Cannabis

Cannabis, also known as marijuana, is a plant that is grown all over the world and has been used as a medicine in diverse cultures for several thousand years [1]. It is only since the 1940s that the plant has been prohibited in the United States and not widely available for medicinal purposes [1].

Possessing cannabis is currently illegal by federal law in the U.S. unless approved for certain research purposes [2]. However, in recent years, a growing number of states have passed laws to legalize medical cannabis and/or recreational marijuana use [1]. In these states, a licensed doctor must certify you in order to purchase cannabis from a registered medical cannabis dispensary (a place where medical marijuana is sold legally) [3].

The two most significant active compounds (called cannabinoids) in cannabis are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which have been shown to cause drug-like effects on the central nervous system and immune system [2]. The main psychoactive cannabinoid in cannabis is THC, while CBD (another active cannabinoid) is reported to relieve pain, lower inflammation and decrease anxiety without causing the “high” of THC [2].

Cannabis has a number of potential therapeutic benefits for cancer patients, notably in the management of symptoms and helping to improve quality of life [1]. Research suggests that cannabis may be useful in combating cancer-related pain, chemotherapy-induced nausea and vomiting, insomnia, peripheral neuropathy, loss of appetite, anxiety and depression [1] [4].

There is considerable anecdotal evidence and abundant reports of cancer patients having remarkable responses from cannabis use as an anticancer agent, especially using highly-concentrated cannabis oil [1]. A growing body of scientific research in laboratory and animal models supports a potential direct anticancer effect of cannabis [1]. Evidence indicates it may induce apoptosis (programmed cell death), inhibit angiogenesis (formation of new blood vessels to tumors) and prevent metastasis (spread of cancer) [1].

However, clinical research is still lacking in humans to confirm safety, efficacy and best therapeutic protocols. Due to anecdotal reports of potential benefits a significant percentage of cancer patients (around 20-25%) report using cannabis to help relieve symptoms or treat the disease [4] [5]. As a result of prohibition, and a lack of high-quality clinical research that would convince a data-driven clinician, many oncologists are unsure how to advise cancer patients on the safe and appropriate use of cannabis [1] [6].

History of Cannabis for Cancer

The first recorded findings of cannabis (cannabis sativa) can be traced back to 12,000 years ago in the Altai Mountains in central Asia [7]. It is an annual flowering herb native to Asia, but is now cultivated around the world [3]. The discovery of cannabis as a medicine dates back to around 3,000 years ago with early records of medicinal use documented in ancient China, Egypt, Greece and later in the Roman empire [7] [8]. It has been employed in traditional medicine as a pain reliever, sleeping aid, hallucinogen, sedative and anti-inflammatory [3]. For thousands of years, the cannabis plant has also been used as a source of industrial fiber, seed oil, and as a recreational drug [3].

Cannabis first entered Western mainstream medicine in the 1840s thanks to W.B.O. Shaughnessy, a surgeon who discovered its medicinal properties while working in India for the British East Indies Company [7]. At the time it was promoted for its pain killing and sedative effects, anti-inflammatory properties and ability to help prevent muscle spasms and convulsions [8]. Cannabis is believed to have been Queen Victoria’s treatment of choice to alleviate pain related to menstrual cramps [8]. However, by the early 1900s other medicines were developed that were indicated for each of the potential applications of cannabis, which resulted in less widespread usage.

In 1937, the U.S. Treasury Department introduced the Marihuana Tax Act, which imposed a tax of $1 per ounce for medicinal use and $100 per ounce for recreational use, which made the cost prohibitive at the time [2]. The American Medical Association (AMA) strongly opposed the Act. They believed that objective evidence of the harmful effects of cannabis was lacking and it would hinder research into its potential medicinal benefits. However, by using the Mexican name for the plant and linking it with crime and other nefarious activities south of the U.S. border, Harry Ansligner, the director of the Federal Bureau of Narcotics and mastermind of the legislation, convinced many physicians of its dangerous effects [8]. Anslinger testified in Congress that “Marijuana is the most violence-causing drug in the history of mankind.” [8]

In 1942, cannabis was removed from the US Pharmacopeia (an official publication describing drugs, chemicals and medicinal preparations) [8]. In 1951, Congress passed the Boggs Act, which classified Cannabis alongside other narcotic drugs for the first time [2]. In 1970, when the Controlled Substances Act came into effect, cannabis was classified by Congress as a Schedule I drug, which defines the substance as having no accepted medicinal purpose and a high potential for abuse, such as heroin, LSD, mescaline, and others [2].

In more recent decades, the neurobiological effects of cannabis have been more deeply studied. The first cannabinoid receptor in the brain, CB1, was discovered in 1988, which has been linked to the central nervous system and digestive organs [2] [7]. The second cannabinoid receptor, CB2 was found in 1993 and is implicated in the regulation of immunity and inflammation [2] [7]. Four years later the first endocannabinoid (cannabinoid naturally produced in the body) was discovered and named anandamide in reference to the Sanskrit word ‘ananda’, which means bliss [7]. Since this discovery there have been tremendous advances in the understanding of the endocannabinoid system in the human body and its role in psychology and physiology [7]. These findings have placed the debate around cannabis prohibition/legalization under a new light and sparked a wave of renewed interest in its potential medicinal properties and therapeutic applications [7].

Research on Cannabis for Cancer

Cannabis use amongst cancer patients is very common according to a survey conducted by the National Cancer Institute, which showed that over 20% of 926 cancer patients reported using cannabis [5]. However, patients also feel that they are not receiving adequate information about the possible therapeutic benefits of cannabis and that oncologists need to be better informed on the subject [5]. Due to a lack of reliable clinical data and research in humans, physicians are undereducated when it comes to cannabis and the endocannabinoid system. Studies have shown that 89.5% of doctors in the U.S. feel unprepared to prescribe, only 35.3% feel ready to answer questions, and only 9% of medical schools in the U.S. have up to date clinical information on cannabis in their curricula [6].

Research shows that cannabis has a range of potential benefits for cancer patients, especially in the management of disease and treatment related symptoms [1]. Clinical research suggests that cannabis has benefits for chemotherapy-induced nausea and vomiting, loss of appetite, and pain [4] [9] [10]. There is promising evidence that cannabis can help to treat chemotherapy-induced peripheral neuropathy, gastrointestinal distress, and sleep disorders, but the literature is not yet strong enough to prescribe cannabis for these problems [4] [10] [11]. There is some evidence, albeit more controversial, that cannabis may help with treatment-related anxiety, depression and fatigue [4]. More rigorous research with greater statistical power (based on large patient numbers) is needed to better elucidate mechanisms of actions, efficacy, and appropriate dosages for different types of patients [4].

Preclinical research (laboratory and animal studies) indicates potential anticancer properties of cannabis. One of the earliest studies suggesting that cannabinoids may have anticancer activity came from the National Cancer Institute in 1975 [12]. A 2014 systematic review of the literature on cannabinoids and glioma cells (brain cancer) analyzed 34 studies [13]. The antitumor activity of cannabinoids included apoptosis (programmed cell death), toxicity to cancer cells, and autophagy (cellular repair and renewal) as well as antiangiogenic properties (stops formation of blood vessels), anti-migratory and anti-metastatic effects (prevents spread of tumors). Reductions in tumor size were also noted [13].

Other reviews of the literature have shown that cannabinoids have anticancer effects in vitro (laboratory studies) and in vivo (animal models) on various different types of cancer cells, inhibit tumor growth and prevent cancer spread [1]. The anticancer effects of cannabis have been shown in research against adenocarcinomas of the lung, breast, colon and pancreas, and also myeloma lymphoma and melanoma [1] [14] [15] [16] .

A 2011 review of the scientific literature reveals that the endocannabinoid system may potentially be targeted to suppress the evolution and progression of breast, prostate and bone cancer as well as helping to alleviate pain associated with these conditions [17]. Furthermore, the review indicates that synthetic cannabinoids and the endocannabinoid system play a role in inhibiting cancer cell proliferation, angiogenesis (formation of blood vessels to tumors), reducing tumor growth and preventing metastases (spread of cancer) in breast, prostate and bone cancer [17].

Despite some promising early research, clinical research in humans on the anticancer effects of cannabis is still lacking. Current research only indicates cannabis for the management of certain specific symptoms commonly experienced by cancer patients. Further research is still needed to determine the therapeutic potential of cannabis in cancer care.

Potential Applications of Cannabis for Cancer

The mechanism of action of cannabinoids (the active components of cannabis) as anticancer agents is still poorly understood and not yet fully elucidated in the scientific literature. It appears that cannabinoids may induce apoptosis (programmed cell death) in cancer cells, most likely via the CB1 receptor, in a wide range of different cancer cell types [1]. Furthermore, tumor growth, angiogenesis, and metastases are hampered by cannabinoids in various animal models of cancer [1] [16]. In addition, cannabinoids have been shown to have potent anti-inflammatory and antioxidant properties, which may also play a supportive role in combating cancer [1].

However, there is not enough clinical research or data to support the application of cannabis as a primary cancer treatment in humans. The National Academy of Medicine issued a report, which stated that conclusive or substantial evidence that cannabis and cannabinoids are effective only applies to three areas [7]:

1. Alleviation of chronic pain in adults (cannabis)
2. Antiemetics in the treatment of chemotherapy-induced nausea and vomiting (oral cannabinoids)
3. Improvement in multiple sclerosis spasticity symptoms (oral cannabinoids)

There is substantial evidence that cannabis and cannabinoids are beneficial in the treatment of chronic cancer-associated pain, including neuropathy [5]. In fact, chronic pain is one of the most commonly cited reasons for the prescription of medical marijuana [5]. There is reasonable evidence that cannabis can be used to help manage pain as a supplement to first-line pain management strategies and potentially reduce opioid usage in advanced cancer patients [4] [18].

Despite a lack of clinical evidence that cannabis has therapeutic application in cancer treatment for humans, there is considerable anecdotal evidence of the potential anticancer effects of cannabis [1]. Widespread reports exist of patients having remarkable responses to high-potency orally ingested concentrates of cannabis oil [1]. Clinical trials on humans need to be conducted to address the potential therapeutic application of cannabis as a cancer treatment and help to determine the legitimacy of the anecdotal reports.

Based on the current literature the scientifically-supported potential applications of cannabis are as follows [3]:

• Pain
• Glaucoma (eye disease)
• Nausea and vomiting (related to cancer treatments)
• Sleep disorders
• Epilepsy
• Multiple sclerosis
• Mood disorders including depression, bipolar, and seasonal affective disorder
• Loss of appetite

Overall, cannabis has an acceptable side-effect profile compared to many other pharmaceutical drugs used by oncologists for the same indications [1]. Furthermore, as a singular therapeutic agent it has a range of potential applications (such as nausea, pain, anorexia, anxiety, and insomnia). Therefore, doctors may prefer to prescribe cannabis rather than 5 or 6 different drugs each with potentially more serious side effects [1]. In this regard, cannabis may provide benefits for cancer patients.

Cannabis has also been shown to be a useful tool in the treatment of other complex diseases or rare conditions that lack safe and effective conventional treatment options, or where side effects outweigh the potential benefits [6]. For example, conditions such as fibromyalgia, chronic fatigue syndrome, migraines, irritable bowel syndrome, multiple sclerosis, neuropathic pain and refractory nausea [6].

However, more research is still needed to determine the full scope of the potential therapeutic applications of cannabis and provide more robust treatment guidelines for doctors and patients [1].

Risks and Side Effects of Cannabis

Cannabis is generally a well tolerated substance without significant negative side effects or risks [4]. Patients often report pleasant side effects (such as euphoria and relaxation) with relatively few and minor short or long-term negative effects [4].

However, cannabis can cause some negative side effects such as anxiety, paranoia and panic attacks, which are primarily related to THC, the psychoactive compound in cannabis [4]. Cognitive abilities such as attention span and memory can be affected by cannabis, while judgment and reaction times can also be impaired [4].

The potential risks and side effects of taking cannabis may include the following [3]:

• Anxiety
• Paranoia
• Hallucinations
• Hunger
• Drowsiness
• Short-term memory loss
• Blood pressure changes
• Difficulty focusing
• Increase heart rate
• Confusion
• Nausea
• Vomiting
• Flushing
• Depression
• Insomnia

Cannabis is contraindicated in pregnancy and lactation. It is also not advised for anyone suffering from psychosis. Caution is advised for anyone with cardiac conditions, such as angina, due to risk of increased heart rate and possible effects on blood pressure [6].

You should always consult your healthcare provider before starting any new medication to discuss potential risks and contraindications.