Temporarily blocking CB2 receptors during vaccination boosted immune responses in both young and old mice
Blocking the CB2 cannabinoid receptor during immunization enhanced both the strength and breadth of antibody responses in young and aged mice, suggesting the endocannabinoid system normally suppresses vaccine responses.
Quick Facts
What This Study Found
The study first demonstrated that immune cells (macrophages and dendritic cells) produce the endocannabinoid 2-AG when activated by antigens, and that 2-AG levels increase in both blood and lymph nodes during vaccination. This endocannabinoid release appears to be a natural brake on immune activation.
Transient administration of the CB2 antagonist AM630 (10 mg/kg) or inverse agonist JTE907 (3 mg/kg) during immunization heightened both the intensity and breadth of antigen-specific immune responses. This worked in both young and aged mice, with the improvement mediated by upregulation of immunomodulatory genes in secondary lymphoid tissues.
This represents the first demonstration that blocking endocannabinoid signaling during vaccination can serve as an immune adjuvant.
Key Numbers
AM630 at 10 mg/kg and JTE907 at 3 mg/kg both enhanced vaccine responses. 2-AG levels were upregulated in serum and lymph nodes during vaccination. Enhanced responses seen in both young and aged mice.
How They Did This
Mice received CB2 antagonist AM630 or inverse agonist JTE907 alongside vaccination. Immune responses were measured by antigen-specific antibody production (intensity and breadth). Endocannabinoid levels were measured in serum and lymph nodes. Gene expression analysis was performed on secondary lymphoid tissues.
Why This Research Matters
Vaccines are less effective in elderly people because of immune senescence. Finding that CB2 blockade boosts vaccine responses in aged mice opens a potential strategy for improving vaccination in the elderly. The discovery that the endocannabinoid system actively suppresses immune responses to vaccines is a fundamental new insight.
The Bigger Picture
The endocannabinoid system appears to function as a natural immune dampener during vaccination, preventing excessive inflammation but also limiting the protective immune response. Temporarily releasing this brake could make vaccines more effective. This has particular relevance for aging populations and immunocompromised individuals who respond poorly to vaccination.
What This Study Doesn't Tell Us
Mouse study that may not translate directly to human vaccination. Only transient CB2 blockade was tested, and chronic blockade could have different effects. The specific vaccine antigens used may not represent all vaccine types. Whether CB2 blockade would affect vaccine safety is unknown.
Questions This Raises
- ?Would CB2 antagonists improve vaccine efficacy in elderly humans?
- ?Does chronic cannabis use (which activates cannabinoid receptors) reduce vaccine effectiveness?
- ?Could CB2 blockade be combined with existing adjuvants for additive benefit?
Trust & Context
- Key Stat:
- CB2 blockade during vaccination enhanced antibody responses in both young and aged mice
- Evidence Grade:
- Animal study demonstrating a novel immune adjuvant mechanism. Published in Scientific Reports with convincing mechanistic data, but human relevance is unconfirmed.
- Study Age:
- Published in 2017. The intersection of the endocannabinoid system and vaccine immunology is an emerging research area.
- Original Title:
- Transient Cannabinoid Receptor 2 Blockade during Immunization Heightens Intensity and Breadth of Antigen-specific Antibody Responses in Young and Aged mice.
- Published In:
- Scientific reports, 7, 42584 (2017)
- Authors:
- Dotsey, Emmanuel, Ushach, Irina, Pone, Egest, Nakajima, Rie, Jasinskas, Algis, Argueta, Donovan A, Dillon, Andrea, DiPatrizio, Nicholas, Davies, Huw, Zlotnik, Albert, Crompton, Peter D, Felgner, Philip L
- Database ID:
- RTHC-01371
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Does cannabis affect vaccine effectiveness?
This study found that the endocannabinoid system suppresses vaccine responses, and blocking CB2 receptors improved them. Whether cannabis use (which activates cannabinoid receptors) reduces vaccine effectiveness in humans has not been directly tested but is a logical question raised by these findings.
Could this help vaccines work better in elderly people?
The study showed improved vaccine responses in aged mice, which is promising for addressing the well-known problem of reduced vaccine effectiveness in elderly people. However, human studies are needed before this could become a practical vaccine enhancement strategy.
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Cite This Study
https://rethinkthc.com/research/RTHC-01371APA
Dotsey, Emmanuel; Ushach, Irina; Pone, Egest; Nakajima, Rie; Jasinskas, Algis; Argueta, Donovan A; Dillon, Andrea; DiPatrizio, Nicholas; Davies, Huw; Zlotnik, Albert; Crompton, Peter D; Felgner, Philip L. (2017). Transient Cannabinoid Receptor 2 Blockade during Immunization Heightens Intensity and Breadth of Antigen-specific Antibody Responses in Young and Aged mice.. Scientific reports, 7, 42584. https://doi.org/10.1038/srep42584
MLA
Dotsey, Emmanuel, et al. "Transient Cannabinoid Receptor 2 Blockade during Immunization Heightens Intensity and Breadth of Antigen-specific Antibody Responses in Young and Aged mice.." Scientific reports, 2017. https://doi.org/10.1038/srep42584
RethinkTHC
RethinkTHC Research Database. "Transient Cannabinoid Receptor 2 Blockade during Immunizatio..." RTHC-01371. Retrieved from https://rethinkthc.com/research/dotsey-2017-transient-cannabinoid-receptor-2
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.