Scientists from Queen Mary, University of London, have discovered a new way to separate the therapeutic benefits of cannabis from its mood-altering side-effects.
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THC binds to and activates proteins in the brain known as 'CB1 cannabinoid receptors'. Activating these receptors can relieve pain and prevent epileptic seizures; but it also causes the mood-altering effect experienced by people who use cannabis as a recreational drug.
Now, SBCS's Professor Maurice Elphick and Dr Michaela Egertová may have found a way of separating out the effects of cannabis – a discovery which could lead to the development of new medicines to treat conditions such as epilepsy, obesity and chronic pain. The research is described in the December 2007 issue of the journal Molecular Pharmacology.
Working in collaboration with scientists from the Department of Pharmacology and Toxicology at the Medical College of Georgia, USA, they have identified a protein that binds to the CB1 receptors in the brain. But unlike THC, this 'Cannabinoid Receptor Interacting Protein' or CRIP1a, suppresses the activity of CB1 receptors.
Professor Elphick explains: "Because CRIP1a inhibits the activity of the brain’s cannabinoid receptors, it may be possible to develop drugs that block this interaction, and in turn enhance CB1 activity. This may give patients the pain relief associated with CB1 activity, without the 'high' that cannabis users experience."
Schizophrenia is associated with an increased use of tobacco and cannabis, with evidence suggesting that patients may use the drug to alleviate neurophysiological symptoms. The benefits of these substances are thought to be mediated through their effects on CHRNA7 and CNR1, respectively, notes the team.
They therefore looked at the effects of variants in the genes encoding CHRNA7 and CNR1 on the risk for schizophrenia and the potential effects of tobacco and cannabis use.
Stanley Zammit, from Cardiff University, and colleagues genotyped 750 patients with schizophrenia and 688 mentally healthy controls for the CHRNA7 promoter polymorphism -86C/T and the CNR1 polymorphism rs1049353. They also gathered information on tobacco and cannabis use via interviews and case-note records.
In addition, the team conducted a case-only study of 493 participants from the schizophrenia group, examining interactions between cannabis use and the Val158Met polymorphism in the COMT gene, as well as the rs737865 and rs165599 single nucleotide polymorphisms (SNPs).
The team reports in the British Journal of Psychiatry that there was no evidence of an association between the CHRNA7 -86C/T genotype and schizophrenia. Schizophrenia patients were 4.4 times more likely than controls to smoke, but among the schizophrenia patients, there was no association between tobacco use and the -86C/T genotype.
Similarly, there was no significant association between the CNR1 rs1049353 genotype and schizophrenia. Schizophrenia patients were 2.6 times more likely than controls to use cannabis, but cannabis use was not affected by rs1049353 genotype among schizophrenia patients.
The results also showed that there were no associations between the Val158Met genotype and cannabis use, or between cannabis use and the variations at rs737865 and rs165599.
The only genetic effect on phenotypes of schizophrenia was a weak association between the -86C/T genotype and a younger age at onset of schizophrenia.
“In summary, we failed to find any evidence that variation at the CHRNA7 or CNR1 locus was associated with schizophrenia, or that the effect of variation at these loci was modified by use of tobacco or cannabis, respectively,” the researchers write.
They add: “Cannabis use was not associated with the presence of valine allele at Val158Met with COMT in our sample, therefore our findings do not support a previous report of a putative gene–environment interaction between COMT genotype and cannabis use on risk of schizophrenia.”