14 DAY TRIAL // Neuroscientists have discovered that all drug addictions involve the action of a certain substance in one specific part of the brain. Both the pleasure generated by drugs and their adverse effects on withdrawal are connected to the same substance. Scientists have now discovered an inhibitor that removes the craving for drugs and the pleasure obtained from them as well as their thorny withdrawal effects.
The team, led by Xia Zhang, associate professor in the University of Saskatchewan department of psychiatry, found that a naturally occurring enzyme known as PTEN acts on the part of the brain where many drugs of abuse exert their rewarding effects - the ventral tegmental area (VTA).
Most drugs have an impact on the brain because they have a chemical structure that resembles the chemical structure of natural neurotransmitters. This resemblance permits them to act like neurotransmitters. As they enter the blood stream, they eventually reach the brain and cause neurons to fire in a way they otherwise wouldn't. This is why people using drugs experience unmotivated pleasure, hallucinations or bursts of creativity.
The problem is that if a certain drug is used repeatedly, the organism adapts to the new situation and produces less of its own natural neurotransmitters. It starts using the drugs in place of its own substances. This is why, in order to have their aimed effects, most drugs have to be used in larger and larger amounts. However, when someone stops using drugs, the organism is suddenly faced with a shortage of neurotransmitters. Until it readapts to the drug-free situation the withdrawal negative effects are experienced.
The neurons in the VTA, the area the causes us to feel pleasure, are sensitive to serotonin, a neurotransmitter also associated with learning, sleep and mood. The team discovered that the PTEN enzyme acts on serotonin receptors present in the VTA, enhancing their receptivity, and thus increases brain cell activity. Without this enzyme the "reward" process sparked by drugs couldn't be turned on.
Thus, in order to reduce the brain sensation of pleasure, without actually reducing the amounts of serotonin (or drugs), the team designed a molecule, a particular peptide, tailored to fit the serotonin receptors and block the PTEN enzyme.
Tests on addicted rats had shown that when they were treated with this PTEN-blocker, not only the drug reward process was shut down, but also the process that induces craving and withdrawal.
"Our results suggest a potential universal strategy for treating drug addiction," Zhang says. "Most drugs of abuse act on the neurons in this area."
However an actual treatment that could help drug addicts is still several years away as further testing, including animal and, finally, human trials are needed. The inhibitor they designed could have all sorts of yet unknown adverse effects such as causing depression (as depression is linked with poor serotonin receptors).
"We have our peptide [the inhibitor], but there's a long way to go before a clinical application," he says.