Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

Editorial Board: Topic, Bianca / Adeli, Hojjat / Buzsaki, Gyorgy / Crawley, Jacqueline / Crow, Tim / Gold, Paul / Holsboer, Florian / Korth, Carsten / Li, Jay-Shake / Lubec, Gert / McEwen, Bruce / Pan, Weihong / Pletnikov, Mikhail / Robbins, Trevor / Schnitzler, Alfons / Stevens, Charles / Steward, Oswald / Trojanowski, John

IMPACT FACTOR 2017: 2.590
5-year IMPACT FACTOR: 3.078

CiteScore 2017: 2.81

SCImago Journal Rank (SJR) 2017: 0.980
Source Normalized Impact per Paper (SNIP) 2017: 0.804

See all formats and pricing
More options …
Volume 30, Issue 1


Cannabidiol effects on prepulse inhibition in nonhuman primates

Patricia G. Saletti
  • Corresponding author
  • Albert Einstein College of Medicine, Rose F. Kennedy Center, Rm 310, 1410 Pelham Parkway South, Bronx, NY 10461, USA
  • Laboratory of Neurosciences and behavior, Department of Physiological Sciences, Institute of Biology, University of Brasilia, Brasilia, DF 70910-900, Brazil
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Carlos Tomaz
  • Laboratory of Neurosciences and behavior, Department of Physiological Sciences, Institute of Biology, University of Brasilia, Brasilia, DF 70910-900, Brazil
  • Neuroscience Research Group, University CEUMA, São Luís, MA 65075-120, Brazil
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-05-24 | DOI: https://doi.org/10.1515/revneuro-2017-0101


Prepulse inhibition (PPI) of acoustic startle reflex is a well-established behavior paradigm to measure sensorimotor gating deficits. PPI is disrupted in several neuropsychiatric disorders, including schizophrenia. PPI tests can be used to screen new drugs for treatment of such disorders. In this review, we discuss how PPI paradigm can help in screening the therapeutic effects of cannabidiol (CBD). We look into recent literature about CBD effects on PPI response in animal models, especially in nonhuman primates. CBD has been shown to modify PPI in N-methyl d-aspartate receptor antagonist models for schizophrenia, both in rodents and in nonhuman primates. These results show CBD as a potential drug for the treatment of neurologic disorders that present alterations in sensorimotor system, such as schizophrenia. Moreover, the PPI paradigm seems to be a useful and relative simple paradigm to test the efficacy of CBD as a potential therapeutic drug.

Keywords: cannabidiol (CBD); Cebus monkeys; endocannabinoid system; prepulse inhibition (PPI); schizophrenia


  • Ahmari, S.E., Risbrough, V.B., Geyer, M.A., and Simpson, H.B. (2012). Impaired sensorimotor gating in unmedicated adults with obsessive-compulsive disorder. Neuropsychopharmacology 37, 1216–1223.CrossrefPubMedGoogle Scholar

  • Ahmari, S.E., Risbrough, V.B., Geyer, M.A., and Simpson, H.B. (2016). Prepulse inhibition deficits in obsessive compulsive disorder are more pronounced in females. Neuropsychopharmacology 41, 2963–2964.PubMedCrossrefGoogle Scholar

  • Auclair, A.L., Kleven, M.S., Barret-Grévoz, C., Barreto, M., Newman-Tancredi, A., and Depoortère, R. (2009). Differences among conventional, atypical and novel putative D2/5-HT1A antipsychotics on catalepsy-associated behaviour in cynomolgus monkeys. Behav. Brain Res. 203, 288–295.CrossrefGoogle Scholar

  • Baker, D., Pryce, G., Giovannoni, G., and Thompson, A.J. (2003). The therapeutic potential of cannabis. Lancet Neurol. 2, 291–298.PubMedCrossrefGoogle Scholar

  • Bakshi, V.P. and Geyer, M.A. (1998). Multiple limbic regions mediate the disruption of prepulse inhibition produced in rats by the noncompetitive NMDA antagonist dizocilpine. J. Neurosci. 18, 8394–8401.PubMedCrossrefGoogle Scholar

  • Berardelli, A., Rothwell, J.C., Day, B.L., and Marsden, C.D. (1985). Pathophysiology of blepharospasm and oromandibular dystonia. Brain 108, 593–608.CrossrefPubMedGoogle Scholar

  • Bhattacharyya, S., Morrison, P.D., Fusar-Poli, P., Martin-Santos, R., Borgwardt, S., Winton-Brown, T., Nosarti, C., O’Carroll, C.M., Seal, M., Allen, P., et al. (2010). Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology 35, 764–774.PubMedCrossrefGoogle Scholar

  • Bisogno, T., Hanuš, L., De Petrocellis, L., Tchilibon, S., Ponde, D.E., Aniello, I.B., Moriello, S., Davis, J.B., Mechoulam, R., and Di Marzo, V. (2001). Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br. J. Pharmacol. 134, 845–852.PubMedCrossrefGoogle Scholar

  • Boyce, S., Rupniak, N.M., Steventon, M.J., Cook, G., and Iversen, S.D. (1991). Psychomotor activity and cognitive disruption attributable to NMDA, but not sigma, interactions in primates. Behav. Brain Res. 42, 115–121.PubMedCrossrefGoogle Scholar

  • Braff, D., Stone, C., Callaway, E., Geyer, M., Glick, I., and Bali, L. (1978). Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 15, 339–343.CrossrefPubMedGoogle Scholar

  • Braff, D.L., Geyer, M.A., Light, G.A., Sprock, J., Perry, W., Cadenhead, K.S., and Swerdlow, N.R. (2001a). Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia. Schizophr. Res. 49, 171–178.CrossrefGoogle Scholar

  • Braff, D.L., Geyer, M.A., and Swerdlow, N.R. (2001b). Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology (Berl.) 156, 234–258.CrossrefGoogle Scholar

  • Campos, A.C. and Guimarães, F.S. (2008). Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology (Berl.) 199, 223–230.CrossrefPubMedGoogle Scholar

  • Campos, A.C., Fogaça, M.V., Sonego, A.B., and Guimarães, F.S. (2016). Cannabidiol, neuroprotection and neuropsychiatric disorders. Pharmacol. Res. 112, 119–127.PubMedCrossrefGoogle Scholar

  • Carlini, E.A. and Cunha, J.M. (1981). Hypnotic and antiepileptic effects of cannabidiol. Clin. Pharmacol. 21, 417–427.CrossrefGoogle Scholar

  • Castellanos, F.X., Fine, E.J., Kaysen, D., Marsh, W.L., Rapoport, J.L., and Hallett, M. (1996). Sensorimotor gating in boys with Tourette’s syndrome and ADHD: preliminary results. Biol. Psychiatry 39, 33–41.CrossrefPubMedGoogle Scholar

  • Chan, W.Y.M. and McNally, G.P. (2009). Conditioned stimulus familiarity determines effects of MK-801 on fear extinction. Behav. Neurosci. 123, 303–314.CrossrefPubMedGoogle Scholar

  • Console-Bram, L., Marcu, J., and Abood, M.E. (2012). Cannabinoid receptors: nomenclature and pharmacological principles. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 38, 4–15.CrossrefGoogle Scholar

  • Crippa, J.A.D.S., Zuardi, A.W., Garrido, G.E.J., Wichert-Ana, L., Guarnieri, R., Ferrari, L., Azevedo-Marques, P.M., Hallak, J.E., McGuire, P.K., and Filho Busatto, G. (2004). Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology 29, 417–426.CrossrefPubMedGoogle Scholar

  • Crippa, J.A.S., Derenusson, G.N., Ferrari, T.B., Wichert-Ana, L., Duran, F.L.S., Martin-Santos, R., Simões, M.V., Bhattacharyya, S., Fusar-Poli, P., Atakan, Z., et al. (2011). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J. Psychopharmacol. 25, 121–130.PubMedCrossrefGoogle Scholar

  • Crippa, J.A.S., Crippa, A.C.S., Hallak, J.E.C., Martín-Santos, R., and Zuardi, A.W. (2016). Δ9-THC intoxication by cannabidiol-enriched cannabis extract in two children with refractory epilepsy: full remission after switching to purified cannabidiol. Front. Pharmacol. 7, 1–6.Google Scholar

  • Cristino, L., de Petrocellis, L., Pryce, G., Baker, D., Guglielmotti, V., and Di Marzo, V. (2006). Immunohistochemical localization of cannabinoid type 1 and vanilloid transient receptor potential vanilloid type 1 receptors in the mouse brain. Neuroscience 139, 1405–1415.CrossrefPubMedGoogle Scholar

  • Dahmen, J.C. and Corr, P. J. (2004). Prepulse-elicited startle in prepulse inhibition. Biol. Psychiatry 55, 98–101.CrossrefPubMedGoogle Scholar

  • Davis, M., Gendelman, D.S., Tischler, M.D., and Gendelman, P.M. (1982). A primary acoustic startle circuit: lesion and stimulation studies. J. Neurosci. 2, 791–805.CrossrefPubMedGoogle Scholar

  • Davis, M., Antoniadis, E.A., Amaral, D.G., and Winslow, J.T. (2008). Acoustic startle reflex in Rhesus monkeys: a review. Rev. Neurosci. 19, 171–185.PubMedGoogle Scholar

  • Dean, B., Sundram, S., Bradbury, R., Scarr, E., and Copolov, D.D. (2001). Studies on [3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use. Neuroscience 103, 9–15.CrossrefPubMedGoogle Scholar

  • De Petrocellis, L., Cascio, M.G., and Di Marzo, V. (2004). The endocannabinoid system: a general view and latest additions. Br. J. Pharmacol. 141, 765–774.CrossrefPubMedGoogle Scholar

  • Deutsch, S.I., Rosse, R.B., Schwartz, B.L., and Mastropaolo, J. (2001). A revised excitotoxic hypothesis of schizophrenia: therapeutic implications. Clin. Neuropharmacol. 24, 43–49.CrossrefPubMedGoogle Scholar

  • Di Marzo, V. and Matias, I. (2005). Endocannabinoid control of food intake and energy balance. Nat. Neurosci. 8, 585–589.PubMedCrossrefGoogle Scholar

  • Di Marzo, V., Bisogno, T., and De Petrocellis, L. (2001). Anandamide: some like it hot. Trends Pharmacol. Sci. 22, 346–349.CrossrefPubMedGoogle Scholar

  • Di Marzo, V., Bifulco, M., and De Petrocellis, L. (2004). The endocannabinoid system and its therapeutic exploitation. Nat. Rev. Drug Discov. 3, 771–784.CrossrefPubMedGoogle Scholar

  • Do Val-da Silva, R.A., Peixoto-Santos, J.E., Kandratavicius, L., de Ross, J.B., Esteves, I., de Martinis, B.S., Alves, M.N.R., Scandiuzzi, R.C., Hallak, J.E.C., Zuardi, A.W., et al. (2017). Protective effects of cannabidiol against seizures and neuronal death in a rat model of mesial temporal lobe epilepsy. Front. Pharmacol. 8, 1–15.Google Scholar

  • Duncan, E.J., Madonick, S.H., Parwani, A., Angrist, B., Rajan, R., Chawravorty, S., Efferen, T.R., Szilagyi, S., Stephanides, M., Chappell, P.B., et al. (2001). Clinical and sensorimotor gating effects of ketamine in normals. Neuropsychopharmacology 25, 72–83.PubMedCrossrefGoogle Scholar

  • Eggan, S.M. and Lewis, D.A. (2007). Immunocytochemical distribution of the cannabinoid CB1 receptor in the primate neocortex: a regional and laminar analysis. Cereb. Cortex 17, 175–191.PubMedGoogle Scholar

  • Ennaceur, A., Michalikova, S., Van Rensburg, R., and Chazot, P.L. (2011). MK-801 increases the baseline level of anxiety in mice introduced to a spatial memory task without prior habituation. Neuropharmacology 61, 981–991.CrossrefPubMedGoogle Scholar

  • Geyer, M. and Mansbach, R. (1989). Disruption of prepulse inhibition of acoustic startile in rats by phencyclidine and MK801. Schizophr. Res. 2, 186.CrossrefGoogle Scholar

  • Geyer, M.A., Krebs-Thomson, K., Braff, D.L., and Swerdlow, N.R. (2001). Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 156, 117–154.CrossrefPubMedGoogle Scholar

  • Giuffrida, A., Leweke, F.M., Gerth, C.W., Schreiber, D., Koethe, D., Faulhaber, J., Klosterkötter, J., and Piomelli, D. (2004). Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology 29, 2108–2114.PubMedCrossrefGoogle Scholar

  • Glass, M. (2001). The role of cannabinoids in neurodegenerative diseases. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 25, 743–765.CrossrefGoogle Scholar

  • Gomes, F.V., Issy, A.C., Ferreira, F.R., Viveros, M.-P., Del Bel, E.A., and Guimaraes, F.S. (2015). Cannabidiol attenuates sensorimotor gating disruption and molecular changes induced by chronic antagonism of NMDA receptors in mice. Int. J. Neuropsychopharmacol. 18, 1–10.Google Scholar

  • Gómez-Wong, E., Martí, M.J., Tolosa, E., and Valls-Solé, J. (1998). Sensory modulation of the blink reflex in patients with blepharospasm. Arch. Neurol. 55, 1233–1237.PubMedCrossrefGoogle Scholar

  • Gong, J.P., Onaivi, E.S., Ishiguro, H., Liu, Q.R., Tagliaferro, P.A., Brusco, A., and Uhl, G.R. (2006). Cannabinoid CB2 receptors: immunohistochemical localization in rat brain. Brain Res. 1071, 10–23.PubMedCrossrefGoogle Scholar

  • Grillon, C., Ameli, R., Charney, D.S., Krystal, J., and Braff, D. (1992). Startle gating deficits occur across prepulse intensities in schizophrenic patients. Biol. Psychiatry 32, 939–943.PubMedCrossrefGoogle Scholar

  • Gururajan, A., Taylor, D.A., and Malone, D.T. (2011). Effect of cannabidiol in a MK-801-rodent model of aspects of schizophrenia. Behav. Brain Res. 222, 299–308.CrossrefGoogle Scholar

  • Hampson, A.J., Grimaldi, M., Axelrod, J., and Wink, D. (1998). Cannabidiol and Δ9-tetrahydrocannabinol are neuroprotective antioxidants. Proc. Natl. Acad. Sci. USA 95, 8268–8273.CrossrefGoogle Scholar

  • Hoenig, K., Hochrein, A., Quednow, B.B., Maier, W., and Wagner, M. (2005). Impaired prepulse inhibition of acoustic startle in obsessive-compulsive disorder. Biol. Psychiatry 57, 1153–1158.PubMedCrossrefGoogle Scholar

  • Hurd, Y.L., Yoon, M., Manini, A.F., Hernandez, S., Olmedo, R., Ostman, M., and Jutras-Aswad, D. (2015). Early phase in the development of cannabidiol as a treatment for addiction: opioid relapse takes initial center stage. Neurotherapeutics 12, 807–815.CrossrefPubMedGoogle Scholar

  • Izquierdo, I., Orsingher, O.A., and Berardi, A.C. (1973). Effect of cannabidiol and of other Cannabis sativa compounds on hippocampal seizure discharges. Psychopharmacologia 28, 95–102.CrossrefPubMedGoogle Scholar

  • Javitt, D.C. and Lindsley, R.W. (2001). Effects of phencyclidine on prepulse inhibition of acoustic startle response in the macaque. Psychopharmacology (Berl.) 156, 165–168.PubMedCrossrefGoogle Scholar

  • Jones, N.A., Glyn, S.E., Akiyama, S., Hill, T.D.M., Hill, A.J., Weston, S.E., Burnett, M.D., Yamasaki, Y., Stephens, G.J., Whalley, B.J., et al. (2012). Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. Seizure 21, 344–352.CrossrefPubMedGoogle Scholar

  • Judd, L.L., McAdams, L., Budnick, B., and Braff, D.L. (1992). Sensory gating deficits in schizophrenia: new results. Am. J. Psychiatry 149, 488–493.CrossrefPubMedGoogle Scholar

  • Jurkus, R., Day, H.L.L., Guimaraes, F.S., Lee, J.L.C., Bertoglio, L.J., and Stevenson, C.W. (2016). Cannabidiol regulation of learned fear: implications for treating anxiety-related disorders. Front. Pharmacol. 7, 1–8.Google Scholar

  • Koch, M. (1999). The neurobiology of startle. Prog. Neurobiol. 59, 107–128.CrossrefPubMedGoogle Scholar

  • Kohl, S., Heekeren, K., Klosterkötter, J., and Kuhn, J. (2013). Prepulse inhibition in psychiatric disorders – apart from schizophrenia. J. Psychiatr. Res. 47, 445–452.PubMedCrossrefGoogle Scholar

  • Kumari, V., Soni, W., and Sharma, T. (1999). Normalization of information processing deficits in schizophrenia with clozapine. Am. J. Psychiatry 156, 1046–1051.PubMedGoogle Scholar

  • Lang, P.J., Bradley, M.M., and Cuthbert, B.N. (1990). Emotion, attention, and the startle reflex. Psychol. Rev. 97, 377–395.CrossrefPubMedGoogle Scholar

  • Lee, J.L.C., Bertoglio, L.J., Guimaraes, F.S., and Stevenson, C.W. (2017). Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders. Br. J. Pharmacol. 174, 3242–3256.PubMedCrossrefGoogle Scholar

  • Levin, R., Peres, F.F., Almeida, V., Calzavara, M.B., Zuardi, A.W., Hallak, J.E.C., Crippa, J.A.S, and Abílio, V.C. (2014). Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain. Front. Pharmacol. 5, 1–10.Google Scholar

  • Leweke, F.M., Giuffrida, A., Wurster, U., Emrich, H.M., and Piomelli, D. (1999). Elevated endogenous cannabinoids in schizophrenia. Neuroreport 10, 1665–1669.CrossrefPubMedGoogle Scholar

  • Leweke, F.M., Gerth, C.W., and Klosterkötter, J. (2004). Cannabis-associated psychosis: current status of research. CNS Drugs 18, 895–910.PubMedCrossrefGoogle Scholar

  • Leweke, F.M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C.W., Hoyer, C., Klosterkötter, J., Hellmich, M., and Koethe, D. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl. Psychiatry 2, e94.CrossrefPubMedGoogle Scholar

  • Li, L., Korngut, L.M., Frost, B.J., and Beninger, R.J. (1998). Prepulse inhibition following lesions of the inferior colliculus: prepulse intensity functions. Physiol. Behav. 65, 133–139.CrossrefPubMedGoogle Scholar

  • Linn, G.S. and Javitt, D.C. (2001). Phencyclidine (PCP)-induced deficits of prepulse inhibition in monkeys. Neuroreport 12, 117–120.PubMedCrossrefGoogle Scholar

  • Linn, G.S., Negi, S.S., Gerum, S.V., and Javitt, D.C. (2003). Reversal of phencyclidine-induced prepulse inhibition deficits by clozapine in monkeys. Psychopharmacology (Berl). 169, 234–239.CrossrefPubMedGoogle Scholar

  • Long, L.E., Malone, D.T., and Taylor, D.A. (2006). Cannabidiol reverses MK-801-induced disruption of prepulse inhibition in mice. Neuropsychopharmacology 31, 795–803.PubMedCrossrefGoogle Scholar

  • Ludewig, S., Ludewig, K., Geyer, M.a., Hell, D., and Vollenweider, F.X. (2002). Prepulse inhibition deficits in patients with panic disorder. Depress. Anxiety 15, 55–60.PubMedCrossrefGoogle Scholar

  • Ludewig, S., Geyer, M.A., Ramseier, M., Vollenweider, F.X., Rechsteiner, E., and Cattapan-Ludewig, K. (2005). Information-processing deficits and cognitive dysfunction in panic disorder. J. Psychiatry Neurosci. 30, 37–43.PubMedGoogle Scholar

  • Lutz, B., Marsicano, G., Maldonado, R., and Hillard, C.J. (2015). The endocannabinoid system in guarding against fear, anxiety and stress. Nat. Rev. Neurosci. 16, 705–718.PubMedCrossrefGoogle Scholar

  • Malfait, A.M., Gallily, R., Sumariwalla, P.F., Malik, A.S., Andreakos, E., Mechoulam, R., and Feldmann, M. (2000). The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc. Natl. Acad. Sci. USA 97, 9561–9566.CrossrefGoogle Scholar

  • Mansbach, R.S. and Geyer, M.A. (1991). Parametric determinants in pre-stimulus modification of acoustic startle: interaction with ketamine. Psychopharmacology (Berl.) 105, 162–168.PubMedCrossrefGoogle Scholar

  • Marinho, A.L.Z., Vila-Verde, C., Fogaça, M.V., and Guimarães, F.S. (2015). Effects of intra-infralimbic prefrontal cortex injections of cannabidiol in the modulation of emotional behaviors in rats: contribution of 5HT1A receptors and stressful experiences. Behav. Brain Res. 286, 49–56.PubMedCrossrefGoogle Scholar

  • Mechoulam, R., Parker, L.A., and Gallily, R. (2002). Cannabidiol: an overview of some pharmacological aspects. J. Clin. Pharmacol. 42, 11S–19S.CrossrefGoogle Scholar

  • Munro, S., Thomas, K.L., and Abu-Shaar, M. (1993). Molecular characterization of a peripheral receptor for cannabinoids. Nature 365, 61–65.PubMedCrossrefGoogle Scholar

  • Newell, K.A., Deng, C., and Huang, X.F. (2006). Increased cannabinoid receptor density in the posterior cingulate cortex in schizophrenia. Exp. Brain Res. 172, 556–560.PubMedCrossrefGoogle Scholar

  • Osborne, A.L., Solowij, N., and Weston-Green, K. (2017). A systematic review of the effect of cannabidiol on cognitive function: relevance to schizophrenia. Neurosci. Biobehav. Rev. 72, 310–324.PubMedCrossrefGoogle Scholar

  • Otnaess, M.K., Brun, V.H., Moser, M.B., and Moser, E.I. (1999). Pretraining prevents spatial learning impairment after saturation of hippocampal long-term potentiation. J. Neurosci. 19, 1–5.Google Scholar

  • Pacher, P., Bátkai, S., Kunos, G. (2006). The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 58, 389–462.CrossrefPubMedGoogle Scholar

  • Pedrazzi, J.F.C., Issy, A.C., Gomes, F.V., Guimarães, F.S., and Del-Bel, E.A. (2015). Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine. Psychopharmacology (Berl.) 232, 3057–3065.CrossrefPubMedGoogle Scholar

  • Peres, F.F., Levin, R., Almeida, V., Zuardi, W.A., Hallak, J.E., Crippa, J.A., and Abílio, V. (2016). Cannabidiol, among other cannabinoid drugs, modulates prepulse inhibition of startle in the SHR animal model: implications for schizophrenia pharmacotherapy. Front. Pharmacol. 7, 303.PubMedGoogle Scholar

  • Peres, F.F., Almeida, V., and Abilio, V.C. (2017). Cannabidiol: an overview of its antipsychotic properties. Handbook of Cannabis and Related Pathologies. V.R. Preedy, ed. Biol. Pharmacol. Diagn. Treat. 787–794.Google Scholar

  • Piomelli, D. (2003). The molecular logic of endocannabinoid signalling. Nat. Rev. Neurosci. 4, 873–884.CrossrefPubMedGoogle Scholar

  • Reijmers, L.G., Vanderheyden, P.M., and Peeters, B.W. (1995). Changes in prepulse inhibition after local administration of NMDA receptor ligands in the core region of the rat nucleus accumbens. Eur. J. Pharmacol. 272, 131–138.PubMedCrossrefGoogle Scholar

  • Ren, Y., Whittard, J., Higuera-Matas, A., Morris, C.V., and Hurd, Y.L. (2009). Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances. J. Neurosci. 29, 14764–14769.CrossrefPubMedGoogle Scholar

  • Resstel, L.B.M., Tavares, R.F., Lisboa, S.F.S., Joca, S.R.L., Corrêa, F.M.A., and Guimarães, F.S. (2009). 5-HT 1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br. J. Pharmacol. 156, 181–188.PubMedCrossrefGoogle Scholar

  • Robson, P.J., Guy, G.W., and Di Marzo, V. (2014). Cannabinoids and schizophrenia: therapeutic prospects. Curr. Pharm. Des. 20, 2194–2204.CrossrefPubMedGoogle Scholar

  • Rock, E.M., Limebeer, C.L., Petrie, G.N., Williams, L.A., Mechoulam, R., and Parker, L.A. (2017). Effect of prior foot shock stress and Δ9-tetrahydrocannabinol, cannabidiolic acid, and cannabidiol on anxiety-like responding in the light-dark emergence test in rats. Psychopharmacology (Berl.) 234, 2207–2217.CrossrefPubMedGoogle Scholar

  • Roesler, R., Vianna, M., Sant’Anna, M.K., Kuyven, C.R., Kruel, A.V, Quevedo, J., and Ferreira, M.B. (1998). Intrahippocampal infusion of the NMDA receptor antagonist AP5 impairs retention of an inhibitory avoidance task: protection from impairment by pretraining or preexposure to the task apparatus. Neurobiol. Learn. Mem. 69, 87–91.PubMedCrossrefGoogle Scholar

  • Rupniak, N.M.J., Boyce, S., Steventon, M.J., Iversen, S.D., and Marsden, C.D. (1992). Dystonia induced by combined treatment with l-dopa and MK-801 in parkinsonian monkeys. Ann. Neurol. 32, 103–105.CrossrefPubMedGoogle Scholar

  • Saletti, P.G., Maior, R.S., Hori, E., Almeida, R.M.De, Nishijo, H., and Tomaz, C. (2014). Whole-body prepulse inhibition protocol to test sensorymotor gating mechanisms in monkeys. PLoS One 9, e105551.PubMedCrossrefGoogle Scholar

  • Saletti, P.G., Maior, R.S., Hori, E., Nishijo, H., and Tomaz, C. (2015). Sensorimotor gating impairments induced by MK-801 treatment may be reduced by tolerance effect and by familiarization in monkeys. Front. Pharmacol. 6, 204.PubMedGoogle Scholar

  • Saletti, P.G., Maior, R.S., Barros, M., Nishijo, H., and Tomaz, C. (2017). Cannabidiol affects MK-801-induced changes in the PPI learned response of capuchin monkeys (Sapajus spp.). Front. Pharmacol. 8, 1–7.Google Scholar

  • Sanders, M.J. and Fanselow, M.S. (2003). Pre-training prevents context fear conditioning deficits produced by hippocampal NMDA receptor blockade. Neurobiol. Learn. Mem. 80, 123–129.PubMedCrossrefGoogle Scholar

  • Saucier, D., Hargreaves, E.L., Boon, F., Vanderwolf, C.H., and Cain, D.P. (1996). Detailed behavioral analysis of water maze acquisition under systemic NMDA or muscarinic antagonism: nonspatial pretraining eliminates spatial learning deficits. Behav. Neurosci. 110, 103–116.CrossrefPubMedGoogle Scholar

  • Schulz, B., Fendt, M., Pedersen, V., and Koch, M. (2001). Sensitization of prepulse inhibition deficits by repeated administration of dizocilpine. Psychopharmacology (Berl.) 156, 177–181.CrossrefPubMedGoogle Scholar

  • Seillier, A. and Giuffrida, A. (2009). Evaluation of NMDA receptor models of schizophrenia: divergences in the behavioral effects of sub-chronic PCP and MK-801. Behav. Brain Res. 204, 410–415.CrossrefPubMedGoogle Scholar

  • Shannon, S. and Opila-Lehman, J. (2016). Effectiveness of cannabidiol oil for pediatric anxiety and insomnia as part of posttraumatic stress disorder: a case report. Perm. J. 20, 108–111.PubMedGoogle Scholar

  • Shapiro, M.L. and O’Connor, C. (1992). N-methyl-D-aspartate receptor antagonist MK-801 and spatial memory representation: working memory is impaired in an unfamiliar environment but not in a familiar environment. Behav. Neurosci. 106, 604–612.CrossrefGoogle Scholar

  • Steinman, S.A., Ahmari, S.E., Choo, T., Kimeldorf, M.B., Feit, R., Loh, S., Risbrough, V., Geyer, M.A., Steinglass, J.E., Wall, M., et al. (2016). Prepulse inhibition deficits only in females with obsessive-compulsive disorder. Depress. Anxiety 33, 238–246.PubMedCrossrefGoogle Scholar

  • Swerdlow, N.R., Benbow, C.H., Zisook, S., Geyer, M.A., and Braff, D.L. (1993). A preliminary assessment of sensorimotor gating in patients with obsessive compulsive disorder. Biol. Psychiatry 33, 298–301.PubMedCrossrefGoogle Scholar

  • Swerdlow, N.R., Karban, B., Ploum, Y., Sharp, R., Geyer, M.A., and Eastvold, A. (2001). Tactile prepuff inhibition of startle in children with Tourette’s syndrome: in search of an “fMRI-friendly” startle paradigm. Biol. Psychiatry 50, 578–585.CrossrefPubMedGoogle Scholar

  • Swerdlow, N.R., Light, G.A., Thomas, M.A., Sprock, J., Calkins, M.E., Green, M.F., Greenwood, T.A., Gur, R.E., Gur, R.C., Lazzeroni, L.C., et al. (2017). Deficient prepulse inhibition in schizophrenia in a multi-site cohort: internal replication and extension.Schizophrenia Res. pii: S0920-9964(17)30272-4.Google Scholar

  • Tamir, I., Mechoulam, R., and Meyer, A.Y. (1980). Cannabidiol and phenytoin: a structural comparison. J. Med. Chem. 23, 220–223.CrossrefPubMedGoogle Scholar

  • Thomas, A., Baillie, G.L., Phillips, A.M., Razdan, R.K., Ross, R.A., and Pertwee, R.G. (2007). Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br. J. Pharmacol. 150, 613–623.PubMedGoogle Scholar

  • Uekita, T. and Okaichi, H. (2005). NMDA antagonist MK-801 does not interfere with the use of spatial representation in a familiar environment. Behav. Neurosci. 119, 548–556.CrossrefGoogle Scholar

  • Vigano, D., Guidali, C., Petrosino, S., Realini, N., Rubino, T., Di Marzo, V., and Parolaro, D. (2009). Involvement of the endocannabinoid system in phencyclidine-induced cognitive deficits modelling schizophrenia. Int. J. Neuropsychopharmacol. 12, 599–614.PubMedCrossrefGoogle Scholar

  • Volk, D.W. and Lewis, D.A. (2016). The role of endocannabinoid signaling in cortical inhibitory neuron dysfunction in schizophrenia. Biol. Psychiatry 79, 595–603.PubMedCrossrefGoogle Scholar

  • Warf, B. (2014). High points: an historical geography of cannabis. Geogr. Rev. 104, 414–438.CrossrefGoogle Scholar

  • Weike, A.I., Bauer, U., and Hamm, A.O. (2000). Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients. Biol. Psychiatry 47, 61–70.PubMedCrossrefGoogle Scholar

  • Winslow, J.T., Parr, L.A., and Davis, M. (2002). Acoustic startle, prepulse inhibition, and fear-potentiated startle measured in rhesus monkeys. Biol. Psychiatry. 51, 859–866.CrossrefPubMedGoogle Scholar

  • Winslow, J.T., Noble, P.L., and Davis, M. (2007). Modulation of fear-potentiated startle and vocalizations in juvenile rhesus monkeys by morphine, diazepam, and buspirone. Biol. Psychiatry 61, 389–395.PubMedCrossrefGoogle Scholar

  • Wolf, R., Dobrowolny, H., Matzke, K., Paelchen, K., Bogerts, B., and Schwegler, H. (2006). Prepulse inhibition is different in two inbred mouse strains (CPB-K and BALB/cJ) with different hippocampal NMDA receptor densities. Behav Brain Res. 166, 78–84.CrossrefPubMedGoogle Scholar

  • Xing, J. and Li, J. (2007). TRPV1 receptor mediates glutamatergic synaptic input to dorsolateral periaqueductal gray (dl-PAG) neurons. J. Neurophysiol. 97, 503–511.PubMedCrossrefGoogle Scholar

  • Zavitsanou, K., Garrick, T., and Huang, X.F. (2004). Selective antagonist [3H]SR141716A binding to cannabinoid CB1 receptors is increased in the anterior cingulate cortex in schizophrenia. Prog. Neuro-Psychopharmacology Biol. Psychiatry 28, 355–360.CrossrefGoogle Scholar

  • Zuardi, A.W., Shirakawa, I., Finkelfarb, E., and Karniol, I.G. (1982). Action of cannabidiol on the anxiety and other effects produced by delta-9-THC in normal subjects. Psychopharmacology (Berl.) 76, 245–250.PubMedCrossrefGoogle Scholar

  • Zuardi, A.W., Antunes Rodrigues, J., and Cunha, J.M. (1991). Effects of cannabidiol in animal models predictive of antipsychotic activity. Psychopharmacology (Berl.) 104, 260–264.CrossrefPubMedGoogle Scholar

  • Zuardi, A.W., Crippa, J.A., Hallak, J.E., Bhattacharyya, S., Atakan, Z., Martin-Santos, R., McGuire, P.K., and Guimarães, F.S. (2012). A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation. Curr. Pharm. Des. 18, 5131–5140.CrossrefPubMedGoogle Scholar

About the article

aCurrent address: Laboratory of Developmental Epilepsy, Saul R. Korey Department of Neurology, Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA

Received: 2017-11-26

Accepted: 2018-03-29

Published Online: 2018-05-24

Published in Print: 2018-12-19

Citation Information: Reviews in the Neurosciences, Volume 30, Issue 1, Pages 95–105, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2017-0101.

Export Citation

©2019 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Comments (0)

Please log in or register to comment.
Log in