The first survey was conducted from March 2016 to September 2017 and assessed the average harm of 33 substances in in 5 dimensions (physical harm to users, psychological harm to users, social harm to users, physical and psychological harm to others, and social harm to others). As shown in Supplementary Figure 1, these dimensions were defined by 16 criteria, which have been validated in several studies of this type ( 5, 9, 10) (see Supplementary Materials—Methods Section). Overall harm to users and overall harm to others comprised 3 (physical, psychological, social) dimensions and 2 (physical & psychological, social) dimensions, respectively (for details see Supplementary Figure 1). The assessments were carried out using 5-point scales (from “not harmful” to “extremely harmful”). Across England and Wales, there were 234,101 people in treatment at any time during 2018. The most common primary drug reported by people starting treatment in Great Britain in 2018 was heroin, with cannabis the second most common. In Northern Ireland in 2017, cannabis was the most common primary substance. 4. Main drugs used in the UK 4.1 Opioids Numerous studies have found an association between use of anticholinergic medicines and adverse outcomes related to physical function, cognition and falls in older people [ 2, 4, 29- 31]. Pasina et al. compared anticholinergic burden derived from both ACB and ARS scales and found strong associations with impairment in cognitive and functional outcomes [ 27]. A study conducted by Rudolph et al. validated higher ARS scores were associated with increased risk of both peripheral and central anticholinergic adverse effects in older people [ 19]. Furthermore, Campbell et al. and Fox et al. conducted studies using ACB scale and found that the use of definite anticholinergics increased the risk of cognitive impairment among older people [ 32, 33]. Overall, research has shown that use of medicines with anticholinergic activity among older people is associated with physical and cognitive decline [ 34, 35]. A citation analysis was performed to identify and compare the clinical utility of individual anticholinergic rating scales to quantify anticholinergic burden and to evaluate its association with adverse outcomes (cognitive, functional, mortality) in older people. Studies that used the rating scales for assessing the adverse outcomes in older people are reported in this review. In 2018, opioids were mentioned or implicated in around 80% of deaths registered in each of the countries of the UK, with the highest proportion in Scotland (86%). 4.2 Cocaine

A drug user is defined as frequent if they have taken the drug more than once a month in the last year. Personal well-being Pasina L, Djade CD, Lucca U, Nobili A, Tettamanti M, Franchi C, et al. Association of anticholinergic burden with cognitive and functional status in a cohort of hospitalized elderly: comparison of the anticholinergic cognitive burden scale and anticholinergic risk scale: results from the REPOSI study. Drugs Aging. 2013;30(2):103–12.

of Psychiatry, Psychotherapy and Psychosomatic Medicine, Evangelisches Krankenhaus Castrop-Rauxel, Academic Teaching Hospital of the University of Duisburg/Essen, Castrop-Rauxel, Germany The number of MDMA-related deaths registered in the UK in 2018 was the highest on record, but was still much lower than the number of deaths involving heroin, benzodiazepines or cocaine. In England and Wales, there was an increase in the number of deaths among people aged under 30. 4.5 Ketamine for Interdisciplinary Addiction Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Approximately 1 in 11 adults aged 16 to 59 years (9.2%; approximately 3 million adults) and approximately 1 in 5 adults aged 16 to 24 years (18.6%; approximately 1.1 million adults) reported last year drug use in the year ending June 2022.

Koshoedo S, Soiza RL, Purkayastha R, Mangoni AA. Anticholinergic drugs and functional outcomes in older patients undergoing orthopaedic rehabilitation. Am J Geriatr Pharmacother. 2012;10(4):251–7. ADS=Anticholinergic Drug Scale; ABC=Anticholinergic Burden Classification; CrAS=Clinician-rated Anticholinergic Score; ARS=Anticholinergic Risk Scale; ACB=Anticholinergic Cognitive Burden Scale; AAS=Anticholinergic Activity Scale; ACL=Anticholinergic Loading Scale; SAA=Serum Anticholinergic Activity. Drug use may not be independently related to lifestyle factors but instead affected by factors such as age, as younger people may be more likely to visit nightclubs or bars. Household and area characteristicsUusvaara J, Pitkala K, Kautiainen H, Tilvis R, Strandberg T. Association of Anticholinergic Drugs with Hospitalization and Mortality among Older Cardiovascular Patients. Drugs Aging. 2011;28(2):131–8. Nishtala PS, McLachlan AJ, Bell JS, Chen TF. Determinants of antipsychotic medication use among older people living in aged care homes in Australia. Int J Geriatr Psychiatry. 2010;25(5):449–57. There was a reduction in the number of adults reporting having taken any Class A drug (see Glossary for definition) in the last year compared with the year ending March 2020. Annual report and data tables from the UK Focal Point on Drugs on the national prevalence, impact, prevention, and treatment of drug use.

A systematic review was conducted to assess the effectiveness of anticholinergic burden scales in predicting adverse outcomes in older individuals. This is particularly relevant as the anticholinergic burden has been associated with negative outcomes in aging populations. Approximately 1 in 11 adults aged 16 to 59 years (9.2%; approximately 3 million adults) and approximately 1 in 5 adults aged 16 to 24 years (18.6%; approximately 1.1 million adults) reported last year drug use in the year ending June 2022; there was no change compared with the year ending March 2020.

StatPearls [Internet].

Anticholinergic Cognitive Burden Scale (ACB) developed by Boustani et al. [ 24] is based on a systematic literature review of medicines with known anticholinergic activity. The ACB scale included medicines that were likely to have a negative impact on cognition [ 27, 28]. A multi-disciplinary panel assessed individual drugs to have none, possible, or definite anticholinergic properties with a score ranging from 0 to 3. ACB scale reported 88 medicines with known anticholinergic activity. Studies that employed the ACB scale have shown that higher anticholinergic burden predicts cognitive impairment in older people. In addition, the study conducted by Pasina L et al. showed that anticholinergic burden quantified by the ACB scale predicted impairment in physical functioning [ 27]. Rudolph JL, Salow MJ, Angelini MC, ET AL (2008). The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. doi: 10.1001/archinternmed.2007.106.

There has been an increase in the prevalence of 15 year olds in England who have used benzodiazepines at some time in their life, from 0.5% in 2014 to 1.7% in 2018. Prevalence has also risen in Scotland, from 1.7% in 2015 to 2.8% in 2018. This has coincided with reports of increased alprazolam use (‘Xanax’) among school children. 4.4 MDMA and ecstasy While this is the first comparable survey data with pre-coronavirus (COVID-19) pandemic data, they are not National Statistics and caution must be taken when using these data. The CSEW statistics presented in this release are based on nine months of data collection between October 2021 and June 2022, rather than the normal 12-month interview period and are based on a lower response rate, which may affect the quality of the estimates. Significance testing has been conducted to compare estimates for the year ending June 2022 with year ending March 2020, year ending March 2012 (ten-year comparison) and year ending December 1995 (earliest data available) to understand trends over time where possible. Other comparison years have been used where these data are not available. The citation analysis of individual scales revealed that ACB scale by Boustani et al. [ 24] was the most frequently validated expert based anticholinergic scale on adverse outcomes (N=13) followed by ARS [ 19] (N=11], ADS by Carnahan et al. [ 9] (N=9), CrAS scale by Han et al. [ 22] (N=3) and 2 other scales [ 23, 26]. The review found only two RCTs that showed an association with higher anticholinergic burden and adverse outcomes. The RCT that used the CrAS scale to quantify anticholinergic burden showed a positive association with functional outcome and quality of life and the RCT using the ADS scale reported a negative association with cognitive functioning. The adverse outcomes reported in the cohort studies included mainly cognitive and physical outcomes. The cognitive outcomes reported included mild-cognitive impairment, confusion, dizziness, falls, delirium, psychomotor speed and executive function. The functional outcomes reported were pertaining to activity of daily living, instrumental activity of daily living, quality of life, physical function, hospitalisation, length of hospital stay, and mortality. A detailed summary of validated studies for individual anticholinergic scales with critical appraisal is illustrated in Table 3. Lowry E, Woodman RJ, Soiza RL, Mangoni AA. Clinical and demographic factors associated with antimuscarinic medication use in older hospitalized patients. Hosp Pract (1995). 2011;39(1):30–6.

How to use these comparators

Using similar methodologies other anticholinergic risk scales have been developed in Australia [ 23], Norway [ 26], France [ 25] and U.S.A. [ 22]. The CrAS scale by Han et al. was validated in palliative care and veteran home settings for cognitive and functional outcomes. The Anticholinergic Activity Scale (AAS) by Ehrt et al., and Anticholinergic Loading Scale (ACL) by Sittironnarit et al. were validated for only cognitive outcomes. In 2014, a group of 40 medical and non-medical addiction experts from 21 EU countries came to the same conclusion ( 10). This survey included 20 substances ( 10). In the interim, as in other Western countries, there have been shifting patterns of substance abuse trends as well as political framework conditions in Germany, especially