A gene variant and its epigenetic state both influence how THC affects fear processing in the brain
Genetic variation at AKT1 rs1130233 and DNA methylation at a nearby site independently influenced how THC altered brain activation during fear processing, with methylation partially mediating the genetic effect.
Quick Facts
What This Study Found
The number of A alleles at AKT1 rs1130233 and methylation percentage at the CpG11-12 site independently predicted greater THC effects on parahippocampal/amygdala activation during fear processing. The genetic effect was partially mediated by methylation in sections of the left parahippocampal gyrus and hippocampus.
Key Numbers
36 healthy males (34 with complete data); 2-session crossover design; THC increased anxiety and psychotomimetic symptoms; AKT1 gene is part of the dopamine signaling cascade
How They Did This
Double-blind, cross-over, randomized placebo-controlled THC administration study in 36 healthy males, with functional MRI during a fear processing task. Genetic (AKT1 rs1130233) and epigenetic (DNA methylation) data were analyzed.
Why This Research Matters
This demonstrates that both inherited genetic variation and modifiable epigenetic factors shape individual responses to THC, helping explain why some people are more vulnerable to cannabis-related anxiety and psychotic symptoms.
The Bigger Picture
Understanding the genetic and epigenetic factors that modify THC sensitivity could eventually enable personalized risk assessment for cannabis use, identifying individuals who may be particularly vulnerable to adverse psychological effects.
What This Study Doesn't Tell Us
Small sample of only males, limiting generalizability. Single acute THC dose may not reflect chronic use effects. Epigenetic measurements from blood may not perfectly reflect brain methylation patterns.
Questions This Raises
- ?Do these genetic and epigenetic factors predict real-world vulnerability to cannabis-related psychosis?
- ?Could epigenetic screening be used clinically to assess cannabis risk?
- ?Do females show the same patterns?
Trust & Context
- Key Stat:
- Both genetic and epigenetic factors independently predicted THC brain effects
- Evidence Grade:
- Small randomized controlled trial with rigorous crossover design but limited to 36 male participants
- Study Age:
- Published in 2021. Pharmacogenomic research on cannabis response is still in early stages.
- Original Title:
- Epigenetic Mediation of AKT1 rs1130233's Effect on Delta-9-Tetrahydrocannabinol-Induced Medial Temporal Function during Fear Processing.
- Published In:
- Brain sciences, 11(9) (2021)
- Authors:
- Blest-Hopley, Grace(10), Colizzi, Marco(10), Prata, Diana, Giampietro, Vincent, Brammer, Michael, McGuire, Philip, Bhattacharyya, Sagnik
- Database ID:
- RTHC-03007
Evidence Hierarchy
Participants are randomly assigned to treatment or placebo groups to test cause and effect.
What do these levels mean? →Frequently Asked Questions
Do genes affect how THC impacts the brain?
Yes. This study found that a specific variant in the AKT1 gene, part of the dopamine signaling pathway, predicted greater THC effects on brain regions involved in fear processing.
What role does epigenetics play in THC response?
DNA methylation near the AKT1 gene independently influenced THC brain effects and partially mediated the genetic effect. This suggests both inherited and modifiable factors shape individual vulnerability to THC.
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Cite This Study
https://rethinkthc.com/research/RTHC-03007APA
Blest-Hopley, Grace; Colizzi, Marco; Prata, Diana; Giampietro, Vincent; Brammer, Michael; McGuire, Philip; Bhattacharyya, Sagnik. (2021). Epigenetic Mediation of AKT1 rs1130233's Effect on Delta-9-Tetrahydrocannabinol-Induced Medial Temporal Function during Fear Processing.. Brain sciences, 11(9). https://doi.org/10.3390/brainsci11091240
MLA
Blest-Hopley, Grace, et al. "Epigenetic Mediation of AKT1 rs1130233's Effect on Delta-9-Tetrahydrocannabinol-Induced Medial Temporal Function during Fear Processing.." Brain sciences, 2021. https://doi.org/10.3390/brainsci11091240
RethinkTHC
RethinkTHC Research Database. "Epigenetic Mediation of AKT1 rs1130233's Effect on Delta-9-T..." RTHC-03007. Retrieved from https://rethinkthc.com/research/blest-hopley-2021-epigenetic-mediation-of-akt1
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.