Cannabis for Symptom Management in Cancer: Do You Know What Your Patients Are Using?

Meg Barbor, MPH

September 2018, Vol 8, No 9 - Medical Marijuana, Symptom Management


Patients with cancer are increasingly using cannabinoids (the chemical component of cannabis) to treat many symptoms, and a minority of them even take cannabis as a treatment for the cancer itself. Recent surveys have revealed that up to 25% of patients with cancer take some form of cannabis, but oncologists and other medical providers are often unaware that their patients are using medical (or recreational) cannabis.

However, societal changes, a contentious public debate, and an increasing acceptance and availability of cannabis in the general public have underscored the need for providers’ knowledge of these medicines and their potential benefits and side effects. In addition, several medical cannabis drugs have been approved by the FDA and are being prescribed by providers.

The role of medical cannabis in cancer treatment has been explored in multiple systematic reviews and meta-analyses. Data from these studies were discussed by Declan Walsh, MD, MSc, Chair, Department of Supportive Oncology, Levine Cancer Institute, Charlotte, NC, who presented on behalf of Mellar P. Davis, MD, FCCP, FAAHPM, Hospice and Palliative Medicine Specialist, Cleveland Clinic Lerner College of Medicine, Palliative Care, Geisinger Medical Center, Danville, PA, in a plenary session at the 2018 Multinational Association of Supportive Care in Cancer meeting.

Medical Cannabis for Cancer Management

In a recent survey, the average age of patients who used medical cannabis was 59.5 years, and approximately 27% were previous recreational cannabis users.1 Of those surveyed, approximately 96% said that they obtained significant symptomatic ­relief, particularly with regard to sleep (78%), pain (78%), weakness (73%), nausea (65%), and lack of appetite (49%), which are some of the most common symptoms in patients with cancer.1

Although more than 100 phytocannabinoids can fall under the umbrella of “medical cannabis”—a class of drugs increasingly promoted as capable of improving symptoms and a potential treatment for cancers—the focus of research has largely been on drugs known as tetrahydrocannabinoids (THCs).

Nausea and Loss of Appetite

Approximately 30 randomized, controlled clinical trials have examined the use of cannabis drugs for chemotherapy-induced nausea and vomiting (CINV), and some have been shown to be slightly better or equivalent to existing antiemetic drugs. However, paradoxical hyperemesis may mimic CINV, and some clinical trials on cancer pain showed emesis to be a side effect of cannabis.

“I think the literature on CINV does not support the use of THC or other cannabinoids,” for this specific purpose, said Dr Walsh.

Loss of appetite and cachexia are complex maladies in patients with cancer. One study showed that the addition of THC to megestrol did not improve outcomes.2

“But there was, nevertheless, some response to the THC,” he noted. “This should be borne in mind as we think about future studies in this area.”

Another study by the Cannabis-In-Cachexia Group showed no improvement in appetite, nausea, weight gain, or quality of life when comparing THC or cannabidiol (Epidiolex), the second most common cannabinoid, with placebo.3

A more recent study looked at the role of the THC dronabinol (Marinol, Syndros) in improving dysgeusia (taste changes),4 a common symptom in patients with cancer. The investigators found that the drug improved taste and premeal appetite, and also increased calories from protein.

“When we think about these drugs, we need to consider the whole symptom profile of patients, so as not to miss potential therapeutic effects,” said Dr Walsh. “If someone experiences a major symptomatic improvement without gaining any weight, that is still worthwhile.”

Psychotic Symptoms and Seizures

Another recent study compared cannabidiol to a widely available antipsychotic drug, amisulpride (not approved in the United States, but available as Solian in other countries), and showed they had approximately equal efficacy in patients with psychotic symptoms, but cannabidiol had fewer side effects.5 “This was an important finding,” Dr Walsh noted.

High-quality randomized, controlled trials of cannabidiol have demonstrated its beneficial effect on seizures in patients with epilepsy. In June 2018, the FDA approved cannabidiol (Epidiolex), the first FDA-­approved drug to contain a purified drug substance derived from marijuana, for the treatment of 2 rare forms of epilepsy—Lennox-Gastaut syndrome and Dravet syndrome.

Sleep and Insomnia

According to Dr Walsh, cannabis and cannabinoids have a complex relationship with sleep. Some studies have shown that cannabis reduces sleep latency and increases slow-wave sleep, but patients can have habituation and tolerance issues with repeated use, and increased dosage is necessary to maintain the drug’s therapeutic effect.6 If users do not increase their dosage and instead choose to stop using cannabis, withdrawal can lead to vivid nightmares, hallucinations, dysphoria, confusion, and insomnia.

In a meta-analysis of 79 clinical trials involving cannabis for sleep problems or pain relief, the majority of individuals who used cannabis had improved sleep, and in pain trials, improved sleep was suggested as the reason for an indirect analgesic effect.7

Other studies have demonstrated the effectiveness of cannabidiol in improving rapid eye movement sleep, nabilone (Cesamet) in improving nightmares and insomnia related to posttraumatic stress disorder, and nabiximols (not approved in the United States, but available as Sativex) in other countries in improving sleep problems related to chronic pain.6,8

However, one study showed that individuals who use THC or other cannabis drugs are more likely to suffer from narcolepsy, although the addition of cannabidiol can counter the somnolence effect caused by THC.9

“So, in essence, cannabinoids can either have a beneficial or an adverse effect on sleep patterns,” Dr Walsh said. “The jury is out on its true therapeutic role in this area.”

Many patients with cancer-related pain use cannabis for sleep disturbances, but the relationship between sleep, pain, and cannabis is under continued investigation in a variety of centers.

“The importance of a good night’s sleep in combating daytime fatigue and improving pain control is a critical issue,” he said. “So, there is some tentative evidence that when appropriately used, some of these drugs may have a beneficial effect in people with sleep and insomnia disorders, including obstructive sleep apnea,” said Dr Walsh.


References

  1. Bar-Lev Schleider L, Mechoulam R, Lederman V, et al. Prospective analysis of safety and efficacy of medical cannabis in large unselected population of patients with cancer. Eur J Intern Med. 2018;49:37-43.
  2. Jatoi A, Windschitl HE, Loprinzi CL, et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol. 2002;20:567-573.
  3. Strasser F, Luftner D, Possinger K, et al. Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol. 2006;24:3394-3400.
  4. Brisbois TD, de Kock IH, Watanabe SM, et al. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Ann Oncol. 2011;22:2086-2093.
  5. Rohleder C, Müller JK, Lange B, Leweke FM. Cannabidiol as a potential new type of an antipsychotic. A critical review of the evidence. Front Pharmacol. 2016;7:422.
  6. Babson KA, Sottile J, Morabito D. Cannabis, cannabinoids, and sleep: a review of the literature. Curr Psychiatry Rep. 2017;19:23.
  7. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313:2456-2473. Errata in: JAMA. 2015;314:520; JAMA. 2015;314:837; JAMA. 2015;314:2308; JAMA. 2016;315:1522.
  8. Jetly R, Heber A, Fraser G, Boisvert D. The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: a preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology. 2015;51:585-588.
  9. Murillo-Rodríguez E, Sarro-Ramírez A, Sánchez D, et al. Potential effects of cannabidiol as a wake-promoting agent. Curr Neuropharmacol. 2014;12:269-272.