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Scientists from The University of Western Australia have identified how using cannabis can alter a person’s DNA structure, causing mutations which can expose them to serious illnesses, and be passed on to their children and several future generations.

Although the association between cannabis use and severe illnesses such as cancer has previously been documented, providing an understanding how this occurs and implications for future generations was not previously understood.

Associate Professor Stuart Reece and Professor Gary Hulse from UWA’s School of Psychiatry and Clinical Sciences completed an extensive analysis of literary and research material to understand the likely causal mechanisms and uncovered alarming information.

Associate Professor Reece said that “through our research we found that cancers and illnesses were likely caused by cell mutations resulting from cannabis properties having a chemical interaction with a person’s DNA,”. “With cannabis use increasing globally in recent years, this has a concerning impact for the population.”

Although a person may appear to be healthy and lead a normal life, the unseen damage to their DNA could also be passed on to their children and cause illnesses for several generations to come.

“Even if a mother has never used cannabis in her life, the mutations passed on by a father’s sperm can cause serious and fatal illnesses in their children,” he said..

“The parents may not realise that they are carrying these mutations, which can lie dormant and may only affect generations down the track, which is the most alarming aspect.”

Associate Professor Reece said that when the chemicals in cannabis changed a person’s DNA structure it could lead to slow cell growth and have serious implications in the foetal development of babies that may cause limbs or vital organs not develop properly or cause cancers.

“The worst cancers are reported in the first few years of life in children exposed in utero to cannabis effects,” he said.

Associate Professor Stuart Reece said that the finding was of major importance with cannabis use increasing in many nations around the world, and many countries legalising its use.

“Some people may say that previous data collected doesn’t show there are serious effects from using cannabis, but many authorities acknowledge that there is now a much larger consumption of cannabis use compared to previous years.

The study carries implications for researchers, medical health professionals and governments in regulating drug use and protecting vulnerable populations.

The research has been published in Mutation Research – Fundamental and Molecular Mechanisms of Mutagenesis

MEDIA REFERENCES

David Stacey (UWA Media and Public Relations Manager)                    (+61 8) 6488 3229 / (+61 4) 32 637 716

Associate Professor Dr Stuart Reece (UWA’s School of Psychiatry and Clinical Services)         (+61 7) 3844 4000

Further Commentary by Papers Authors

Whilst drug addiction is well known to be commonly associated with mysterious and confusing behaviour the features observed amongst addicted patients clinically have long posed many mysteries for their treating doctors.  With regard to cannabis some of these mysteries include the following important questions:  How can cannabis use be associated with cancers in so many different tissues – mouth and throat, lung, testes, leukaemia, cervix, brain and prostate?   Why are they so aggressive?  And why do they occur so much younger?  Why are some cancers apparently inherited so that they occur much more commonly in young children (< five years) and infants (< one year) ?  This relates to cancers of nerve cells, leukaemia and muscle.  Cancer occurring in children is due to inherited genetic damage – so how is it be passed on to the next generation?  How many generations would be affected?

The reproductive effects of cannabis were also very confusing.  Many papers have described that the rates of major heart malformations (of at least five different types), large gaping holes at the top and bottom of the spinal cord (called by doctors encephalocoele and spina bifida respectively), absent and shrunken ears and eyes, major bowel abnormalities including babies born with the bowels hanging out, could all occur at greatly increased rates, from 3 to 30 times usual, in the offspring of cannabis exposed mothers?  And what of the various limb deformities which have been described – fingers joined together, extra fingers, and greatly shrunken arms or absent arms, which seemed to be reminiscent of thalidomide babies?  How could all of these possibly be related?

Whilst it is true that cannabis smoke contains most of the tars which have been found in tobacco smoke, and whilst carcinogenic effects have previously been described with certain cannabis extracts (called cannabinoids) when tested in the lab, still this diverse and varied toxicological profile appeared to be very confusing.  What could possibly be going wrong to cause the varied effects in many different tissues?    It seemed like an enigma wrapped in a puzzle inside a mystery….

Then in 2015 one of the foremost genetics laboratories in the world published their findings from New York relating to how and why chromosomal shattering occurred.  Through careful studies of gene sequences scientists had become aware in the last few years that chromosomes, which carry the genetic material of our DNA, could become cut up, and might then become re-joined in apparently strange and haphazard ways.  But how this occurred was quite unclear.

It was known at the time that when cells divide the chromosomes separate along "train tracks" by travelling along “rails” formed of microtubules.  Anything that causes the chromosomes to lose their attachments to these microtubules would make them become “de-railed”, and effectively escape from the normal mitotic process.  When cells divide two new nuclei are formed.  But a chromosome which became detached from this system would end up isolated in a nucleus all by itself.  This tiny nucleus containing one or a few chromosomes was called a micronucleus.  The great insight by the New Yorkers was to show that in these micronuclei, the DNA did not have enough enzymes and proteins around it to look after it properly.  So when the DNA was cut, as happens normally when DNA is copied to form either new DNA or to transcribe RNA and then proteins, it could not be handled properly, and it was effectively shattered into pieces.  These tiny pieces could then be re-joined haphazardly effectively creating genetic chaos.

This was the molecular equivalent of a “bomb going off” in the genome.

Mostly micronucleus formation caused cell death due to excessive genomic damage.  But it was also known that in occasional surviving cells this process could lead to major abnormalities in newborn babies, to cancer, and indeed to heritable cancers in several subsequent generations.

Cannabis, THC and some of its other extracts were known to interfere with the operation of the microtubule “train tracks”, to cause micronucleus formation, and to damage eggs and sperm, the careful and meticulous wrapping and packaging of DNA inside sperm, the proteins around which DNA is wrapped inside the nucleus, and the “software” code which genes carry which determines when they will be switched on and off – called the epigenetic code.

Worryingly, many of the genetic tests showed a threshold effect which had to be crossed for these effects to become obvious.

Suddenly a train of causation became obvious.  By interfering with cell growth in utero abnormalities would be appear in organs growing at that time.  Cancer formation was now expected.  Moreover as cannabis consumption rises these effects will become increasingly common.

Hence these findings, which now imply causality, have major implications for doctors, pharmaceutical companies, and the public health burden of disease globally.  They are of particular concern to parents.