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The Science of Marijuana

Why is marijuana so effective on a wide range of medical conditions? Our bodies (in fact all mammals) contain an endocannabinoid system. The endocannabinoid system acts as a modulator for the other systems in our body. Due to strict controls placed on marijuana, research has been extremely limited on the whole raw plant, in the United States. However, there are many studies showing a wide range of medical benefits from the cannabinoids, which are chemical compounds found in marijuana. The strict controls have limited studies and comparisons of various whole plant marijuana strains which offer a wide variety of different marijuana cannabinoid profiles. Combinations of all the cannabinoids are only found in the whole plant, rather than synthetic options which focus on just one cannabinoid. One thing that researchers have come to learn is that there is a synergy from the cannabinoids found in the whole plant that work together in what has come to be known as the "entourage effect."

THC is one of the most commonly known cannabinoids in marijuana. THC is the marijuana compound scientifically known as tetrahydrocannabinol. There is a synthetic pharmaceutical version of THC available with a prescription known as Marinol. Marinol has been prescribed to cancer patients to help control nausea and vomiting. However, since Marinol is produced in a lab as an isolate, Marinol lacks the additional cannabinoids found in the whole marijuana plant. Plus the terpenes of the whole plant are missing, and terpenes also influence the cannabinoids. In the whole plant, cannabinoids have been shown to have an effect on each other. Often patients describe the effect of Marinol as too intense, dizzying, or ineffective.

For instance, in the whole plant, Cannabidiol, commonly known as CBD, reduces the euphoric or "high" effect of THC. So a strain of marijuana that has 10% THC and 1% CBD will produce a different effect than a strain that has 10% THC and 6% CBD. Although both strains have the same amount of THC, (which is known for producing the high effect), the strain with more CBD will reduce the "high" effect of the THC, by counteracting the THC. Marinol on the other hand has no CBD to counter the effect of the THC, not to mention any of the other cannabinoids found in the whole marijuana plant.

The above example uses just 2 of the over 85 known cannabinoids found in the whole plant. Interactions between the cannabinoids offer even more complexity and variation, not to mention the subatomic quirks and quarks that can not be duplicated in a lab. The whole plant offers a wide range of medical uses. Over time growers may focus on breeding plants with higher cannabinoid content of lesser known cannabinoids as benefits of the lesser known cannabinoids are revealed. For now most of the focus is on THC, and CBD content.

Another very important component of marijuana are the terpenes. Terpenes produce the different smells found in different strains of marijuana. For instance limonene produces a citrus smell and is often found in uplifting varieties of marijuana. Limonene is also found in citrus fruits. Alpha-pinene is found in piney smelling varieties. The terpenes present in marijuana interact with the cannabinoids and affect the outcome the patient experiences. A patient who is allergic to mangoes for instance may have a reaction to strains containing high amounts of myrcene which is the terpene also found in mangoes.

Below are some exerts from a sampling of studies done with various marijuana cannabinoids.

Science: Arthritis - CBD was administered after onset of clinical symptoms, and in both models of arthritis the treatment effectively blocked progression of arthritis. Study: The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis National Academy of Science

Science: Epilepsy - According to research at the Radboud University in Nijmegen, The Netherlands, the endocannabinoid system protects against spontaneous seizures. The scientists blocked this system with the cannabinoid receptor antagonist rimonabant in 13 rats for three weeks. In three rats convulsive seizures where observed in the limbic region of the brain after 5 to 8 days. (Source: van Rijn CM, et al. Pharmacol Rep 2011;63(1):165-8.)

Science: Pain - Researchers at Huazhong University of Science and Technology in Wuhan, China, investigated the inhibitory effects of cannabinoids on vanilloid 1 receptors. They used the synthetic cannabinoid WIN 55,212-2 to study the mechanisms of action of peripheral cannabinoids in pain relieving actions on trigeminal ganglion nerve cells. (Source: Wang W, et al. Neurol Sci. 2011 May 17. [in press])

Science: Breast cancer - According to research at the Beth Israel Deaconess Medical Center in Boston, USA, the non-psychotropic cannabinoid cannabidiol (CBD) induces programmed cell death in breast cancer cells by coordinating the crosstalk between apoptosis and autophagy. CBD increased the generation of reactive oxygen species. (Source: Shrivastava A, et al. Mol Cancer Ther. 2011 May 12. [in press])

Science: Aging Restriction of food intake is a robust means of extending lifespan and postponing age-related disease in many species, including yeast, nematode worms, flies and rodents. Researchers at Buck Institute for Research on Aging in Novato, USA, demonstrated that N-acylethanolamines, which includes the endocannabinoid anandamide, are involved in the process of lifespan extension in a nematode worm (C. elegans). (Source: Lucanic M, et al. Nature 2011;473(7346):226-9.)

Science: Inflammation of the bowel - According to a research group in Brussels, Belgium, increasing the levels of the endocannabinoid 2-AG (2-arachidonoylglycerol) reduced colitis and related systemic inflammation in mice. 2-AG levels were increased by inhibiting monoacylglycerol lipase (MAGL), the primary enzyme responsible for the degradation of 2-AG. (Source: Alhouayek M, et al. FASEB J. 2011 May 6. [in press])

Science: Neuropathic pain - According to research at the University of Georgia in Athens, USA, rats self-administer a synthetic CB2 receptor agonist (AM1241) to reduce neuropathic pain. Neuropathic pain was produced by nerve injury and rats could self-administer the cannabinoid by pressing down a lever. (Source: Gutierrez T, et al. Pain. 2011 May 6. [in press])

Science: Depression - According to research at the University of Maharastra, India, the endocannabinoid system is involved in the antidepressant effects of fluoxetine, a broadly used antidepressant. A CB1 receptor antagonist blocked the effects of fluoxetine. Scientists concluded that "the study indicates an interaction between endocannabinoid and serotonergic system in regulation of depressive and compulsive-like behavior." (Source: Umathe SN, et al. Behav Brain Res. 2011 Apr 28. [in press])

Science: Alzheimer's disease - According to research at the University of California in Irvine, USA, certain brain regions (mid frontal and temporal cortex) of subjects with Alzheimer's disease contain lower levels of the endocannabinoid anandamide than control subjects. Scientists concluded from their study that an impairment in brain anandamide mobilization caused by the amyloid-beta peptide, which is toxic for nerve cells, contributes to cognitive dysfunction in Alzheimer's disease. (Source: Jung KM, et al. Neurobiol Aging. 2011 May 3. [in press])

Science: Epilepsy - According to research at the Radboud University in Nijmegen, The Netherlands, the endocannabinoid system protects against spontaneous seizures. The scientists blocked this system with the cannabinoid receptor antagonist rimonabant in 13 rats for three weeks. In three rats convulsive seizures where observed in the limbic region of the brain after 5 to 8 days. (Source: van Rijn CM, et al. Pharmacol Rep 2011;63(1):165-8.)

Science: Pain - Researchers at Huazhong University of Science and Technology in Wuhan, China, investigated the inhibitory effects of cannabinoids on vanilloid 1 receptors. They used the synthetic cannabinoid WIN 55,212-2 to study the mechanisms of action of peripheral cannabinoids in pain relieving actions on trigeminal ganglion nerve cells. (Source: Wang W, et al. Neurol Sci. 2011 May 17. [in press])

Science: Breast cancer - According to research at the Beth Israel Deaconess Medical Center in Boston, USA, the non-psychotropic cannabinoid cannabidiol (CBD) induces programmed cell death in breast cancer cells by coordinating the crosstalk between apoptosis and autophagy. CBD increased the generation of reactive oxygen species. (Source: Shrivastava A, et al. Mol Cancer Ther. 2011 May 12. [in press])

Science: Aging - Restriction of food intake is a robust means of extending lifespan and postponing age-related disease in many species, including yeast, nematode worms, flies and rodents. Researchers at Buck Institute for Research on Aging in Novato, USA, demonstrated that N-acylethanolamines, which includes the endocannabinoid anandamide, are involved in the process of lifespan extension in a nematode worm (C. elegans). (Source: Lucanic M, et al. Nature 2011;473(7346):226-9.)

Science: Inflammation of the bowel - According to a research group in Brussels, Belgium, increasing the levels of the endocannabinoid 2-AG (2-arachidonoylglycerol) reduced colitis and related systemic inflammation in mice. 2-AG levels were increased by inhibiting monoacylglycerol lipase (MAGL), the primary enzyme responsible for the degradation of 2-AG. (Source: Alhouayek M, et al. FASEB J. 2011 May 6. [in press])

Science: Neuropathic pain - According to research at the University of Georgia in Athens, USA, rats self-administer a synthetic CB2 receptor agonist (AM1241) to reduce neuropathic pain. Neuropathic pain was produced by nerve injury and rats could self-administer the cannabinoid by pressing down a lever. (Source: Gutierrez T, et al. Pain. 2011 May 6. [in press])

Science: Depression - According to research at the University of Maharastra, India, the endocannabinoid system is involved in the antidepressant effects of fluoxetine, a broadly used antidepressant. A CB1 receptor antagonist blocked the effects of fluoxetine. Scientists concluded that "the study indicates an interaction between endocannabinoid and serotonergic system in regulation of depressive and compulsive-like behavior." (Source: Umathe SN, et al. Behav Brain Res. 2011 Apr 28. [in press])

Science: Alzheimer's disease - According to research at the University of California in Irvine, USA, certain brain regions (mid frontal and temporal cortex) of subjects with Alzheimer's disease contain lower levels of the endocannabinoid anandamide than control subjects. Scientists concluded from their study that an impairment in brain anandamide mobilization caused by the amyloid-beta peptide, which is toxic for nerve cells, contributes to cognitive dysfunction in Alzheimer's disease. (Source: Jung KM, et al. Neurobiol Aging. 2011 May 3. [in press])