Singewald N, Schmuckermair C, Whittle N, Holmes A, Ressler KJ. Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders. Pharmacol Ther. 2015;149:150–90. https://doi.org/10.1016/j.pharmthera.2014.12.004.
CAS
Article
PubMed
Google Scholar
Tovote P, Fadok JP, Luthi A. Neuronal circuits for fear and anxiety. Nat Rev Neurosci. 2015;16:317–31. https://doi.org/10.1038/nrn3945.
CAS
Article
Google Scholar
Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci. 2015;17:327–35.
PubMed
PubMed Central
Google Scholar
• Craske MG, Stein MB, Eley TC, Milad MR, Holmes A, Rapee RM, et al. Anxiety disorders. Nat Rev Dis Primers. 2017;3:17024. https://doi.org/10.1038/nrdp.2017.24 A useful primer on anxiety-related disorders.
Article
PubMed
Google Scholar
Hendriks SM, Spijker J, Licht CMM, Hardeveld F, de Graaf R, Batelaan NM, et al. Long-term disability in anxiety disorders. BMC Psychiatry. 2016;16:248. https://doi.org/10.1186/s12888-016-0946-y.
Article
PubMed
PubMed Central
Google Scholar
Tipps ME, Raybuck JD, Lattal KM. Substance abuse, memory, and post-traumatic stress disorder. Neurobiol Learn Mem. 2014;112:87–100. https://doi.org/10.1016/j.nlm.2013.12.002.
Article
PubMed
Google Scholar
Watkins LE, Sprang KR, Rothbaum BO. Treating PTSD: a review of evidence-based psychotherapy interventions. Front Behav Neurosci. 2018;12:258. https://doi.org/10.3389/fnbeh.2018.00258.
Article
PubMed
PubMed Central
Google Scholar
Murrough JW, Yaqubi S, Sayed S, Charney DS. Emerging drugs for the treatment of anxiety. Expert Opin Emerg Drugs. 2015;20:393–406. https://doi.org/10.1517/14728214.2015.1049996.
CAS
Article
PubMed
PubMed Central
Google Scholar
Bystritsky A, Khalsa SS, Cameron ME, Schiffman J. Current diagnosis and treatment of anxiety disorders. P T. 2013;38:30–57.
PubMed
PubMed Central
Google Scholar
Guina J, Rossetter SR, DeRhodes BJ, Nahhas RW, Welton RS. Benzodiazepines for PTSD: a systematic review and meta-analysis. J Psychiatr Pract. 2015;21:281–303. https://doi.org/10.1097/pra.0000000000000091.
Article
PubMed
Google Scholar
• Ligresti A, Petrocellis LD, Marzo VD. From phytocannabinoids to cannabinoid receptors and endocannabinoids: pleiotropic physiological and pathological roles through complex pharmacology. Physiol Rev 2016;96:1593–1659. doi:https://doi.org/10.1152/physrev.00002. 2016. A comprehensive review of cannabinoid receptor signalling.
Russo EB. Cannabis therapeutics and the future of neurology. Front Integr Neurosci. 2018;12:51. https://doi.org/10.3389/fnint.2018.00051.
Article
PubMed
PubMed Central
Google Scholar
Scherma M, Masia P, Deidda M, Fratta W, Tanda G, Fadda P. New perspectives on the use of cannabis in the treatment of psychiatric disorders. Medicines (Basel). 2018;5(4). https://doi.org/10.3390/medicines5040107.
Article
Google Scholar
Lee JLC, Bertoglio LJ, Guimaraes FS, Stevenson CW. Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders. Br J Pharmacol. 2017;174:3242–56. https://doi.org/10.1111/bph.13724.
CAS
Article
PubMed
PubMed Central
Google Scholar
Crippa JA, Zuardi AW, Martin-Santos R, Bhattacharyya S, Atakan Z, McGuire P, et al. Cannabis and anxiety: a critical review of the evidence. Hum Psychopharmacol. 2009;24:515–23. https://doi.org/10.1002/hup.1048.
CAS
Article
PubMed
Google Scholar
Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology. 1982;76:245–50.
CAS
Article
Google Scholar
Crippa JA, Zuardi AW, Garrido GE, Wichert-Ana L, Guarnieri R, Ferrari L, et al. Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology. 2004;29:417–26. https://doi.org/10.1038/sj.npp.1300340.
CAS
Article
PubMed
Google Scholar
Fusar-Poli P, Crippa JA, Bhattacharyya S, Borgwardt SJ, Allen P, Martin-Santos R, et al. Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry. 2009;66:95–105. https://doi.org/10.1001/archgenpsychiatry.2008.519.
CAS
Article
PubMed
Google Scholar
Fusar-Poli P, Allen P, Bhattacharyya S, Crippa JA, Mechelli A, Borgwardt S, et al. Modulation of effective connectivity during emotional processing by Delta 9-tetrahydrocannabinol and cannabidiol. Int J Neuropsychopharmacol. 2010;13:421–32. https://doi.org/10.1017/s1461145709990617.
CAS
Article
PubMed
Google Scholar
Parker LA, Burton P, Sorge RE, Yakiwchuk C, Mechoulam R. Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. Psychopharmacology. 2004;175:360–6. https://doi.org/10.1007/s00213-004-1825-7.
CAS
Article
PubMed
Google Scholar
Vann RE, Gamage TF, Warner JA, Marshall EM, Taylor NL, Martin BR, et al. Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Delta(9)-tetrahydrocannabinol. Drug Alcohol Depend. 2008;94:191–8. https://doi.org/10.1016/j.drugalcdep.2007.11.017.
CAS
Article
PubMed
PubMed Central
Google Scholar
Katsidoni V, Anagnostou I, Panagis G. Cannabidiol inhibits the reward-facilitating effect of morphine: involvement of 5-HT1A receptors in the dorsal raphe nucleus. Addict Biol. 2013;18:286–96. https://doi.org/10.1111/j.1369-1600.2012.00483.x.
CAS
Article
PubMed
Google Scholar
Iffland K, Grotenhermen F. An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis Cannabinoid Res. 2017;2:139–54. https://doi.org/10.1089/can.2016.0034.
CAS
Article
PubMed
PubMed Central
Google Scholar
Billakota S, Devinsky O, Marsh E. Cannabinoid therapy in epilepsy. Curr Opin Neurol. 2019;32:220–6. https://doi.org/10.1097/wco.0000000000000660.
CAS
Article
PubMed
Google Scholar
Lee JLC, Nader K, Schiller D. An update on memory reconsolidation updating. Trends Cogn Sci. 2017;21:531–45. https://doi.org/10.1016/j.tics.2017.04.006.
Article
PubMed
PubMed Central
Google Scholar
Levin R, Almeida V, Peres FF, Calzavara MB, da Silva ND, Suiama MA, et al. Antipsychotic profile of cannabidiol and rimonabant in an animal model of emotional context processing in schizophrenia. Curr Pharm Des. 2012;18:4960–5.
CAS
Article
Google Scholar
Norris C, Loureiro M, Kramar C, Zunder J, Renard J, Rushlow W, et al. Cannabidiol modulates fear memory formation through interactions with serotonergic transmission in the mesolimbic system. Neuropsychopharmacology. 2016;41:2839–50. https://doi.org/10.1038/npp.2016.93.
CAS
Article
PubMed
PubMed Central
Google Scholar
Stern CAJ, da Silva TR, Raymundi AM, de Souza CP, Hiroaki-Sato VA, Kato L, et al. Cannabidiol disrupts the consolidation of specific and generalized fear memories via dorsal hippocampus CB1 and CB2 receptors. Neuropharmacology. 2017;125:220–30. https://doi.org/10.1016/j.neuropharm.2017.07.024.
CAS
Article
PubMed
Google Scholar
Rossignoli MT, Lopes-Aguiar C, Ruggiero RN, Do Val da Silva RA, Bueno-Junior LS, Kandratavicius L, et al. Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: reduced dopaminergic modulation and immediate gene expression in limbic circuits. Neuroscience. 2017;350:85–93. https://doi.org/10.1016/j.neuroscience.2017.03.019.
CAS
Article
PubMed
Google Scholar
Resstel LB, Joca SR, Moreira FA, Correa FM, Guimaraes FS. Effects of cannabidiol and diazepam on behavioral and cardiovascular responses induced by contextual conditioned fear in rats. Behav Brain Res. 2006;172:294–8. https://doi.org/10.1016/j.bbr.2006.05.016.
Article
PubMed
Google Scholar
Lemos JI, Resstel LB, Guimaraes FS. Involvement of the prelimbic prefrontal cortex on cannabidiol-induced attenuation of contextual conditioned fear in rats. Behav Brain Res. 2010;207:105–11. https://doi.org/10.1016/j.bbr.2009.09.045.
CAS
Article
PubMed
Google Scholar
Jurkus R, Day HLL, Guimarães FS, Lee JLC, Bertoglio LJ, Stevenson CW. Cannabidiol regulation of learned fear: implications for treating anxiety-related disorders. Front Pharmacol. 2016;7:454. https://doi.org/10.3389/fphar.2016.00454.
CAS
Article
PubMed
PubMed Central
Google Scholar
Song C, Stevenson CW, Guimaraes FS, Lee JL. Bidirectional effects of cannabidiol on contextual fear memory extinction. Front Pharmacol. 2016;7:493. https://doi.org/10.3389/fphar.2016.00493.
CAS
Article
PubMed
PubMed Central
Google Scholar
Gomes FV, Resstel LB, Guimaraes FS. The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors. Psychopharmacology. 2011;213:465–73. https://doi.org/10.1007/s00213-010-2036-z.
CAS
Article
PubMed
Google Scholar
Gomes FV, Reis DG, Alves FH, Correa FM, Guimaraes FS, Resstel LB. Cannabidiol injected into the bed nucleus of the stria terminalis reduces the expression of contextual fear conditioning via 5-HT1A receptors. J Psychopharmacol. 2012;26:104–13. https://doi.org/10.1177/0269881110389095.
CAS
Article
PubMed
Google Scholar
Fogaca MV, Reis FM, Campos AC, Guimaraes FS. Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: involvement of 5HT1A receptors and previous stressful experience. Eur Neuropsychopharmacol. 2014;24:410–9. https://doi.org/10.1016/j.euroneuro.2013.10.012.
CAS
Article
PubMed
Google Scholar
Marinho AL, Vila-Verde C, Fogaca MV, Guimaraes FS. Effects of intra-infralimbic prefrontal cortex injections of cannabidiol in the modulation of emotional behaviors in rats: contribution of 5HT(1)A receptors and stressful experiences. Behav Brain Res. 2015;286:49–56. https://doi.org/10.1016/j.bbr.2015.02.023.
CAS
Article
PubMed
Google Scholar
Stern CA, Gazarini L, Takahashi RN, Guimaraes FS, Bertoglio LJ. On disruption of fear memory by reconsolidation blockade: evidence from cannabidiol treatment. Neuropsychopharmacology. 2012;37:2132–42. https://doi.org/10.1038/npp.2012.63.
CAS
Article
PubMed
PubMed Central
Google Scholar
Stern CAJ, Gazarini L, Vanvossen AC, Zuardi AW, Galve-Roperh I, Guimaraes FS, et al. Δ9-Tetrahydrocannabinol alone and combined with cannabidiol mitigate fear memory through reconsolidation disruption. Eur Neuropsychopharmacol. 2015;25:958–65. https://doi.org/10.1016/j.euroneuro.2015.02.001.
CAS
Article
PubMed
Google Scholar
Gazarini L, Stern CA, Piornedo RR, Takahashi RN, Bertoglio LJ. PTSD-like memory generated through enhanced noradrenergic activity is mitigated by a dual step pharmacological intervention targeting its reconsolidation. Int J Neuropsychopharmacol. 2015;18:pyu026. https://doi.org/10.1093/ijnp/pyu026.
CAS
Article
Google Scholar
Bitencourt RM, Pamplona FA, Takahashi RN. Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats. Eur Neuropsychopharmacol. 2008;18:849–59. https://doi.org/10.1016/j.euroneuro.2008.07.001.
CAS
Article
PubMed
Google Scholar
Do Monte FH, Souza RR, Bitencourt RM, Kroon JA, Takahashi RN. Infusion of cannabidiol into infralimbic cortex facilitates fear extinction via CB1 receptors. Behav Brain Res. 2013;250:23–7. https://doi.org/10.1016/j.bbr.2013.04.045.
CAS
Article
PubMed
Google Scholar
Das RK, Kamboj SK, Ramadas M, Yogan K, Gupta V, Redman E, et al. Cannabidiol enhances consolidation of explicit fear extinction in humans. Psychopharmacology. 2013;226:781–92. https://doi.org/10.1007/s00213-012-2955-y.
CAS
Article
PubMed
Google Scholar
Bergamaschi MM, Queiroz RH, Chagas MH, de Oliveira DC, De Martinis BS, Kapczinski F, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology. 2011;36:1219–26. https://doi.org/10.1038/npp.2011.6.
CAS
Article
PubMed
PubMed Central
Google Scholar
Crippa JA, Derenusson GN, Ferrari TB, Wichert-Ana L, Duran FL, Martin-Santos R, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol. 2011;25:121–30. https://doi.org/10.1177/0269881110379283.
CAS
Article
PubMed
Google Scholar
Shannon S, Opila-Lehman J. Effectiveness of cannabidiol oil for pediatric anxiety and insomnia as part of posttraumatic stress disorder: a case report. Perm J. 2016;20:108–11. https://doi.org/10.7812/tpp/16-005.
Article
Google Scholar
Elms L, Shannon S, Hughes S, Lewis N. Cannabidiol in the treatment of post-traumatic stress disorder: a case series. J Altern Complement Med. 2018. https://doi.org/10.1089/acm.2018.0437.
Article
Google Scholar
Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol in anxiety and sleep: a large case series. Perm J. 2019;23:18–041. https://doi.org/10.7812/TPP/18-041.
Article
PubMed
PubMed Central
Google Scholar
Ibeas Bih C, Chen T, Nunn AV, Bazelot M, Dallas M, Whalley BJ. Molecular targets of cannabidiol in neurological disorders. Neurotherapeutics. 2015;12:699–730. https://doi.org/10.1007/s13311-015-0377-3.
CAS
Article
PubMed
PubMed Central
Google Scholar
Campos AC, Guimaraes FS. Evidence for a potential role for TRPV1 receptors in the dorsolateral periaqueductal gray in the attenuation of the anxiolytic effects of cannabinoids. Prog Neuro-Psychopharmacol Biol Psychiatry. 2009;33:1517–21. https://doi.org/10.1016/j.pnpbp.2009.08.017.
CAS
Article
Google Scholar
Stern CA, Gazarmi L, Vanvossen AC, Zuardi AW, Guimarães FS, Takahashi RN, Bertoglio LJet al. P.1.j.006 Involvement of the prelimbic cortex in the disruptive effect of cannabidiol on fear memory reconsolidation. Eur Neuropsychopharmacol 2014;24:S322. doi:https://doi.org/10.1016/S0924-977X(14)70511-5.
Article
Google Scholar
Hanus LO, Tchilibon S, Ponde DE, Breuer A, Fride E, Mechoulam R. Enantiomeric cannabidiol derivatives: synthesis and binding to cannabinoid receptors. Org Biomol Chem. 2005;3:1116–23. https://doi.org/10.1039/b416943c.
CAS
Article
PubMed
Google Scholar
Castillo Pablo E, Younts Thomas J, Chávez Andrés E, Hashimotodani Y. Endocannabinoid signaling and synaptic function. Neuron. 2012;76:70–81. https://doi.org/10.1016/j.neuron.2012.09.020.
CAS
Article
PubMed
PubMed Central
Google Scholar
Ahn K, McKinney MK, Cravatt BF. Enzymatic pathways that regulate endocannabinoid signaling in the nervous system. Chem Rev. 2008;108:1687–707. https://doi.org/10.1021/cr0782067.
CAS
Article
PubMed
PubMed Central
Google Scholar
Urquhart P, Nicolaou A, Woodward DF. Endocannabinoids and their oxygenation by cyclo-oxygenases, lipoxygenases and other oxygenases. Biochim Biophys Acta. 2015;1851:366–76. https://doi.org/10.1016/j.bbalip.2014.12.015.
CAS
Article
PubMed
Google Scholar
Maccarrone M. Metabolism of the endocannabinoid anandamide: open questions after 25 years. Front Mol Neurosci. 2017;10:166. https://doi.org/10.3389/fnmol.2017.00166.
CAS
Article
PubMed
PubMed Central
Google Scholar
Lazary J, Lazary A, Gonda X, Benko A, Molnar E, Hunyady L, et al. Promoter variants of the cannabinoid receptor 1 gene (CNR1) in interaction with 5-HTTLPR affect the anxious phenotype. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:1118–27. https://doi.org/10.1002/ajmg.b.31024.
CAS
Article
PubMed
Google Scholar
Lazary J, Eszlari N, Juhasz G, Bagdy G. Genetically reduced FAAH activity may be a risk for the development of anxiety and depression in persons with repetitive childhood trauma. Eur Neuropsychopharmacol. 2016;26:1020–8. https://doi.org/10.1016/j.euroneuro.2016.03.003.
CAS
Article
PubMed
Google Scholar
Dincheva I, Drysdale AT, Hartley CA, Johnson DC, Jing D, King EC, et al. FAAH genetic variation enhances fronto-amygdala function in mouse and human. Nat Commun. 2015;6:6395. https://doi.org/10.1038/ncomms7395.
CAS
Article
PubMed
PubMed Central
Google Scholar
Demers CH, Drabant Conley E, Bogdan R, Hariri AR. Interactions between anandamide and corticotropin-releasing factor signaling modulate human amygdala function and risk for anxiety disorders: an imaging genetics strategy for modeling molecular interactions. Biol Psychiatry. 2016;80:356–62. https://doi.org/10.1016/j.biopsych.2015.12.021.
CAS
Article
PubMed
PubMed Central
Google Scholar
•• Gee DG, Fetcho RN, Jing D, Li A, Glatt CE, Drysdale AT, et al. Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species. PNAS. 2016;113:4500–5. https://doi.org/10.1073/pnas.1600013113 Cross-species study demonstrating important links between FAAH polymorphism, frontolimbic circuit connectivity, and anxiety-related behavior.
CAS
Article
PubMed
Google Scholar
Lester KJ, Coleman JR, Roberts S, Keers R, Breen G, Bogels S, et al. Genetic variation in the endocannabinoid system and response to cognitive behavior therapy for child anxiety disorders. Am J Med Genet B Neuropsychiatr Genet. 2017;174:144–55. https://doi.org/10.1002/ajmg.b.32467.
CAS
Article
PubMed
Google Scholar
Hill MN, Bierer LM, Makotkine I, Golier JA, Galea S, McEwen BS, et al. Reductions in circulating endocannabinoid levels in individuals with post-traumatic stress disorder following exposure to the World Trade Center attacks. Psychoneuroendocrinology. 2013;38:2952–61. https://doi.org/10.1016/j.psyneuen.2013.08.004.
CAS
Article
PubMed
Google Scholar
Neumeister A, Normandin MD, Pietrzak RH, Piomelli D, Zheng MQ, Gujarro-Anton A, et al. Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study. Mol Psychiatry. 2013;18:1034–40. https://doi.org/10.1038/mp.2013.61.
CAS
Article
PubMed
PubMed Central
Google Scholar
Hauer D, Schelling G, Gola H, Campolongo P, Morath J, Roozendaal B, et al. Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder. PLoS One. 2013;8:e62741. https://doi.org/10.1371/journal.pone.0062741.
CAS
Article
PubMed
PubMed Central
Google Scholar
Bisogno T, Maccarrone M. Latest advances in the discovery of fatty acid amide hydrolase inhibitors. Expert Opin Drug Discovery. 2013;8:509–22. https://doi.org/10.1517/17460441.2013.780021.
CAS
Article
Google Scholar
De Petrocellis L, Ligresti A, Moriello AS, Allara M, Bisogno T, Petrosino S, et al. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol. 2011;163:1479–94. https://doi.org/10.1111/j.1476-5381.2010.01166.x.
CAS
Article
PubMed
PubMed Central
Google Scholar
Elmes MW, Kaczocha M, Berger WT, Leung K, Ralph BP, Wang L, et al. Fatty acid-binding proteins (FABPs) are intracellular carriers for Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD). J Biol Chem. 2015;290:8711–21. https://doi.org/10.1074/jbc.M114.618447.
CAS
Article
PubMed
PubMed Central
Google Scholar
Korem N, Zer-Aviv TM, Ganon-Elazar E, Abush H, Akirav I. Targeting the endocannabinoid system to treat anxiety-related disorders. J Basic Clin Physiol Pharmacol. 2016;27:193–202. https://doi.org/10.1515/jbcpp-2015-0058.
CAS
Article
PubMed
Google Scholar
Batista PA, Fogaca MV, Guimaraes FS. The endocannabinoid, endovanilloid and nitrergic systems could interact in the rat dorsolateral periaqueductal gray matter to control anxiety-like behaviors. Behav Brain Res. 2015;293:182–8. https://doi.org/10.1016/j.bbr.2015.07.019.
CAS
Article
PubMed
Google Scholar
Uliana DL, Hott SC, Lisboa SF, Resstel LB. Dorsolateral periaqueductal gray matter CB1 and TRPV1 receptors exert opposite modulation on expression of contextual fear conditioning. Neuropharmacology. 2016;103:257–69. https://doi.org/10.1016/j.neuropharm.2015.12.020.
CAS
Article
PubMed
Google Scholar
Faraji N, Komaki A, Salehi I. Interaction between the cannabinoid and vanilloid systems on anxiety in male rats. Basic Clin Neurosci. 2017;8:129–37. https://doi.org/10.18869/nirp.bcn.8.2.129.
CAS
Article
PubMed
PubMed Central
Google Scholar
Back FP, Carobrez AP. Periaqueductal gray glutamatergic, cannabinoid and vanilloid receptor interplay in defensive behavior and aversive memory formation. Neuropharmacology. 2018;135:399–411. https://doi.org/10.1016/j.neuropharm.2018.03.032.
CAS
Article
PubMed
Google Scholar
Patel S, Hill MN, Cheer JF, Wotjak CT, Holmes A. The endocannabinoid system as a target for novel anxiolytic drugs. Neurosci Biobehav Rev. 2017;76(Pt A:56–66. https://doi.org/10.1016/j.neubiorev.2016.12.033.
CAS
Article
PubMed
PubMed Central
Google Scholar
Lomazzo E, Bindila L, Remmers F, Lerner R, Schwitter C, Hoheisel U, et al. Therapeutic potential of inhibitors of endocannabinoid degradation for the treatment of stress-related hyperalgesia in an animal model of chronic pain. Neuropsychopharmacology. 2015;40:488–501. https://doi.org/10.1038/npp.2014.198.
CAS
Article
PubMed
Google Scholar
Llorente-Berzal A, Terzian AL, di Marzo V, Micale V, Viveros MP, Wotjak CT. 2-AG promotes the expression of conditioned fear via cannabinoid receptor type 1 on GABAergic neurons. Psychopharmacology. 2015;232:2811–25. https://doi.org/10.1007/s00213-015-3917-y.
CAS
Article
PubMed
Google Scholar
Morena M, Leitl KD, Vecchiarelli HA, Gray JM, Campolongo P, Hill MN. Emotional arousal state influences the ability of amygdalar endocannabinoid signaling to modulate anxiety. Neuropharmacology. 2016;111:59–69. https://doi.org/10.1016/j.neuropharm.2016.08.020.
CAS
Article
PubMed
Google Scholar
Bedse G, Bluett RJ, Patrick TA, Romness NK, Gaulden AD, Kingsley PJ, et al. Therapeutic endocannabinoid augmentation for mood and anxiety disorders: comparative profiling of FAAH, MAGL and dual inhibitors. Transl Psychiatry. 2018;8:92. https://doi.org/10.1038/s41398-018-0141-7.
CAS
Article
PubMed
PubMed Central
Google Scholar
Hermanson DJ, Hartley ND, Gamble-George J, Brown N, Shonesy BC, Kingsley PJ, et al. Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation. Nat Neurosci. 2013;16:1291–8. https://doi.org/10.1038/nn.3480.
CAS
Article
PubMed
PubMed Central
Google Scholar
Gamble-George JC, Baldi R, Halladay L, Kocharian A, Hartley N, Silva CG et al. Cyclooxygenase-2 inhibition reduces stress-induced affective pathology. eLife 2016;5:e14137. doi:https://doi.org/10.7554/eLife.14137.
Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature. 2002;418:530–4. https://doi.org/10.1038/nature00839.
CAS
Article
PubMed
Google Scholar
• Mayo LM, Asratian A, Linde J, Holm L, Natt D, Augier G, et al. Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice. Mol Psychiatry. 2018. https://doi.org/10.1038/s41380-018-0215-1 Cross-species study demonstrating important links between FAAH polymorphism, anandamide levels, and stress resilience.
Suzuki A, Josselyn SA, Frankland PW, Masushige S, Silva AJ, Kida S. Memory reconsolidation and extinction have distinct temporal and biochemical signatures. J Neurosci. 2004;24:4787–95. https://doi.org/10.1523/jneurosci.5491-03.2004.
CAS
Article
PubMed
Google Scholar
Pamplona FA, Bitencourt RM, Takahashi RN. Short- and long-term effects of cannabinoids on the extinction of contextual fear memory in rats. Neurobiol Learn Mem. 2008;90:290–3. https://doi.org/10.1016/j.nlm.2008.04.003.
CAS
Article
PubMed
Google Scholar
De Oliveira Alvares L, Genro BP, Diehl F, Quillfeldt JA. Differential role of the hippocampal endocannabinoid system in the memory consolidation and retrieval mechanisms. Neurobiol Learn Mem. 2008;90:1–9. https://doi.org/10.1016/j.nlm.2008.01.009.
CAS
Article
PubMed
Google Scholar
Kuhnert S, Meyer C, Koch M. Involvement of cannabinoid receptors in the amygdala and prefrontal cortex of rats in fear learning, consolidation, retrieval and extinction. Behav Brain Res. 2013;250:274–84. https://doi.org/10.1016/j.bbr.2013.05.002.
CAS
Article
PubMed
Google Scholar
Gunduz-Cinar O, MacPherson KP, Cinar R, Gamble-George J, Sugden K, Williams B, et al. Convergent translational evidence of a role for anandamide in amygdala-mediated fear extinction, threat processing and stress-reactivity. Mol Psychiatry. 2013;18:813–23. https://doi.org/10.1038/mp.2012.72.
CAS
Article
PubMed
Google Scholar
Zubedat S, Akirav I. The involvement of cannabinoids and mTOR in the reconsolidation of an emotional memory in the hippocampal-amygdala-insular circuit. Eur Neuropsychopharmacol. 2017;27:336–49. https://doi.org/10.1016/j.euroneuro.2017.01.011.
CAS
Article
PubMed
Google Scholar
Segev A, Korem N, Mizrachi Zer-Aviv T, Abush H, Lange R, Sauber G, et al. Role of endocannabinoids in the hippocampus and amygdala in emotional memory and plasticity. Neuropsychopharmacology. 2018;43:2017–27. https://doi.org/10.1038/s41386-018-0135-4.
CAS
Article
PubMed
Google Scholar
Kishimoto Y, Cagniard B, Yamazaki M, Nakayama J, Sakimura K, Kirino Y, et al. Task-specific enhancement of hippocampus-dependent learning in mice deficient in monoacylglycerol lipase, the major hydrolyzing enzyme of the endocannabinoid 2-arachidonoylglycerol. Front Behav Neurosci. 2015;9:134. https://doi.org/10.3389/fnbeh.2015.00134.
CAS
Article
PubMed
PubMed Central
Google Scholar
Hartley ND, Gunduz-Cinar O, Halladay L, Bukalo O, Holmes A, Patel S. 2-arachidonoylglycerol signaling impairs short-term fear extinction. Transl Psychiatry 2016;6:e749-e. doi:https://doi.org/10.1038/tp.2016.26.
CAS
Article
Google Scholar
Morena M, Roozendaal B, Trezza V, Ratano P, Peloso A, Hauer D, et al. Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training. PNAS. 2014;111:18333–8. https://doi.org/10.1073/pnas.1420285111.
CAS
Article
PubMed
Google Scholar
Ratano P, Petrella C, Forti F, Passeri PP, Morena M, Palmery M, et al. Pharmacological inhibition of 2-arachidonoilglycerol hydrolysis enhances memory consolidation in rats through CB2 receptor activation and mTOR signaling modulation. Neuropharmacology. 2018;138:210–8. https://doi.org/10.1016/j.neuropharm.2018.05.030.
CAS
Article
PubMed
Google Scholar
de Oliveira Alvares L, de Oliveira LF, Camboim C, Diehl F, Genro BP, Lanziotti VB, et al. Amnestic effect of intrahippocampal AM251, a CB1-selective blocker, in the inhibitory avoidance, but not in the open field habituation task, in rats. Neurobiol Learn Mem. 2005;83:119–24. https://doi.org/10.1016/j.nlm.2004.10.002.
CAS
Article
PubMed
Google Scholar
de Oliveira Alvares L, Engelke DS, Diehl F, Scheffer-Teixeira R, Haubrich J, de Freitas Cassini L, et al. Stress response recruits the hippocampal endocannabinoid system for the modulation of fear memory. Learn Mem. 2010;17:202–9. https://doi.org/10.1101/lm.1721010.
CAS
Article
PubMed
Google Scholar
Mackowiak M, Chocyk A, Dudys D, Wedzony K. Activation of CB1 cannabinoid receptors impairs memory consolidation and hippocampal polysialylated neural cell adhesion molecule expression in contextual fear conditioning. Neuroscience. 2009;158:1708–16. https://doi.org/10.1016/j.neuroscience.2008.11.037.
CAS
Article
PubMed
Google Scholar
Sachser RM, Crestani AP, Quillfeldt JA, Mello EST, de Oliveira Alvares L. The cannabinoid system in the retrosplenial cortex modulates fear memory consolidation, reconsolidation, and extinction. Learn Mem. 2015;22:584–8. https://doi.org/10.1101/lm.039891.115.
CAS
Article
PubMed
PubMed Central
Google Scholar
Nasehi M, Davoudi K, Ebrahimi-Ghiri M, Zarrindast MR. Interplay between serotonin and cannabinoid function in the amygdala in fear conditioning. Brain Res. 2016;1636:142–51. https://doi.org/10.1016/j.brainres.2016.01.034.
CAS
Article
PubMed
Google Scholar
Garcia-Gutierrez MS, Ortega-Alvaro A, Busquets-Garcia A, Perez-Ortiz JM, Caltana L, Ricatti MJ, et al. Synaptic plasticity alterations associated with memory impairment induced by deletion of CB2 cannabinoid receptors. Neuropharmacology. 2013;73:388–96. https://doi.org/10.1016/j.neuropharm.2013.05.034.
CAS
Article
PubMed
Google Scholar
Li Y, Kim J. CB2 cannabinoid receptor knockout in mice impairs contextual long-term memory and enhances spatial working memory. Neural Plast. 2016;2016:9817089. https://doi.org/10.1155/2016/9817089.
Article
PubMed
Google Scholar
Nasehi M, Hajikhani M, Ebrahimi-Ghiri M, Zarrindast MR. Interaction between NMDA and CB2 function in the dorsal hippocampus on memory consolidation impairment: an isobologram analysis. Psychopharmacology. 2017;234:507–14. https://doi.org/10.1007/s00213-016-4481-9.
CAS
Article
PubMed
Google Scholar
Ratano P, Everitt BJ, Milton AL. The CB1 receptor antagonist AM251 impairs reconsolidation of pavlovian fear memory in the rat basolateral amygdala. Neuropsychopharmacology. 2014;39:2529–37. https://doi.org/10.1038/npp.2014.103.
CAS
Article
PubMed
PubMed Central
Google Scholar
Lin HC, Mao SC, Gean PW. Effects of intra-amygdala infusion of CB1 receptor agonists on the reconsolidation of fear-potentiated startle. Learn Mem. 2006;13:316–21. https://doi.org/10.1101/lm.217006.
CAS
Article
PubMed
PubMed Central
Google Scholar
Santana F, Sierra RO, Haubrich J, Crestani AP, Duran JM, de Freitas Cassini L, et al. Involvement of the infralimbic cortex and CA1 hippocampal area in reconsolidation of a contextual fear memory through CB1 receptors: effects of CP55,940. Neurobiol Learn Mem. 2016;127:42–7. https://doi.org/10.1016/j.nlm.2015.11.016.
CAS
Article
PubMed
Google Scholar
Suzuki A, Mukawa T, Tsukagoshi A, Frankland PW, Kida S. Activation of LVGCCs and CB1 receptors required for destabilization of reactivated contextual fear memories. Learn Mem. 2008;15:426–33. https://doi.org/10.1101/lm.888808.
CAS
Article
PubMed
PubMed Central
Google Scholar
Lee JL, Flavell CR. Inhibition and enhancement of contextual fear memory destabilization. Front Behav Neurosci. 2014;8:144. https://doi.org/10.3389/fnbeh.2014.00144.
Article
PubMed
PubMed Central
Google Scholar
Lin HC, Mao SC, Chen PS, Gean PW. Chronic cannabinoid administration in vivo compromises extinction of fear memory. Learn Mem. 2008;15:876–84. https://doi.org/10.1101/lm.1081908.
CAS
Article
PubMed
Google Scholar
ElBatsh MM, Assareh N, Marsden CA, Kendall DA. Anxiogenic-like effects of chronic cannabidiol administration in rats. Psychopharmacology. 2012;221:239–47. https://doi.org/10.1007/s00213-011-2566-z.
CAS
Article
PubMed
Google Scholar
Cheng D, Low JK, Logge W, Garner B, Karl T. Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1E9 mice. Psychopharmacology. 2014;231:3009–17. https://doi.org/10.1007/s00213-014-3478-5.
CAS
Article
PubMed
Google Scholar
De Gregorio D, McLaughlin RJ, Posa L, Ochoa-Sanchez R, Enns J, Lopez-Canul M, et al. Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain. 2019;160:136–50. https://doi.org/10.1097/j.pain.0000000000001386.
CAS
Article
PubMed
Google Scholar
Cohen K, Weinstein A. The effects of cannabinoids on executive functions: evidence from cannabis and synthetic cannabinoids - a systematic review. Brain Sci. 2018;8:40. https://doi.org/10.3390/brainsci8030040.
CAS
Article
PubMed Central
Google Scholar
Szkudlarek HJ, Desai SJ, Renard J, Pereira B, Norris C, Jobson CEL, et al. Delta-9-tetrahydrocannabinol and cannabidiol produce dissociable effects on prefrontal cortical executive function and regulation of affective behaviors. Neuropsychopharmacology. 2019;44:817–25. https://doi.org/10.1038/s41386-018-0282-7.
CAS
Article
PubMed
Google Scholar
Uhernik AL, Montoya ZT, Balkissoon CD, Smith JP. Learning and memory is modulated by cannabidiol when administered during trace fear-conditioning. Neurobiol Learn Mem. 2018;149:68–76. https://doi.org/10.1016/j.nlm.2018.02.009.
CAS
Article
PubMed
Google Scholar
Dhopeshwarkar A, Mackie K. CB2 cannabinoid receptors as a therapeutic target - what does the future hold? Mol Pharmacol. 2014;86:430–7. https://doi.org/10.1124/mol.114.094649.
CAS
Article
PubMed
PubMed Central
Google Scholar
Laricchiuta D, Centonze D, Petrosini L. Effects of endocannabinoid and endovanilloid systems on aversive memory extinction. Behav Brain Res. 2013;256:101–7. https://doi.org/10.1016/j.bbr.2013.08.010.
CAS
Article
PubMed
Google Scholar
Gobira PH, Lima IV, Batista LA, de Oliveira AC, Resstel LB, Wotjak CT, et al. N-arachidonoyl-serotonin, a dual FAAH and TRPV1 blocker, inhibits the retrieval of contextual fear memory: role of the cannabinoid CB1 receptor in the dorsal hippocampus. J Psychopharmacol. 2017;31:750–6. https://doi.org/10.1177/0269881117691567.
CAS
Article
PubMed
Google Scholar
Dow-Edwards D, Silva L. Endocannabinoids in brain plasticity: cortical maturation, HPA axis function and behavior. Brain Res. 2017;1654(Pt B):157–64. https://doi.org/10.1016/j.brainres.2016.08.037.
CAS
Article
PubMed
Google Scholar
Mendiguren A, Aostri E, Pineda J. Regulation of noradrenergic and serotonergic systems by cannabinoids: relevance to cannabinoid-induced effects. Life Sci. 2018;192:115–27. https://doi.org/10.1016/j.lfs.2017.11.029.
CAS
Article
PubMed
Google Scholar
Karschner EL, Darwin WD, McMahon RP, Liu F, Wright S, Goodwin RS, et al. Subjective and physiological effects after controlled Sativex and oral THC administration. Clin Pharmacol Ther. 2011;89:400–7. https://doi.org/10.1038/clpt.2010.318.
CAS
Article
PubMed
Google Scholar
Todd SM, Arnold JC. Neural correlates of interactions between cannabidiol and Delta(9)-tetrahydrocannabinol in mice: implications for medical cannabis. Br J Pharmacol. 2016;173:53–65. https://doi.org/10.1111/bph.13333.
CAS
Article
PubMed
Google Scholar