SpenniesThe sexy genes of CB1 Knockout Mice
May 8th 2007 02:17
Here is a bioethical dilemma concerning recreational drugs and our society’s ongoing quest for a final solution.
We are all aware of delta9-tetrahydrocannabinol (THC), the principle psychoactive ingredient in marijuana. Marijuana is a psychoactive cannabinoid and in humans, psychoactive cannabinoids like marijuana produce euphoria, enhancement of sensory perception, difficulties in concentration and impairment of memory. Anyone who has ever smoked a jay or knows someone who has can vouch for this. The cognitive deficiencies seem to persist after withdrawal, which is why we’re taught that taking recreational drugs is bad and why we’re forced to look at those posters on city buses of kids looking sad because they apparently smoked some pot.
Anyway.
Cannabinoids (marijuana and other drugs in this category) are regulated in the body by G protein-coupled cannabinoid receptors, which maintain the body’s resistance to the effects of these drugs. The main receptor is called the CB1 receptor, which is found predominantly in the brain, with the highest densities in the hippocampus, cerebellum and striatum.
These dopaminergic circuits (related to the neurotransmitter dopamine) play a pivotal role in mediating the rewarding effects of most drugs of abuse.
Thus, cannabinoids share a common neuronal action with other major drugs of abuse such as morphine, ethanol and nicotine in producing facilitation of the dopamine system.
The cannabinoid receptors are also related to processes involved in cognition, memory, anxiety, control of appetite, emesis, inflammatory, and immune responses. Agonists that stimulate the CB1 receptor (such as some recreational drugs) may induce hyperactivity and severe motor deficits at larger doses. Antagonists that block the CB1 receptor (such as some pharmaceutical drugs) have been show to reduce the motivation for sucrose, beer and alcohol consumption.
The drug Acomplia is a CB1 antagonist – it blocks the CB1 receptor. It has been marketed as an appetite suppressant for overweight people as well as a drug to help people quit smoking. But being a CB1 receptor antagonist, Acomplia also attenuates the effects of marijuana and boosts cognition. So really, it’s quite a nice package you’re getting there if you happen to be taking it.
And now we get to the crux of the matter: to further monitor the effects of drugs such as Acomplia, scientists genetically modified mice without the CB1 receptor altogether. These mice are called CB1 Knockout Mice. Under controlled laboratory tests, these mice showed no effects when given marijuana and other psychoactive cannabinoid recreational drugs. They were simply immune to the effects or drugs. So, if it’s possible to genetically modify mice this way, it is certainly true that we could genetically modify humans this way too.
So, the question is – SHOULD we (because it’s quite evident now that we CAN) ever genetically modify humans without the CB1 receptor to make a society that is completely immune to the effects of recreational drugs? Could things ever get so bad that this step would be considered? And if it were to be considered, could any harm come from such a decision?
Less extreme, could governments ever force people to take pharmaceutical CB1 antagonist drugs like Acomplia that block the CB1 receptor? Surely a society where everyone is fit, smart, doesn’t smoke or take drugs is something to strive for, right? Just how important is personal freedom when searching for a higher goal such as that?
We are all aware of delta9-tetrahydrocannabinol (THC), the principle psychoactive ingredient in marijuana. Marijuana is a psychoactive cannabinoid and in humans, psychoactive cannabinoids like marijuana produce euphoria, enhancement of sensory perception, difficulties in concentration and impairment of memory. Anyone who has ever smoked a jay or knows someone who has can vouch for this. The cognitive deficiencies seem to persist after withdrawal, which is why we’re taught that taking recreational drugs is bad and why we’re forced to look at those posters on city buses of kids looking sad because they apparently smoked some pot.
Anyway.
Cannabinoids (marijuana and other drugs in this category) are regulated in the body by G protein-coupled cannabinoid receptors, which maintain the body’s resistance to the effects of these drugs. The main receptor is called the CB1 receptor, which is found predominantly in the brain, with the highest densities in the hippocampus, cerebellum and striatum.
These dopaminergic circuits (related to the neurotransmitter dopamine) play a pivotal role in mediating the rewarding effects of most drugs of abuse.
Thus, cannabinoids share a common neuronal action with other major drugs of abuse such as morphine, ethanol and nicotine in producing facilitation of the dopamine system.
The cannabinoid receptors are also related to processes involved in cognition, memory, anxiety, control of appetite, emesis, inflammatory, and immune responses. Agonists that stimulate the CB1 receptor (such as some recreational drugs) may induce hyperactivity and severe motor deficits at larger doses. Antagonists that block the CB1 receptor (such as some pharmaceutical drugs) have been show to reduce the motivation for sucrose, beer and alcohol consumption.
And now we get to the crux of the matter: to further monitor the effects of drugs such as Acomplia, scientists genetically modified mice without the CB1 receptor altogether. These mice are called CB1 Knockout Mice. Under controlled laboratory tests, these mice showed no effects when given marijuana and other psychoactive cannabinoid recreational drugs. They were simply immune to the effects or drugs. So, if it’s possible to genetically modify mice this way, it is certainly true that we could genetically modify humans this way too.
So, the question is – SHOULD we (because it’s quite evident now that we CAN) ever genetically modify humans without the CB1 receptor to make a society that is completely immune to the effects of recreational drugs? Could things ever get so bad that this step would be considered? And if it were to be considered, could any harm come from such a decision?
Less extreme, could governments ever force people to take pharmaceutical CB1 antagonist drugs like Acomplia that block the CB1 receptor? Surely a society where everyone is fit, smart, doesn’t smoke or take drugs is something to strive for, right? Just how important is personal freedom when searching for a higher goal such as that?
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