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Cannabis and Opioid Receptors Are More Alike Than We Think

Jessica McKeil
Opioid receptors will respond to painkillers in this opium poppy

Cannabis and opium do many of the same jobs in the body, but ultimately the former could save you from the lethal effects of the latter.

Cannabis and opioids are both plant-based medicines that humans have used across many different cultures for millennia. Despite the long history of the medicinal application behind both, scientists only discovered opioid receptors cannabinoid receptors in the latter half of the twentieth century. The opium poppy and cannabis have each gone through their share of controversy, but both are integral aspects of modern-day medicine.

The Role of Opioid Receptors

Opium, a substance produced by a species of poppy, has thousands of years of medicinal use behind it. Yet, despite how long humans have relied on opium-based medicines (and later morphine, codeine, and other derivatives), scientists still didn’t understand the mechanism of action. In fact, it was only in 1973 that scientists discovered the opioid receptor.

Opioid receptors and all neuro-receptors are proteins. They exist on the surface of neurons, and communicate through the release of chemicals known as neurotransmitters. The receptors in the human brain bind with neurotransmissions like a hand fitting into a glove. When a neurotransmitter binds with a receptor, it delivers a message to turn on or off the cellular activity. There are now four known subtypes of opioid receptors, called mu, delta, epsilon, and kappa receptors. Each has a slightly different biological purpose.

Endogenous molecules (called peptides) activate the various opioid receptors to regulate pain, reward, and addictive behaviors. There is also some suggestion that endogenous peptides may manage the release of reproductive hormones and influence the immune system. Some examples of endogenous peptides include enkephalins and endorphins.

Plant-based or synthetic opioids (called exogenous opioids) mimic the neurotransmitters produced within the human body to influence these same processes.

For example, pharmaceutical opioids trigger a flood of dopamine. Dopamine is responsible for the experience of pleasure, movement, emotion, cognition, and motivation. Since opioids stimulate a flood of dopamine not generally experienced with endogenous molecules, it can create feelings of euphoria and may lead to addiction.

opioid receptors would work with the opioid gum this farmer is collecting from opium poppies

Farmer collecting gum from poppy in order to make opiates.

The Role of Cannabinoid Receptors

As with opium and its derivatives, cannabis has an equally long history of medicinal consumption, across many diverse cultures. Also, like opium, scientists did not understand the mechanism of action behind cannabis until only recently.

The discovery of how cannabis worked in the human brain eventually led to the detection of an entirely new biological system, called the endocannabinoid system. This relatively recent discovery is a body-wide network of receptors and chemical transmissions which manage the immune system, pain regulation, memory, mood, and so much more.

Scientists made the first breakthrough in 1988, with the discovery of THC’s neurological binding sites. A few years later, in 1992, another team of researchers uncovered the first endogenous cannabinoid (anandamide) and the first cannabinoid receptor site: the CB1 receptor. Soon after, the second cannabinoid receptor, CB2, was also uncovered. With the discovery of receptors and endogenous cannabinoids, the foundations of the endocannabinoid system were laid.

Cannabinoid receptors, just like opioid receptors, are proteins that live on the surface of cells. In response to chemical transmissions, these endocannabinoid receptors turn on or off. Scientists have determined that CB1 receptors exist in concentrated levels in the brain and central nervous system.

There are higher concentrations of CB2 receptors in the immune system and gastrointestinal system. Cannabinoid receptors work with human-produced chemicals (like anandamide) as well as with phytocannabinoids found in the cannabis plant. The most common examples of phytocannabinoids are THC and CBD.

The Intersection Between Cannabinoid and Opioid Receptors

The opioid system and the endocannabinoid system do not operate in vacuums. Scientists strongly believe these systems interact with each other in ways that manage various physiological processes.

For starters, both systems play a significant role in pain management. It’s why many people manage and treat various types of pain today with opioids, cannabis, or a combination. There is also some overlap on mood, memory/learning, as well as with addiction.

According to a review, published in Frontiers of Pharmacology (2015), “these two systems share neuroanatomical, neurochemical, and pharmacological, characteristics.” The authors pay particular attention to how the opioid and endocannabinoid systems play a role in the development (and control) of addictions.

opioid receptors would work in tandem with these opium poppies

Opium poppy field

Cannabinoid Receptors as a Target for Opioid Addiction

With opioid addiction an ongoing and deadly epidemic across North America, there is a frantic push to find new therapeutic solutions. With the overlap between the endocannabinoid and the opioid systems, the endocannabinoid system has become a novel new therapeutic target for addiction treatment.

In 2017 researchers, with funding provided by the National Institute on Drug Abuse, conducted a proof-of-concept study, “examining the potential efficacy of a cannabinoid receptor (CB1) partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal.” Dronabinol is a synthetic form of THC, sold under the trade name Marinol. Marinol is approved as an appetite stimulant and an anti-nauseant.

Over five weeks, scientists maintained twelve opioid-dependent participants with a daily dose of oxycodone. The study participants attended a variety of test sessions throughout the study, with some given dronabinol for the tests. To measure the effectiveness of dronabinol on the symptoms of withdrawal, researchers randomly gave some participants a placebo instead of oxycodone before their test session.

Study Conclusions

After analysis, the authors of this study concluded, “CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal,” but admitted dronabinol was not an ideal candidate. Dronabinol, while approved in many countries, is a synthetic and isolated compound. The adverse effects of dronabinol are reportibly worse than those associated with medical cannabis consumption. Anecdotally, both physicians and patients, report a preference for flower over the pharmaceutical if given a choice.

A review published in the Journal of Cannabis and Cannabinoid Research, examined the state of research into cannabis for the treatment of opioid addiction. The authors, Beth Wiese and Adrianne R. Wilson-Poe, concluded: “The evidence summarized in this article demonstrates the potential cannabis has to ease opioid withdrawal symptoms, reduce opioid consumption, ameliorate opioid cravings, prevent opioid relapse, improve OUD treatment retention, and reduce overdose deaths.”

This preliminary review confirms the potential of cannabinoids for the treatment of addiction, but as always, there needs to be much more robust clinical study to draw any conclusions.

cannabis field which would work with cannabinoid receptors

Cannabis field

Future Possibilities of Working with Cannabinoid and Opioid Receptors

It is remarkable just how similar the histories of opium and cannabis are. They both have significant heritage as a powerful medicine, they have each been semi-controversial over the last century (and more), and scientists discovered each associated receptor within the last fifty years.

There is also an extraordinary overlap between the cannabinoid and opioid systems. Both systems work with endogenous as well as exogenous chemicals for therapeutic benefits. Both systems regulate similar biological processes, like pain, reward, and memory. Of most interest today is the intersection between the two for addiction treatment.

In practice, cannabis is already a useful replacement for opioids in the treatment of chronic pain. With more clinical study, there could also be a firm place for cannabinoids as a treatment for opioid addictions. Ultimately, there is much more to uncover about the relationship between cannabinoid and opioid receptors. This knowledge could benefit thousands of addicts.

Jessica McKeil
Jessica McKeil

Jessica McKeil is a freelance writer focused on the medical marijuana industry, from production methods to medicinal applications. She is lucky enough to live in beautiful British Columbia, Canada where the cannabis industry is exploding. When not writing, she spends much of her time exploring in the coastal forests.

  • Avatar

    We should be aware of the important points in this article about cannabis and opioid receptors. Thid would surely be a huge help. Thanks for notching this one out.

    February 15, 2020 at 4:35 pm Reply
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    Inge Kellermann

    What I have learned is, that the reason why nobody have died from cannabis is, that there are very few cannabis receptors in the part og the brain, that controls respiration. However, there is a lot of opioid receptors in that area. So if they share receptors it should be obvious that one could die from overdose of cannabis? Or is there another explanation?

    March 11, 2020 at 10:15 am Reply
    • Jennifer Grant

      The problem is the number of opioid receptors in the respiratory centre of the brain. But, the receptors for opioids and cannabis are not the same just very alike in action and mechanism.

      March 12, 2020 at 1:03 pm Reply

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