Illicit Drugs

Drugs of abuse are thought to promote addiction in part by "hijacking" brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and in vivo single-neuron calcium imaging, we found that drugs of abuse augment dopaminoceptive ensemble activity in the nucleus accumbens (NAc) and disorganize overlapping ensemble responses to natural rewards in a cell type-specific manner. Combining FOS-Seq, CRISPR-perturbation, and single-nucleus RNA sequencing, we identified Rheb as a molecular substrate that regulates cell type-specific signal transduction in NAc while enabling drugs to suppress natural reward consumption. Mapping NAc-projecting regions activated by drugs of abuse revealed input-specific effects on natural reward consumption. These findings characterize the dynamic, molecular and circuit basis of a common reward pathway, wherein drugs of abuse interfere with the fulfillment of innate needs.

Adulteration is a well-known practice of drug manufacturers at different stages of drug production. The intentional addition of active ingredients to adulterate the primary drug may enhance or mask pharmacological effects or may produce more potent drugs to increase the number of available doses and the dealer's profit. Adulterants found in different drugs change over time in response to different factors. A systematic literature search in PubMed and Scopus databases and official international organizations' websites according to PRISMA guidelines was performed. A total of 724 studies were initially screened, with 145 articles from PubMed and 462 from Scopus excluded according to the criteria described in the Method Section. The remaining 117 records were further assessed for eligibility to exclude articles without sufficient data. Finally, 79 studies were classified as "non-biological" (n = 35) or "biological" (n = 35 case reports; n = 9 case series) according to the samples investigated. Although the seized samples analyses revealed the presence of well-established adulterants such as levamisole for cocaine or paracetamol/acetaminophen for heroin, the reported data disclosed new adulteration practices, such as the use of NPS as cutting agents for classic drugs of abuse and other NPS. For example, heroin adulterated with synthetic cannabinoids or cocaine adulterated with fentanyl/fentalogues raised particular concern. Notably, adulterants play a role in some adverse effects commonly associated with the primary drug, such as levamisole-adulterated cocaine that may induce vasculitis via an autoimmune process. It is essential to constantly monitor adulterants due to their changing availability that may threaten drug consumers' health.

BackgroundProviding sterile drug smoking materials to people who use drugs can prevent the acquisition of infectious diseases and reduce overdose risk. However, there is a lack of understanding of how these practices are being implemented and received by people who use drugs globally.MethodsA systematic review of safer smoking practices was conducted by searching PubMed, PsycInfo, Embase for relevant peer-reviewed, English-language publications from inception or the availability of online manuscripts through December 2022.ResultsOverall, 32 peer-reviewed papers from six countries were included. 30 studies exclusively included people who use drugs as participants (n = 11 people who use drugs; generally, n = 17 people who smoke drugs, n = 2 people who inject drugs). One study included program staff serving people who use drugs, and one study included staff and people who use drugs. Sharing smoking equipment (e.g., pipes) was reported in 25 studies. People who use drugs in several studies reported that pipe sharing occurred for multiple reasons, including wanting to accumulate crack resin and protect themselves from social harms, such as police harassment. Across studies, smoking drugs, as opposed to injecting drugs, were described as a crucial method to reduce the risk of overdose, disease acquisition, and societal harms such as police violence. Ten studies found that when people who use drugs were provided with safer smoking materials, they engaged in fewer risky drug use behaviors (e.g., pipe sharing, using broken pipes) and showed improved health outcomes. However, participants across 11 studies reported barriers to accessing safer smoking services. Solutions to overcoming safer smoking access barriers were described in 17 studies and included utilizing peer workers and providing safer smoking materials to those who asked.ConclusionThis global review found that safer smoking practices are essential forms of harm reduction. International policies must be amended to help increase access to these essential tools. Additional research is also needed to evaluate the efficacy of and access to safer smoking services, particularly in the U.S. and other similar countries, where such practices are being implemented but have not been empirically studied in the literature.

ImportanceThe monthly opioid overdose death rate in the US has declined by 50% from its peak in the summer of 2023 through fall of 2024, and the factors associated with this decline are not fully understood.ObjectiveTo examine the association between the proportion of fentanyl reports in illicit drug seizures and opioid overdose deaths during periods of rising and falling mortality.Design and settingThis secondary analysis of state-month level panel data from the National Forensic Laboratory Information System and US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) was conducted from January 2018 to September 2024 and included all 50 US states and Washington, DC. CDC WONDER data were collected from recorded death certificates; National Forensic Laboratory Information System data were obtained from drug reports submitted by forensic laboratories. The data were analyzed from July to August 2025.ExposurePercentage of illicit drug seizures that contained fentanyl or fentanyl-related compounds. Illicit drug seizures were defined as seizures that contained any of the following: fentanyl or fentanyl-related compounds, heroin, methamphetamine, cocaine, and xylazine.Main outcomes and measuresThe monthly count of opioid overdose deaths, given by uniform claim descriptor codes X40 to 44, X60 to 64, X85, and Y10 to Y14, with additional multiple cause of death codes of T40.0 to 4 and T40.6. Death rates were calculated using yearly population estimates from the American Community Survey.ResultsFrom a peak in the summer of 2023 through the fall of 2024, the monthly opioid overdose death rate declined by 50%, from 2.2 to 1.1 per 100 000. This decline was was accompanied by a decline in the fentanyl reports as a proportion of total illicit drug seizures from 28.8% to 23.2%. In a 2-way, fixed-effects model, a 1-percentage point reduction in fentanyl prevalence was associated with 0.018 fewer overdose deaths per 100 000 population per month (95% CI, 0.016-0.019; P Conclusions and relevanceThe study results suggest that current decline in the proportion of fentanyl reports in illicit drug seizures is associated with 9.2% of the total observed decline in mortality. Additional contributing factors may include other shifts in the drug supply not captured by fentanyl prevalence in illicit drug seizures, shifts in drug use behavior, and the effect of public health programs, interventions, and policies.