A Look at the Major and Minor Cannabinoids

Cannabinoids are natural chemical compounds found in the stalk, seed, and flowers of cannabis plants. Scientists have so far identified more than 85 of them. When a person consumes cannabis, these compounds interact with your body’s endocannabinoid system, eliciting a variety of effects.

Cannabinoids and the Endocannabinoid System

Researchers have found that cannabinoids elicit many of their effects through their interaction with the body’s endocannabinoid system (ECS).

The ECS is a vital cellular signaling system that is responsible for regulating a person’s pain, appetite, mood, memory, and cellular life and death cycles. The system’s receptors, known as CB₁ and CB₂, are found in the brain and throughout the body’s nervous system. The cannabinoids that a person ingests when they consume cannabis react with these CB₁ and CB₂ receptors, which in turn help the endocannabinoid system in its efforts to regulate properly and achieve homeostasis.

The cannabinoids you get from cannabis are phytocannabinoids, meaning they come from plantlife. When the ECS is performing properly, it naturally produces endocannabinoids. Some research suggests that a condition referred to as “endocannabinoid deficiency syndrome,” in which the body does not generate enough endocannabinoids, could be the root cause of many autoimmune disorders, including migraines, fibromyalgia, irritable bowel syndrome, and more.

The cannabinoids a person gets from cannabis therefore can supplement what the body is missing so that the ECS can better regulate body processes and encourage healing.

Please refer to the video below for a comprehensive and detailed analysis of the Endocannabinoid System:

The Major Cannabinoids: THC and CBD

The two best-known cannabinoids found in cannabis are tetrahydrocannabinol, or THC, and cannabidiol, also known as CBD. THC is the cannabinoid most people think of when they think of cannabis because it’s responsible for the psychoactive effects and will cause users to experience a “high.” CBD is non-psychoactive, so it won’t cause a high and even counters the psychoactive properties of THC.

Different cannabis strains contain varying levels of cannabinoids. Some cannabis contains far more THC than CBD. Strains that contain less than 0.3% THC and an abundance of CBD are considered hemp.

The Entourage Effect: Compounds Working Together

Some researchers believe that cannabis is more therapeutically beneficial when all the compounds found in the plant — including its a wide range of cannabinoids, terpenes and flavinoids — are administered together. The theory known as the entourage effect suggests that all of the various chemical compounds in cannabis interact and work together synergistically to produce therapeutic benefits and regulatory effects.

The Therapeutic Effects of Cannabinoids: What Research Shows

Scientists are still learning about the therapeutic benefits of cannabis and its cannabinoids. THC and CBD are the best-understood and most studied cannabinoids, but cannabinol (CBN) and cannabichromene (CBC) have also shown to have therapeutic values.

Below are summaries of each of the more well-known cannabinoids what we’ve learned so far about them from research:

Tetrahydrocannabinol (THC)

THC is the most commonly known cannabinoid because it’s the psychotropic compound that produces the “high” that recreational cannabis users are seeking. While there is a risk of some negative side effects from THC, it is not possible to have a fatal overdose. Still, THC and cannabis are Schedule I controlled substances, which is a category of substances considered to be illegal according to the U.S. government.

You can only legally access THC if you are a registered medical cannabis patient in a state that has passed comprehensive medical cannabis legislation. Eight states have passed adult use cannabis laws and allow adults ages 21 and older to consume cannabis without a prescription or having to register with the stage.

Studies have found that THC is effective at managing nausea and vomiting, stimulating appetite, improving sleep, and providing pain relief.

THC has also demonstrated that it’s potentially beneficial for the treatment of the following diseases and disorders:

• Alzheimer’s Disease – THC effectively lower levels of amyloid-beta peptide, the hallmark characteristic and key contributor to the progression of Alzheimer’s disease. Research has also shown it also enhances mitochondrial function, suggesting that THC could be therapeutically beneficial in treating Alzheimer’s disease through multiple functions²¹.

• Amyotrophic Lateral Sclerosis (ALS) – In several animal trials, THC has shown to delay the onset of ALS, prolong the survival of neurons, and slow the disease’s progression once it has manifested^14,22,102. THC also reduces the pain, appetite loss, depression, and drooling symptoms associated with the disease3.

• Anorexia – THC effectively stimulates hunger and increases pleasure when eating29. THC has also shown to increase average weight gain compared to a placebo⁴.

• Arnold-Chiari Malformation and Syringomyelia – THC helps those with Arnold-Chiaro malformation and syringomyelia better manage the symptoms associated with their conditions. Studies have shown it significantly improves pain, sleep, and mood^10,118,122.

• Arthritis – THC has shown to possess anti-inflammatory properties and efficacy at fighting inflammation of the joints⁴⁶. In addition, THC helps manage pain caused by joint diseases¹⁸.

• Autism – THC has shown to significantly improve hyperactivity, lethargy, irritability, stereotypy, and inappropriate speech in an autistic child following regular treatments⁶³. Additionally, THC’s activation of the CB₂ receptors may be able to help restore neural communication and proper cell function⁴³.

• Bone Health – THC’s activation of CB₂ receptors stimulates bone formation and inhibits bone breakdown⁸.

• Cachexia – THC stimulates appetite in patients that have cachexia related to cancer^56,89,90. It has also demonstrated to be effective at increasing appetite and stabilizing body weight in AIDS-cachexia patients¹¹.

• Cancer – THC has shown to possess anti-cancer properties, even reducing tumor sizes in the brain¹⁰8. It is also proven effective at reducing both conditioned rejection and chemotherapy-induced nausea, allowing chemotherapy patients to more comfortably undergo treatments⁷¹. When combined with CBD, THC significantly reduces pain levels in cancer patients with intractable pain⁵⁸. In cancer patients experiencing cachexia, THC has shown to significantly stimulate appetite^56,89,90.

• Crohn’s Disease / Irritable Bowel Syndrome – THC’s anti-inflammatory properties make it effective at combatting Crohn’s disease, even helping some patients achieve complete remission⁸⁶. In addition, THC reduces the abdominal pain, nausea, and diarrhea symptoms associated with inflammatory bowel disease¹⁰⁵.

• Depression – THC has also been shown to decrease brain activity in response to negative stimuli, thereby helping to reduce the social withdrawal, apathy, inability to experience pleasure, and limited emotional expression associated with depression¹⁷.

• Diabetes – THC reduces glucose intolerance, improves glucose tolerance, and increases insulin sensitivity to reduce the risk of diabetes¹²³. In human studies, cannabis use has been correlated to a lower prevalence of diabetes¹⁰⁰.

• Leukemia – THC has been shown to kill leukemia cells⁹⁹. Evidence also suggests that combining THC with other established cytotoxic agents further enhances leukemia cancer cell death⁷².

• Lupus – THC’s anti-inflammatory properties makes it beneficial for treating inflammatory disorders like lupus⁸⁷. THC also assists in the management of pain commonly associated with inflammation-related diseases and disorders²⁶.

• Migraines – THC effectively inhibits the pain response caused by migraines^1,10,44.

• Multiple Sclerosis – THC effectively reduces the pain associated with multiple sclerosis and provides relief from MS-related spasticity^9,66,106.

• Nail-Patella Syndrome – THC manages the pain associated with nail-patella syndrome^10,85,97.

• Nausea – Studies have found that cannabinoids, including THC, are effective at controlling nausea, and can prevent the anticipatory nausea experienced by chemotherapy patients⁹⁴.

• Obesity – The exposure to THC in cannabis smoke has found to be associated with a lower rate of obesity compared to non-cannabis users⁶⁷.

• Pain – THC has been shown effective for lowering pain levels associated with a wide variety of conditions, including spasticity, headache, migraines, and other acute pain and chronic pain conditions^10,57.

• Parkinson’s Disease – THC shown to help prevent damage caused by free radicals and that it activatesa receptor to encourage mitochondria formation, thus helping in the treatment of Parkinson’s disease¹³². In addition, smoking cannabis has shown to significantly improve motor disability and impairments, tremors, rigidity, bradykinesia, sleep and pain in Parkinson’s disease patients⁷⁴.

• Post-Traumatic Stress Disorder (PTSD) – Cannabis use has been shown to significantly reduce PTSD symptoms⁴⁵. Users with PTSD experience better sleep and fewer nightmares¹³. Studies suggest that cannabis has the potential to dampen the strength and emotional impact of traumatic memories⁹⁵. In addition, administering THC shortly after a traumatic event can help prevent the development of PTSD-like symptoms²⁰.

• Sickle Cell Anemia – Cannabis and THC have proven effective at lowering pain associated with sickle-cell anemia⁶¹. In addition, THC’s anti-inflammatory properties can help minimize the vascular occlusion and tissue infarction commonly caused by the disorder¹¹¹.

• Spasms – THC has shown effective for significantly improving muscle spasticity^16,113.

• Spinal Cord Disease – Cannabis (THC) can improve the pain, sleeping problems, bladder control, spasticity, muscle twitching, and depression commonly associated with spinal cord diseases^3,22. In addition, animal trials have demonstrated that cannabinoids can prolong the survival of neurons and slow the progression of spinal cord diseases¹⁴.

• Spinal Cord Injuries – THC has shown to reduce swelling and compression lesion volume, and help preserve white matter and myelin when administered shortly after a spinal cord injury^6,48.  It’s also been shown to improve locomotor functional recovery⁶⁴.

• Traumatic Brain Injury – By interacting with the CB1 and CB² receptors, THC stimulates the release of minocycline, which reduces brain swelling and neurological impairment, and diffuses further injuries to the brain’s axons following a TBI⁷³. In addition, one study found that when individuals have detectable levels of THC in their bloodstream, they are less likely to die as a result of a traumatic brain injury⁹¹.

Cannabidiol (CBD)

While THC is the cannabinoid that gets most of the attention, the relatively recent monumental findings on the potential therapeutic benefits of cannabidiol (CBD) are finally giving the non-psychoactive compound its due shine.

Studies indicate that CBD safely and effectively reduces nausea and vomiting, suppresses seizure activity, combats psychosis disorders, contests inflammatory disorders, counters neurodegenerative disorders, fights tumor and cancer cells, and battles anxiety and depression disorders^42,135. Because of these notable effects, CBD shows exciting potential as a treatment option for neuroinflammation disorders, epilepsy, oxidative injury, vomiting and nausea, and anxiety and schizophrenia⁴².

CBD has shown to potentially be beneficial for the treatment of the following diseases and disorders:

• Alzheimer’s Disease – CBD limits the progression of Alzheimer’s disease by blocking microglial activation, thus providing neuroprotection^19,78,104. The combination of neuroprotective, anti-oxidative, and anti-apoptotic effects provided by CBD decreases the oxidative stress associated with Alzheimer’s disease⁵⁴.

• Amytotraphic Lateral Sclerosis (ALS) – CBD can significantly slow the onset of ALS¹²⁷. In addition, it can help reduce the pain, appetite loss, depression, sleeping problems, spasticity, and drooling that can are commonly associated with ALS^3,22.

• Anxiety Disorder – CBD has effects on the limbic and paralimbic areas of the brain that reduce anxiety and significantly decreases subjective anxiety³⁰. It’s also been shown to significantly reduce the anxiety, cognitive impairment, and discomfort associated with public speaking in individuals with Generalized Social Anxiety Disorder (SAD)¹².

• Arthritis – With its anti-inflammatory benefits and potent anti-arthritic effects that protect joints, CBD limits the progression of arthritis⁷⁷.

• Bone Health – CBD enhances the maturation of collagen, the protein in the bone’s connective tissue that holds the bone together, to significantly improve the strength and the healing process of bones⁶⁰.

• Cancer – CBD has shown to inhibit the progression of cancers located in the breast, lung, prostate and colon in animal models, suggesting it could also be effective at mediating cancer cell death in human subjects^69,81,93. In one study, it inhibited human breast cancer cell proliferation and invasion, and decreased the gene expression in cancer cells, thus lowering the tumor’s aggressiveness and significantly reducing its size⁷⁹. CBD acid (CBDA) has shown the capability of down-regulating invasive human brain cancer cells and therefore preventing their growth^80,116.

• Cardiovascular Disease – CBD reduces myocardial dysfunction, cardiac fibrosis, oxidative-nitrative stress, inflammation, cell death, and interrelated signaling pathways, which collectively offer therapeutic benefits in the treatment of cardiovascular diseases¹⁰¹. In addition, administering CBD shortly after a heart attack has been shown to reduce infarct size and myocardial inflammation, thus showing potential as a treatment for myocardial ischemia³⁷.

• Cirrhosis (Liver Disease) – Studies suggest that CBD helps combat the progression of cirrhosis by assisting in the death of hepatic stellate cells (HSCs), which proliferate and produce excess collagen, causing the accumulation of scarring on the liver⁷⁰. CBD has also been shown to restore liver function in mice experiencing liver failure⁷. In addition, CBD provides protection against ischemia reperfusion, the pivotal mechanism of tissue damage in cirrhosis, by reducing the force of key inflammatory pathways and oxidative/nitrative tissue injury⁸⁴.

• Crohn’s Disease (Irritable Bowel Syndrome) – CBD encourages anti-inflammation of the digestive track by controlling the pro-inflammatory response caused by the disease^33,40.

• Depression – CBD has demonstrated both antidepressant and anti-anxiety effects in animal models^35,131.

• Diabetes – CBD has shown to significantly reduce pro-inflammatory cytokines in the bloodstream and the incidence of diabetes in non-obese mice¹²⁵. It’s also been shown to be effective at curtailing the manifestations of the disease¹²⁶. Research has found CBD treatments provide significant protection from diabetic retinopathy³⁹.

• Epilepsy and Seizure Disorders – CBD has demonstrated the ability to reduce or even eliminate seizures^{15,36,107,114}. Research also finds that cannabis is effective in the treatment of severe pediatric epilepsy disorders like Dravet syndrome, Doose syndrome, and Lennox-Gastaut syndrome98. CBD has also been shown to improve sleep (53%), alertness (71%), and mood (63%) in epileptic children⁵⁰.

• Leukemia – CBD helps prevent complications that can occur after a leukemia patient receives a stem cell or bone marrow transplant¹²⁹. In addition, it has been found to help cancer patients manage the nausea, vomiting, pain, and appetite suppression associated with traditional cancer treatments.

• Migraines – CBD is effective at reducing pain associated with a wide variety of conditions, including headache and migraines^10<s/up>.

• Multiple Sclerosis – CBD combats the inflammation associated with multiple sclerosis, therefore providing neuroprotection and limiting the disease’s progression^62,82. CBD effectively reduces the spasticity caused by multiple sclerosis²⁸. In addition, it has demonstrated the ability to reduce the neuropathic pain associated with multiple sclerosis⁹.

• Nausea – Studies have found that cannabinoids, including CBD, are effective at treating the more difficult to control symptoms of nausea, as well as preventing anticipatory nausea in chemotherapy patients⁹⁴.

• Obesity – CBD has been shown to significant decrease body weight gain and reduce lipid levels^53,112.

• Pain – CBD has been shown effective at lowering pain levels associated with a wide variety of conditions, including spasticity, headache, migraines, and other acute pain and chronic pain conditions^10,57.  

• Parkinson’s Disease – CBD has neuroprotective properties and supports the health of neural cells mitochondria, thus helping to prevent neurodegeneration^32,42,134. Significant improvements in well being and quality of life scores were found in Parkinson’s disease patients undergoing CBD treatment²⁵. CBD may help Parkinson’s disease patients experiencing psychosis¹³⁴.

• Post-Traumatic Stress Disorder (PTSD) – CBD’s interaction with the cannabinoid receptors (CB₁ and CB₂) modulates the release of neurotransmitter that increases a sense of pleasure and initiates alternation of memory processes¹³. CBD can also block the continuous retrieval of the traumatic event, thus enhancing its extension and reducing its associated anxiety^2,95,117.

• Schizophrenia – CBD has anxiolytic and antipsychotic properties. Schizophrenia patients treated with CBD in trials have shown that CBD is a safe and well-tolerated alternative treatment for schizophrenia^68,133.

• Sickle Cell Anemia – Cannabinoids have shown to be effective at helping curtail the severe pain associated with sickle cell disease^49,61.

• Spinal Cord Disease – CBD improves bladder control, muscle spasms, and spasticity in patients with spinal cord diseases and damage¹²¹.

• Spinal Cord Injuries – When administered shortly after a spinal cord injury, CBD stimulates a neuroprotective response to limit damage⁶. CBD has shown to improve motor scores following a spinal cord injury⁶⁴.

• Stroke – Administering CBD shortly after a stroke protects neurons and astrocytes from damage, and therefore leads to improved functional, histological, biochemical, and neurobehavior recovery⁶⁵.

• Traumatic Brain Injury – CBD has shown to provide a neuroprotective effect and limit brain damage following a traumatic brain injury^23,83,96.

Cannabinol (CBN)

We’re only just getting acquainted with cannabinol, or CBN. Studies suggest that it provides a variety of therapeutic benefits — most notably serving as an effective sleep aid.

CBN is the product of degradation, or oxidation, of THC. When THC is exposed to oxygen and heat, over time it breaks down to CBN, which is only mildly psychoactive.

While scientific research is significantly lacking compared to the more notable cannabinoids, evidence does suggest that CBN offers a variety of therapeutic benefits, including promoting sleep, stimulating appetite, encouraging bone growth, preventing glaucoma, and providing antibacterial, anti-inflammatory and analgesic effects.

Research has so far shown CBN to be therapeutically beneficial in the following ways:

• Sleep aid – Of all the cannabinoids, CBN is the most sedative, making it a potential therapeutic option for those with insomnia, sleep apnea, or other sleep disorders. CBN and its derivatives have shown effective at significantly prolonging sleeping time in mice^115,120,130. Research suggests that sleeping improvements are even greater when CBN is combined with THC⁵⁹.

• Antibacterial – Evidence shows CBN could be an effective anti-bacterial. When applied topically, it was effective against MRSA⁵.

• Pain relief – CBN has shown to be effective at reducing sensitivity to pain by stimulating the release of calcitonin gene-related peptide from sensory nerves. This pain relief response is performed without interacting with the CB₁ and CB₂ receptors, which suggests that CNB could provide even a stronger pain relief when used alongside CBD, which does lower pain through activation of the CB₁ and CB₂¹³⁶.

• Anti-inflammatory – CBN has shown to have anti-inflammatory properties, suggesting it could assist in the treatment of inflammatory diseases and disorders like multiple sclerosis, rheumatoid arthritis, diabetes, allergic asthma, and Crohn’s disease³¹.

• Appetite stimulant – CBN has shown to increase appetite, which suggests it could assist in the treatment of cachexia and anorexia, and help improve eating desires in those with cancer or HIV/AIDS⁴¹.

• Anti-convulsive – CBN has shown effective at significantly prolonging seizure latency in mice, suggesting it could assist in the treatment of epilepsy and other seizure disorders^120,130.

• Prevents glaucoma – CBN, when administered topically, has shown to considerably lower ocular tension, thus reducing the risk and progression of glaucoma²⁷.

• Bone stimulation – CBN is among the cannabinoids that are effective at stimulating bone growth^51,52,92,110. As a result, CBN and other cannabinoids reduce the risk of osteoporosis and other bone diseases and support bone health.

Cannabichromene (CBC)

Cannabichromene (CBC) is an often-overlooked cannabinoid found in cannabis. Despite being abundant in certain strains of cannabis, it’s the least studied of all major cannabinoids.

While CBC hasn’t demonstrated groundbreaking therapeutic benefits like THC or CBD, research shows that it does have pain relieving, antidepressant, antimicrobial, anti-inflammatory, anti-proliferative, anti-anxiety, and bone and brain cell stimulating effects that can assist in the treatment of a variety of conditions.

Research has so far shown CBN may be therapeutically beneficial in the following ways:

• Pain reliever – CBC has shown to have pain-relieving properties. When combined with CBD, it demonstrated effectiveness at reducing sensitivity to pain⁷⁶.

• Relieves symptoms of depression – CBC has shown to provide significant antidepressant-like effects when administered on its own, as well as when combined with THC³⁸. In addition, CBC has shown to encourage new brain cell birth, in turn helping prevent the decline of growth in these cells, which is thought to contribute to disorders like depression¹⁰⁹.

• Inhibits growth of fungus – CBC has demonstrated “strong” antibacterial and antifungal effects, showing it can fight against bacteria like E. coli and staph¹¹⁹.

• Relieves anxiety – CBC can reduce anxiety and stress levels. By interacting with CB₁ receptors, CBC stimulates the release of natural chemicals that reduce the excitability of brain cells¹⁰³.

• Reduces inflammation – CBC has demonstrated itself as an effective anti-inflammatory agent, suggesting it could assist with inflammatory-related conditions like arthritis or cardiovascular disease^34,128. In mice, it’s shown to reduce inflammation of the gastrointestinal system, indicating that could help treat Crohn’s disease or other inflammatory bowel diseases⁵⁵. Its anti-inflammatory properties are not caused by interacting with cannabinoid receptors, which means CBC could possibly be combined with other cannabinoid receptor-stimulating cannabinoids that to produce even greater anti-inflammatory effects⁵⁵.

• Inhibits cancer growth – CBC has shown to help inhibit the uptake of anandamide, a human-produced endocannabinoid that has anti-cancer effects, allowing it to remain in the body’s system and work at fighting cancer. Cannabinoids like CBC have also shown inhibits the growth of cancerous tumors in mice, suggesting they may be used as a cancer chemopreventive agent in the future⁸⁸.

• Promotes bone growth – Cannabinoids, like CBC, have shown to be effective at activating human osteoclasts, thus increasing bone density and reducing the risk of bone health conditions like osteoporosis¹²⁴.

• Promotes growth of new brain cells – CBC has been shown to encourage neurogenesis (birth of new brain cells), an important process for memory and learning, and to increase the viability of developing brain cells. The decline of growth in these cells is thought to contribute to disorders like Alzheimer’s disease and depression¹⁰⁹.

 

References:

1.  Akerman, S., Holland, P.R., Lasalandra, M.P., and Goadsby, P.J. (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.
2.  Akirav, I. (2013). Targeting the endocannabinoid system to treat haunting traumatic memories. Frontiers in Behavioral Neuroscience, 7, 124. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776936/.
3.  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.
4.  Andries, A., Frystyk, J., Flyvbjerg, A., and Stoving, R.K. (2014, January). Dronabinol in severe, enduring anorexia nervosa: a randomized controlled trial. The International Journal of Eating Disorders, (47)1, 18-23.
5.  Appendino, G., Gibbons, S., Giana, A. Pagani, A., Grassi, G., Stavri, M., Smith, E., and Rahman, M.M. (2008, August). Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. Journal of Natural Products, 71(8), 1427-30.
6.  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.
7.  Avraham, Y., Grigoriadis, N., Poutahidis, T., Vorobiev, L., Magen, I., Ilan, Y., Mechoulam, R., and Berry, E. (2011, April). Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice. British Journal of Pharmacology, 162(7), 1650-8.
8.  Bab, I., Zimmer, A., and Melamed, E. (2009). Cannabinoids and the skeleton: from Cannabis to reversal of bone loss. Annals of Medicine. 41(8), 560-7.
9.   Barnes, M.P. (2006, April). Sativex: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain. Expert Opinion on Pharmacotherapy, 7(5), 607-15.
10. Baron, E.P. (2015, June). Comprehensive Review of Medicinal Cannabis, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It’s Been. Headache, 55(6), 885-916.
11. Beal, J.E., Olson, R., Laubenstein, L., Morales, J.O., Bellman, P., Yangco, B., Lefkowitz, L, Plasse, T.F., and Shephard, K.V. (1995, February). Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. Journal of Pain and System Management, 10(2), 89-97.
12. Bergamaschi, M.M., Queiroz, R.H., Chagas, M.H., de Oliveira, D.C., De Martinis, B.S., Kapczinski, F., Quevedo, J., Roesler, R., Schroder, N., Nardi, A.E., Martin-Santos, R., Hallak, J.E., Zuardo, A.W., and Crippa, J.A. (2011, May). Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology, 36(6), 1219-26.
13. Betthauser, K., Pilz, J., and Vollmer, L.E. (2015, August). Use and effects of cannabinoids in military veterans with posttraumatic stress disorder. American Journal of Health-System Pharmacy, 72(15), 1279-84.
14. 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.
15. 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.
16. Borgelt, L.M., Franson, K.L., Nussbaum, A.M., and Wang, G.S. (2013, February). The pharmacologic and clinical effects of cannabinoids. Pharmacotherapy, 33(2), 195-209.
17. Bossong, M.G., van Hell, H.H., Jager, G., Kahn, R.S., Ramsey, N.F., and Jansma, J.M. (2013, December). The endocannabinoid system and emotional processing: A pharmacological fMRI study with delta-9-tetrahydrocannabinol. European Neuropsychopharmacology, 23(12), 1687-1697.
18. Burston, J.J., Sagar, D.R., Shao, P., Bai, M., King, E., Brailsford, L., Turner, J.M., Hathway, G.J., Bennett, A.J., Walsh, D.A., Kendall, D.A., Lichtman, A., and Chapman, V. (2013, November 25). Cannabinoid CB2 receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint. PLOS One, doi: 10.1371/journal.pone.0080440.
19. Campbell, V.A., and Gowran, A. (2007, November). Alzheimer’s disease, taking the edge off with cannabinoids? British Journal of Phamacology, 152(5), 655-662.
20. Campos, A.C., Ferreira, F.R., and Guimaraes, F.S. (2012, November). Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5Ht1A receptors. Journal of Psychiatric Research, 46(11), 1501-10.
21. Cao, C., Li, Y., Liu, H., Bai, G., Mayl, J., Lin, X., Sutherland, K., Nabar, N., and Cai, J. (2014). The potential therapeutic effects of THC on Alzheimer’s disease. Journal of Alzheimer’s Disease, 42(3), 973-84.
22. 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.
23. Castillo, A., Tolon, M.R., Fernandez-Ruiz, J., Romero, J., Martinez-Orgado, J. (2010, February). The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic-ischemic brain damage in mice is mediated by CB(2) and adenosine receptors. Neurobiology of Disease, 37(2), 434-40.
24. Chagas, M.H., Eckeli, A.L., Zuardi, A.W., Pena-Pereira, M.A., Sobreira-Neto, M.A., Sobreira, E.T., Camilo, M.R., Bergamaschi, M.M., Schenck, C.H., Hallack, J.E., Tumas, V., and Crippa, J.A. (2014, October). Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson’s disease patients: a case serious. Journal of Clinical Pharmacy and Therapeutics, 39(5), 564-6.
25. Chagas, M.H., Zuardi, A.W., Tumas, V., Pena-Pereira, M.A., Sobreira, E.T., Bergamaschi, M.M., dos Santos, A.C., Teixeira, A.L., Hallak, J.E., and Crippa, J.A. (2014, November). Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial. Journal of Psychopharmacology, 29(11), 1088-98.
26. Clayton, N., Marshall, F.H., Bountra, C., and O’Shaughnessy, C.T. (2002, April). CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain. Pain, 96(3), 253-60.
27. Colasanti, B.K., Craig, C.R., and Allara, R.D. (1984, September). Intraocular pressure, ocular toxicity and neurotoxicity after administration of cannabinol or cannabigerol. Experimental Eye Research, 39(3), 251-9.
28. Collin, C., Ehler, E., Waberzinek, G., Alsindi, Z., Davies, P., Powell, K., Notcutt, W., O’Leary, C., Ratcliffe, S., Novakova, I., Zapletalova, O., Pikova, J., and Ambler, Z. (2010, June). A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurological Research, 32(5), 451-9.
29. Cota, D., Marsicano, G., Lutz, B., Vicennati, V., Stalla, G.K., Pasquali, R., and Pagotto, U. (2013, March). Endogenous cannabinoid system as a modulator of food intake. International Journal of Obesity and Related Metabolic Disorders, 27(3), 289-301.
30. Crippa, J.A., Derenusson, G.N., Ferrari, T.B., Wichert-Ana, L., Duran, F.L., Martin-Santos, R., Simoes, M.V., Bhattacharyya, S., Fusar-Poli, P., Atakan, Z., Santos Filho, A., Freitas-Ferrari, M.C., McGuire, P.K., Zuardi, A.W., Busatto, G.F., and Hallak, J.E. (2011, January). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. Journal of Psychopharmacology, 25(1), 121-30.
31. Croxford, J.L., and Yamamura, T. (2005, September). Cannabinoids and the immune system: potential for the treatment of inflammatory diseases? Journal of Neuroimmunology, 166(1-2), 3-18.
32. 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
33. De Filippis, D., Esposito, G., Cirillo, C., Cipriano, M., De Winter, B.Y., Scuderi, C., Sarnellil, G., Cuomo, R., Steardo, L., De Man, J.G., and Iuvone, T. (2011). Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis. PLos One, 6(12), e28159.
34. DeLong, G.T., Wolf, C.E., Poklis, A., and Lichtman, A.H. (2010, November 1). Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by (9)-tetrahydrocannabinol. Drug and Alcohol Dependence, 112(1-2), 126-33.
35. de Mello Schier, A.R., de Oliveira Ribeiro, N.P., Coutinho, D.S., Machado, S., Arias-Carrion, O., Crippa, J.A., Zuardi, A.W., Nardi, A.E., and Silva, A.C. (2014). Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa. CNS & Neurological Disorders Drug Targets, 13(6), 953-60.
36. Devinsky, O., Cilio, M.R., Cross, H., Fernandez-Ruiz, J., French, J., Hill, C., Katz, R., Di Marzo, V., Jutras-Asward, 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.
37. Durst, R., Danenberg, H., Gallily, R., Mechoulam, R., Meir, K., Grad, E., Beeri, R., Pugatsch, T., Tarsish, E., and Lotan, C. (2007, December). Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury. American Journal of Physiology: Heart and Circulatory Physiology, 293(6), H3602-7.
38. El-Alfy, A.T., Ivey, K., Robinson, K., Ahmed, S., Radwan, M., Slade, D., Khan, I., ElSohly, M., and Ross, S. (2010, June). Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacology, Biochemistry, and Behavior, 95(4), 434-42.
39. El-Remessy, A.B., Al-Shabrawey, M., Khalifa, Y., Tsai, N.T., Caldwell, R.B., and Liou, G.I. (2006, January). Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes. American Journal of Pathology, 168(1), 235-44.
40. Esposito, G., Filippis, D.D., Cirillo, C., Iuvone, T., Capoccia, E., Scuderi, C., Steardo, A., Cuomo, R., and Steardo, L. (2013, May). Cannabidiol in inflammatory bowel diseases: a brief overview. Phytotherapy Research, 27(5), 633-6.
41. Farrimond, J.A., Whalley, B.J., and Williams, C.M. (2012, September). Cannabinol and cannabidiol exert opposing effects on rat feeding patterns. Psychopharmacology, 223(1), 117-29.
42. Fernandez-Ruiz, J., Sagredo, O., Pazos, M.R., Garcia, C., Pertwee, R., Mechoulam, R., and Martinez-Orgado, J. (2013, February). Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? British Journal of Clinical Pharmacology, 75(2), 323-33.
43. Foldy, C., Malenka, R.C., and Sudhof, T.C. (2013, May 8). Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling. Neuron, 78(3), 498-509.
44. 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.
45. Greer, G.R., Grob, C.S., and Halberstadt, A.L. (2014, January-March). PTSD symptom reports of patients evaluated for the New Mexico Cannabinoids Program. Journal of Psychoactive Drugs, 46(1), 73-7.
46. Gui, H., Liu, X., Wang, Z.W., He, D.Y., Su, D.F., and Dai, S.M. (2014). Expression of cannabinoid receptor 2 and its inhibitory effects on synovial fibroblasts in rheumatoid arthritis. Rheumatology, doi: 10.1093/rheumatology/ket447.
47. Guzman, M. (2003, October). Cannabinoids: potential anticancer agents. Nature Reviews, 3(10), 745-55.
48. Hong, J., Nandiwada, V., Jones, V., Lu, M., Warner, D.S., Mukhopadhyay, S., and Sheng, H. (2015, June 15). CB1 cannabinoid receptor agonist inhibits matrix metalloproteinase activity in spinal cord injury: A possible mechanism of improved recovery. Neuroscience Letters, 597, 19-24.
49. Howard, J., Anie, K.A., Holdcroft, A., Korn, S. and Davies, S.C. (2005, October). Cannabis use in sickle cell disease: a questionnaire study. British Journal of Haematology, 131(1), 123-8.
50. Hussain, S.A., Zhou, R., Jacobson, C., Weng, J., Cheng, E., Lay, J., Hung, P., Lerner, J.T., and Sankar, R. (2015, June). Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy & Behavior, 47, 138-41.
51. Idris, A.I., van’t Hof, R.J., Greig, I.R., Ridge, S.A., Baker, D., Ross, R.A., and Ralston, S.H. (2005, July). Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nature Medicine, 11(7), 774-9.
52. Idris, A.I., Sophocleous, A., Landao-Bassonga, E., van’t Hof, R.J., and Ralston, S.H. (2008, November). Regulation of bone mass, osteoclast function, and ovariectomy-induced bone loss by the type 2 cannabinoid receptor. Endocrinology, 149(11), 5619-26.
53. Ignatowska-Jankowska, B., Jankowski, M.M., and Swiergiel, A.H. (2011, February 18). Cannabidiol decreases body weight gain in rats: involvement of CB2 receptors. Neuroscience Letters, 490(1), 82-4.
54. Iuvone, T., Esposito, G., Esposito, R., Santamaria, R., Di Rosa, M., and Izzo, A.A. (2004, April). Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. Journal of Neurochemistry, 89(1), 134-41.
55. Izzo, A.A., Capasso, R., Aviello, G., Borrelli, F., Romano, B., Piscitelli, F., Gallo, L., Capasso, F., Orlando, P., and De Marzo, V. (2012, June). Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. British Journal of Pharmacology, 166(4), 1444-60.
56. Jatoi, A., Windschitl, H.E., Loprinzi, C.L., Sloan, J.A., Dakhil, S.R., Mailliard, J.A., Pundaleeka, S., Kardinal, C.G., Fitch, T.R., Krook, J.E., Novotny, P.J., and Christensen, B. (2002). Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. Journal of Clinical Oncology, 20(2), 567-73.
57. Jensen, B., Chen, J., Furnish, T., and Wallace, M. (2015, October). Cannabinoids and Chronic Pain: a Review of Basic Science and Clinical Evidence. Current Pain and Headache Reports, 19(10), 524.
58. Johnson, J.R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E.D., Potts, R., and Fallon, M.T. (2010, February). Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC: CBD extract and THC extract in patients with intractable cancer-related pain. Journal of Pain and Symptom Management, 39(2), 167-79.
59. Karniol, I.G., Shirakawa, I., Takahashi, R.N., Knobel, E., and Musty, R.E. (1975). Effects of delta9-tetrahydrocannabinol and cannabinol in man. Pharmacology, 13(6), 502-12.
60. Kogan, N.M., Melamed, E., Wasserman, E., Raphael, B., Breuer, A., Stok, K. S., Sondergaard, R., Escudero, A. V., Baraghithy, S., Attar-Namdar, M., Friedlander-Barenboim, S., Mathavan, N., Isaksson, H., Mechoulam, R., Müller, R., Bajayo, A., Gabet, Y., and Bab, I. (2015), Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts. Journal of Bone and Mineral Research. doi: 10.1002/jbmr.2513.
61. Kohli, D.R., Li, Y., Khasabov, S.G., Gupta, P., Kehl, L.J., Ericson, M.E., Nguyen, J., Gupta, V., Hebbel, R.P., Simone, D.A., and Gupta, K. (2010, July 22). Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin: modulation by cannabinoids. Blood, 116(3), 456-65.
62. Kozela, E., Lev., N., Kauschansky, N., Eilam, R., Rimmerman, N., Levy, R., Ben-Nun, A., Juknat, A., and Vogel, Z. (2011, August). Cannabidiol inhibits pathogentic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL-6 mice. British Journal of Pharmacology, 163(7), 1507-19.
63. Kurz, R., and Blass, K. (2010). Use of dronabinol (delta-9-THC) in autism: A prospective single-case-study with an early infantile autistic child. Cannabinoids, 5(4), 4-6.
64. Kwiatkoski, M., Guimaraes, F.S., Del-Bel, E. (2012, April). Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury. Neurotoxicity Research, 21(3), 271-80.
65. 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.
66. Lakhan, S.E., & Rowland, M. (2009). Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC Neurology, 9, 59.
67. Le Foll, B., Trigo, J.M., Sharkey, K.A., and Le Strat, Y. (2013, May). Cannabis and delta9-tetrahydrocannabinol (THC) for weight loss? Medical Hypothesis, 80(5), 564-7.
68. Leweke, F.M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C.W., Hoyer, C., Klosterkotter, J., Hellmich, M., and Koeth, D. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translation Psychiatry, 2, e94.
69. Ligresti, A., Moriello, A.S., Starowicz, K., Matias, I., Pisanti, S., De Petrocellis, L., Laezza, C., Portella, G., Bifulco, M., and Di Marzo, V. (2006, September). Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. Journal of Pharacologogy and Experimental Therapeutics, 318(3), 1375-87.
70. Lim, M.P., Devi, L.A., and Rozenfeld, R. (2011). Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis. Cell Death & Disease. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168994/.
71. Limebeer, C.L., and Parker, L.A. (1999, December 16). Delta-9-tetrahydrocannabinol interferes with the establishment and the expression of conditioned rejection reactions produced by cyclophosphamide: a rat model of nausea. Neuroreport, 10(19), 3769-72.
72. Liu, W.M., Scott, K.A., Shamash, J., Joel, S., and Powles, T.B. (2008, September). Enhancing the in vitro cytotoxic activity of Delta9-tetrahydrocannabinol in leukemic cells through a combinatorial approach. Leukemia & Lymphoma, 49(9), 1800-9.
73. Lopez-Rodriguez, A.B., Siopi, E., Finn, D.P., Marchand-Leroux, C., Garcia-Segura, L.M., Jafarian-Tehrani, M., and Viveros, M.P. (2015, January). CB1 and CB2 cannabinoid receptor antagonists prevent minocycline-induced neuroprotection following traumatic brain injury in mice. Cerebral Cortex, 25(1), 35-45.
74. Lotan, I., Treves, T.A., Roditi, Y., and Djaldetti, R. (2014, March-April). Cannabis (medical Cannabis) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study. Clinical Neuropharmacology, 37(2), 41-4.
75. Maa, E., and Figi, P. (2014, June). The case for medical Cannabis in epilepsy. Epilepsia, 55(6), 783-6.
76. Maione, S., Piscitelli, F., Gatta, L., Vita, D., De Petrocellis, L., Palazzo, E., de Novellis, V., and Di Marzo, V. (2011, February). Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. British Journal of Pharmacology, 162(3), 584-96.
77. Malfait, A.M., Gallily, R., Sumariwalla, P.F., Malik, A.S., Andreakos, E., Mechoulam, R., and Feldmann, M. (2000). The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proceedings of the National Academy of Sciences of the United States of America, 97(17), 9561–9566.
78. Martin-Moreno, A.M., Reigada, D., Ramirez, B.G., Mechoulam, R., Innamorato, N., Cuadrado, A., and de Ceballos, M.L. (2011, June). Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer’s disease. Molecular Pharmacology, 79(6), 964-73.
79. McAllister, S.D., Christian, R.T., Horowitz, M.P., Garcia, A., and Desprez, P.Y. (2007, November). Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. Molecular Cancer Therapeutics, 6(11), 2921-7.
80. McAllister, S.D., Murase, R., Christian, R.T., Lau, D., Zielinski, A.J., Allison, J., Almanza, C., Pakdel, A., Lee, J., Limbad, C., Liu, Y, Debs, R.J., Moore, D.H., and Desprez, P.Y. (2011, August). 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.
81. McAllister, S.D., Soroceanu, L., and Desprez, P.Y. (2015, June). The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids. Journal of Neuroimmune Pharmacology, 10(2), 255-67.
82. Mecha, M., Feliu, A., Inigo, P.M., Mestre, L., Carrillo-Salinas, F.J., and Guaza, C. (2013, November). Cannabidiol provides long-lasting protection against the deletrious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors. Neurobiology of Disease, 59, 141-50.
83. Mechoulam, R., and Shohami, E. (2007, August). Endocannabinoids and traumatic brain injury. Molecular Neurobiology, 36(1), 68-74.
84. Mukhopadhyay, P., Monanraj, R., and Pacher, P. (2011, May 15). Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death. Free Radical Biology & Medicine, 50(10), 1368-1381.
85. Nadolska, K., and Gos., R. (2008). Possibilities of applying cannabinoids’ in the treatment of glaucoma. Klinika Oczna, 110(7-9), 314-7.
86. Naftali, T., Bar-Lev Schleider, L., Dotan, I., Lansky, E.P., Sklerovsky Benjaminov, F., and Konikoff, F.M. (2013, October). Cannabis induces a clinical response in patients with Crohn’s disease: a prospective placebo-controlled study. Clinical Gastroenterology and Hepatology, 11(10), 1276-1280.
87. Nagarkatti, P., Pandey, R., Rieder, S.A., Hegde, V.L., and Nagarkatti, M. (2009, October). Cannabinoids as novel anti-inflammatory drugs. Future Medicinal Chemistry, 1(7), 1333-49.
88. Nakajima, J., Nakae, D., and Yasukawa, K. (2013, August). Structure-dependent inhibitory effects of synthetic cannabinoids against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and skin tumour promotion in mice. Journal of Pharmacy and Pharmacology, 65(8), 1223-1230.
89. Nauck, F., Klaschik, E. (2004, June). Cannabinoids in the treatment of the cachexia-anorexia syndrome in palliative care patients. Schmerz, 18(3), 197-202.
90. Nelson, K., Walsh, D., Deeter, P., and Sheehan, F. (1994). A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. Journal of Palliative Care, 10(1), 14-8.
91. Nguyen, B.M., Kim, D., Bricker, S., Bongard, F., Neville, A., Putnam, B., Smith J., and Plurad, D. (2014, October). Effect of Cannabis use on outcomes in traumatic brain injury. The American Surgeon, 80(10), 979-83.
92. Ofek, O., Karsak, M., Leclerc, N., Fogel, M., Frenkel, B., Wright, K., Tam, J., Attar-Namdar, M., Kram, V., Shohami, E., Mechoulam, R., Zimmer, A., and Bab, I. (2006, January 17). Peripheral cannabinoid receptor, CB2, regulates bone mass. Proceedings of the National Academy of Sciences of the United States of America, 103(3), 696-701.
93. Orellana-Serradell, O., Poblete, C.E., Sanchez, C., Castellon, E.A., Gallegos, I., Huidobro, C., Llanos, M.N., and Contreras, H.R. (2015, April). Proapoptotic effect of endocannabinoids in prostate cancer cells. Oncology Reports, 33(4), 1599-608.
94. Parker, L.A., Rock, E.M., and Limbeer, C.L. (2011, August). Regulation of nausea and vomiting by cannabinoids. British Journal of Pharmacology, 163(7), 1411-22.
95. Passie, T., Emrich, H.M., Karst, M., Brandt, S.D. and Halpern, J.H. (2012, July-August). Mitigation of post-traumatic stress symptoms by Cannabis resin: a review of the clinical and neurobiological evidence. Drug Testing and Analysis, 4(7-8), 649-59.
96. Pazos, M.R., Mohammed, N., Lafuente, H., Santos, M., Martinez-Pinilla, E., Moreno, E., Valdizan, E., Romero, J., Pazos, A., Franco, R., Hillard, C.J., Alvarez, F.J., Martinez-Orgado, J. (2013, August). Mechanisms of cannabidiol neuroprotection in hyopoxic-ischemic newborn pigs: role of 5HT(1A) and CB2 receptors. Neuropharmacology, 71, 282-91.
97. Pinar-Sueiro, S., Rodriguez-Puertas, R., and Vecino, E. (2011, January). Cannabinoid applications in glaucoma. Archivos de la Sociedad Espanola de Oftalmologia, 86(1), 16-23.
98. Porter, B.E., and Jacobson, C. (2013, December). Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy & Behavior, 29(3), 574-7.
99. Powles, T., te Poele, R., Shamash, J., Chaplin, T., Propper, D., Joel, S., Oliver, T., and Liu, W.M. (2005, February 1). Cannabis-induced cytotoxicity in leukemia cell lines: the role of the cannabinoid receptors and the MAPK pathway. Blood, 105(3), 1214-21.
100.  Rajavashisth, T.B., Shaheen, M., Norris, K.C., Pan, D., Sinha, S.K., Oretega, J., Friedman, T.C. (2012). Decreased prevalence of diabetes in Cannabis users: cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) III. BMJ Open, 2, e000494.
101.  Rajesh, M., Mukhopadhyay, P., Batkai, S., Patel, V., Saito, K., Matsumoto, S., Kashiwaya, Y., Horvath, B., Mukhopadhyay, B., Becker, L., Hasko, G., Liaudet, L., Wink, D.A., Veves, A., Mechoulam, R., and Pacher, P. (2010, December 14). Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy, Journal of the American College of Cardiology, 56(25), 2115-25.
102.  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.
103.  Ramikie, T.S., Nyilas, R., Bluett, R.J., Gamble-George, J.C., Hartley, N.D., Mackie, K., Watanabe, M., Katona, I., and Patel, S. (2014, March 5). Multiple mechanistically distinct modes of endocannabinoid mobilation of central amygdala glutamatergic synapses. Neuron, 81(5), 1111-25.
104.  Ramirez, B.G., Blazquez, C., Gomez del Pulgar, T., Guzman, M., and de Ceballos, M.L. (2005, February). Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. Journal of Neuroscience, 25(8), 1904-13.
105.  Ravikoff Allegretti, J., Courtwright, A., Lucci, M., Korzenik, J.R., and Levine, J. (2013, December). Cannabis use patterns among patients with inflammatory bowel disease. Inflammatory Bowel Diseases, 19(13), 2809-14.
106.  Rog, D.J., Nurmikko, T.J., and Young, C.A. (2007, September). Oromucosal delta9-tetrahydrocannabinol-cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clinical Therapeutics, 29(9), 2068-79.
107.  Rosenberg, E.C., Tsien, R.W., Whalley, B.J., and Devinsky, O. (2015, August 18). Cannabinoids and Epilepsy. Neurotherapeutics, Epub ahead of print. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/26282273.
108.  Salazar, M., Carracedo, A., Salanueva, Í.J., Hernández-Tiedra, S., Lorente, M., Egia, A., Vazquez, P., Blazquez, C., Torres, S., Garcia, S., Nowak, J., Fimia, G.M., Piacentini, M., Cecconi, F., Pandolfi, P.P., Gonzalez-Geria, L., Iovanna, J.L., Guzman, M., Boya, P., and Velasco, G. (2009). Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. The Journal of Clinical Investigation, 119(5), 1359–1372. http://doi.org/10.1172/JCI37948
109.  Shinjyo, N., and Di Marzo, V. (2013, November). The effect of cannabichromene on adult neural stem/progenitor cells. Neurochemistry International, 63(5), 432-437.
110.  Scutt, A., and Willilamson, E.M. (2007). Cannabinoids stimulate fibroblastic colony formation by bone marrow cells indirectly via CB2 receptors. Calcified Tissue International, 80, 50-59.
111.  Signorelli, A.A., Ribeiro, S.B., Moraes-Souza, H., de Oliveira, L.F., Ribeiro, J.B., da Silva, S.H., de Oliveira, D.F., and Ribeiro, MF. (2013). Pain measurement as part of primary healthcare of adult patients with sickle cell disease. Revista Brasilileira de Hematologia e Hemoterapia, 35(4), 272-7.
112.  Silvestri, C., Paris, D., Martella, A., Melck, D., Guadagnino, I., Cawthorne, M., Motta, A., and Di Marzo, V. (2015, June). Two non-psychoactive cannabinoids reduce intracellular lipid levels and inhibit hepatosteatosis. Journal of Heptology, 62(6), 1382-900.
113.  Syed, Y.Y., McKeage, K., and Scott, L.J. (2014, April). Delta-9-tetrahydrocannabinol-cannabidiol (Sativex): a review of its use in patients with moderate to severe spasticity due to multiple sclerosis. Drugs, 74(5), 563-78.
114.  Szaflarski, J.P., and Bebin, E.M. (2014, December). Cannabis, cannabidiol, and epilepsy–from receptors to clinical response. Epilepsy & Behavior, 41, 277-82.
115.  Takahaski, R.N., Karniol, I.G. (1975). Pharmacologic interaction between cannabinol and delta9-tetrahydrocannabinol. Psychopharmacologia, 41(3), 277-84.
116.  Takeda, S., Okazaki, H., Ikeda, E., Abe, S., Yoshioka, Y, Watanabe, K., and Aramaki, H. (2014). Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells. The Journal of Toxicological Sciences, 39(5), 711-6.
117.  Trezza, V., and Campolongo, P. (2013, August 9). The endocannabinoid system as a possible target to treat both the cognitive and emotional features of post-traumatic stress disorder (PTSD). Frontiers in Behavioral Neuroscience, 7, 100.
118.  Tripp, D.A., Nickel, J.C., Katz, L., Krsmanovic, A., Ware, M.A., and Santor, D. (2014, November). A survey of cannabis (Cannabis) use and self-reported benefit in men with chronic prostatitis/chronic pelvic pain syndrome. Canadian Urological Association Journal, 8(11-12). Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277530/.
119.  Turner, C.D., and Elsohly, M.A. (1981, August-September). Biological activity of cannabichromene, its homologs and isomers. Journal of Clinical Pharmacology, 21 (8-9 Suppl), 238S-291S.
120.  Usami, N., Kobana, K., Yoshida, H., Kimura, T., Watanabe, K., Yoshimura, H., and Yamamoto, I. (1998, September). Synthesis and pharmacological activities in mice of halogenated delta 9-tetrahydrocannabinol derivatives. Chemical & Pharmaceutical Bulletin, 46(9), 1462-7.
121.  Wade, D.T., Robson, P., House, H., Makela, P., and Aram, J. (2003, February). A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clinical Rehabilitation, 17(1), 21-9.
122.  Ware, M.A., Doyle, C.R., Woods, R., Lynch, M.E., and Clark, A.J. (2003, March). Cannabis use for chronic non-cancer pain: results of a prospective survey. Pain, 102(1-2).
123.  Wargent, E.T., Zaibi, M.S., Silvestri, C., Hislop, D.C., Stocker, C.J., Stott, C.G., Guy, G.W., Duncan, M., Di Marzo, V., and Cawthorne, M.A. (2013, May 27). The cannabinoid 9-tetrahycrocannabivarian (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutrition & Diabetes, 3, e68.
124.  Whyte, L.S., Ford, L., Ridge, S.A., Cameron, G.A., Rogers, M.J., and Ross, R.A. (2012, April). Cannabinoids and bone: endocannabinoids modulate human osteoclast function in vitro. British Journal of Pharmacology. 165(8), 2584-97.
125.  Weiss, L., Zeira, M., Reich, S., Har-Noy, M., Mechoulam, R., Slavin, S., and Gallily, R. (2006, March). Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity, 39(2), 143-51.
126.  Weiss, L., Zeira, M., Reich, S., Slavin, S., Raz, I., Mechoulam, R., and Gallily, R. (2008, January). Cannabidiol arrests onset of autoimmune diabetes in NOD mice. Neuropharmacology, 54(1), 244-9.
127.  Weydt, P., Hong, S., Witting, A., Moller, T., Stella, N. and Kliot, M. (2005). Cannabidiol delays symptom onset in SOD1 transgenic mice without affecting survival. Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders, 6(3), 182-184.
128.  Wirth, P.W., Watson, E.S., ElSohly, M., Turner, C.E., and Murphy, J.C. (1980, June 9). Anti-inflammatory properties of cannabichromene. Life Sciences, 26(23), 1991-5.
129.  Yeshurun, M., Shpilberg, O., Herscovici, C., Shargian, L., Dreyer, J., Peck, A., Israeli, M., Levy-Assaraf, M., Gruenewald, T., Mechoulam, R., Raanani, P., and Ram, R. (2015, October). Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study. Biology of Blood and Marrow Transplantation, 21(10), 1770-5.
130.  Yoshida, H., Usami, N., Ohishi, Y, Watanabe, K., Yamamoto, I., and Yoshimura, H. (1995, February). Synthesis and pharmacological effects in mice of halogenated cannabinol derivatives. Chemical & Pharmaceutical Bulletin, 43(2), 335-7.
131.  Zanelati, T.V., Biojone, C., Moreira, F.A., Guimaraes, F.S., and Joca, S.R. (2010, January). Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors. British Journal of Pharmacology, 159(1), 122-8.
132.  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.
133.  Zuardi, A.W., Crippa, J.A., Hallak, J.E., Moreira, F.A., and Guimaraes, F.S. (2006, April). Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Brazilian Journal of Medical and Biological Research, 39(4), 421-9.
134.  Zuardi, A.W., (2008, September). Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Revista Brasileira De Psiquiatria, 30(3), 271-80.
135.  Zuardi, A.W., Crippa, J.A., Hallak, J.E., Pinto, J.P., Chagas, M.H., Rodrigues, G.G., Dursun, S.M., and Tumas, V. (2009, November). Cannabidiol for the treatment of psychosis in Parkinson’s disease. Journal of Psychopharmacology, 23(8), 979-83.
136.  Zygmunt, P.M., Andersson, D.A., and Hogestatt, E.D. (2002, June 1). 9-Tetrahydrocannabinol and Cannabinol Activate Capsaicin-Sensitive Sensory Nerves via a CB1 and CB2 Cannabinoid Receptor-Independent Mechanism. The Journal of Neuroscience, 22(11), 4720-4727