Oral Annual Conference of the Genetics Society of Australasia with the NZ Society for Biochemistry & Molecular Biology

Identifying methylome changes in response to heavy, long-term cannabis use, in a large longitudinal cohort (519)

Amy Osborne 1 , John Pearson 1 , Tim Hore 2 , John Horwood 1 , Donia Macartney-Coxson 3 , Neil Gemmell 2 , Martin Kennedy 1
  1. University of Otago Christchurch, Christchurch City, New Zealand
  2. Anatomy, University of Otago, Christchurch, New Zealand
  3. Biomarkers Team, Health Programme, Institute of Environmental Science and Research Limited (ESR), Porirua, New Zealand

Marijuana has been highly publicised of late, with controversy and debate surrounding legalisation and its application for medical purposes. These debates have emphasised the medicinal and therapeutic benefits of cannabis, but there is also strong evidence for negative psychosocial consequences of prolonged cannabis use. Much of the evidence on health effects derives from the work of the Christchurch Health and Development Study (CHDS) which has followed the lives of 1265 people since they were born in 1977.  Many drugs impact on the pattern of epigenetic marks that control genome function, and while the effects of cannabis at a genomic level are not well understood, we do know that cigarette smokers, have distinct patterns of cytosine methylation compared with non-smokers and these “methylome” changes likely impact on the regulation of genes that underlie the effects of cigarettes.  It stands to reason that cannabis may similarly affect the methylome, so we recently carried out a genome wide analysis of methylation in blood of 96 CHDS subjects (48 cannabis smokers vs. 48 controls). Preliminary analyses identified many intriguing differentially methylated regions (DMRs) in heavy cannabis users, the majority are which are novel, and include genomic sites near the opioid receptor (OPRM1) and the glutamate transporter (SLC17A7) genes. Interestingly, these cannabis-associated DMRs do not appear to be differentially methylated in tobacco smokers.  We hypothesise that many are specifically affected by cannabis constituents, and that these genomic regions are, or contain, important regulatory sites for genes and biochemical pathways relevant to the effects of cannabis.