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Current Neuropharmacology



ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Nightmares and the Cannabinoids

Author(s): Mortimer Mamelak*

Volume 18, Issue 8, 2020

Page: [754 - 768] Pages: 15

DOI: 10.2174/1570159X18666200114142321

Price: $65


The cannabinoids, Δ9 tetrahydrocannabinol and its analogue, nabilone, have been found to reliably attenuate the intensity and frequency of post-traumatic nightmares. This essay examines how a traumatic event is captured in the mind, after just a single exposure, and repeatedly replicated during the nights that follow. The adaptive neurophysiological, endocrine and inflammatory changes that are triggered by the trauma and that alter personality and behavior are surveyed. These adaptive changes, once established, can be difficult to reverse. But cannabinoids, uniquely, have been shown to interfere with all of these post-traumatic somatic adaptations. While cannabinoids can suppress nightmares and other symptoms of post-traumatic stress disorder, they are not a cure. There may be no cure. The cannabinoids may best be employed, alone, but more likely in conjunction with other agents, in the immediate aftermath of a trauma to mitigate or even abort the metabolic changes which are set in motion by the trauma and which may permanently alter the reactivity of the nervous system. Steps in this direction have already been taken.

Keywords: Nightmares, sleep, episodic memory, sharp wave ripple complex, cannabinoids, post-traumatic stress disorder.

Graphical Abstract
Morgenthaler, T.I.; Auerbach, S.; Casey, K.R.; Kristo, D.; Maganti, R.; Ramar, K.; Zak, R.; Kartje, R. Position paper for the treatment of nightmare disorder in adults: an american academy of sleep medicine position paper. J. Clin. Sleep Med., 2018, 14(6), 1041-1055.
[] [PMID: 29852917]
Fraser, G.A. The use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD). CNS Neurosci. Ther., 2009, 15(1), 84-88.
[] [PMID: 19228182]
Cameron, C.; Watson, D.; Robinson, J. Use of a synthetic cannabinoid in a correctional population for posttraumatic stress disorder-related insomnia and nightmares, chronic pain, harm reduction, and other indications: a retrospective evaluation. J. Clin. Psychopharmacol., 2014, 34(5), 559-564.
[] [PMID: 24987795]
Jetly, R.; Heber, A.; Fraser, G.; Boisvert, D. The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology, 2015, 51, 585-588.
[] [PMID: 25467221]
Zurier, R.B.; Burstein, S.H. Cannabinoids, inflammation, and fibrosis. FASEB J., 2016, 30(11), 3682-3689.
[] [PMID: 27435265]
Roitman, P.; Mechoulam, R.; Cooper-Kazaz, R.; Shalev, A. Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder. Clin. Drug Investig., 2014, 34(8), 587-591.
[] [PMID: 24935052]
Hindocha, C.; Cousijn, J.; Rall, M.; Bloomfield, M.A.P. the effectiveness of cannabinoids in the treatment of posttraumatic stress disorder (PTSD): A systematic review. J. Dual Diagn., 2019, 1-20.
[] [PMID: 31479625]
The International Classification of Sleep Disorders. Diagnostic and Coding Manual; Westchester: Illinois, 2005.
Diagnostic and Statistical Manual of Mental Disorders (DSM-5); American Psychiatric Publishing: Arlington, VA, 2013.
Corballis, M.C. Cambridge Handb. Conscious; Zelazo, P.D.; Moscovitch, M; Thompson, E., Ed.; 571-596.
Stickgold, R. Learning, and dreams: off-line memory reprocessing. Science, 2001, 294, 1052-1057.
Tulving, E. Memory and consciousness. Can. Psychol., 1985, 26, 1-12.
Wittmann, L.; Schredl, M.; Kramer, M. Dreaming in posttraumatic stress disorder: A critical review of phenomenology, psychophysiology and treatment. Psychother. Psychosom., 2007, 76(1), 25-39.
[] [PMID: 17170561]
Freyberger, H.J.; Freyberger, H. Sechzig Jahre danach: Posttraumatische Belastungsstörungen, salutogene Faktoren und gutachterliche Einschätzungen bei Holocaust-Uberlebenden im Langzeitverlauf. Z. Psychosom. Med. Psychother., 2007, 53(4), 380-392.
[] [PMID: 18187015]
Schreuder, B.J.N.; Kleijn, W.C.; Rooijmans, H.G.M. Nocturnal re-experiencing more than forty years after war trauma. J. Trauma. Stress, 2000, 13(3), 453-463.
[] [PMID: 10948485]
Born, J.; Wilhelm, I. System consolidation of memory during sleep. Psychol. Res., 2012, 76(2), 192-203.
[] [PMID: 21541757]
Buzsáki, G. Two-stage model of memory trace formation: a role for “noisy” brain states. Neuroscience, 1989, 31(3), 551-570.
[] [PMID: 2687720]
Buzsáki, G. The hippocampo-neocortical dialogue. Cereb. Cortex, 1996, 6(2), 81-92.
[] [PMID: 8670641]
Buzsáki, G. Hippocampal sharp wave-ripple: A cognitive biomarker for episodic memory and planning. Hippocampus, 2015, 25(10), 1073-1188.
[] [PMID: 26135716]
Kitamura, T.; Ogawa, S.K.; Roy, D.S.; Okuyama, T.; Morrissey, M.D.; Smith, L.M.; Redondo, R.L.; Tonegawa, S. Engrams and circuits crucial for systems consolidation of a memory. Science (80-. ) , 2017. 356, . , 73-78.
[ ]
O’Neill, J.; Pleydell-Bouverie, B.; Dupret, D.; Csicsvari, J. Play it again: reactivation of waking experience and memory. Trends Neurosci., 2010, 33(5), 220-229.
[] [PMID: 20207025]
Sekeres, M.J.; Winocur, G.; Moscovitch, M. The hippocampus and related neocortical structures in memory transformation. Neurosci. Lett., 2018, 680, 39-53.
[] [PMID: 29733974]
Lewis, P.A.; Durrant, S.J. Overlapping memory replay during sleep builds cognitive schemata.Trends Cogn. Sci. (Regul. Ed.),; , 2011, 15, pp. (8)343-351.
[] [PMID: 21764357]
Chrobak, J.J.; Buzsáki, G. Selective activation of deep layer (V-VI) retrohippocampal cortical neurons during hippocampal sharp waves in the behaving rat. J. Neurosci., 1994, 14(10), 6160-6170.
[] [PMID: 7931570]
Boyce, R.; Williams, S.; Adamantidis, A. REM sleep and memory. Curr. Opin. Neurobiol., 2017, 44, 167-177.
[] [PMID: 28544929]
Giuditta, A. Sleep memory processing: the sequential hypothesis. Front. Syst. Neurosci., 2014, 8, 219.
[] [PMID: 25565985]
Tang, W.; Jadhav, S.P. Sharp-wave ripples as a signature of hippocampal-prefrontal reactivation for memory during sleep and waking states. Neurobiol. Learn. Mem., 2019, 160, 11-20.
[] [PMID: 29331447]
Fosse, M.J.; Fosse, R.; Hobson, J.A.; Stickgold, R.J. Dreaming and episodic memory: a functional dissociation? J. Cogn. Neurosci., 2003, 15(1), 1-9.
[] [PMID: 12590838]
Nir, Y.; Tononi, G. Dreaming and the brain: from phenomenology to neurophysiology.Trends Cogn. Sci. (Regul. Ed.); , 2010, 14, pp. (2)88-100.
[] [PMID: 20079677]
Hasselmo, M.E. Neuromodulation: acetylcholine and memory consolidation.Trends Cogn. Sci. (Regul. Ed.); , 1999, 3, pp. (9)351-359.
[] [PMID: 10461198]
Mizuseki, K.; Miyawaki, H. Hippocampal information processing across sleep/wake cycles. Neurosci. Res., 2017, 118, 30-47.
[] [PMID: 28506629]
Rasch, B.; Pommer, J.; Diekelmann, S.; Born, J. Pharmacological REM sleep suppression paradoxically improves rather than impairs skill memory. Nat. Neurosci., 2009, 12(4), 396-397.
[] [PMID: 18836440]
Siegel, J.M. REM sleep: a biological and psychological paradox. Sleep Med. Rev., 2011, 15(3), 139-142.
[] [PMID: 21482156]
Vertes, R.P.; Eastman, K.E. The case against memory consolidation in REM sleep. Behav. Brain Sci., 2000, 23(6), 867-876.
[] [PMID: 11515146]
Fogel, S.M.; Smith, C.T. The function of the sleep spindle: a physiological index of intelligence and a mechanism for sleep-dependent memory consolidation. Neurosci. Biobehav. Rev., 2011, 35(5), 1154-1165.
[] [PMID: 21167865]
Gulati, T.; Ramanathan, D.S.; Wong, C.C.; Ganguly, K. Reactivation of emergent task-related ensembles during slow-wave sleep after neuroprosthetic learning. Nat. Neurosci., 2014, 17(8), 1107-1113.
[] [PMID: 24997761]
Boyce, R.; Glasgow, S.D.; Williams, S.; Adamantidis, A. Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation. Science (80-. ), 2016. 352. , 812-816.
Klinzing, J.G.; Niethard, N.; Born, J. Publisher Correction: Mechanisms of systems memory consolidation during sleep. Nat. Neurosci., 2019, 22(10), 1743-1744.
[] [PMID: 31511701]
Nishida, M.; Pearsall, J.; Buckner, R.L.; Walker, M.P. REM sleep, prefrontal theta, and the consolidation of human emotional memory. Cereb. Cortex, 2009, 19(5), 1158-1166.
[] [PMID: 18832332]
Sopp, M.R.; Michael, T.; Weeß, H.G.; Mecklinger, A. Remembering specific features of emotional events across time: The role of REM sleep and prefrontal theta oscillations. Cogn. Affect. Behav. Neurosci., 2017, 17(6), 1186-1209.
[] [PMID: 29063522]
Xia, Z.; Storm, D. Role of circadian rhythm and REM sleep for memory consolidation. Neurosci. Res., 2017, 118, 13-20.
[] [PMID: 28434990]
Phelps, A.J.; Kanaan, R.A.A.; Worsnop, C.; Redston, S.; Ralph, N.; Forbes, D. An ambulatory polysomnography study of the post-traumatic nightmares of post-traumatic stress disorder. Sleep (Basel), 2018, 41(1), zsx188
[] [PMID: 29182727]
Richards, A.; Kanady, J.C.; Neylan, T.C. Sleep disturbance in PTSD and other anxiety-related disorders: an updated review of clinical features, physiological characteristics, and psychological and neurobiological mechanisms. Neuropsychopharmacology, 2020, 45(1), 55-73.
[] [PMID: 31443103]
Schredl, M.; Schmitt, J.; Hein, G.; Schmoll, T.; Eller, S.; Haaf, J. Nightmares and oxygen desaturations: is sleep apnea related to heightened nightmare frequency? Sleep Breath., 2006, 10(4), 203-209.
[] [PMID: 17061140]
Passie, T.; Emrich, H.M.; Karst, M.; Brandt, S.D.; Halpern, J.H. Mitigation of post-traumatic stress symptoms by Cannabis resin: a review of the clinical and neurobiological evidence. Drug Test. Anal., 2012, 4(7-8), 649-659.
[] [PMID: 22736575]
Gates, P.J.; Albertella, L.; Copeland, J. The effects of cannabinoid administration on sleep: a systematic review of human studies. Sleep Med. Rev., 2014, 18(6), 477-487.
[] [PMID: 24726015]
Nicholson, A.N.; Turner, C.; Stone, B.M.; Robson, P.J. Effect of Δ-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. J. Clin. Psychopharmacol., 2004, 24(3), 305-313.
[] [PMID: 15118485]
Babson, K.A.; Sottile, J.; Morabito, D. Cannabis, cannabinoids, and sleep: a review of the literature. Curr. Psychiatry Rep., 2017, 19(4), 23.
[] [PMID: 28349316]
Destexhe, A.; Hughes, S.W.; Rudolph, M.; Crunelli, V. Are corticothalamic ‘up’ states fragments of wakefulness? Trends Neurosci., 2007, 30(7), 334-342.
[] [PMID: 17481741]
Girardeau, G.; Zugaro, M. Hippocampal ripples and memory consolidation. Curr. Opin. Neurobiol., 2011, 21(3), 452-459.
[] [PMID: 21371881]
Payne, J.D. Sleep on it!: stabilizing and transforming memories during sleep. Nat. Neurosci., 2011, 14(3), 272-274.
[] [PMID: 21346743]
Schwindel, C.D.; McNaughton, B.L. Hippocampal-cortical interactions and the dynamics of memory trace reactivation. Prog. Brain Res.,, 2011, 193, 163-177.
[] [PMID: 21854962]
Sirota, A.; Csicsvari, J.; Buhl, D.; Buzsáki, G. Communication between neocortex and hippocampus during sleep in rodents. Proc. Natl. Acad. Sci. USA, 2003, 100(4), 2065-2069.
[] [PMID: 12576550]
Buzsáki, G. Rhythm. Brain; Oxford University Press, 2006, pp. 334-356.
Wilson, M.; McNaughton, B. Reactivation of hippocampal ensemble memories during sleep. Science (80-.), 1994, 265, 676-679.
Ji, D.; Wilson, M.A. Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat. Neurosci., 2007, 10(1), 100-107.
[] [PMID: 17173043]
Qin, Y-L.; McNaughton, B.L.; Skaggs, W.E.; Barnes, C.A. Memory reprocessing in corticocortical and hippocampocortical neuronal ensembles. Philos. Trans. R. Soc. Lond. B Biol. Sci., 1997, 352(1360), 1525-1533.
[] [PMID: 9368941]
Ego-Stengel, V.; Wilson, M.A. Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat. Hippocampus, 2010, 20(1), 1-10.
[PMID: 19816984]
Girardeau, G.; Benchenane, K.; Wiener, S.I.; Buzsáki, G.; Zugaro, M.B. Selective suppression of hippocampal ripples impairs spatial memory. Nat. Neurosci., 2009, 12(10), 1222-1223.
[] [PMID: 19749750]
Peigneux, P.; Laureys, S.; Fuchs, S.; Collette, F.; Perrin, F.; Reggers, J.; Phillips, C.; Degueldre, C.; Del Fiore, G.; Aerts, J.; Luxen, A.; Maquet, P. Are spatial memories strengthened in the human hippocampus during slow wave sleep? Neuron, 2004, 44(3), 535-545.
[] [PMID: 15504332]
Colgin, L.L. Rhythms of the hippocampal network. Nat. Rev. Neurosci., 2016, 17(4), 239-249.
[] [PMID: 26961163]
Nakashiba, T.; Buhl, D.L.; McHugh, T.J.; Tonegawa, S. Hippocampal CA3 output is crucial for ripple-associated reactivation and consolidation of memory. Neuron, 2009, 62(6), 781-787.
[] [PMID: 19555647]
Jadhav, S.P.; Kemere, C.; German, P.W.; Frank, L.M. Awake hippocampal sharp-wave ripples support spatial memory. Science (80), 2012, 336, 1454-1458.
Robbe, D.; Montgomery, S.M.; Thome, A.; Rueda-Orozco, P.E.; McNaughton, B.L.; Buzsaki, G. Cannabinoids reveal importance of spike timing coordination in hippocampal function. Nat. Neurosci., 2006, 9(12), 1526-1533.
[] [PMID: 17115043]
Maier, N.; Morris, G.; Schuchmann, S.; Korotkova, T.; Ponomarenko, A.; Böhm, C.; Wozny, C.; Schmitz, D. Cannabinoids disrupt hippocampal sharp wave-ripples via inhibition of glutamate release. Hippocampus, 2012, 22(6), 1350-1362.
[] [PMID: 21853502]
Sun, Y.; Norimoto, H.; Pu, X-P.; Matsuki, N.; Ikegaya, Y. Cannabinoid receptor activation disrupts the internal structure of hippocampal sharp wave-ripple complexes. J. Pharmacol. Sci., 2012, 118(2), 288-294.
[] [PMID: 22293299]
Sandler, R.A.; Fetterhoff, D.; Hampson, R.E.; Deadwyler, S.A.; Marmarelis, V.Z. Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3. PLOS Comput. Biol., 2017, 13(7), e1005624
[] [PMID: 28686594]
Bragin, A.; Engel, J., Jr; Wilson, C.L.; Fried, I.; Buzsáki, G. High-frequency oscillations in human brain. Hippocampus, 1999, 9(2), 137-142.
[<137::AID-HIPO5>3.0.CO;2-0] [PMID: 10226774]
Axmacher, N.; Elger, C.E.; Fell, J. Ripples in the medial temporal lobe are relevant for human memory consolidation. Brain, 2008, 131(Pt 7), 1806-1817.
[] [PMID: 18503077]
Vaz, A.P.; Inati, S.K.; Brunel, N.; Zaghloul, K.A. Coupled ripple oscillations between the medial temporal lobe and neocortex retrieve human memory. Science (80-.), 2019, 363, 975-978.
Wu, C-T.; Haggerty, D.; Kemere, C.; Ji, D. Hippocampal awake replay in fear memory retrieval. Nat. Neurosci., 2017, 20(4), 571-580.
[] [PMID: 28218916]
Easton, A.; Douchamps, V.; Eacott, M.; Lever, C. A specific role for septohippocampal acetylcholine in memory? Neuropsychologia, 2012, 50(13), 3156-3168.
[] [PMID: 22884957]
Norimoto, H.; Mizunuma, M.; Ishikawa, D.; Matsuki, N.; Ikegaya, Y. Muscarinic receptor activation disrupts hippocampal sharp wave-ripples. Brain Res., 2012, 1461, 1-9.
[] [PMID: 22608077]
Buzsáki, G. Theta oscillations in the hippocampus. Neuron, 2002, 33(3), 325-340.
[] [PMID: 11832222]
Colgin, L.L. Mechanisms and functions of theta rhythms. Annu. Rev. Neurosci., 2013, 36, 295-312.
[] [PMID: 23724998]
Holderith, N.; Németh, B.; Papp, O.I.; Veres, J.M.; Nagy, G.A.; Hájos, N. Cannabinoids attenuate hippocampal γ oscillations by suppressing excitatory synaptic input onto CA3 pyramidal neurons and fast spiking basket cells. J. Physiol., 2011, 589(Pt 20), 4921-4934.
[] [PMID: 21859823]
Gulyás, A.I.; Szabó, G.G.; Ulbert, I.; Holderith, N.; Monyer, H.; Erdélyi, F.; Szabó, G.; Freund, T.F.; Hájos, N. Parvalbumin-containing fast-spiking basket cells generate the field potential oscillations induced by cholinergic receptor activation in the hippocampus. J. Neurosci., 2010, 30(45), 15134-15145.
[] [PMID: 21068319]
Goonawardena, A.V.; Robinson, L.; Hampson, R.E.; Riedel, G. Cannabinoid and cholinergic systems interact during performance of a short-term memory task in the rat. Learn. Mem., 2010, 17(10), 502-511.
[] [PMID: 20876271]
Carta, G.; Nava, F.; Gessa, G.L. Inhibition of hippocampal acetylcholine release after acute and repeated Δ9-tetrahydrocannabinol in rats. Brain Res., 1998, 809(1), 1-4.
[] [PMID: 9795096]
Kucewicz, M.T.; Tricklebank, M.D.; Bogacz, R.; Jones, M.W. Dysfunctional prefrontal cortical network activity and interactions following cannabinoid receptor activation. J. Neurosci., 2011, 31(43), 15560-15568.
[] [PMID: 22031901]
Rolls, E.T. The storage and recall of memories in the hippocampo-cortical system. Cell Tissue Res., 2018, 373(3), 577-604.
[] [PMID: 29218403]
Thompson, J.M.; Neugebauer, V. Amygdala plasticity and pain. Pain Res. Manag., 2017, 2017, 8296501
[] [PMID: 29302197]
Thompson, J.M.; Neugebauer, V. Cortico-limbic pain mechanisms. Neurosci. Lett., 2019, 702, 15-23.
[] [PMID: 30503916]
Eichenbaum, H. Prefrontal-hippocampal interactions in episodic memory. Nat. Rev. Neurosci., 2017, 18(9), 547-558.
[] [PMID: 28655882]
Benchenane, K.; Peyrache, A.; Khamassi, M.; Tierney, P.L.; Gioanni, Y.; Battaglia, F.P.; Wiener, S.I. Coherent theta oscillations and reorganization of spike timing in the hippocampal- prefrontal network upon learning. Neuron, 2010, 66(6), 921-936.
[] [PMID: 20620877]
Jones, M.W.; Wilson, M.A. Theta rhythms coordinate hippocampal-prefrontal interactions in a spatial memory task. PLoS Biol., 2005, 3, e402
Siapas, A.G.; Lubenov, E.V.; Wilson, M.A. Prefrontal phase locking to hippocampal theta oscillations. Neuron, 2005, 46(1), 141-151.
[] [PMID: 15820700]
Colgin, L.L. Oscillations and hippocampal-prefrontal synchrony. Curr. Opin. Neurobiol., 2011, 21(3), 467-474.
[] [PMID: 21571522]
Inostroza, M.; Born, J. Sleep for preserving and transforming episodic memory. Annu. Rev. Neurosci., 2013, 36, 79-102.
[] [PMID: 23642099]
Maingret, N.; Girardeau, G.; Todorova, R.; Goutierre, M.; Zugaro, M. Hippocampo-cortical coupling mediates memory consolidation during sleep. Nat. Neurosci., 2016, 19(7), 959-964.
[] [PMID: 27182818]
Tang, W.; Shin, J.D.; Frank, L.M.; Jadhav, S.P. Hippocampal-prefrontal reactivation during learning is stronger in awake compared with sleep states. J. Neurosci., 2017, 37(49), 11789-11805.
[] [PMID: 29089440]
Girardeau, G.; Inema, I.; Buzsáki, G. Reactivations of emotional memory in the hippocampus-amygdala system during sleep. Nat. Neurosci., 2017, 20(11), 1634-1642.
[] [PMID: 28892057]
Wang, D.V.; Yau, H-J.; Broker, C.J.; Tsou, J-H.; Bonci, A.; Ikemoto, S. Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation. Nat. Neurosci., 2015, 18(5), 728-735.
[] [PMID: 25867120]
Burgos-Robles, A.; Kimchi, E.Y.; Izadmehr, E.M.; Porzenheim, M.J.; Ramos-Guasp, W.A.; Nieh, E.H.; Felix-Ortiz, A.C.; Namburi, P.; Leppla, C.A.; Presbrey, K.N.; Anandalingam, K.K.; Pagan-Rivera, P.A.; Anahtar, M.; Beyeler, A.; Tye, K.M. Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment. Nat. Neurosci., 2017, 20(6), 824-835.
[] [PMID: 28436980]
Namburi, P.; Beyeler, A.; Yorozu, S.; Calhoon, G.G.; Halbert, S.A.; Wichmann, R.; Holden, S.S.; Mertens, K.L.; Anahtar, M.; Felix-Ortiz, A.C.; Wickersham, I.R.; Gray, J.M.; Tye, K.M. A circuit mechanism for differentiating positive and negative associations. Nature, 2015, 520(7549), 675-678.
[] [PMID: 25925480]
Hortensius, R.; Terburg, D.; Morgan, B.; Stein, D.J.; van Honk, J.; de Gelder, B. The dynamic consequences of amygdala damage on threat processing in Urbach-Wiethe Disease. A commentary on Pishnamazi et al. (2016). Cortex, 2017, 88, 192-197.
[] [PMID: 27531670]
Pishnamazi, M.; Tafakhori, A.; Loloee, S.; Modabbernia, A.; Aghamollaii, V.; Bahrami, B.; Winston, J.S. Attentional bias towards and away from fearful faces is modulated by developmental amygdala damage. Cortex, 2016, 81, 24-34.
[] [PMID: 27173975]
Marek, R.; Sun, Y.; Sah, P. Neural circuits for a top-down control of fear and extinction. Psychopharmacology (Berl.), 2019, 236(1), 313-320.
[] [PMID: 30215217]
Milad, M.R.; Quirk, G.J. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature, 2002, 420(6911), 70-74.
[] [PMID: 12422216]
Senn, V.; Wolff, S.B.; Herry, C.; Grenier, F.; Ehrlich, I.; Gründemann, J.; Fadok, J.P.; Müller, C.; Letzkus, J.J.; Lüthi, A. Long range connectivity defines behavioral specificity of amygdala neurons. Neuron, 2014, 81(2), 428-437.
[] [PMID: 24462103]
Lisboa, S.F.; Vila-Verde, C.; Rosa, J.; Uliana, D.L.; Stern, C.A.J.; Bertoglio, L.J.; Resstel, L.B.; Guimaraes, F.S. Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies. Psychopharmacology (Berl.), 2019, 236(1), 201-226.
[] [PMID: 30604182]
Kiritoshi, T.; Sun, H.; Ren, W.; Stauffer, S.R.; Lindsley, C.W.; Conn, P.J.; Neugebauer, V. Modulation of pyramidal cell output in the medial prefrontal cortex by mGluR5 interacting with CB1. Neuropharmacology, 2013, 66, 170-178.
[] [PMID: 22521499]
Kiritoshi, T.; Ji, G.; Neugebauer, V. Rescue of impaired mGluR5-driven endocannabinoid signaling restores prefrontal cortical output to inhibit pain in arthritic rats. J. Neurosci., 2016, 36(3), 837-850.
[] [PMID: 26791214]
Marsicano, G.; Wotjak, C.T.; Azad, S.C.; Bisogno, T.; Rammes, G.; Cascio, M.G.; Hermann, H.; Tang, J.; Hofmann, C.; Zieglgänsberger, W.; Di Marzo, V.; Lutz, B. The endogenous cannabinoid system controls extinction of aversive memories. Nature, 2002, 418(6897), 530-534.
[] [PMID: 12152079]
Woodhams, S.G.; Chapman, V.; Finn, D.P.; Hohmann, A.G.; Neugebauer, V. The cannabinoid system and pain. Neuropharmacology, 2017, 124, 105-120.
[] [PMID: 28625720]
Hammoud, M.Z.; Peters, C.; Hatfield, J.R.B.; Gorka, S.M.; Phan, K.L.; Milad, M.R.; Rabinak, C.A. Influence of Δ9-tetrahydrocannabinol on long-term neural correlates of threat extinction memory retention in humans. Neuropsychopharmacology, 2019, 44(10), 1769-1777.
[] [PMID: 31096264]
Rabinak, C.A.; Angstadt, M.; Lyons, M.; Mori, S.; Milad, M.R.; Liberzon, I.; Phan, K.L. Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans. Neurobiol. Learn. Mem., 2014, 113, 125-134.
[] [PMID: 24055595]
Rabinak, C.A.; Peters, C.; Marusak, H.A.; Ghosh, S.; Phan, K.L. Effects of acute Δ9-tetrahydrocannabinol on next-day extinction recall is mediated by post-extinction resting-state brain dynamics. Neuropharmacology, 2018, 143, 289-298.
[] [PMID: 30291940]
Arnsten, A.F.T. Stress signalling pathways that impair prefrontal cortex structure and function. Nat. Rev. Neurosci., 2009, 10(6), 410-422.
[] [PMID: 19455173]
Henigsberg, N.; Kalember, P.; Petrović, Z.K.; Šečić, A. Neuroimaging research in posttraumatic stress disorder - Focus on amygdala, hippocampus and prefrontal cortex. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2019, 90, 37-42.
[] [PMID: 30419321]
Kang, D.; McAuley, J.H.; Kassem, M.S.; Gatt, J.M.; Gustin, S.M. What does the grey matter decrease in the medial prefrontal cortex reflect in people with chronic pain? Eur. J. Pain, 2019, 23(2), 203-219.
[] [PMID: 30101509]
McIntyre, C.; Roozendaal, B. Neural Plast. Mem; CRC Press, 2007, pp. 265-283.
Beldjoud, H.; Barsegyan, A.; Roozendaal, B. Noradrenergic activation of the basolateral amygdala enhances object recognition memory and induces chromatin remodeling in the insular cortex. Front. Behav. Neurosci., 2015, 9, 108.
[] [PMID: 25972794]
de Quervain, D.; Wolf, O.T.; Roozendaal, B. Glucocorticoid-induced enhancement of extinction-from animal models to clinical trials. Psychopharmacology (Berl.), 2019, 236(1), 183-199.
[] [PMID: 30610352]
Roozendaal, B.; Luyten, L.; de Voogd, L.D.; Hermans, E.J. Importance of amygdala noradrenergic activity and large-scale neural networks in regulating emotional arousal effects on perception and memory. Behav. Brain Sci., 2016, 39, e222
[] [PMID: 28347385]
Cahill, L.; Babinsky, R.; Markowitsch, H.J.; McGaugh, J.L. The amygdala and emotional memory. Nature, 1995, 377(6547), 295-296.
[] [PMID: 7566084]
Schiff, H.C.; Johansen, J.P.; Hou, M.; Bush, D.E.A.; Smith, E.K.; Klein, J.E.; LeDoux, J.E.; Sears, R.M. β-Adrenergic receptors regulate the acquisition and consolidation phases of aversive memory formation through distinct, temporally regulated signaling pathways. Neuropsychopharmacology, 2017, 42(4), 895-903.
[] [PMID: 27762270]
Atsak, P.; Hauer, D.; Campolongo, P.; Schelling, G.; McGaugh, J.L.; Roozendaal, B. Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory. Proc. Natl. Acad. Sci. USA, 2012, 109(9), 3504-3509.
[] [PMID: 22331883]
de Quervain, D.J-F.; Roozendaal, B.; Nitsch, R.M.; McGaugh, J.L.; Hock, C. Acute cortisone administration impairs retrieval of long-term declarative memory in humans. Nat. Neurosci., 2000, 3(4), 313-314.
[] [PMID: 10725918]
de Quervain, D.J-F.; Aerni, A.; Roozendaal, B. Preventive effect of β-adrenoceptor blockade on glucocorticoid-induced memory retrieval deficits. Am. J. Psychiatry, 2007, 164(6), 967-969.
[] [PMID: 17541058]
Roozendaal, B.; Hahn, E.L.; Nathan, S.V.; de Quervain, D.J.; McGaugh, J.L. Glucocorticoid effects on memory retrieval require concurrent noradrenergic activity in the hippocampus and basolateral amygdala. J. Neurosci., 2004, 24(37), 8161-8169.
[] [PMID: 15371517]
Roozendaal, B.; Okuda, S.; de Quervain, D.J-F.; McGaugh, J.L. Glucocorticoids interact with emotion-induced noradrenergic activation in influencing different memory functions. Neuroscience, 2006, 138(3), 901-910.
[] [PMID: 16310958]
Schwabe, L.; Römer, S.; Richter, S.; Dockendorf, S.; Bilak, B.; Schächinger, H. Stress effects on declarative memory retrieval are blocked by a β-adrenoceptor antagonist in humans. Psychoneuroendocrinology, 2009, 34(3), 446-454.
[] [PMID: 19028019]
Akirav, I. The role of cannabinoids in modulating emotional and non-emotional memory processes in the hippocampus. Front. Behav. Neurosci., 2011, 5, 34.
[] [PMID: 21734875]
Morena, M.; Roozendaal, B.; Trezza, V.; Ratano, P.; Peloso, A.; Hauer, D.; Atsak, P.; Trabace, L.; Cuomo, V.; McGaugh, J.L.; Schelling, G.; Campolongo, P. Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training. Proc. Natl. Acad. Sci. USA, 2014, 111(51), 18333-18338.
[] [PMID: 25489086]
Campolongo, P.; Roozendaal, B.; Trezza, V.; Hauer, D.; Schelling, G.; McGaugh, J.L.; Cuomo, V. Endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory. Proc. Natl. Acad. Sci. USA, 2009, 106(12), 4888-4893.
[] [PMID: 19255436]
Atsak, P.; Roozendaal, B.; Campolongo, P. Role of the endocannabinoid system in regulating glucocorticoid effects on memory for emotional experiences. Neuroscience, 2012, 204, 104-116.
[] [PMID: 21893167]
Pamplona, F.A.; Takahashi, R.N. WIN 55212-2 impairs contextual fear conditioning through the activation of CB1 cannabinoid receptors. Neurosci. Lett., 2006, 397(1-2), 88-92.
[] [PMID: 16406322]
Ramot, A.; Akirav, I. Cannabinoid receptors activation and glucocorticoid receptors deactivation in the amygdala prevent the stress induced enhancement of a negative learning experience. Neurobiol. Learn. Mem., 2012, 97(4), 393-401.
[] [PMID: 22445897]
Merz, C.J.; Hamacher-Dang, T.C.; Stark, R.; Wolf, O.T.; Hermann, A. Neural underpinnings of cortisol effects on fear extinction. Neuropsychopharmacology, 2018, 43(2), 384-392.
[] [PMID: 28948980]
Morena, M.; Campolongo, P. The endocannabinoid system: an emotional buffer in the modulation of memory function. Neurobiol. Learn. Mem., 2014, 112, 30-43.
[] [PMID: 24382324]
Atsak, P.; Morena, M.; Schoenmaker, C.; Tabak, E.; Oomen, C.A.; Jamil, S.; Hill, M.N.; Roozendaal, B. Glucocorticoid endocannabinoid uncoupling mediates fear suppression deficits after early - Life stress. Psychoneuroendocrinology, 2018, 91, 41-49.
[] [PMID: 29524763]
Hill, M.N.; McEwen, B.S. Involvement of the endocannabinoid system in the neurobehavioural effects of stress and glucocorticoids. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2010, 34(5), 791-797.
[] [PMID: 19903506]
Di, S.; Malcher-Lopes, R.; Halmos, K.C.; Tasker, J.G. Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism. J. Neurosci., 2003, 23(12), 4850-4857.
[] [PMID: 12832507]
Phan, K.L.; 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(10), 2313-2319.
[] [PMID: 18322078]
Herkenham, M.; Lynn, A.B.; Little, M.D.; Johnson, M.R.; Melvin, L.S.; de Costa, B.R.; Rice, K.C. Cannabinoid receptor localization in brain. Proc. Natl. Acad. Sci. USA, 1990, 87(5), 1932-1936.
[] [PMID: 2308954]
Puighermanal, E.; Busquets-Garcia, A.; Maldonado, R.; Ozaita, A. Cellular and intracellular mechanisms involved in the cognitive impairment of cannabinoids. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2012, 367(1607), 3254-3263.
[] [PMID: 23108544]
Al-Zoubi; Morales; Reggio Structural insights into CB1 receptor biased signaling. Int. J. Mol. Sci., 2019, 20, 1837.
Hoeffer, C.A.; Klann, E. mTOR signaling: at the crossroads of plasticity, memory and disease. Trends Neurosci., 2010, 33(2), 67-75.
[] [PMID: 19963289]
Nogueras-Ortiz, C.; Yudowski, G.A. The Multiple Waves of Cannabinoid 1 Receptor Signaling. Mol. Pharmacol., 2016, 90(5), 620-626.
[] [PMID: 27338082]
Bie, B.; Wu, J.; Foss, J.F.; Naguib, M. An overview of the cannabinoid type 2 receptor system and its therapeutic potential. Curr. Opin. Anaesthesiol., 2018, 31(4), 407-414.
[] [PMID: 29794855]
Zoppi, S.; Madrigal, J.L.; Caso, J.R.; García-Gutiérrez, M.S.; Manzanares, J.; Leza, J.C.; García-Bueno, B. Regulatory role of the cannabinoid CB2 receptor in stress-induced neuroinflammation in mice. Br. J. Pharmacol., 2014, 171(11), 2814-2826.
[] [PMID: 24467609]
Sun, R.; Zhang, Z.; Lei, Y.; Liu, Y.; Lu, C.; Rong, H.; Sun, Y.; Zhang, W.; Ma, Z.; Gu, X. Hippocampal activation of microglia may underlie the shared neurobiology of comorbid posttraumatic stress disorder and chronic pain. Mol. Pain, 2016, 12, 1-13.
[] [PMID: 27852966]
Muhie, S.; Gautam, A.; Chakraborty, N.; Hoke, A.; Meyerhoff, J.; Hammamieh, R.; Jett, M. Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post-traumatic stress disorder. Transl. Psychiatry, 2017, 7(5), e1135-e1135.
[] [PMID: 28534873]
Donzis, E.J.; Tronson, N.C. Modulation of learning and memory by cytokines: signaling mechanisms and long term consequences. Neurobiol. Learn. Mem., 2014, 115, 68-77.
[] [PMID: 25151944]
Goshen, I.; Kreisel, T.; Ounallah-Saad, H.; Renbaum, P.; Zalzstein, Y.; Ben-Hur, T.; Levy-Lahad, E.; Yirmiya, R. A dual role for interleukin-1 in hippocampal-dependent memory processes. Psychoneuroendocrinology, 2007, 32(8-10), 1106-1115.
[] [PMID: 17976923]
Jones, M.E.; Lebonville, C.L.; Barrus, D.; Lysle, D.T. The role of brain interleukin-1 in stress-enhanced fear learning. Neuropsychopharmacology, 2015, 40(5), 1289-1296.
[] [PMID: 25430780]
Loflin, M.J.E.; Babson, K.A.; Bonn-Miller, M.O. Cannabinoids as therapeutic for PTSD. Curr. Opin. Psychol., 2017, 14, 78-83.
[] [PMID: 28813324]
Orsolini; Chiappini; Volpe; Berardis; Latini; Papanti; Corkery Use of Medicinal Cannabis and Synthetic Cannabinoids in Post-Traumatic Stress Disorder (PTSD): A Systematic Review. Medicina (B. Aires), 2019, 55, 525.
Ney, L.J.; Matthews, A.; Bruno, R.; Felmingham, K.L. Cannabinoid interventions for PTSD: Where to next? Prog. Neuropsychopharmacol. Biol. Psychiatry, 2019, 93, 124-140.
[] [PMID: 30946942]
Conti, S.; Costa, B.; Colleoni, M.; Parolaro, D.; Giagnoni, G. Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat. Br. J. Pharmacol., 2002, 135(1), 181-187.
[] [PMID: 11786493]
Tsang, C.C.; Giudice, M.G. Nabilone for the Management of Pain. Pharmacotherapy, 2016, 36(3), 273-286.
[] [PMID: 26923810]
Tournier, C.; Hours, M.; Charnay, P.; Chossegros, L.; Tardy, H. Five years after the accident, whiplash casualties still have poorer quality of life in the physical domain than other mildly injured casualties: analysis of the ESPARR cohort. BMC Public Heal., 2016, 16, 13.
Sarrami, P.; Armstrong, E.; Naylor, J.M.; Harris, I.A. Factors predicting outcome in whiplash injury: a systematic meta-review of prognostic factors. J. Orthop. Traumatol., 2017, 18(1), 9-16.
[] [PMID: 27738773]
Holbrook, T.L.; Galarneau, M.R.; Dye, J.L.; Quinn, K.; Dougherty, A.L. Morphine use after combat injury in Iraq and post-traumatic stress disorder. N. Engl. J. Med., 2010, 362(2), 110-117.
[] [PMID: 20071700]
Amos, T.; Stein, D.J.; Ipser, J.C. Pharmacological interventions for preventing post-traumatic stress disorder (PTSD). Cochrane Database Syst. Rev., 2014, (7), CD006239
[] [PMID: 25001071]
Yao, J.; Johnson, R.W. Induction of interleukin-1 β-converting enzyme (ICE) in murine microglia by lipopolysaccharide. Brain Res. Mol. Brain Res., 1997, 51(1-2), 170-178.
[] [PMID: 9427519]
Rohleder, N.; Wolf, J.M.; Kirschbaum, C.; Wolf, O.T. Effects of cortisol on emotional but not on neutral memory are correlated with peripheral glucocorticoid sensitivity of inflammatory cytokine production. Int. J. Psychophysiol., 2009, 72(1), 74-80.
[] [PMID: 18824040]

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