New Prevention Against Cocaine Overdose and Addiction?

You’re dancing at a club with some friends when you see someone in the corner doing several lines of cocaine. They get back onto the dance floor but are soon twitching and sweating profusely. Suddenly, they are on the ground seizing. What if it was possible to ensure this situation never happened? Research by Li et al. (2018) has found a way to protect mice from cocaine overdose and cocaine-seeking behavior, possibly preventing addiction before it occurs. Using CRISPR, a technique for editing genomes, these researchers modified the hBChE enzyme. This enzyme breaks down the acetylcholine neurotransmitter, which helps activate muscles, but it also breaks down cocaine at a much lower efficiency rate. With the help of CRISPR, they amplified the enzyme’s efficiency by over 4,400 times, without negatively affecting the effects of acetylcholine.

For this procedure, certain stem cells found in the skin were extracted, modified in vitro – outside of the human body – and grafted back onto the donor. This process is safer and cheaper than viral vector gene therapy, where genetic material is brought into cells by viruses. This study confirmed that the modified cells would not change the cells’ typical multiplication or specialization. Additionally, removing a skin graft is relatively simple, so any hypothetical errors can be dealt with quickly.

Cocaine is addictive because it increases the level of dopamine in the user’s brain. This results in more reward-related behaviors such as drug-seeking. Li et al. compared mice grafted with the hBChE-expressing cells and control mice. They found that when injected with cocaine, the experimental group removed cocaine from their system faster and had less dopamine in the reward pathway of the brain.

Li et al. then measured both the rewarding effects of cocaine and the effect of cocaine-induced reinstatement. In both studies, they found that control mice spent significantly more time in a cocaine-associated location while GhBChE mice showed no preference. The engineered enzyme diminishes cocaine’s reward, decreasing the motivational pull of cocaine. Additionally, a 100% lethal dose of cocaine in control mice had 0% lethality in the experimental mice, meaning the edited enzyme protected these mice from cocaine overdose. While this research shows the potential of aiding in addiction and acute treatment of overdoses, future studies need to be done where the drug is administered willingly, rather than through injections. The modified enzyme appears to be cocaine-specific. The lethality and rewarding effect experiments were repeated with methamphetamine and ethanol respectively, and the treatment group reacted the same as the control group.

This study implies the possibility of reducing the rewarding aspect of cocaine in humans, preventing addiction before it occurs. If cocaine addiction can be prevented, then who should get this treatment? Should parents be “vaccinating” their kids against cocaine addiction? Future studies may find this to be a safe and cheap therapy for cocaine abuse, but for now, it would be realistic to see this technique as an effective prevention measure. Deciding for whom, however, presents an ethical dilemma.

Li, Y., Kong, Q., Yue, J., Gou, X., Xu, M., & Wu, X. (2018). Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose. Nature Biomedical Engineering, 3(2), 105-113. doi: 10.1038/s41551-018-0293-z

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Gabe Brosius


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