Cannabis users have long reported therapeutic properties of the plant for a variety of conditions, some of which include nausea, emesis, seizures, cancer, neurogenic diseases and pain control. Research has elucidated many cannabinoid pharmacodynamic and pharmacokinetic properties, expanding the potential use of cannabinoids as a medical therapy. Due to the inconsistent delivery and control of the active components involved with smoking, pharmaceutical companies are investigating and prioritizing routes other than smoke inhalation for therapeutic use of cannabinoids. In this relatively new field of pharmaceutical development, ongoing drug development promises great benefit from targeted endocannabinoid receptor agonism. Available in Canada and Europe, nabiximols, a specific extract from the Cannabis plant, has demonstrated great benefit in the treatment of pain related to spasticity in multiple sclerosis, cancer and otherwise chronic pain conditions. The cannabidiol oral solution Epidiolex®, which is available in the USA, is indicated for management of refractory epilepsy but may offer therapeutic relief to chronic pain conditions as well. Current investigative drugs, such as those developed by Cara Therapeutics and Zynerba Pharmaceuticals, are synthetic cannabinoids which show promise to specifically target neuropsychiatric conditions and chronic pain symptoms such as neuropathy and allodynia. The objective of this review is to provide clinicians with an update of currently available and promising developmental cannabis pharmaceutical derivatives which may stand to greatly benefit patients with otherwise difficult-to-treat chronic conditions.
Keywords: Cannabidiol; Cannabinoids; Epidiolex; Nabiximols; Tetrahydrocannabinol.
For pain relief, he recommends a dose of 15mg THC (0.0005 oz) to 15 mg CBD. In his experience, doses of THC less than 15 mg generally don’t provide pain relief. Doses may be increased if necessary, best guided under a doctor’s orders, to achieve pain relief without unacceptable side effects.
The FDA’s View on Cannabis for Pain
The form/route of administration may also play a role in the pain effects of cannabis. Medical cannabis comes in herbal (marijuana), tincture, oil, and edible forms. It can be smoked, vaporized, ingested in edible or other oral forms, taken sublingually (under the tongue), or applied topically (oil). Research on the efficacy of different routes of administration for pain is sparse. However, a 2013 randomized, placebo-controlled, double-dummy, double-blind study compared analgesic effects of smoked marijuana and dronabinol. 7 The results indicated that under controlled conditions, marijuana and dronabinol both decreased pain. However, compared with marijuana, dronabinol produced longer-lasting decreases in pain sensitivity and lower ratings of abuse-related subjective effects, which can be predictive of use and abuse patterns. Other studies suggest that smoking cannabis produces rapid effects, while oral forms take longer to work but may last longer. 8
Approval by the US Food and Drug Administration has, so far, been limited to synthetic or pharmaceutical-grade components of cannabis. In June 2018, the agency approved Epidiolex (GW Pharmaceuticals) — a high CBD, low THC whole-plant alcohol extract — for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients age 2 and older. FDA has also approved Marinol (AbbVie) and Syndros (Insys Therapeutics), which both contain dronabinol, or synthetic THC. Both are indicated for weight loss associated with anorexia and HIV. Marinol is also indicated for severe nausea associated with cancer chemotherapy, as is FDA-approved Cesamet (Meda Pharmaceuticals). Cesamet contains the active ingredient nabilone, which has a chemical structure similar to THC.
“There is little consistency in plant constituents between products’ strain names,” said David Bearman, MD, a physician in private practice who specializes in pain management and has more than 40 years of experience in managing substance abuse. “These names are mainly marketing tools and tell little about the constituents of the product. The best advice is to read the label and understand it.”
The chemical complexity of cannabis itself has made it difficult for researchers to untangle its effects on pain and, at the same time, difficult for clinicians and patients to find the most effective species and route of administration. Cannabis is the genus name for a disputed number of plant species. The two most widely accepted species are Cannabis sativa and Cannabis indica, though hybrid species are also common.
Hemp products — including oils, extracts, and even “gummies” — aimed at relieving pain and anxiety abound on the internet. But what is hemp and how does it differ from marijuana? The conventional answer is that hemp and marijuana are two different species of the Cannabis genus of plants.
Purchase from reputable sources. Like vitamins and other supplements, CBD products aren’t regulated or FDA approved to treat disease, so buyer beware. Look for products that have been tested by an independent third party lab “so you don’t end up with a product that has THC in it or a product contaminated with heavy metals or pesticides,” says Boehnke.
The scientific evidence around CBD use is thin, a fact that is mainly due to politics. “Cannabis has been a Schedule 1 drug for a long time, which has limited the type of research needed to figure out how best to use it therapeutically,” says Kevin Boehnke, Ph.D., research investigator in the department of anesthesiology and the Michigan Medicine Chronic Pain and Fatigue Research Center. Under the U.S. Federal Controlled Substances Act, Schedule 1 drugs are defined as having no currently accepted medical use and a high potential for abuse.
Yet marijuana has been used as a medicinal plant for thousands of years, he notes. In fact, one of the first recorded uses of cannabis was for rheumatism, also known as arthritis. Cannabis products were widely used as medicines in the 19th and early 20th centuries, and were listed in the U.S. Pharmacopoeia before the onset of Federal restriction in 1937 under the Marijuana Tax Act.
Want to learn more on this topic? Listen to this podcast from the Rogel Cancer Center on Medical Marijuana for Cancer Patients.
Much of the research literature around CBD in particular supports its use as a treatment for childhood epilepsy. Indeed, in 2018 the FDA approved the CBD-based drug Epidiolex as a drug for childhood epileptic conditions. In a substantial policy shift, Epidiolex was designated as Schedule V, which is the least restrictive drug schedule and indicates little potential for abuse.
While there aren’t any published clinical trials on CBD in pain, Boehnke notes that ongoing preclinical studies in animals have demonstrated that CBD reduces pain and inflammation, and studies of CBD in humans show that it is well-tolerated and has few negative side effects. “There are also observational studies that ask why people use CBD and if it’s effective, and results tend to be quite positive. People report using CBD for anxiety, pain, sleep — all things that go hand-in-hand with chronic pain,” he says. The passage of the 2018 Farm Bill removed hemp-derived CBD (<0.3% THC) from the Controlled Substances Act, and many people are since testing it out. Boehnke says, “Even though there isn’t clinical trial literature for most common uses of CBD, people don’t necessarily follow what clinical trials say.”
CBD, short for cannabidiol, is undergoing a surge in popularity as the hot new supplement, with a promise to treat a variety of conditions including pain, anxiety, and insomnia, just to name a few. It’s also available in all manner of forms, from lotions and oils to CBD-infused food and drink. But does it work?
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