Saturday, April 14, 2018

Degenerative Neurological Disorder and Neuroprotective Applications with Medical Cannabis

At the November 2017 medical cannabis Advisory Board Hearing, Doctors recommended to add Degenerative Neurological Disorder / Neuroprotective Applications into the New Mexico Medical Cannabis Program with a 5-0 Vote. The final decision rest with Secretary Lynn Gallagher at the Department of Health and that decision is expected at the next hearing on May 11th 2018. 
View the Petition Here:

Neurological disorders are a group of diseases and conditions that affect the brain, spinal cord and nervous system. Studies have shown medical cannabis can delay the onset or limit the progression of various disorders as well as manage their associated spasms, seizures, tics, pain and other symptoms.
Rare Neurological Disorder in New Mexico
Over 1.5 million people all over the country are afflicted by the potentially deadly condition, called Cerebral Cavernous Malformation, but the disease is oddly concentrated in this specific demographic.

The malformation occurs when abnormal blood vessels form angiomas, or clusters, in the brain or spinal cord. If the angiomas bleed or experience pressure from pushing against structures in the central nervous system, the consequences range from headaches to seizures, neurological deficits or hemorrhages.

According to Senator Tom Udall (D – NM), the Spanish immigrants that settled the New Mexico area in the 1580s carried the disease, and it has since been passed down from generation to generation. As a result, the rare disorder primarily plagues New Mexican Hispanics.

Since there has been little research on the rare disease, it cannot be determined exactly how many New Mexico Hispanics are affected by it, but the number is estimated to be in the thousands.

“Very little is known about this genetic disease that disproportionately affects Hispanic New Mexicans, but can result in seizure, stroke and death,” Sen. Udall said, according to a press release on his website.(Source: Fox News 2015)

Overview of Neurological Disorders
Neurological disorders are disorders of the body’s nervous system, which consists of the brain, spinal cord, and nerves. According to the University of California San Francisco Medical Center, there are more than 600 neurological disorders. Neurological disorders are diseases that affect the brain and the central and autonomic nervous systems. The most common types include Parkinson’s disease, epilepsy, stroke, multiple sclerosis, migraine, tumors of the brain and spinal cord, Tourette syndrome, peripheral neuropathy, spinal cord injury, and amyotrophic lateral sclerosis (ALS).
Damage to the body’s nervous system can be caused by a genetic disorder, a trauma event that causes a brain or spinal cord injury, tumors, degeneration, autoimmune disorders or blood flow disruptions. The cause of some neurological disorders, like Parkinson’s disease, remains unknown.
While symptoms of neurological disorders vary significantly depending on the specific type of disorder, they can include muscle weakness, loss of muscle control or poor coordination, paralysis, loss of sensation, spasms, seizures, loss of mental control, loss of consciousness, confusion and pain.
There is no cure for most neurological disorders, so the focus of treatment is on limiting the progression of the disorder and managing symptoms. Medications can be used to control pain, spasms and seizures.

Cannabinoids as Antioxidants and Neuroprotectants
Cannabinoids have been found to have antioxidant properties, unrelated to NMDA receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia. Non-psychoactive cannabinoids, such as CBD & THCA, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention. A particular disclosed class of cannabinoids useful as neuroprotective antioxidants is formula (I) wherein the R group is independently selected from the group consisting of H, CH3, and COCH3.

Medical Cannabis, Neurological Disorders, and Neurological Applications
Research has shown that cannabis possesses neuroprotective effects, which in turn support the health of the brain, spinal cord and nerves, and help in preventing and limiting the progression of various neurological disorders. The major cannabinoids found in cannabis, including cannabidiol (CBD) and tetrahydrocannabinol (THC), have both shown they can help protect neurons, modulate the inflammatory response and encourage neuroregeneration (Lafuente, et al., 2011) (Kubajewska & Constantinescu, 2010) (Croxford, et al., 2008).
A short list of the 600 neurological disorders: 
Amyotrophic Lateral Sclerosis (ALS)
The cannabinoids in cannabis have shown they are capable of delaying the onset of ALS, prolonging neuron survival and slowing the progression of the disease (Bilsland, et al., 2006) (Carter, Abood, Aggarwal & Weiss, 2010) (Raman, et al., 2004). CBD specifically has been found to significantly slow the onset of ALS (Weydt, et al., 2005). Cannabis can also help with managing the pain, appetite loss, depression, sleeping problems, spasticity and drooling associated with ALS (Amtmann, et al., 2004) (Carter, Abood, Aggarwal & Weiss, 2010).
In numerous studies, CBE has demonstrated the ability to reduce or even eliminate seizures (Blair, Deshpande & DeLorenzo, 2015) (Rosenberg, Tsien, Whalley & Devinsky, 2015) (Szaflarski & Bebin, 2014) (Devinsky, et al., 2014).
Through their activation of the CB1 and CB2, cannabinoids effectively inhibits the pain response caused by migraines (Akerman, Holland, Lasalandra & Goardsby, 2013) (Baron, 2015) (Greco, et al., 2014).
Multiple Sclerosis (MS)
Cannabis’ cannabinoids slow the neurodegenerative process of multiple sclerosis by helping to regulate the body’s immune system, modulating its inflammatory response and encouraging neuroregeneration (Kubajewska & Constantinescu, 2010) (Croxford, et al., 2008). One study showed that cannabinoids reduced the damage to myelin caused from inflammation, thereby offering neuroprotection (Pryce, et al., 2003). Another found that cannabinoids reduced neurological disability, improved motor coordination and limited the progression of the MS in animals with a model of multiple sclerosis (de Lago, et al., 2012).
Parkinson’s Disease
Studies show that cannabis’ neuroprotective effects can slow the progression of Parkinson’s. Its cannabinoids suppress excitotoxicity, glial activation and oxidative injury that lead to neuron degeneration. They improve the mitochondria function and the clearance of cellular debris, which also supports neuron health (More & Choi, 2015) (Garcia-Arencibia, Garcia & Fernandez-Ruiz, 2009) (Lastres-Becker & Fernandez-Ruiz, 2006) (Zeissler, et al., 2013). THC specifically prevents neuron damage caused by free radicals and activates a receptor that encourages the formation of new mitochondria (Zeissler, et al., 2013). CBD has also shown to support the health of neural cells mitochondria (da Silva, et al., 2014) (Zuardi, 2008).
Peripheral Neuropathy
Cannabis effectively reduces neuropathic pain (Jensen, Chen, Furnish & Wallace, 2015) (Baron, 2015) (McDonough, McKenna, McCreary & Downer, 2014). Cannabis-based medicines have even shown they can reduce chronic neuropathic pain that had previously proven refractory to other treatments (Boychuk, Goddard, Mauro & Orellana, 2015).
Prion Diseases
CBD has shown to protect neurons against prion toxicity and therefore reduced the risk of prion diseases, a group of rare degenerative brain disorders (Dirikoc, et al., 2007).
Spinal Cord Injury
Cannabis’ cannabinoids limit neurological damage caused by a spinal cord injury if administered shortly after the traumatic event. The cannabinoids reduce the proinflammatory cytokines and delay the atrophy and degeneration of neurons and thereby protect the white matter and myelin sheath surrounding the cord and nerves (Arevalo-Martin, Garcia-Ovejero & Molina-Holgado, 2010) (Latini, et al., 2014) (Arevalo-Martin, Garcia-Ovejero & Molina-Holgado, 2010) (Arevalo-Martin, et al., 2012). An animal trial have found the administration of cannabinoids shortly after a spinal cord injury caused an improvement in locomotor functional recovery (Kwiatkoski, Guimaraes & Del-Bel, 2012). In addition, cannabis has found to be among the most effective pain relief treatments for people with spinal cord injuries (Wilsey, et al., 2013) (Heutink, Post, Wollaars & van Asbeck, 2011).
Cannabinoids reduce infarct volume and improving functional outcome following strokes (England, Hind, Rasid & O’Sullivan, 2015). When administered shortly after a stroke, CBD specifically protects neurons and astrocytes from damage, and therefore leads to improved functional, histological, biochemical, and neurobehavior recovery (Lafuente, et al., 2011).
Tourette Syndrome
Cannabis effectively suppresses tics and improves behavioral problems associated with Tourette syndrome (Muller-Vahl, 2013) (Muller-Vahl, et al., 2002).
Tumors of the Brain and Spinal Cord
CBD has shown it has anti-tumor properties, with one study showing it significantly inhibited the growth of cancer cells (Massi, et al., 2004).

Recent Studies:
    • Cannabis delays the onset of ALS and slow the progression of the disease.Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials.(
    • CBD-enriched cannabis reduced seizure frequency in 85% of children and caused complete seizure freedom in 14% of children.Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. (
    • Cannabinoids administered shortly following spinal cord injury limits damage.Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery. ( cannabis significantly improved tremors, rigidity and bradykinesia in Parkinson’s disease patients.Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study.(
    • CBD administered shortly following an ischemic event increased the recovery of electrical activity in the brain by about 50% and reduced seizures by 50%.Neuroprotective effects of the nonpsychoactive cannabinodi cannabidiol in hypoxic-ischemic newborn piglets. ( reduced neurological disability and the progression of multiple sclerosis in mice.Cannabinoids ameliorate disease progression in a model of multiple sclerosis in mice, acting preferentially through CB1 receptor-mediated anti-inflammatory effects. (
    • Four weeks of cannabis treatment significantly improved spasms in MS patients.A randomized double-blind-placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex(®)), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. (
    • Cannabis significantly improves neuropathic pain that was refractory to other treatments.The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review.(
    • Six weeks of cannabis treatment reduced tics in patients with Tourette’s syndrome.Cannabinoids reduce symptoms of Tourette’s syndrome.(

Akerman, S., Holland, P.R., Lasalandra, M.P. and Goadsby, PJ. (2013, September). Endocannabinoids in the brainstem modulate dural trigeminovascular nociceptive traffic via CB1 and “triptan” receptors: implications in migraine. Journal of Neuroscience, 33(37), 14869-77.
Amtmann, D., Weydt, P., Johnson, K.L., Jensen, M.P., and Carter, G.T. (2004). Survey of cannabis use in patients with amyotrophic lateral sclerosis. The American Journal of Hospice and Palliative Care, 21(2), 94-104.
Arevalo-Martin, A., Garcia-Ovejero, D., and Molina-Holgado, E. (2010, May). The endocannabinoid 2-arachidonoylglycerol reduces lesion expansion and white matter damage after spinal cord injury. Neurobiology of Disease, 38(2), 304-12.
Arevalo-Martin, A., Garcia-Ovejero, D., Sierra, Palomares, Y., Paniagua-Torija, B., Gonzalez-Gil, I., Oretega-Gutierrez, S., and Molina-Holgado, E. (2012). Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery. PLos One, 7(11), e49057.
Baron, E.P. (2015, June). Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It’s Been… Headache, 55(6), 885-916.
Bilsland, L.G., Dick, J.R., Pryce, G., Petrosino, S., Di Marzo, V., Baker, D., and Greensmith, L. (2006). Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 mice. The FASEB Journal, 20(7), 1003-1005.
Blair, R.E., Deshpande, L.S., and DeLorenzo, R.J. (2015, September). Cannabinoids: is there a potential treatment role in epilepsy? Expert Opinion on Pharmacology, 16(13), 1911-4.
Boychuk, D.G., Goddard, G., Mauro, G., and Orellana, M.R. (2015, Winter). The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. Journal of Oral & Facial Pain and Headache, 29(1), 7-14.
Carter, G.T., Abood, M.E., Aggarwal, S.K and Weiss, M.D. (2010). Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials. American Journal of Hospice & Palliative Medicine, 27(5), 347-356.
Croxford, J.L., Pryce, G., Jackson, S.J., Ledent, C., Giovannoni, G., Pertwee, R.G., Yamamura, T., and Baker, D. (2008, January). Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis. Journal of Neuroimmunology, 193(1-2), 120-9.
da Silva, V.K., de Freitas, B.S., da Silva Dornelles, A., Nery, L.R., Falavigna, L., Ferreira, R.D., Bogo, M.R., Hallak, J.E., Zuardi, A.W., Crippa, J.A., and Schroder, N. (2014, February). Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection. Molecular Neurobiology, 49(1), 222-33.
de Lago, E., Moreno-Martet, M., Cabranes, A., Ramos, J.A., and Fernandez-Ruiz, J. (2012, June). Cannabinoids ameliorate disease progression in a model of multiple sclerosis in mice, acting preferentially through CB1 receptor-mediated anti-inflammatory effects. Neuropharmacology, 62(7), 2299-308.
Devinsky, O., Cilio, M.R., Cross, H., Fernandez-Ruiz, J., French, J., Hill, C., Katz, R., Di Marzo, V., Jutras-Aswad, D., Notcutt, W.G., Martinez-Orgado, J., Robson, P.J., Rohrback, B.G., Thiele, E., Whalley, B., and Friedman, D. (2014, June). Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia, 55(6), 791-802.
Dirikoc, S., Priola, S.A., Marella, M., Zsurger, N., and Chabry, J. (2007, September 5). Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity. Journal of Neuroscience, 27(36), 9537-44.
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England, T.J., Hind, W.H., Rasid, N.A., and O’Sullivan, S.E. (2015, March). Cannabinoids in experimental stroke: a systematic review and meta-analysis. Journal of Cerebral Blood Flow and Metabolism, 35(3), 348-58.
Garcia-Arencibia, M., Garcia, C., and Fernandez-Ruiz, J. (2009, December). Cannabinoids and Parkinson’s disease. CNS & Neurological Disorders Drug Targets, 8(6), 432-9.
Greco, R., Mangione, A.S., Sandrini, G., Nappi, G. and Tassorelli, C. (2014, March). Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model. The Journal of Headache and Pain, 15, 14.
Heutink, M., Post, M.W., Wollaars, M.M., and van Asbeck, F.W. (2011). Chronic spinal cord injury pain: pharmacological and non-pharmacological treatments and treatment effectiveness. Disability and Rehabilitation, 33(5), 433-40.
Jensen, B., Chen, J., Furnish, T., and Wallace, M. (2015, October). Medical Marijuana and Chronic Pain: a Review of Basic Science and Clinical Evidence. Current Pain and Headache Reports, 19(10), 524.
Kubajewska, I., and Constantinescu, C.S. (2010, August). Cannabinoids and experimental models of multiple sclerosis. Immunobiology, 215(8), 647-57.
Kwiatkoski, M., Guimaraes, F.S., and Del-Bel, E. (2012, April). Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury. Neurotoxicity Research, 21(3), 271-80.
Lafuente, H., Alvarez, F.J., Pazos, M.R., Alvarez, A., Rey-Santano, M.C., Mielgo, V., Murgia-Esteve, X., Hilario, E., and Martinez-Orgado, J. (2011, September). Cannabidiol reduces brain damage and improves functional recovery after acute hypoxia-ischemia in newborn pigs. Pediatric Research, 70(3), 272-7.
Lastres-Becker, I., and Fernandez-Ruiz, J. (2006). An overview of Parkinson’s disease and the cannabinoid system and possible benefits of cannabinoid-based treatments. Current Medicinal Chemistry, 13(30< 3705-18.
Latini, L., Bisicchia, E., Sasso, V., Chiurchiu, V., Cavallucci, V., Molinari, M., Maccarrone, M., and Viscomi, M.T. (2014, September 4). Cannabinoid CB2 receptor (CB2R). stimulation delays rubrospinal mitochondrial-dependent degeneration and improves functional recovery after spinal cord hemisection by ERK1/2 inactivation. Cell Death & Disease, e1404.
Massi, P., Vaccani, A., Ceruti, S., Colombo, A. Abbracchio, M.P., and Parolaro, D. (2004, March). Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. The Journal of Pharmacology and Experimental Therapeutics, 308(3), 838-45.
McDonough, P., McKenna, J.P., McCreary, C., and Downer, E.J. (2014, October). Neuropathic orofacial pain: cannabinoids as a therapeutic avenue. The International Journal of Biochemistry & Cell Biology, 55, 72-8.
More, S.V., and Choi, D.K. (2015, April). Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to neuroprotection. Molecular Neurodegeneration, 10, 17.
Muller-Vahl, K.R. (2013). Treatment of Tourette syndrome with cannabinoids. Behavioral Neurology, 27(1), 119-24.
Muller-Vahl, K.R., Schneider, U., Koblenz, A., Jobges, M., Kolbe, H., Daldrup, T., and Emrich, H.M. (2002, March). Treatment of Tourette’s syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial. Pharmacopsychiatry, 35(2), 57-61.
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Raman, C., McAllister, S.D., Rizvi, G., Patel, S.G., Moore, D.H., and Abood, M.E. (2004). Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders, 5(1), 33-30.
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Weydt, P., Hong, S., Witting, A., Moller, T., Stella, N., and Kliot, M. (2005). Cannabinol delays symptom onset in SOD1 transgenic mice without affecting survival. Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders, 6(3), 182-184.
Wilsey, B., Marcotte, T.D., Deutsch, R., Gouaux, B., Sakai, S., and Donaghe, H. (2003, February). Low dose vaporized cannabis significantly improves neuropathic pain. Journal of Pain, 14(2), 136-148.
Zeissler, M.L., Eastwood, J., Hanemann, C.O., Zajicek,J., and Carroll, C., (2013). 9-Tetrahydrocannabinol is protective through PPARy dependent mitochondrial biogenesis in a cell culture model of Parkinson’s disease. Journal of Neurology, Neurosurgery and Psychiatry, 84.
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