Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine
Abstract
Rationale The information processing appears to be deficient in schizophrenia. Prepulse inhibition (PPI), which measures the inhibition of a motor response by a weak sensory event, is considered particularly useful to understand the biology of information processing in schizophrenia patients. Drugs that facilitate dopaminergic neurotransmission such as amphetamine induce PPI disruption in human and rodents. Clinical and neurobiological findings suggest that the endocannabinoid system and cannabinoids may be implicated in the pathophysiology and treatment of schizophrenia. Cannabidiol (CBD), a non-psychotomimetic constituent of the Cannabis sativa plant, has also been reported to have potential as an antipsychotic.Objective Our aim was to investigate if CBD pretreatment was able to prevent PPI disruption induced by amphetamine. Since one possible mechanism of CBD action is the facilitation of endocannabinoid-mediated neurotransmission through anandamide, we tested the effects of an anandamide hydrolysis inhibitor (URB597) in the amphetamine-induced PPI disruption.Methods Male Swiss mice were treated with CBD systemic or intra-accumbens, or URB597 (systemic) prior to amphetamine and were exposed to PPI test.Results Amphetamine (10 mg/kg) disrupted PPI while CBD (15-60 mg/kg) or URB597 (0.1-1 mg/kg) administered alone had no effect. Pretreatment with CBD attenuated the amphetamine-disruptive effects on PPI test after systemic or intra-accumbens administration. Similar effects were also found with the inhibitor of anandamide hydrolysis.Conclusion These results corroborate findings indicating that CBD induces antipsychotic-like effects. In addition, they pointed to the nucleus accumbens as a possible site of these effects. The increase of anandamide availability may be enrolled in the CBD effects.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CBD is able to decrease hyperlocomotion and pre-pulse inhibition (PPI) impairment induced by amphetamine in both mice and rats.
“Later, we showed that CBD is also able to decrease hyperlocomotion and pre-pulse inhibition (PPI) impairment induced by amphetamine in both mice and rats (67, 69) (Table 2).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [69]
Cites
The Dopamine Hypothesis of Schizophrenia: Version III--The Final Common Pathway
Howes, O. D., & Kapur, S. (2009) · Schizophrenia Bulletin · doi:10.1093/schbul/sbp006 · Cited by 2,693 · see citing works
Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide
Zygmunt, P. M., Petersson, J., Andersson, D. A., Chuang, H.-H., Sørgård, M., Di Marzo, V., Julius, D., & Högestätt, E. D. (1999) · Nature · doi:10.1038/22761 · Cited by 2,142 · see citing works
Pertwee, R. G. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707442 · Cited by 1,953 · see citing works
Bunney, W. E., Hippius, H., Laakmann, G., & Schmauß, M. (1990) · Springer eBooks · doi:10.1007/978-3-642-74034-3 · Cited by 1,523 · see citing works
Geyer, M. A., Krebs-Thomson, K., Braff, D. L., & Swerdlow, N. R. (2001) · Psychopharmacology · doi:10.1007/s002130100811 · Cited by 1,484 · see citing works
Bisogno, T., Hanuš, L., PETROCELLIS, L. D., Tchilibon, S., Ponde, D. E., Brandi, I., Moriello, A. S., Davis, J. B., Mechoulam, R., & Marzo, V. D. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704327 · Cited by 1,315 · see citing works
Sensorimotor Gating and Schizophrenia
Braff, D. L. (1990) · Archives of General Psychiatry · doi:10.1001/archpsyc.1990.01810140081011 · Cited by 1,312 · see citing works
Koch, M. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00098-7 · Cited by 1,287 · see citing works
Prestimulus Effects on Human Startle Reflex in Normals and Schizophrenics
BRAFF, D. L., Stone, C., Callaway, E., Geyer, M. A., Glick, I. D., & Bali, L. (1978) · Psychophysiology · doi:10.1111/j.1469-8986.1978.tb01390.x · Cited by 1,171 · see citing works
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C. W., Hoyer, C., Klosterkötter, J., Hellmich, M., & Koethe, D. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.15 · Cited by 1,059 · see citing works
Swerdlow, N. R., Geyer, M. A., & BRAFF, D. L. (2001) · Psychopharmacology · doi:10.1007/s002130100799 · Cited by 1,053 · see citing works
Gating and Habituation of the Startle Reflex in Schizophrenic Patients
Braff, D. L. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820030038005 · Cited by 1,027 · see citing works
Atypical antipsychotics: Mechanism of action
Seeman, P. (2002) · The Canadian Journal of Psychiatry · doi:10.1177/070674370204700106 · Cited by 899 · see citing works
Agonistic properties of cannabidiol at 5-HT1a receptors
Russo, E. B., Burnett, A., Hall, B., & Parker, K. K. (2005) · Neurochemical Research · doi:10.1007/s11064-005-6978-1 · Cited by 878 · see citing works
Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb
Izzo, A. A., Borrelli, F., Capasso, R., Marzo, V. D., & Mechoulam, R. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.07.006 · Cited by 851 · see citing works
Assessing the Validity of an Animal Model of Deficient Sensorimotor Gating in Schizophrenic Patients
Swerdlow, N. R. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950020063007 · Cited by 708 · see citing works
The Role of Serotonin in Antipsychotic Drug Action
Meltzer, H. M. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00046-9 · Cited by 664 · see citing works
To Model a Psychiatric Disorder in Animals Schizophrenia As a Reality Test
Lipska, B. K. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00137-8 · Cited by 650 · see citing works
Action of cannabidiol on the anxiety and other effects produced by ?9-THC in normal subjects
Zuardi, A. W., Shirakawa, I., Finkelfarb, E., & Karniol, I. G. (1982) · Psychopharmacology · doi:10.1007/bf00432554 · Cited by 608 · see citing works
Dopaminergic stimulation disrupts sensorimotor gating in the rat
Mansbach, R. S., Geyer, M. A., & BRAFF, D. L. (1988) · Psychopharmacology · doi:10.1007/bf00212846 · Cited by 608 · see citing works
Mechoulam, R., & Shvo, Y. (1963) · Tetrahedron · doi:10.1016/0040-4020(63)85022-x · Cited by 486 · see citing works
Giuffrida, A., Leweke, F. M., Gerth, C. W., Schreiber, D., Koethe, D., Faulhaber, J., Klosterkötter, J., & Piomelli, D. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300558 · Cited by 481 · see citing works
Campos, A. C., Moreira, F. A., Gomes, F. V., Del Bel, E. A., & Guimarães, F. S. (2012) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2011.0389 · Cited by 475 · see citing works
Self-citationCannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment
Englund, A., Morrison, P. D., Nottage, J. F., Hague, D., Kane, F., Bonaccorso, S., Stone, J. M., Reichenberg, A., Brenneisen, R., Holt, D., et al. (2012) · Journal of Psychopharmacology · doi:10.1177/0269881112460109 · Cited by 462 · see citing works
Pharmacological Profile of the Selective FAAH Inhibitor KDS-4103 (URB597)
Piomelli, D., Tarzia, G., Duranti, A., Tontini, A., Mor, M., Compton, T. R., Dasse, O. A., Monaghan, E. P., Parrott, J. A., & Putman, D. (2006) · CNS Drug Reviews · doi:10.1111/j.1527-3458.2006.00021.x · Cited by 445 · see citing works
Swerdlow, N. R., BRAFF, D. L., & Geyer, M. A. (2000) · Behavioural Pharmacology · doi:10.1097/00008877-200006000-00002 · Cited by 392 · see citing works
Symptom Correlates of Prepulse Inhibition Deficits in Male Schizophrenic Patients
BRAFF, D. L., Swerdlow, N. R., & Geyer, M. A. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.4.596 · Cited by 366 · see citing works
Campos, A. C., & Guimarães, F. S. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1168-x · Cited by 364 · see citing works
Self-citationCentral dopamine hyperactivity in rats mimics abnormal acoustic startle response in schizophrenics
Swerdlow, N. R., BRAFF, D. L., Geyer, M. A., & Koob, G. F. (1986) · Biological Psychiatry · doi:10.1016/0006-3223(86)90005-3 · Cited by 341 · see citing works
Campos, A. C., Ortega, Z., Palazuelos, J., Fogaça, M. V., Aguiar, D. C., Díaz-Alonso, J., Ortega-Gutiérrez, S., Vázquez-Villa, H., Moreira, F. A., Guzmán, M., et al. (2013) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712001502 · Cited by 313 · see citing works
Self-citationMoore, H., West, A. R., & Grace, A. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00078-5 · Cited by 257 · see citing works
Comparative Receptor Binding Analyses of Cannabinoid Agonists and Antagonists
Thomas, B. F., Gilliam, A. F., Burch, D. F., Roche, M. J., & Seltzman, H. H. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37365-3 · Cited by 242 · see citing works
Reversal of Dopamine D2Receptor Responses by an Anandamide Transport Inhibitor
Beltramo, M., de Fonseca, F. R., Navarro, M. A., Calignano, A., Gorriti, M. Á., Grammatikopoulos, G., Sadile, A. G., Giuffrida, A., & Piomelli, D. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-09-03401.2000 · Cited by 232 · see citing works
Mishima, K., Hayakawa, K., Abe, K., Ikeda, T., Egashira, N., Iwasaki, K., & Fujiwara, M. (2005) · Stroke · doi:10.1161/01.str.0000163083.59201.34 · Cited by 225 · see citing works
Waldo Zuardi, A., Alexandre S. Crippa, J., E.C. Hallak, J., Bhattacharyya, S., Atakan, Z., Martin-Santos, R., K. McGuire, P., & Silveira Guimaraes, F. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212802884681 · Cited by 222 · see citing works
Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients
Weike, A. I., Bauer, U., & Hamm, A. O. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00229-2 · Cited by 206 · see citing works
Cannabidiol inhibits the hyperlocomotion induced by psychotomimetic drugs in mice
Moreira, F. A., & Guimarães, F. S. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.02.040 · Cited by 206 · see citing works
Self-citationSwerdlow, N. R., BRAFF, D. L., & Geyer, M. A. (1990) · Brain Research · doi:10.1016/0006-8993(90)91754-5 · Cited by 206 · see citing works
Environmental animal models for sensorimotor gating deficiencies in schizophrenia: a review
Weiss, I. C., & Feldon, J. (2001) · Psychopharmacology · doi:10.1007/s002130100800 · Cited by 194 · see citing works
Effects of cannabidiol in animal models predictive of antipsychotic activity
Zuardi, A. W., Antunes Rodrigues, J., & Cunha, J. M. (1991) · Psychopharmacology · doi:10.1007/bf02244189 · Cited by 191 · see citing works
Petitet, F., Jeantaud, B., Reibaud, M., Impérato, A., & Dubroeucq, M. C. (1998) · Life Sciences · doi:10.1016/s0024-3205(98)00238-0 · Cited by 180 · see citing works
Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice
Long, L. E., Malone, D. T., & TAYLOR, D. A. H. B. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300838 · Cited by 173 · see citing works
Kim‐Mitsuyama, S., Yamamoto, E., Tanaka, T., Zhan, Y., Izumi, Y., Izumiya, Y., Ioroi, T., Wanibuchi, H., & Iwao, H. (2005) · Stroke · doi:10.1161/01.str.0000163084.16505.e3 · Cited by 173 · see citing works
Swerdlow, N. R., Caine, S. B., & Geyer, M. A. (1992) · Psychopharmacology · doi:10.1007/bf02245306 · Cited by 157 · see citing works
Martín, A. B. B., Fernández‐Espejo, E., Ferrer, B., Gorriti, M. Á., Bilbao, A., Navarro, M. A., de Fonseca, F. R., & Moratalla, R. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301558 · Cited by 155 · see citing works
Peng, R. Y., Mansbach, R. S., BRAFF, D. L., & Geyer, M. A. (1990) · PubMed · Cited by 137 · see citing works
Role of dopamine in prepulse inhibition of acoustic startle
Zhang, J., Forkstam, C., Engel, J., & Svensson, L. (2000) · Psychopharmacology · doi:10.1007/s002130000369 · Cited by 129 · see citing works
Limbic/mesolimbic connections and the pathogenesis of schizophrenia
Csernansky, J. G., Murphy, G. M., & Faustman, W. O. (1991) · Biological Psychiatry · doi:10.1016/0006-3223(91)90295-w · Cited by 120 · see citing works
Extrapyramidal side effects are unacceptable
Kane, J. M. (2001) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(01)00109-2 · Cited by 110 · see citing works
Cannabidiol as a potential treatment for psychosis
Schubart, C. D., Sommer, I. E., Fusar‐Poli, P., de Witte, L. D., Kahn, R. S., & Boks, M. P. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.11.002 · Cited by 100 · see citing works
Angiotensin, LDL peroxidation and atherosclerosis
Keidar, S. (1998) · Life Sciences · doi:10.1016/s0024-3205(98)00014-9 · Cited by 93 · see citing works
Effect of cannabidiol in a MK-801-rodent model of aspects of Schizophrenia
Gururajan, A., TAYLOR, D. A. H. B., & Malone, D. T. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.03.053 · Cited by 89 · see citing works
Cannabidiol increases Fos expression in the nucleus accumbens but not in the dorsal striatum
Guimaraes, V. H. (2004) · Life Sciences · doi:10.1016/j.lfs.2004.01.015 · Cited by 75 · see citing works
Carlson, S., & Willott, J. F. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.79.5.2603 · Cited by 75 · see citing works
Levin, R. R., Peres, F. F., de Almeida, V., Calzavara, M. B., Zuardi, A. W., Hallak, J. E. C., Crippa, J. A. S., & Abílio, V. C. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00010 · Cited by 74 · see citing works
Levin, R. R., Calzavara, M. B., Santos, C. M., Medrano, W. A., Niigaki, S. T., & Abílio, V. C. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.06.003 · Cited by 71 · see citing works
Accumbens D2 modulation of sensorimotor gating in rats: Assessing anatomical localization
Wan, F. J., Geyer, M. A., & Swerdlow, N. R. (1994) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(94)90470-7 · Cited by 70 · see citing works
Facilitation of CB1 receptor-mediated neurotransmission decreases marble burying behavior in mice
Gomes, F. V., Casarotto, P. C., Resstel, L. B. M., & Guimarães, F. S. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.11.027 · Cited by 69 · see citing works
Self-citationLack of phencyclidine-induced effects in mice with reduced neuronal nitric oxide synthase
Bird, D., Bujas‐Bobanovic, M., Robertson, H. A., et al. (2001) · Psychopharmacology · doi:10.1007/s002130100705 · Cited by 49 · see citing works
Rojas, M. J. L., Galeano, P., Suárez, J., Araos, P. F., Santín, L. J., de Fonseca, F. R., & Blanco, E. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712000569 · Cited by 38 · see citing works
Nitric oxide modulation of methylphenidate-induced disruption of prepulse inhibition in Swiss mice
Issy, A. C., Salum, C., & Bel, E. A. D. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.08.003 · Cited by 36 · see citing works
Self-citationElevated neuronal nitric oxide synthase expression in chronic haloperidol-treated rats
Lau, Y. (2003) · Neuropharmacology · doi:10.1016/s0028-3908(03)00314-9 · Cited by 35 · see citing works
Flood, D. G., Zuvich, E., Marino, M. J., & Ga̧sior, M. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1901-0 · Cited by 11 · see citing works
Issy, A. C., & Bel, E. A. D. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.12.042 · Cited by 9 · see citing works
Self-citationZuardi, A. W., Guimarães, F. S., Hallak, J. E. C., & Crippa, J. A. S. (2011) · Expert Review of Neurotherapeutics · doi:10.1586/ern.11.89 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age
Crippa, J. A., Guimarães, F. S., Campos, A. C., & Zuardi, A. W. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02009 · Cited by 308 · see citing works
Self-citationGarcía-Gutiérrez, M. S., Navarrete, F., Gasparyan, A., Austrich-Olivares, A., Sala, F., & Manzanares, J. (2020) · Biomolecules · doi:10.3390/biom10111575 · Cited by 306 · see citing works
Campos, A. C., Fogaça, M. V., Scarante, F. F., Joca, S. R. L., Sales, A. J., Gomes, F. V., Sonego, A. B., Rodrigues, N. S., Galve-Roperh, I., & Guimarães, F. S. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00269 · Cited by 175 · see citing works
Self-citation
- Authors
- Pedrazzi, J. F. C., Issy, A. C., Gomes, F. V., Guimarães, F. S., & Del-Bel, E. A.
- Affiliations
- Universidade de São Paulo (BR)
- Corresponding author
- Del-Bel, E. A.
- Venue
- Psychopharmacology
- Published
- 2015-05-06
- Volume
- 232
- Issue
- 16
- Pages
- 3057-3065
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W802881471
- Cited by
- 76
- References
- 65
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 10 · 2020: 7 · 2019: 9 · 2018: 9 · 2017: 10 · 2016: 7
- FWCI
- 6.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universidade de São Paulo
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Keywords
- cannabidiol, prepulse inhibition, amphetamine, schizophrenia, endocannabinoid system, anandamide, URB597, nucleus accumbens, antipsychotic effects, dopamine signaling, information processing deficits
- MeSH terms
- Amphetamine, Animals, Benzamides, Cannabidiol, Carbamates, Inhibition, Psychological, Male, Nucleus Accumbens, Reflex, Startle, Mice, Prepulse Inhibition
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
