration to hippocampal volume and shape confined to cannabis dependence: a multi-site study. Addict Biol. 2019;24:822–34. doi:10.1111/adb.2019.24.issue-4.
  • Lopez-Quintero C, Pérez de Los Cobos J, Hasin DS, Okuda M, Wang S, Grant BF, Blanco C. Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Drug Alcohol Depend. 2011;115:120–30. doi:10.1016/j.drugalcdep.2010.11.004.
  • Lorenzetti V, Lubman DI, Whittle S, Solowij N, Yücel M. Structural MRI findings in long-term cannabis users: what do we know?. Subst Use Misuse. 2010;45:1787–808. doi:10.3109/10826084.2010.482443.
  • Volkow ND, Compton WM, Weiss SRB. Adverse health effects of marijuana use. N Engl J Med. 2014;371:879. doi:10.1056/NEJMoa1410490.
  • Mokrysz C, Freeman TP, Korkki S, Griffiths K, Curran HV. Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males. Transl Psychiatry. 2016;6:e961. doi:10.1038/tp.2016.225.
  • Jager G, Ramsey NF. Long-term consequences of adolescent cannabis exposure on the development of cognition, brain structure and function: an overview of animal and human research. Curr Drug Abuse Rev. 2008;1:114–23. doi:10.2174/1874473710801020114.
  • Cousijn J, Wiers RW, Ridderinkhof KR, van Den Brink W, Veltman DJ, Goudriaan AE. Grey matter alterations associated with cannabis use: results of a VBM study in heavy cannabis users and healthy controls. NeuroImage. 2012;59:3845–51. doi:10.1016/j.neuroimage.2011.09.046.
  • Gilman JM, Kuster JK, Lee S, Lee MJ, Kim BW, Makris N, van der Kouwe A, Blood AJ, Breiter HC. Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users. J Neurosci Off J Soc Neurosci. 2014;34:5529–38. doi:10.1523/JNEUROSCI.4745-13.2014.
  • Koenders L, Cousijn J, Vingerhoets WAM, van Den Brink W, Wiers RW, Meijer CJ, Machielsen MWJ, Veltman DJ, Goudriaan AE, de Haan L, et al. grey matter changes associated with heavy cannabis use: a longitudinal sMRI study. PLoS One. 2016;11:e0152482. doi:10.1371/journal.pone.0152482.
  • Moreno-Alcázar A, Gonzalvo B, Canales-Rodríguez EJ, Blanco L, Bachiller D, Romaguera A, Monté-Rubio GC, Roncero C, McKenna PJ, Pomarol-Clotet E. Larger Gray matter volume in the basal ganglia of heavy Cannabis users detected by voxel-based morphometry and subcortical volumetric analysis. Front Psychiatry. 2018;9:175. doi:10.3389/fpsyt.2018.00175.
  • Weiland BJ, Thayer RE, Depue BE, Sabbineni A, Bryan AD, Hutchison KE. Daily marijuana use is not associated with brain morphometric measures in adolescents or adults. J Neurosci Off J Soc Neurosci. 2015;35:1505–12. doi:10.1523/JNEUROSCI.2946-14.2015.
  • Pagliaccio D, Barch DM, Bogdan R, Wood PK, Lynskey MT, Heath AC, Agrawal A. Shared predisposition in the association between cannabis use and subcortical brain structure. JAMA Psychiatry. 2015;72:994–1001. doi:10.1001/jamapsychiatry.2015.1054.
  • Gillespie NA, Neale MC, Bates TC, Eyler LT, Fennema-Notestine C, Vassileva J, Lyons MJ, Prom-Wormley EC, McMahon KL, Thompson PM, et al. Testing associations between cannabis use and subcortical volumes in two large population-based samples. Addict Abingdon Engl. 2018. doi:10.1111/add.v113.9.
  • Arnone D, Barrick TR, Chengappa S, Mackay CE, Clark CA, Abou-Saleh MT. Corpus callosum damage in heavy marijuana use: preliminary evidence from diffusion tensor tractography and tract-based spatial statistics. NeuroImage. 2008;41:1067–74. doi:10.1016/j.neuroimage.2008.02.064.
  • Becker MP, Collins PF, Lim KO, Muetzel RL, Luciana M. Longitudinal changes in white matter microstructure after heavy cannabis use. Dev Cogn Neurosci. 2015;16:23–35. doi:10.1016/j.dcn.2015.10.004.
  • Gruber SA, Silveri MM, Dahlgren MK, Yurgelun-Todd D. Why so impulsive? White matter alterations are associated with impulsivity in chronic marijuana smokers. Exp Clin Psychopharmacol. 2011;19:231–42. doi:10.1037/a0023034.
  • Zalesky A, Solowij N, Yücel M, Lubman DI, Takagi M, Harding IH, Lorenzetti V, Wang R, Searle K, Pantelis C, et al. Effect of long-term cannabis use on axonal fibre connectivity. Brain J Neurol. 2012;135:2245–55. doi:10.1093/brain/aws136.
  • Filbey F, Yezhuvath U. Functional connectivity in inhibitory control networks and severity of cannabis use disorder. Am J Drug Alcohol Abuse. 2013;39:382–91. doi:10.3109/00952990.2013.841710.
  • Price JS, McQueeny T, Shollenbarger S, Browning EL, Wieser J, Lisdahl KM. Effects of marijuana use on prefrontal and parietal volumes and cognition in emerging adults. Psychopharmacology (Berl.). 2015;232:2939–50. doi:10.1007/s00213-015-3931-0.
  • Lorenzetti V, Alonso-Lana S, Youssef GJ, et al. Adolescent Cannabis use: what is the evidence for functional brain alteration?. Curr Pharm Des. 2016;22:6353–65.
  • Scott JC, Rosen AFG, Moore TM, Roalf DR, Satterthwaite TD, Calkins ME, Ruparel K, Gur RE, Gur RC. Cannabis use in youth is associated with limited alterations in brain structure. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2019;44:1362–69. doi:10.1038/s41386-019-0347-2.
  • Orr C, Spechler P, Cao Z, Albaugh M, Chaarani B, Mackey S, D’Souza D, Allgaier N, Banaschewski T, Bokde ALW, et al. Grey matter volume differences associated with extremely low levels of cannabis use in adolescence. J Neurosci Off J Soc Neurosci. 2019;39:1817–27. doi:10.1523/JNEUROSCI.3375-17.2018.
  • Hasin DS, Saha TD, Kerridge BT, Goldstein RB, Chou SP, Zhang H, Jung J, Pickering RP, Ruan WJ, Smith SM, et al. Prevalence of Marijuana use disorders in the United States between 2001-2002 and 2012-2013. JAMA Psychiatry. 2015;72:1235–42. doi:10.1001/jamapsychiatry.2015.1858.
  • Mauro PM, Carliner H, Brown QL, Hasin DS, Shmulewitz D, Rahim-Juwel R, Sarvet AL, Wall MM, Martins SS. Age differences in daily and nondaily Cannabis use in the United States, 2002-2014. J Stud Alcohol Drugs. 2018;79:423–31. doi:10.15288/jsad.2018.79.423.
  • Kim D-J, Schnakenberg Martin AM, Shin Y-W, Jo HJ, Cheng H, Newman SD, Sporns O, Hetrick WP, Calkins E, O’Donnell BF. Aberrant structural-functional coupling in adult cannabis users. Hum Brain Mapp. 2019;40:252–61. doi:10.1002/hbm.v40.1.
  • Sagar KA, Gruber SA. Interactions between recreational cannabis use and cognitive function: lessons from functional magnetic resonance imaging. Ann. N Y Acad Sci. 2018. doi:10.1111/nyas.13990.
  • Yanes JA, Riedel MC, Ray KL, Kirkland AE, Bird RT, Boeving ER, Reid MA, Gonzalez R, Robinson JL, Laird AR, et al. Neuroimaging meta-analysis of cannabis use studies reveals convergent functional alterations in brain regions supporting cognitive control and reward processing. J Psychopharmacol Oxf Engl. 2018;32:283–95. doi:10.1177/0269881117744995.
  • Atakan Z, Bhattacharyya S, Allen P, Martín-Santos R, Crippa JA, Borgwardt SJ, Fusar-Poli P, Seal M, Sallis H, Stahl D, et al. Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: a functional magnetic resonance imaging study with healthy volunteers. Psychol Med. 2013;43:1255–67. doi:10.1017/S0033291712001924.
  • Harding IH, Solowij N, Harrison BJ, Takagi M, Lorenzetti V, Lubman DI, Seal ML, Pantelis C, Yücel M. Functional connectivity in brain networks underlying cognitive control in chronic cannabis users. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2012;37:1923–33. doi:10.1038/npp.2012.39.
  • Chang L, Yakupov R, Cloak C, Ernst T. Marijuana use is associated with a reorganized visual-attention network and cerebellar hypoactivation. Brain J Neurol. 2006;129:1096–112. doi:10.1093/brain/awl064.
  • Jager G, Kahn RS, Van Den Brink W, Van Ree JM, Ramsey NF. Long-term effects of frequent cannabis use on working memory and attention: an fMRI study. Psychopharmacology (Berl.). 2006;185:358–68. doi:10.1007/s00213-005-0298-7.
  • Jager G, Van Hell HH, De Win MML, Kahn RS, Van Den Brink W, Van Ree JM, Ramsey NF. Effects of frequent cannabis use on hippocampal activity during an associative memory task. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol. 2007;17:289–97. doi:10.1016/j.euroneuro.2006.10.003.
  • Kanayama G, Rogowska J, Pope HG, Gruber SA, Yurgelun-Todd DA. Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study. Psychopharmacology (Berl.). 2004;176:239–47. doi:10.1007/s00213-004-1885-8.
  • Bechara A, Tranel D, Damasio H. Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions. Brain J Neurol. 2000;123:2189–202. doi:10.1093/brain/123.11.2189.
  • Nestor L, Hester R, Garavan H. Increased ventral striatal BOLD activity during non-drug reward anticipation in cannabis users. NeuroImage. 2010;49:1133–43. doi:10.1016/j.neuroimage.2009.07.022.
  • Vaidya JG, Block RI, O’Leary DS, Ponto LB, Ghoneim MM, Bechara A. Effects of chronic marijuana use on brain activity during monetary decision-making. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2012;37:618–29. doi:10.1038/npp.2011.227.
  • Wesley MJ, Hanlon CA, Porrino LJ. Poor decision-making by chronic marijuana users is associated with decreased functional responsiveness to negative consequences. Psychiatry Res. 2011;191:51–59. doi:10.1016/j.pscychresns.2010.10.002.
  • King GR, Ernst T, Deng W, Stenger A, Gonzales RMK, Nakama H, Chang L. Altered brain activation during visuomotor integration in chronic active cannabis users: relationship to cortisol levels. J Neurosci Off J Soc Neurosci. 2011;31:17923–31. doi:10.1523/JNEUROSCI.4148-11.2011.
  • Gruber SA, Rogowska J, Yurgelun-Todd DA. Altered affective response in marijuana smokers: an FMRI study. Drug Alcohol Depend. 2009;105:139–53. doi:10.1016/j.drugalcdep.2009.05.022.
  • Bourque J, Mendrek A, Durand M, Lakis N, Lipp O, Stip E, Lalonde P, Grignon S, Potvin S. Cannabis abuse is associated with better emotional memory in schizophrenia: a functional magnetic resonance imaging study. Psychiatry Res. 2013;214:24–32. doi:10.1016/j.pscychresns.2013.05.012.
  • Lichenstein SD, Musselman S, Shaw DS, Sitnick S, Forbes EE. Nucleus accumbens functional connectivity at age 20 is associated with trajectory of adolescent cannabis use and predicts psychosocial functioning in young adulthood. Addict Abingdon Engl. 2017;112:1961–70. doi:10.1111/add.v112.11.
  • Chang L, Chronicle EP. Functional imaging studies in cannabis users. Neurosci Rev J Bringing Neurobiol Neurol Psychiatry. 2007;13:422–32.
  • Cheng H, Skosnik PD, Pruce BJ, Brumbaugh MS, Vollmer JM, Fridberg DJ, O’Donnell BF, Hetrick WP, Newman SD. Resting state functional magnetic resonance imaging reveals distinct brain activity in heavy cannabis users - a multi-voxel pattern analysis. J Psychopharmacol Oxf Engl. 2014;28:1030–40. doi:10.1177/0269881114550354.
  • Pujol J, Blanco-Hinojo L, Batalla A, López-Solà M, Harrison BJ, Soriano-Mas C, Crippa JA, Fagundo AB, Deus J, de la Torre R, et al. Functional connectivity alterations in brain networks relevant to self-awareness in chronic cannabis users. J Psychiatr Res. 2014;51:68–78. doi:10.1016/j.jpsychires.2013.12.008.
  • Manza P, Tomasi D, Volkow ND. Subcortical local functional hyperconnectivity in cannabis dependence. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3:285–93. doi:10.1016/j.bpsc.2017.11.012.
  • Cuttler C, McLaughlin RJ, Graf P. Mechanisms underlying the link between cannabis use and prospective memory. PLoS One. 2012;7:e36820. doi:10.1371/journal.pone.0036820.
  • Solowij N, Jones KA, Rozman ME, Davis SM, Ciarrochi J, Heaven PCL, Lubman DI, Yücel M. Verbal learning and memory in adolescent cannabis users, alcohol users and non-users. Psychopharmacology (Berl.). 2011;216:131–44. doi:10.1007/s00213-011-2203-x.
  • Moreno M, Estevez AF, Zaldivar F, Montes JMG, Gutiérrez-Ferre VE, Esteban L, Sánchez-Santed F, Flores P. Impulsivity differences in recreational cannabis users and binge drinkers in a university population. Drug Alcohol Depend. 2012;124:355–62. doi:10.1016/j.drugalcdep.2012.02.011.
  • Solowij N, Jones KA, Rozman ME, Davis SM, Ciarrochi J, Heaven PCL, Pesa N, Lubman DI, Yücel M. Reflection impulsivity in adolescent cannabis users: a comparison with alcohol-using and non-substance-using adolescents. Psychopharmacology (Berl.). 2012;219:575–86. doi:10.1007/s00213-011-2486-y.
  • Whitlow CT, Liguori A, Livengood LB, Hart SL, Mussat-Whitlow BJ, Lamborn CM, Laurienti PJ, Porrino LJ. Long-term heavy marijuana users make costly decisions on a gambling task. Drug Alcohol Depend. 2004;76:107–11. doi:10.1016/j.drugalcdep.2004.04.009.
  • Verdejo-Garcia A, Benbrook A, Funderburk F, David P, Cadet J-L, Bolla KI. The differential relationship between cocaine use and marijuana use on decision-making performance over repeat testing with the Iowa Gambling Task. Drug Alcohol Depend. 2007;90:2–11. doi:10.1016/j.drugalcdep.2007.02.004.
  • Gilman JM, Calderon V, Curran MT, Hopfer CJ, Mikulich-Gilbertson SK. Young adult cannabis users report greater propensity for risk-taking only in non-monetary domains. Drug Alcohol Depend. 2015;147:26–31. doi:10.1016/j.drugalcdep.2014.12.004.
  • Becker B, Wagner D, Gouzoulis-Mayfrank E, Spuentrup E, Daumann J. The impact of early-onset cannabis use on functional brain correlates of working memory. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:837–45. doi:10.1016/j.pnpbp.2010.03.032.
  • Jager G, Block RI, Luijten M, et al. Cannabis use and memory brain function in adolescent boys: a cross-sectional multicenter functional magnetic resonance imaging study. J Am Acad Child Adolesc Psychiatry. 2010;49:561–572, 572.e1-3.
  • Abdullaev Y, Posner MI, Nunnally R, Dishion TJ. Functional MRI evidence for inefficient attentional control in adolescent chronic cannabis abuse. Behav Brain Res. 2010;215:45–57. doi:10.1016/j.bbr.2010.06.023.
  • Cousijn J, Wiers RW, Ridderinkhof KR, van Den Brink W, Veltman DJ, Porrino LJ, Goudriaan AE. Individual differences in decision making and reward processing predict changes in cannabis use: a prospective functional magnetic resonance imaging study. Addict Biol. 2013;18:1013–23. doi:10.1111/adb.2013.18.issue-6.
  • Behan B, Connolly CG, Datwani S, Doucet M, Ivanovic J, Morioka R, Stone A, Watts R, Smyth B, Garavan H. Response inhibition and elevated parietal-cerebellar correlations in chronic adolescent cannabis users. Neuropharmacology. 2014;84:131–37. doi:10.1016/j.neuropharm.2013.05.027.
  • Block RI, O’Leary DS, Hichwa RD, Augustinack JC, Boles Ponto LL, Ghoneim MM, Arndt S, Hurtig RR, Watkins GL, Hall JA, et al. Effects of frequent marijuana use on memory-related regional cerebral blood flow. Pharmacol Biochem Behav. 2002;72:237–50. doi:10.1016/S0091-3057(01)00771-7.
  • Bolla KI, Eldreth DA, Matochik JA, CADET J. Neural substrates of faulty decision-making in abstinent marijuana users. NeuroImage. 2005;26:480–92. doi:10.1016/j.neuroimage.2005.02.012.
  • Bogaty SER, Lee RSC, Hickie IB, Hermens DF. Meta-analysis of neurocognition in young psychosis patients with current cannabis use. J Psychiatr Res. 2018;99:22–32. doi:10.1016/j.jpsychires.2018.01.010.
  • Gonzalez R, Pacheco-Colón I, Duperrouzel JC, Hawes SW. Does Cannabis use cause declines in neuropsychological functioning? A Review of longitudinal studies. J Int Neuropsychol Soc JINS. 2017;23:893–902. doi:10.1017/S1355617717000789.
  • Cosker E, Schwitzer T, Ramoz N, Ligier F, Lalanne L, Gorwood P, Schwan R, Laprévote V. The effect of interactions between genetics and cannabis use on neurocognition. Review Prog Neuropsychopharmacol Biol Psychiatry. 2018;82:95–106. doi:10.1016/j.pnpbp.2017.11.024.
  • Crane NA, Schuster RM, Gonzalez R. Preliminary evidence for a sex-specific relationship between amount of cannabis use and neurocognitive performance in young adult cannabis users. J Int Neuropsychol Soc JINS. 2013;19:1009–15. doi:10.1017/S135561771300088X.
  • Liem-Moolenaar M, Te Beek ET, de Kam ML, Franson KL, Kahn RS, Hijman R, Touw D, van Gerven JM. Central nervous system effects of haloperidol on THC in healthy male volunteers. J Psychopharmacol Oxf Engl. 2010;24:1697–708. doi:10.1177/0269881109358200.
  • Metrik J, Kahler CW, Reynolds B, McGeary JE, Monti PM, Haney M, de Wit H, Rohsenow DJ. Balanced placebo design with marijuana: pharmacological and expectancy effects on impulsivity and risk taking. Psychopharmacology (Berl.). 2012;223:489–99. doi:10.1007/s00213-012-2740-y.
  • Morrison PD, Zois V, McKeown DA, Jennaway M, Basudewa IDG, Taylor R. The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol Med. 2009;39:1607–16. doi:10.1017/S0033291708004893.
  • Ramaekers JG, Kauert G, van Ruitenbeek P, Theunissen EL, Schneider E, Moeller MR. High-potency marijuana impairs executive function and inhibitory motor control. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2006;31:2296–303. doi:10.1038/sj.npp.1301068.
  • Ramaekers JG, Moeller MR, van Ruitenbeek P, Theunissen EL, Schneider E, Kauert G. Cognition and motor control as a function of Delta9-THC concentration in serum and oral fluid: limits of impairment. Drug Alcohol Depend. 2006;85:114–22. doi:10.1016/j.drugalcdep.2006.03.015.
  • Weinstein A, Brickner O, Lerman H, Greemland M, Bloch M, Lester H, Chisin R, Sarne Y, Mechoulam R, Bar-Hamburger R, et al. A study investigating the acute dose-response effects of 13 mg and 17 mg Delta 9- tetrahydrocannabinol on cognitive-motor skills, subjective and autonomic measures in regular users of marijuana. J Psychopharmacol Oxf Engl. 2008;22:441–51. doi:10.1177/0269881108088194.
  • Anderson BM, Rizzo M, Block RI, Pearlson GD, O’Leary DS. Sex, drugs, and cognition: effects of marijuana. J Psychoact Drugs. 2010;42:413–24. doi:10.1080/02791072.2010.10400704.
  • Ramaekers JG, Kauert G, Theunissen EL, Toennes SW, Moeller MR. Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users. J Psychopharmacol Oxf Engl. 2009;23:266–77. doi:10.1177/0269881108092393.
  • Ranganathan M, Carbuto M, Braley G, Elander J, Perry E, Pittman B, Radhakrishnan R, Sewell RA, D’Souza DC. Naltrexone does not attenuate the effects of intravenous Δ9-tetrahydrocannabinol in healthy humans. Int J Neuropsychopharmacol. 2012;15:1251–64. doi:10.1017/S1461145711001830.
  • Theunissen EL, Heckman P, de Sousa Fernandes Perna EB, Kuypers KPC, Sambeth A, Blokland A, Prickaerts J, Toennes SW, Ramaekers JG. Rivastigmine but not vardenafil reverses cannabis-induced impairment of verbal memory in healthy humans. Psychopharmacology (Berl). 2015;232:343–53. doi:10.1007/s00213-014-3667-2.
  • Crane NA, Schuster RM, Fusar-Poli P, et al. Effects of cannabis on neurocognitive functioning: recent advances, neurodevelopmental influences, and sex differences. Neuropsychol Rev. 2013;23:117–37.
  • Dougherty DM, Mathias CW, Dawes MA, Furr RM, Charles NE, Liguori A, Shannon EE, Acheson A. Impulsivity, attention, memory, and decision-making among adolescent marijuana users. Psychopharmacology (Berl.). 2013;226:307–19. doi:10.1007/s00213-012-2908-5.
  • Gonzalez R, Schuster RM, Mermelstein RJ, Vassileva J, Martin EM, Diviak KR. Performance of young adult cannabis users on neurocognitive measures of impulsive behavior and their relationship to symptoms of cannabis use disorders. J Clin Exp Neuropsychol. 2012;34:962–76. doi:10.1080/13803395.2012.703642.
  • Grant JE, Chamberlain SR, Schreiber L, Odlaug BL. Neuropsychological deficits associated with cannabis use in young adults. Drug Alcohol Depend. 2012;121:159–62. doi:10.1016/j.drugalcdep.2011.08.015.
  • Lisdahl KM, Price JS. Increased marijuana use and gender predict poorer cognitive functioning in adolescents and emerging adults. J Int Neuropsychol Soc JINS. 2012;18:678–88. doi:10.1017/S1355617712000276.
  • Rogers RD, Wakeley J, Robson PJ, Bhagwagar Z, Makela P. The effects of low doses of delta-9 tetrahydrocannabinol on reinforcement processing in the risky decision-making of young healthy adults. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2007;32:417–28. doi:10.1038/sj.npp.1301175.
  • Lane SD, Cherek DR, Tcheremissine OV, Lieving LM, Pietras CJ. Acute marijuana effects on human risk taking. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2005;30:800–09. doi:10.1038/sj.npp.1300620.
  • Vadhan NP, Hart CL, van Gorp WG, Gunderson EW, Haney M, Foltin RW. Acute effects of smoked marijuana on decision making, as assessed by a modified gambling task, in experienced marijuana users. J Clin Exp Neuropsychol. 2007;29:357–64. doi:10.1080/13803390600693615.
  • Schmetzer AD. Book review: cannabis and cognitive functioning, by Nadia Solowij. Ann Clin Psychiatry. 2000;12:254–57. doi:10.1023/A:1009051030174.
  • Solowij N, Battisti R. The chronic effects of cannabis on memory in humans: a review. Curr Drug Abuse Rev. 2008;1:81–98. doi:10.2174/1874473710801010081.
  • Solowij N, Stephens R, Roffman RA, et al. Does marijuana use cause long-term cognitive deficits?. JAMA. 2002;287:2653–2654; author reply 2654.
  • Fontes MA, Bolla KI, Cunha PJ, Almeida PP, Jungerman F, Laranjeira RR, Bressan RA, Lacerda ALT. Cannabis use before age 15 and subsequent executive functioning. Br J Psychiatry J Ment Sci. 2011;198:442–47. doi:10.1192/bjp.bp.110.077479.
  • Hester R, Nestor L, Garavan H. Impaired error awareness and anterior cingulate cortex hypoactivity in chronic cannabis users. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2009;34:2450–58. doi:10.1038/npp.2009.67.
  • Tait RJ, Mackinnon A, Christensen H. Cannabis use and cognitive function: 8-year trajectory in a young adult cohort. Addict Abingdon Engl. 2011;106:2195–203. doi:10.1111/j.1360-0443.2011.03574.x.
  • Jackson NJ, Isen JD, Khoddam R, Irons D, Tuvblad C, Iacono WG, McGue M, Raine A, Baker LA. Impact of adolescent marijuana use on intelligence: results from two longitudinal twin studies. Proc Natl Acad Sci USA. 2016;113:E500–508. doi:10.1073/pnas.1516648113.
  • Meier MH, Caspi A, Ambler A, Harrington H, Houts R, Keefe RSE, McDonald K, Ward A, Poulton R, Moffitt TE. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci USA. 2012;109:E2657–2664. doi:10.1073/pnas.1206820109.
  • Mokrysz C, Freeman TP, Commentary on Meier, et al. 2018: smoke and mirrors-are adolescent cannabis users vulnerable to cognitive impairment? Addict Abingdon Engl. 2018;113:266–67. doi:10.1111/add.14055.
  • Fletcher PC, Honey GD. Schizophrenia, ketamine and cannabis: evidence of overlapping memory deficits. Trends Cogn Sci. 2006;10:167–74. doi:10.1016/j.tics.2006.02.008.
  • Ranganathan M, D’Souza DC. The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology (Berl.). 2006;188:425–44. doi:10.1007/s00213-006-0508-y.
  • Solowij N, Pesa N. [Cognitive abnormalities and cannabis use]. Rev Bras Psiquiatr Sao Paulo Braz. 2010;32:S31–40.
  • Broyd SJ, van Hell HH, Beale C, Yücel M, Solowij N. Acute and chronic effects of cannabinoids on human cognition-a systematic review. Biol Psychiatry. 2016;79:557–67. doi:10.1016/j.biopsych.2015.12.002.
  • Ganzer F, Bröning S, Kraft S, Sack P-M, Thomasius R. Weighing the evidence: a systematic review on long-term neurocognitive effects of Cannabis use in abstinent adolescents and adults. Neuropsychol Rev. 2016;26:186–222. doi:10.1007/s11065-016-9316-2.
  • Thames AD, Arbid N, Sayegh P. Cannabis use and neurocognitive functioning in a non-clinical sample of users. Addict Behav. 2014;39:994–99. doi:10.1016/j.addbeh.2014.01.019.
  • Wagner D, Becker B, Gouzoulis-Mayfrank E, Daumann J. Interactions between specific parameters of cannabis use and verbal memory. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:871–76. doi:10.1016/j.pnpbp.2010.04.004.
  • Morgan CJA, Gardener C, Schafer G, Swan S, Demarchi C, Freeman TP, Warrington P, Rupasinghe I, Ramoutar A, Tan N, et al. Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being. Psychol Med. 2012;42:391–400. doi:10.1017/S0033291711001322.
  • Solowij N, Stephens RS, Roffman RA, et al. Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA. 2002;287:1123–31.
  • Bilkei-Gorzo A, Albayram O, Draffehn A, Sanjiv K, Myrberg IH, Paulin CBJ, Heshmati Y, Hagenkort A, Kutzner J, Page BDG, et al. A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nat Med. 2017;23:782–87. doi:10.1038/nm.4265.
  • Martín-Moreno AM, Brera B, Spuch C, Carro E, García-García L, Delgado M, Pozo MA, Innamorato NG, Cuadrado A, de Ceballos ML. Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice. J Neuroinflammation. 2012;9:8. doi:10.1186/1742-2094-9-8.
  • Ramírez BG, Blázquez C, Gómez Del Pulgar T, et al. Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci Off J Soc Neurosci. 2005;25:1904–13.
  • Osborne AL, Solowij N, Weston-Green K. A systematic review of the effect of cannabidiol on cognitive function: relevance to schizophrenia. Neurosci Biobehav Rev. 2017;72:310–24. doi:10.1016/j.neubiorev.2016.11.012.
  • Calabrese EJ, Rubio-Casillas A. Biphasic effects of THC in memory and cognition. Eur J Clin Invest. 2018;48:e12920. doi:10.1111/eci.2018.48.issue-5.
  • Levine A, Clemenza K, Rynn M, Lieberman J. Evidence for the risks and consequences of adolescent Cannabis exposure. J Am Acad Child Adolesc Psychiatry. 2017;56:214–25. doi:10.1016/j.jaac.2016.12.014.
  • Lisdahl KM, Wright NE, Kirchner-Medina C, Maple KE, Shollenbarger S. Considering Cannabis: the effects of regular Cannabis use on neurocognition in adolescents and young adults. Curr Addict Rep. 2014;1:144–56. doi:10.1007/s40429-014-0019-6.
  • Meier MH, Caspi A, Danese A, Fisher HL, Houts R, Arseneault L, Moffitt TE. Associations between adolescent cannabis use and neuropsychological decline: a longitudinal co-twin control study. Addict Abingdon Engl. 2018;113:257–65. doi:10.1111/add.v113.2.
  • Mokrysz C, Landy R, Gage SH, Munafò MR, Roiser JP, Curran HV. Are IQ and educational outcomes in teenagers related to their cannabis use? A prospective cohort study. J Psychopharmacol Oxf Engl. 2016;30:159–68. doi:10.1177/0269881115622241.
  • Becker MP, Collins PF, Luciana M. Neurocognition in college-aged daily marijuana users. J Clin Exp Neuropsychol. 2014;36:379–98. doi:10.1080/13803395.2014.893996.
  • Fridberg DJ, Queller S, Ahn W-Y, Kim W, Bishara AJ, Busemeyer JR, Porrino L, Stout JC. Cognitive mechanisms underlying risky decision-making in chronic Cannabis users. J Math Psychol. 2010;54:28–38. doi:10.1016/j.jmp.2009.10.002.
  • Schuster RM, Gilman J, Schoenfeld D, et al. One month of Cannabis abstinence in adolescents and young adults is associated with improved memory. J Clin Psychiatry. 2018;79.
  • Medina KL, Hanson KL, Schweinsburg AD, COHEN-ZION M, NAGEL BJ, TAPERT SF. Neuropsychological functioning in adolescent marijuana users: subtle deficits detectable after a month of abstinence. J Int Neuropsychol Soc JINS. 2007;13:807–20. doi:10.1017/S1355617707071032.
  • Winward JL, Hanson KL, Tapert SF, Brown SA. Heavy alcohol use, marijuana use, and concomitant use by adolescents are associated with unique and shared cognitive decrements. J Int Neuropsychol Soc JINS. 2014;20:784–95. doi:10.1017/S1355617714000666.
  • Hooper SR, Woolley D, De Bellis MD. Intellectual, neurocognitive, and academic achievement in abstinent adolescents with cannabis use disorder. Psychopharmacology (Berl.). 2014;231:1467–77. doi:10.1007/s00213-014-3463-z.
  • Pope HG, Gruber AJ, Hudson JI, Huestis MA, Yurgelun-Todd D. Neuropsychological performance in long-term cannabis users. Arch Gen Psychiatry. 2001;58:909–15. doi:10.1001/archpsyc.58.10.909.
  • Schreiner AM, Dunn ME. Residual effects of cannabis use on neurocognitive performance after prolonged abstinence: a meta-analysis. Exp Clin Psychopharmacol. 2012;20:420–29. doi:10.1037/a0029117.
  • Scott JC, Slomiak ST, Jones JD, Rosen AFG, Moore TM, Gur RC. Association of Cannabis with cognitive functioning in adolescents and young adults: a systematic review and meta-analysis. JAMA Psychiatry. 2018;75:585–95. doi:10.1001/jamapsychiatry.2018.0335.
  • Colizzi M, Bhattacharyya S. Does Cannabis composition matter? Differential effects of delta-9-tetrahydrocannabinol and Cannabidiol on human cognition. Curr Addict Rep. 2017;4:62–74. doi:10.1007/s40429-017-0142-2.
  • Ciccone CD. Medical Marijuana: just the Beginning of a long, strange trip?. Phys Ther. 2017;97:239–48.
  • Curran HV, Freeman TP, Mokrysz C, Lewis DA, Morgan CJA, Parsons LH. Keep off the grass? Cannabis, cognition and addiction. Nat Rev Neurosci. 2016;17:293–306. doi:10.1038/nrn.2016.28.
  • Karila L, Roux P, Rolland B, Benyamina A, Reynaud M, Aubin H-J, Lancon C. Acute and long-term effects of cannabis use: a review. Curr Pharm Des. 2014;20:4112–18. doi:10.2174/13816128113199990620.
  • Leung L. Cannabis and its derivatives: review of medical use. J Am Board Fam Med JABFM. 2011;24:452–62. doi:10.3122/jabfm.2011.04.100280.
  • Franz CA, Frishman WH. Marijuana use and Cardiovascular disease. Cardiol Rev. 2016;24:158–62. doi:10.1097/CRD.0000000000000103.
  • Sidney S. Cardiovascular consequences of marijuana use. J Clin Pharmacol. 2002;42:64S–70S.
  • Biehl JR, Burnham EL. Cannabis smoking in 2015: a concern for lung health? Chest. 2015;148:596–606. doi:10.1378/chest.15-0447.
  • Papatheodorou SI, Buettner H, Rice MB, Mittleman MA. Recent marijuana use and associations with exhaled nitric oxide and pulmonary function in adults in the United States. Chest. 2016;149:1428–35. doi:10.1016/j.chest.2015.12.033.
  • Sagar KA, Gruber SA. Marijuana matters: reviewing the impact of marijuana on cognition, brain structure and function, & exploring policy implications and barriers to research. Int Rev Psychiatry Abingdon Engl. 2018;30:251–67. doi:10.1080/09540261.2018.1460334.
  • Gruber SA, Sagar KA, Dahlgren MK, Yao X, Levine SJ. Splendor in the Grass? A pilot study assessing the impact of medical Marijuana on executive function. Front Pharmacol. 2016;7:355. doi:10.3389/fphar.2016.00323.
  • Hyder AA, Wunderlich CA, Puvanachandra P, et al. The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation. 2007;22:341–53.
  • Sun J-H, Tan L, Yu J-T. Post-stroke cognitive impairment: epidemiology, mechanisms and management. Ann Transl Med. 2014;2:80.
  • Grundy RI. The therapeutic potential of the cannabinoids in neuroprotection. Expert Opin Investig Drugs. 2002;11:1365–74. doi:10.1517/13543784.11.10.1365.
  • Latorre JGS, Schmidt EB. Cannabis, Cannabinoids, and cerebral metabolism: potential applications in stroke and disorders of the central nervous system. Curr Cardiol Rep. 2015;17:627. doi:10.1007/s11886-015-0627-3.
  • Magid L, Heymann S, Elgali M, Millis SR, Scott C, Pearson C. Role of CB2 receptor in the recovery of mice after traumatic brain injury. J Neurotrauma. 2019;36:1836–46. doi:10.1089/neu.2018.5873.
  • Shohami E, Cohen-Yeshurun A, Magid L, Facciolo F, Rendina EA, Page C, Cazzola M, Orlandi A. Endocannabinoids and traumatic brain injury. Br J Pharmacol. 2011;163:1402–10. doi:10.1111/j.1476-5381.2011.01339.x.
  • Hussain S, Sankar R. Pharmacologic treatment of intractable epilepsy in children: a syndrome-based approach. Semin Pediatr Neurol. 2011;18:171–78. doi:10.1016/j.spen.2011.06.003.
  • Wirrell EC. Treatment of Dravet Syndrome. Can J Neurol Sci J Can Sci Neurol. 2016;43:S13–18. doi:10.1017/cjn.2016.249.
  • Szaflarski JP, Bebin EM. Cannabis, cannabidiol, and epilepsy–from receptors to clinical response. Epilepsy Behav EB. 2014;41:277–82. doi:10.1016/j.yebeh.2014.08.135.
  • Hussain SA, Zhou R, Jacobson C, Weng J, Cheng E, Lay J, Hung P, Lerner JT, Sankar R. Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy Behav EB. 2015;47:138–41. doi:10.1016/j.yebeh.2015.04.009.
  • Sirven JI. Cannabis, cannabidiol, and epilepsies: the truth is somewhere in the middle. Epilepsy Behav EB. 2014;41:270–71. doi:10.1016/j.yebeh.2014.09.006.
  • Cilio MR, Thiele EA, Devinsky O. The case for assessing cannabidiol in epilepsy. Epilepsia. 2014;55:787–90. doi:10.1111/epi.2014.55.issue-6.
  • Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, Miller I, Flamini R, Wilfong A, Filloux F, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15:270–78. doi:10.1016/S1474-4422(15)00379-8.
  • Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, Lyons PD, Taylor A, Roberts C, Sommerville K, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Lond Engl. 2018;391:1085–96. doi:10.1016/S0140-6736(18)30136-3.
  • McCoy B, Wang L, Zak M, Al‐Mehmadi S, Kabir N, Alhadid K, McDonald K, Zhang G, Sharma R, Whitney R, et al. A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome. Ann Clin Transl Neurol. 2018;5:1077–88. doi:10.1002/acn3.2018.5.issue-9.
  • Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017;376:2011–20. doi:10.1056/NEJMoa1611618.
  • Mitchell JT, Sweitzer MM, Tunno AM, Kollins SH, McClernon FJ, Lidzba K. “I use weed for my ADHD”: A qualitative analysis of online forum discussions on Cannabis use and ADHD. PLoS One. 2016;11:e0156614. doi:10.1371/journal.pone.0156614.
  • Ferner M Number of children seeking medical Marijuana soars in Colorado [Internet]. HuffPost. Available from: https://www.huffpost.com/entry/medical-marijuana-children_n_4768219.
  • Hadland SE, Knight JR, Harris SK. Medical marijuana: review of the science and implications for developmental-behavioral pediatric practice. J Dev Behav Pediatr JDBP. 2015;36:115–23. doi:10.1097/DBP.0000000000000129.
  • Rasmussen J, Casey BJ, van Erp TGM, Tamm L, Epstein JN, Buss C, Bjork JM, Molina BSG, Velanova K, Mathalon DH, et al. ADHD and cannabis use in young adults examined using fMRI of a Go/NoGo task. Brain Imaging Behav. 2016;10:761–71. doi:10.1007/s11682-015-9438-9.
  • Kelly C, Castellanos FX, Tomaselli O, Lisdahl K, Tamm L, Jernigan T, Newman E, Epstein JN, Molina BSG, Greenhill LL, et al. Distinct effects of childhood ADHD and cannabis use on brain functional architecture in young adults. NeuroImage Clin. 2017;13:188–200. doi:10.1016/j.nicl.2016.09.012.
  • Charach A, Yeung E, Climans T, Lillie E. Childhood attention-deficit/hyperactivity disorder and future substance use disorders: comparative meta-analyses. J Am Acad Child Adolesc Psychiatry. 2011;50:9–21. doi:10.1016/j.jaac.2010.09.019.
  • Klein RG, Mannuzza S, Olazagasti MAR, Craig M, Hallahan B, Murphy C, Johnston P, Spain D, Gillan N, Brammer M, et al. Clinical and functional outcome of childhood attention-deficit/hyperactivity disorder 33 years later. Arch Gen Psychiatry. 2012;69:1295–303. doi:10.1001/archgenpsychiatry.2012.513.
  • Lee SS, Humphreys KL, Flory K, Liu R, Glass K. Prospective association of childhood attention-deficit/hyperactivity disorder (ADHD) and substance use and abuse/dependence: a meta-analytic review. Clin Psychol Rev. 2011;31:328–41. doi:10.1016/j.cpr.2011.01.006.
  • Molina BSG, Hinshaw SP, Eugene Arnold L, Swanson JM, Pelham WE, Hechtman L, Hoza B, Epstein JN, Wigal T, Abikoff HB, et al. Adolescent substance use in the multimodal treatment study of attention-deficit/hyperactivity disorder (ADHD) (MTA) as a function of childhood ADHD, random assignment to childhood treatments, and subsequent medication. J Am Acad Child Adolesc Psychiatry. 2013;52:250–63. doi:10.1016/j.jaac.2012.12.014.
  • Zamberletti E, Gabaglio M, Parolaro D. The endocannabinoid system and autism spectrum disorders: insights from animal models. Int J Mol Sci. 2017;18.
  • Karhson DS, Krasinska KM, Dallaire JA, Libove RA, Phillips JM, Chien AS, Garner JP, Hardan AY, Parker KJ. Plasma anandamide concentrations are lower in children with autism spectrum disorder. Mol Autism. 2018;9:18. doi:10.1186/s13229-018-0203-y.
  • Wei D, Lee D, Cox CD, Karsten CA, Peñagarikano O, Geschwind DH, Gall CM, Piomelli D. Endocannabinoid signaling mediates oxytocin-driven social reward. Proc Natl Acad Sci USA. 2015;112:14084–89. doi:10.1073/pnas.1509795112.
  • Gu B. Cannabidiol provides viable treatment opportunity for multiple neurological pathologies of autism spectrum disorder. Glob. Drugs Ther. Internet]. 2017 [cited 2019 Jun 10];2. Available from: http://www.oatext.com/cannabidiol-provides-viable-treatment-opportunity-for-multiple-neurological-pathologies-of-autism-spectrum-disorder.php
  • Kaplan JS, Stella N, Catterall WA, Westenbroek RE. Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome. Proc Natl Acad Sci USA. 2017;114:11229–34. doi:10.1073/pnas.1711351114.

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