Tetrahydrocannabinol, or THC, is the most abundant cannabinoid found in cannabis. Studies have shown it safely and effectively provides a plethora of therapeutic benefits.
Overview of THC
Tetrahydrocannabinol (THC) is the most abundant cannabinoid in cannabis. The psychoactive cannabinoid activates the CB1 and CB2 receptors of the endocannabinoid system within the body. Located in the nervous system, the CB1 receptors are responsible for stimulating the psychoactive effect of THC. The CB2 receptors, however, are located in the immune and gastrointestinal system and when activated stimulate processes that offer therapeutic benefits.
Findings: Effects of Cannabis on Effects of THC
Studies have found that THC is effective at managing nausea and vomiting, stimulating appetite, improving sleep and providing pain relief. THC, which has anti-inflammatory properties, has also demonstrated beneficial in the treatment of a variety of diseases and disorders.
THC has been found to be effective at lowering levels of amyloid-beta peptide, the hallmark characteristic and key contributor to the progression of Alzheimer’s, as well as enhancing mitochondrial function, demonstrating that THC could be a potential therapeutic treatment option for Alzheimer’s disease through multiple functions (Cao, et al., 2014).
Numerous animal trials have demonstrated that THC can delay the onset of ALS, prolong the survival of neurons and slow the disease’s progression (Bilsland, et al., 2006) (Carter, Abood, Aggarwal & Weiss, 2010) (Raman, et al., 2004). In addition, it helps reduce pain, appetite loss, depression and drooling symptoms associated with the disease (Amtmann, et al., 2004).
THC effectively stimulates hunger and increases the pleasure felt when eating (Cota, et al., 2003). THC has also shown to increase average weight gain compared to a placebo (Andries, et al., 2014).
THC helps those with Arnold-Chiaro malformation and syringomyelia better manage the symptoms associated with their conditions. It has been shown to significantly improve pain, sleep, and mood (Ware, et al., 2003) (Baron, 2015) (Tripp, et al., 2014).
THC has been determined to have anti-inflammatory effects and have demonstrated effectiveness at fighting inflammation of the joints (Gui, et al., 2013). In addition, THC helps manage pain from joint diseases (Burston, et al., 2013).
THC has shown to significantly improve hyperactivity, lethargy, irritability, stereotypy and inappropriate speech when regularly given to an autistic child (Kurz & Blass, 2010). THC’s activation of the CB2 receptors may be able to help restore neural communication and proper cell function (Foldy, Malenka & Sudhof, 2013).
THC’s activation of the CB2 receptor stimulates bone formation and inhibits bone breakdown (Bab, Zimmer & Melamed, 2009).
THC has shown to significantly stimulate appetite in patients that have cachexia related to cancer (Jatoi, et al., 2002) (Nauck & Klaschik, 2004). In addition, it has demonstrated effective at increasing appetite and stabilizing body weight in AIDS-cachexia patients (Beal, et al., 1995).
THC has shown to have anti-cancer properties, reducing tumor sizes in the brain (Salazar, et al., 2009). It is also effective at reducing both conditioned rejection and chemotherapy-induced nausea, allowing for chemotherapy patients to more comfortably undergo treatments (Limbeer & Parker, 1999). In addition, when combined with CBD, THC has shown to significantly reduce pain levels in cancer patients with intractable pain (Johnson, et al., 2010). THC has shown to significantly stimulate appetite in patients that have cachexia related to cancer (Jatoi, et al., 2002) (Nauck & Klaschik, 2004).
Crohn’s Disease (Irritable Bowel Syndrome)
THC’s anti-inflammatory effects make it effective at combatting Crohn’s disease and even has shown evidence at helping individuals achieve complete remission (Naftali, et al, 2013). In addition, THC helps reduce abdominal pain, nausea and diarrhea associated with inflammatory bowel disease (Ravikoff, et al., 2013).
THC has also been shown to decrease brain activity in response to negative stimuli (but not positive stimuli) (Bossong, et al., 2013).
THC has shown to reduce glucose intolerance, improve glucose tolerance and increase insulin sensitivity in obese mice, thus reducing the risk of diabetes (Wargent, et al., 2013). In human studies, cannabis use has been correlated to a lower prevalence of diabetes (Rajavashisth, et al., 2012).
THC has been shown to induce apoptosis, or death, or leukemia cells (Powles, et al., 2005). In addition, evidence suggests that combining THC with other established cytotoxic agents could further enhance leukemia cancer cell death (Liu, et al., 2008).
THC’s anti-inflammatory effects allow it to act as a potential treatment modality against inflammatory disorders, like lupus (Nagarkatti, et al., 2009). THC can also assist in the management of pain associated with inflammation-related diseases and disorders (Clayton, et al., 2002).
THC has shown effective at inhibiting the pain response caused by migraines (Akerman, Holland, Lasalandra & Goardsby, 2013) (Baron, 2015) (Greco, et al., 2014).
THC effectively reduces the pain associated with multiple sclerosis (Rog, Nurmikko & Young, 2007) (Barnes, 2006). THC also provides relief from MS-related spasticity (Lakhan & Rowland, 2009).
THC manages pain levels associated with nail-patella syndrome (Baron, 2015).
Studies have found that cannabinoids, including THC, are effective at treating the more difficult to control symptoms of nausea, as well as preventing anticipatory nausea in chemotherapy patients (Parker, Rock & Limbeer, 2011).
Cannabis use — more specifically, exposure to THC that’s present in cannabis smoke, has found to be associated with a lower rate of obesity when compared to non-cannabis users (Le Foll, Trigo, Sharkey & Le Strat, 2013).
THC 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 (Jensen, Chen, Furnish & Wallace, 2015) (Baron, 2015).
THC has been shown to help prevent damage caused by free radicals and activate a receptor to encourage mitochondria formation, thus helping in the treatment of Parkinson’s disease (Zeissler, et al., 2016). In addition, smoking cannabis has shown to significantly improve motor disability and impairments, tremors, rigidity, bradykinesia, sleep and pain in Parkinson’s disease patients (Lotan, Treves, Roditi & Djaldetti, 2014).
Cannabis use has been shown to significantly reduce PTSD symptoms (Greer, Grob & Halberstadt, 2014). Users experience better sleep and fewer nightmares. (Betthauser, Piilz, Vollmer, 2015). Studies suggest that cannabis has the potential to dampen the strength and emotional impact of traumatic memories (Passie, et al., 2013).
Cannabis and THC have proven effective at lowering pain associated with sickle-cell anemia (Kohli, et al., 2010). In addition, THC’s anti-inflammatory properties can help minimize the vascular occlusion and tissue infarction commonly caused by the disorder (Signorelli, et al., 2013).
THC has shown effective for significantly improving muscle spasticity (Borgelt, Franson, Nussbaum & Wang, 2013) (Syed, McKeage & Scott, 2014).
Cannabis (THC) can improve pain, sleeping problems, bladder control, spasticity, muscle twitching and depression commonly associated with spinal cord diseases (Amtmann, et al., 2004) (Carter, Abood, Aggarwal & Weiss, 2010). In addition, animal trials have demonstrated that the administration of cannabinoids can prolong the survival of neurons and slow the progression of spinal cord diseases (Bilsland, et al., 2006).
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 (Arevalo-Martin, et al., 2012) (Hong, et al., 2015). It’s also been shown to improve locomotor functional recovery (Kwiatkoski, Guimaraes & Del-Bel, 2012).
THC activates the CB1 and CB2 receptors, which stimulate the release of minocycline, which reduces brain swelling and neurological impairment, and diffuses further injuries to the brain’s axons following a TBI (Lopez-Rodriguez, et al., 2015). 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 injury (Nguyen, et al., 2014).
Akerman, S., Holland, PR., Lasalandra, MP. 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/.
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/.
Amtmann, D., Weydt, P., Johnson, KL., Jensen, MP. And Carter, GT. (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.
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. Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1002/eat.22173/full.
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/.
Bab, I., Zimmer, A. and Melamed, E. (2009). Cannabinoids and the skeleton: from marijuana to reversal of bone loss. Annals of Medicine. 41(8), 560-7. Retrieved from http://www.tandfonline.com/doi/full/10.1080/07853890903121025?needAccess=true.
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. Retrieved from http://www.tandfonline.com/doi/full/10.1517/14656522.214.171.1247?needAccess=true.
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.Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1111/head.12570/full.
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. Retrieved from http://www.jpsmjournal.com/article/0885-3924(94)00117-4/pdf.
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. Retrieved from http://www.ajhp.org/content/72/15/1279.long.
Bhattacharyya, S., Morrison, P.D., Fusar-Poli, P., Martin-Santos, R., Borgwardt, S., Winton-Brown, T., Nosarti, C., O’ Carroll, C.M., Seal, M., Allen, P., Mehta, M.A., Stone, J.M., Tunstall, N., Giampietro, V., Kapur, S., Murray, R.M., Zuardi, A.W., Crippa, J.A., and Atakan ZMcGuire, P.K. (2010). Opposite Effects of Δ-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology. Neuropsychopharmacology, 35(3), 764–774. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055598/.
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.
Borgelt, L.M., Franson, K.L., Nussbaum, A.M., and Wang, G.S. (2013, February). The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy, 33(2), 195-209. Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1002/phar.1187/full.
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. Retrieved from http://www.europeanneuropsychopharmacology.com/article/S0924-977X(13)00195-8/fulltext.
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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840025/.
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. Retrieved from http://content.iospress.com/articles/journal-of-alzheimers-disease/jad140093.
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/.
Chen, J., Lee, C.T., Errico, S., Deng, X., Cadet, J.L., and Freed, W.J. (2005). Protective effects of Δ9-tetrahydrocannabinol against N-methyl-D-aspartate-induced AF5 cell death. Brain Research. Molecular Brain Research, 134(2), 215–225. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1824211/.
Clayton, N., Marshall, FH., Bountra, C., and O’Shaughnessy, CT. (2002, April). CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain. Pain, 96(3), 253-60. Retrieved from http://journals.lww.com/pain/pages/articleviewer.aspx?year=2002&issue=04000&article=00005&type=abstract.
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. Retrieved from http://www.nature.com/ijo/journal/v27/n3/full/0802250a.html.
El-Alfy, A.T., Ivey, K., Robinson, K., Ahmed, S., Radwan, M., Slade, D., Khan, I., ElSohly, M., and Ross, S. (2010). Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacology, Biochemistry, and Behavior, 95(4), 434–442. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866040/.
Elmes, M.W., Kaczocha, M., Berger, W.T., Leung, K., Ralph, B.P., Wang, L., Sweeney, J.M., Miyauchi, J.T., Tsirka, S.E., Ojima, I., and Deutsch, D.G. (2015). Fatty Acid-binding Proteins (FABPs) Are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD). The Journal of Biological Chemistry, 290(14), 8711–8721. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423662/.
El-Remessy, A.B., Khalil, I.E., Matragoon, S., Abou-Mohamed, G., Tsai, N.J., Roon, P., Caldwell, R.B., Caldwell, R.W., Green, K., and Liou, G.I. (2003). Neuroprotective Effect of(−)Δ9-Tetrahydrocannabinol and Cannabidiol in N-Methyl-d-Aspartate-Induced Retinal Neurotoxicity : Involvement of Peroxynitrite. The American Journal of Pathology, 163(5), 1997–2008. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892413/.
Fairbairn, J.W., and Pickens, J.T. (1981, March). Activity of cannabis in relation to its delta’-trans-tetrahydro-cannabinol content. British Journal of Pharmacology, 72(3), 401-409. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2071597/.
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.
Foldy, C., Malenka, RC. and Sudhof, TC. (2013, May 8). Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling. Neuron, 78(3), 498-509. Retrieved from http://www.cell.com/neuron/fulltext/S0896-6273(13)00225-0.
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/.
Greer, G.R., Grob, C.S., and Halberstadt, A.L. (2014, January-March). PTSD symptom reports of patients evaluated for the New Mexico Medical Cannabis Program. Journal of Psychoactive Drugs, 46(1), 73-7. Retrieved from http://www.tandfonline.com/doi/full/10.1080/02791072.2013.873843?needAccess=true.
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. Retrieved from https://academic.oup.com/rheumatology/article/53/5/802/1798167/Expression-of-cannabinoid-receptor-2-and-its.
Guzmán, M., Duarte, M. J., Blázquez, C., Ravina, J., Rosa, M. C., Galve-Roperh, I., Sanchez, C., Velasco, G., and González-Feria, L. (2006). A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. British Journal of Cancer, 95(2), 197–203. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360617/.
Hampson, A.J., Grimaldi, M., Axelrod, J., and Wink, D. (1998). Cannabidiol and (−)Δ9-tetrahydrocannabinol are neuroprotective antioxidants. Proceedings of the National Academy of Sciences of the United States of America, 95(14), 8268–8273. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20965/.
Hartley, J.P.R., Nogrady, S.G., and Graham, J.D.P. (1978). Brochodiltor Effect of Δ1-Tetrahydrocannabinol. British Journal of Clinical Pharmacology, 5, 523-535. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1429361/pdf/brjclinpharm00292-0050.pdf.
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. Retrieved from http://www.sciencedirect.com/science/article/pii/S0304394015002979.
Huber, G.L., Pochay, V.E., Pereira, W., Shea, J.W., Hinds, W.C., First, M.W., and Sornberger, G.C. (1980, March). Marijuana, Tetrahydrocannabinol, and Pulmonary Antibacterial Defenses. Chest, 77(3), 403-10. Retrieved from http://www.sciencedirect.com/science/article/pii/S0012369215415533.
Jamontt, J., Molleman, A., Pertwee, R., and Parsons, M. (2010). The effects of Δ9-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis. British Journal of Pharmacology, 160(3), 712–723. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931570/.
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. Retrieved from http://ascopubs.org/doi/full/10.1200/JCO.2002.20.2.567.
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. Retrieved from http://www.jpsmjournal.com/article/S0885-3924(09)00787-8/fulltext.
Kohli, D.R., Li, Y., Khasabov, S.G., Gupta, P., Kehl, L.J., Ericson, ME., Nguyen, J., Gupta, V., Hebbel, RP., Simone, DA. 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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913454/.
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. Retrieved from https://cannabis-med.org/data/pdf/en_2010_04_1.pdf.
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. Retrieved from http://link.springer.com/article/10.1007%2Fs12640-011-9273-8.
Lakhan, S.E., and Rowland, M. (2009). Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC Neurology, 9, 59. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793241/.
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. Retrieved from http://www.medical-hypotheses.com/article/S0306-9877(13)00042-X/fulltext.
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. Retrieved from http://journals.lww.com/neuroreport/pages/articleviewer.aspx?year=1999&issue=12160&article=00009&type=abstract.
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. Retrieved from https://academic.oup.com/cercor/article-lookup/doi/10.1093/cercor/bht202.
Lotan, I., Treves, T.A., Roditi, Y., and Djaldetti, R. (2014, March-April). Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study. Clinical Neuropharmacology, 37(2), 41-4.Retrieved from http://journals.lww.com/clinicalneuropharm/pages/articleviewer.aspx?year=2014&issue=03000&article=00001&type=abstract.
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. Retrieved from http://www.tandfonline.com/doi/full/10.1080/10428190802239188?needAccess=true.
Marcu, J.P., Christian, R.T., Lau, D., Zielinski, A.J., Horowitz, M.P., Lee, J., Pakdel, A., Allison, J., Limbad, C., Moore, D.H., Yount, G.L., Desprez, P.Y, and McAllister, S.D. (2010). Cannabidiol enhances the inhibitory effects of Δ9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Molecular Cancer Therapeutics, 9(1), 180–189. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806496/.
McKinney, D.L., Cassidy, M.P., Collier, L.M., Martin, B.R., Wiley, J.L., Selley, D.E., and Sim-Selley, L.J. (2008). Dose-Related Differences in the Regional Pattern of Cannabinoid Receptor Adaptation and in Vivo Tolerance Development to Δ9-Tetrahydrocannabinol. The Journal of Pharmacology and Experimental Therapeutics, 324(2), 664–673. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637548/.
Morgan, C.J., Freeman, T.P., Schafer, G.L., and Curran, H.V. (2010). Cannabidiol Attenuates the Appetitive Effects of Δ9-Tetrahydrocannabinol in Humans Smoking Their Chosen Cannabis. Neuropsychopharmacology, 35(9), 1879–1885. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906701/.
Morel, L.J., Giros, B., and Dauge, V. (2009, October). Adolescent exposure to chronic delta-9-tetrahydrocannabinol blocks opiate dependence in maternally deprived rats. Neuropsychopharmacology, 34(11), 2469-76. Retrieved from http://www.nature.com/npp/journal/v34/n11/full/npp200970a.html.
Muller-Vahl, K.R., Koblenz, A., Jobges, M., Kolbe, H., Emrich, H.M., and Schneider, U. (2001, January). Influence of Treatment of Tourette Syndrome with Δ9-Tetrahydrocannabinol (Δ9-THC) on Neuropsychological Performance. Pharmacopsychiatry, 34(1), 19-24. Retrieved from https://www.thieme-connect.com/DOI/DOI?10.1055/s-2001-15191.
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.
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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/.
Nauck, F., Klaschik,E. (2004, June). Cannabinoids in the treatment of the cachexia-anorexia syndrome in palliative care patients. Schmerz, 18(3), 197-202. Retrieved from http://link.springer.com/article/10.1007%2Fs00482-003-0277-z.
Naftali, T., Bar-Lev Schleider, L., Dotan, I., Lansky, EP., Sklerovsky Benjaminov, F. and Konikoff, FM. (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. Retrieved from http://www.cghjournal.org/article/S1542-3565(13)00604-6/fulltext.
Nicholson, A.N., Turner, C., Stone, B.M., and Robson, P.J. (2004, June). Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. Journal of Clinical Psychopharmacology, 24(3), 305-13. Retrieved from http://journals.lww.com/psychopharmacology/pages/articleviewer.aspx?year=2004&issue=06000&article=00011&type=abstract.
Nguyen, B.M., Kim, D., Bricker, S., Bongard, F., Neville, A., Putnam, B., Smith J., and Plurad, D. (2014, October). Effect of marijuana use on outcomes in traumatic brain injury. The American Surgeon, 80(10), 979-83. Retrieved from http://www.ingentaconnect.com/content/sesc/tas/2014/00000080/00000010/art00015.
Passie, T., Emrich, HM., Karst, M., Brandt, SD. and Halpern, JH. (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. Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1002/dta.1377/full.
Pertwee, R.G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. British Journal of Pharmacology, 153(2), 199–215. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219532/.
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. Retrieved from http://www.elsevier.es/ficheros/publicaciones/03656691/addon/S036566911000290X/S300/en/296v86n01a90001302pdf001_2.pdf.
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. Retrieved from http://www.bloodjournal.org/content/105/3/1214.long?sso-checked=true.
Preet, A., Ganju, R.K.., and Groopman, J.E. (2008, January). Δ9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene, 27(3), 339-46. Retrieved from http://www.nature.com/onc/journal/v27/n3/full/1210641a.html.
Rajavashisth, T.B., Shaheen, M., Norris, K.C., Pan, D., Sinha, S.K., Oretega, J., Friedman, T.C. (2012). Decreased prevalence of diabetes in marijuana users: cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) III. BMJ Open, 2, e000494. Retrieved from http://bmjopen.bmj.com/content/2/1/e000494.
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. Retrieved from http://www.tandfonline.com/doi/abs/10.1080/14660820310016813.
Ravikoff Allegretti, J., Courtwright, A., Lucci, M., Korzenik, JR. and Levine, J. (2013, December). Marijuana use patterns among patients with inflammatory bowel disease. Inflammatory Bowel Diseases,19(13), 2809-14. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126607/.
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. Retrieved from http://www.clinicaltherapeutics.com/article/S0149-2918(07)00294-9/abstract.
Roitman, P., Mechoulam, R., Cooper-Kazaz, R., and Shalev, A. (2014, August). Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder. Clinical Drug Investigation, 34(8), 587-591. Retrieved from http://link.springer.com/article/10.1007%2Fs40261-014-0212-3.
Russo, E., and Guy, G.W. (2006). A tale of two cannabinoids: The therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Medical Hypotheses, 66(2), 234-46. Retrieved from http://www.medical-hypotheses.com/article/S0306-9877(05)00431-7/abstract.
Salazar, M., Carracedo, A., Salanueva, Í. J., Hernández-Tiedra, S., Lorente, M., Egia, A., … 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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673842/.
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, M.F. (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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789433/.
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. Retrieved from http://link.springer.com/article/10.1007%2Fs40265-014-0197-5.
Tripp, D.A., Nickel, J.C., Katz, L., Krsmanovic, A., Ware, M.A., Santor, D. (2014, November). A survey of cannabis (marijuana) 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/.
van der Stelt, M., Veldhuis, W.B., Bar, P.R., Veldink, G.A., Vliegenthart, J.F., and Nicolay, K. (2001, September 1). Neuroprotection by Δ9-Tetrahydrocannabinol, the Main Active Compound in Marijuana, against Ouabain-Induced In Vivo Excitotoxicity. The Journal of Neuroscience, 21(17), 6475-9. Retrieved from http://www.jneurosci.org/content/21/17/6475.long.
Van Klingeren, B., and Ten Ham, H. (1976). Antibacterial activity of Δ9-tetrahydrocannabinol and cannabidiol. Antonie Van Leeuwenhoek, 42(1-2), 9-12. Retrieved from http://link.springer.com/article/10.1007/BF00399444.
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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671751/.
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). Retrieved from http://journals.lww.com/pain/Abstract/2003/03000/Cannabis_use_for_chronic_non_cancer_pain__results.23.aspx.
Yang, X., Hegde, V.L., Rao, R., Zhang, J., Nagarkatti, P.S., and Nagarkatti, M. (2014). Histone Modifications Are Associated with Δ9-Tetrahydrocannabinol-mediated Alterations in Antigen-specific T Cell Responses. The Journal of Biological Chemistry, 289(27), 18707–18718. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081916/.
Zeissler, M.L., Eastwood, J., McCorry, K., Hanemann, C.O., Zajicek, J.P., and Carroll, C. B. (2016). Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis. Oncotarget, 7(29), 46603–46614. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216821/.
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