Cannabis produces a wide range of physical and cognitive changes by interacting with receptors designed for our own internal cannabinoids, which are called “endocannabinoids.” These effects are the product of many chemical compounds in cannabis, such as terpenes, flavonoids, and, as this article will focus on, cannabinoids like THC (tetrahydrocannabinol).
Scientists have found ways to synthesize man-made cannabinoids, some of which have been FDA-approved medicines for several decades. But how do artificial cannabinoids compare to the real thing? Are they equally effective as medical marijuana for treating illness or pain? Read on to find out.
Marijuana Vs. Synthetic Cannabinoid Medications: What Works Better?
There are three main sources of cannabinoids:
- Naturally occurring cannabinoids in cannabis, such as THC and CBD (cannabidiol). Cannabis contains over 100 different cannabinoids, but THC and CBD are the best-known and most heavily researched.
- Naturally occurring cannabinoids in your own body, such as AEA (Anandamide) and 2-AG (2-Arachidonoylglycerol). These types of cannabinoids are called “endocannabinoids,” because they are produced inside of your body. (The prefix “endo-” simply means “inner” or “within.”)
- Synthetic cannabinoids that are produced in laboratories, rather than being produced by your body or coming directly from the cannabis flower.
All three work in the same fashion: by activating receptors designated “CB1” and “CB2.” Some of these receptors are located in your brain, while others are spread throughout your body in other types of tissue and organs.
By binding to these receptors, AEA and 2-AG regulate basic, core sensations and functions, including pain, hunger, and mood. Using cannabis causes THC and other cannabinoids to bind to the same receptors, which is why marijuana works to combat pain, stimulate appetite, and improve mood.
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Synthetic cannabinoids can produce similar effects, though there are some issues with efficacy, tolerability, and, on the research side, FDA testing. We’ll discuss those issues in a few moments, but before we continue, it’s critically important to make a distinction between FDA-approved synthetic cannabinoid medications, such as Marinol (dronabinol), and street synthetic cannabinoids that are used recreationally.
The latter category is often described as “synthetic marijuana” and includes substances like “Spice” or “K-2.” Unlike synthetic cannabinoid medications, which are formulated by experienced chemists working under tightly controlled conditions, Spice or K-2 is simply plant matter that has been sprayed with. Well, that’s precisely the problem. It’s impossible for consumers to know exactly what goes into these dangerous, harmful products, which have been criminalized in most parts of the world due to causing effects that range from convulsions to heart attacks to, in extreme cases, fatal organ failure.
You should absolutely never purchase or use these products, regardless of your medical background. I cannot emphasize that strongly enough. There is a very real risk of death from using Spice or K-2! There are many other names for these sort of street cannabinoids. Don’t be fooled.
Now that we’ve cleared that up, let’s take a look at how synthetic cannabinoid medications stack up against the actual cannabis flower. First of all, let’s identify some of the main medications that are currently available, and what each one is primarily used to treat.
First, there are FDA-approved synthetic cannabinoids:
- Marinol – The active ingredient in Marinol, which is made by AbbVie Inc., is dronabinol, a man-made version of THC. Marinol comes in capsule form and has two patient groups: HIV/AIDS patients, who use it to improve appetite and fight weight loss, and cancer patients, who use it to relieve nausea and vomiting caused by chemotherapy.
- Cesamet – Like Marinol, Cesamet is an older medication that was introduced to the consumer market during the 1980s. Cesamet’s active ingredient is nabilone, a synthetic cannabinoid or man-made imitation THC. Meda Pharmaceuticals, the company that currently owns Cesamet, describes it as “a prescription medicine that may help relieve nausea or vomiting caused by chemotherapy,” adding, “It’s for people who continue to feel nauseous or vomit even though they’ve already taken medicine to treat these symptoms.” The manufacturer cautions that Cesamet, like inhaled cannabis and oral cannabinoid-based medications, may not be safe for women who are pregnant or nursing, or for people who have heart conditions.
Cesamet and Marinol have been around for decades, but more recently, two additional medications have been (or are on their way to being) FDA-approved. These are purified but derived from cannabis, and include:
- Epidiolex – Epidiolex contains CBD, a naturally occurring cannabinoid in marijuana. However, Epidiolex isolates CBD from the dozens of other cannabinoids which are also present in marijuana. Epidiolex is made by GW Pharmaceuticals, which describes this medication as “a liquid formulation of pure plant-derived cannabidiol (CBD) as a treatment for various orphan pediatric epilepsy syndromes.” In other words, Epidiolex is a mouth spray for children with very rare genetic causes of epilepsy — not common types of epilepsy.
- Sativex – Sativex is also made by GW Pharmaceuticals, which calls the product “an oromucosal spray of a formulated extract of the cannabis sativa plant that contains the principal cannabinoids THC and CBD as well as specific minor cannabinoids and other non-cannabinoid components.” This oral spray is meant to relieve muscle spasticity (stiffness and lack of control) related to multiple sclerosis (MS).
While these medications can be somewhat effective – and some, like Epidiolex, have the benefit of treating children without causing the “high” produced by ingesting or inhaling cannabis – they suffer from an absence of “the entourage effect,” which is a term describing the combined effects of all cannabinoids working together to relieve symptoms. As I mentioned earlier, cannabis contains over 100 different cannabinoids – and frankly, medical researchers just don’t know where the effects of one end and the effects of another begin.
Think of it this way: the English alphabet contains a mere 26 letters, which can be combined to make millions of different words. Now multiply that by about four, add terpenes and flavonoids to the equation, and you can imagine how challenging it would be, even for a computer, just to spit out every possible combination. Then, think of how long it would take for researchers to get approval to test – then actually test – every combination on a sufficiently large study population.
It would require multiple lifetimes, even with a huge team of researchers. The Food and Drug Administration (FDA), which approves medications for use in the United States, simply lacks the framework for handling botanical cannabis like other substances. FDA testing rubric is set up for single compounds, like the atorvastatin in Lipitor, or the fluoxetine in Prozac – not for hundreds of compounds like those found in cannabis. The FDA’s model is essentially “test substance x for illness y,” which completely overlooks and excludes the medical benefits of marijuana associated with the entourage effect.
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Finally, most patients simply tolerate botanical cannabis better than synthetic cannabinoid medications. For most people, the acute (immediate/short-term) side effects of cannabis are dry mouth, sleepiness, increased appetite, and possibly sore throat or coughing depending on the method of administration. Some people can also experience short-lived anxiety or paranoia, particularly if the dose is large, or if they’re in an environment where they feel uncomfortable.
By comparison, the side effects of Marinol, according to the drug’s official website, include “loss of memory, anxiety/nervousness, lack of motor coordination, confusion, depersonalization, dizziness, paranoid reaction, sleepiness, abnormal thinking, weakness, irregular or rapid heartbeat, facial flush, abdominal pain, nausea, and vomiting.”
Marinol is, quite frankly, not used very often as patients report taking it only once and then vowing never to try it again because of the extreme intoxication.
Jordan Tishler, M.D. is a physician, cannabis specialist, and faculty at Harvard Medical School. He is also the president of the Association of Cannabis Specialists, and CEO of InhaleMD — a private institute of cannabis medicine. He has spent years assisting patients with cannabis. For more information, or to set up a consultation with the team at InhaleMD, call (617) 861-8519.
