Cannabis and Opioid Receptors Have Important Connection

Turns out cannabinoid and opioid receptors have something in common.

Is cannabis the answer to the opioid crisis? Increasingly, prominent research seems to suggest so. For starters, access to legal cannabis reduces opioid-related deaths. Researchers have discovered that certain cannabinoids, like CBD, reduce some of the most challenging symptoms of opioid withdrawal. Recent studies have also told us that a vast majority of patients prefer medical cannabis than popping pills. Now, research tells us that cannabis and opioids receptors work best when targeted conjunctively.

The current crisis has severely damaged the medicinal reputation of opioids, and rightfully so. However, there is therapeutic value to this medicine, under the right conditions, and with proper oversight. Could new research into the synergistic effects of cannabis and opioids reduce the harm, and increase the benefits?

A Look Into the Opioid Crisis

It’s worth reviewing the numbers to understand the seriousness of the crisis better. According to the Centers for Disease Control and Prevention (CDC), there have been 770,000 opioid-related deaths since 1999. Out of all the drug-related deaths in the country in the 2019 reporting period, almost 50 percent were from opioids alone.

On average, 128 people die in the U.S every day from an opioid overdose. Sadly, approximately eighty percent of people with an opiate addiction starts with a prescription. Prescription opiates have a strong association with the development of dependency.

Although the numbers from 2019 seem to suggest these numbers are finally going down, opioids remain the single most dangerous drug in terms of deaths.

Legal medical cannabis and better access are having positive impacts on opioid prescriptions, deaths, and addictions. A new field of research also seems to suggest that treatment with cannabis and opioids, at the same time, may be safer than with opioids alone.

Opioid Receptors and the CB1 Receptor

All mammals have an endocannabinoid system. It is a vast network of receptors and chemical messengers, which exist in almost every part of the body. This network is responsible for regulating pain, digestion, memory, the immune system, inflammation, and mood.

The endocannabinoid system works to fight off infection, to trigger pain relief, to produce an anti-inflammatory response, as well as maintain homeostasis. It does this by sending chemical messengers, such as 2-AG and anandamide, to endocannabinoid receptors, CB1 and CB2.

Remarkably, cannabinoids also work within this system to mimic the body’s own chemical messengers, which is what makes the plant a powerful ally in many chronic conditions.

Opioids and the opioid receptors networks, in many ways, mimic the endocannabinoid system and cannabinoids. In the words of author Katia Befort, from the department of Neuropôle de Strasbourg at the Université de Strasbourg, Strasbourg, France, “These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction.” As per Befort’s paper, there is significant cross-talk between these two systems – which is all the more argument for studying these compounds in tandem for pain relief. ^[1]Cooper, Z. D., Bedi, G., Ramesh, D., Balter, R., Comer, S. D., & Haney, M. (2018). Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability.

Cannabis and Opioid Synergy in The Cold-Pressor Test

Research published in Neuropsychopharmacology (2018) explored the relationship between opioids, cannabis, and CB1 receptors. The team of researchers gave participants different doses of cannabis, oxycodone, or some combination of the two, then subjected them to Cold-Pressor Test (holding their hands in a bucket of cold water). The results are enough to make many ask, is there a place for cannabis alongside treatment with prescription opioids? ^[2]Neuropsychopharmacology: Official publication of the American College of Neuropsychopharmacology, 43(10), 2046–2055. https://doi.org/10.1038/s41386-018-0011-2

This double-blind, placebo-controlled, and first of its kind, study determined that cannabis improved the pain alleviation properties of oxycodone. Although the optimal dose of oxycodone by itself was five mg, this dose could be cut in half if participants also consumed a dose of cannabis.

Interestingly, by itself, neither cannabis nor the half dose of oxycodone was enough to reduce the experience of pain. Still, together they had a similar effect as an entire dose (5mg) of an opioid.

In 2020, in the European Neuropsychopharmacology researchers, Shanna Babalonis and Sharon L. Walsh reviewed the state of the research into cannabis and opioids. In this literature review, the results were more complicated than the piece from 2018. ^[3]Babalonis, S., & Walsh, S. L. (2020). Therapeutic potential of opioid/cannabinoid combinations in humans: Review of the evidence. European Neuropsychopharmacology. doi: … Continue reading

Although animal studies of cannabinoid and opioid co-treatment demonstrate synergistic pain-relieving benefits, the authors didn’t find this in preclinical or clinical studies. As they state, “the extant controlled clinical data do not support the role of cannabinoids for opioid replacement or opioid-sparing effects when treating opioid use disorder or chronic pain.” Clearly, we need much more investigation in this area of study.

The Role of Cannabis in the Opioid Crisis

The interaction between cannabis and opioids may all come down to the CB1 receptor. THC binds with the CB1 receptor, and this receptor is responsible for the feelings of euphoria (among other things) caused by opiates and cannabis. As per Befort, “CB1 receptor also appears as a modulator of opioid reward.” Although this friendly relationship is still poorly understood, it may hint about why there is such a synergy between cannabis and opioids.

There are three ways in which cannabis mitigates the need for high doses of opioids. First, it interacts with the CB1 receptor to boost mood. Second, because it activates the CB1 receptor, it promotes increased communication to the opioid receptor — a synergistic relationship. Thirdly, it increases the body’s ability to reduce its own pain through naturally increased opioid production.

Cannabis is Helping the Opioid Epidemic

While researchers continue to get to the bottom of the opioid-cannabis relationship, there is already evidence that cannabis is helping to fight the opioid epidemic in states with legal access to cannabis. It’s still early days, but statistics strongly suggest that increased legalization will reduce the need for so many opioid prescriptions.

A study released in the Journal of Health Economics (2014) was one of the first to suggest a relationship between legal cannabis and a reduction in related opioid overdoses. Subsequent studies have clarified and confirmed this idea. So long as patients have easy, affordable access to legal cannabis, it eventually erodes the reliance on opioid prescriptions and complications. ^[4]Bachhuber, M. A., Saloner, B., Cunningham, C. O., & Barry, C. L. (2014). Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010. JAMA Internal Medicine, … Continue reading ^[5]Powell, D., Pacula, R. L., & Jacobson, M. (2018). Do medical marijuana laws reduce addictions and deaths related to pain killers? Journal of Health Economics, 58, 29–42. doi: … Continue reading

Certainly, the relationship between cannabis and opioids deserves more attention. If cannabis is repeatedly preferred for pain relief by patients, helps reduce opioid deaths, and more generally improves the pain relief properties of opioids, with lower doses – there is a driving need to pursue these lines of study further.