A gut (microbiome) feeling about addiction: Interactions with stress and social systems.

In recent years, an increasing attention has given to the intricate and diverse connection of microorganisms residing in our gut and their impact on brain health and central nervous system disease. There has been a shift in mindset to understand that drug addiction is not merely a condition that affects the brain, it is now being recognized as a disorder that also involves external factors such as the intestinal microbiota, which could influence vulnerability and the development of addictive behaviors. Furthermore, stress and social interactions, which are closely linked to the intestinal microbiota, are powerful modulators of addiction. This review delves into the mechanisms through which the microbiota-stress-immune axis may shape drug addiction and social behaviors. This work integrates preclinical and clinical evidence that demonstrate the bidirectional communication between stress, social behaviors, substance use disorders and the gut microbiota, suggesting that gut microbes might modulate social stress having a significance in drug addiction.

A probabilistic model of relapse in drug addiction.

More than 60% of individuals recovering from substance use disorder relapse within one year. Some will resume drug consumption even after decades of abstinence. The cognitive and psychological mechanisms that lead to relapse are not completely understood, but stressful life experiences and external stimuli that are associated with past drug-taking are known to play a primary role. Stressors and cues elicit memories of drug-induced euphoria and the expectation of relief from current anxiety, igniting an intense craving to use again; positive experiences and supportive environments may mitigate relapse. We present a mathematical model of relapse in drug addiction that draws on known psychiatric concepts such as the "positive activation; negative activation" paradigm and the "peak-end" rule to construct a relapse rate that depends on external factors (intensity and timing of life events) and individual traits (mental responses to these events). We analyze which combinations and ordering of stressors, cues, and positive events lead to the largest relapse probability and propose interventions to minimize the likelihood of relapse. We find that the best protective factor is exposure to a mild, yet continuous, source of contentment, rather than large, episodic jolts of happiness.

[The analysis of main causes of increasing of cost of social aftermath of drug addiction in the region according to results of repeated evaluation].

The article presents an attempt to evaluate what factors could contribute into significant changes of both amount and structure of social cost of drug consumption in the region. The analysis, based on preserved basic principles of assessment, was applied to processes that occurred in both state and non-state spheres. The purpose of the study was to analyze main causes of dynamics of social cost of drug consumption during re-assessment. MATERIALS AND METHODS: The social cost of drug consumption in the Samara Oblast was re-assessed in 2017-2020 (first assessment was implemented in 2007-2010). The main causes of increasing of social cost of drug consumption were analyzed on the basis of the study results. RESULTS: In Samara Oblast, due to financial and structural changes in state and non-state spheres, occurred increasing of social cost of drug consumption from 18.0 billion to 25.4 billion rubles per year. At that, percentage of social cost of drug consumption in the gross domestic product decreased from 2.9% to 1.6%. In general structure of expenses greatest changes affected percentage of social aftermath of drug addiction (increase from 17.8% to 26.1%) and expenses of drug consumers (decrease from 69.7% to 62.3%). CONCLUSIONS: The increase of absolute values of financial expenditures of the Oblast related to drug consumption conditioned by financial and structural changes in society, is accompanied by decreasing of percentage of ocial cost of drug consumption in value of gross domestic product. The main cause of its dynamics is significant increasing of gross regional product.

Prenatal and postnatal cocaine exposure enhances the anxiety- and depression-like behaviors in rats during cocaine withdrawal.

Prenatal drug exposure is a public health problem, which results in profound behavioral problems during childhood and adolescence, mainly represented by an increase in the risk of cocaine abuse at an early age. In rodents, prenatal and postnatal cocaine exposure enhanced locomotor activity and cocaine- or nicotine-induced locomotor sensitization. Various authors consider that the adverse emotional states (anxiety and depression) that occur during cocaine withdrawal are the main factors that precipitate, relapse, and increase chronic cocaine abuse, which could increase the risk of relapse of cocaine abuse. Therefore, the objective of this study was to characterize anxiety- and depression-like behaviors at different times (30, 60, 90, and 120 days) of cocaine withdrawal in rats born to females exposed prenatally and postnatally to cocaine. A group of pregnant female Wistar rats were administered daily from day GD0 to GD21 with cocaine (cocaine preexposure group), and another group of pregnant female rats was administered daily with saline (saline preexposure group). Of the litters resulting from the cocaine-pre-exposed and saline-pre-exposed pregnant female groups, only the male rats were used for the recording of the anxiety- and depression-like behaviors at different times (30, 60, 90, and 120 days) of cocaine withdrawal The study found that prenatal and postnatal cocaine exposure dose-dependent enhanced anxiety- and depression-like behaviors. This suggests that prenatal and postnatal cocaine exposure can result in enhanced vulnerability to cocaine abuse in young and adult humans.

Custodial and perinatal care patterns of women who received prenatal care while incarcerated in the Arkansas state prison system, 2014-2019.

BACKGROUND: The extraordinary growth in women's incarceration over the past several decades has resulted in calls for expansion of research into their unique needs and experiences, including those related to pregnancy and perinatal care. However, while research into the health outcomes of women who are incarcerated while pregnant has grown, research on women's custodial and perinatal care patterns has remained nearly non-existent. Here, we sought to describe (1) the characteristics of the population of women who came to be incarcerated in a state prison system during pregnancy and (2) the characteristics of women's custodial and perinatal care patterns during and after incarceration. METHODS: We conducted a retrospective chart review of the population of women who received perinatal care while incarcerated in the Arkansas state prison system over a 5-year period from June 2014 to May 2019. Electronic medical records and state prison records were merged to form our study population. Data were from 212 women (Mage = 28.4 years; 75.0% non-Latina White) with a singleton pregnancy who received at least one obstetric care visit while incarcerated. RESULTS: Drug-related convictions were the most common crimes leading to women's incarceration while pregnant, and violent crime convictions were rare. Nearly half (43.4%) of women who gave birth in custody did so within 90 days of admission and the great majority (80.4%) released within 1-year of giving birth, including 13.3% who released within 30 days. DISCUSSION: The frequency with which women who became incarcerated while pregnant released from prison either prior to or shortly after giving birth was a striking, novel finding of this study given the implications for perinatal care disruption among a high-risk population and the harms of forced separation from infants within hours of birth. CONCLUSIONS: Diversionary programs for pregnant women convicted of crimes, particularly in states without current access, are urgently needed and should be a priority for future policy work.

SNP-based and haplotype-based genome-wide association on drug dependence in Han Chinese.

BACKGROUND: Drug addiction is a serious problem worldwide and is influenced by genetic factors. The present study aimed to investigate the association between genetics and drug addiction among Han Chinese. METHODS: A total of 1000 Chinese users of illicit drugs and 9693 healthy controls were enrolled and underwent single nucleotide polymorphism (SNP)-based and haplotype-based association analyses via whole-genome genotyping. RESULTS: Both single-SNP and haplotype tests revealed associations between illicit drug use and several immune-related genes in the major histocompatibility complex (MHC) region (SNP association: log10BF = 15.135, p = 1.054e-18; haplotype association: log10BF = 20.925, p = 2.065e-24). These genes may affect the risk of drug addiction via modulation of the neuroimmune system. The single-SNP test exclusively reported genome-wide significant associations between rs3782886 (SNP association: log10BF = 8.726, p = 4.842e-11) in BRAP and rs671 (SNP association: log10BF = 7.406, p = 9.333e-10) in ALDH2 and drug addiction. The haplotype test exclusively reported a genome-wide significant association (haplotype association: log10BF = 7.607, p = 3.342e-11) between a region with allelic heterogeneity on chromosome 22 and drug addiction, which may be involved in the pathway of vitamin B12 transport and metabolism, indicating a causal link between lower vitamin B12 levels and methamphetamine addiction. CONCLUSIONS: These findings provide new insights into risk-modeling and the prevention and treatment of methamphetamine and heroin dependence, which may further contribute to potential novel therapeutic approaches.

Immune and glial cell alterations in the rat brain after repeated exposure to the synthetic cannabinoid JWH-018.

The use of synthetic cannabinoid receptor agonists (SCRAs) poses major psychiatric risks. We previously showed that repeated exposure to the prototypical SCRA JWH-018 induces alterations in dopamine (DA) transmission, abnormalities in the emotional state, and glial cell activation in the mesocorticolimbic DA circuits of rats. Despite growing evidence suggesting the relationship between substance use disorders (SUD) and neuroinflammation, little is known about the impact of SCRAs on the neuroimmune system. Here, we investigated whether repeated JWH-018 exposure altered neuroimmune signaling, which could be linked with previously reported central effects. Adult male Sprague-Dawley (SD) rats were exposed to JWH-018 (0.25 mg/kg, i.p.) for fourteen consecutive days, and the expression of cytokines, chemokines, and growth factors was measured seven days after treatment discontinuation in the striatum, cortex, and hippocampus. Moreover, microglial (ionized calcium-binding adaptor molecule 1, IBA-1) and astrocyte (glial fibrillary acidic protein, GFAP) activation markers were evaluated in the caudate-putamen (CPu). Repeated JWH-018 exposure induces a perturbation of neuroimmune signaling specifically in the striatum, as shown by increased levels of cytokines [interleukins (IL) -2, -4, -12p70, -13, interferon (IFN) γ], chemokines [macrophage inflammatory protein (MIP) -1α, -3α], and growth factors [macrophage colony-stimulating factor (M-CSF), vascular endothelial growth factor (VEGF)], together with increased IBA-1 and GFAP expression in the CPu. JWH-018 exposure induces persistant brain region-specific immune alterations up to seven days after drug discontinuation, which may contribute to the behavioral and neurochemical dysregulations in striatal areas that play a role in the reward-related processes that are frequently impaired in SUD.

The dynamics of heroin and illicit opioid use disorder, casual use, treatment, and recovery: A mathematical modeling analysis.

A leading crisis in the United States is the opioid use disorder (OUD) epidemic. Opioid overdose deaths have been increasing, with over 100,000 deaths due to overdose from April 2020 to April 2021. This paper presents a mathematical model to address illicit OUD (IOUD), initiation, casual use, treatment, relapse, recovery, and opioid overdose deaths within an epidemiological framework. Within this model, individuals remain in the recovery class unless they relapse back to use and due to the limited availability of specialty treatment facilities for individuals with OUD, a saturation treatment function was incorporated. Additionally, a casual user class and its corresponding specialty treatment class were incorporated. We use both heroin and all-illicit opioids datasets to find parameter estimates for our models. Bistability of equilibrium solutions was found for realistic parameter values for the heroin-only dataset. This result implies that it would be beneficial to increase the availability of treatment. An alarming effect was discovered about the high overdose death rate: by 2046, the disorder-free equilibrium would be the only stable equilibrium. This consequence is concerning because it means the epidemic would end due to high overdose death rates. The IOUD model with a casual user class, its sensitivity results, and the comparison of parameters for both datasets, showed the importance of not overlooking the influence that casual users have in driving the all-illicit opioid epidemic. Casual users stay in the casual user class longer and are not going to treatment as quickly as the users of the heroin epidemic. Another result was that the users of the all-illicit opioids were going to the recovered class by means other than specialty treatment. However, the change in the relapse rate has more of an influence for those individuals than in the heroin-only epidemic. The results above from analyzing this model may inform health and policy officials, leading to more effective treatment options and prevention efforts.

Analysis and study of the mechanism of narcotic addiction and withdrawal.

Narcotic drugs refer to drugs that have anesthetic effects on the central nervous system, and they easily produce physical dependence and mental dependence and can be addictive due to continuous use, abuse or unreasonable use. In this paper, bioinformatics and data analysis and mining techniques were used to analyze the methylation differences in transcriptional and clinical data of narcotic addiction in public databases, to explore the mechanism of narcotic addiction, and to mine some norepinephrine drugs. This study confirmed the possibility of using norepinephrine as an auxiliary drug for drug addiction rehabilitation. In addition, we also conducted a similar analysis on the addiction of three drugs. The results showed that the differences in the body caused by the ingestion of opiates and cocaine were significantly greater than those caused by the ingestion of methamphetamine.

Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders.

Estrogen regulates a wide range of neuronal functions in the brain, such as dendritic spine formation, remodeling of synaptic plasticity, cognition, neurotransmission, and neurodevelopment. Estrogen interacts with intracellular estrogen receptors (ERs) and membrane-bound ERs to produce its effect via genomic and non-genomic pathways. Any alterations in these pathways affect the number, size, and shape of dendritic spines in neurons associated with psychiatric diseases. Increasing evidence suggests that estrogen fluctuation causes changes in dendritic spine density, morphology, and synapse numbers of excitatory and inhibitory neurons differently in males and females. In this review, we discuss the role of estrogen hormone in rodents and humans based on sex differences. First, we explain estrogen role in learning and memory and show that a high estrogen level alleviates the deficits in learning and memory. Secondly, we point out that estrogen produces a striking difference in emotional memories in men and women, which leads them to display sex-specific differences in underlying neuronal signaling. Lastly, we discuss that fluctuations in estrogen levels in men and women are related to neuropsychiatric disorders, including schizophrenia, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BPD), major depressive disorder (MDD), substance use disorder (SUD), and anxiety disorders.

Evaluation of clinical knowledge of drugs causing addiction and associated social determinants among male pharmacy and nursing students in Riyadh, Saudi Arabia - A Cross-Sectional study.

Drug abuse is a rising psychological concept in many countries, and its use among individuals is increasing. Therefore, this study aimed to assess the Knowledge and demographic factors associated with drug abuse among male pharmacy and nursing students at King Saud University, Riyadh, Saudi Arabia. This study used a cross-sectional design targeting male entry-level pharmacy and nursing students in their first and second years of Bachelor of Nursing and Doctor of Pharmacy courses. Of them, 85.3 % of the pharmacy and 75.3 % of nursing students thought that cocaine causes drug addiction, followed by heroin (pharmacy 80.7 %; nursing students 71 %), and morphine (pharmacy 75.2 %; nursing students 59.1 %). In this study, 52 % (n = 105) claimed low awareness, whereas 48 % (n = 97) indicated good understanding regarding drug addictions. Furthermore, the mean knowledge score among pharmacy students was higher (7.073 ± 2.570) in comparison to nursing (5.806 ± 2.494) (t = 3.540; p = 0. 0001). In addition, the father's occupation was found to be significantly associated with the mean knowledge score of drug addiction (F = 2.667; p = 0.034). According to the findings, 52 % of male students had insufficient knowledge about drugs that cause addiction. Age, course of study, and father's occupation all had a substantial impact on knowledge scores. The knowledge score on the complications of addictive substances was not significantly associated with the characteristics of the students (p = 0.05). As a result, we advocate for the introduction of educational initiatives that educate students about the harmful consequences of drug addiction and how to avoid issues.

Individual differences in GHB consumption in a new voluntary GHB self-administration model in outbred rats.

BACKGROUND AND PURPOSE: The use of the recreational drug gamma-hydroxybutyric acid (GHB) has increased over the past decade, concomitantly leading to a higher incidence of GHB use disorder. Evidence-based treatment interventions are hardly available and cognitive effects of long-term GHB use remain elusive. In order to study the development of GUD and the causal effects of chronic GHB consumption, a GHB self-administration model is required. EXPERIMENTAL APPROACH: Long Evans rats had access to GHB in their home cage according to a two-bottle choice procedure for 3 months. Intoxication and withdrawal symptoms were assessed using an automated sensor-based setup for longitudinal behavioral monitoring. Rats were trained in an operant environment according to a fixed ratio (FR) 1, 2, and 4 schedule of reinforcement. Addiction-like behaviors were assessed through progressive ratio-, non-reinforced-, and quinine-adulterated operant tests. In addition, the novel object recognition test and elevated plus maze test were performed before and after GHB self-administration to assess memory performance and anxiety-like behavior, respectively. KEY RESULTS: All rats consumed pharmacologically relevant levels of GHB in their home cage, and their intake remained stable over a period of 3 months. No clear withdrawal symptoms were observed following abstinence. Responding under operant conditions was characterized by strong inter-individual differences, where only a subset of rats showed high motivation for GHB, habitual GHB-seeking, and/or continued responding for GHB despite an aversive taste. Male rats showed a reduction in long-term memory performance 3 months after home-cage GHB self-administration. Anxiety-like behavior was not affected by GHB self-administration. CONCLUSION AND IMPLICATIONS: The GHB self-administration model was able to reflect individual susceptibility for addiction-like behavior. The reduction in long-term memory performance upon GHB self-administration calls for further research into the cognitive effects of chronic GHB use in humans.

Comparative Effects of Cognitive Rehabilitation and Photobiomodulation on Drug Craving in Treatment-Seeking Opioid Addicts.

Background: Drug addiction refers to a maladaptive pattern of drug use that frequently leads to substance abuse problems and accompanying cognitive and behavioral symptoms. Among the crucial criteria of drug addiction, craving stands out as a potent factor contributing to ongoing drug abuse and relapse following period of abstinence. To date, there is no definitive method for eradicating opioid cravings. The introduction of novel neurocognitive interventions, such as cognitive rehabilitation and photobiomodulation (PBM), into the realm of psychiatric treatments holds promise due to the parallels between drug addiction and other psychiatric disorders. These innovative techniques offer potential value in addressing drug addiction. Objective: This study aimed to assess and compare the efficacy of cognitive rehabilitation and PBM in alleviating drug cravings among individuals undergoing addiction treatment in clinical settings. Methods: The research used randomized clinical trial as the chosen research method. The statistical population encompassed all clients receiving treatment for addiction at clinics, selected through the convenience sampling method, with α = 0.05 significance level and an effect size of 85%. Gpower software was utilized to determine three equal groups. Sixty-three participants, each having a mean total score higher than 3 out of 5 on the Desire for Drug Questionnaire (DDQ), were randomly assigned to two experimental groups (n = 21 each) and a control group (n = 21). For the assessment of immediate and periodic opioid craving, the DDQ and the Obsessive Compulsive Drug Use Scale were used. In the low-level laser group, an 810 nm wavelength with continuous irradiation was applied twice a week at a distance of 1 cm by 1 cm to the prefrontal part of the brain for duration of 6 weeks (12 sessions). In the brain rehabilitation group, the stop signal and n-back tasks software were used twice a week for period of 6 weeks (comprising 12 sessions, each lasting 30 min). Results: The results demonstrated that each intervention significantly reduced drug craving in both the post-test and follow-up phases compared to the control group. The Bonferroni post hoc test indicated that PBM was more effective than cognitive rehabilitation in terms of working memory (WM) and inhibitory control for reducing drug craving (p < 0.05). Conclusions: While both PBM and cognitive rehabilitation targeting WM and inhibitory control effectively reduced opioid drug craving, low-level laser therapy proved to be more effective than cognitive rehabilitation in this regard.

Oral self-administration of pregabalin in a mouse model and the resulting drug addiction features.

Prescription drug abuse is an issue that is rapidly growing globally. Pregabalin, an anticonvulsant, analgesic, and anxiolytic medication, is effective in the management of multiple neurological disorders; however, there is increasing concern regarding its widespread illicit use. It has been previously reported in mice that pregabalin can induce conditioned place preference. In this current investigation, the potential of pregabalin to elicit free-choice drinking in a mouse model of drug addiction, and its effect on recognition and withdrawal behaviors after forced abstinence, were studied. Twenty-two male BALB/c mice were randomly divided into three groups (n = 7-8/group); control, pregabalin-30, and pregabalin-60. The study had three phases: habituation (days 1-5) with free water access, free-choice drinking (days 6-13) with pregabalin groups receiving one water and one pregabalin bottle, and forced abstinence (days 14-21) with free water access. On day 13, the first open field test was conducted, followed by the Novel Object Recognition Test. On day 21, the second open field test was performed, followed by the Tail Suspension Test and Forced Swimming Test. Pregabalin elicited voluntary drinking in the higher-dose group, concurrently causing a decline in recognition memory performance in the novel object recognition test. Moreover, pregabalin induced withdrawal behavior after a period of forced abstinence in the forced swimming and tail suspension tests. This is the first report to establish an animal model of free-choice pregabalin drinking that may be used for further molecular studies and targeted therapy for pregabalin addiction.

Why do people use drugs? A neglected question.

The aim of this article is to revisit the multivariate causes of drug use. From the initial drive to experiment, to a progression towards dependence, this review endeavours to extrapolate the aetiology of causation. In doing so, prevalence of, and attitudes towards drug use are firstly examined. Influences on why people use illicit drugs are subsequently explored through the lens of established risk factors. Drug use and dependence are embedded within a complex interplay of invidual, genetic, cultural, and socio-economic components. By exploring the aetiology of drug use in a holistic sense, this will not only aid the therapeutic quality of intervention from clinicians, but enable the development of more comprehensive and tailored intervention plans in supporting recovery.

Biperiden reverses the increase in 50-kHz ultrasonic vocalizations but not the increase in locomotor activity induced by cocaine.

Cocaine use disorder (CUD) is a worldwide public health problem, associated with severe psychosocial and economic impacts. Currently, no FDA-approved treatment is available for CUD. However, an emerging body of evidence from clinical and preclinical studies suggests that biperiden, an M1 muscarinic receptor antagonist, presents potential therapeutic use for CUD. These studies have suggested that biperiden may reduce the reinforcing effects of cocaine. It is well established that rodents emit 50-kHz ultrasonic vocalizations (USV) in response to natural rewards and stimulant drugs, including cocaine. Nonetheless, the effects of biperiden on the cocaine-induced increase of 50-kHz USV remains unknown. Here, we hypothesized that biperiden could antagonize the acute effects of cocaine administration on rat 50-kHz USV. To test this hypothesis, adult male Wistar rats were divided into four experimental groups: saline, 5 mg/kg biperiden, 10 mg/kg cocaine, and biperiden/cocaine (5 and 10 mg/kg, i.p., respectively). USV and locomotor activity were recorded in baseline and test sessions. As expected, cocaine administration significantly increased the number of 50-kHz USV. Biperiden administration effectively antagonized the increase in 50-kHz USV induced by cocaine. Cocaine administration also increased the emission of trill and mixed 50 kHz USV subtypes and this effect was antagonized by biperiden. Additionally, we showed that biperiden did not affect the cocaine-induced increase in locomotor activity, although biperiden administration per se increased locomotor activity. In conclusion, our findings indicate that administering biperiden acutely reduces the positive affective effects of cocaine, as demonstrated by its ability to inhibit the increase in 50-kHz USV.

Microglia-mediated calcium-permeable AMPAR accumulation in the nucleus accumbens drives hyperlocomotion during cocaine withdrawal.

During withdrawal from cocaine, calcium permeable-AMPA receptors (CP-AMPAR) progressively accumulate in nucleus accumbens (NAc) synapses, a phenomenon linked to behavioral sensitization and drug-seeking. Recently, it has been suggested that neuroimmune alterations might promote aberrant changes in synaptic plasticity, thus contributing to substance abuse-related behaviors. Here, we investigated the role of microglia in NAc neuroadaptations after withdrawal from cocaine-induced conditioned place preference (CPP). We depleted microglia using PLX5622-supplemented diet during cocaine withdrawal, and after the place preference test, we measured dendritic spine density and the presence of CP-AMPAR in the NAc shell. Microglia depletion prevented cocaine-induced changes in dendritic spines and CP-AMPAR accumulation. Furthermore, microglia depletion prevented conditioned hyperlocomotion without affecting drug-context associative memory. Microglia displayed fewer number of branches, resulting in a reduced arborization area and microglia control domain at late withdrawal. Our results suggest that microglia are necessary for the synaptic adaptations in NAc synapses during cocaine withdrawal and therefore represent a promising therapeutic target for relapse prevention.

From existing to living: Exploring the meaning of recovery and a sober life after a long duration of a substance use disorder.

Aim: The study explores how former patients with substance use disorder (SUD) experience the benefits and challenges of a reoriented identity and way of living. Methods: Semi-structured interviews were conducted with 10 participants who had completed treatment for SUD and considered themselves either recovered or in an ongoing rehabilitation process. Interview transcripts were analysed using the content analysis approach. Results: The analysis furthers our understanding of several purposeful aspects of a reorientation towards a sober life in terms of: (1) avoiding illegal drugs, (2) avoiding contact with the substance use relations and milieu, (3) renewing relations and social network, (4) daily occupation, (5) discovering the value of the great, little things in everyday life, (6) new coping strategies, and (7) developing a new identity. Conclusion: The study indicates that rehabilitation from SUDs should take a broader focus than just sobriety. With attention to the present findings, a focus on psychosocial aspects of recovery could contribute to a more overarching framework for SUD treatment.

Optimizing Digital Tools for the Field of Substance Use and Substance Use Disorders: Backcasting Exercise.

BACKGROUND: Substance use trends are complex; they often rapidly evolve and necessitate an intersectional approach in research, service, and policy making. Current and emerging digital tools related to substance use are promising but also create a range of challenges and opportunities. OBJECTIVE: This paper reports on a backcasting exercise aimed at the development of a roadmap that identifies values, challenges, facilitators, and milestones to achieve optimal use of digital tools in the substance use field by 2030. METHODS: A backcasting exercise method was adopted, wherein the core elements are identifying key values, challenges, facilitators, milestones, cornerstones and a current, desired, and future scenario. A structured approach was used by means of (1) an Open Science Framework page as a web-based collaborative working space and (2) key stakeholders' collaborative engagement during the 2022 Lisbon Addiction Conference. RESULTS: The identified key values were digital rights, evidence-based tools, user-friendliness, accessibility and availability, and person-centeredness. The key challenges identified were ethical funding, regulations, commercialization, best practice models, digital literacy, and access or reach. The key facilitators identified were scientific research, interoperable infrastructure and a culture of innovation, expertise, ethical funding, user-friendly designs, and digital rights and regulations. A range of milestones were identified. The overarching identified cornerstones consisted of creating ethical frameworks, increasing access to digital tools, and continuous trend analysis. CONCLUSIONS: The use of digital tools in the field of substance use is linked to a range of risks and opportunities that need to be managed. The current trajectories of the use of such tools are heavily influenced by large multinational for-profit companies with relatively little involvement of key stakeholders such as people who use drugs, service providers, and researchers. The current funding models are problematic and lack the necessary flexibility associated with best practice business approaches such as lean and agile principles to design and execute customer discovery methods. Accessibility and availability, digital rights, user-friendly design, and person-focused approaches should be at the forefront in the further development of digital tools. Global legislative and technical infrastructures by means of a global action plan and strategy are necessary and should include ethical frameworks, accessibility of digital tools for substance use, and continuous trend analysis as cornerstones.