Potential Benefits of Cannabis
Ashley Shafer
American College of Healthcare Sciences 12/17/22
Abstract
For this integrative literature review, cannabis, Cannabis sativa L., is examined for its therapeutic health benefits and potential medicinal use in patient care. From physical and social to mental medical use, there is strong evidence urging further investigation to better understand our endocannabinoid system and its role in various health conditions. Using the American College of Healthcare Sciences library launchpad, ten primary research articles are reviewed to examine the health benefits of the medicinal use of cannabis in an attempt to rediscover this form of plant medicine for its available compounds and how they interact with our endocannabinoid system. Questions of dosing, administration, and drug interactions are valid concerns for patients who want to use this form of contemporary alternative healing medicine but overall, patients experienced symptom relief in various conditions with the use of cannabis in their treatment plan. With emerging positive research, future generations can better understand cannabis, opt to take a proactive approach to health, and integrate cannabis into patient care.
Throughout history, cannabis has been used in traditional Chinese medicine and Native American healing dating back two thousand years (Stasilowicz et al., 2021). Used as a drug for both recreational and entheogenic purposes, Cannabis sativa L. has chemical compounds, phytocannabinoids, and terpenes, that have wide pharmacological uses because of the interaction with the receptors in the human endocannabinoid system (ECS). Our endocannabinoid system is a complex biological system in all vertebrae species that plays a vital role in modulating health and disease by maintaining normal cerebral and physiological functions (Marcu, 2015). Considered the master conductor, the ECS sends chemical messages to trigger biological actions throughout the body that are critical to health and well-being. Because of its active constituents, the cannabis plant should be thought of medicinally rather than recreationally. If backed by research and clinical trials, cannabis can change modern-day medicine as we know it.
Since its classification as a Schedule 1 drug by the United States Congress in the 1970 Controlled Substances Act, initiatives to use cannabis as herbal medicine have been challenging based on its stigma and classification (Purcell et al., 2022). The United States' biggest funder, the U.S. National Institute on Drug Abuse (NIDA), has funded research for cannabis misuse and negative effects rather than as a therapeutic treatment which in turn inhibits the forward progress of medical cannabis for the betterment of patients. More research dollars are being put forth for the understanding of potential harms and cannabis misuse, not on the medical potential of cannabis (Purcell et al., 2022). Stasilowicz et al. (2021) suggest utilizing natural cannabis is a practice lost within a short century in western medicine because of its classification and misunderstandings. Backed by political agendas and the Drug Enforcement Agency, grants and other research funding are difficult if not privately funded. Meanwhile, patients looking for alternative medicine suffer the cost of corporate greed (Purcell et al., 2022).
Recently, medical cannabis has gained a global market despite its governing challenges and has become more socially acceptable as people seek alternative medicine. Thus, creating a massive demand for food and beverage products for people to utilize plant medicine. Because of this demand, more research has been done on its medicinal properties, which fueled the reinvention of cannabis products since the market value is estimated to more than triple in size by 2026 (Rascera et al., 2021).
People are demanding safer, effective, and innovative ways to manage their health, making cannabis very desirable for people to try. According to Barratta et al. (2022), the influence of media, economic interests, and the demand of associations safeguard patients' health. A scientific, evidence-based approach is necessary to explore its potential medical benefits (Shafik et al., 2020). Education and clinical research are vital pieces to the puzzle. This paper aims to investigate available research to shine a light on the health benefits of the medicinal use of cannabis. Cannabis has great therapeutic value, which promotes natural alternatives for patient care.
Methods
Sources for this integrative literature review of cannabis’s medicinal value to promote natural alternatives for patient care were gathered from multiple databases accessed through the American College of Healthcare Sciences (ACHS) Library Launchpad. Utilized HerbMedPro from American Botanical Council: Herb Library Portal for a compendium of Cannabis sativa
clinical trials and case studies. Other databases included ProQuest Central, ProQuest RefWorks, Library and Information Resources Network (LIRN), and PubMed. Key search terms included “cannabis and health,” “cannabis and health benefits,” “cannabis and clinical trial,” “marijuana and medical use,” and “cannabis as medicine.”
Initial search criteria included “peer-review” and “full-text” documents within the past decade. From these criteria and search words, solid secondary sources were found. After scanning system reviews and meta-analysis reports, primary sources were uncovered from the secondary sources reference list. The bulk of primary sources was found in HerbMedPro where the clinical trials and case reports were compiled and categorized in a list of human data for evidence of efficacy. Most of the trials were conducted within the last 10 years. Because the subject in the review is of herbaceous nature, the herbal medicine research database portal was very helpful.
The aim of the database search was to uncover primary journal articles, based on human clinical trails, that were specific to the benefits of cannabis for health conditions. Keeping health conditions broad scope allowed this literature review to see big-picture medicinal realizations. Search results yielded 24 total relevant articles selected for this literature review. Of those articles, 13 resources including five double-blind, parallel-group pilot studies, three randomized cross-over clinical trials, and a cross-sectional study placebo-controlled study. Both quantitative and qualitative research are well-represented in this review with surveys and cross-sectional assessments. Literature reviews fill in the gaps for background information, assessments of potential limitations in research, and implications for medical marijuana. Articles not focused on cannabis and how it relates to specific health problems were not included.
Results
Cannabis and Effects
Based on cannabis's genetic makeup, the herb is a potential treatment for various health conditions. A review article by Abrams (2022) reported that the Cannabis sativa plant offers over 100 cannabinoids, all of which have medicinal benefits. Marcu (2015) provides insight into our biological system, the endocannabinoid system (ECS), which keeps humans cerebral and physiological functions in order, modulating health and disease. The interaction between our ECS and cannabinoids is vital to proper human functioning. Each compound or cannabinoid found in either marijuana or hemp offers different therapeutic properties. Still, with questionable regulatory status around the globe, randomized control trials are scant for this botanical therapy. The efficacy and safety are in question with this complementary form of medicine.
Bridgeman and Abazia (2017) review cannabiss' historical significance, the use of medicinal cannabis in pharmacokinetics (movement of drugs within the body), and regulation's effect on acute care hospitals. Botanical cannabis medicine has been around for over 5000 years and was used medicinally worldwide, dating back to 400 AD. United States Pharmacopoeia had cannabis as part of its pharmacy in 1850. Cannabis was also used as plant medicine in the 19th and 20th centuries in the United States. Still, under prohibition, the plant was criminalized, deeming it of "no medical value" Schedule 1 controlled substance which ended research, clinical trials, and utilization of the plant. As a Schedule 1 substance in the United States, research has been difficult to pursue with its no accepted medical use, concerns for dependence, high abuse potential, and lack of safety under medical supervision. However, interest in botanical medicine has increased in present-day health care. Despite limited clinical evidence, medical conditions, and associated symptoms, U.S. state legislatures allow cannabis for medical marijuana use in 37 states in the U.S., including the District of Columbia, Guam, and Puerto Rico. Legislation governing the use of the cannabis plant has continually evolved, forcing healthcare facilities to address the implications of this form of treatment (Bridgeman & Abazia, 2017).
The most popular and well-known cannabinoid is delta-tetrahydrocannabinol (THC). According to Abrams (2022), this compound is responsible for psychoactive effects and is just one compound found in the female plant of cannabis. This touts non-psychoactive cannabidiol and 100 other therapeutic cannabinoids available to be clinically studied for medicinal purposes. Cannabidiol (CBD), a compound concentrated in cannabis, has no psychoactive effects yet substantial therapeutic efficacy (Costa et al., 2007). Flavonoids and terpenes available in the plant have potential health benefits in addition to cannabinoids. Terpenes are responsible for how plants smell and are abundant in cannabis and other plants, fruits, and herbs which also offer healing properties. Flavonoids are phytonutrients concentrated in plants' natural substances that have beneficial effects to contribute to potential health (Abrams, 2022). These work synergistically to utilize the whole plant, not just individual compounds and cannabinoids.
All vertebrae species have two cannabinoid receptors, cannabinoid receptor type 1(CB1) in the central nervous system and cannabinoid receptor type 2 (CB2) in the peripheral nervous system (Marcu, 2015). These receptors help facilitate homeostasis or balance within the body through our biological system, the endocannabinoid system, which regulates physiological processes. The discovery of our ECS has been relatively recent, dating back to 1994, when scientists could begin to explain observations of neurological and neurodegenerative disorders treatment with cannabis (Marcu, 2015). Endocannabinoids and receptors are found in our nervous system, internal organs, connective tissues, glands, and immune cells (Bridgeman & Abazia, 2017). The main pharmacological effects of THC are analgesia, muscle relaxation, antiemesis, appetite stimulation, and psychoactivity paired with CBD to promote anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, antioxidant, and antipsychotic activity to reduce anxiety and psychoactive effects of THC (Johnson et al., 2009). Whether just THC was used or a 1:1 ratio of THC: CBD, therapeutic efficacy can be extended to seizure disorders, psychotic symptoms, anxiety, depression, inflammation, cancer, cardiovascular diseases, neurodegeneration, symptoms of multiple sclerosis, and chronic pain, all of which has no demonstrated dependence or abuse (Corroon & Phillips, 2018). With a deficiency in endocannabinoids, phytocannabinoids (plant cannabinoids) derived from cannabis are introduced by different consumption methods.
Four clinically studied cannabis-derived pharmaceuticals are available today, as reported by Abrams (2022). Since 1986, a treatment for chemotherapy-induced nausea and vomiting has been administered by the names of Dronabinol and nabilone. Epidiolex is a medication prescribed as a treatment for children with refractory epilepsy. Lastly, a whole-plant extract, Nabiximols, is licensed and approved to treat spasticity with multiple sclerosis (Abrams, 2022).
Physical Medical Use
Medical cannabis may improve the quality of life in patients when it comes to their physical body health. Peterson et al. (2021) measured the relationship between pain and quality of life related to their health by using marijuana. Patients over 18 years of age enrolled in the Pennsylvania Medical Marijuana program, where they conducted a series of surveys using the eleven-item Qualtrics Survey tool measuring pain. Five surveys were given, one for initial screening and four for study surveys. The final sample size was 181 people with an average age of 41. The results showed that chronic medical marijuana users significantly improved pain and health-related quality of life over six weeks. Some limitations of specific product information like dosing, administrations, and cannabinoid concentration would have helped to determine the impact on quality of life. It should be noted that participants were incentivized with a coupon discount at a dispensary. The relationship between health-related quality of life and medical marijuana was positively correlated (Peterson et al., 2021).
Mondello et al. (2018) recently found significant effective pain management for patients with failed back surgery syndrome (FBSS) from cannabis. FBSS is spinal pain that persists after surgical intervention in the same spot, which causes chronic pain in the patient. Current therapeutic strategies prove ineffective, resulting in opioid use not being well tolerated. A retrospective study was performed over two years with 100 mg THC/CBD oral cannabinoids in eleven patients. The study concluded that the THC/CBD combination achieved analgesic effects, decreased refractory pain, and helped enhance mood in patients, thus making it a valid strategy for an improved quality of life. In further studies, larger control groups would help broaden the scope (Mondello et al., 2018).
Our endocannabinoid system is the critical endogenous system for pain regulation, which people experience differently. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD by Langford et al. (2012) found central neuropathic pain due to multiple sclerosis benefiting from using the treatment because of interactions with endocannabinoid receptors. In a two-phase study, a 1:1 THC: CBD spray was administered during a fourteen-week time frame to evaluate the efficacy of cannabinoids to a study group of 339 individuals (167 received THC/CBD spray and 172 received placebo). The study failed to show statistical differences between placebo and THC: CBD spray, which can be attributed to contradicting results and dosing design. Although the spray demonstrated an analgesic effect and patients felt a reduction in pain, a balanced dosing regimen is critical for the study's success (Langford et al., 2012).
In another study focused on cancer-related pain, opioids left patients feeling unrelieved, so the analgesic effect from THC/CBD was desired because of its endocannabinoid system modulator capabilities. Johnson et al., 2009 concluded that THC/CBD extract was an effective treatment for advanced cancer-patients pain that was not relieved by opioids. There were 177 patients with cancer pain who entered into a two-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. The Numerical Rating Scale showed statistical significance for reducing pain severity from the THC/CBD extract compared to the placebo group. It should be noted that no statistically significant differences in sleep quality or nausea were found with treatment in this study, and potential inaccuracies of patient-completed diary data could be refined in longer-term studies. Also, in this study, the THC/CBD combination proved more efficacy than THC extract alone, implicating a synergistic effect of the two compounds. The reductions in pain scores were attributed to the effects of THC/CBD, which were positive and encouraging (Johnson et al., 2009).
A randomized, double-blind, placebo-controlled, parallel-group pilot study by Irving et al. (2018) revealed that CBD-rich botanical extract might be beneficial for treating ulcerative colitis. Some people with mild to moderate ulcerative colitis resist standard therapies and need alternative medicine. The anti-inflammatory and immune-modulating properties of cannabidiol improved inflammatory bowel disease. An alternative option, cannabis, is studied with approximately 240 adults per 100,000 people in are with chronic, releasing, and remitting inflammatory bowel disease. In the United Kingdom, 39 patients 18 or older took a CBD-rich botanical extract or placebo capsules for ten weeks to see what percentage of patients went into remission after treatment using a 10% significance level. Tablets were taken twice daily by mouth, each 50 mg, 30 minutes before morning and evening meals. It turns out, at the end of the treatment, remission rates were very similar between the CBD-rich extract (28%) and the placebo (26%); however, a per-protocol analysis was done to reveal illness severity, global impression of change, and quality of life outcomes had improvement from the CBD extract. From this study, the CBD-rich extract may have provided therapeutic benefits (Irving et al., 2018).
A descriptive study by Hoffenberg et al. (2019) supported the medical benefits of cannabis in treating irritable bowel syndrome (IBS). Patients with IBS use complementary and alternative therapies, including cannabis oil, with different delivery methods and concentrations. A group of fifteen patients 13-23 years old at Children's Hospital Colorado with irritable bowel disease were followed for six to twelve months and then given an assessment comparing results using independent t-tests and Fisher's exact tests between cannabinoid oil users and non-user groups. Scores for pain, appetite, and disease activity were alike for non-users, although cannabis oil users had perceived improved sleep quality and were less nauseous (Hoffenberg et al., 2019).
Social Use
Alternative options for health are becoming increasingly accepted by people of all ages. Corroon & Phillips (2018) found that consumers use CBD for multiple medical conditions, including anxiety, depression, and sleep disorders. Their cross-sectional study used an online survey involving 2409 people characterizing who, how, and why people use CBD. Almost 62% of the responders reported using CBD to treat a medical condition, pain being the most common. The most common forms of treatment were sprays, drops, and tinctures. Most people (76% of responders) get their CBD information for internet searches, family members, or friends. 36% of respondents thought CBD for the treatment of medical conditions worked very well by itself. Because of the vast age of respondents, sample size, and geographic representations make this an intense study. On the downside, limitations include self-selected samples, favorable response options, and internet connectivity could have distorted results. A large percentage of respondents indicated it helped with medical issues in the absence of conventional medicine and had no serious adverse effects giving compelling reason to explore further therapeutic potential (Corroon & Phillips, 2018).
The safety and efficacy of treatment are parallel to the success of the integration of medical cannabis in healthcare. Abuhasira et al. (2018) highlighted common indications for the elderly population's use of cannabis. Astounding 97.3% of the study participants reported improvement in their condition after six months, and it decreased the use of opioid medications. In six months, 2,736 patients over 65 years old answered a questionnaire indicating pain and cancer conditions were improved with cannabis. Some adverse effects were noted that including dizziness and dry mouth. 18% of the participants stopped using opioid analgesics or reduced their dose. Not only is the treatment effective, but it was also deemed safe with little to no statistically significant adverse effects (Abuhasira et al., 2018).
Abo et al. (2022) examined a questionnaire-based cross-sectional study that demonstrated family physicians see the potential in prescribing cannabis but require more research to recommend it. Physicians stated that medical indications and psychiatric and neurological adverse effects should be studied more to improve their knowledge base and support medical cannabis. Although out of 152 family physicians, 78% supported medical cannabis, including 63% legalizing it, only 28% believed they should recommend it for the reasons listed above. Over 80% of the physicians thought it could help with chronic pain and cancer. 95% believed the barrier for them to be able to recommend was the potential for abuse (Abo et al., 2022).
Mental Use
Adverse effects associated with THC on cognition can be counteracted with CBD because of its non-psychoactive effects. In this study, Hotz et al. (2021) tested verbal episodic memory in healthy young adults. The study used a double-blind, placebo-controlled, randomized crossover trial in 39 subjects vaping cannabidiol at the University of Basel. The study used a placebo e-liquid, comparing the effect of 12.5 mg CBD e-liquid. The participants were 18-30 years old, with a specific body mass index, and spoke fluent German. With the inclusion of the study, the subjects were randomly assigned a placebo or CBD using block randomization. Participants were tested for T.H.C. consumption before the survey and sleep times, psychoactive drug use, and alcohol before the visit, so these factors did not interrupt the results. The primary outcome measure was to show participants a series of unrelated German nouns and recall those words in a verbal learning task. The study showed that subjects who vaped CBD recalled 10% more words than the placebo group, which suggests that CBD has no negative impact on essential cognitive functions. The dose-response relationship cannot be generalized to other forms of CBD administration but rather just for the single-use CBD e-liquid. Health status was self-declared and not clinically tested, which could affect results. The results were reported with a flow diagram of the process through study phases, a table of baseline consumption characteristics, outcome measures, and differences between conditions. Also, a figure on the effect of CBD on episodic memory performance and body mass index was included, which was statistically analyzed by linear mixed models with dependent and independent variables to show results. All in all, CBD was found to be easily applicable and non-psychoactive, which could prove to be helpful to help memory in psychiatric disorders, neurodegenerative disorders, and stress-related episodic memory recall (Hotz et al., 2021).
Anxiety is a mental health issue for which medicinal cannabis is being prescribed, along with post-traumatic stress disorder (P.T.S.D.). Evident in clinical trials and laboratory studies, Berger et al. (2022) reviewed the anxiety-reducing effects of CBD. They report that anxiety is the second most common reason to prescribe cannabis in Australia, the number one being chronic pain. 17% of prescriptions are CBD-dominant oils or capsules, while liquid products that contain THC make up 33%, and vaporizations at 50%. Some people choose to self-medicate and source cannabis illegally. Patients should start with a low dose and increase it slowly to minimize adverse effects and drug interactions when treating an anxiety disorder. The side effects include nausea, dizziness, increased appetite, euphoria, and potential dependence. CBD was proven to reduce anxiety in doses of 300-800 mg daily in several small trials, but more extensive trials are lacking. There is a need for tests with lower CBD dose ranges (Berger et al., 2022).
Discussion
The purpose of this paper was to investigate the health benefits of the medicinal use of cannabis. The reviewed research shows that cannabis can be effectively used in pain management as well as for treating ulcerative colitis, irritable bowel disease, sleep disorders, anxiety, and depression. This literature review found that clinal research studies are sparse yet encouraging, what complications came from the studies, and how we can continue to progress cannabis in the future.
Research is predominantly backed by science, in turn the distribution and function of the components of our endocannabinoid system have garnished significant research focus with major milestones. By researching and understanding our endocannabinoid system, the human body's central operating system, we understand our physiological workings on a deeper level which can contribute to therapeutic success for various ailments when treated with cannabis. Using cannabis, people can benefit not only physically but mentally and socially. All these are vital to our overall health, but the plant has been misunderstood because of its ideation.
Since the relatively recent "discovery" of our endocannabinoid system, ECS, and the strained political climate with classification and legalization, many barriers and challenges have affected solid research. The lack of extensive trials can be felt across the board, as legislation and adverse interests fund trials that are counterproductive to unleashing medical possibilities (Purcell et al., 2022). With scientific data lacking because of extenuating circumstances, current tests remain inconclusive and discordant without substantial research. Larger studies are needed to broaden results (Mondello et al., 2018; Irving et al., 2018; Hotz et al. 2021).
The need for more clinical trials is here and now. The reasons hindering clinical research trials have not been successfully submitted to Human Research Governance Offices include cannabis product selection, accurate dosing and administration, adverse effects, drug interactions, proper consent, and post-trail access to cannabis products (Martin et al., 2020). Cannabis has the potential to be a new and promising therapy, but with limitations in place to prevent clinical trials, it is a challenge to demonstrate efficacy and safety. The therapeutic effects show validity to having this be a treatment option, so the scientific community and food and beverage industry are working together to ensure safety in stability, dose, shelf-life, and packaging (Rascera et al., 2021).
Considerable controversy has affected the scientific community for conducting further trials on cannabis. Plant species to be used, efficacy and safety of use, routes of administration, methods of preparation, and type and dosage of cannabinoids have been in question and make for too many variables in an environmental setting. Coupled with survey issues/ errors, the duration of the study and self-declared health statuses have all skewed results, lowering confidence in research and limiting findings. In conjunction with variables conducting the research itself, legalization and classification of the cannabis herb has shrouded initiatives to gain a better understanding and acceptance as a viable health treatment. Ultimately, limiting future potential of cannabis because of preconceived notions hinders the growth mindset with outdated political propaganda where the focus should be future implications of limitless potential as cannabis is reintroduced into society. Making it safe and effective with appropriate regulation should be the shifted focus for constituents.
Reviews in this paper found therapeutic value in cannabis for treating chronic conditions. Peterson et al. (2021) reported that the general quality of life for patients with chronic pain was improved with cannabis. Patients with failed back surgery syndrome found effective pain management with cannabis when opioids were not cutting it (Mondello et al., 2018). Langford et al. (2012) found neuropathic pain from multiple sclerosis benefited from using cannabis as a treatment option. Cancer-related pain was reduced because of the analgesic effect of cannabis and its interaction with our endocannabinoid system to modulate (Johnson et al., 2009). Ulcerative colitis and irritable bowel syndrome found cannabis therapy as an excellent alternative medicine resulting in remission seen by Irving et al. (2018) and Hoffenberg et al. (2019). The therapeutic potential was also recognized in treating anxiety, depression, and sleep disorders found by Corroon & Phillips (2018) and Berger et al. (2022). Lastly, cannabis was found to help with memory recall and episodic performance (Hotz et al., 2021). These results are very encouraging of the potential of cannabis interacting with our endocannabinoid system and how that can help people in and out of the hospitals. These clinical trials have had highly beneficial health effects with limited side effects, which make it a viable treatment option in today's integrative medicine regimen.
The strength of current findings is that despite all research challenges, results are encouraging and show limitless potential for cannabinoids found in cannabis. On the downside, as each culture and country examines cannabis, a united consensus has yet to be achieved for various reasons beyond our control. As each clinical trial is established, progress is being made to substantiate the claim that cannabis has great medicinal value and promotes a natural, healthy lifestyle.
Humans need to be able to trust the earth and its herbal medicine when taking care of themselves. By having more promising clinical research, we would provide a more trusted and understood alternative for personal care based on science. Conventional medicine treats symptoms and diseases for sick people; that is tradition. Implicated by the current findings of Abo et al. (2022), contemporary and alternative medicine need to work synergistically for an integrated approach in healthcare. Physicians would be educated on our endocannabinoid system and how complementary therapies could be utilized in conjunction with traditional treatment options to better the patient's care experience and quality of life. Cannabis can be a powerful tool in the healthcare providers' toolbox that can be backed by scientific research. Big picture view, society would be taking the focus off of sick care and promoting health care.
Conclusions and Recommendations
Cannabis and its compounds promise to treat a wide range of diseases and disorders. However, there is a lack of research evaluating the potential medical benefits of cannabis because of barriers in United States federal law. As a result, many patients are choosing to use marijuana and hemp-derived products to treat serious illnesses that have not been researched, backed by clinical trials, and not approved by the Food and Drug Administration (FDA)— resulting in a lack of information regarding on interactions with other medications or appropriate dose and delivery method to consume.
Medical treatments should be based on sound science, and sick people deserve safe medications that have been proven effective. I clearly recommend ramping up scientific research to make this treatment option valid for cannabis compounds and active constituents in this herb. If we reduce barriers restricting cannabis research, patient care will be improved by offering natural alternatives and promoting excellent medicinal value for human health- mind, body, and spirit.
References
Abo Ziad, R., Grynbaum, M. B., Peleg, R., & Treister-Goltzman, Y. (2022). The attitudes and beliefs of family physicians regarding the use of medical cannabis, knowledge of side effects, and barriers to use: a comparison between residents and specialists. American Journal of Therapeutics, 29(4), e400–e409. https://doi.org/10.1097/ MJT.0000000000001236
Abrams, D. I. (2022). Cannabis, cannabinoids and cannabis-based medicines in cancer care. Integrative Cancer Therapies. https://doi.org/10.1177/15347354221081772
Abuhasira, R., Schleider, L. B., Mechoulam, R., & Novack, V. (2018). Epidemiological characteristics, safety and efficacy of medical cannabis in the elderly. European Journal of Internal Medicine, 49, 44–50. https://doi.org/10.1016/j.ejim.2018.01.019
Barratta, F., Pignata, I., Ravetto Enri, L., & Brusa, P. (2022). Cannabis for medical use: analysis of recent clinical trials in view of current legislation. Frontiers in Pharmacology. https:// doi.org/10.3389/fphar.2022.888903
Berger, M., Amminger, G. P., & McGregor, I. S. (2022). Medicinal cannabis for the treatment of anxiety disorders. Australian Journal of General Practice, 51(8), 586-592. Retrieved from https://www.proquest.com/scholarly-journals/medicinal-cannabis-treatment- anxiety-disorders/docview/2697448558/se-2
Bridgeman, MB., Abazia DT., (2017). Medicinal cannabis: history, pharmacology, and implications for the acute care setting. PubMed Central. 42(3): 180–188. https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC5312634/
Corroon, J., & Phillips, J. A. (2018). A cross-sectional study of cannabidiol users. Cannabis and Cannabinoid Research, 3(1), 152–161. https://doi.org/10.1089/can.2018.0006
Costa, B., Trovato, A., Comelli, F., Giagnoni, G., Colleoni, M. (2007). The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. European Journal of Pharmacology, Vol. 556, Issues 1-3. https://doi.org/10.1016/j.ejphar.2006.11.006
Hoffenberg, E., McWilliams, S., Mikulich-Gilbertson, S., Murphy, B., Hoffenberg, A., Hopfer, C. (2019). Cannabis oil use by adolescents and young adults with inflammatory bowel disease. Journal of Pediatric Gastroenterology and Nutrition: (68)3, 348-352. doi:
Hotz. J., Fehlmann, B., Papassotiropoulos, D., Schicktanz, N. (2021). Cannabidiol enhances verbal episodic memory in healthy young participants: A randomized clinical trial. Journal of Psychiatric Research,Vol. 143. https://doi.org/10.1016/ j.jpsychires.2021.09.007
Irving, P. M., Iqbal, T., Nwokolo, C., Subramanian, S., Bloom, S., Prasad, N., Hart, A., Murray, C., Lindsay, J. O., Taylor, A., Barron, R., & Wright, S. (2018). A randomized, double- blind, placebo-controlled, parallel-group, pilot study of cannabidiol-rich botanical extract in the symptomatic treatment of ulcerative colitis. Inflammatory Bowel Diseases, 24(4), 714–724. https://doi.org/10.1093/ibd/izy002
Johnson, J. R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E. D., Potts, R., & Fallon, M. T. (2010). 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), 167–179. https://doi.org/10.1016/j.jpainsymman.2009.06.008
Langford, R. M., Mares, J., Novotna, A., Vachova, M., Novakova, I., Notcutt, W., & Ratcliffe, S. (2013). A double-blind, randomized, placebo-controlled, parallel-group study of THC/ CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. Journal of neurology, 260(4), 984–997. https://www.researchgate.net/profile/Stuart-Ratcliffe/publication/ 233770159_A_double-blind_randomized_placebo-controlled_parallel- group_study_of_THCCBD_oromucosal_spray_in_combination_with_the_existing_treat ment_regimen_in_the_relief_of_central_neuropathic_pain_in_patients_wi/links/ 57d8111a08ae6399a39912da/A-double-blind-randomized-placebo-controlled-parallel- group-study-of-THC-CBD-oromucosal-spray-in-combination-with-the-existing- treatment-regimen-in-the-relief-of-central-neuropathic-pain-in-patien.pdf
Martin, J.H., Hill, C., Walsh, A., Efron, D., Taylor, K., Kennedy, M., Galettis, R., Lightfoot, P., Hanson, J., Irving, H., Agar, M., Lacey, J. (2020). Clinical trials with cannabis medicines —guidance for ethics committees, governance officers and researchers to streamline ethics applications and ensuring patient safety: considerations from the Australian experience. Trials 21, 932. https://doi.org/10.1186/s13063-020-04862-6
Marcu, J. (2015). The biochemical system controlling the effects of cannabis- an introduction. Herbalgram, 107 (36-39). http://herbalgram.org/resources/herbalgram/issues/107/ table-of-contents/hg107-cannabisup-cannabinoid/
Mondello, E., Quattrone D., Cardia L., Bova G., Mallamace R., Barbagallo AA., Mondello C., Mannucci C., Di Pietro M., Arcoraci V., Calapai G. (2018). Cannabinoids and spinal cord stimulation for the treatment of failed back surgery syndrome refractory pain. J Pain Res, 11:1761-1767. https://doi.org/10.2147/JPR.S166617
Peterson, A.M., Le, C., Dautrich T. (2021). Measuring the change in health-related quality of life in patients using marijuana for pain relief. Medical Cannabis Cannabinoids, 114-120. https://doi.org/10.1159/000517857
Purcell, J., Passley, T., Leheste, J. (2022). The cannabidiol and marijuana research expansion act: promotion of scientific knowledge to prevent health crisis. The Lancet Regional Health- Americas, Vol. 14. https://doi.org/10.1016/j.lana.2022.100325
Rascera, G., Ohara, A., & Ruann, J. (2021). Innovative and emerging applications of cannabis in food and beverage products: From an illicit drug to a potential ingredient for health promotion. Trends in Food Science & Technology, Vol. 115, p31-41. https://doi.org/ 10.1016/j.tifs.2021.06.035
Shafik, B., Justin, M., R, N. M., Elman, Kaye, A. D., Jason, Y. R., & Urman, R. D. (2020). The role of cannabidiol (CBD) in chronic pain management: An assessment of current evidence. Current Pain and Headache Reports, 24(2). doi:https://doi.org/10.1007/
s11916-020-0835-4
Stasilowicz, A., Tomala, A., Podolak, I., Cielecka-Piontek, J., (2021). Cannabis sativa L. as a natural drug meeting the criteria of a multi-target approach to treatment. International Journal of Molecular Sciences. (22)2. https://doi.org/10.3390/ijms22020778
