A Treasure Trove of CBD research compiled from (only) recent and peer-reviewed, scientific journals!
Table of Contents:
1. CBD – General Information
2. Methamphetamine Use
3. Mood, Stress, and Depression
4. Pain-Killer Enhancement, Seizures, and Strokes
5. Whole flower preparations have been found to be more effective than CBD isolates
6. Entourage Effect
7. Neuroprotection
8. Treatment-resistant epilepsy
9. Schizophrenia
10. Osteoarthritis
11. Cancer Therapy/Tumors
12. Breast Cancer
13. Acne
14. Inflammatory Bowel Disease / Ulcerative Colitis
15. Spinal Disc Degeneration
16. Parkinson’s Disease
17. Social Anxiety Disorder / Animals & Humans
18. CBD Drug Interactions
19. Multiple Sclerosis and Mobility
1. CBD – General Information
The cannabis plant contains many biologically active chemicals, including ~60 cannabinoids. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are typically the most concentrated chemical components of cannabis and believed to primarily drive therapeutic benefit. There is evidence that CBD has a number of beneficial pharmacological effects. It is anti-inflammatory, antioxidative, antiemetic, antipsychotic, and neuroprotective. The review of 132 original studies by Bergamaschi et al. describes the safety profile of CBD by highlighting that catalepsy is not induced and physiological parameters (heart rate, blood pressure, and body temperature) are not altered. Moreover, psychomotor and psychological functions are not negatively affected. High doses of up to 1,500 mg per day and chronic use have been repeatedly shown to be well tolerated by humans. Additionally, there is also evidence that CBD may reduce the negative psychotropic effects, memory impairment, and appetite stimulation, anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions.
Rudroff, T., & Sosnoff, J. (2018). Cannabidiol to improve mobility in people with multiple sclerosis. Frontiers in Neurology, 9, 183. doi:10.3389/fneur.2018.00183
2. Methamphetamine Use
In a groundbreaking study by Hay et al. (2018), “Cannabidiol [CBD] administration reduces the motivation to self-administer methamphetamine and relapse to methamphetamine-seeking behavior following abstinence [in rats].”
Hay, G. L., Baracz, S. J., Everett, N. A., Roberts, J., Costa, P. A., Arnold, J. C., … Cornish, J. L. (2018). Cannabidiol treatment reduces the motivation to self-administer methamphetamine and methamphetamine-primed relapse in rats. Journal of Psychopharmacology, 32(12), 1369–1378. https://doi.org/10.1177/0269881118799954
3. Mood, Stress, and Depression
According to Viudez-Martínez, García-Gutiérrez, and Manzanares (2018), Use of cannabidiol in mood-related disorders, due to its anxiolytic and antidepressant-like effects. These have been partially attributed to its action as an allosteric modulator of 5-HTR1A.” “…Cannabidiol at low (5 mg/kg) and intermediate doses (15 mg/kg) successfully blocked the effects induced by acute stress on corticotropin-releasing factor, pro-opiomelanocortin and glucocorticoid receptor gene expression.”
Viudez-Martínez, A., S García-Gutiérrez, M., & Manzanares, J. (2018). Cannabidiol regulates the expression of hypothalamus-pituitary-adrenal axis-related genes in response to acute restraint stress. Journal of Psychopharmacology, 32(12), 1379–1384. https://doi.org/10.1177/0269881118805495
4. Pain-Killer Enhancement, Seizures, and Strokes
According to Rodríguez-Muñoz et al. (2018), “Cannabidiol [CBD] enhances morphine efficacy, diminishes NMDA-mediated seizures and reduces stroke damage via the sigma 1 receptor.”
Rodríguez-Muñoz, M., Onetti, Y., Cortés-Montero, E., Garzón, J., & Sánchez-Blázquez, P. (2018). Cannabidiol enhances morphine antinociception, diminishes NMDA-mediated seizures and reduces stroke damage via the sigma 1 receptor. Molecular Brain, 11(1), 1-12. doi:10.1186/s13041-018-0395-2
5. Whole flower preparations have been found to be more effective than CBD isolates
“To date, there have been over 500 diferent compounds reported to be found within the Cannabis plant of which at least 144 were classifed as phytocannabinoids. Recent findings suggest that diferent phytocannabinoids exhibit diverse pharmacological and biological activities and that they act on multiple targets. A recent review by Russo supports this supposition stating that phytocannabinoids and combinations of cannabinoids can, in certain situations, be more effective than THC or CBD alone. In 2015, Dr. Sanchez-Ramos described how physicians may not be aware that prescribing THC alone (e.g., Marinol® or dronabinol) may not be as efcacious as utilizing the full plant for many types of patients sufering from cancer, neuropathic pain, multiple sclerosis, and bladder-diseases. Turner et al. and Morales et al. suggested that the relative proportions of each phytocannabinoid type will additionally infuence the pharmacological efects of whole Cannabis extracts, either through a polypharmacological efect of the phytocannabinoids themselves, or through modulation of phytocannabinoid efects by the non-cannabinoid content of the plant since they act on multiple targets.
Degradation or alteration of the biosynthesized phytocannabinoids can be dependent on storage time and methods used to process, extract and formulate the plant material. All these variable and unpredictable conditions may change a well-defned Cannabis preparation into a product with signifcantly diferent biological effects.”
Berman, P., Futoran, K., Lewitus, G. M., Mukha, D., Benami, M., Shlomi, T., & Meiri, D. (2018). A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in cannabis. Scientific Reports, 8(1), 1-15. doi:10.1038/s41598-018-32651-4
6. Entourage Effect
An important aspect in cannabinoid compounds is the entourage effect. The entourage effect means that the compounds in cannabis work more sufficient together than if the compounds are isolated. Therefore, CBD products may contain more cannabis compounds, including THC, to increase the effectiveness of the product.
Rudroff, T., & Sosnoff, J. (2018). Cannabidiol to improve mobility in people with multiple sclerosis. Frontiers in Neurology, 9, 183. doi:10.3389/fneur.2018.00183
7. Neuroprotection
“Iron accumulation in the brain has been recognized as a common feature of both normal aging and neurodegenerative diseases. Cognitive dysfunction has been associated to iron excess in brain regions in humans. We have previously described that iron overload leads to severe memory deficits, including spatial, recognition, and emotional memory impairments in adult rats. In the present study we investigated the effects of neonatal iron overload on proteins involved in apoptotic pathways, such as Caspase 8, Caspase 9, Caspase 3, Cytochrome c, APAF1, and PARP in the hippocampus of adult rats, in an attempt to establish a causative role of iron excess on cell death in the nervous system, leading to memory dysfunction. Cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa, was examined as a potential drug to reverse iron-induced effects on the parameters analyzed. Male rats received vehicle or iron carbonyl (30 mg/kg) from the 12th to the 14th postnatal days and were treated with vehicle or CBD (10 mg/kg) for 14 days in adulthood. Iron increased Caspase 9, Cytochrome c, APAF1, Caspase 3 and cleaved PARP, without affecting cleaved Caspase 8 levels. CBD reversed iron-induced effects, recovering apoptotic proteins Caspase 9, APAF1, Caspase 3 and cleaved PARP to the levels found in controls. These results suggest that iron can trigger cell death pathways by inducing intrinsic apoptotic proteins. The reversal of iron-induced effects by CBD indicates that it has neuroprotective potential through its anti-apoptotic action.”
Vanessa Kappel, d. S., Betânia Souza, d. F., Rebeca Carvalho, L. G., Ricardo, T. M., Hallak, J. E., Antônio, W. Z., . . . Schröder, N. (2018). Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload. Translational Psychiatry, 8, 1-8.
8. Treatment-resistant epilepsy
“Our findings suggest that cannabidiol might reduce seizure frequency and might have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy.”
Devinsky, O., Dr Prof, Marsh, E., MD, Friedman, D., MD, Thiele, E., Prof, Laux, L., MD, Sullivan, J., MD, . . . Cilio, M. R., Prof. (2016). Cannabidiol in patients with treatment-resistant epilepsy: An open-label interventional trial. Lancet Neurology, the, 15(3), 270-278. doi:10.1016/S1474-4422(15)00379-8
9. Schizophrenia
“CBD has beneficial effects in patients with schizophrenia. As CBD’s effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder.”
McGuire, P., Robson, P., Cubala, W. J., Vasile, D., Morrison, P. D., Barron, R., . . . Wright, S. (2018). Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: A multicenter randomized controlled trial. American Journal of Psychiatry, 175(3), 225-231. doi:10.1176/appi.ajp.2017.17030325
10. Osteoarthritis
“Local administration of CBD [in rats] blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.”
Philpott, H. T., OʼBrien, 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. doi:10.1097/j.pain.0000000000001052
11. Cancer Therapy/Tumors
“Several studies have demonstrated anti‐proliferative and pro‐apoptotic actions of cannabinoids on various tumors [SIC], together with their anti‐angiogenic properties. The non‐psychoactive cannabinoid cannabidiol (CBD) effectively inhibits the growth of different types of tumors in vitro and in vivo and down‐regulates some pro‐angiogenic signals produced by glioma cells. This study reveals that CBD inhibits angiogenesis by multiple mechanisms. Its dual effect on both tumor and endothelial cells supports the hypothesis that CBD has potential as an effective agent in cancer therapy.”
Solinas, M., Massi, P., Cantelmo, A., Cattaneo, M., Cammarota, R., Bartolini, D., . . . Parolaro, D. (2012). Cannabidiol inhibits angiogenesis by multiple mechanisms. British Journal of Pharmacology, 167(6), 1218-1231. doi:10.1111/j.1476-5381.2012.02050.x
12. Breast Cancer
“We show that CBD inhibits human breast cancer cell proliferation and invasion through differential modulation of the extracellular signal-regulated kinase (ERK) and reactive oxygen species (ROS) pathways, and that both pathways lead to down-regulation of Id-1 expression. Moreover, we demonstrate that CBD up-regulates the pro-differentiation factor, Id-2. Using immune competent mice, we then show that treatment with CBD significantly reduces primary tumor mass as well as the size and number of lung metastatic foci in two models of metastasis. Our data demonstrate the efficacy of CBD in pre-clinical models of breast cancer. The results have the potential to lead to the development of novel non-toxic compounds for the treatment of breast cancer metastasis, and the information gained from these experiments broaden our knowledge of both Id-1 and cannabinoid biology as it pertains to cancer progression.”
McAllister, S. D., Murase, R., Christian, R. T., Lau, D., Zielinski, A. J., Allison, J., . . . Desprez, P. (2011). Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. Breast Cancer Research and Treatment, 129(1), 37-47. doi:10.1007/s10549-010-1177-4
13. Acne
“The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation.” “…Due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris [the formation of comedones, papules, pustules, nodules, and/or cysts as a result of obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying sebaceous gland].”
Oláh, A., Tóth, B. I., Borbíró, I., Sugawara, K., Szöllõsi, A. G., Czifra, G., . . . Bíró, T. (2014). Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. The Journal of Clinical Investigation, 124(9), 3713-3724. doi:10.1172/JCI64628
14. Inflammatory Bowel Disease / Ulcerative Colitis
“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, representing a very important link between the nervous and immune systems in the intestine. Cannabidiol (CBD) is an interesting compound because of its ability to control reactive gliosis in the CNS, without any unwanted psychotropic effects. Therefore the rationale of our study was to investigate the effect of CBD on intestinal biopsies from patients with ulcerative colitis (UC) and from intestinal segments of mice with LPS-induced intestinal inflammation. CBD markedly counteracted reactive enteric gliosis in LPS-mice trough the massive reduction of astroglial signalling neurotrophin S100B. Histological, biochemical and immunohistochemical data demonstrated that S100B decrease was associated with a considerable decrease in mast cell and macrophages in the intestine of LPS-treated mice after CBD treatment. Moreover the treatment of LPS-mice with CBD reduced TNF-α expression and the presence of cleaved caspase-3. Similar results were obtained in ex vivo cultured human derived colonic biopsies. In biopsies of UC patients, both during active inflammation and in remission stimulated with LPS+INF-γ, an increased glial cell activation and intestinal damage were evidenced. CBD reduced the expression of S100B and iNOS proteins in the human biopsies confirming its well documented effect in septic mice. The activity of CBD is, at least partly, mediated via the selective PPAR-gamma receptor pathway. 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. Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.”
De Filippis, D., Esposito, G., Cirillo, C., Cipriano, M., De Winter, B. Y., Scuderi, C., . . . Iuvone, T. (2011). Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis. PloS One, 6(12), e28159. doi:10.1371/journal.pone.0028159
15. Spinal disc degeneration
“Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content. Cannabidiol is the main non-psychotropic component of the Cannabis sativa with protective and anti-inflammatory properties. However, possible therapeutic effects of cannabidiol on intervertebral disc degeneration have not been investigated yet. The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI) and histological analyses. Disc injury was induced in the tail of male Wistar rats via a single needle puncture. The discs selected for injury were punctured percutaneously using a 21-gauge needle. MRI and histological evaluation were employed to assess the results. The effects of intradiscal injection of cannabidiol (30, 60 or 120 nmol) injected immediately after lesion were analyzed acutely (2 days) by MRI. The experimental group that received cannabidiol 120 nmol was resubmitted to MRI examination and then to histological analyses 15 days after lesion/cannabidiol injection. The needle puncture produced a significant disc injury detected both by MRI and histological analyses. Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration.”
Silveira, J. W., Issy, A. C., Castania, V. A., Salmon, C. E. G., Nogueira-Barbosa, M. H., Guimarães, F. S., . . . Del Bel, E. (2014). Protective effects of cannabidiol on lesion-induced intervertebral disc degeneration. PloS One, 9(12), e113161. doi:10.1371/journal.pone.0113161
16. Parkinson’s Disease
“Parkinson’s disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target. The groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 [well-being and quality of life instrument] (p = 0.05). Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities.”
Chagas, M. H. N., Zuardi, A. W., Tumas, V., Pena-Pereira, M. A., Sobreira, E. T., Bergamaschi, M. M., . . . Crippa, J. A. S. (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.
17. Social Anxiety Disorder / Animals & Humans
“Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naive patients with SAD. In the first session, subjects were given an oral dose of CBD (400*mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.”
Crippa, J. A. S., Derenusson, G. N., Ferrari, T. B., Wichert-Ana, L., Duran, F. L., Martin-Santos, R., . . . Hallak, J. E. C. (2011). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report. Journal of Psychopharmacology, 25(1), 121-130. doi:10.1177/0269881110379283
18. CBD Drug Interactions
“Serious drug interactions have not been seen with CBD in combination with any other drugs. However, CBD and other plant cannabinoids can potentially interact with many pharmaceuticals. For example, the activity of liver enzymes such as cytochrome P450 is impacted. More than 60 percent of marketed pharmaceuticals are metabolized by this group of enzymes. At high enough dosages, CBD will temporarily deactivate these liver enzymes, thereby altering how a wide range of compounds is metabolized. The exact mechanisms are unknown and more human studies, which monitor CBD-drug interactions are needed (22). PwMS who are taking any prescription medications are strongly advised to consult with a medical professional.”
Rudroff, T., & Sosnoff, J. (2018). Cannabidiol to improve mobility in people with multiple sclerosis. Frontiers in Neurology, 9, 183. doi:10.3389/fneur.2018.00183
19. Multiple Sclerosis and Mobility
“It is our opinion that CBD supplementation maybe advisable for PwMS to reduce fatigue, pain, spasticity, and ultimately improve mobility.”
Rudroff, T., & Sosnoff, J. (2018). Cannabidiol to improve mobility in people with multiple sclerosis. Frontiers in Neurology, 9, 183. doi:10.3389/fneur.2018.00183
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