I. Introduction

Cannabis – Medicinal Plant and Recreational Drug

Cannabis is a plant with known recreational and medicinal properties. However, while the increasing acceptance of cannabis for different purposes has led to debates and research on its benefits and risks, it is important to acknowledge that excessive recreational use can have potentially negative effects on individuals and society, such as addiction, impaired driving, and potential negative mental health effects [1]. Scientists are studying how its active ingredients, especially THC and CBD, can treat various health problems such as pain, mental disorders, neurodegeneration, and cancer [2][3][4][5].

The medical and recreational cannabis markets are likely to diverge as more evidence-based treatments emerge from research. The medical cannabis industry will focus on creating specific natural medicines for different conditions, while the recreational market will cater to general consumers. This distinction is important for consumer safety and responsible use of cannabis-derived products.

This article delves into the potential of medical cannabis, discussing the anticipated continued growth in research and its impact on product development, as well as exploring the implications of the divergence between medical and recreational markets. It also addresses the challenges and opportunities that lie ahead, emphasizing the importance of continued support for research and development, responsible regulation, and public education.

II. Background

Historical Use of Cannabis

Cannabis has a long and complex history of human use, spanning across different cultures and eras for various purposes. Archaeological and historical evidence indicates that cannabis was consumed for medical and recreational reasons by ancient civilizations in China, Egypt and India, where it was valued for its therapeutic and psychoactive effects [6][7][8]. However, the global perception and regulation of cannabis changed dramatically in the 20th century, as cannabis users faced social stigma and legal sanctions. The Marijuana Tax Act of 1937 effectively banned cannabis in the United States and was fully influenced by political motives to suppress anti-war and minority groups, as revealed by a former Nixon aide in an interview in 1994 [9][10]. The War on Drugs further intensified the criminalization of cannabis, despite its potential medical benefits and cultural significance.

Resurgence in Medical Cannabis Research

Despite the historical stigma and misconceptions surrounding cannabis, there has been a remarkable revival of interest in its therapeutic potential in recent decades. This has sparked a wave of legalization and research initiatives across the world. Science has revealed that cannabis and its derivatives work by modulating the endocannabinoid system, which is involved in various physiological processes such as pain, inflammation, and neuroprotection. Cannabis-based treatments have shown promise for addressing several unmet medical needs, especially in chronic and neurological conditions. The medical cannabis industry is at the forefront of advancing evidence-based research and responsible regulation to develop safe and effective therapies for patients.

The global cannabis market has witnessed significant growth in recent years, owing to the legal and regulatory changes in various countries and states that have allowed the use of cannabis for medical and recreational purposes [11]. The medical cannabis industry has expanded rapidly, developing and approving a range of cannabis-based products for specific medical conditions, such as Sativex for spasticity associated with multiple sclerosis, and Epidyolex for certain types of epilepsy [12][13].

Recreational Cannabis Market

The recreational cannabis industry has also grown substantially, attracting consumers who seek cannabis products for personal enjoyment and relaxation. The industry has innovated diverse products, such as edibles, topicals, and concentrates, to meet the different preferences of consumers. However, the industry also faces significant challenges, such as the emergence of semisynthetic cannabinoids as legal substitutes for THC.

Semisynthetic cannabinoids are compounds that are derived from natural cannabinoids or hemp by modifying their structure or adding other chemical groups. Some of these compounds have not been adequately studied in humans and may turn out to have markedly different pharmacological effects than THC. For example, some semisynthetic cannabinoids have much higher affinity and efficacy at the CB1 receptor than THC, which may result in stronger psychoactive effects and increased risk of harm. The recreational industry needs to address the presence and potential impact of these compounds on consumers’ health and safety. The demand for semisynthetic cannabinoids may decline as more countries legalize and accept recreational cannabis, as most consumer prefer natural cannabinoids to synthetic ones [14]. These substances pose significant challenges for regulation and public education and have the potential to cause unintended societal damages if not properly regulated.

Cannabis research has made remarkable progress in recent years, enhancing our knowledge of the plant’s properties and effects on the human body. One of the key breakthroughs was the discovery of the endocannabinoid system (ECS), a network of receptors and molecules that regulate various physiological functions and respond to cannabis-derived compounds, such as THC and CBD [15]. These compounds show promising therapeutic potential for various medical conditions, based on their interactions with the ECS [16]. Importantly, cannabis is much more complex than the two well-known phytocannabinoids THC and CBD. An active area of research is the exploration of the synergistic effects of different phytochemicals, including other cannabinoids, terpenes, and flavonoids, which have shown to be able to modify or fine-tune the therapeutic effects of the plant [17]. 

III. The Medical Potential of Cannabis

The Endocannabinoid System

Phytocannabinoids are the main active substances in cannabis that interact with the human endocannabinoid system (ECS), a network of receptors and molecules that regulates various bodily functions [15]. Among the 100+ phytocannabinoids identified in the plant, THC and CBD are the most studied ones due to their distinct effects and reasonably defined mechanisms of action [16]. THC is responsible for the psychoactive effects of cannabis, as it binds to CB1 receptors mainly located in the brain. CBD, however, does not cause intoxication and acts on multiple targets within and outside the ECS.

The modulation of the ECS by cannabinoids such as THC and CBD offers a promising avenue for treating various medical conditions. The ECS is involved in controlling immune responses, pain sensation, mood, appetite, and memory [18][19]. Both THC and CBD have shown to have pain-relieving, anti-inflammatory, and neuroprotective properties in animal and human studies [20]. These results have stimulated the development of new therapies based on cannabinoids or cannabis extracts. In addition, research indicates that other components of cannabis, such as phytocannabinoids, terpenes, and flavonoids, may work together synergistically to enhance the therapeutic effects of cannabinoids, a phenomenon known as the “entourage effect” [17]. This suggests that using whole-plant cannabis extracts or formulations that include multiple components may have more benefits than using isolated cannabinoids alone, leading to the development of novel cannabis-based medicines with improved efficacy, safety, and patient outcomes.

Clinical Research and Cannabis

It is important to note, however, that much of the RCT-based research on medical cannabis is limited by methodological caveats, such as small sample sizes, lack of standardized dosing, and short study durations. Placebo responses in RCTs with cannabis are also problematic, especially in studies evaluating pain, as non-opioid placebo-analgesia is mediated by the CB1 receptor [21]. This means that both the active group and the placebo group likely experience analgesia through the same mechanism of action, i.e. modulation of CB1 receptor activity. In addition, some studies may be subject to bias, such as funding bias or selection bias, which may influence the reported outcomes. Therefore, while the current evidence suggests that medical cannabis may be effective in treating certain medical conditions, further research is needed to establish its safety and efficacy in different patient groups and indications, and to develop evidence-based treatments that can be tailored to individual patient needs.

Cannabis-based Medicines

Some cannabis-based medicines have already been approved by regulatory agencies, such as Sativex, a THC/CBD sublingual spray approved in many countries for treating multiple sclerosis spasticity [12], and Epidiolex, a purified CBD oral solution approved for treating certain forms of epilepsy [13]. More research is underway to explore the potential benefits and mechanisms of action of cannabis-derived compounds in treating a growing list of indications and to develop targeted, evidence-based treatments for diverse patient needs. As the scientific body of evidence continues to grow, novel medical cannabis products for new indications are likely to emerge.

IV. The future of medical cannabis

Cannabis Research is Exponential

The therapeutic potential of cannabis-derived compounds has attracted increasing attention from researchers in recent years. This is reflected in the exponential growth in scientific publications on the topic (see Figure 1). As more discoveries and insights emerge on the pharmacology and therapeutic applications of cannabinoids and other cannabis-derived compounds, new and improved medical cannabis products will be developed. Such products may include refined formulations and innovative delivery systems that can expand the range of treatable conditions and further enhance the safety and efficacy of cannabis-based medicines.

Figure 1. Published articles/year from PubMed (1992-2022) using keyword search for “marijuana”. Exponential trendline fits with R²=0.99

However, the legal and regulatory status of cannabis and its derived compounds can pose challenges for research in some regions. The stigma surrounding cannabis, as well as inconsistent regulations between states and countries, can hinder research efforts and impede progress towards evidence-based treatments.

Individualized Treatment

Medical cannabis is evolving towards personalized and targeted approaches that aim to meet the diverse needs of individual patients, considering their genetic makeup, disease causes, and personal preferences. These approaches are based on the growing understanding of the intricate interactions between cannabinoids and the human endocannabinoid system, as well as the synergistic effects of various cannabis-derived compounds [2]. These insights may lead to the creation of highly specific, personalized treatments that leverage these mechanisms. Genetic testing and pharmacogenomics will soon help to determine how patients likely will respond to different cannabis-derived treatments, enabling more accurate dosing and customized cannabinoid profiles. Additionally, future targeted therapies may involve unique combinations of lesser known cannabinoids or other cannabis-derived compounds that selectively target specific pathways in the endocannabinoid system, reducing adverse effects and enhancing therapeutic outcomes.

Challenges and Barriers

Medical cannabis faces several challenges, such as regulatory hurdles and public perception. The legal status of cannabis is inconsistent across different regions, which is a significant barrier to research, product development, and patient access. To overcome these barriers, it is essential to advocate for evidence-based policies and harmonize regulatory frameworks.

Another challenge is the public perception of cannabis, which may be influenced by concerns about its abuse and adverse effects, especially in the context of recreational use. To address these concerns, it is important to promote responsible use, differentiate medical and recreational cannabis, and educate the public about the scientific evidence for the therapeutic potential of cannabis-derived compounds.

Moreover, the regulation of cannabis-derived medicines is complex and dynamic. The lack of standardized regulations can make it hard for patients to access safe, high-quality medical cannabis products. It can also create confusion among patients and healthcare providers about their safety and efficacy. Therefore, efforts to simplify regulatory processes and ensure consistent quality control standards are critical to ensure the safety and efficacy of medical cannabis treatments.

V. The divergence of medical and recreational markets

Medical and recreational cannabis markets are likely to diverge further as scientific research reveals more therapeutic benefits of cannabis and its derivatives. This divergence stems from the demand for specific, evidence-based treatments for various medical conditions, which require accurate dosing, controlled formulations, and strict quality standards [22]. On the other hand, recreational cannabis products are mainly designed for consumer satisfaction and preferences, with a wider range of product types and a continuous focus on THC potencies [23].

This divergence has several implications for both industries. For the medical cannabis industry, it requires continuous investment in research and development, clinical trials, and regulatory compliance to ensure the safety and efficacy of cannabis-derived treatments. This emphasis on evidence-based medicine may also attract the attention of pharmaceutical companies and healthcare providers, leading to more collaboration and integration of cannabis-derived therapies into conventional healthcare. A potential challenge that may affect the development and accessibility of cannabis-derived therapies is the conflict of interest between the pharmaceutical industry and the medical cannabis industry. Pharmaceutical companies, which have historically dominated the drug development and marketing field, may view the growth of medical cannabis as a threat to their established revenue sources. This conflict of interest could result (is resulting?) in the pharmaceutical industry actively lobbying against the widespread acceptance and adoption of cannabis-derived therapies, possibly hindering research funding, product development, and regulatory approvals [24].

Both the pharmaceutical and the recreational cannabis industries face the challenge of ensuring consumer safety and responsible use. To overcome this challenge, they need to collaborate and communicate transparently, with a common focus on improving patient outcomes. By partnering with medical cannabis researchers, pharmaceutical companies can benefit from their expertise and resources, and foster innovation in developing safe and effective treatments.

The recreational cannabis industry may also have to comply with more stringent regulations and scrutiny as the distinction between medical and recreational use becomes clearer. Quality control, labeling, and marketing standards may be enforced to protect consumers and promote responsible use.

It is vital to keep medical and recreational cannabis products separate and distinct. Medical products should be based on scientific evidence, follow quality and dosing guidelines, and minimize adverse effects and drug interactions [25]. Labeling and packaging should clearly indicate that they are for medical use only and prevent confusion with recreational products. Recreational products also need to have measures to reduce harm, such as age limits, consumer education, increased quality control, and potency limits. By respecting these distinctions, both industries can coexist and serve their respective goals and priorities, while benefiting patients and consumers.

VI. Conclusion

The medical cannabis industry is on the verge of discovering new natural medicines from various cannabis-derived compounds and cannabinoid combinations, thanks to the rapid growth of scientific research on cannabis and its effects on the endocannabinoid system and other signaling pathways in the human body [26][27]. However, cannabis use is not without risks and side effects. A subset of users may develop a dependence or tolerance over time and experience cognitive impairments, especially in memory and attention. Furthermore, chronic cannabis use may potentially worsen mental health problems such as anxiety, depression, and psychosis in some individuals. Certain patient groups, such as pregnant women and adolescents, may also face negative consequences from medical cannabis use, such as fetal development issues and increased risk of cognitive dysfunction. Therefore, healthcare professionals should carefully evaluate the potential benefits and risks of medical cannabis use for each patient, considering their medical history, current medications, and any possible contraindications. Future research and development may lead to innovative cannabis-based treatments for a variety of medical conditions and enhance patient outcomes.

Another key factor for the success of the medical cannabis industry is efficient regulation and public education. Regulatory approaches have a significant impact on the availability, affordability, and quality of medical cannabis products, as well as on patients’ access to therapies [28]. Therefore, regulatory frameworks should be globally harmonized based on evidence and best practices, and should provide clear guidelines for product quality, testing, and labeling [29]. Streamlined approval processes can promote industry growth while ensuring safety and innovation [30].

The future of medical cannabis hinges on continued support for research and development in the field. This support is essential for uncovering new insights into the pharmacology, safety, and efficacy of cannabis-derived compounds and advancing the development of targeted, evidence-based treatments. By fostering collaboration among researchers, healthcare providers, pharmaceutical companies, and regulators, the medical cannabis industry can continue to innovate and expand its therapeutic applications, ultimately benefiting patients and the broader healthcare community.

The medical cannabis industry faces significant challenges that require the involvement of healthcare professionals, such as physicians, nurses, and pharmacists. They can contribute to the advancement of cannabis-derived therapies by providing patient education, personalized treatment plans, and research efforts. For this to happen, unbiased education about the ECS needs to be incorporated into medical textbooks and curricula, which is not the case today. Healthcare professionals are the gatekeepers with the power to help patients to access safe, effective, and evidence-based treatments. For this to happen, our healthcare systems needs to free themselves from the many lingering misconceptions and stigma about cannabis that the politized War on Drugs has fed us for such a long time.

These challenges need to be addressed by policymakers and stakeholders who can work together to introduce evidence-based unbiased education, reduce regulatory barriers, increase funding for research, and promote public awareness and acceptance of medical cannabis. Moreover, efforts to establish insurance coverage for medical cannabis treatments and improve patient access to medical professionals with expertise in cannabis-based medicine is highly encouraged.

Another important challenge for the medical cannabis industry is the need for standardization and quality control measures. Standardized testing methods, quality assurance protocols, and dosing guidelines will help ensure that medical cannabis products are safe, effective, and consistent in their potency and composition [22][25]. The development of international standards and treatment guidelines for medical cannabis could be instrumental in facilitating the integration of cannabis-derived therapies into mainstream healthcare systems, improving patient access, and driving further research and development in the field. Recently, novel guidelines for treating chronic pain and comorbid conditions were published in the journal Cannabis and Cannabinoid Research [31]. Whether these new guidelines will have an impact on the perception of medical cannabis among healthcare professionals remains to be seen, however their existence is crucial in order to destigmatize and legitimize the use of cannabinoid-based medicines in modern healthcare.

Stefan Broselid, Ph.D.
Editor-In-Chief, Aurea Care Medical Science Journal

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