A recent study on mice found that administering cannabidiol helped extinguish the preference for cocaine. It also restored gut microbiota diversity disrupted by cocaine. The research was published in Progress in Neuro-Psychopharmacology & Biological Psychiatry.
Cocaine is a powerful stimulant drug derived from the leaves of the coca plant, native to South America. It is commonly used recreationally because it induces euphoria, increased energy, and heightened alertness. However, cocaine is highly addictive. Its use leads to severe physical and psychological health issues, including heart attacks, strokes, and mental disorders. Cocaine is illegal in most of the world.
Cocaine use leads to the development of cocaine use disorder, a condition characterized by addiction to cocaine. After addiction develops, the addicted individual feels a compulsive urge to use cocaine, regardless of consequences. This leads to further health problems. At the moment there are no completely effective ways to reduce craving for cocaine and its use in individuals with cocaine use disorder.
Study author Rose Chesworth and her colleagues wanted to explore whether cannabidiol can be used to treat cocaine use disorder. They were particularly interested whether cannabidiol can affect the changes to the brain reward system induced by cocaine (i.e. addiction) and also whether these effects are linked to changes in the gut microbiome. Cannabidiol is a non-psychoactive compound found in cannabis plants, known for its potential therapeutic effects, such as reducing anxiety, pain, and inflammation.
Recent novel findings indicate that the gut and microorganisms living in it (the gut microbiota) are affected by cocaine use. The composition of microbiota living in the gut is altered in individuals using cocaine. Gut microbiota composition is linked to processes in the brain via a bidirectional communication pathway known as the microbiota-gut-brain axis. Therefore, it is possible that inducing changes to the gut microbiome will lead to changes in brain functioning related to cocaine and vice versa.
These authors conducted a series of experiments on 48 8-week-old male C57BL/6JABR mice (a strain of laboratory mice commonly used in research) at Western Sydney University, Australia. The mice were housed 2-3 per cage and had free access to food and water.
Mice were randomly divided into 4 treatment groups. Each group received 2 sets of injections. One group received injections of cannabidiol and cocaine (in the form of cocaine hydrochloride). The second group received injections of cannabidiol along with injections with no active substances. The third group received injections of cocaine along with injections with no active substances. The fourth group just received two sets of injections with no active substances. They received two injections per day. The dosage for cocaine was 20 mg/kg.
Mice received injections when they ventured into a specific part of their living area, a process known as conditioned place preference (CPP). This method created an association between the environment and the effects of the injections, allowing researchers to measure how much time the mice spent in the area associated with the drug.
Over the course of 14 days, researchers conditioned the mice to associate either cocaine or saline injections with one side of the CPP apparatus. After the conditioning period, they measured the mice’s preference for the drug-paired side, both immediately and at intervals of 2 and 4 weeks post-treatment to assess the persistence of cocaine preference and the potential long-term effects of cannabidiol.
Results showed that mice treated with cocaine tended to move around more afterward (increased locomotor activity). This increase in activity was even stronger in mice that received both cocaine and cannabidiol. Mice treated with cocaine developed preferences for areas where they received injections, and this preference was present for up to 4 weeks after injections ceased.
However, the preference for cocaine injection areas was reduced in mice who also received cannabidiol. These mice showed a preference for the injection area immediately after the treatments ended, but not 2 or 4 weeks after the treatments. This indicates that cannabidiol facilitated the extinction of preference for cocaine.
Further analyses showed that cannabidiol reversed changes to gut microbiome diversity that cocaine induces – these changes were absent in mice that also received cannabidiol. Study authors also found that the preference for cocaine was associated with the abundance of specific strains of microorganisms in the gut.
“Here we show that CBD [cannabidiol] facilitates cocaine extinction memory and reverses persistent cocaine-induced changes to gut microbe diversity. Furthermore, CBD increases the abundance of gut microbes which have anti-inflammatory properties. This suggests that CBD may act via the gut to reduce the memory of cocaine reward. Our data suggest that improving gut health and using CBD could limit cocaine abuse,” the study author concluded.
The study is one of the first to present the links between cocaine-induced changes to neural functioning and gut microbiota, as well as how these can be affected by cannabidiol. However, the study was conducted on mice. Although mice and humans share many physiological similarities, they are still very different species. Results on humans might not be identical.
The paper, “Cannabidiol (CBD) facilitates cocaine extinction and ameliorates cocaine-induced changes to the gut microbiome in male C57BL/6JArc mice,” was authored by Rose Chesworth, Howard Chi-Ho Yim, Georgia Watt, Emad El-Omar, and Tim Karl.