Does the press release accurately reflect the study?
‘I think they have produced a good summary, which is understandable and has the right amount of space.’

Is the study of good quality? Are the conclusions backed up by solid data?
‘In my opinion, the study is very well designed and correctly carried out. The data and its treatment, together with the conclusions, are coherent.’

How does this work fit in with existing evidence?
‘There is no solid evidence for the pharmacological treatment of cocaine dependence, despite the use of a large number of drugs, belonging to various therapeutic groups, which have not been approved by any drug agency’.

Have the authors taken confounding factors into account? Are there any important limitations to be considered?
‘Yes. The article considers the difficulty of evaluating some aspects and deals with them well. On the other hand, a series of limitations of the study are pointed out, for example, the number of participants which we always want to be higher’.

What are the implications for the real world?
‘I think this study is an important step in the development of the drug which will require one or more further phase 3 studies and that, if the results in phase 3 are positive, we could have the first treatment for cocaine dependence. For the moment we can say that mavoglurant is at the stage of ‘promising drug’ for cocaine dependence.

For years, a large number of drugs have been used to treat cocaine dependence, including various antidepressants, mood stabilisers, dopamine agonists, psychostimulants, neurotransmitter precursors, opioids, as well as a long list of drugs in the experimental phase. However, none of them has been approved by the drug agencies for the treatment of patients dependent on this drug.

In this sense, a subtype of the metabotropic glutamate receptor, mGluR5, is thought to be involved in the modulation of cocaine-induced addictive behaviour. Mavoglurant is a negative allosteric modulator that acts as an antagonist of this receptor and has proven effective in animal and clinical trials in reducing cocaine administration. These data, together with the good tolerability and safety demonstrated by mavoglurant in patients with fragile X syndrome, obsessive-compulsive disorder and Parkinson's disease, stimulated the realisation of a phase 2 clinical trial, as a comparison with placebo, in patients with cocaine abuse.

The results of this study show that mavoglurant was safe and generally well tolerated and reduced cocaine use (demonstrated by lower levels of benzoylecgonine, a urinary metabolite of cocaine used as a marker), compared to the placebo group. Furthermore, the clinical evaluation (CGI) of clinical improvement at the end of the study was much higher for the mavoglurant group (90.9%) than with the placebo (46.6%). If these data are confirmed in subsequent studies involving a larger number of patients, there would be sufficient arguments for possible approval by the drug agencies of the first drug to treat cocaine addiction'.

This is a well-designed and promising phase 2 clinical trial that addresses one of the great challenges in addiction medicine: the absence of effective pharmacological treatments for cocaine use disorder. The authors evaluated mavoglurant, a selective mGluR5 receptor antagonist, which showed a statistically significant reduction in cocaine use compared to placebo. In addition, a parallel reduction in alcohol consumption was observed, which could indicate shared neurobiological mechanisms between the two substances.

However, the study has significant limitations. The sample was small, predominantly composed of white males, and the duration of follow-up was short. It would be essential to evaluate this drug in more diverse populations, including regions with a high burden of consumption such as Latin America, and to consider other routes of drug administration.

Furthermore, although the results are encouraging from a clinical point of view, important questions remain unanswered: what will the cost of the drug be if it is finally approved? Will it be accessible to consumers who, for the most part, belong to vulnerable groups with few resources? Will governments be willing to finance its use in public health systems if it proves effective in the long term? These are key questions for the actual implementation of this potential therapy.