The CBD Story Part 2: Effects of CBD in the Body

In The CBD Story – Part 1, we explored what CBD is, CBD and the endocannabinoid system (ECS), and how ECS dysfunction can negatively impact health. We saw how CBD is an important modulator of the ECS that might help to restore balance when the ECS is disrupted by things like stress and poor diet. Here, we explore the effects of CBD in the body, and the role of CBD in several clinical conditions. 

What are the Effects of CBD in the Body?

The complexity of CBD’s physiological effects increases exponentially when you consider that while CBD is clearly involved with the ECS, it actually has more than 65 molecular targets in the body¹. Of these, approximately 49% are enzymatic, 20% are membrane and cellular transporters, 15% are receptors, and 15% are ion channels¹. CBD is said to exhibit “promiscuous pharmacological activity” because it affects such a wide range of receptor targets, including the serotonin, adenosine, opioid, and dopamine systems². Cannabinoid receptors, which CBD affects both directory and indirectly (through effects on AEA and 2-AG levels) also modify the release of many types of neurotransmitters, including those that both increase and decrease synaptic function, through a type of retrograde signaling³. As such, it is not surprising that CBD has been found to exhibit widespread effects in the body. 

CBD has been reported to help with a vast array of health concerns. While people are understandably skeptical about how a single molecule can be of benefit in so many seemingly different ways, this can be explained by the widespread involvement of the ECS in virtually all systems in the body. In fact, scientists from the National Institutes of Health declared in 2013 that “modulating endocannabinoid system activity may have therapeutic potential in almost all diseases affecting humans.”⁴However, not all of the claims made about CBD’s benefits are well supported by research evidence. Here, we present the most current research for some of the most well-investigated conditions. 

Pain

Pain research to date has been heavily focused on the use of THC and a combination of THC and CBD, rather than CBD in isolation. As such, the majority of research comes from pre-clinical models, which has shown very promising results. In animal models of pain conditions that widely affect humans, including arthritis^5,6 and myofascial pain⁷, CBD has been shown to be a safe and effective treatment. In fact, a recent review article stated that there is an “overwhelming” body of preclinical research supporting the use of CBD for pain⁸. Based on existing research, a group of expert clinicians recently rated the CBD in the treatment of chronic neuropathic pain at 75/100. In contrast, oxycodone scored in the 40s, and morphine and fentanyl in the 30s⁹. 

Sleep

CBD is widely promoted as a sleep aid, although research has also shown that it can also promote wakefulness. Whether CBD is sedating or alerting seems to depend on dose. A recent article reviewed the research on CBD’s wakefulness and sleep promoting effects and concluded that low to moderate doses are stimulating, while high doses are sedating¹⁰, although it should also be noted that the dose effects of CBD on sleep in humans have not been thoroughly investigated. CBD may additionally benefit sleep by reducing anxiety^10,11, and it appears to help people with Parkinson’s Disease suffering from REM Sleep Behaviour Disorder¹².

Anxiety

Human studies that have used CBD to treat anxiety disorders have shown benefit. CBD reduced anxiety in adolescents with SAD¹³ and in adults with social phobia in a simulated public speaking environment¹⁴. Similarly, CBD combined with medication and psychotherapy reduced the severity of PTSD symptoms in adults after eight weeks¹⁵, and PTSD anxiety was also reduced in a 10-year old child treated with CBD for four months¹⁶. And, in a study of psychiatric patients experiencing both anxiety and sleep concerns, nearly 80% showed a reduction in anxiety within the first month that was sustained over several months¹⁷. Several studies have also demonstrated CBD’s ability to reduce anxiety in healthy subjects. CBD effectively reduced anxiety in healthy adults placed in a simulated public speaking environment ^18,19. Two other studies in healthy subjects found that CBD decreased anxiety, while at the same time showing changes in brain areas involved in the control of emotions^20,21. There is some evidence that the effect of CBD on anxiety is U shaped, with efficacy at intermediate but not low or high doses^22,23, although this finding is not unequivocal, as high doses of CBD also reduce anxiety in some studies²³.

Depression

Most research on CBD and depression has used a pre-clinical rodent model. In these studies, CBD has consistently been found to be very effective in reducing depressive behaviour. CBD has also been found to induce positive changes in rodent brains, such as increasing the growth and development of new brain cells²⁴. Given the positive effects of CBD in animal models of depression, and its interactions with multiple systems involved in depression, CBD has been proposed as a possible “novel antidepressant”²⁵. Although limited, observational human research has also been positive, with a recent study finding that among 400 patients who reported using CBD to achieve “mood-improving” effects, 250 reported that CBD worked “very well by itself”²⁶. 

Dermatology

Topically applied CBD has shown to be beneficial in the treatment of many dermatological conditions. In humans, application of a CBD enriched ointment on the skin of 20 patients with psoriasis, atopic dermatitis, or scars resulted in improved hydration, transepidermal water loss, and elasticity when used twice daily for three months. Other improvements were noted in some patients, including reduced skin blemishes, scars, papules, pustules, and psoriasis²⁷. Similarly, a small study of three pediatric patients found that topical CBD applied as an oil, cream or spray by their parents reduced pain and blistering and improved wound healing in patients with epidermiolysis bullosa²⁸. In animals, CBD was found to reduce inflammation in a mouse model of ear irritation²⁹, as well as research with human skin cells, which found that CBD inhibited the release of mediators involved in inflammation and wound injury³⁰. Research with human skin cells has also found that CBD reduces sebum production and inflammation, suggesting a possible application in the treatment of acne³¹. 

Epilepsy

CBD has been well researched for its role in reducing seizures. As previously mentioned, the prescription drug Epidiolex has FDA approval to treat two rare forms of childhood epilepsy (Dravet and Lennox-Gastot syndromes), as well as for the treatment of seizures in tuberous sclerosis, a rare genetic disease. Epidiolex consists of highly concentrated CBD oil in a suspension with sesame seed oil, ethanol, strawberry flavor, and sucralose. In these conditions, Epidiolex is used as an adjunct treatment along with other medications³². CBD’s ability to reduce seizures is thought to relate not to effects on cannabinoid receptors, but rather via effects on other targets such as ion channels such as TRPV1 and neurotransmitter receptors³³. Although the majority of clinical studies have focused on treatment resistant epilepsy in infants, children, and adolescents, some studies have also included adults, with a reduction in seizure frequency seen across demographic groups³⁴. Interestingly, a 2018 meta-analysis found that compared to patients using purified CBD (usually as Epidiolex), patients using a CBD rich cannabis extract reported using lower average doses and reported fewer adverse events³⁵. 

Autism

In the last three years there has been an increasing amount of research attention focused on the use of CBD in the treatment of autism spectrum disorder (ASD), although clinical research is limited. Most studies have used CBD with a very small amount of THC. In one study, 1/3 of children with ASD who took cannabis oil containing 30% CBD and 1.5% THC reported benefits³⁶. In another study, there was an overall improvement of 74.5% of children with ASD taking a ratio of 20:1 CBD:THC³⁷, while a retrospective study of children with ASD taking CBD-rich cannabis also found improvements in the majority subjects³⁸. It should be noted, however, that many parents of children in these studies reported side effects such as restlessness and sleepiness, and a small number of children in the studies worsened with treatment. The improvement of autism symptoms may relate to the ability of AEA to influence oxytocin, with increases in AEA activity at CB1 receptors improving social impairment in a rodent model³⁹. 

Alzheimer’s Disease

CBD is currently recommended in the management of Alzheimer’s Disease (AD) by organizations such as Dementia Care Central, a consumer education program, although others (such as the Alzheimer’s Society) are quick to point out the lack of clinical research in this area. While limited to pre-clinical research, findings from recent studies are extremely encouraging. In research conducted almost 15 years ago, CBD was found to reduce brain inflammation associated with injection of human beta-amyloid, the protein that causes the characteristic plaques, in a mouse model of AD⁴⁰. Subsequent research showed that CBD can enhance the growth and development of new brain cells, reduce the abnormal responses of glial cells in the brain, and reverse and prevent the development of cognitive deficits in animal models⁴¹. More recently, in an in vitro model of AD using human hippocampal neurons (the part of the brain most associated with memory), application of CBD was able to reverse deficits in cellular mechanisms⁴². Similarly, it was found to extend the lifespan and healthspan in worms genetically modified to express human beta-amyloid⁴³. In healthy humans, CBD has been found to improve blood flow in the brain, which is reduced in AD patients⁴⁴. This suggests that effects on blood flow may be another of CBD’s brain protecting mechanisms. The rate of publication of studies related to CBD and AD is increasing rapidly, and this is an incredibly active area of current research. 

Parkinson’s Disease

As already mentioned, CBD appears to help people with Parkinson’s Disease (PD) suffering from REM Sleep Behaviour Disorder¹², and it also may exert other benefits. PD is a movement disorder that involves dysfunction of the basal ganglia and several neurotransmitter networks, including dopamine, GABA and glutamate. The ECS, which plays a critical role in neurotransmitter modulation in the brain (especially via CB1), has emerged as a potential target in the treatment of PD, since CBD has been shown to influence brain neurotransmitters, reduce oxidative stress, and decrease brain inflammation⁴⁵. Interestingly, the first research studies using CBD in PD treatment were done back in 1986, which showed that CBD helped to reduce side effects associated with levodopa treatment (the main treatment for PD that is associated with severe side effects) but did not help the disease itself⁴⁶. Subsequently, CBD was found to decrease PD psychosis⁴⁷, increase functioning and general well-being⁴⁸, and decrease anxiety and tremor⁴⁹. Several pre-clinical studies have also shown benefit, although clinical and preclinical research is not unequivocal⁴⁵. It has been proposed that CBD might be helpful in early, but not late, PD, since later stages of the disease involve widespread death of dopamine neurons45. 

This blog is the second in a three-part series on CBD. In The CBD Story – Part 3, we will explore the forms of CBD and CBD pharmacokinetics and safety. 

1. Ibeas Bih, C., Chen, T., Nunn, A. V., Bazelot, M., Dallas, M., & Whalley, B. J. (2015). Molecular Targets of Cannabidiol in Neurological Disorders. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 12(4), 699–730. https://doi.org/10.1007/s13311-015-0377-3
2. Zlebnik, N. E., & Cheer, J. F. (2016). Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?. Annual review of neuroscience, 39, 1–17. https://doi.org/10.1146/annurev-neuro-070815-014038
3. Castillo, P. E., Younts, T. J., Chávez, A. E., & Hashimotodani, Y. (2012). Endocannabinoid signaling and synaptic function. Neuron, 76(1), 70–81. https://doi.org/10.1016/j.neuron.2012.09.020
4. Pacher, P., & Kunos, G. (2013). Modulating the endocannabinoid system in human health and disease–successes and failures. The FEBS journal, 280(9), 1918–1943. https://doi.org/10.1111/febs.12260
5. Philpott, H. T., O’Brien, M., & McDougall, J. J. (2017). Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain, 158(12), 2442–2451. https://doi.org/10.1097/j.pain.0000000000001052
6. Verrico, C. D., Wesson, S., Konduri, V., Hofferek, C. J., Vazquez-Perez, J., Blair, E., Dunner, K., Jr, Salimpour, P., Decker, W. K., & Halpert, M. M. (2020). A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. Pain, 161(9), 2191–2202. https://doi.org/10.1097/j.pain.00000000000018
7. Wong, H., & Cairns, B. E. (2019). Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain. Archives of oral biology, 104, 33–39. https://doi.org/10.1016/j.archoralbio.2019.05.028
8. Donvito, G., Nass, S. R., Wilkerson, J. L., Curry, Z. A., Schurman, L. D., Kinsey, S. G., & Lichtman, A. H. (2018). The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 43(1), 52–79. https://doi.org/10.1038/npp.2017.204
9. Nutt, David J., Phillips, Lawrence D., Barnes, Michael, Brander, Brigitta, Curran, H. Valerie, Fayaz, Alan, Finn, David P., Horsted, Tina, Moltke, Julie, Sakal, Chloe, Sharon, Haggai, O’Sullivan, Saoirse, Williams, Tim, Zorn, Gregor and Schlag, Anne Katrin (2021) A multicriteria decision analysis comparing pharmacotherapy for chronic neuropathic pain, including cannabinoids and cannabis-based medical products. Cannabis and Cannabinoid Research. ISSN 2578-5125 (In Press). http://eprints.lse.ac.uk/108967/
10. Babson, K. A., Sottile, J., & Morabito, D. (2017). Cannabis, Cannabinoids, and Sleep: a Review of the Literature. Current psychiatry reports, 19(4), 23. https://doi.org/10.1007/s11920-017-0775-9
11. Shannon, S., Lewis, N., Lee, H., & Hughes, S. (2019). Cannabidiol in Anxiety and Sleep: A Large Case Series. The Permanente journal, 23, 18–041. https://doi.org/10.7812/TPP/18-041
12. Chagas, M. H., Eckeli, A. L., Zuardi, A. W., Pena-Pereira, M. A., Sobreira-Neto, M. A., Sobreira, E. T., Camilo, M. R., Bergamaschi, M. M., Schenck, C. H., Hallak, J. E., Tumas, V., & Crippa, J. A. (2014). Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson’s disease patients: a case series. Journal of clinical pharmacy and therapeutics, 39(5), 564–566. https://doi.org/10.1111/jcpt.12179
13. Masataka N. (2019). Anxiolytic Effects of Repeated Cannabidiol Treatment in Teenagers With Social Anxiety Disorders. Frontiers in psychology, 10, 2466. https://doi.org/10.3389/fpsyg.2019.02466
14. Bergamaschi, M. M., Queiroz, R. H., Chagas, M. H., de Oliveira, D. C., 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. (2011). Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 36(6), 1219–1226. https://doi.org/10.1038/npp.2011.6
15. Elms, L., Shannon, S., Hughes, S., & Lewis, N. (2019). Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series. Journal of alternative and complementary medicine (New York, N.Y.), 25(4), 392–397. https://doi.org/10.1089/acm.2018.0437
16. Shannon, S., & Opila-Lehman, J. (2016). Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. The Permanente journal, 20(4), 16-005. https://doi.org/10.7812/TPP/16-005
17. Shannon, S., Lewis, N., Lee, H., & Hughes, S. (2019). Cannabidiol in Anxiety and Sleep: A Large Case Series. The Permanente journal, 23, 18–041. https://doi.org/10.7812/TPP/18-041
18. Zuardi, A. W., Cosme, R. A., Graeff, F. G., & Guimarães, F. S. (1993). Effects of ipsapirone and cannabidiol on human experimental anxiety. Journal of psychopharmacology (Oxford, England), 7(1 Suppl), 82–88. https://doi.org/10.1177/026988119300700112
19. Linares, I. M., Zuardi, A. W., Pereira, L. C., Queiroz, R. H., Mechoulam, R., Guimarães, F. S., & Crippa, J. A. (2019). Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test. Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), 41(1), 9–14. https://doi.org/10.1590/1516-4446-2017-0015
20. 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 flow. Neuropsychopharmacology. 2004 Feb;29(2):417-26. doi: 10.1038/sj.npp.1300340. PMID: 14583744.
21. Crippa, J. A., Derenusson, G. N., Ferrari, T. B., Wichert-Ana, L., Duran, F. L., Martin-Santos, R., Simões, M. V., Bhattacharyya, S., Fusar-Poli, P., Atakan, Z., Santos Filho, A., Freitas-Ferrari, M. C., McGuire, P. K., Zuardi, A. W., Busatto, G. F., & Hallak, J. E. (2011). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. Journal of psychopharmacology (Oxford, England), 25(1), 121–130. https://doi.org/10.1177/0269881110379283
22. García-Gutiérrez, M. S., Navarrete, F., Gasparyan, A., Austrich-Olivares, A., Sala, F., & Manzanares, J. (2020). Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders. Biomolecules, 10(11), 1575. https://doi.org/10.3390/biom10111575
23. Blessing, E. M., Steenkamp, M. M., Manzanares, J., & Marmar, C. R. (2015). Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 12(4), 825–836. https://doi.org/10.1007/s13311-015-0387-1
24. Silote, G. P., Sartim, A., Sales, A., Eskelund, A., Guimarães, F. S., Wegener, G., & Joca, S. (2019). Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms. Journal of chemical neuroanatomy, 98, 104–116. https://doi.org/10.1016/j.jchemneu.2019.04.006
25. Calapai, G., Mannucci, C., Chinou, I., Cardia, L., Calapai, F., Sorbara, E. E., Firenzuoli, B., Ricca, V., Gensini, G. F., & Firenzuoli, F. (2019). Preclinical and Clinical Evidence Supporting Use of Cannabidiol in Psychiatry. Evidence-based complementary and alternative medicine : eCAM, 2019, 2509129. https://doi.org/10.1155/2019/2509129
26. Corroon, J., & Phillips, J. A. (2018). A Cross-Sectional Study of Cannabidiol Users. Cannabis and cannabinoid research, 3(1), 152–161. https://doi.org/10.1089/can.2018.0006
27. Palmieri, B., Laurino, C., & Vadalà, M. (2019). A therapeutic effect of cbd-enriched ointment in inflammatory skin diseases and cutaneous scars. La Clinica terapeutica, 170(2), e93–e99. https://doi.org/10.7417/CT.2019.2116
28. Chelliah, M. P., Zinn, Z., Khuu, P., & Teng, J. (2018). Self-initiated use of topical cannabidiol oil for epidermolysis bullosa. Pediatric dermatology, 35(4), e224–e227. https://doi.org/10.1111/pde.13545
29. Tubaro, A., Giangaspero, A., Sosa, S., Negri, R., Grassi, G., Casano, S., Della Loggia, R., & Appendino, G. (2010). Comparative topical anti-inflammatory activity of cannabinoids and cannabivarins. Fitoterapia, 81(7), 816–819. https://doi.org/10.1016/j.fitote.2010.04.009
30. Sangiovanni, E., Fumagalli, M., Pacchetti, B., Piazza, S., Magnavacca, A., Khalilpour, S., Melzi, G., Martinelli, G., & Dell’Agli, M. (2019). Cannabis sativa L. extract and cannabidiol inhibit in vitro mediators of skin inflammation and wound injury. Phytotherapy research : PTR, 33(8), 2083–2093. https://doi.org/10.1002/ptr.6400
31. Oláh, A., Tóth, B. I., Borbíró, I., Sugawara, K., Szöllõsi, A. G., Czifra, G., Pál, B., Ambrus, L., Kloepper, J., Camera, E., Ludovici, M., Picardo, M., Voets, T., Zouboulis, C. C., Paus, R., & Bíró, T. (2014). Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. The Journal of clinical investigation, 124(9), 3713–3724. https://doi.org/10.1172/JCI64628
32. Sekar, K., & Pack, A. (2019). Epidiolex as adjunct therapy for treatment of refractory epilepsy: a comprehensive review with a focus on adverse effects. F1000Research, 8, F1000 Faculty Rev-234. https://doi.org/10.12688/f1000research.16515.1
33. Lattanzi, S., Brigo, F., Trinka, E., Zaccara, G., Cagnetti, C., Del Giovane, C., & Silvestrini, M. (2018). Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis. Drugs, 78(17), 1791–1804. https://doi.org/10.1007/s40265-018-0992-5
34. Silvestro, S., Mammana, S., Cavalli, E., Bramanti, P., & Mazzon, E. (2019). Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials. Molecules (Basel, Switzerland), 24(8), 1459. https://doi.org/10.3390/molecules24081459
35. Pamplona, F. A., da Silva, L. R., & Coan, A. C. (2018). Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis. Frontiers in neurology, 9, 759. https://doi.org/10.3389/fneur.2018.00759
36. Bar-Lev Schleider, L., Mechoulam, R., Saban, N., Meiri, G., & Novack, V. (2019). Real life Experience of Medical Cannabis Treatment in Autism: Analysis of Safety and Efficacy. Scientific reports, 9(1), 200. https://doi.org/10.1038/s41598-018-37570-y
37. Barchel, D., Stolar, O., De-Haan, T., Ziv-Baran, T., Saban, N., Fuchs, D. O., Koren, G., & Berkovitch, M. (2019). Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-morbidities. Frontiers in pharmacology, 9, 1521. https://doi.org/10.3389/fphar.2018.01521
38. Aran, A., Cassuto, H., Lubotzky, A., Wattad, N., & Hazan, E. (2019). Brief Report: Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems-A Retrospective Feasibility Study. Journal of autism and developmental disorders, 49(3), 1284–1288. https://doi.org/10.1007/s10803-018-3808-2
39. Wei, D., Dinh, D., Lee, D., Li, D., Anguren, A., Moreno-Sanz, G., Gall, C. M., & Piomelli, D. (2016). Enhancement of Anandamide-Mediated Endocannabinoid Signaling Corrects Autism-Related Social Impairment. Cannabis and cannabinoid research, 1(1), 81–89. https://doi.org/10.1089/can.2015.0008
40. Esposito, G., Scuderi, C., Savani, C., Steardo, L., Jr, De Filippis, D., Cottone, P., Iuvone, T., Cuomo, V., & Steardo, L. (2007). Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression. British journal of pharmacology, 151(8), 1272–1279. https://doi.org/10.1038/sj.bjp.070733
41. Watt, G., & Karl, T. (2017). In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer’s Disease. Frontiers in pharmacology, 8, 20. https://doi.org/10.3389/fphar.2017.00020
42. Hughes, B., & Herron, C. E. (2019). Cannabidiol Reverses Deficits in Hippocampal LTP in a Model of Alzheimer’s Disease. Neurochemical research, 44(3), 703–713. https://doi.org/10.1007/s11064-018-2513-z
43. Wang, Z., Zheng, P., Xie, Y., Chen, X., Solowij, N., Green, K., Chew, Y. L., & Huang, X. F. (2021). Cannabidiol regulates CB1-pSTAT3 signaling for neurite outgrowth, prolongs lifespan, and improves health span in Caenorhabditis elegans of Aβ pathology models. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35(5), e21537. https://doi.org/10.1096/fj.202002724R
44. Bloomfield, M., Green, S. F., Hindocha, C., Yamamori, Y., Yim, J., Jones, A., Walker, H. R., Tokarczuk, P., Statton, B., Howes, O. D., Curran, H. V., & Freeman, T. P. (2020). The effects of acute cannabidiol on cerebral blood flow and its relationship to memory: An arterial spin labelling magnetic resonance imaging study. Journal of psychopharmacology (Oxford, England), 34(9), 981–989. https://doi.org/10.1177/0269881120936419
45. Patricio, F., Morales-Andrade, A. A., Patricio-Martínez, A., & Limón, I. D. (2020). Cannabidiol as a Therapeutic Target: Evidence of its Neuroprotective and Neuromodulatory Function in Parkinson’s Disease. Frontiers in pharmacology, 11, 595635. https://doi.org/10.3389/fphar.2020.595635
46. Consroe, P., Sandyk, R., & Snider, S. R. (1986). Open label evaluation of cannabidiol in dystonic movement disorders. The International journal of neuroscience, 30(4), 277–282. https://doi.org/10.3109/00207458608985678
47. Zuardi, A. W., Crippa, J. A., Hallak, J. E., Pinto, J. P., Chagas, M. H., Rodrigues, G. G., Dursun, S. M., & Tumas, V. (2009). Cannabidiol for the treatment of psychosis in Parkinson’s disease. Journal of psychopharmacology (Oxford, England), 23(8), 979–983. https://doi.org/10.1177/0269881108096519
48. Chagas, M. H., Zuardi, A. W., Tumas, V., Pena-Pereira, M. A., Sobreira, E. T., Bergamaschi, M. M., dos Santos, A. C., Teixeira, A. L., Hallak, J. E., & Crippa, J. A. (2014). Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial. Journal of psychopharmacology (Oxford, England), 28(11), 1088–1098. https://doi.org/10.1177/0269881114550355
49. de Faria, S. M., de Morais Fabrício, D., Tumas, V., Castro, P. C., Ponti, M. A., Hallak, J. E., Zuardi, A. W., Crippa, J., & Chagas, M. (2020). Effects of acute cannabidiol administration on anxiety and tremors induced by a Simulated Public Speaking Test in patients with Parkinson’s disease. Journal of psychopharmacology (Oxford, England), 34(2), 189–196. https://doi.org/10.1177/0269881119895536

The contents in this blog; such as text, content, graphics are intended for educational purposes only. The Content is not intended to substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your healthcare provider.