Therapeutic Potential of Psychedelic Drugs: Navigating High Hopes, Strong Claims, Weak Evidence, and Big Money.

Therapeutic claims about many psychedelic drugs have not been evaluated in any studies of even modest rigor. The science of psychedelic drugs is strengthening however, making it easier to differentiate some promising findings amid the hype that suffuses this research area. Ketamine has risks of adverse side effects (e.g., addiction and cystitis), but multiple studies suggest it can benefit individuals with treatment-resistant depression. Other therapeutic signals from psychedelic drug research that merit rigorous replication studies include 3,4-Methylenedioxymethamphetamine (MDMA) for post-traumatic stress disorder (PTSD) and psilocybin for depression, end of life dysphoria, and alcohol use disorder. The precise mechanisms through which psychedelic drugs can produce benefit and harm are not fully understood. Rigorous research is the best path forward for evaluating the therapeutic potential and mechanisms of psychedelic drugs. Policies governing the clinical use of these drugs should be informed by evidence and prioritize the protection of public health over the profit motive.

Assessing daily patterns in stimulant use during the COVID-19 pandemic in Melbourne, Australia using wastewater analysis.

During the COVID-19 pandemic, one of Australia's biggest cities, Melbourne, experienced three major isolation ("lockdown") periods in 2020 (160 days) and in 2021 (111 days) which makes it one of the most locked down cities world-wide. This study assessed how the pandemic affected temporal trends in methamphetamine, MDMA and cocaine consumption using wastewater-based epidemiology. Daily samples were collected for most of 2020 and 2021 (n = 660 days). Concentrations were measured using direct-injection LC-MS/MS and back-calculated to consumption estimates. Results indicate that methamphetamine use was increasing before the first lockdown and decreased after the end of the first lockdown in 2020. Methamphetamine trends appeared to have remained steady throughout the second lockdown period before increasing steeply after it ended. For most of 2020, cocaine use remained steady, with an increase after the second lockdown. MDMA use decreased after the start of the first lockdown and remained steady throughout most of 2020 and 2021. In comparison to 2020, trends in 2021 were less variable and stimulant use did not appear to be as associated with COVID-19 restrictions. Overall, this study was able to show the impact of lockdown periods and the related social restrictions on illicit stimulant use. ENVIRONMENTAL IMPLICATION: Illicit drugs are hazardous chemicals, of concern both to humans and the environment. While studies have been undertaken to understand their temporal trends, this work utilizes wastewater-based epidemiology and daily sampling to provide a comprehensive understanding of the impact of the COVID-19 pandemic on the use of methamphetamine, MDMA and cocaine on one of the most locked-down cities in the world. Understanding the consequences of this significant intervention on illicit drug use could provide valuable insights into its potential environmental impact.

Crafting effective regulatory policies for psychedelics: What can be learned from the case of cannabis?

The turn of the century brought a resurgence of interest in psychedelics as a treatment for addiction and other psychiatric conditions, accompanied by extensive positive media attention and private equity investment. Government regulatory bodies in Australia, Israel, Canada and the United States now permit use of psychedelics for medical purposes. In the United States, citizen action and corporate financing have led to petitions and ballot initiatives to legalize psilocybin and other psychedelics for medical and recreational use. Given this momentum, policymakers must grapple with important questions that define whether and how psychedelics are made available to the public, as well as how companies produce and promote them. The current push to broaden the production, sale, and use of psychedelics bears many parallels to the movement to legalize cannabis in the United States and other nations-most notably, the use of poorly-evidenced therapeutic claims to create a de facto recreational market via the health care system. Experience with cannabis highlights the value of debating the question of legalization for nonmedical use as such rather than misrepresenting it as a medical issue. The lessons of cannabis policy also suggest a need to challenge hyping of psychedelic research findings; to promote rigorous clinical research on dosing and potency; to minimize the influence of for-profit industry in shaping policies to their economic advantage; and to coordinate federal, state, and local governments to regulate the manufacture, sale and distribution of psychedelic drugs (regardless of whether they are legalized for medical and/or recreational use).

Commentary: The Conflict Between Protecting Public Health and Raising Tax Revenue.

When Canada created a legal market for cannabis, it gave priority to public health by restricting marketing using branding and promotion via social and other media sources. These restrictions to protect the public from harmful use are under increasing pressure from the legal cannabis industry, which claims that they prevent them from outcompeting and replacing the illicit market. Public health advocates are reasonably concerned that these restrictions will not hold given our experience with alcohol, tobacco and gambling where governments' fiscal dependence on tax revenue favours the liberalization of regulation.

Seven-years of alcohol consumption in Australia by wastewater analysis: Exploring patterns by remoteness and socioeconomic factors.

BACKGROUND: Wastewater analysis provides a complementary measure of alcohol use in whole communities. We assessed absolute differences and temporal trends in alcohol consumption by degree of remoteness and socioeconomics indicators in Australia from 2016 to 2023. METHODS: Alcohol consumption estimates from 50 wastewater treatment plants (WWTP) in the Australian National Wastewater Drug Monitoring Program were used. Trends were analysed based on 1) site remoteness: Major Cities, Inner Regional and a combined remoteness category of Outer Regional and Remote, and 2) using two socioeconomic indexes from the Australian Bureau of Statistics (ABS) relating to advantage and disadvantage for Income, education, occupation, and housing. RESULTS: Consumption estimates were similar for Major Cities and Inner Regional areas (14.3 and 14.4L/day/1000 people), but significantly higher in Outer Regional and Remote sites (18.6L/day/1000 people). Consumption was decreasing in Major cities by 4.5% annually, Inner Regional by 2.4%, and 3.5% in the combined Outer Regional and Remote category. Consumption estimates were higher in socioeconomically advantaged quartiles than those of lower advantage (0%-25% mean = 13.0, 75%-100% mean = 17.4). Consumption in all quartiles decreased significantly over the 7 year period with annual rates of decrease of 0.9%, 3.7%, 3.6%, and 3.0% for the lowest to highest quartile, respectively. CONCLUSIONS: Declines in Australian alcohol consumption have been steeper in large urban areas than regional and remote areas. There were smaller annual decreases in the most socioeconomically disadvantaged areas. If continued, these trends may increase Australian health inequalities. Policy and prevention work should be appropriately targeted to produce more equitable long-term outcomes.

Effectiveness of cannabis use and cannabis use disorder interventions: a European and international data synthesis.

This data synthesis examined the effectiveness of behavioural and pharmacological approaches for cannabis treatment. We integrated findings from high level evidence studies and prioritised data from Europe when available. The synthesis found that only a relatively small number of published behavioural and pharmacological studies on cannabis interventions have been conducted in Europe. Applying both European and non-European data, it was found that Cognitive Behavioural Therapy (CBT) and/or Motivational Enhancement Therapy (MET) improved short-term outcomes in the frequency of cannabis use and dependency severity, although abstinence outcomes were less consistent. These improvements were typically not maintained nine months after treatment. CBT and MET (or combined CBT + MET) treatments that extend beyond four sessions were more effective than fewer sessions over a shorter duration. Combining CBT or MET (or combined CBT + MET) with adjunctive Contingency Management (CM) improved therapeutic outcomes. No pharmacotherapies have been approved for the management of cannabis use, cannabis use disorders or cannabis withdrawal. Despite only weak evidence to support the use of pharmacological agents, some are used 'off-label' to manage withdrawal symptoms outside clinical trials.

A retrospective study of the characteristics and toxicology of cases of lysergic acid diethylamide (LSD)- and psilocybin-related death in Australia.

BACKGROUND AND AIMS: Lysergic acid diethylamide (LSD) and psilocybin are used as recreational drugs, and there is renewed interest in their clinical use. The current study aimed to (1) determine the circumstances of death and case characteristics of LSD- and psilocybin-related death in Australia, 2000-23; and (2) determine the toxicological profile and major autopsy findings of these cases. METHODS: This was a retrospective exploratory study of all cases of LSD- and psilocybin-related death in Australia, 2000-23, retrieved from the National Coronial Information System. RESULTS: A total of 43 cases were identified: 33 LSD and 10 psilocybin. The median ages were 24 years [interquartile range (IQR) = 13, range = 16-53] (LSD) and 26 years (IQR = 18.5, range = 20-58) (psilocybin), and fewer than five cases were female. The most common circumstance of death among both groups was traumatic accident (LSD 36.4%, psilocybin 40.0%). There were 12 cases of self-harm, all of which involved LSD, all by physical means. In a fifth, death was attributed to multiple drug toxicity (LSD 18.2%, psilocybin 20.0%). In one case, death was attributed solely to LSD toxicity, while in a further two cases death was attributed to a cardiovascular event following LSD consumption (one LSD only, one multiple drug toxicity). In four psilocybin cases, the cause of death was undetermined. The most common clinical presentation was severe agitation (LSD 27.3%, psilocybin 20.0%). Median blood concentrations were LSD 0.8 µg/l (IQR = 1.7, range = 0.1-3), psilocin 20 µg/l (IQR = 53.5, range = 6-83). LSD was the only drug present in 25.0% of LSD cases and psilocybin in 20.0% of psilocybin cases. Pre-existing organ pathology was uncommon. CONCLUSIONS: Lysergic acid diethylamide (LSD)- and psilocybin-related death in Australia from 2000 to 2023 was primarily due to traumatic injury, whether through accident or self-harm. Cases of acute toxic reactions that were attributed solely to LSD were rare.

Will Australia's tightened prescription system reduce nicotine vaping among young people?

BACKGROUND: Australia introduced a prescription only policy for e-cigarettes in 2011 to prevent uptake among youth while allowing smokers to access e-cigarettes for cessation. This is one of the restrictive forms of regulation for e-cigarettes recommended by the World Health Organisation. AIMS: To assess whether the policy has prevented e-cigarette youth uptake and facilitated smokers' access to e-cigarettes for cessation; and to examine a proposed toughening of the policy. METHODS: An analysis of survey and administrative data on e-cigarette use and smoking and a critical analysis of the contents of submissions to parliamentary inquiries into the policy. RESULTS: E-cigarette use among youth and young adults has increased steeply since 2016 but very few of these products have been obtained through the prescription system, because medical authorities discourage their use. A policy change in 2021 to increase the prescription of e-cigarettes has not reduced e-cigarette use among youth and only marginally increased rates of prescribing. Australian policy makers have nonetheless tightened the prescription system by banning any use of e-cigarettes unless prescribed by a doctor and dispensed by a pharmacist. IMPLICATIONS: Australia's tightened prescription policy for e-cigarettes may reduce adolescent vaping but at the risk of reducing smokers' access to e-cigarettes and increasing the size of the illicit market for combustible cigarettes and e-cigarettes. A more effective policy would allow vapes to be sold as consumer products by licensed tobacconists under regulations that require prior product approval, plain packaging, bans on their promotion and enforced age restrictions on purchases.

Restricting supply of tobacco products to pharmacies: a scoping review.

OBJECTIVE: We synthesised the published literature on proposals to restrict tobacco supply to pharmacies, covering (1) policy concept/rationale/attempts, (2) policy impact and implementation and (3) policy and research recommendations. DATA SOURCES: We searched eight databases (PubMed, CINAHL, Scopus, Web of Science, Embase, IPA, ProQuest and OATD) for publications with at least an English-language abstract. We searched reference lists of included publications manually. STUDY SELECTION: One author screened all publications, and a second author reviewed a 10% subset. We focused on approaches to restrict the supply of tobacco products to pharmacies, without any restrictions on study design, location, participants or publication date. DATA EXTRACTION: Data extraction adhered to the JBI Scoping Review Methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. DATA SYNTHESIS: We included 18 publications. Among the 13 studies conducted in specific geographical contexts, 8 were from Aotearoa/New Zealand. Most publications (n=8) focused on effectiveness domains, indicating potential reductions in retailer density, smoking prevalence, disease burden, cost and increased opportunities for cessation advice. Seven explored policy acceptability among experts, pharmacists and people who smoke. Publications noted that pharmacy-only supply aligns with other programmes involving pharmacists, such as needle exchange programmes, but conflicts with efforts to phase out tobacco sales from the US and Canadian pharmacies. CONCLUSIONS: Progress in tobacco retailing policy (eg, licensing, retailer incentives) and research (eg, assessment of policy equity and durability, application in other geographical contexts) are needed before a pharmacy-only tobacco supply model would be feasible.

The prevalence of cannabis use disorders in people who use medicinal cannabis: A systematic review and meta-analysis.

BACKGROUND: The prevalence of cannabis use disorders (CUDs) in people who use cannabis recreationally has been estimated at 22%, yet there is a dearth of literature exploring CUDs among people who use medicinal cannabis. We aimed to systematically review the prevalence of CUDs in people who use medicinal cannabis. METHODS: In our systematic review and meta-analysis, we followed PRISMA guidelines and searched three databases (PsychInfo, Embase and PubMed) to identify studies examining the prevalence of CUDs in people who use medicinal cannabis. Meta-analyses were calculated on the prevalence of CUDs. Prevalence estimates were pooled across different prevalence periods using the DSM-IV and DSM-5. RESULTS: We conducted a systematic review of 14 eligible publications, assessing the prevalence of CUDs, providing data for 3681 participants from five different countries. The systematic review demonstrated that demographic factors, mental health disorders and the management of chronic pain with medicinal cannabis were associated with an elevated risk of CUDs. Meta-analyses were conducted on the prevalence of CUDs. For individuals using medicinal cannabis in the past 6-12 months, the prevalence of CUDs was 29% (95% CI: 21-38%) as per DSM-5 criteria. Similar prevalence was observed using DSM-IV (24%, CI: 14-38%) for the same period. When including all prevalence periods and using the DSM-5, the prevalence of CUDs in people who use medicinal cannabis was estimated at 25% (CI: 18-33%). CONCLUSIONS: The prevalence of CUDs in people who use medicinal cannabis is substantial and comparable to people who use cannabis for recreational reasons, emphasizing the need for ongoing research to monitor the prevalence of CUDs in people who use medicinal cannabis.

Sensitivity analysis of paediatric knee kinematics to the graft surgical parameters during anterior cruciate ligament reconstruction: A sequentially linked neuromusculoskeletal-finite element analysis.

BACKGROUND AND OBJECTIVE: Incidence of paediatric anterior cruciate ligament (ACL) rupture has increased substantially over recent decades. Following ACL rupture, ACL reconstruction (ACLR) surgery is typically performed to restore passive knee stability. This surgery involves replacing the failed ACL with a graft, however, surgeons must select from range of surgical parameters (e.g., type, size, insertion, and pre-tension) with no robust evidence guiding these decisions. This study presents a systemmatic computational approach to study effects of surgical parameter variation on kinematics of paediatric knees. METHODS: This study used sequentially-linked neuromusculoskeletal (NMSK) finite element (FE) models of three paediatric knees to estimate the: (i) sensitivity of post-operative knee kinematics to four surgical parameters (type, size, insertion, and pre-tension) through multi-input multi-output sensitivity analysis; (ii) influence of motion and loading conditions throughout stance phase of walking gait on sensitivity indices; and (iii) influence of subject-specific anatomy (i.e., knee size) on sensitivivty indices. A previously validated FE model of the intact knee for each subject served as a reference against which ACLR knee kinematics were compared. RESULTS: Sensitivity analyses revealed significant influences of surgical parameters on ACLR knee kinematics, albeit without discernible trend favouring any one parameter. Graft size and pre-tension were primary drivers of variation in knee translations and rotations, however, their effects fluctuated across stance indicating motion and loading conditions affect system sensitivity to surgical parameters. Importantly, the sensitivity of knee kinematics to surgical parameter varied across subjects, indicating geometry (i.e., knee size) influenced system sensitivity. Notably, alterations in graft parameters yielded substantial effects on kinematics (normalized root-mean-square-error > 10 %) compared to intact knee models, indicating surgical parameters vary post-operative knee kinematics. CONCLUSIONS: Overall, this initial study highlights the importance of surgical parameter selection on post-operative kinematics in the paediatric ACLR knee, and provides evidence of the need for personalized surgical planning to ultimately enhance patient outcomes.

E-cigarettes: A framework for comparative history and policy.

BACKGROUND: England, Australia and the United States have approached the regulation of e-cigarettes in very different ways, yet all three countries have appealed to the concept of evidence as underpinning policy responses. We compared these policy responses using a combination of the methodologies of historians and policy scientists in order to elucidate the factors that had influenced policy in each country. ARGUMENT/ANALYSIS: Each country's evidence and values intersected in different ways, producing very different responses within specific national contexts and histories. Our analysis accordingly emphasized the historical precursors of the policy issues raised by e-cigarettes and placed the policy debate within the context of regulatory bodies and the networks of researchers and advocates who influenced policy. Issues also of importance were the nature of the state; political context; the pre-history of nicotine for smoking cessation; the role of activism and its links with government; the influence of harm reduction ideas from drugs and HIV; and finally, whom policy was perceived to benefit. In the United Kingdom, based on this pre-history of the smoking issue, it was the existing smoker, while in the United States and Australia, protecting children and adolescents has played a central role. CONCLUSIONS: Structural and historical factors appear to underpin differences in e-cigarette policy development in England, Australia and the United States.

Cannabis use and cannabis use disorders and their treatment in the Europe.

This paper introduces the special issue on cannabis use in Europe. It describes data on the prevalence of cannabis use in Europe and the more limited data on the prevalence of cannabis use disorders, one of the most common forms of drug problem treated in many countries in Europe. It summarises what research has indicated about the adverse effects of acute and chronic cannabis use and discusses potential health system responses that may reduce some of these harms. These include public education about the risks of cannabis use; screening and brief interventions in primary medical settings; and specialist treatment for cannabis use disorders. It briefly indicates the special issues that may need to be addressed in dealing with the high rates of comorbidity between cannabis use disorders, other types of drug use disorders, and common mental disorders.

Designing observational studies for credible causal inference in addiction research-Directed acyclic graphs, modified disjunctive cause criterion and target trial emulation.

Randomized controlled trials (RCTs) are considered the gold standard for causal inference. With a sufficient sample size, randomization removes confounding up to the time of randomization and allows the treatment effect to be isolated. However, RCTs may have limited generalizability and transportability and are often not feasible in addiction research due to ethical or logistical constraints. The importance of observational studies from real-world settings has been increasingly recognized in research on health. This paper provides an overview of modern approaches to designing observational studies that enable causal inference. It illustrates three key techniques, Directed Acyclic Graphs (DAGs), modified Disjunctive Cause Criterion and Target Trial Emulation, and discusses the strengths and limitations of their applications.

Wastewater-based monitoring of the nitazene analogues: First detection of protonitazene in wastewater.

Synthetic opioids, particularly the nitazene analogues class, have become a public health concern due to their high potency. Wastewater-based epidemiology can detect community use of these compounds. The objective of this work was to detect nitazene analogues in wastewater from samples collected from eight sites in the United States. Influent wastewater samples were collected from eight sites in seven states (Arizona, Oregon, New Mexico, Illinois, New Jersey, Washington and Georgia) in the United States. Samples were collected from each site on three days between 27 December 2022 and 4 January 2023, acidified on collection, stored frozen and shipped to Arizona State University (Tempe, AZ) for sample processing. Samples were then shipped to The University of Queensland (Brisbane, Australia) for sample analysis. Protonitazene was found in samples collected from two sites in Washington and Illinois. The concentration was estimated up to 0.5 ng/L, with estimated excreted mass loads up to 0.3 mg/day/1000 people. This work has shown that it is possible to detect nitazene analogues in wastewater using a combination of sample pre-concentration and sensitive instrumentation, thereby further expanding the utility of wastewater-based epidemiology.