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A selective review of medical cannabis in cancer pain management

Contributions: (I) Conception and design: A Blake, E Chow, S O’Hearn; (II) Administrative support: BA Wan, L Malek, P Diaz; (III) Provision of study materials or patients: N Lao; (IV) Collection and assembly of data: A Blake, BA Wan, L Malek, S O’Hearn; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Ms. Alexia Blake, MSc. MedReleaf Corp, Markham Industrial Park, Markham, Ontario, Canada. Email: [email protected] .

Abstract: Insufficient management of cancer-associated chronic and neuropathic pain adversely affects patient quality of life. Patients who do not respond well to opioid analgesics, or have severe side effects from the use of traditional analgesics are in need of alternative therapeutic options. Anecdotal evidence suggests that medical cannabis has potential to effectively manage pain in this patient population. This review presents a selection of representative clinical studies, from small pilot studies conducted in 1975, to double-blind placebo-controlled trials conducted in 2014 that evaluated the efficacy of cannabinoid-based therapies containing tetrahydrocannabinol (THC) and cannabidiol (CBD) for reducing cancer-associated pain. A review of literature published on Medline between 1975 and 2017 identified five clinical studies that evaluated the effect of THC or CBD on controlling cancer pain, which have been reviewed and summarised. Five studies that evaluated THC oil capsules, THC:CBD oromucosal spray (nabiximols), or THC oromucosal sprays found some evidence of cancer pain reduction associated with these therapies. A variety of doses ranging from 2.7–43.2 mg/day THC and 0–40 mg/day CBD were administered. Higher doses of THC were correlated with increased pain relief in some studies. One study found that significant pain relief was achieved in doses as low as 2.7–10.8 mg THC in combination with 2.5–10.0 mg CBD, but there was conflicting evidence on whether higher doses provide superior pain relief. Some reported side effects include drowsiness, hypotension, mental clouding, and nausea and vomiting. There is evidence suggesting that medical cannabis reduces chronic or neuropathic pain in advanced cancer patients. However, the results of many studies lacked statistical power, in some cases due to limited number of study subjects. Therefore, there is a need for the conduct of further double-blind, placebo-controlled clinical trials with large sample sizes in order to establish the optimal dosage and efficacy of different cannabis-based therapies.

Keywords: Medical cannabis; cancer; pain

Submitted Jul 04, 2017. Accepted for publication Aug 03, 2017.


Cancer patients often present with chronic pain, which may stem from direct tumour involvement, or present as a side effect of cancer treatment (1). As pain negatively impacts the physical, functional, and emotional domains of life, effective pain management strategies are essential for restoring and maintaining quality of life of cancer patients (2). Unfortunately, the current standard treatment regimens for chronic or neuropathic pain in end-stage cancer patients rely heavily on opioid analgesics, which are problematic for some patients (3,4). This can be due to a combination of factors, including differences in individual responses to these drugs, and the presence of serious side effects such as severe constipation, that may prevent the administration of sufficient doses for pain relief (3). In addition, imprudent dosing runs the dangerous risk of patients developing dependency, or overdosing on opioids (4). Therefore, identifying alternative classes of analgesics that can effectively manage pain in cancer patients is of great importance.

Alternative pharmacological interventions include prescription medications such as acetaminophen, or nonsteroidal anti-inflammatory drugs like ibuprofen (5). Non-medicated approaches include therapies such as acupuncture, physical therapy, in addition to psychological or behavioural approaches (6). In addition to the management strategies listed above, compounds derived from the plant species Cannabis Sativa L. have demonstrated the potential to alleviate pain. The most commonly studied examples include tetrahydrocannabinol (THC), and cannabidiol (CBD) from the family of compounds known as cannabinoids (7). These compounds are commonly administered via inhalation, orally as oils or oil-filled capsules, or oromucosally via sprays containing either THC alone, or a combination of THC:CBD (8). Several pre-clinical studies have been conducted in animal models, investigating the mechanism of cannabinoid modulation of pain pathways (9,10). One of the identified mechanisms is the interaction of these compounds with one of the body’s endogenous signalling systems, known as the “endocannabinoid” system (11). This system acts independently of the opioid pathway to control pain signalling, immune activation, and inflammation (11). While there is an abundance of existing anecdotal evidence of the analgesic properties of medical cannabis, its efficacy has not yet been validated through high-quality clinical studies that provide strong evidence supporting its utility in the clinical setting (12).

This selective review is an overview of clinical studies conducted historically and up until the present day that aimed to investigate the efficacy of medical cannabis in managing pain in advanced cancer patients.


A search of literature published on Medline between 1975 and 2017 through using key words including “cannabis”, “THC”, “CBD”, “Nabiximol”, “cancer”, and “pain” was conducted. Five clinical studies that evaluated the effect of THC or CBD on controlling cancer pain were evaluated for a selective review. Information regarding the study population, interventions, pain response, and side effects was reviewed and summarised.


Patient populations and selection criteria

Five studies were selected based on their evaluation of cannabinoids to manage chronic pain in advanced cancer patients. An early pilot study conducted in 1975 by Noyes et al. assessed pain in ten advanced cancer patients (eight women and two men, average 51 years old) (13). In a similar pain management study, Noyes et al. compared the effects of THC and codeine in 36 cancer patients (consisting of 26 women and 10 men) (14). Non-study medications were withheld from patients from both studies by Noyes et al. during the study period (13,14). Johnson et al. conducted a multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of nabiximols and THC in patients with intractable cancer-related pain, using a well-distributed population of 177 advanced cancer patients, who recorded non-study breakthrough analgesics (15). In this study, the mean age, gender, primary disease sites, and pain classification were distributed similarly between the three treatment arms; THC, nabiximols, and placebo (15). In 2012, Portenoy et al. conducted a randomized, placebo-controlled, graded-dose trial involving 360 patients with advanced cancer, looking at the efficacy of THC or nabiximols. Patients were chosen based on having previously responded poorly to opioid analgesics, but were allowed to take breakthrough opioid analgesics as required (16). Patients who had received long-term methadone treatment for pain were excluded. Pain characteristics were categorized as mixed (48%), bone (24%), visceral (15%), and neuropathic (11%), and were distributed approximately equally across the study arms. Finally, Lynch et al. conducted a double-blind, placebo-controlled, crossover pilot trial including 16 cancer patients who had persistent neuropathic pain 3 months after their cancer treatment (17). These patients had an average 7-day pain intensity ≥4 on 0–10 NRS, stable concurrent analgesic treatment for 14 days prior to study initiation, and were not taking breakthrough analgesics.

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Evaluation of pain

In the clinical studies of cannabinoids for cancer pain management included in this review, several methods of measuring changes in pain intensity were employed. Early studies by Noyes et al. used a 4-point pain scoring system in which 0= absent, 1= mild, 2= moderate, and 3= severe (13,14). Since then, many studies have employed the numerical rating scale (NRS) to evaluate pain on a 0–10 scale, with “0” representing “no pain” to “10” representing “pain as bad as you can imagine”. Patients with neuropathic pain studied by Lynch et al. completed the NRS at baseline, and the last day of each week of dosing (17). The change in NRS score from baseline to the week in which a stable dose was reached was used as the primary endpoint in determining cannabis efficacy. In the study by Johnson et al., patients used the NRS in addition to recording their long-term and break-through pain medications in a pain diary (15). Portenoy et al. asked patients to report their average pain on the brief pain inventory (BPI), as well as through an interactive voice recording system (16). The two remaining studies used the BPI to assess change in pain as the primary endpoint (18,19).

Efficacy of interventions

Overall, four out of the five studies found that cannabis was significantly associated with a decrease in cancer-associated pain. Table 1 presents a summary of the efficacy of THC or CBD on cancer pain.

Table 1 An overview of randomized controlled trials (RCTs) involving medical cannabis for cancer pain
Full table

THC oil capsules and THC, CBD oromucosal sprays

Studies included in this review assessed the efficacy of THC oil capsules, and oromucosal sprays containing THC extract, or THC:CBD extract, also known as nabiximols. Since nabiximols have CBD in addition to THC, they may potentially target more pain pathways when compared to THC extract alone.

Two early clinical studies on the efficacy of THC extract in sesame oil capsules were published by Noyes et al. in 1975 (13,14). The first was a pilot study that identified a correlation between higher doses of THC and increased pain relief (P<0.001) (13). The second study found a significant difference in pain reduction between placebo and 20 mg THC (P<0.05), in favour of THC treatment (14).

Oromucosal sprays have been a common method of administration for cannabinoid-based medicines in clinical investigations, to date (12). Both THC extracts and nabiximols, administered oromucosally, were studied by Johnson et al. (15). They did not observe a significant change in mean pain score from baseline for THC spray compared to placebo, but did report a statistically significant change in favour of nabiximols treatment compared to placebo (P=0.024). In addition, they reported that patients taking nabiximols required significantly fewer doses of breakthrough pain medications when compared to placebo (P=0.004). Portenoy et al. found that compared to placebo, nabiximols were significantly more effective for reducing average daily pain when comparing scores from baseline to the end of the study period (P=0.038) (16). These findings are in contrast with the study by Lynch et al. in which there was no statistically significant difference between placebo and nabiximols treatment groups amongst the 16 patients experiencing cancer-related neuropathic pain (17).


Studies assessed the efficacy of different doses of medication, or allowed patients to self-titrate up to a maximum dose, as dictated by study protocols.

Evaluation of the effect of 5, 10, 15, and 20 mg of THC in oil capsules by Noyes et al. found that the amount of pain relief increased with dose (13). Out of 10 patients in each cohort, 5 received substantial relief from 15 mg, and 7 patients received substantial relief from 20 mg. In the second study by Noyes et al., two different THC doses of 10 and 20 mg were compared to placebo and 60 mg codeine (14). A 60 mg dose of codeine is a standard daily opioid analgesic regimen used in the management of many pain types, including cancer pain (20). A significant difference in pain reduction was observed with the administration of 20 mg THC when compared to placebo (P<0.05). Additionally, no significant difference in pain relief was observed when comparing the 10 mg THC cohort to those receiving 60 mg codeine (P<0.05). This suggests the non-inferiority of 10 mg of THC in comparison to a commonly used opioid treatment.

Evaluation of the efficacy of THC oromucosal spray by Johnson et al. followed a self-titration method of dosing (15). Patients who used THC sprays used an average of 8.3 sprays/day, corresponding to 22.5 mg of THC/day following dose titration up to a ceiling dose of 48 sprays/day. Patients were considered to have reached their optimal dose upon experiencing relief of pain, or the development of side-effects. The authors found the optimal dose of THC reached across patients provided greater pain relief compared with placebo as measured by the average NRS pain score reduction (THC −1.01 vs. placebo −0.69) however, statistical significance was not reached (P=0.245).

In the three studies on nabiximols included in this review, self-titration was recommended up to a maximum dose of 8 sprays/3-hour period (15), and 11–16 sprays/day (16,17). In one of the studies, patients were divided into three dose groups categorized by titration ranges of mild (1–4 sprays/day, or 2.7–10.8 mg THC, 2.5–10.0 mg CBD), moderate (6–10 sprays/day, or 10.8–16.2 mg THC, 10.0–15 mg CBD), and high (11–16 sprays/day, or 29.7–43.2 mg THC, 27.5–40 mg CBD) (16). The doses found to produce significant pain relief include an average of 8.75 sprays/day (15), 1–4 sprays/day (16), and 6–10 sprays/day (16). It was observed that the high dose group of patients who utilised 11–16 sprays/day did not experience significant pain relief compared to placebo. Similarly, Lynch et al. found that at a high dose of an average of 8 sprays/day there was no significant pain relief observed in comparison to placebo (17).

Side effects and adverse events

Side effects reported in studies included in this review were consistent with those reported in literature investigating the use of cannabinoid-based therapies for several other indications (7). Table 2 summarises the five most commonly reported side effects of the five studies. In both studies by Noyes et al., side effects of 15 and 20 mg of THC included mental clouding (60–70%), drowsiness (70–100%), and euphoria (40–50%) (13,14). Not all side effects were experienced by all patients, and side effects tended to become more prevalent with higher doses.

Common treatment-related adverse events reported by Johnson et al. include somnolence (nabiximols 13%, THC 14%, placebo 10%), dizziness (nabiximols 12%, THC 12%, placebo 5%), confusion (nabiximols 7%, THC 2%, placebo 2%), nausea (nabiximols 10%, THC 7%, placebo 7%), and hypotension (nabiximols 5%, THC 0%, placebo 0%) (15). These were reportedly more frequent in patients receiving the nabiximols extract and the THC only extract, when compared with placebo. The adverse events identified by Portenoy et al. were significantly more frequent in the higher nabiximols dose group, whereas little difference was observed between the low dose and placebo groups (17). Lynch et al. identified fatigue (nabiximols n=7, placebo n=0), dry mouth (nabiximols n=5, placebo n=1), dizziness (nabiximols n=6, placebo n=0), and nausea (nabiximols n=6, placebo n=1) to be the most common side effects, which were more often observed in the treatment arm compared to placebo, although the significance of this difference was not assessed. However, patients also reported that the majority of side effects were transient and mild, and could be reduced through adjusting treatment dose. Side effects did not lead to any study drop-outs (13-17).

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The paucity of clinical data available on medical cannabis for treatment of cancer pain is partly due its classification as a schedule I agent by the Controlled Substances Act in 1970, which restricted its investigation as a potential medical product (8). However, the few studies that were produced on the use of medical cannabis for cancer pain management have results that suggest it does possess therapeutic potential, and is at least worthy of further investigation.

There is a lack of dosing guidelines for the use of cannabinoid-based therapies in clinical practice. The ideal dosage would be one that provides effective pain management, but does not produce intolerable side effects. However, there are challenges in establishing this optimal dose in the advanced cancer patient population. One of these is inter-patient variability, in keeping with results from studies on narcotics and other prescription analgesics. As optimal doses were found to vary from patient to patient, physicians need to understand how to determine the correct dosage when prescribing to a new patient. In addition, advanced cancer patients are likely to present with complex symptomologies that make it difficult to accurately assess side effects derived from cannabis treatments, and are often taking multiple concurrent medications. That said, a number of these studies reported that observed side-effects tended not to be treatment-limiting, and could be controlled through dose titration, with pain relief in as little administration of 2.7–10.8 mg THC in combination with 2.5–10.0 mg CBD (17). This highlights the importance of establishing and validating a titration protocol that will allow researchers to identify effective and tolerated dosages in a safe and controlled manner.

Several studies presented in this review were underpowered due to small sample sizes, with three out of the five studies reviewed enrolling less than 50 patients. Therefore, the generalizability of the results may be limited, and future studies on medical cannabis are warranted to establish its efficacy and side effect profile in the cancer pain population. This includes additional efforts to identify the efficacies of specific cannabis compounds and their combinations, as well as ideal methods of administration through the assessment of relevant endpoints. Subsequent clinical trials should also consider the differences in cannabinoid pharmacokinetics and pharmacodynamics among individuals. Moreover, standardized and validated evaluation and reporting of cannabis-associated side effects is warranted in order to enable more accurate comparisons across studies. Ultimately, this will contribute to the development of clinical guidelines for the dosing and administration of cannabis as a pain medication for the large population of cancer patients in need of pain management, particularly those for whom alternative analgesics are insufficient, intolerable, or unsafe.


Current research shows that there is a potential role for medical cannabis in cancer pain management. However, the scale and quality of studies conducted to date are somewhat limited (12). Therefore, further research is needed to establish the efficacy of medical cannabis, either as an alternative to opiates or as an adjunctive therapy, and to identify the most appropriate methods of administration to achieve optimal therapeutic efficacy with minimal side effects.


We thank the generous support of Bratty Family Fund, Michael and Karyn Goldstein Cancer Research Fund, Joey and Mary Furfari Cancer Research Fund, Pulenzas Cancer Research Fund, Joseph and Silvana Melara Cancer Research Fund, and Ofelia Cancer Research Fund. This study was conducted in collaboration with MedReleaf.


Conflicts of Interest: The authors have no conflicts of interest to declare.


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Cite this article as: Blake A, Wan BA, Malek L, DeAngelis C, Diaz P, Lao N, Chow E, O’Hearn S. A selective review of medical cannabis in cancer pain management. Ann Palliat Med 2017;6(Suppl 2):S215-S222. doi: 10.21037/apm.2017.08.05

CBD in Treating Cancer and Related Symptoms

An Emerging and Alternative Therapy That Still Requires Much Investigation

Verywell Health articles are reviewed by board-certified physicians and healthcare professionals. These medical reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more.

Gagandeep Brar, MD, is a board-certified hematologist and medical oncologist in Los Angeles, California.

Cannabidiol (CBD) is one of many compounds (called cannabinoids) found in the marijuana plant Cannabis sativa. CBD is known for its relaxing and pain-soothing effects.

CBD is non-psychoactive, so it does not give you the classic mind-altering euphoria or “high” felt from using marijuana—that effect comes from the cannabinoid called THC (tetrahydrocannabinol).

While the research is still very early, experts speculate that CBD may play a role in treating cancer, specifically by slowing tumor growth and inducing the death of cancer cells. CBD may also help manage unpleasant symptoms related to cancer and chemotherapy, such as pain, nausea, and vomiting.

CBD and Treating Cancer

There are a number of studies supporting CBD’s potential anti-cancer role—however, the majority are limited to in vitro and animal studies. For example, in various studies, there is evidence that CBD decreases the growth of lung and prostate tumors, provokes the cell death of colon, lung, and brain cancer cells, and reduces the spread (metastasis) of breast cancer.  

While promising, large human clinical trials are needed to better understand whether CBD is truly effective in helping to treat cancer. Clinical trials would also allow experts to tease out issues like dosage, interaction with other cancer drugs, and CBD’s safety profile.

As of now, there are only a handful of human studies that have examined CBD’s anti-cancer role.

Here are a few examples:

  • In one study of 119 cancer patients (most of the cancers were metastatic and traditional cancer therapies had been exhausted), CBD oil was given on a three day on and three days off schedule. In most of the patients, an improvement in their cancer was noted, such as a decrease in tumor size. No side effects from CBD were reported.
  • In a case study, an elderly man with lung cancer refused traditional chemotherapy and radiation for his cancer treatment and instead, self-administered CBD oil. After one month of taking the CBD oil, a computed tomography (CT) scan revealed near-total resolution of his lung tumor along with a reduction in the number and size of chest lymph nodes.
  • In another study, two patients with aggressive gliomas (a type of brain tumor) were given CBD capsules in addition to chemoradiation and a multidrug regimen. Both patients had a positive response to the treatment with no evidence of disease worsening for at least two years.

Keep in mind—these studies are extremely small and lack a control group, so no finite conclusions can be drawn from them. Nevertheless, they spark further interest in the possible role of CBD in treating cancer.

CBD and Treating Cancer-Related Symptoms

There is scientific evidence, although limited and not robust, that CBD, THC, or a combination of the two, may be effective in alleviating certain cancer-related symptoms, such as pain, appetite loss, and chemotherapy-induced nausea and vomiting.

For instance, the drugs Marinol (dronabinol) and Cesamet (nabilone), which are synthetic forms of THC, are approved in the United States for treating chemotherapy-induced nausea and vomiting. Research suggests that dronabinol may also improve the taste of food, appetite, sleep, and quality of life in cancer patients.  

In addition, a mouth spray that contains both THC and CBD (called Sativex) is being investigated for its role in treating cancer pain (especially nerve-related pain) that is poorly controlled by opioids.   The drug is currently not available in the United States, but it is available in Canada for treating advanced cancer pain.

Lastly, research has found that in the general population (so not necessarily patients with cancer), CBD can reduce anxiety and improve sleep quality.   This finding is helpful, considering the diagnosis and treatment of cancer is often overwhelming and wrought with fear and worry.

CBD Considerations

With the potentially emerging use of CBD in treating cancer and/or its related symptoms, there are a few issues to consider.


CBD oil is perhaps the most commonly utilized formulation of CBD, as it’s easy to use and allows for a high dose of consumption. However, CBD comes in many other forms—gummies, tinctures, capsules, vapes, and ointments, to name a few.

Sorting out how to best administer CBD to patients with cancer may prove to be challenging, as various formulations may work or absorb differently.

Side Effects

While research suggests that CBD is generally well-tolerated, we need to more closely examine potential side effects in patients with cancer. In addition, we still do not know the long-term effects of taking CBD, or how it interacts with other medications.

Short-term side effects of CBD may include:  

  • Reduced or increased appetite
  • Weight gain or loss
  • Tiredness
  • Diarrhea
  • Increase in liver enzymes

If CBD is combined with THC (in the form of medical marijuana), other side effects may occur, such as:  

  • Dizziness
  • Dry mouth
  • Nausea
  • Disorientation and confusion
  • Loss of balance
  • Hallucinations


While CBD by itself is federally legal (as long as the product is derived from hemp and contains no more than 0.3% THC), marijuana is not (although, it is legal in some states).

CBD is only available by prescription in the United States in the form of a drug called Epidiolex. This drug is used to treat refractory epilepsy.

Due to these legal conundrums, CBD products may not be as tightly regulated as hoped. With that, products that claim they have a certain CBD dosage may actually contain a different amount or even contain traces of THC. This is why it is important to only take CBD under the guidance of your personal healthcare provider.

A Word From Verywell

The prospect of incorporating CBD into cancer care is intriguing but still requires much more investigation. Until then, if you are considering trying CBD (whether you have cancer or not), it’s best to talk out the pros and cons with your healthcare provider.