The Cannabinoid and Opioid Systems Interact Closely, Suggesting Cannabis Could Help Manage Opiate Withdrawal | Research

The takeaway

A review of animal and clinical evidence found extensive cannabinoid-opioid system interactions, particularly in the brain's stress response center, suggesting the endocannabinoid system could be targeted to manage opiate dependence and withdrawal.

Read this if you are interested in how the cannabinoid system interacts with opioids and the implications for addiction treatment.

CB1 and opioid receptors co-exist in the locus coeruleus, a key circuit in opiate withdrawal

What the researchers found

The review detailed how cannabinoid and opioid receptors interact at the molecular level, particularly in the locus coeruleus-norepinephrine (LC-NE) system, a key circuit in the negative effects of opiate addiction. Both receptor types are present in the LC, and their activation produces overlapping effects on norepinephrine release.

Animal studies showed that endocannabinoid manipulation could modify opiate withdrawal severity. Clinical observations suggested that marijuana use among opiate addicts may serve as self-medication for withdrawal symptoms. The review proposed that targeting the endocannabinoid system could provide novel interventions for managing opiate dependence and withdrawal.

Why it matters

With the opioid epidemic causing hundreds of thousands of deaths, new approaches to managing opiate dependence are urgently needed. The extensive interaction between cannabinoid and opioid systems suggests that cannabinoid-based interventions could complement existing treatments.

The numbers in context

Locus coeruleus contains both CB1 and opioid receptors. Both systems modulate norepinephrine release. Endocannabinoid manipulation modified opiate withdrawal in animal models.

How the study worked

Narrative review covering molecular interactions between cannabinoid and opioid receptors, animal studies of cannabinoid effects on opiate withdrawal, and clinical observations of marijuana use in opiate-dependent populations.

What this study cannot tell us

Much of the evidence was preclinical. The clinical observations were not from controlled trials. The complexity of cannabinoid-opioid interactions means effects may differ depending on the specific cannabinoid, opioid, dose, and timing. Self-medication with marijuana introduces its own risks.

How to read the evidence

Review combining preclinical and clinical evidence; moderate evidence for cannabinoid-opioid interaction relevance.

When this study was published

Published in 2013. The potential role of cannabis in the opioid crisis has become a major research and policy topic.

The bigger picture

This review was prescient in highlighting the cannabinoid-opioid interaction at a time when the opioid epidemic was intensifying. The concept of using cannabis-based approaches to manage opiate withdrawal has since gained traction, with some states reporting reduced opioid prescribing in association with medical cannabis access.

Questions still open

Could targeted endocannabinoid modulation reduce opioid withdrawal severity in humans? Would cannabis access reduce opioid dependence at a population level? Could combining cannabinoids with existing opioid addiction medications improve outcomes?

Common questions

Can cannabis help with opioid withdrawal?

Animal studies suggest that modulating the endocannabinoid system can affect opiate withdrawal severity, and some clinical observations show marijuana use among opiate addicts. However, controlled human trials specifically testing cannabis for opioid withdrawal were lacking at the time of this review. The concept is biologically plausible given the extensive overlap between cannabinoid and opioid systems in the brain.

How do the cannabinoid and opioid systems interact?

Both systems use similar signaling mechanisms and their receptors are often found in the same brain regions, particularly the locus coeruleus (the brain's norepinephrine center involved in withdrawal symptoms). Activating one system can modulate the other, which explains why cannabinoid and opioid drugs can have overlapping pain-relieving effects and why manipulating one system can affect withdrawal from the other.

Read the original research

Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal.

Neuroscience, 248, 637-54

View on PubMed ↗Publisher’s paper ↗

Citation

Scavone, J L; Sterling, R C; Van Bockstaele, E J. (2013). Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal.. Neuroscience, 248, 637-54. https://doi.org/10.1016/j.neuroscience.2013.04.034