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Current Neuropharmacology

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

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Review Article

The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders

Author(s): Sari Goldstein Ferber, Dvora Namdar, Danielle Hen-Shoval, Gilad Eger, Hinanit Koltai, Gal Shoval*, Liat Shbiro and Aron Weller

Volume 18, Issue 2, 2020

Page: [87 - 96] Pages: 10

DOI: 10.2174/1570159X17666190903103923

Price: $65

Abstract

Mood disorders are the most prevalent mental conditions encountered in psychiatric practice. Numerous patients suffering from mood disorders present with treatment-resistant forms of depression, co-morbid anxiety, other psychiatric disorders and bipolar disorders. Standardized essential oils (such as that of Lavender officinalis) have been shown to exert clinical efficacy in treating anxiety disorders. As endocannabinoids are suggested to play an important role in major depression, generalized anxiety and bipolar disorders, Cannabis sativa was suggested for their treatment. The endocannabinoid system is widely distributed throughout the body including the brain, modulating many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. CB1 and CB2 receptors primarily serve as the binding sites for endocannabinoids as well as for phytocannabinoids, produced by cannabis inflorescences. However, ‘cannabis’ is not a single compound product but is known for its complicated molecular profile, producing a plethora of phytocannabinoids alongside a vast array of terpenes. Thus, the “entourage effect” is the suggested positive contribution derived from the addition of terpenes to cannabinoids. Here, we review the literature on the effects of cannabinoids and discuss the possibility of enhancing cannabinoid activity on psychiatric symptoms by the addition of terpenes and terpenoids. Possible underlying mechanisms for the anti-depressant and anxiolytic effects are reviewed. These natural products may be an important potential source for new medications for the treatment of mood and anxiety disorders.

Keywords: Cannabidiol, terpenes, mood disorders, depression, anxiety, entourage.

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[1]
Bondy, B. Pathophysiology of depression and mechanisms of treatment. Dialogues Clin. Neurosci., 2002, 4(1), 7-20.
[2]
Portman, M.E.; Riskind, J.H.; Rector, N.A. Generalized anxiety disorder.Encycl. Hum. Behav; Second Ed., 2012, pp. 215-220.
[http://dx.doi.org/10.1016/B978-0-12-375000-6.00175-0]
[3]
Geddes, J. Bipolar disorder bipolar disorder. Lithium, 2003, 346, 6-8.
[http://dx.doi.org/10.1016/S0140-6736(15)00241-X]
[4]
Coplan, J.D.; Gopinath, S.; Abdallah, C.G.; Berry, B.R. A Neurobiological hypothesis of treatment-resistant depression- mechanisms for selective serotonin reuptake inhibitor non-efficacy. Front. Behav. Neurosci., 2014, 8, 189.
[http://dx.doi.org/10.3389/ fnbeh.2014.00189]
[5]
Pigott, H.E.; Leventhal, A.M.; Alter, G.S.; Boren, J.J. Efficacy and effectiveness of antidepressants: Current status of research. Psychother. Psychosom., 2010, 79(5), 267-79.
[http://dx.doi.org/10. 1159/000318293]
[6]
Fornaro, M.; Kardash, L.; Novello, S.; Fusco, A.; Anastasia, A.; De Berardis, D.; Perna, G.; Carta, M.G. Progress in bipolar disorder drug design toward the development of novel therapeutic Targets: A clinician’s perspective. Expert Opin. Drug Discov., 2018, 13(3), 221-228.
[http://dx.doi.org/10.1080/17460441.2018.1428554]
[7]
Cascade, E.; Kalali, A.H.; Kennedy, S.H. Real-world data on SSRI antidepressant side effects. Psychiatry (Edgmont.), 2009, 6(2), 16-18.
[8]
Abrams, D.I. The therapeutic effects of cannabis and cannabinoids: An update from the national academies of sciences, engineering and medicine report. Eur. J. Intern. Med., 2018, 49, 7-11.
[http://dx.doi.org/10.1016/j.ejim.2018.01.003]
[9]
Soares, V.P.; Campos, A.C. Evidences for the anti-panic actions of cannabidiol. Curr. Neuropharmacol., 2017, 15(2), 291-299.
[http://dx.doi.org/10.2174/1570159X14666160509123955]
[10]
Hanuš, L.O.; Meyer, S.M.; Muñoz, E.; Taglialatela-Scafati, O.; Appendino, G. Phytocannabinoids: A unified critical inventory. Nat. Prod. Reports, 2016, 33(12), 1357-1392.
[http://dx.doi.org/10.1039/c6np00074f.]
[11]
Matsuda, L.A.; Lolait, S.J.; Brownstein, M.J.; Young, A.C.; Bonner, T.I. Structure of a cannabinoid receptor and functional expression of the cloned CDNA. Nature, 1990, 346(6284), 561-564.
[http://dx.doi.org/10.1038/346561a0]
[12]
Munro, S.; Thomas, K.L.; Abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature, 1993, 365(6441), 61-65.
[http://dx.doi.org/10.1038/365061a0]
[13]
Wilsey, B.; Marcotte, T.; Tsodikov, A.; Millman, J.; Bentley, H.; Gouaux, B.; Fishman, S. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J. Pain, 2008, 9(6), 506-521.
[http://dx.doi.org/10.1016/j.jpain.2007.12.010]
[14]
Porter, B.E.; Jacobson, C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav., 2013, 29(3), 574-577.
[http://dx.doi.org/10.1016/ j.yebeh.2013.08.037]
[15]
O’Sullivan, S.E. Cannabinoids go nuclear: Evidence for activation of peroxisome proliferator-activated receptors. Br. J. Pharmacol., 2007, 152(5), 576-582.
[http://dx.doi.org/10.1038/sj.bjp.0707423]
[16]
Grotenhermen, F. Pharmacology of cannabinoids. Neuroendocrinolo. Lett., 2004, 25(1-2), 14-23.
[http://dx.doi.org/NEL251204R01]
[17]
Pertwee, R.G. Endocannabinoids and their pharmacological actions. Handb. Exp. Pharmacol, 2015, 231, 1-37.
[http://dx.doi.org/10. 1007/978-3-319-20825-1_1.]
[18]
Ashton, C.H.; Moore, P.B. Endocannabinoid system dysfunction in mood and related disorders. Acta Psychiatr. Scand., 2011, 124(4), 250-261.
[http://dx.doi.org/10.1111/j.1600-0447.2011.01687.x]
[19]
Karhson, D.S.; Hardan, A.Y.; Parker, K.J. Endocannabinoid signaling in social functioning: An RDoC perspective. Transl. Psychiatry, 2016, 6(9)e905
[http://dx.doi.org/10.1038/tp.2016.169]
[20]
Russo, E.B.; McPartland, J.M. Cannabis and cannabis extracts: greater than the sum of their parts? J. Cannabis Ther., 2001.
[http://dx.doi.org/10.1300/J175v01n03_08]
[21]
Maykut, M.O. Health consequences of acute and chronic marihuana use. Prog. Neuropsychopharmacol. Biol. Psychiatry, 1985.
[http://dx.doi.org/10.1016/0278-5846(85)90085-5]
[22]
Ashton, C.H.; Moore, P.B.; Gallagher, P.; Young, A.H. Cannabinoids in bipolar affective disorder: A review and discussion of their therapeutic potential. J. Psychopharmacol., 2005.
[http://dx.doi.org/10.1177/0269881105051541]
[23]
Pertwee, R.G. The pharmacology of cannabinoid receptors and their ligands: An overview. Intl. J. Obesity., 2006, 30(Suppl. 1), S13-S18.
[http://dx.doi.org/10.1038/sj.ijo.0803272]
[24]
Micale, V.; Di Marzo, V.; Sulcova, A.; Wotjak, C.T.; Drago, F. Endocannabinoid system and mood disorders: Priming a target for new therapies. Pharmacol. Ther., 2013, 138(1), 18-37.
[http://dx.doi.org/10.1016/j.pharmthera.2012.12.002]
[25]
Silva, L.; Black, R.; Michaelides, M.; Hurd, Y.L.; Dow-Edwards, D. Sex and age specific effects of delta-9-Tetrahydrocannabinol during the periadolescent period in the rat: The unique susceptibility of the prepubescent animal. Neurotoxicol. Teratol., 2016, 58, 88-100.
[http://dx.doi.org/10.1016/j.ntt.2016.02.005]
[26]
Cuttler, C.; Spradlin, A.; McLaughlin, R. J. A Naturalistic examination of the perceived effects of cannabis on negative affect. J. Affect. Disord., 2018, 235, 198-205.
[http://dx.doi.org/10.1016/j.jad. 2018.04.054]
[27]
Iseger, T.A.; Bossong, M.G. A Systematic review of the antipsychotic properties of cannabidiol in humans. Schizophr. Res., 2015, 162(1-3), 153-161.
[http://dx.doi.org/10.1016/j.schres.2015.01.033]
[28]
Murphy, M.; Mills, S.; Winstone, J.; Leishman, E.; Wager-Miller, J.; Bradshaw, H.; Mackie, K. Chronic adolescent Δ9-Tetrahydrocannabinol treatment of male mice leads to long-term cognitive and behavioral dysfunction, which are prevented by concurrent cannabidiol treatment. Cannabis Cannabinoid Res., 2017, 2(1), 235-246.
[http://dx.doi.org/10.1089/can.2017.0034]
[29]
Izquierdo, G. Multiple sclerosis symptoms and spasticity management: New data. Neurodegener. Dis. Manag., 2017, 7(6s), 7-11.
[http://dx.doi.org/10.2217/nmt-2017-0034.]
[30]
Campos, A.C.; Fogaça, M.V.; Sonego, A.B.; Guimarães, F.S. Cannabidiol, neuroprotection and neuropsychiatric disorders. Pharmacol. Res., 2016, 112, 119-127.
[http://dx.doi.org/10.1016/ j.phrs.2016.01.033]
[31]
Morales, P.; Reggio, P. H.; Jagerovic, N. An overview on medicinal chemistry of synthetic and natural derivatives of cannabidiol. Front. Pharmacol., 2017, 8, 422.
[http://dx.doi.org/10.3389/fphar.2017.00422.]
[32]
Blessing, E.M.; Steenkamp, M.M.; Manzanares, J.; Marmar, C.R. Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics, 2015, 12(4), 825-836.
[http://dx.doi.org/10.1007/s13311-015-0387-1]
[33]
Shoval, G.; Shbiro, L.; Hershkovitz, L.; Hazut, N.; Zalsman, G.; Mechoulam, R.; Weller, A. Prohedonic effect of cannabidiol in a rat model of depression. Neuropsychobiology, 2016, 73(2), 123-129.
[http://dx.doi.org/10.1159/000443890]
[34]
Zanelati, T.V.; Biojone, C.; Moreira, F.A.; Guimarães, F.S.; Joca, S.R.L. Antidepressant-like effects of cannabidiol in mice: Possible involvement of 5-HT 1A receptors. Br. J. Pharmacol., 2010, 159(1), 122-128.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00521.x]
[35]
Breuer, A.; Haj, C. G.; Fogaça, M. V.; Gomes, F. V.; Silva, N. R.; Pedrazzi, J. F.; Bel, E. A. D.; Hallak, J. C.; Crippa, J. A.; Zuardi, A. W.; Mechoulam, R.; Guimarães, F.S. Fluorinated cannabidiol derivatives: Enhancement of activity in mice models predictive of anxiolytic, antidepressant and antipsychotic effects. PLoS One, 2016, 11(8), e0162087.
[http://dx.doi.org/10.1371/journal.pone.0158779.]
[36]
Morales, P.; Hurst, D.P.; Reggio, P.H. Molecular targets of the phytocannabinoids: A complex picture. Prog. Chem. Org. Nat. Products., 2017, 103, 103-113.
[http://dx.doi.org/10.1007/978-3-319-45541-9_4]
[37]
Shbiro, L.; Hen-Shoval, D.; Hazut, N.; Rapps, K.; Dar, S.; Zalsman, G.; Mechoulam, R.; Weller, A.; Shoval, G. Effects of cannabidiol in males and females in two different rat models of depression. Physiol. Behav., 2019, 201, 59-63.
[http://dx.doi.org/10. 1016/j.physbeh.2018.12.019.]
[38]
Réus, G.Z.; Stringari, R.B.; Ribeiro, K.F.; Luft, T.; Abelaira, H.M.; Fries, G.R.; Aguiar, B.W.; Kapczinski, F.; Hallak, J.E.; Zuardi, A.W.; Crippa, J.A.; Quevedo, J. Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala. Acta Neuropsychiatr., 2011, 23(5), 241-248.
[http://dx.doi.org/10.1111/j.1601-5215.2011.00579.x]
[39]
Schiavon, A.P.; Bonato, J.M.; Milani, H.; Guimarães, F.S.; Weffort de Oliveira, R.M. Influence of single and repeated cannabidiol Administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2016, 64, 27-34.
[http://dx.doi.org/10.1016/j.pnpbp.2015.06.017]
[40]
Sartim, A. G.; Guimarães, F. S.; Joca, S. R. L. Antidepressant-like Effect of cannabidiol injection into the ventral medial prefrontal cortex-possible involvement of 5-HT1A and CB1 receptors. Behav. Brain Res., 2016, 303, 218-27.
[http://dx.doi.org/10.1016/j.bbr. 2016.01.033]
[41]
Lisboa, S.F.; Gomes, F.V.; Terzian, A.L.B.; Aguiar, D.C.; Moreira, F.A.; Resstel, L.B.M.; Guimarães, F.S. The endocannabinoid system and anxiety. Vitam. Horm., 2017, 103, 193-279.
[http://dx.doi.org/10.1016/bs.vh.2016.09.006]
[42]
Marco, E.M.; Pérez-Alvarez, L.; Borcel, E.; Rubio, M.; Guaza, C.; Ambrosio, E.; File, S.E.; Viveros, M.P. Involvement of 5-HT1A receptors in behavioural effects of the cannabinoid receptor agonist CP 55,940 in bale Rats. Behav. Pharmacol., 2004, 15(1), 21-27.
[http://dx.doi.org/10.1097/00008877-200402000-00003]
[43]
Patel, S. Pharmacological Evaluation of cannabinoid receptor ligands in a mouse model of anxiety: Further evidence for an anxiolytic role for endogenous cannabinoid signaling. J. Pharmacol. Exp. Ther., 2006, 318(1), 304-311.
[http://dx.doi.org/10.1124/jpet.106.101287]
[44]
Rubino, T.; Realini, N.; Castiglioni, C.; Guidali, C.; Viganó, D.; Marras, E.; Petrosino, S.; Perletti, G.; Maccarrone, M.; Di Marzo, V.; Parolaro, D. Role in anxiety behavior of the endocannabinoid system in the prefrontal cortex. Cereb. Cortex, 2008, 18(6), 1292-1301.
[http://dx.doi.org/10.1093/cercor/bhm161]
[45]
Bortolato, M.; Campolongo, P.; Mangieri, R.A.; Scattoni, M.L.; Frau, R.; Trezza, V.; La Rana, G.; Russo, R.; Calignano, A.; Gessa, G.L.; Cuomo, V.; Piomelli, D. Anxiolytic-like properties of the anandamide transport inhibitor AM404. Neuropsychopharmacology, 2006, 31(12), 2652-2659.
[http://dx.doi.org/10.1038/sj.npp.1301061]
[46]
Kathuria, S.; Gaetani, S.; Fegley, D.; Valiño, F.; Duranti, A.; Tontini, A.; Mor, M.; Tarzia, G.; La Rana, G.; Calignano, A.; Giustino, A.; Tattoli, M.; Palmery, M.; Cuomo, V.; Piomelli, D. Modulation of anxiety through blockade of anandamide hydrolysis. Nat. Med., 2003, 9(1), 76-81.
[http://dx.doi.org/10.1038/nm803]
[47]
García-Gutiérrez, M.S.; García-Bueno, B.; Zoppi, S.; Leza, J.C.; Manzanares, J. Chronic blockade of cannabinoid CB 2 receptors Induces anxiolytic-like actions associated with alterations in GABA a receptors. Br. J. Pharmacol., 2012, 165(4), 951-964.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01625.x]
[48]
Bahi, A.; Al Mansouri, S.; Al Memari, E.; Al Ameri, M.; Nurulain, S. M.; Ojha, S. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice. Physiol. Behav., 2014, 135, 119-24.
[http://dx.doi.org/10.1016/j. physbeh.2014.06.003.]
[49]
Martin, M.; Ledent, C.; Parmentier, M.; Maldonado, R.; Valverde, O. Involvement of CB1 cannabinoid receptors in emotional behaviour. Psychopharmacology (Berl.), 2002.
[http://dx.doi.org/10.1007/ s00213-001-0946-5]
[50]
Patel, S.; Hill, M. N.; Cheer, J. F.; Wotjak, C. T.; Holmes, A. The endocannabinoid system as a target for novel anxiolytic drugs. Neurosci. Biobehav. Rev., 2017.
[http://dx.doi.org/10.1016/j.neubiorev. 2016.12.033]
[51]
Bergamaschi, M.M.; Queiroz, R.H.C.; Chagas, M.H.N.; De Oliveira, D.C.G.; De Martinis, B.S.; Kapczinski, F.; Quevedo, J.; Roesler, R.; Schröder, N.; Nardi, A.E.; Martín-Santos, R.; Hallak, J.E.; Zuardi, A.W.; Crippa, J.A. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology, 2011, 36(6), 1219-1226.
[http://dx.doi.org/10.1038/npp.2011.6]
[52]
Crippa, J.A.S.; Nogueira, D.G.; Borduqui, F.T.; Wichert-Ana, L.; Duran, F.L.S.; Martin-Santos, R.; Vinícius, S.M.; Bhattacharyya, S.; Fusar-Poli, P.; Atakan, Z.; Santos, F.A.; Freitas-Ferrari, M.C.; McGuire, P.K.; Zuardi, A.W.; Busatto, G.F.; Hallak, J.E. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report. J. Psychopharmacol., 2011, 25(1), 121-130.
[http://dx.doi.org/10.1177/0269881110379283]
[53]
Whiting, P. F.; Wolff, R. F.; Deshpande, S.; Di Nisio, M.; Duffy, S.; Hernandez, A. V.; Keurentjes, J.C.; Lang, S.; Misso, K.; Ryder, S.; Schmidlkofer, S.; Westwood, M.; Kleijnen, J. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA, 2015, 313(24), 2456-2473.
[http://dx.doi.org/10.1001/jama.2015.6358. ]
[54]
Wong, S.S.; Wilens, T.E. Medical cannabinoids in children and Adolescents: A systematic review. Pediatrics, 2017, 140(5)e20171818
[http://dx.doi.org/10.1542/peds.2017-1818]
[55]
Valvassori, S.S.; Elias, G.; De Souza, B.; Petronilho, F.; Dal-Pizzol, F.; Kapczinski, F.; Trzesniak, C.; Tumas, V.; Dursun, S.; Nisihara, C.M.H.; Chagas, M.H.; Hallak, J.E.; Zuardi, A.W.; Quevedo, J.; Crippa, J.A. Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania. J. Psychopharmacol., 2011, 25(2), 274-280.
[http://dx.doi.org/10.1177/ 0269881109106925]
[56]
Ashton, H.; Young, A.H. GABA-ergic drugs: Exit stage left, enter stage right. J. Psychopharmacol., 2003, 17(2), 174-178.
[http://dx.doi.org/10.1177/0269881103017002004]
[57]
Porter, R.; Ferrier, N.; Ashton, H. Anticonvulsants as mood stabilisers. Adv. Psychiatr. Treat., 2007, •••, 96-103.
[http://dx.doi.org/10.1192/apt.5.2.96]
[58]
Crippa, J.A.; Guimarães, F.S.; Campos, A.C.; Zuardi, A.W. Translational investigation of the therapeutic potential of cannabidiol (CBD): Toward a new age. Front. Immunol., 2018, 9, 2009.
[http://dx.doi.org/10.3389/fimmu.2018.02009]
[59]
Haller, J.; Varga, B.; Ledent, C.; Barna, I.; Freund, T.F. Context-dependent effects of CB1 cannabinoid gene disruption on anxiety-like and social behaviour in mice. Eur. J. Neurosci., 2004, 19(7), 1906-1912.
[http://dx.doi.org/10.1111/j.1460-9568.2004.03293.x]
[60]
Akinshola, B.E.; Chakrabarti, A.; Onaivi, E.S. In-Vitro and in-Vivo action of cannabinoids. Neurochem. Res., 1999, 24(10), 1233-1240.
[http://dx.doi.org/10.1023/A:1020968922151]
[61]
Navarro, M.; Hernández, E.; Muñoz, R.M.; Del Arco, I.; Villanúa, M.A.; Carrera, M.R.A.; Rodríguez De Fonseca, F. Acute administration of the CB1cannabinoid receptor antagonist SR 141716A induces anxiety-like responses in the rat. Neuroreport, 1997, 8(2), 491-496.
[http://dx.doi.org/10.1097/00001756-199701200-00023]
[62]
Mendiguren, A.; Aostri, E.; Pineda, J. Regulation of noradrenergic and serotonergic systems by cannabinoids: Relevance to cannabinoid-Induced effects. Life Sci., 2018, 192, 115-127.
[http://dx.doi.org/10.1016/j.lfs.2017.11.029]
[63]
Niederhoffer, N.; Hansen, H.H.; Fernandez-Ruiz, J.J.; Szabo, B. Effects of cannabinoids on adrenaline release from adrenal medullary cells. Br. J. Pharmacol., 2001.
[http://dx.doi.org/10.1038/ sj.bjp.0704359]
[64]
Bisogno, T.; Hanuš, L.; De Petrocellis, L.; Tchilibon, S.; Ponde, D.E.; Brandi, I.; Moriello, A.S.; Davis, J.B.; Mechoulam, R.; Di Marzo, V. 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., 2001, 134(4), 845-852.
[http://dx.doi.org/10.1038/sj.bjp.0704327]
[65]
Ranganathan, M.; Braley, G.; Pittman, B.; Cooper, T.; Perry, E.; Krystal, J.; D’Souza, D.C. The effects of cannabinoids on serum cortisol and prolactin in humans. Psychopharmacology (Berl.), 2009, 203(4), 737-744.
[http://dx.doi.org/10.1007/s00213-008-1422-2]
[66]
Farzaei, M.H.; Bahramsoltani, R.; Rahimi, R.; Abbasabadi, F. Abdollahi, M. A systematic review of plant-derived natural compounds for anxiety disorders. Curr. Top. Med. Chem., 2016, 16(17), 1924-1942.
[http://dx.doi.org/10.2174/1568026616666160204121039]
[67]
Aizpurua-Olaizola, O.; Soydaner, U.; Öztürk, E.; Schibano, D.; Simsir, Y.; Navarro, P.; Etxebarria, N.; Usobiaga, A. Evolution of the cannabinoid and terpene content during the growth of cannabis sativa plants from different chemotypes. J. Nat. Prod., 2016, 79(2), 324-331.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00949]
[68]
ElSohly, M.A.; Slade, D. Chemical constituents of marijuana: The complex mixture of natural cannabinoids. Life Sci., 2005, 78(5), 539-548.
[http://dx.doi.org/10.1016/j.lfs.2005.09.011]
[69]
Wagner, H. Synergy research: Approaching a new generation of phytopharmaceuticals. Fitoterapia, 2011, 82(1), 34-37.
[http://dx.doi.org/10.1016/j.fitote.2010.11.016]
[70]
Chen, F.; Tholl, D.; Bohlmann, J.; Pichersky, E. The Family of terpene synthases in plants: A mid-size family of genes for specialized metabolism that is highly diversified throughout the kingdom. Plant J., 2011, 66(1), 212-29.
[http://dx.doi.org/10.1111/j.1365-313X. 2011.04520.x.]
[71]
Iijima, Y. The Biochemical and molecular basis for the divergent patterns in the biosynthesis of terpenes and phenylpropenes in the peltate glands of three cultivars of basil. Plant Physiol., 2004, 136(3), 3724-3736.
[http://dx.doi.org/10.1104/pp.104.051318]
[72]
Russo, E. B.; Taming, T. H.C. Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br. J. Pharmacol., 2011, 163(7), 1344-64.
[http://dx.doi.org/10.1111/j.1476-5381.2011. 01238.x.]
[73]
Gershenzon, J.; Dudareva, N. The function of terpene natural products in the natural world. Nat. Chem. Biol., 2007, 3(7), 408-414.
[http://dx.doi.org/10.1038/nchembio.2007.5]
[74]
Perry, N.; Perry, E. Aromatherapy in the management of psychiatric disorders. CNS Drugs, 2006, 20(4), 257-280.
[http://dx.doi.org/10.2165/00023210-200620040-00001]
[75]
Li, Y.J.; Xuan, H.Z.; Shou, Q.Y.; Zhan, Z.G.; Lu, X.; Hu, F.L. Therapeutic effects of propolis essential oil on anxiety of restraint-stressed mice. Hum. Exp. Toxicol., 2012, 31(2), 157-165.
[http://dx.doi.org/10.1177/0960327111412805]
[76]
Georgiadou, G.; Tarantilis, P.A.; Pitsikas, N. Effects of the active constituents of Crocus Sativus L. Crocins, in an animal model of Obsessive-compulsive disorder. Neurosci. Lett., 2012, 528(1), 27-30.
[http://dx.doi.org/10.1016/j.neulet.2012.08.081]
[77]
De Sousa, D.P.; De Almeida, S.H.P.; Andrade, L.N.; Andreatini, R. A systematic review of the anxiolytic-like effects of dssential oils in animal models. Molecules, 2015, 20(10), 18620-18660.
[http://dx.doi.org/10.3390/molecules201018620]
[78]
Kasper, S.; Gastpar, M.; Müller, W.E.; Volz, H.P.; Möller, H.J.; Schläfke, S.; Dienel, A. Lavender oil preparation silexan is effective in generalized anxiety disorder - A randomized, double-blind comparison to placebo and paroxetine. Int. J. Neuropsychopharmacol., 2014, 17(6), 859-869.
[http://dx.doi.org/10.1017/S1461145714000017]
[79]
Cline, M.; Taylor, J.E.; Flores, J.; Bracken, S.; McCall, S.; Ceremuga, T.E. Investigation of the anxiolytic effects of linalool, a Lavender extract, in the gale Sprague-Dawley rat. AANA J., 2008, 76(1), 47-52.
[80]
Lima, N.G.P.B.; De Sousa, D.P.; Pimenta, F.C.F.; Alves, M.F.; De Souza, F.S.; MacEdo, R.O.; Cardoso, R.B.; De Morais, L.C.S.L.; Melo, D. M. D. F. F.; De Almeida, R. N. Anxiolytic-like Activity and GC-MS Analysis of (R)-(+)-Limonene fragrance, a natural compound gound in goods and plants. Pharmacol. Biochem. Behav., 2013.
[http://dx.doi.org/10.1016/j.pbb.2012.09.005]
[81]
De Almeida, A.A.C.; De Carvalho, R.B.F.; Silva, O.A.; De Sousa, D.P.; De Freitas, R.M. Potential antioxidant and anxiolytic effects of (+)-Limonene epoxide in mice after marble-burying test. Pharmacol. Biochem. Behav., 2014, 118, 69-78.
[http://dx.doi.org/10. 1016/j.pbb.2014.01.006.]
[82]
Guzmán-Gutiérrez, S.L.; Bonilla-Jaime, H.; Gómez-Cansino, R.; Reyes-Chilpa, R. Linalool and β-Pinene exert their antidepressant-like activity through the monoaminergic pathway. Life Sci., 2015.
[http://dx.doi.org/10.1016/j.lfs.2015.02.021]
[83]
Goldstein, B.I.; Kemp, D.E.; Soczynska, J.K.; McIntyre, R.S. Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder: A systematic review of the literature. J. Clin. Psychiatry, 2009, 70(8), 1078-1090.
[http://dx.doi.org/10.4088/JCP.08r04505]
[84]
Jones, K.A.; Thomsen, C. The Role of the innate immune system in psychiatric disorders. Mol. Cell. Neurosci., 2013, 53, 52-62.
[http://dx.doi.org/10.1016/j.mcn.2012.10.002]
[85]
Miller, A. H. Depression and immunity: A role for T cells? Brain, Behav. Immun., 2010, 24(1), 1-8.
[http://dx.doi.org/10.1016/j.bbi. 2009.09.009.]
[86]
Yirmiya, R.; Goshen, I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav. Immun., 2011.
[http://dx.doi.org/10.1016/j.bbi.2010.10.015]
[87]
Walter, L.; Franklin, A.; Witting, A.; Wade, C.; Xie, Y.; Kunos, G.; Mackie, K.; Stella, N. Nonpsychotropic cannabinoid receptors Regulate microglial cell migration. J. Neurosci., 2018, 23(4), 1398-1405.
[http://dx.doi.org/10.1523/jneurosci.23-04-01398.2003]
[88]
Malfait, A.M.; Gallily, R.; Sumariwalla, P.F.; Malik, A.S.; Andreakos, E.; Mechoulam, R.; Feldmann, M. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc. Natl. Acad. Sci. USA, 2000, 97(17), 9561-9566.
[http://dx.doi.org/10.1073/pnas.160105897]
[89]
Börner, C.; Höllt, V.; Kraus, J. Activation of human T cells induces Upregulation of cannabinoid receptor Type 1 transcription. Neuroimmunomodulation, 2007, 14(6), 281-286.
[http://dx.doi.org/10.1159/ 000117809]
[90]
Borner, C.; Bedini, A.; Hollt, V.; Kraus, J. Analysis of promoter regions regulating basal and interleukin-4-inducible expression of the human CB1 receptor gene in T Lymphocytes. Mol. Pharmacol., 2007, 73(3), 1013-1019.
[http://dx.doi.org/10.1124/mol.107.042945]
[91]
Lunn, C.A. A Novel Cannabinoid peripheral cannabinoid receptorselective inverse agonist blocks leukocyte recruitment in Vivo. J. Pharmacol. Exp. Ther., 2006, 316(2), 780-8.
[http://dx.doi.org/10. 1124/jpet.105.093500.]
[92]
Tanasescu, R.; Constantinescu, C.S. Cannabinoids and the immune system: an overview. Immunobiology, 2010, 215(8), 588-597.
[http://dx.doi.org/10.1016/j.imbio.2009.12.005]
[93]
Lombard, C.; Nagarkatti, M.; Nagarkatti, P. CB2 Cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents. Clin. Immunol., 2007, 122(3), 259-270.
[http://dx.doi.org/10.1016/ j.clim.2006.11.002]
[94]
Provenza, F.D.; Villalba, J.J. The role of natural plant products in modulating the immune system: An adaptable approach for combating disease in grazing animals. Small Rumin. Res., 2010, 89, 131-139.
[http://dx.doi.org/10.1016/j.smallrumres.2009.12.035]
[95]
Okada, Y.; Matono, N.; Shiono, M.; Takai, T.; Hikida, M.; Ohmori, H. Suppression of in Vitro cellular immune response by nitrogen-containing terpene alcohol derivatives. Biol. Pharm. Bull., 2011, 19(11), 1443-1446.
[http://dx.doi.org/10.1248/bpb.19.1443]
[96]
da Silva, S.L.; Figueiredo, P.M.S.; Yano, T. Chemotherapeutic Potential of the volatile oils from Zanthoxylum Rhoifolium Lam leaves. Eur. J. Pharmacol., 2007, 576(1-3), 180-188.
[http://dx.doi.org/10.1016/j.ejphar.2007.07.065]
[97]
Jeong, Y.T.; Yang, B.K.; Jeong, S.C.; Kim, S.M.; Song, C.H. Ganoderma applanation: A promising mushroom for antitumor and Immunomodulating activity. Phytother. Res., 2008, 22(5), 614-619.
[http://dx.doi.org/10.1002/ptr.2294]
[98]
Slyepchenko, A.; Maes, M.; Köhler, C. A.; Anderson, G.; Quevedo, J.; Alves, G. S.; Berk, M.; Fernandes, B. S.; Carvalho, A. F. T helper 17 cells may drive neuroprogression in major depressive disorder: Proposal of an integrative model. Neurosci. Biobehav. Rev., 2016, 64, 83-100.
[http://dx.doi.org/10.1016/j.neubiorev. 2016.02.002.]
[99]
Foster, J.A.; McVey Neufeld, K.A. Gut-brain axis: How the microbiome influences anxiety and depression. Trends Neurosci., 2013, 36(5), 305-312.
[http://dx.doi.org/10.1016/j.tins.2013.01.005]
[100]
Luna, R.A.; Foster, J.A. Gut brain axis: Diet microbiota interactions and implications for modulation of anxiety and depression. Curr. Opin. Biotechnol., 2015, 32, 35-41.
[http://dx.doi.org/10.1016/ j.copbio.2014.10.007]
[101]
Wong, M.L.; Inserra, A.; Lewis, M.D.; Mastronardi, C.A.; Leong, L.; Choo, J.; Kentish, S.; Xie, P.; Morrison, M.; Wesselingh, S.L.; Rogers, G.B.; Licinio, J. Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition. Mol. Psychiatry, 2016, 21(6), 797-805.
[http://dx.doi.org/10.1038/mp.2016.46]
[102]
Sherwin, E.; Dinan, T.G.; Cryan, J.F. Recent developments in understanding the role of the gut microbiota in brain health and disease. Ann. N. Y. Acad. Sci., 2018, 1420(1), 5-25.
[http://dx.doi.org/10.1111/nyas.13416]
[103]
Ben-Shabat, S.; Fride, E.; Sheskin, T.; Tamiri, T.; Rhee, M.H.; Vogel, Z.; Bisogno, T.; De Petrocellis, L.; Di Marzo, V.; Mechoulam, R. An entourage effect: Inactive endogenous fatty acid glycerol esters enhance 2-Arachidonoyl-Glycerol cannabinoid activity. Eur. J. Pharmacol., 1998, 17, 353(1), 23-31.
[http://dx.doi.org/10. 1016/S0014-2999(98)00392-6.]
[104]
Russo, E. B. The case for the entourage effect and conventional breeding of clinical cannabis: No “Strain,” no gain Front. Plant Sci., 2019. [Epub a head of Print].
[http://dx.doi.org/10.3389/fpls. 2018.01969.]
[105]
Berman, P.; Futoran, K.; Lewitus, G.M.; Mukha, D.; Benami, M.; Shlomi, T.; Meiri, D. A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in cannabis. Sci. Rep., 2018, 8(1), 14280.
[http://dx.doi.org/10.1038/s41598-018-32651-4]
[106]
Nallathambi, R.; Mazuz, M.; Namdar, D.; Shik, M.; Namintzer, D.; Vinayaka, A.C.; Ion, A.; Faigenboim, A.; Nasser, A.; Laish, I.; Fred, M.K.; Hinanit, K. Identification of synergistic interaction between cannabis-derived compounds for cytotoxic activity in colorectal cancer cell lines and colon polyps that induces apoptosis-related cell death and distinct gene expression. Cannabis Cannabinoid Res., 2018, 31, 120-135.
[http://dx.doi.org/10.1089/can.2018.0010]
[107]
Koltai, H.; Poulin, P.; Namdar, D. Promoting cannabis products to pharmaceutical drugs. Eur. J. Pharm. Sci., 2019, 132, 118-120.
[http://dx.doi.org/10.1016/j.ejps.2019.02.027]

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