A selective breeding study in mice found that adolescent locomotor sensitivity to THC was moderately heritable (strongest in females from F2 to S3 generations) and that mice bred for THC sensitivity also showed increased anxiety-like behavior.
Genetics researchers studying cannabis vulnerability; neuroscience researchers interested in gene-environment interactions; anyone interested in why cannabis affects people differently.
Mice bred for THC sensitivity also showed increased anxiety-like behavior
What the researchers found
Researchers selectively bred mice for sensitivity or resistance to the locomotor effects of a single THC dose (10 mg/kg) during adolescence.
THC-locomotor sensitivity proved to be moderately heritable, with the strongest heritability estimates seen in females from the F2 to S3 generations.
An important correlated trait emerged: mice selected for THC-locomotor sensitivity also showed increased anxiety-like activity in the open field test, suggesting shared genetic factors between THC sensitivity and anxiety.
This is the first demonstration that adolescent THC-locomotor sensitivity can be influenced through selective breeding, establishing a genetic basis for individual differences in cannabis response.
Why it matters
Individual differences in cannabis response are well-documented but poorly understood. This study establishes a genetic foundation for these differences and reveals that genetic predisposition to THC sensitivity co-occurs with anxiety-related traits, which could help explain why some individuals are more vulnerable to negative cannabis effects.
The numbers in context
THC dose: 10 mg/kg. Selection was moderately heritable. Greatest heritability estimates in females from F2 to S3 generations. THC-sensitive lines showed significantly increased anxiety-like behavior in open field.
How the study worked
Short-term selective breeding (bidirectional selection) for adolescent locomotor response to acute THC (10 mg/kg i.p.) in the open field test. Heritability estimated across generations. Anxiety-like behavior assessed as a correlated trait.
What this study cannot tell us
Mouse model may not fully translate to human genetics of cannabis response. Short-term selective breeding (few generations). Only locomotor sensitivity was selected for; other aspects of THC response (reward, cognition) were not directly assessed.
How to read the evidence
Preliminary. Novel selective breeding approach establishing heritability, but early-stage animal work requiring replication and extension.
When this study was published
Published in 2018. Genetic studies of cannabis response have continued to advance, though translating animal genetics to human populations remains challenging.
The bigger picture
The co-selection of THC sensitivity with anxiety traits is intriguing because anxiety is both a common reason people use cannabis and a common adverse effect. This genetic overlap could help explain the paradox of why cannabis sometimes worsens the very symptoms it is used to treat.
Questions still open
- Do the genetic variants driving THC sensitivity in mice have human homologs? Would THC-sensitive mice also show greater vulnerability to cannabis dependence? Does the THC sensitivity-anxiety link hold across different THC doses?
Common questions
What does "locomotor sensitivity" to THC mean?
Why were females more heritable than males?
Read the original research
Short-Term Genetic Selection for Adolescent Locomotor Sensitivity to Delta9-Tetrahydrocannabinol (THC).
Behavior genetics, 48(3), 224-235
Citation
Kasten, Chelsea R; Zhang, Yanping; Mackie, Ken; Boehm, Stephen L. (2018). Short-Term Genetic Selection for Adolescent Locomotor Sensitivity to Delta9-Tetrahydrocannabinol (THC).. Behavior genetics, 48(3), 224-235. https://doi.org/10.1007/s10519-018-9894-2
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