A summary of the health harms of drugs Technical document 1 Health harms of drugs Reader information box Document purpose For information Gateway reference 16365 Title A summary of the health harms of drugs: technical document Author The Centre for Public Health, Faculty of Health & Applied Social Science, Liverpool John Moore's University, on behalf of the Department of Health and National Treatment Agency for Substance Misuse Publication date August 2011 Target audience Medical directors, directors of public health, allied health professionals, GPs, non-medical policy and communications teams across government, and drug treatment and recovery services, commissioners and service users Circulation list Government drug strategy partners, including colleagues at the FRANK drugs information and advice service, drug treatment and recovery services, clinicians, commissioners and service users Description This technical document accompanies ‘A summary of the health harms of drugs’. It summarises methodological aspects of the work; articles identified through literature searches; and references for literature used Cross reference A summary of the health harms of drugs Superseded documents Dangerousness of drugs – a guide to the risks and harms associated with substance misuse Action required N/A Timing N/A Contact details Alex Fleming Policy information manager National Treatment Agency for Substance Misuse 6th Floor Skipton House 80 London Road London SE1 6LH [email protected] 2 Health harms of drugs A summary of the health harms of drugs Technical document August 2011 Prepared by Lisa Jonesa, Geoff Batesa, Mark Bellisa, Caryl Beynona, Paul Duffya, Michael Evans- Browna, Adam Mackridgeb, Ellie McCoya, Harry Sumnalla, Jim McVeigha aCentre for Public Health, Research Directorate, Faculty of Health & Applied Social Sciences bSchool of Pharmacy & Biomolecular Sciences, Liverpool John Moores University For further information about this document please contact: Lisa Jones Evidence Review and Research Manager, Substance Use Centre for Public Health Research Directorate, Faculty of Health and Applied Social Sciences Liverpool John Moores University Henry Cotton Campus (2nd floor), 15-21 Webster Street, Liverpool L3 2ET Tel: (0151) 231 4452 Email: [email protected] About this document This technical report accompanies ‘A summary of the health harms of drugs: Final report’. It includes a summary of the main methodological aspects of the work, a series of evidence tables summarising data from the articles identified through the literature searches, and reference details of the literature used to produce the updated tables. 3 Health harms of drugs Contents Part one: Methods 5 Part two: Summary of cohort, case-control and cross- sectional studies 9 1. Amphetamines 10 2. MDMA and related analogues 13 3. Anabolic agents 17 4. Cannabis 18 5. Cocaine and crack cocaine 20 6. Ketamine 23 7. Gamma-hydroxybutyrate 24 8. Novel synthetic drugs 25 9. Opioids 26 10. Khat and Salvia divinorum 28 11. Polysubstance use 29 12. Cross-cutting themes 33 Part three: Summary of case reports 35 13. Ketamine 36 14. Serotonergic hallucinogens 37 15. Novel synthetic drugs 38 16. Nitrites 39 17. Khat and Salvia divinorum 40 Part four: References 41 4 Health harms of drugs PART ONE METHODS 5 HHHeeeaaalllttthhh hhhaaarrrmmmsss ooofff dddrrruuugggsss A summary of the health harms of drugs 1. Methods The methods developed to update the tables from the 2003 report were based on the systematic retrieval and collection of relevant peer reviewed literature. In addition, a lead expert for each licit and illicit drug was designated from within the research team. Alongside the senior researcher and research assistants, the lead expert reviewed the evidence and guided the update of the tables for their relevant areas. 1.1 Literature retrieval A search strategy was developed for searching electronic sources and relevant websites. Searches were undertaken in MEDLINE, PsycINFO and TOXLINE. Key reports, monographs and reference sources suggested by the lead experts were also used to identify relevant articles and evidence of the health harms of licit and illicit substances. 1.2 Review of new evidence Study selection proceeded in two phases. In the first stage, titles and abstracts were screened by the research team to identify potentially relevant references. Full text copies of references identified as potentially relevant in phase one were examined further by the lead researcher to determine whether they met the criteria described below. For substances included in the 2003 report, only articles published since 2003 were eligible for inclusion. For any new drugs considered for the update, inclusion of articles was not limited according to the date of publication. Data from articles meeting the inclusion criteria were extracted by the research team onto a standardised form to record concisely, details about the study methods, participants and findings. 1.3 Inclusion and exclusion criteria Type of population Studies that included users of licit and illicit drugs in the UK or from countries outside the UKa were eligible for inclusion. Animal studies or studies using non-drug-using volunteers enrolled in prospective research were generally excluded, but where a lack of evidence was available from drug using populations, evidence from such studies has been included. Type of exposure The list of drugs to be included in the update was agreed between the research team, NTA and DH and included: • Alcohol • Amphetamines and amphetamine-type stimulants (amphetamine sulphate, methamphetamine, MDMA [‘ecstasy’] and analogues) • Anabolic agents (anabolic-androgenic steroids, growth hormone, clenbuterol, [human and non- human] chorionic gonadotropin [hCG]2) a Limited primarily to evidence from OECD countries (i.e. Australia, Austria, Belgium, Canada, Chile, Czech Republic, Denmark, Estonia, 6 Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Japan, Korea, Luxembourg, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Slovak Republic, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States) HHeeaalltthh hhaarrmmss ooff ddrruuggss • Cannabis • Classical hallucinogens (LSD, psilocybin, mescaline, dimethyltryptamine [DMT]) • Cocaine powder (cocaine hydrochloride) and freebase cocaine (crack/rock cocaine) • Dissociative anaesthetics (ketamine, phencyclidine [PCP]) • Gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL) • Nitrites (amyl nitrite, butyl nitrite and isobutyl nitrite) • Novel synthetic drugs – Cannabinoids (‘Spice’) – Cathinones (4-methylmethcathinone [4-MMC], mephedrone, methylenedioxypyrovalerone [MDPV], naphyrone, pyrovalerone) – Piperazines (benzylpiperazine [BZP], metachlorophenylpiperazine [mCPP], trifluoromethylphenylpiperazine [TFMPP]) – 2C series phenethylamines (2C-B and related compounds) – Tryptamines (5-MeO-DMT and related compounds) – Other (‘Bromo-dragonFLY’) • Opioids – Illicit opioids (heroin) – Prescription opioids (methadone, tramadol, dihydrocodeine, oxycodone) • Over-the-counter products – Dextromethorphan – Codeine containing products (co-proxamol, co-codamol) • Plant/herbal products – Khat (Catha edulis Forsk) – Salvia divinorum • Prescription drugs – Benzodiazepines (temazepam, diazepam, nitrazepam, clonazepam) – Non-benzodiazepine hypnotics (zaleplon, zolpidem, zopiclone) – CNS stimulants (dexamphetamine, methylphenidate, modafinil) • Tobacco • Volatile substances (glues, thinners, aerosols, paints and lighter fuel). Type of outcome Studies that examined acute and/or chronic health harms arising from licit and illicit substance use and misuse, including physical (mortality and morbidity) harms, psychological/psychiatric harms, and those relating to dependence, tolerance and withdrawal, were eligible for inclusion. Studies that only reported on surrogate measures of harm (e.g. neuroimaging studies) were excluded. Type of studies Evidence from a wide range of sources was eligible for inclusion in the updated tables; however, evidence from systematic reviews and well-designed observational studies (including cohort studies, 77 HHeeaalltthh hhaarrmmss ooff ddrruuggss case-control studies and cross-sectional studies) was prioritised for inclusion. For drugsb where there was a limited evidence base, fatal and non-fatal acute harms identified in case reports and case series have also been collated. 1.3 The updated tables New evidence identified from the articles retrieved through the literature searches was used to update the evidence presented in the 2003 report. The basic layout of the tables follows the ‘framework for typology of dangerousness of drugs’ as outlined in the 2003 report, focusing on the acute and chronic problems associated with each substance and factors that mediate or moderate the risk. Following the format of the 2003 report, evidence on specific harms associated with different contextual factors related to drug use (different routes of administration, polypharmacy, and age and gender-related factors) have been included in the updated tables for each specific drug, and as a set of new tables addressing these as cross-cutting themes across the included substances. Two additional tables also consider the potential health risks arising from adulterants drawing on recent research conducted by the team1,2. b Dissociative anaesthetics, hallucinogens, novel synthetic drugs, nitrites, khat and salvia divinorum 88 Health harms of drugs PART TWO SUMMARY OF COHORT, CASE-CONTROL AND CROSS-SECTIONAL STUDIES 9 HHeeaalltthh hhaarrmmss ooff ddrruuggss 1. Amphetamines STUDY STUDY POPULATION DATA COLLECTION RESULTS Degenhardt et al., 1,943 adolescents (14-15 years) recruited Baseline survey: 14-15 years Adolescent amphetamine use (age 15-17 (2007)3 from secondary schools in Victoria; 78% Follow-up: 11 years years) was associated with poor mental Australia followed up Methods: self-report health and cannabis use. By young Victoria Adolescent Sex: 49% male questionnaire adulthood (age 24-25 years), adolescent amphetamine users were more likely to Health Cohort Study Age: 14-15 years Measure(s): amphetamine use; meet criteria for dependence upon a range Cohort study Ethnicity: NR alcohol consumption/ of drugs, to have greater psychological Substance use: cannabis, tobacco, alcohol dependence; tobacco use; morbidity and to have some limitations in cannabis use/dependence; educational attainment. Most of these Clinical Interview Schedule associations were not sustained after (CIS-R); Self Report of Early adjustment for early-onset cannabis use Delinquency Scale; educational, occupational and social measures; Standardised Assessment of Personality; General Health Questionnaire Potential confounders/covariates: other drug use; mental health Ito et al., (2009)4 59 adults (>49 years) who were discharged Baseline survey: hospitalised Methamphetamine abusers were found to USA with a primary diagnosis of either between January 2002 and June have a more severe form of dilated cardiomyopathy or heart failure and had a 2004 cardiomyopathy compared with non- Case-control study transthoracic echocardiogram performed Follow-up: NA abusers. Patients who abused during hospitalization methamphetamine had larger left ventricular Methods: comparison of Sex: 64% male echocardiams between end-diastolic volume (LVEDV), end-systolic volume, LAV, right ventricular dimensions, Age: mean 38 years amphetamine and non- and lower LVEF than patients who did not Ethnicity: 48% Pacific Islanders amphetamine using participants abuse methamphetamine Substance use: 48% used Measure(s): left ventricular methamphetamine; 12% cocaine; 17% volume; left atrial volume; alcohol; 10% cannabis; 32% tobacco transmitral flow velocity; left ventricular ejection fraction; left ventricular mass Potential confounders/covariates: age, gender, cardiac risk factors Kinner & Degenhardt 750 regular and current ecstasy users who Baseline survey: 2006 Compared with participants who had used (2008)5 participated in the 2006 Ecstasy and Follow-up: NA only other forms of methamphetamine, Australia related Drug Reporting System Methods: quantitative survey recent crystal methamphetamine users were Cross-sectional study Sex: NR Measure(s): demographic data m≥4o8r eh loikuerlsy. Ntoo hna-svme o‘bkiinngge cdr’y ostna ld rugs for Age: NR including patterns of lifetime and methamphetamine users (n=78) more often Ethnicity: NR recent use, and some risk-taking reported recent injecting and heroin use. Substance use: 81% reported recent use items; methamphetamine Recent smokers were more likely to report of methamphetamine dependence assessed using the greater polydrug use, to have recently Severity of Dependence Scale overdosed on a ‘party drug’, and have (SDS) accessed medical services for their drug use. Potential confounders/covariates: However, many of these associations were accounted for by their injecting and heavier frequency of methamphetamine use 10