- Neurological Disorders
THE FOLLOWING INFORMATION IS PRESENTED FOR EDUCATIONAL PURPOSES ONLY. MEDICAL MARIJUANA INC. PROVIDES THIS INFORMATION TO PROVIDE AN UNDERSTANDING OF THE POTENTIAL APPLICATIONS OF CANNABIDIOL. LINKS TO THIRD PARTY WEBSITES DO NOT CONSTITUTE AN ENDORSEMENT OF THESE ORGANIZATIONS BY MEDICAL MARIJUANA INC. AND NONE SHOULD BE INFERRED.Neurological disorders are a group of diseases and conditions that affect the brain, spinal cord and nervous system. Studies have shown 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.
OVERVIEW OF NEUROLOGICAL DISORDERSNeurological 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 nervous system diseases. 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.
FINDINGS: EFFECTS OF CANNABIS ON NEUROLOGICAL DISORDERSResearch 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 have shown they can help protect neurons, modulate the inflammatory response and encourage neuroregeneration (Kubajewska & Constantinescu, 2010) (Croxford, et al., 2008).
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). 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).
Epilepsy
In numerous studies, cannabinoids have demonstrated the ability to reduce or even eliminate seizures (Wallace, Martin & DeLorenzo, 2002).
Migraine
Through their activation of the CB1 and CB2, cannabinoids effectively inhibits the pain response caused by migraines (Akerman, Holland, Lasalandra & Goardsby, 2013).
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 (Garcia-Arencibia, Garcia & Fernandez-Ruiz, 2009) (Lastres-Becker & Fernandez-Ruiz, 2006).
Peripheral Neuropathy
Cannabis effectively reduces neuropathic pain (McDonough, McKenna, McCreary & Downer, 2014). Low doses of cannabis have even shown they can reduce chronic neuropathic pain that had previously proven refractory to other treatments (Wilsey, et al., 2013).
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). 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).
Tourette Syndrome
Cannabis effectively suppresses tics and improves behavioral problems associated with Tourette syndrome (Muller-Vahl, et al., 2002).
Tumors of the Brain and Spinal Cord
Cannabinoids have shown they have anti-tumor properties, with one study showing it significantly inhibited the growth of cancer cells (Blazquez, et al., 2003).
STATES THAT HAVE APPROVED MEDICAL MARIJUANA FOR NEUROLOGICAL DISORDERSNo states include “neurological disorders” on their list of approved conditions for medical marijuana, although Pennsylvania and West Virginia allow medicinal cannabis for “damage to the nervous tissue of the spinal cord with objective neurological indication of intractable spasticity.” Additionally, many other states allow medical marijuana for the treatment of specific neurological disorders.
For example, Arizona, Arkansas, Connecticut, Delaware, Florida, Georgia, Maine, Massachusetts, Michigan, Minnesota, New Hampshire, New Jersey, New Mexico, New York, North Dakota, Ohio, Pennsylvania and West Virginia have approved medical marijuana for the treatment of ALS.
Alabama, Connecticut, Delaware, Florida, Georgia, Iowa, Louisiana, Maine, Mississippi, Missouri, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Pennsylvania, South Carolina, Texas, Utah, Virginia, West Virginia, Wisconsin, and Wyoming have approved medical marijuana for the treatment of either epilepsy or seizure disorders.
California and Illinois have specifically approved medical marijuana for the treatment of migraines.
Arkansas, Montana, New Mexico, New York, Pennsylvania and West Virginia have approved medical marijuana for the treatment of neuropathy.
New Hampshire, New Mexico, New York, North Dakota, Ohio and Pennsylvania have approved medical marijuana specifically for the treatment of spinal cord injuries.
Arkansas, Illinois, Minnesota and Ohio have approved medical marijuana specifically for the treatment of Tourette syndrome.
Connecticut, Florida, Georgia, Illinois, Maine, Massachusetts, New Hampshire, New Mexico, New York, Ohio, Pennsylvania and West Virginia have approved medical marijuana for the treatment of Parkinson’s disease.
Alaska, Connecticut, Florida, Georgia, Illinois, Maine, Massachusetts, New Hampshire, New Jersey, New Mexico, New York, Ohio, Pennsylvania, Vermont and West Virginia allow medical marijuana for the treatment of multiple sclerosis.
Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Illinois, Louisiana, Maine, Massachusetts, Michigan, Minnesota, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Dakota, Ohio, Oregon, Pennsylvania, Rhode Island, Vermont, Washington and West Virginia legally allow medical marijuana for the treatment of cancer, including tumors.
Currently, no states have approved medical marijuana specifically for the treatment of stroke.
However, in Washington D.C., any condition can be approved for medical marijuana as long as a DC-licensed physician recommends the treatment. Plus, various other states will consider allowing medical marijuana to be used for the treatment of neurological disorders with the recommendation from a physician. These states include: California (any debilitating illness where the medical use of marijuana has been recommended by a physician), Connecticut (other medical conditions may be approved by the Department of Consumer Protection), Massachusetts (other conditions as determined in writing by a qualifying patient’s physician), Nevada (other conditions subject to approval), Oregon (other conditions subject to approval), Rhode Island (other conditions subject to approval), and Washington (any “terminal or debilitating condition”).
In addition, various states have approved medical marijuana for symptoms commonly associated with neurological disorders. Many states have approved medical marijuana specifically to treat chronic pain. These states include: Alaska, Arizona, California, Colorado, Delaware, Hawaii, Maine, Maryland, Michigan, Montana, New Mexico, Ohio, Oregon, Pennsylvania, Rhode Island and Vermont. The states of Nevada, New Hampshire, North Dakota, Montana, Ohio, Vermont and West Virginia allow medical marijuana to treat “severe pain.” The states of Arkansas, Minnesota, Ohio, Pennsylvania and Washington have approved cannabis for the treatment of “intractable pain.”
Alaska, Arizona, Arkansas, California, Colorado, Delaware, Hawaii, Louisiana, Maryland, Michigan, Minnesota, Montana, Nevada, New Hampshire, North Dakota, Ohio, Oregon, Pennsylvania(intractable seizures), Rhode Island, Tennessee (intractable seizures), Vermont, Washington and West Virginia have approved medical marijuana to treat seizures.
Arizona, Arkansas, California, Colorado, Delaware, Florida, Hawaii, Maryland, Michigan, Minnesota, Montana, Nevada, New Hampshire, Oregon, Rhode Island and Washington have approved medical marijuana for the treatment of spasms. Pennsylvania permits marijuana for the treatment of any spastic movement disorder.
RECENT STUDIES ON CANNABIS’ EFFECT ON NEUROLOGICAL DISORDERS
OVERVIEW OF NEUROLOGICAL DISORDERSNeurological 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 nervous system diseases. 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.
FINDINGS: EFFECTS OF CANNABIS ON NEUROLOGICAL DISORDERSResearch 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 have shown they can help protect neurons, modulate the inflammatory response and encourage neuroregeneration (Kubajewska & Constantinescu, 2010) (Croxford, et al., 2008).
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). 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).
Epilepsy
In numerous studies, cannabinoids have demonstrated the ability to reduce or even eliminate seizures (Wallace, Martin & DeLorenzo, 2002).
Migraine
Through their activation of the CB1 and CB2, cannabinoids effectively inhibits the pain response caused by migraines (Akerman, Holland, Lasalandra & Goardsby, 2013).
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 (Garcia-Arencibia, Garcia & Fernandez-Ruiz, 2009) (Lastres-Becker & Fernandez-Ruiz, 2006).
Peripheral Neuropathy
Cannabis effectively reduces neuropathic pain (McDonough, McKenna, McCreary & Downer, 2014). Low doses of cannabis have even shown they can reduce chronic neuropathic pain that had previously proven refractory to other treatments (Wilsey, et al., 2013).
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). 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).
Tourette Syndrome
Cannabis effectively suppresses tics and improves behavioral problems associated with Tourette syndrome (Muller-Vahl, et al., 2002).
Tumors of the Brain and Spinal Cord
Cannabinoids have shown they have anti-tumor properties, with one study showing it significantly inhibited the growth of cancer cells (Blazquez, et al., 2003).
STATES THAT HAVE APPROVED MEDICAL MARIJUANA FOR NEUROLOGICAL DISORDERSNo states include “neurological disorders” on their list of approved conditions for medical marijuana, although Pennsylvania and West Virginia allow medicinal cannabis for “damage to the nervous tissue of the spinal cord with objective neurological indication of intractable spasticity.” Additionally, many other states allow medical marijuana for the treatment of specific neurological disorders.
For example, Arizona, Arkansas, Connecticut, Delaware, Florida, Georgia, Maine, Massachusetts, Michigan, Minnesota, New Hampshire, New Jersey, New Mexico, New York, North Dakota, Ohio, Pennsylvania and West Virginia have approved medical marijuana for the treatment of ALS.
Alabama, Connecticut, Delaware, Florida, Georgia, Iowa, Louisiana, Maine, Mississippi, Missouri, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Pennsylvania, South Carolina, Texas, Utah, Virginia, West Virginia, Wisconsin, and Wyoming have approved medical marijuana for the treatment of either epilepsy or seizure disorders.
California and Illinois have specifically approved medical marijuana for the treatment of migraines.
Arkansas, Montana, New Mexico, New York, Pennsylvania and West Virginia have approved medical marijuana for the treatment of neuropathy.
New Hampshire, New Mexico, New York, North Dakota, Ohio and Pennsylvania have approved medical marijuana specifically for the treatment of spinal cord injuries.
Arkansas, Illinois, Minnesota and Ohio have approved medical marijuana specifically for the treatment of Tourette syndrome.
Connecticut, Florida, Georgia, Illinois, Maine, Massachusetts, New Hampshire, New Mexico, New York, Ohio, Pennsylvania and West Virginia have approved medical marijuana for the treatment of Parkinson’s disease.
Alaska, Connecticut, Florida, Georgia, Illinois, Maine, Massachusetts, New Hampshire, New Jersey, New Mexico, New York, Ohio, Pennsylvania, Vermont and West Virginia allow medical marijuana for the treatment of multiple sclerosis.
Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Illinois, Louisiana, Maine, Massachusetts, Michigan, Minnesota, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Dakota, Ohio, Oregon, Pennsylvania, Rhode Island, Vermont, Washington and West Virginia legally allow medical marijuana for the treatment of cancer, including tumors.
Currently, no states have approved medical marijuana specifically for the treatment of stroke.
However, in Washington D.C., any condition can be approved for medical marijuana as long as a DC-licensed physician recommends the treatment. Plus, various other states will consider allowing medical marijuana to be used for the treatment of neurological disorders with the recommendation from a physician. These states include: California (any debilitating illness where the medical use of marijuana has been recommended by a physician), Connecticut (other medical conditions may be approved by the Department of Consumer Protection), Massachusetts (other conditions as determined in writing by a qualifying patient’s physician), Nevada (other conditions subject to approval), Oregon (other conditions subject to approval), Rhode Island (other conditions subject to approval), and Washington (any “terminal or debilitating condition”).
In addition, various states have approved medical marijuana for symptoms commonly associated with neurological disorders. Many states have approved medical marijuana specifically to treat chronic pain. These states include: Alaska, Arizona, California, Colorado, Delaware, Hawaii, Maine, Maryland, Michigan, Montana, New Mexico, Ohio, Oregon, Pennsylvania, Rhode Island and Vermont. The states of Nevada, New Hampshire, North Dakota, Montana, Ohio, Vermont and West Virginia allow medical marijuana to treat “severe pain.” The states of Arkansas, Minnesota, Ohio, Pennsylvania and Washington have approved cannabis for the treatment of “intractable pain.”
Alaska, Arizona, Arkansas, California, Colorado, Delaware, Hawaii, Louisiana, Maryland, Michigan, Minnesota, Montana, Nevada, New Hampshire, North Dakota, Ohio, Oregon, Pennsylvania(intractable seizures), Rhode Island, Tennessee (intractable seizures), Vermont, Washington and West Virginia have approved medical marijuana to treat seizures.
Arizona, Arkansas, California, Colorado, Delaware, Florida, Hawaii, Maryland, Michigan, Minnesota, Montana, Nevada, New Hampshire, Oregon, Rhode Island and Washington have approved medical marijuana for the treatment of spasms. Pennsylvania permits marijuana for the treatment of any spastic movement disorder.
RECENT STUDIES ON CANNABIS’ EFFECT ON NEUROLOGICAL DISORDERS
- 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.
(http://journals.sagepub.com/doi/pdf/10.1177/1049909110369531) - 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.
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496738/) - Smoking 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.
(http://journals.lww.com/clinicalneuropharm/pages/articleviewer.aspx?year=2014&issue=03000&article=00001&type=abstract) - Cannabinoids 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.
(http://www.sciencedirect.com/science/article/pii/S0028390812000500) - Six weeks of cannabis treatment reduced tics in patients with Tourette’s syndrome.
Cannabinoids reduce symptoms of Tourette’s syndrome.
(http://www.tandfonline.com/doi/pdf/10.1517/14656566.4.10.1717?needAccess=true)
- Cannabis delays the onset of ALS and slow the progression of the disease.
- 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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771033/.
- 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. Retrieved from http://journals.sagepub.com/doi/pdf/10.1177/104990910402100206.
- 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. Retrieved from http://www.sciencedirect.com/science/article/pii/S0969996110000409.
- 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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496738/.
- 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. Retrieved from http://www.fasebj.org/content/20/7/1003.long.
- Blázquez, C., Casanova, M.L., Planas, A., Gómez Del Pulgar, T., Villanueva, C., Fernández-Aceñero, M.J., Aragonés, J., Huffman, J.W., Jorcano, J.L., Guzmán, M. (2003, March). Inhibition of tumor angiogenesis by cannabinoids. FASEB Journal, 17(3), 529-31. Retrieved from http://www.fasebj.org/content/early/2003/03/02/fj.02-0795fje.long.
- Blázquez, C., Chiarlone, A., Bellocchio, L., Resel, E., Pruunsild, P., García-Rincón, D., Sendtner, M., Timmusk, T., Lutz, B., Galve-Roperh, I., and Guzmán, M. (2015). The CB1 cannabinoid receptor signals striatal neuroprotection via a PI3K/Akt/mTORC1/BDNF pathway. Cell Death and Differentiation, 22(10), 1618–1629. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563779/.
- 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. Retrieved from http://journals.sagepub.com/doi/pdf/10.1177/1049909110369531.
- Castelli, M.P., Madeddu, C., Casti, A., Casu, A., Casti, P., Scherma, M., Fattore, L., Fadda, P., and Ennas, M.G. (2014). Δ9-Tetrahydrocannabinol Prevents Methamphetamine-Induced Neurotoxicity. PLoS ONE, 9(5), e98079. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028295/.
- 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. Retrieved from http://www.jni-journal.com/article/S0165-5728(07)00396-7/fulltext.
- 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. Retrieved from http://www.sciencedirect.com/science/article/pii/S0028390812000500.
- Disorder Index. (n.d.). National Institute of Neurological Disorders and Stroke. Retrieved from http://www.ninds.nih.gov/disorders/disorder_index.htm#A.
- Fernández-Ruiz, J., Romero, J., Velasco, G., Tolon, R.M., Ramos, J.A., and Guzman, M. (2007, January). Cannabinoid CB2 receptor: a new target for controlling neural cell survival. Trends in Pharmaceutical Sciences, 28(1), 39-45. Retrieved from http://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(06)00267-7.
- Fishbein, M., Gov, S., Assaf, F., Gafni, M., Keren, O., and Sarne, Y. (2012, September). Long-term behavioral and biochemical effects of an ultra-low dose of Δ9-tetrahydrocannabinol (THC): neuroprotection and ERK signaling. Experimental Brain Research, 221(4), 437-48. Retrieved from http://link.springer.com/article/10.1007%2Fs00221-012-3186-5.
- 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. Retrieved from http://www.eurekaselect.com/93569/article.
- 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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995520/.
- Hampson, A.J., Grimaldi, M., Lolic, M., Wink, D., Rosenthal, R., and Axelrod, J. (2000). Neuroprotective antioxidants from marijuana. Annals of the New York Academy of Sciences, 899,274-82. Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1111/j.1749-6632.2000.tb06193.x/full.
- 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. Retrieved from http://www.tandfonline.com/doi/full/10.3109/09638288.2010.498557?needAccess=true.
- Jiang, W., Zhang, Y., Xiao, L., Van Cleemput, J., Ji, S.P., Bai, G., and Zhang, X. (2005). Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. Journal of Clinical Investigation, 115(11), 3104–3116. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1253627/.
- Kim, S.H., Won, S.J., Mao, X.O., Jin, K., and Greenberg, D.A. (2006, March). Molecular mechanisms of cannabinoid protection from neuronal excitotoxicity. Molecular Pharmacology, 69(30), 691-6. Retrieved from http://molpharm.aspetjournals.org/content/69/3/691.long.
- Kubajewska, I., and Constantinescu, C.S. (2010, August). Cannabinoids and experimental models of multiple sclerosis. Immunobiology, 215(8), 647-57. Retrieved from http://www.sciencedirect.com/science/article/pii/S0171298509001442.
- 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. Retrieved from http://www.eurekaselect.com/58342/article.
- 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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540196/.
- López Rodríguez, A.B., Siopi, E., Finn, D.P., Marchand-Leroux, C., Garcia-Segura, L.M., Jafarian-Tehrani, M.H., and Viveros, M.P. (2013). CB1 and CB2 cannabinoid receptor antagonists prevent minocycline-induced neuroprotection following traumatic brain injury in mice. Cerebral Cortex. Retrieved from http://cercor.oxfordjournals.org/content/early/2013/08/19/cercor.bht202.abstract.
- Lotan, I., Treves, T., Roditi, Y., and Djaldetti, R. (2014, March/April). Cannabis (medical marijuana) treatment for motor and nonmotor symptoms of Parkinson disease: an open-label bbservational study. Clinical Neuropharmacology, 37(2), 41-44. Retrieved from http://journals.lww.com/clinicalneuropharm/pages/articleviewer.aspx?year=2014&issue=03000&article=00001&type=abstract.
- Marsicano, G., Goodenough, S., Monory, K., Hermann, H., Eder, M., Cannich, A., Azad, S.C., Cascio, M.G., Gutiérrez, S.O., van der Stelt, M., López-Rodriguez, M.L., Casanova, E., Schütz, G., Zieglgänsberger, W., Di Marzo, V., Behl, C., and Lutz, B. (2003, October 3). CB1 Cannabinoid Receptors and On-Demand Defense Against Excitotoxicity. Science, 302(5642), 84-8. Retrieved from http://science.sciencemag.org/content/302/5642/84.
- 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. Retrieved from http://www.sciencedirect.com/science/article/pii/S1357272514002581.
- 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. Retrieved from https://www.thieme-connect.com/DOI/DOI?10.1055/s-2002-25028.
- Muller-Vahl, K.R. (2003). Cannabinoids reduce symptoms of Tourette’s syndrome. Expert Opinion on Pharmacotherapy, 4(10), 1717-1725. Retrieved from http://www.tandfonline.com/doi/pdf/10.1517/14656566.4.10.1717?needAccess=true.
- Neurological Disorders. (n.d.). UCSF Medical Center. Retrieved from http://www.ucsfhealth.org/conditions/neurological_disorders/.
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