Introduction

Cannabis sativa L. is one of the oldest flowering medicinal plants in the Cannabaceae family used by humans for recreational and palliative care purposes to alleviate pain, as well as to improve quality of life in terminal stages of diseases, including cancer [1] [25]. The three main species of cannabis are C. sativa, C. indica, and C. ruderalis [11]. The industrial cultivation of Cannabis (marijuana) for its fiber, seeds, medicinal, and psychoactive properties has occurred for thousands of years. In recent years, there has been growing interest in cannabis research and the potential health benefits. One of the key areas of cannabis research is its impact on the endocannabinoid system.

The endocannabinoid system (ECS) is a complex neuromodulatory network of signaling molecules and receptors that plays a role in a wide range of physiological processes, including pain modulation, inflammation, mood, appetite, blood pressure, and embryogenesis. The ECS also plays a role in pathological conditions, such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and multiple sclerosis [2] [6]. Cannabis is a complex plant with over a hundred chemical metabolites and cannabinoid compounds. These include tetrahydrocannabinol (THC), delta-8-tetrahydrocannabinol (delta-8 THC), and cannabidiol (CBD), which can interact with the endocannabinoid system to produce a variety of effects [3].

Research indicates CBD has a wide range of potential therapeutic health benefits for cancer treatments, including reducing pain and inflammation, improving sleep quality, and relieving anxiety and depression [4]. On the other hand, cannabis can also cause side effects, such as anxiety, paranoia, and impaired cognitive function [15].

Definitions

Marijuana 

Marijuana is a substance composed of parts of the plant Cannabis sativa, including the leaves, flowers, seeds, and the resin extracted from any part of the plant. Marijuana contains the psychoactive phytocannabinoid compound tetrahydrocannabinol (THC), short for delta-9-tetrahydrocannabinol, along with other phytocannabinoids [9].

Hemp 

Hemp is a genetic variant of Cannabis sativa bred to maximize its fiber content and minimize its phytocannabinoid content. The term “hemp” refers to the plant Cannabis sativa L. and any part of that plant, including the seeds and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers [10].

Cannabis 

Cannabis is a genus of flowering plants in the family Cannabaceae, used for both medicinal and recreational purposes [1]. Cannabis contains a variety of cannabinoids, including THC and CBD, and is ingested in various forms, including smoked, vaped, or consumed as edibles.

Cannabinoids 

Cannabinoids are a class of chemical compounds found in the cannabis plant that interact with cannabinoid receptors in the body and produce a variety of effects, including pain relief, appetite stimulation, inflammation reduction, and mood modulation [4] [5]. The two most well-known cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive compound in cannabis responsible for euphoria, and CBD is a non-psychoactive compound shown to have a wide range of potential health benefits.

CBD (cannabidiol) 

CBD is A non-psychoactive compound (the second most prevalent active ingredient in cannabis or marijuana) shown to have a wide range of potential health benefits, including anti-inflammatory and anti-anxiety properties, improving sleep quality, and relieving anxiety and depression [7].

Hemp Oil/ CBD Oil 

Hemp oil/CBD oil is a solution of a solvent extract from Cannabis flowers and/or leaves dissolved in an edible oil; it often contains 1%-5% CBD [20].

THC (tetrahydrocannabinol) 

THC is the primary psychoactive compound in cannabis. THC binds to cannabinoid receptors in the brain and is responsible for the “high” experienced during cannabis consumption [6].

Endocannabinoid system 

The endocannabinoid system is a complex cell-signaling system of molecules and receptors that plays a role in a wide range of physiological processes, including synaptic plasticity, pain sensation, inflammation, mood, and appetite. It is the primary target of cannabinoids [2].

Medical cannabis (MC) 

MC refers to the therapeutic use of herbal cannabis and its constituents as recommended by a doctor in the treatment of a medical condition. Indications for medical cannabis include pain management in patients with cancer. MC is used in several countries, including most of the United States, Canada, Israel, the United Kingdom, and others [8].

Legal cannabis for medical use 

Cannabis that is legal to use for medical purposes in a particular state and available for treating specified medical conditions under a regulated framework.

Cannabis for Pain Management in Cancer 

The use of cannabis or its derivatives to alleviate pain symptoms associated with cancer, either alone or in conjunction with other treatments.

Federal and State Regulations 

Laws and policies governing the medical use, sale, and possession of cannabis can differ between federal and state jurisdictions.

Terpenes 

Terpenes are aromatic hydrocarbons produced by the cannabis plant, along with phytocannabinoids that produce the unique smell and taste of different cannabis strains. Common terpenes in cannabis include limonene, pinene, myrcene, delta-3-carene, eucalyptol, and humulene [16].

Cannabis and the Endocannabinoid System:

The endocannabinoid system (ECS) consists of endocannabinoids, which are molecules that bind to cannabinoid receptors. Cannabinoids are a component of the cannabis plant. The two most well-known cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD) [3].

When cannabinoids from cannabis bind to cannabinoid receptors in the body, they can produce a variety of effects, depending on the type of cannabinoid and the location of the receptor [11]. For example, THC can bind to CB1 cannabinoid receptors in the brain to produce the psychoactive effects of euphoria, relaxation, and altered perception [12]. THC also binds to CB2, the peripheral receptor for cannabinoids in the immune system, to reduce inflammation [13].

CBD can bind to cannabinoid receptors throughout the body to produce anti-inflammatory, analgesic, and anti-anxiety effects [12]. CBD can inhibit the breakdown of endocannabinoids, which allows them to have a longer-lasting effect; CBD also activates other receptors in the body, such as the 5-HT1a receptor involved in mood regulation [14].

Additional prominent cannabinoids include: [40]

• Cannabigerol (CBG): A non-psychoactive cannabinoid thought to have anti-inflammatory, analgesic, and anti-convulsant effects.
• Cannabichromene (CBC): A non-psychoactive cannabinoid thought to have anti-inflammatory, analgesic, and anti-depressant effects.
• Cannabicyclol (CBL): A non-psychoactive cannabinoid thought to have anti-inflammatory, analgesic, and anti-anxiety effects.
• Delta-8-tetrahydrocannabinol (delta-8 THC): A less potent psychoactive cannabinoid with fewer side effects when compared to THC.
• Tetrahydrocannabivarin (THCV): A psychoactive cannabinoid thought to have appetite-suppressant and anti-psychotic effects.

Indications for Use 

Medical Conditions 

Medical cannabis may treat a variety of medical conditions, including: [17]

• Anxiety and Depression
• Epilepsy
• Multiple sclerosis
• Cancer-related side effects
• Parkinson’s disease
• Alzheimer’s disease
• Crohn’s disease and ulcerative colitis
• Glaucoma
• Migraines
• Tourette syndrome
• Post-traumatic stress disorder (PTSD)
• Fibromyalgia
• Chronic Fatigue Syndrome,
• Insomnia
• Appetite loss

Symptoms 

While THC can cause adverse effects (dizziness, somnolence or drowsiness, dry mouth, disorientation, anxiety, and acute psychosis), it may be effective for the treatment of a variety of symptoms, including: [16]

• Pain
• Inflammation
• Nausea and vomiting
• Poor appetite
• Sleep problems
• Muscle tension
• Chronic pain
• Chemotherapy-induced nausea and vomiting

Cannabidiol (CBD) also has potential health benefits, including reducing pain and inflammation, relieving nausea and vomiting, reducing anxiety and depression, treating seizures, reducing muscle spasms, and improving sleep quality [16].

Past, Current, and Future Research

Several studies have shown cannabis and cannabinoids to be safe and effective in managing pain in a variety of conditions. The most common side effects are mild and include dry mouth, dizziness, and lightheadedness [20].

In 2017, the National Academies of Sciences, Engineering, and Medicine (NASEM) published a report on the health effects of cannabis and cannabinoids. The report indicated conclusive and substantial evidence that cannabis-based products are effective for the treatment of chronic pain in adults, chemotherapy-induced nausea and vomiting (oral cannabinoids), and multiple sclerosis spasticity (oral cannabinoids) [30].

A 2019 study of more than 1,000 patients published in the Journal of Oncology Practice supports evidence that medical cannabis can help reduce the severity of nausea, pain, insomnia, and other side effects associated with cancer and its treatment [22].

A 2021 study published in the Journal of Pain Medicine found that cannabis was effective in reducing pain and improving quality of life in patients with chronic cancer pain over a six-month period. The study participants reported that cannabis was more effective than traditional pain medications, such as opioids [19].

A 2023 multicenter registry study, published in BMJ Supportive & Palliative Care, reported that medicinal cannabis can safely relieve cancer pain while curbing the total number of meds and opioids taken [21].

A small randomized, placebo-controlled, double-blinded clinical trial found that Nabiximols (an oral spray with delta-9-THC and CBD given by mouth) treated refractory nausea and vomiting caused by chemotherapy [24].

An oral spray of Cannabis extract given with temozolomide to treat recurrent glioblastoma multiforme appears to prolong the survival of patients with glioblastoma multiforme in a small, select cohort of patients [25].

In a small study, vaporized cannabis given with morphine relieved pain better than morphine alone, while vaporized Cannabis given with oxycodone did not give greater pain relief [26].

In a study of 74 patients diagnosed with head and neck cancer, Cannabis users had lower anxiety or depression and less pain or discomfort than the nonusers. The Cannabis users also had less fatigue, more appetite, and greater feelings of well-being [27].

Federal and State Regulations

As of Oct 2023, the Food and Drug Administration (FDA) has not approved cannabis or cannabinoids for use as a cancer treatment. However, two cannabinoids – dronabinol (Marinol and Syndros) and nabilone (Cesamet) – were approved for the treatment of nausea and vomiting caused by chemotherapy in patients who have not responded to standard antiemetic therapy [23].

Legal cannabis for medical use in the United States is the use of cannabis for medicinal purposes under the law. As of April 2023, medical cannabis is legal in 38 states, three out of five inhabited U.S. territories, and the District of Columbia [28]. Individual states have their own medical cannabis laws in terms of eligible qualifying conditions, the purchasing of medical cannabis, and the regulation of the medical cannabis industry.

To obtain medical cannabis, patients must first obtain a recommendation from a licensed healthcare provider. Medical cannabis is available in a variety of forms, including dried flower, edibles, vaporized concentrates, and topical products [29]. Cannabis remains a Schedule I substance under federal law and is considered to have a high potential for abuse with no currently accepted medical use. As a result, it is a federal crime to distribute cannabis [28].

Legalization in Different Countries

Countries where medical cannabis is used for pain management in cancer:

North America 

• United States: Medical cannabis is illegal at the federal level, but 38 states have legalized its medical use, including for cancer pain.
• Canada: A sublingual cannabinoid pharmaceutical known as Sativex is legal and used for various conditions, including cancer-related pain and multiple sclerosis (MS)-related neuropathic pain or spasticity [31].

Europe 

• Germany: Doctors can prescribe medical cannabis for severe cases of pain, including cancer pain [32].
• United Kingdom: The legalization of medical cannabis occurred in 2018. Use may occur in rare cases where other treatments have failed.
• The Netherlands: Medical cannabis is available by prescription, including for cancer pain, neuropathic pain, spasms, and pain related to MS. It is also available for lack of appetite, nausea, and vomiting related to cancer or HIV/AIDS [33].

Australia: A regulatory framework allows access to medicinal cannabis, but this can vary between states and territories [34].

New Zealand: The legalization of medical cannabis occurred in 2020 for indications including cancer pain [35].

South America 

• Uruguay: This was the first country to fully legalize medical and recreational marijuana in 2013 for indications including managing cancer pain [36].
• Colombia: Therapeutic use of medical cannabis is allowed for indications, including cancer-related pain [37].

Asia 

• Israel: A pioneer in medical cannabis research, Israel allows the use of medical cannabis for cancer pain [38].

Africa 

• South Africa: Medical cannabis is approved for specific medical conditions, though regulations are evolving [39].

Implications for Nursing Practice

The medical use of cannabis has implications for nursing practice. Nurses need to be knowledgeable about the medical uses of cannabis, including its potential risks and side effects. This includes an understanding of the diverse administration methods of cannabis, the different strains and effects, and how to interact with patients about their cannabis use.

Nurses should be able to educate patients about the safe and effective use of cannabis and provide information about different delivery methods, dosing, and potential interactions with other medications.

• Ethical and Legal Considerations: Nurses must understand the legal landscape in their jurisdiction.
• Liability: The improper administration of cannabis can result in legal consequences for healthcare providers.
• Confidentiality: Given the stigma around cannabis use, nurses must take extra care to maintain patient confidentiality.
• Certifications: Some states and organizations offer specialized training and certifications in medical cannabis administration.

Conclusion

Cannabis can have some adverse effects, including dizziness, somnolence, dry mouth, disorientation, anxiety, and acute psychosis. However, research indicates that Cannabis-based products are effective for the treatment of several medical conditions, including chronic pain, chemotherapy-induced nausea and vomiting, multiple sclerosis spasticity, and seizures. Further research is needed to determine the safety and efficacy of cannabis for specific cancer symptoms and side effects, as well as the optimal dosage and delivery methods for each symptom.