Studies & Medicinal Applications
There are several different types of anxiety disorders. Examples include generalized anxiety disorder, panic disorder, and social anxiety disorder. Symptoms of disorders span the range of:
- Restlessness or feeling wound-up or on edge
- Difficulty concentrating or having their minds go blank
- Difficulty controlling the worry
- Sudden and repeated attacks of intense fear
- Fear or avoidance of places where panic attacks have occurred in the past
- Feeling highly anxious about being with other people and having a hard time talking to them
- Being very afraid that other people will judge them
- Feeling nauseous or sick to your stomach when other people are around
In a study of of the effects of CBD on anxiety and brain chemistry, results were consistent with CBD acting as an allosteric modulator, or facilitator of 5-HT1A signaling. The 5-HT1A receptor is an established anxiolytic target found in the cerebral cortex, hippocampus and amygdala. (1) Symptoms of anxiety can be triggered by the THC cannabinoid, decreasing efficacy cannabis use as treatment of anxiety disorders. WeLa's full spectrum THC free CBD carries the anxiolytic action of cannabis without the psychoactive effects. A double blind study where patients received CBD, showed "decreased activity in the left amygdala-hippocampus complex" compatible anxiolytic action. (2)
Post Traumatic Stress Disorder
Post-traumatic stress disorder (PTSD) is a mental health condition that's triggered by a terrifying event — either experiencing it or witnessing it. Symptoms may include flashbacks, nightmares and severe anxiety, as well as uncontrollable thoughts about the event.
In 2012, the Journal of Psychiatric research published a study on CBD and chronic predator stress, indicative of a possible model for post traumatic stress disorder. “CBD administered daily one hour after predator stress reduced long-lasting anxiogenic effects of chronic predator stress..”(3) A second study involved the effects of CBD on the pars reticulata, a portion of the substantia nigra involved in the regulation of GABA, a nervous system messenger responsible for decreasing neuron excitability.(4) Cannabidiol “had a clear anti aversive effect, decreasing the duration of defensive alertness”often experienced during episodes of heightened fear and stress.
Chronic pain is often defined as any pain lasting more than 12 weeks. Whereas acute pain is a normal sensation that alerts us to possible injury, chronic pain is very different. Chronic pain persists—often for months or even longer. Phytocannabinoid, cannabidiol (CBD) is known to modulate the activity of many cellular effectors, including CB1 and CB2 receptors.
When CBD activates the vanilloid receptor, the resultant brain activity alleviates pain and inflammation. Chronic pain medications typically reduce pain via orthosteric modulators that bind to a receptor site known as the the orthosteric, or primary, site. (5) This enables them to directky activate pain receptors. Cannabidiol is a negative alosteric modulator, meaning it influences pain receptors by binding to an effector molecule at a site other than the primary. (6) This makes a strong case for why CBD has no adverse long term effects or dependency.
Fibromyalgia is a chronic pain state in which the nerve stimuli causing pain originates mainly in the tissues of the body. Hence the increased pain on movement and the aggravation of fibromyalgia by strenuous exertion. Some of the symptoms of fibromyalgia include:
- Chronic Pain
The ability of CBD to work as an analgesic was supported in a review of 18 randomized trials on chronic pain non-cancer pain.(8) The findings were conclusive supporting the hypothesis that CBD is an effective option as part of a pain treatment plan. Preclinical studies on cannabinoid based headache intervention “It has been postulated that a general deficiency in endocannabinoid tone could underlie headache disorders. Cannabis also shows potential to interrupt specific stages in the pathogenesis of headaches, including glutamate signaling leading to CSD and cranial blood vessel dilation.”(9)
"The non-psychoactive cannabinoid, cannabidiol (CBD), differentially modulates IL-2 and IFN-γ production depending on the magnitude to which T cells are activated. Overall, these results demonstrate that cannabinoids enhance cytokine production in response to suboptimal T cell activation and suggest that cannabinoids should be classified as immunomodulatory." (10) Interleukin-2 (IL-2) and IFNγ, or type II interferon, are cytokines involved in regulating white blood cells, or leukocytes, such as macrophages and lymphocytes. The properties aid increased immune response and innate immunity against bacterial and viral infections.
Parkinson's disease (PD) is a neurodegenerative disorder that affects predominately dopamine-producing (“dopaminergic”) neurons in a specific area of the brain called substantia nigra.
As PD progresses, cell death occurring in the basal ganglia and the presence of Lewy bodies within nerve cells decreases the levels of dopamine in these areas. This leads to autonomic disfunction, cognition problems and increased tremors and rigidity.
Recent studies have shown “the activation of CB(2) receptors leads to a slower progression of neurodegeneration.” This is believed to be caused by the endocannibinoid system’s upregulation and activation of CB2 receptors, which have been found to be downregulating in people with PD.(11) Regulation capabilities of the ECS may also aid in “limiting the toxicity of microglial cells for neurons and, in particular, by reducing the generation of proinflammatory factors.”(12)
A disease caused by an uncontrolled division of abnormal cells in a part of the body.
While CBD has analgesic properties beneficial to the pain associated with chemotherapy and radiation, there is also research to show “the decrease in tumor growth after the administration of cannabidiol.”(13) “Cannabinoids possess anti-proliferative and pro-apoptotic effects and they are known to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization.”(14)
A study on breast cancer research and treatment showed administration of CBD caused mediation of the upregulation of extracellular signal-regulated kinase phosphorylation (pERK), a protein that has a direct cellular response on the regulation of mitosis in cells.(15)
Crohn's disease is an inflammatory bowel disease (IBD). It causes inflammation of your digestive tract, which can lead to abdominal pain, severe diarrhea, fatigue, weight loss and malnutrition.
The wall of the gastrointestinal tract contains both CB1 and CB2 receptors. CB receptor activation has shown to cause T cells to under apoptosis and decrease proliferation in colitis.(16) This in turn decreases the inflammatory response. Activation of CB receptors in the intestinal tract may reduce hyper mobility of the GI tract. This could decrease stimulation of the enteric nervous system resulting in reduced diarrhea and the abdominal pain associated with it.(17)
“Enteric glial cells (EGC) actively mediate acute and chronic inflammation in the gut; EGC proliferate and release neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response. CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients. These actions lead to a reduction of intestinal damage mediated by PPARgamma receptor pathway.”(18)
1. Rock EM, Bolognini D, Limebeer CL, et al. Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus. Br J Pharmacol 2012;165:2620-2634.
2. Crippa JA, Zuardi AW, Garrido GE, Wichert-Ana L, Guarnieri R, Ferrari L, Azevedo-Marques PM, Hallak JE, McGuire PK, Filho Busatto G. Effects of cannabidiol (CBD) on regional cerebral blood ow. Neuropsychopharmacol. 2004;29(2):417-26.
3.Campos AC, Ferreira FR, Guimaraes FS. Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors. J Psychiatr Res 2012;46:1501-1510.
4. da Silva JA, Biagioni AF, Almada RC, et al. Dissociation between the panicolytic effect of cannabidiol microinjected into the substantia nigra, pars reticulata, and fear-induced antinociception elicited by bicuculline administration in deep layers of the superior colliculus: The role of CB-cannabinoid receptor in the ventral mesencephalon. Eur J Pharmacol 2015;758:153-163.
5. Hayakawa K, Mishima K, Hazekawa M, Sano K, Irie K, Orito K et al. (2008). Cannabidiol potentiates pharmacological effects of Delta(9)-tetrahydrocannabinol via CB(1) receptor-dependent mechanism. Brain Res 1188: 157–164.
6. Laprairie, R. B., Bagher, A. M., Kelly, M. E. M., and Denovan-Wright, E. M. (2015) Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. British Journal of Pharmacology, 172: 4790–4805. doi: 10.1111/bph.13250.
7. Anand P, Whiteside G, Fowler CJ, Hohmann AG. Targeting CB2 receptorsand the endocannabinoid systemfor the treatment of pain. Brain Res Rev 2008; 60: 255–66.
8. Lynch, M. E. and Campbell, F. (2011), Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. British Journal of Clinical Pharmacology, 72: 735–744. doi:10.1111/j.1365-2125.2011.03970.x
9. Lochte Bryson C., Beletsky Alexander, Samuel Nebiyou K., and Grant Igor. Cannabis and Cannabinoid Research. April 2017, 2(1): 61-71. https://doi.org/10.1089/can.2016.0033
10. Cabral, G.A. J Neuroimmune Pharmacol (2010) 5(Suppl 1): 3. https://doi.org/10.1007/s11481-010-9196-9
11. Javed H, Azimullah S, Haque ME and Ojha SK (2016) Cannabinoid Type 2 (CB2) Receptors Activation Protects against Oxidative Stress and Neuroinflammation Associated Dopaminergic Neurodegeneration in Rotenone Model of Parkinson's Disease. Front. Neurosci. 10:321. doi: 10.3389/fnins.2016.00321
12. Fernández-Ruiz, J., Moreno-Martet, M., Rodríguez-Cueto, C., Palomo-Garo, C., Gómez-Cañas, M., Valdeolivas, S., Guaza, C., Romero, J., Guzmán, M., Mechoulam, R. and Ramos, J. A. (2011), Prospects for cannabinoid therapies in basal ganglia disorders. British Journal of Pharmacology, 163: 1365–1378. doi:10.1111/j.1476-5381.2011.01365.x
13. Johnson, J.R., Lossignol, D., Burnell-Nugent, M., and Fallon, M.T. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. J Pain Symptom Manage. 2012; ([Epub ahead of print])
14. Massi P., Solinas M., Cinquina V., Parolaro D. (2013). Cannabidiol as potential anticancer drug. Br. J. Clin. Pharmacol. 75 303–312. 10.1111/j.1365-2125.2012.04298.x
15. McAllister SD, Murase R, Christian RT, Lau D, Zielinski AJ, Allison J, Almanza C, Pakdel A, Lee J, Limbad C, Liu Y, Debs RJ, Moore DH, Desprez PY. Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. Breast Cancer Res Treat. 2011;129:37–47.
16. Di Sabatino A, Battista N, Biancheri P, Rapino C, Rovedatti L, Astarita G, Vanoli A, Dainese E, Guerci M, Piomelli D, Pender SL, MacDonald TT, Maccarrone M, Corazza GR: The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease. Mucosal Immunol 2011;4:574-583.
17. Marquéz L, Suárez J, Iglesias M, Bermudez-Silva FJ, Rodríguez de Fonseca F, Andreu M: Ulcerative colitis induces changes on the expression of the endocannabinoid system in the human colonic tissue. PLoS One 2009;4:e6893.
18. De Filippis D, Esposito G, Cirillo C, Cipriano M, De Winter BY, Scuderi C, Sarnelli G, Cuomo R, Steardo L, De Man JG, Iuvone T (2011) Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis. PLoS One 6:e28159. doi: 10.1371/journal.pone.0028159