As we have just mentioned, the biology of CBD in the organism is due to the relationship of its molecular structure.
Specifically the CBD, unlike the THC, does not produce psychoactive effects, this is due to its null influence on the cerebral CB1 receptors, since it is known that the toxic action of the THC is due to its activity on intramitochondrial CB1 receptors, thus destabilizing the neuronal energy balance.
As far as CBD is concerned, a multitude of biologic effects have been described, and it is also very interesting to highlight its positive synergy that it can exert with the rest of the terpenes of the plant, which is known as entourage effect.
|Recognized Pharmacology||Terpenic synergy|
|Antioxidant||Limoneno et al.|
|Anxiolytic via 5-HT1A||Linalool, Limonene|
|Cytotoxic in breast tumors||Limonene|
|Increased signaling via Adenosine A2A receptors||Linalool|
|Effective against MRSA||Pinene|
|Decreases sebaceous/sebaceous secretion||Pinene, Limonene, Linalool|
|Active in addiction treatment||Cariofilene|
CBD has an analgesic[i] effect, neuroprotective and with a higher antioxidant metabolic effect than vitamin C or E (Ascorbate or Tocopherol, respectively)[ii], and without being a COX[iii] inhibitor acts as a TRPV1 agonist (vaniloid receptor) analogous to capsaicin (natural compound of plants of the genus Capsicum), but without its harmful effects[iv], besides that it also acts inhibiting the uptake of AEA (arachidonyl ethanolamine or anandamide); endocannabinoid ester (Anandamide with arachidonic acid) and weakly inhibiting its hydrolysis.
The CBD is an antagonist to GPR55 and GPR18, possibly in this way supporting a role in cell migration phenomena[v].
CBD also has anticonvulsant[vi], antiemetic[vii], cytotoxic activity in breast tumors[viii] and many other cell lines, and is also an antioxidant for the rest of unprocessed cell types[ix], antagonizes the TNF factor-α, boosts the signal from the adenosine A2A receptor via inhibition of an adenosine transporter[x], and prevents the accumulation of prion proteins and neuronal toxicity[xi]. The extract has also been shown to show greater antihypergensic activity than the pure compound in models of rats with decreased allodynia (a type of fibromyalgia pain), improved thermal perception and nerve growth factor levels, as well as decreased oxidative damage[xii].
CBD also shows activity against MRSA (Staphylococcus aureus methicillin resistant), with a minimum inhibitory concentration ranging from 0.5-2 mg/mL[xiii].
In 2005 the agonist activity on 5-HT1A receptors was demonstrated at a minimum concentration of 16 mM[xiv] and that despite being a very high concentration, some anxiolytic activity[xv] is underlying. It has also been shown to reduce the risk of thrombotic events[xvi], have antiemetic properties[xvii] and the ability to provide cognitive improvement in mouse models with hepatic encephalopathy[xviii].
A recent study has shown that CBD at a dose of 30 mg/kg reduced immobility time in the forced swimming test compared to the tricyclic antidepressant Imipramine (P<0.01), a blocked effect of pre-treatment with the agonist 5-HT1A WAY100635[xix] supporting the consideration of CBD as a likely antidepressant.
CBD also inhibits lipid synthesis in adipocytes, and produces high-dose apoptosis in an acne model. An example of the antagonistic effects of CBD over THC is the observation of lymphopenia in rats (CBD 5 mg/kg) mediated by a possible reverse agonism of CB2 receptors[xx], an effect not observed in humans even at doses of CBD up to 800 mg[xxi].
CBD has been shown to be critical in cannabis extracts as a potent analgesic in cancer patients[xxii] (30% pain reduction from baseline), showing a positive synergy in this regard in pharmaceutical preparations already on the market.
For more information about the CBD, do not hesitate to consult the supporting bibliography that we make available to all of you.
[i] Costa B, Trovato AE, Comelli F, Giagnoni G, Colleoni M (2007). The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur J Pharmacol 556: 75–83.
[ii] Hampson AJ, Grimaldi M, Axelrod J, Wink D (1998). Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci USA 95: 8268–8273.
[iii] Stott CG, Guy GW, Wright S, Whittle BA (2005). The effects of cannabis extracts Tetranabinex and Nabidiolex on human cytochrome P450-mediated metabolism. In: Symposium on the Cannabinoids, June 27. International Cannabinoid Research Association, Clearwater, FL, p. 163.
[iv] Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I et al. (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.
[v] McHugh D, Hu SS, Rimmerman N, Juknat A, Vogel Z, Walker JM et al. (2010). N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor. BMC Neurosci 11: 44.
[vi] Jones NA, Hill AJ, Smith I, Bevan SA, Williams CM, Whalley BJ et al. (2010). Cannabidiol displays antiepileptiform and antiseizure
properties in vitro and in vivo. J Pharmacol Exp Ther 332: 569–577.
[vii] Parker LA, Mechoulam R, Schlievert C (2002). Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats. Neuroreport 13: 567–570.
[viii] Ligresti A, Moriello AS, Starowicz K, Matias I, Pisanti S, De Petrocellis L et al. (2006). Antitumor activity of plant
cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J Pharmacol Exp Ther 318: 1375–1387.
[ix] Parolaro D, Massi P (2008). Cannabinoids as potential new therapy for the treatment of gliomas. Expert Rev Neurother 8: 37–49.
[x] Carrier EJ, Auchampach JA, Hillard CJ (2006). Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism
of cannabinoid immunosuppression. Proc Natl Acad Sci USA 103: 7895–7900.
[xi] Dirikoc S, Priola SA, Marella M, Zsurger N, Chabry J (2007). Nonpsychoactive cannabidiol prevents prion accumulation and
protects neurons against prion toxicity. J Neurosci 27: 9537–9544.
[xii] Comelli F, Bettoni I, Colleoni M, Giagnoni G, Costa B (2009). Beneficial effects of a Cannabis sativa extract treatment on
diabetes-induced neuropathy and oxidative stress. Phytother Res 23: 1678–1684.
[xiii] Appendino G, Gibbons S, Giana A, Pagani A, Grassi G, Stavri M et al. (2008). Antibacterial cannabinoids from Cannabis sativa: a
structure-activity study. J Nat Prod 71: 1427–1430.
[xiv] Russo EB, Burnett A, Hall B, Parker KK (2005). Agonistic properties of cannabidiol at 5-HT-1a receptors. Neurochem Res 30: 1037–1043.
[xv] Resstel LB, Tavares RF, Lisboa SF, Joca SR, Correa FM, Guimaraes FS (2009). 5-HT1A 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.
Soares Vde P, Campos AC, Bortoli VC, Zangrossi H Jr, Guimaraes FS, Zuardi AW (2010). Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors. Behavioural Brain Res 213: 225–229.
[xvi] Mishima K, Hayakawa K, Abe K, Ikeda T, Egashira N, Iwasaki K et al. (2005). Cannabidiol prevents cerebral infarction via a
serotonergic 5-hydroxytryptamine1A receptor-dependent mechanism. Stroke 36: 1077–1082.
[xvii] Rock EM, Limebeer CL, Mechoulam R, Parker LA (2009). Cannabidiol (the non-psychoactive component of cannabis) may
act as a 5-HT1A auto-receptor agonist to reduce toxin-induced nausea and vomiting. Proceedings 19th Annual Symposium on the
Cannabinoids. International Cannabinoid Research Society: St. Charles, IL, p. 29.
[xviii] Magen I, Avraham Y, Ackerman Z, Vorobiev L, Mechoulam R, Berry EM (2009). Cannabidiol ameliorates cognitive and motor
impairments in mice with bile duct ligation. J Hepatol 51: 528–534.
[xix] Zanelati TV, Biojone C, Moreira FA, Guimaraes FS, Joca SR (2010). Antidepressant-like effects of cannabidiol in mice: possible
involvement of 5-HT1A receptors. Br J Pharmacol 159: 122–128.
[xx] Ignatowska-Jankowska B, Jankowski M, Glac W, Swiergel AH (2009). Cannabidiol-induced lymphopenia does not involve NKT and NK cells. J Physiol Pharmacol 60 (Suppl. 3): 99–103.
[xxi] Crippa JA, Zuardi AW, Hallak JE (2010). [Therapeutical use of the cannabinoids in psychiatry]. Rev Bras Psiquiatr 32 (Suppl. 1):
[xxii] Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT (2010). Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage 39: 167–179.