A review of animal studies found the endocannabinoid system regulates both the physical and emotional aspects of opiate withdrawal, but through distinct brain regions, with CB1 receptor activation and blockade having different effects depending on the brain area.
Read this if you are interested in whether cannabis could help with opioid withdrawal or if you work in addiction medicine.
CB1 receptor effects on opiate withdrawal are brain region-specific, affecting somatic and affective withdrawal through different circuits.
What the researchers found
This review synthesized animal research on how manipulating the endocannabinoid system affects opiate withdrawal. The key insight was a dissociation between somatic (physical) and affective (emotional) withdrawal.
Somatic withdrawal symptoms (diarrhea, tremor, wet dog shakes) and affective withdrawal (aversion, anxiety, dysphoria) are mediated by different brain regions. The endocannabinoid system modulates both, but differently depending on where in the brain CB1 receptors are activated or blocked.
CB1 agonists can alleviate some somatic withdrawal symptoms. CB1 antagonists can precipitate withdrawal in dependent animals. But the effects are brain region-specific: what helps in one area may not help in another.
The review also discussed how these findings relate to the conditioned place aversion paradigm, which measures the emotional/motivational aspects of withdrawal that are thought to drive continued drug use.
Why it matters
Opiate withdrawal is a major driver of continued opioid use and relapse. If the endocannabinoid system can modulate withdrawal, cannabis or cannabinoid-based treatments could potentially help people detox from opioids. But the brain region-specific effects mean that simple "cannabis for withdrawal" approaches may be too simplistic.
The numbers in context
The review covered studies using CB1 agonists (WIN55,212-2, THC), CB1 antagonists (SR141716A/rimonabant), FAAH inhibitors, and endocannabinoid system modulators. Brain regions discussed include the basolateral amygdala, central amygdala, bed nucleus of the stria terminalis, ventral tegmental area, and periaqueductal gray.
How the study worked
Review of preclinical animal literature examining the effects of pharmacological modulation of the endocannabinoid system on opiate withdrawal. Covered both acutely and chronically dependent animal models, somatic and affective withdrawal measures, and brain region-specific manipulations.
What this study cannot tell us
Entirely based on animal studies. The pharmacological manipulations used (direct brain infusions, systemic CB1 agonists/antagonists) do not precisely replicate how humans use cannabis. Species differences in endocannabinoid systems may affect translation. The review focuses on acute withdrawal, not the long-term aspects of opioid recovery.
How to read the evidence
Moderate evidence from a comprehensive review of preclinical animal studies, providing mechanistic insights that await human translation.
When this study was published
Published in 2016. Interest in cannabinoids for opioid withdrawal management has grown substantially since this review.
The bigger picture
The opioid crisis has driven interest in cannabinoid-based approaches to opioid withdrawal management. This review provides the mechanistic foundation: the endocannabinoid system does modulate withdrawal, but the effects are complex and depend on which brain circuits are engaged. This complexity explains why cannabis may help some aspects of opioid withdrawal while not addressing others.
Questions still open
- Would cannabis or CBD help with the emotional aspects of opioid withdrawal specifically? Could region-specific endocannabinoid modulation be achieved with drug design? Do the somatic and affective withdrawal circuits respond differently to whole-plant cannabis versus isolated cannabinoids?
Common questions
Can cannabis help with opioid withdrawal?
How do the cannabinoid and opioid systems interact?
Read the original research
Effect of Pharmacological Modulation of the Endocannabinoid System on Opiate Withdrawal: A Review of the Preclinical Animal Literature.
Frontiers in pharmacology, 7, 187
Citation
Wills, Kiri L; Parker, Linda A. (2016). Effect of Pharmacological Modulation of the Endocannabinoid System on Opiate Withdrawal: A Review of the Preclinical Animal Literature.. Frontiers in pharmacology, 7, 187. https://doi.org/10.3389/fphar.2016.00187
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