The experimental data presented here show an overall change in the pattern of drug use as a result of the unusual situation linked to the COVID-19 pandemic.

The strict limitations imposed on the movement and gatherings of people as a rapid response to the pandemic have greatly restricted social opportunities to use drugs [24]. The restrictions affected both the locations where those who use drugs generally gather and their ability to socialize. Pubs and clubs have been closed, and festivals have been cancelled. Additionally, the movements of people and social interactions have been severely limited by the implementation of quarantine and confinement measures [24].

These situations have commonly been cited as leading reasons for the decrease in the use of recreational drugs, such as MDMA and cocaine, as demonstrated in this study, which are typically related to nightlife and party settings [24]. Unlike the findings for cocaine and MDMA, a less marked effect on cannabis use during the lockdown has been reported in some studies [24,25].

The results from the present study show a general tendency to move from the use of a single substance to polysubstance use in the post-lockdown period. Furthermore, 80% of those who abandoned the use of illicit drugs during the lockdown period later returned to using the primary drug, and most of these individuals combined it with other substances. These results suggest that there was full drug availability due to the reopening of the clandestine market right after the lockdown.

By analyzing the trends of individual drugs, our results show a significant decrease in cannabis use during the lockdown, although it tended to return to pre-lockdown levels in the post-lockdown period. A decrease in cannabis use could reflect a reduced availability of the drug in times of social lockdown since the borders were closed, dealers had a harder time going around unnoticed, and prices increased due to increased demand [25]. Our data also show a reduction in heroin use during lockdown in the high-risk drug use population in Italy in this study. In some countries, it was reported that opioid users experienced a sharp decline in their primary sources of income (including panhandling and sex work) and a restriction in their ability to access drugs from their usual drug dealers [24]. This crisis led some heroin users to access drug treatment services, while others switched to using other more readily available substances, such as alcohol and BZDs [24]. In fact, in our study, 30% of the patients replaced the use of the drug that they previously used with BZDs during the lockdown. During this period of home confinement, drug users may not have been looking for substances that are often consumed in social settings, but rather for psychotropic drugs that are more often consumed alone [26].

The trends highlighted in this study show an overall increase in the consumption of BZDs, which has remained high, even in the post-lockdown period. BZDs enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABA_A receptor, resulting in sedative, hypnotic (sleep-inducing), anxiolytic, anticonvulsant and muscle-relaxant properties [27].

BZDs have a high potential for abuse and misuse, and they are typically co-abused in patients with SUDs, in whom the most frequent primary abuse drugs are opioids and/or alcohol. BZDs are misused to enhance the euphoric effects of other drugs, to reduce the unwanted effects of drugs, such as insomnia due to stimulant use and to alleviate withdrawal symptoms between doses [27]. The side effects of BZDs are common and include blurred or double vision, headache, vertigo, nausea and vomiting, tremor and depression [27]. Elderly patients are more likely to develop significant adverse effects [27].

In our study, the increased use of BZDs was associated with an increased use of alcohol, both during and after lockdown. Despite extensive research, the precise mechanism of action of ethanol remains not fully understood [28]. However, ethanol has shown a similarity in its effects to positive allosteric modulators of the GABA_A receptor, such as BZDs, barbiturates, and various general anesthetics with which alcohol has a synergistic interaction as a CNS depressor [28].

Changes in patterns of alcohol use have been fairly commonly reported in the EMCDDA Trendspotter briefings [24], including drinking more frequently, consuming greater quantities of alcohol and drinking alone. Increased alcohol consumption is commonly observed after a crisis [29]. There are several reasons why alcohol consumption may increase during the COVID-19 pandemic. These include boredom and disruption to routines caused by the lockdown, the threat of the disease, changes to life circumstances and associated distress [30].

A study of 754 adults from the USA demonstrated that psychological distress caused by the COVID-19 pandemic was associated with increased alcohol consumption, whereas the perceived threat from the virus itself was not associated with increased alcohol consumption [31]. Other reasons people drink during a crisis include the inhibiting effect of alcohol on the nervous system offering temporary relief from emotions, anxiety, anger, sleep disorders, depression and post-traumatic stress disorders associated with a lockdown [30].

Interestingly, the consumption of all the substances analyzed (heroin, cocaine, MDMA and cannabis) at the end of the lockdown returned to levels similar to those found prior to the lockdown, except for alcohol and BZDs, the consumption of which has remained at the higher levels reached during lockdown. Although patients in the study had fairly high baseline EtG values, since alcohol is among the most frequently reported secondary substance problems for drug addicts, the highly significant increase in alcohol consumption, especially among cannabis and cocaine users, observed during and after the lockdown can be attributed to the effects of the pandemic, as highlighted by other authors [32,33,34].

Periods of isolation and loneliness can have long-lasting negative consequences on individuals’ physical and mental well-being, which can lead to an increase in the consumption of self-care substances such as alcohol and BZDs, both of which are central nervous system depressants that can result in a range of adverse health effects [26,30,31]. Overall, the COVID-19 pandemic could lead to a spike in alcohol abuse, relapses and potentially the development of alcohol use disorders combined with the concomitant abuse of other drugs in at-risk individuals.

Severe short- and long-term physical, psychological and social consequences related to alcohol and/or drug abuse during the COVID-19 pandemic will inevitably put further pressure on drug and alcohol dependence services and the health service in general during the post-pandemic period [15,27,32].