Cannabis and Multiple Sclerosis

M. Maccarrone, R. Maldonado, M. Casas, T. Henze and D. Centonze. Cannabinoids therapeutic use: what is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others? Expert Rev Clin Pharmacol. 10(4)443-55. PMID: 28276775

This article reviews the most important current (2017) data involving the eCB system in relation to human diseases, to reflect the present (based mainly on the most used prescription cannabinoid medicine, THC/CBD oromucosal spray) and potential future uses of cannabinoid-based therapy. It is noteworthy that THC/CBD oromucosal spray has been in clinical use for approximately five years in numerous countries world-wide for the management of multiple sclerosis (MS)-related moderate to severe resistant spasticity.  Clinical trials have already confirmed its efficacy and tolerability. Other diseases in which different cannabinoids are currently being investigated include various pain states, Alzheimer's disease, Parkinson's disease, Huntington's disease and epilepsy.

 

C. Mannucci, M. Navarra, F. Calapai, E. Spagnolo, E. Busardò, R. Da Cas, F. Ippolito and G. Calapai. Neurological aspects of medical use of cannabidiol. CNS Neurol Disord Drug Targets PMID: 28412918

This was a review article on the potential role of Cannabidiol in Parkinson's disease, Alzheimer's disease, multiple sclerosis, Huntington's disease, amyotrophic lateral sclerosis andcerebral ischemia were examined.  The researchers have concluded that CBD can possibly produce beneficial effects in Parkinson's disease, Alzheimer's disease, multiple sclerosis patients as well as patients affected by refractory epilepsy. 

Cannabis as Possible Treatment for Alzheimer’s and Parkinson’s Disease

C. Mannucci, M. Navarra, F. Calapai, E. Spagnolo, E. Busardò, R. Da Cas, F. Ippolito and G. Calapai. Neurological aspects of medical use of cannabidiol. CNS Neurol Disord Drug Targets PMID: 28412918

This was a review article on the potential role of Cannabidiol in Parkinson's disease, Alzheimer's disease, multiple sclerosis, Huntington's disease, amyotrophic lateral sclerosis andcerebral ischemia were examined.  The researchers have concluded that CBD can possibly produce beneficial effects in Parkinson's disease, Alzheimer's disease, multiple sclerosis patients as well as patients affected by refractory epilepsy. 

Cannabis as a Possible Treatment for Anxiety and Substance Abuse

J. L. Lee, L. J. Bertoglio, F. S. Guimaraes and C. W. Stevenson. Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders. Br J Pharmacol

This is a review study on the anxiolytic effects of cannabidiol in general as well  its effects on various fear and drug memory processes.  The researchers claim that the understanding of how cannabidiol regulates emotion and emotional memory processing may eventually lead to its use as a treatment for anxiety-related and substance abuse disorders.

Cannabis and Treatment of Inflammatory Bowel Diseases

C. Hasenoehrl, M. Storr and R. Schicho. Cannabinoids for treating inflammatory bowel diseases: where are we and where do we go? Expert Rev Gastroenterol Hepatol. 11(4)329-37. PMID: 28276820

This article concludes that cannabinoids could be helpful for certain symptoms of IBD, but there is still a lack of clinical studies to prove efficacy, tolerability and safety of cannabinoid-based medication for IBD patients, leaving medical professionals without evidence and guidelines.

 

A. Fabisiak and J. Fichna. Cannabinoids as gastrointestinal anti-inflammatory drugs. Neurogastroenterol Motil.Mar 29(3)PMID: 28239924

In this mini-review, they focus on the potential of the endocannabinoid system as a target for novel therapies to treat gastrointestinal (GI) inflammation. The authors discuss the organization of the endocannabinoid signaling and present possible pharmacological sites in the endocannabinoid system and refer to recent clinical findings in the field.  Finally they point at the potential use of cannabinoids at low, non-psychoactive doses to counteract non-inflammatory pathological events in the GI tract.

Cannabis as Treatment for Cancer

S. Gandhi, G. Vasisth and A. Kapoor. Systematic review of the potential role of cannabinoids as antiproliferative agents for urological cancers. Can Urol Assoc J 11(3-4)E138-E142. PMID: 28515817

The aim of this review is to look at the current evidence on the antiproliferative effects of cannabinoids in urological malignancies, including renal, prostate, bladder, and testicular cancers.   To date, there are various in vitro studies elucidating the potential mechanism of action of cannabinoids for urological cancers, along with population-based studies specifically for testicular malignancies. 

 

 

S. Torres, M. Lorente, F. Rodriguez-Fornes, S. Hernandez-Tiedra, M. Salazar, E. Garcia-Taboada, J. Barcia, M. Guzman and G. Velasco. A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol Cancer Ther 10(1)90-103.

Glioblastoma multiforme is a type of brain cancer which is resistant to any known type of current cancer treatments.  These researchers showed some promising results of treatment with an allopathic treatment when combined with THC and CBD.  These two compounds are the main compounds known in Cannabis. 

Cannabis as Treatment for Epilepsy and Seizures

B. K. O'Connell, D. Gloss and O. Devinsky. Cannabinoids in treatment-resistant epilepsy: A review. Epilepsy Behav 70(Pt B)341-348.

 

M. Bialer, S. I. Johannessen, R. H. Levy, E. Perucca, T. Tomson and H. S. White. Progress report on new antiepileptic drugs: A summary of the Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII). Epilepsia 58(2)181-221.

This was a report on the Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII) took place in Madrid, Spain, on June 26-29, 2016.  12 drugs in phase I-III clinical development (adenosine, allopregnanolone, bumetanide, cannabidiol, cannabidivarin, 2-deoxy-d-glucose, everolimus, fenfluramine, huperzine A, minocycline, SAGE-217, and valnoctamide).   Many of the drugs discussed in this report show innovative mechanisms of action and many have shown promising results in patients with pharmacoresistant epilepsies, including previously neglected rare and severe epilepsy syndromes.

 

M. Hausman-Kedem and U. Kramer. Efficacy of Medical Cannabis for Treatment of Refractory Epilepsy in Children and Adolescents with Emphasis on the Israeli Experience. Isr Med Assoc J 19(2)76-78. This was a discussion on the use of Cannabis in children with resistance to medication to alleviate epilepsy.  In summary they concluded that  the good outcome in a significant number of patients, which is not significantly worse than other accepted options for patients with refractory epilepsy, it seems that medical cannabis should be considered a viable treatment option.  Further research is warranted

Cannabis as Treatment for Pain

M. Lynch and F. Campbell. Cannabinoids for Treatment of Chronic Non-Cancer Pain; a Systematic Review of Randomized Trials. Arch Pediatr Adolesc Med: 163(7)601-7. . PMID: 21426373

This was a systematic review of eighteen randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabis based medicine, nabilone, dronabinol and a novel THC analogue. Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Fifteen of the  trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects and all were generally well tolerated, mild to moderate in severity and led to withdrawal from the studies in only a few cases. Overall there is evidence that cannabinoids are safe and modestly effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis.

 

H. Meng, B. Johnston, M. Englesakis, D. E. Moulin and A. Bhatia. Selective Cannabinoids for Chronic Neuropathic Pain: A Systematic Review and Meta-analysis. Anesth Analg.

This was a review on randomized controlled trials that compared selective cannabinoids (dronabinol, nabilone, nabiximols) with conventional treatments (eg, pharmacotherapy, physical therapy, or a combination of these) or placebo in patients with chronic neuropathic pain.  The researchers found that many of these studies did find that selective cannabinoids provide a small analgesic benefit in patients with chronic pain and the use was also associated with improvements in quality of life and sleep with no major adverse effects.

 

P. S. Kim and M. A. Fishman. Cannabis for Pain and Headaches: Primer. Curr Pain Headache Rep 21(4)19.

This article will review relevant literature regarding medical use of marijuana and cannabinoid pharmaceuticals with an emphasis on pain and headaches.   Phytocannabinoids have been identified as key compounds involved in analgesia and anti-inflammatory effects.   Other compounds found in cannabis such as flavonoids and terpenes are also being investigated individually or synergistically with other compounds of the plant.

 

M. A. Ware, T. Wang, S. Shapiro, A. Robinson, T. Ducruet, T. Huynh, A. Gamsa, G. J. Bennett and J. P. Collet. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ 182(14)E694-701. PMC2950205

This study randomized 23 individuals with post-traumatic or post surgery neuropathic pain and measured the effect of cannabis on mood, sleep and quality of life, as well as adverse events.  The researchers found that a single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated (did not have significant adverse effects).

Soy Aids Bone Health

Bitto, A, Burnett, BP, et al. Effects of Genistein Aglycone in Osteoporotic, Ovariectomized Rats: A Comparison with Alendronate, Raloxifene and Oestradiol. Br J Pharmacol 155(6)896-905. PMC2515927

This was a study done on mice.  It was found that consumption of soy could aid in the prevention of postmenopausal osteoporosis.  This study showed increased bone mass density as well as bone mineral density.

Anti-cancer Effects of Legumes

Faris, MA, Takruri, HR, et al. Chemopreventive Effect of Raw and Cooked Lentils (Lens Culinaris L) and Soybeans (Glycine Max) against Azoxymethane-Induced Aberrant Crypt Foci. Nutr Res 29(5)355-62.

This study was done on rats and showed the potential of lentil consumption as a protective agent against colon carcinogenesis.   It also indicated that lentils could slow down the development of the disease.

 

Tajaddini, A, Pourzand, A, et al. Dietary Resistant Starch Contained Foods and Breast Cancer Risk: A Case-Control Study in Northwest of Iran. Asian Pac J Cancer Prev 16(10)4185-92.

This was a study done on 306 women with breast cancer and 309 healthy controls.  The results show that certain foods, in particular whole wheat bread, legumes and boiled potato may reduce breast cancer risk, whereas higher intake of white bread and biscuits may be related to increased BC risk.

The Nightshades

Lablokov, V, Sydora, BC, et al. Naturally Occurring Glycoalkaloids in Potatoes Aggravate Intestinal Inflammation in Two Mouse Models of Inflammatory Bowel Disease. Dig Dis Sci 55(11)3078-85.

This was a study done on mice.  It demonstrated that consumption of potato skins containing glycoalkaloids can significantly aggravate intestinal inflammation in predisposed individuals.

 

 

Childers, N and Margoles, M. An Apparent Relation of Nightshades (Solanaceae) to Arthritis. Journal of Neurological and Orthopedic Medical Surgery 12(227-31.

This study describes the relationship between the consumption of nightshades and the development of arthritis.  Blackpepper is exempted frm this list.

 

 

Tingey, W. Glycoalkaloids as Pest Resistance Factors. American Potato Journal 61(157)

This study showed the potato glycoalkaloids have antimicrobal and pesticidal properties to protect them from their natural enemies.

 

 

Patel, B, Schutte, R, et al. Potato Glycoalkaloids Adversely Affect Intestinal Permeability and Aggravate Inflammatory Bowel Disease. Inflamm Bowel Dis 8(5)340-6.

This study found that concentrations of glycoalkaloids normally available while eating potatoes can adversely affect the mammalian intestine and can aggravate inflammatory bowel disease

 

 

Nisha, P, Abdul Nazar, P, et al. A Comparative Study on Antioxidant Activities of Different Varieties of Solanum Melongena. Food Chem Toxicol 47(10)2640-4.

This study showed that extracts from purple colour small size eggplant fruit demonstrated better antioxidant activities than the other bigger samples.  This my be attributed to the higher phenolic and anthocyanin content.

 

 

 

Mushrooms and Cognitive Function

Ray, B, Chauhan, NB, et al. The"Aged Garlic Extract:"(Age) and One of Its Active Ingredients S-Allyl-L-Cysteine (Sac) as Potential Preventive and Therapeutic Agents for Alzheimer's Disease (Ad). Curr Med Chem. 18(22)3306 -13. PMID: 21728972

 

This random controlled trial showed improved cognitive function in 30 Japanese men and women between the age of 50 and 80 years.  All of these participants had mild cognitive impairment.  This improvement was shown after 16 weeks of consumption of dry powder of the Yamabushitake mushroom

Anti-cancer effect of Alliums

Munday, R and Munday, CM. Relative Activities of Organosulfur Compounds Derived from Onions and Garlic in Increasing Tissue Activities of Quinone Reductase and Glutathione Transferase in Rat Tissues. Nutr Cancer 40(2)205-10.

This study confirmed suggestions from previous research that the organosulfur compounds of garlic and onions could help in the prevention and cure of cancer.  It is done by speeding up the second phase of the liver detox system.  This is a mechanism which could speed up detoxification as a whole, eliminating toxic waste in the body.

 

Cipolla, BG, Mandron, E, et al. Effect of Sulforaphane in Men with Biochemical Recurrence after Radical Prostatectomy. Cancer Prev Res (Phila) 8(8)712-9.

This was a double-blinded, randomized, placebo-controlled, multicenter trial including 78 prostate patients.  It showed that the daily administration of free sulforaphane shows promise in the management of prostate cancer after radical prostatectomy.  It might also help to reduce the risk of recurrence of the cancer.

 

Okano, J, Fujise, Y, et al. Chemoprevention against Hepatocellular Carcinoma. Clin J Gastroenterol. 4(4)185-97. PMID: 26189518

In this review article, sulpforaphane is listed as one of the natural substaces wich has protective activity against liver cancer.  This is valuable as many chronic liver conditions such as hepatitis may result in liver cancer if no protective measures are taken.

Cholesterol and Lipid Lowering Effect of Garlic and Mushroom

Mathew, B, Prasad, N, et al. Cholesterol-Lowering Effect of Organosulphur Compounds from Garlic: A Possible Mechanism of Action. Kathmandu Univ Med J 2(2)100-2. PMID: 15821374

 

This article tried to explain the mechanism by which organosulfur compounds lowers blood lipids.  It appears that the anti-cancer mechanism could be responsible for this action, blocking lipogenic pathways.  This make garlic useful as a protective mechanism in two major modern diseases namely cancer and hyper cholesterolemia.

 

Khatun, K, Mahtab, H, et al. Oyster Mushroom Reduced Blood Glucose and Cholesterol in Diabetic Subjects. Mymensingh Med J 16(1)94-9.

 

This study was undertaken to assess the effect of Oyster Mushrooms in reducing blood glucose, cholesterol and triglycerides (TG) in diabetic patients while testing for toxicity.  Thirty patients who all complied with a 24 day protocol were included in the study. It was found that the consumption of mushrooms lowered blood lipids, total cholesterol and TG significantly.

Garlic and Mushrooms Increases Immunity

Guo, NL, Lu, DP, et al. Demonstration of the Anti-Viral Activity of Garlic Extract against Human Cytomegalovirus in Vitro. Chin Med J (Engl) 106(2)93-6.

 

This study was done in a petri dish on human tissue infected by a virus, in this case the human cytomegalovirus .  It was found that the addition of garlic extract to the culture had an inhibitory effect on the virus which remained even after removal of the extract.  It was also found that continuous addition of the extract had a more powerful effect

 

 

Wesa, KM, Cunningham-Rundles, S, et al. Maitake Mushroom Extract in Myelodysplastic Syndromes (Mds): A Phase II Study. Cancer Immunol Immunother 64(2)237-47. PMC4317517

 

This study done on 21 patients showed mechanisms by which the consumption of maitake mushroom extract increased immunity.  It increased neutrofil and monocyte production as well as production of reactive oxygen species.  All of these target pathogens and consequently increase immunity.

Carotenoids and Eye Health

Macular degeneration

Parisi, V, Tedeschi, M, et al. Carotenoids and Antioxidants in Age-Related Maculopathy Italian Study: Multifocal Electroretinogram Modifications after 1 Year. Ophthalmology 115(2)324-33 e2.

This was a randomized control trial where 27 patients with age - related macular degeneration were enrolled.  They were tested for the effect of supplementation with vit C, vit E and carotenoids on the progression of the disease.  It was found that these nutrients did not only stop the progression, but even improved the condition of the retina, particularly the central area.

 

Cataracts

Christen, WG, Liu, S, et al. Dietary Carotenoids, Vitamins C and E, and Risk of Cataract in Women: A Prospective Study. Arch Ophthalmol 126(1)102-9. PMC2396535

 These prospective observational data examined the relation between dietary intake of carotenoids and vitamins C and E and the risk of cataract in 35 551 profesional women.  It was concluded that higher dietary intakes of these nutrients from food and supplements were associated with significantly decreased risks of cataract.

Carotenoids and bone health

Wu, A, Huang, C, et al. The Relationship between Vitamin a and Risk of Fracture: Meta-Analysis of Prospective Studies. J Bone Miner Res. 29(9)2032-9.

This was a meta analysis done on studies published in Medline and Embase to determine the relationship between vitamin A intake and the risk of hip fractures.  It was found that both high and low blood levels of retinol and vitamin A proposed a risk for fracturing a hip.  Because certain vegetables provide the body with carotenoids which develop into retinol and vitamin A as the body needs it, the authors of the study suggest that consumption of vegetables rich in caretonoids (specifically alpha and Beta carotene).  These nutrients, which should be converted to retinol in blood, may be better than intake of retinol from meat, which is directly absorbed into blood after intake, resulting in too high levels.

Carotenoids and Cancer

Bladder Cancer

Ros, M, Bueno-de-Mesquita, B, et al. Plasma Carotenoids and Vitamin C Concentrations and Risk of Urothelial Cell Carcinoma in the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr. 2012 Oct ;96(4):902-10. Epub 2012 Sep 5. PMID: 96(4)902-10. PMID: 22952186

 

This study showed that higher plasma carotenoids and vitamin C reduced therisk and severity of urothelial cell carcinoma (UCC) in humans.  856 patients with new;y diagnosed UCC participated this case-control study nested within the European Prospective Investigation into Cancer and Nutrition.

 

Pancreatic Cancer

Chen, J, Jiang, W, et al. Association between Intake of Antioxidants and Pancreatic Cancer Risk: A Meta-Analysis. Int J Food Sci Nutr.  30(1-13. PMID: 27356952

 

This was a meta-analysis to systematically evaluate the association between antioxidants intake and pancreatic cancer risk. Relevant articles were retrieved from PUBMED and EMBASE databases and a total of 18 studies were included. Comparing the highest with lowest categories, intakes of selenium, vitamin C, vitamin E, β-carotene and β-cryptoxanthin were associated with development of pancreatic cancer risk.  In conclusion, higher dietary intake of selenium, vitamin C, vitamin E, β-carotene and β-cryptoxanthin was inversely associated with pancreatic cancer risk.

 

Endometrial Cancer

Pelucchi, C, Dal Maso, L, et al. Dietary Intake of Carotenoids and Retinol and Endometrial Cancer Risk in an Italian Case-Control Study. Cancer Causes Control 19(10)1209-15.

This study provides information on the relation between intake of carotenoids and retinol and endometrial cancer.  454 women with endometrial cancer and 908 controls were studied.  The results supported previous reports that these nutrients could lower the risk of endometrial cancer in women.

 

LiverCancer

Polesel, J, Talamini, R, et al. Nutrients Intake and the Risk of Hepatocellular Carcinoma in Italy. Eur J Cancer 43(16)2381-7.

A hospital-based case-control study was conducted in Italy in 1999-2002, including 185 patients with liver cancer and 412 cancer-free controls.  It looked at the effect of dietary consumption of linoleic acid and beta carotene on the risk of developing liver cancer. It found an inverse correlation between these variables, suggesting the consuption of foods rich in these nutrients protected against the disease.

 

Cancer of the mouth

Garewal, HS, Katz, RV, et al. Beta-Carotene Produces Sustained Remissions in Patients with Oral Leukoplakia: Results of a Multicenter Prospective Trial. Arch Otolaryngol Head Neck Surg 125(12)1305-10.

This study was done to confirm reports that beta-carotene produces regressions in patients with oral leukoplakia, a premalignant condition of the mouth.  Fifty four patients were studied for six months.  It was found that beta carotene helped to improve this condition, preventing it to develop in cancer.