An integrative overview of the cannabinergic system and mental health

Oscar E. Prospéro García, Pavel E. Rueda Orozco, Octavio Amancio Belmont, Alejandra E. Ruiz Contreras, Mónica Méndez Díaz

DOI: https://doi.org/10.17711/SM.0185-3325.2017.015

Abstract


Background. The endocannabinoid system (eCBs) is one of the modulatory systems widely expressed in the brain. It consists of receptors expressed in the cytoplasmic (CB1 and CB2), the mitochondrial membrane (CB1), and the endogenous ligands known as endocannabinoids, such as anandamide, 2AG and oleamide. CB1 has been found in excitatory and inhibitory neurons in the pre- and post-synaptic membranes. It is expressed in several brain areas such as the hippocampus, dorsal, and ventral striatum, amygdala and prefrontal cortex. The eCBs has been involved in the regulation of learning and memory, mood, energy balance, sleep, and drug addiction.

Objective. Integrate existing information about the eCBs and its role in brain function and mental health.

Method. Review of the information of basic and clinical relevance obtained from indexed scientific journals (PubMed/Medline, Scopus).

Results. Basic and clinical research on eCBs related to central nervous system function is described.

Discussion and conclusion. At present, the study of eCBs is of importance. The development of drugs that affect this system may be clinically useful to control different debilitating diseases. This is an area of interest to the scientific community and health care providers.


Keywords


Cannabinoid system; endocannabinoids; cannabinoid receptor 1; cannabinoid receptor 2; mental health

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References


Alger, B. E. (2002). Retrograde signaling in the regulation of synaptic transmission: Focus on endocannabinoids. Progress in Neurobiology, 68(4), 247-286. doi:10.1016/S0301-0082(02)00080-1

Arenos, J. D., Musty, R. E., & Bucci, D. J. (2006). Blockade of cannabinoid CB1 receptors alters contextual learning and memory. European Journal of Pharmacology, 539(3), 177-183. doi:10.1016/j.ejphar.2006.04.017

Azad, S. C., Eder, M., Marcicano, G., Lutz, B., Zieglgänsberger, W., & Rammes, G. (2003). Activation of the Cannabinoid Receptor Type 1 Decreases Glutamatergic and GABAergic Synaptic Transmission in the Lateral Amygdala of the Mouse. Learning & Memory, 10(2), 116-128. doi:10.1101/lm.53303

Berding, G., Schneider, U., Gielow, P., Buchert, R., Donnerstag, F., Brandau, W., … & Müller-Vahl, K. (2006). Feasibility of Central Cannabinoid CB1 Receptor Imaging with [124I]AM281 PET Demonstrated in a Schizophrenic Patient. Psychiatry Research-Neuroimaging, 147(2), 249-256. doi:10.1016/j.pscychresns.2006.02.002

Bisogno, T., & Maccarrone, M. (2014). Endocannabinoid signaling and its regulation by nutrients. BioFactors, 40(4), 373-380. doi:10.1002/biof.1167

Bisogno, T., Ligresti, A., & di Marzo, V. (2005). The endocannabinoid signalling system: Biochemical aspects. Pharmacology, Biochemistry and Behavior, 81, 224-238. doi:10.1016/j.pbb.2005.01.027

Burns, H. D., Van Laere, K., Sanabria-Bohórquez, S., Hamill, T. G., Bormans, G., Eng, W. S., … & Hargreaves, R. J. (2007). [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proceedings of the National Academy of Sciences of the United States of America, 104(23), 9800-9805. doi:10.1073/pnas.0703472104

Cadas, H., di Tomaso, E., & Piomelli, D. (1997). Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain. Journal of Neuroscience, 17(4), 1226-1242.

Carlson, G., Wang, Y., & Alger, B. E. (2002). Endocannabinoids facilitate the induction of LTP in the hippocampus. Nature Neuroscience, 5(8), 723-724. doi:10.1038/nn879

Ceccarini, J., Kuepper, R., Kemels, D., van Os, J., Henquet, C., & van Laere, K. (2015). [18F]MK-9470 PET measurement of cannabinoid CB1 receptor availability in chronic cannabis users. Addiction Biology, 20(2), 357-367. doi:10.1111/adb.12116

Chen, J., Marmur, R., Pulles, A., Paredes, W., & Gardner, E. L. (1993). Ventral tegmental microinjection of delta9-tetrahydrocannabinol enhances ventral tegmental somatodendritic dopamine levels but not forebrain dopamine levels: evidence for local neural action by marijuana’s psychoactive ingredient. Brain Research, 621(1), 65-70. doi:10.1016/0006-8993(93)90298-2

Comings, D. E. (1998). Polygenic inheritance and micro/minisatellites. Molecular Psychiatry, 3, 21-31.

Cravatt, B. F., Saghatelian, A., Hawkins, E. G., Clement, A. B., Bracey, M. H., & Lichtman, A. H. (2004). Functional disassociation of the central and peripheral fatty acid amide signaling systems. Proceedings of the National Academy of Sciences of the United States of America, 101(29), 10821-10826. doi:10.1073/pnas.0401292101

de Marchi, N. de, Petrocellis, L. de, Orlando, P., Daniele, F., Fezza, F., & di Marzo, V. (2003). Endocannabinoid signalling in the blood of patients with schizophrenia. Lipids in Health and Disease, 9(2), 5.

Devane, W. A., Dysarz, F. A., Johnson, M. R., Melvin, L. S., & Howlett, A. C. (1988). Determination and characterization of a cannabinoid receptor in rat brain. Molecular Pharmacology, 34(5), 605-613.

Devane, W. A., Hanus, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., … & Mechoulam, R. (1992). Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 258(5090), 1946-1949. doi:10.1126/science.1470919

Egertová, M., Giang, D. K., Cravatt, B. F., & Elphick, M. R. (1998). A new perspective on cannabinoid signalling: complementary localization of fatty acid amide hydrolase and the CB1 receptor in rat brain. Proceedings. Biological Sciences/ The Royal Society, 265(1410), 2081-2085. doi:10.1098/rspb.1998.0543

Eggan, S., Hashimoto, T., & Lewis, D. (2008). Reduced cortical cannabinoid 1 receptor messenger RNA and protein expression in schizophrenia. Psychiatry Research-Neuroimaging, 65(7), 772-784.

Ferdinand, R. F., Sondeijker, F., van der Ende, J., Selten, J. P., Huizink, A., & Verhulst, F. C. (2005). Cannabis use predicts future psychotic symptoms, and vice versa. Addiction, 100(5), 612-618. doi:10.1111/j.1360-0443.2005.01070.x

Gaoni, Y., & Mechoulam, R. (1971). The isolation and structure of delta-1-tetrahydrocannabinol and other neutral cannabinoids from hashish. Journal of the American Chemical Society, 93(1), 217-224. doi:10.1021/ja00730a036

Gerdeman, G., & Lovinger, D. M. (2008). CB1 Cannabinoid receptor inhibits synaptic release of glutamate in rat dorsolateral striatum. Journal of Neurophysiology, 85(1), 468-471.

Gessa, G. L., Casu, M. A., Carta, G., & Mascia, M. S. (1998). Cannabinoids decrease acetylcholine release in the medial-prefrontal cortex and hippocampus, reversal by SR 141716A. European Journal of Pharmacology, 355(2), 119-124. doi:10.1016/S0014-2999(98)00486-5

Giuffrida, A., Leweke, F. M., Gerth, C. W., Schreiber, D., Koethe, D., Faulhaber, J., … & Piomelli, D. (2004). Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology, 29(11), 2108-2114. doi:10.1038/sj.npp.1300558

Giuffrida, A., Parsons, L. H., Kerr, T. M., de Fonseca, F. R., Navarro, M., & Piomelli, D. (1999). Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nature Neuroscience, 2(4), 26-30.

Hernández-Tristán, R., Arévalo, C., Canals, S., & Leret, M. L. (2000). The effects of acute treatment with Δ9-THC on exploratory behaviour and memory in the rat. Journal of Physiology and Biochemistry, 56(1), 17-24. doi:10.1007/BF03179772

Heyser, C. J., Hampson, R. E., & Deadwyler, S. A. (1993). Effects of delta-9 tetrahydrocannabinol on delayed match to sample performance in rats: alternations in short-term memory associated with changes in task specific firing of hippocampal cells. Journal of Pharmacology and Experimental Therapeutic, 264(1), 294-307.

Howlett, A. C., Breivogel, C. S., Childers, S. R., Deadwyler, S. A., Hampson, R. E., & Porrino, L. J. (2004). Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology, 47(Suppl. 1), 345-358. doi:10.1016/j.neuropharm.2004.07.030

Jentsch, J. D., Andrusiak, E., Tran, A., Bowers Jr., M. B., & Roth, R. H. (1997). Delta9-tetrahydrocannabinol increases prefrontal cortical catecholaminergic utilization and impairs spatial working memory in the rat: blockade of dopaminergic effects with HA966. Neuropsychopharmacology, 16(6), 426-432.

Katona, I., Rancz, E. A., Acsády, L., Ledent, C., Mackie, K., Hajos, N., & Freund, T. F. (2001). Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission. The Journal of Neuroscience, 21(23), 9506-9518. doi:21/23/9506 [pii]

Katona, I., Sperlágh, B., Maglóczky, Z., Sántha, E., Köfalvi, A., Czirják, S., … & Freund, T. F. (2000). GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus. Neuroscience, 100(4), 797-804. doi:10.1016/S0306-4522(00)00286-4

Katona, I., Urbán, G. M., Wallace, M., Ledent, C., Jung, K., Piomelli, D., … & Freund, T. F. (2006). Molecular composition of the endocannabinoid system at glutamatergic synapses. Journal of Neuroscience, 26(21), 5628-5637. doi:10.1523/JNEUROSCI.0309-06.2006

Kendall, D. A., & Yudowski, G. A. (2017). Cannabinoid receptors in the central nervous system: their signaling and roles in disease. Frontiers in Cellular Neuroscience, 10, 294. doi:10.3389/fncel.2016.00294

Khaspekov, L. G., Verca, M. S. B., Frumkina, L. E., Hermann, H., Marsicano, G., & Lutz, B. (2004). Involvement of brain-derived neurotrophic factor in cannabinoid receptor-dependent protection against excitotoxicity. European Journal of Neuroscience, 19(7), 1691-1698. doi:10.1111/j.1460-9568.2004.03285.x

Leweke, F. M., Giuffrida, A., Wurster, U., Emrich, H. M., & Piomelli, D. (1999). Elevated endogenous cannabinoids in schizophrenia. Neuroreport, 10(8), 1665-1669. doi:10.1097/00001756-199906030-00008

Lichtman, A. H., Dimen, K. R., & Martin, B. R. (1995). Systemic or intrahippocampal cannabinoid administration impairs spatial memory in rats. Psychopharmacology, 119(3), 282-290. doi:10.1007/BF02246292

Maccarrone, M., & Finazzi-Agro, A. (2004). Anandamide hydrolase: a guardian angel of human reproduction? Trends in Pharmacological Sciences, 25(7), 353-357. doi:10.1016/j.tips.2004.05.002

Marichal-Cancino, B., Fajardo-Valdéz, A., Ruiz-Contreras, A., Méndez-Díaz, M., & Prospéro-García, O. (2016). Advances in the physiology of GPR55 in the central nervous system. Current Neuropharmacology, 14(999), 1-1. doi:10.2174/1570159X14666160729155441

Marsicano, G., Wotjak, C. T., Azad, S. C., Bisogno, T., Rammes, G., Cascio, M. G., … & Lutz, B. (2002). The endogenous cannabinoid system controls extinction of aversive memories. Nature, 418(6897), 530-534. doi:10.1038/nature00839

Martínez-Gras, I., Hoenicka, J., Ponce, G., Rodríguez-Jiménez, R., Jiménez-Arriero, M. A., Pérez-Hernandez, E., … & Rubio, G. (2006). (AAT) n repeat in the cannabinoid receptor gene, CNR1: association with schizophrenia in a Spanish population. European Archives of Psychiatry and Clinical Neuroscience, 256(7), 437-441.

Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A C., & Bonner, T. I. (1990). Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature, 346(6284), 561-564. doi:10.1038/346561a0

Meier, M. H., Caspi, A., Ambler, A., Harrington, H., Houts, R., Keefe, R. S. E., … & Moffitt, T. E. (2012). Persistent cannabis users show neuropsychological decline from childhood to midlife. Proceedings of the National Academy of Sciences, 109(40), E2657-E2664. doi:10.1073/pnas.1206820109

Muñoz-Arenas, G., Paz-Bermúdez, F., Báez-Cordero, A., Caballero-Florán, R., González-Hernández, B., Florán, B., & Limón, I. D. (2015). Cannabinoid CB1 receptors activation and coactivation with D2 receptors modulate GABAergic neurotransmission in the globus pallidus and increase motor asymmetry. Synapse, 69(3), 103-114. doi:10.1002/syn.21796

Munro, S., Thomas, K. L., & Abu-Shaar, M. (1993). Molecular characterization of peripheral receptor for cannabinoids. Nature, 365(6441), 61.

Ohno-Shosaku, T., Maejima, T., & Kano, M. (2001). Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals. Neuron, 29(3), 729-738. doi:10.1016/S0896-6273(01)00247-1

Palkovits, M., Harvey-White, J., Liu, J., Kovacs, Z. S., Bobest, M., Lovas, G., … & Kunos, G. (2008). Regional distribution and effects of postmortal delay on endocannabinoid content of the human brain. Neuroscience, 152(4), 1032-1039. doi:10.1016/j.neuroscience.2008.01.034

Pamplona, F., & Takahashi, T. (2006). WIN 55212-2 impairs contextual fear conditioning through the activation of CB1 cannabinoid receptors. Neuroscience Letters, 397(1-2), 88-92. doi:10.1016/j.neulet.2005.12.026

Pamplona, F., Prediger, R., Pandolfo, P., & Takahashi, R. (2006). The cannabinoid receptor agonist WIN 55,212-2 facilitates the extinction of contextual fear memory and spatial memory in rats. Psychopharmacology, 188(4), 641-649. doi:10.1007/s00213-006-0514-0

Pettit, D. A., Harrison, M. P., Olson, J. M., Spencer, R. F., & Cabral, G. A. (1998). Immunohistochemical localization of the neural cannabinoid receptor in rat brain. Journal of Neuroscience Research, 51(3), 391-402.

Piomelli, D. (2003). The molecular logic of endocannabinoid signalling. Nature Reviews Neuroscience, 4(11), 873-884.

Pistis, M., Ferraro, L., Pira, L., Flore, G., Tanganelli, S., Luigi, G., & Devoto, P. (2002). D9-Tetrahydrocannabinol decreases extracellular GABA and increases extracellular glutamate and dopamine levels in the rat prefrontal cortex: An in vivo microdialysis study. Brain Research, 948(1), 155-158.

Rueda-Orozco, P. E., Montes-Rodriguez, C. J., Soria-Gomez, E., Méndez-Díaz, M., & Prospéro-García, O. (2008). Impairment of endocannabinoids activity in the dorsolateral striatum delays extinction of behavior in a procedural memory task in rats. Neuropharmacology, 55(1), 55-62.

Ruiz, A. E., Carrillo, K., Gómez, N., Vadillo, F., Hernández, S., Carnevale, A., … & Prospéro-García, O. (2013). Working memory performance in young adults is associated to the AATn polymorphism of the CNR1 gene. Behavioural Brain Research, 236(1), 62-66. doi:10.1016/j.bbr.2012.08.031

Ruiz-Contreras, A., Delgado-Herrera, M., García-Vaca, P., Almeida-Rosas, G., Soria-Rodríguez, G., Soriano-Bautista, A., … & Prospéro-García, O. (2011). Involvement of the AATn polymorphism of the CNR1 gene in the efficiency of procedural learning in humans. Neuroscience Letters, 494(3), 202-206. doi:10.1016/j.neulet.2011.03.013

Soria, E., Matias, I., Rueda, P. E., Cisneros, M., Petrosino, S., Navarro, L., … & Prospéro, O. (2007). Pharmacological enhancement of the endocannabinoid system in the nucleus accumbens shell stimulates food intake and increases c-Fos expression in the hypothalamus. British Journal of Pharmacology, 151(7), 1109-1116. doi:10.1038/sj.bjp.0707313

Takahashi, R. N., Pamplona, F. A., & Fernandes, M. S. (2005). The cannabinoid antagonist SR141716A facilitates memory acquisition and consolidation in the mouse elevated T-maze. Neuroscience Letters, 380(3), 270-275. doi:10.1016/j.neulet.2005.01.049

Tsou, K., Brown, S., Sañudo-Peña, M., Mackie, K., & Walker, J. (1998). Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience, 83(2), 393-411. doi:10.1016/S0306-4522(97)00436-3

Ujike, H., Takaki, M., Nakata, K., Tanaka, Y., Takeda, T., Kodama, M., … & Kuroda, S. (2002). CNR1, central cannabinoid receptor gene, associated with susceptibility to hebephrenic schizophrenia. Molecular Psychiatry, 7(5), 515-518.

van Laere, K., Koole, M., Sanabria Bohorquez, S. M., Goffin, K., Guenther, I., Belanger, M. J., … & Burns, H. D. (2008). Whole-body biodistribution and radiation dosimetry of the human cannabinoid type-1 receptor ligand 18F-MK-9470 in healthy subjects. Journal of Nuclear Medicine, 49(3), 439-445. doi:10.2967/jnumed.107.047290

Varvel, S. A., Wise, L. E., Niyuhire, F., Cravatt, B. F., & Lichtman, A. H. (2007). Inhibition of fatty-acid amide hydrolase accelerates acquisition and extinction rates in a spatial memory task. Neuropsychopharmacology, 32(5), 1032-1041. doi:1301224 [pii]r10.1038/sj.npp.1301224

Vinod, K. Y., & Hungund, B. L. (2005). Endocannabinoid lipids and mediated system: implications for alcoholism and neuropsychiatric disorders. Life Sciences, 77(14), 1569-1583. doi:10.1016/j.lfs.2005.05.041

World Health Organization. (2016). The health and social effects of nonmedical cannabis use. Geneva.

Xi, Z.-X., Peng, X.-Q., Li, X., Song, R., Zhang, H., Liu, Q.-R., … & Gardner, E. L. (2011). Brain cannabinoid CB(2) receptors modulate cocaine’s actions in mice. Nature Neuroscience, 14(9), 1160-1166. doi:10.1038/nn.2874

Yeh, M. L., Selvam, R. & Levine, E. S. (2017). BDNF-induced endocannabinoid release modulates neocortical glutamatergic neurotransmission. Synapse. doi:10.1002/syn.21962

Zavitsanou, K., Garrick, T., & Huang, X. F. (2004). Selective antagonist [3H]SR141716A binding to cannabinoid cb1 receptors is increased in the anterior cingulate cortex in schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 28(2), 355-360. doi:10.1016/j.pnpbp.2003.11.005