CBD vs THC
THC is a psychoactive substance while CBD is not.
CBD and THC are the main substances extracted from cannabis plants. Although CBD and THC were isolated in 1940, THC, which were believed to be the ‘active’ component, were researched extensively while CBD was neglected. However, as the therapeutic potential of CBD is discovered, more research is underway to take advantage of it. [1]
Although they are both extracts from cannabis, THC is the only psychoactive substance that causes a ‘high’ sensation. The psychoactivity of THC comes from its ability to bind to cell receptors called CB1 which are mostly present in the central nervous system including the brain. On the other hand, CBD, which has a significantly different 3D structure from THC, has a much lower chance of binding to the CB1 receptor. Therefore, CBD does not induce psychotic events nor many side effects [2].
Where can CBD be used?
The well-known mechanism of cannabinoid (all the substances extracted from cannabis) is through cell receptors CB1 and CB2. However, CBD has many ways to interact with the human body other than being a weak agonist to the CB1 receptor. While THC makes people ‘high’, CBD usually has the opposite effects. More research is showing CBD’s therapeutic abilities. CBDs are now shown to be capable of protecting neurons, modulate the immune response, kill or downregulate cancer cells, and treat some psychological disturbances. Below are some of the list of diseases that CBD is currently being researched as a potential treatment.
- Anxiety
- Problem: One method of treatment for general social anxiety disorder (SAD) is anti-anxiety drugs. Although they are powerful in mitigating the immediate condition, the patients cannot take it for a long time due to tolerance build-up. As a result, only 30% of patients achieve true recovery.
- Why CBD? Unlike these anti-anxiety drugs, CBD is known to develop no tolerance with extensive use [3],[4]. Many studies show that patients treated with CBD have a significant anxiety score improvement compared to placebo similar to currently used drugs [20].
- Schizophrenia
- Problem: schizophrenia is a serious mental illness affecting cognitive ability and emotions. Since the pathology of schizophrenia is still not fully understood, the only method of treatment is to manage symptoms through psychosocial treatments and antipsychotic medications. However, these antipsychotic drugs have some long-term side effects; some are motor disturbances, sexual dysfunction, and weight gain.
- What CBD? CBD was tested against placebo and current antipsychotic medication, amisulpride. In these researches, patients treated with CBD showed similar improvement in schizophrenia scoring as patients treated with amisulpride and significant improvement against placebo. Unlike amisulpride, CBD did not cause any weight gain, motor disturbances, sexual dysfunction, adverse effects on cardiac and hepatic functions [5],[6].
- Alzheimer’s Disease
- Problem: Alzheimer's is a disease associated with neuroinflammation and neural damages. However, CBD is known to have multiple mechanisms for protecting neurons and can modulate immune responses to reduce inflammation. These properties can help patients with Alzheimer’s disease.
- Why CBD? Current Alzheimer’s disease treatment cannot stop or reverse the damage. However, CBD in the animal model showed a reduction of the inflammatory response in neural cells and even promote the creation of new neurons [7].
- Anti-tumor
- The antitumor ability of different plant-based cannabinoids is being tested. THCs are shown to have some effects but have unwanted psychotic effects. Therefore, more research is being done on CBD’s anti-cancer efficacy. Some of the findings in animal studies with human cancer cells show that CBD can prevent proliferation, metastasis, and cause cancer cell death for some specific types of cancers. Unfortunately, there haven’t been many human clinical trials with CBD.
- Animal study: In vivo studies show the direct injection of CBD shows a significant reduction of tumor mass and proliferation, and significantly prevent cancer cell metastasis in breast cancer and glioma cancers [8],[9].
- Clinical study: Significant reduction in tumor mass in human clinical data with 119 various cancer patients. The study was not pre-designed so the efficacy of CBD cannot be proved. However, such a high reduction of cancer mass shows the need for further clinical studies with CBD. [10]
- Rheumatoid arthritis
- Problem: Rheumatoid arthritis can be defined as an autoimmune disease where own immune cells mistakenly attack synovium, a lining surrounding joints. Current medications have side effects ranging from stomach irritation and bone thinning to increased risk of infection.
- Why CBD? In several rat model research, CBD is shown to decrease the joint damage, and decrease chemical release that would cause inflammation [11][12]. There is no clinical evidence supporting the model, but it is worth a clinical trial in the future. Considering CBD does not have many side effects even with a relatively high dose and extensive use, it can be used to improve the current treatment for arthritis.
Safety and Addiction
CBD, unlike THC, is known to have no addictive property. It even has potential as a treatment for addiction to other psychoactive drugs such as opioids [13]. The overdose of CBD is also highly unlikely to happen. Various doses of CBD were clinically tested but there were little to no side effects even to young children [14][15]. For instance, high doses of CBD (up to 1500 mg/day) are well tolerated in animals and humans. Also, it does not change heart rate, blood pressure, or body temperature, does not induce catalepsy and does not alter psychomotor or psychological functions like THC [16]. CBD has varying half-lives depending on administration methods but has a half-life of only a few hours if oral and buccal administration [17],[18]. The short half-life contributes to its safety as well.
Sources
- Roger Adams, Madison Hunt, and J. H. Clark. Structure of Cannabidiol, a Product Isolated from the Marihuana Extract of Minnesota Wild Hemp. I. Journal of the American Chemical Society 1940 62 (1), 196-200
- Burstein S. (2015). Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorganic & medicinal chemistry, 23(7), 1377–1385.
- Crippa, J. A. S., Derenusson, G. N., Ferrari, T. B., et al. (2011). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. Journal of Psychopharmacology, 25(1), 121–130.
- K. Hayakawa, K. Mishima, M. Nozaka, et al. (2007). Repeated treatment with cannabidiol but not D -tetrahydrocannabinol has a neuroprotective effect without the development of tolerance. Neuropharmacology, 52(4), 1079-1087
- Mcguire, P., Robson, P., Cubala, W. J., Vasile, D., et al. (2018). Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial. American Journal of Psychiatry,175(3), 225-231.
- Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D., et al. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational Psychiatry,2(3).
- Watt, G., & Karl, T. (2017). In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer's Disease. Frontiers in Pharmacology,8:20.
- Ligresti, A., Moriello, A. S., Starowicz, K., Matias, I., et al. (2006). Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma. Journal of Pharmacology and Experimental Therapeutics,318(3), 1375-1387.
- Massi, P., Vaccani, A., Ceruti, S., Colombo, A., Abbracchio, M. P., & Parolaro, D. (2003). Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, on Human Glioma Cell Lines. Journal of Pharmacology and Experimental Therapeutics,308(3), 838-845.
- Kenyon, J., Liu, W., & Dalgleish, A. (2018). Report of Objective Clinical Responses of Cancer Patients to Pharmaceutical-grade Synthetic Cannabidiol. Anticancer Research,38(10), 5831-5835.
- Hammell, D., Zhang, L., Ma, F., Abshire, S., Mcilwrath, S., Stinchcomb, A., & Westlund, K. (2015). Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. European Journal of Pain,20(6), 936-948.
- Malfait, A. M., Gallily, R., Sumariwalla, P. F., Malik, A. S., et al. (2000). The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proceedings of the National Academy of Sciences,97(17), 9561-9566.
- Hurd, Y.L., Yoon, M., Manini, A.F. et al.(2015). Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage. Neurotherapeutics12, 807–815.
- Devinsky, O., Marsh, E., Friedman, D., Thiele, E., Laux, et al. (2016). Cannabidiol in patients with treatment-resistant epilepsy: An open-label interventional trial. The Lancet Neurology,15(3), 270-278
- Bergamaschi, M. M., Queiroz, R. H., Zuardi, A. W., & Crippa, J. A. (2011). Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent. Current Drug Safety,6(4), 237-249.
- Iffland, K., & Grotenhermen, F. (2017). An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis and Cannabinoid Research,2(1), 139-154.
- Atsmon, J., Heffetz, D., Deutsch, L., Deutsch, F., & Sacks, H. (2017). Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology. Clinical Pharmacology in Drug Development,7(7), 751-758.
- G. W. Guy & P. J. Robson (2004) A Phase I, Open Label, Four-Way Crossover Study to Compare the Pharmacokinetic Profiles of a Single Dose of 20 mg of a Cannabis Based Medicine Extract (CBME) Administered on 3 Different Areas of the Buccal Mucosa and to Investigate the Pharmacokinetics of CBME per Oralin Healthy Male and Female Volunteers (GWPK0112), Journal of Cannabis Therapeutics, 3:4, 79-120,
- Blessing, E.M., Steenkamp, M.M., Manzanares, J. et al.(2015). Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics12, 825–836.
- Crippa, J. A., Derenusson, G. N., Ferrari, T. B., Wichert-Ana, L., et al. (2010). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report. Journal of Psychopharmacology,25(1), 121-130.