Background and aims
Cannabis products with high delta‐9‐tetrahydrocannabinol (THC) concentrations carry an increased risk of addiction and mental health disorders, while it has been suggested that ...cannabidiol (CBD) may moderate the effects of THC. This study aimed to systematically review and meta‐analyse changes in THC and CBD concentrations in cannabis over time (PROSPERO registration: CRD42019130055).
Design
Embase, MEDLINE® and Epub Ahead of Print, In‐Process and Other Non‐Indexed Citations and Daily, Global Health, PsycINFO and Scopus were searched from inception to 27/03/2019 for observational studies reporting changes in mean THC and/or CBD concentration in cannabis over at least three annual time points. Searches and extraction were conducted by two independent reviewers. Random effects meta‐regression models estimated annual changes in THC and CBD for each product within each study; these estimates were pooled across studies in random effects models.
Results
We identified 12 eligible studies from the USA, UK, Netherlands, France, Denmark, Italy and New Zealand. For all herbal cannabis, THC concentrations increased by 0.29% each year (95% CI: 0.11, 0.47), P < 0.001 based on 66 747 cannabis samples from eight studies, 1970–2017. For cannabis resin, THC concentrations increased by 0.57% each year (95% CI: 0.10, 1.03), P = 0.017 based on 17 371 samples from eight studies, 1975–2017. There was no evidence for changes in CBD in herbal cannabis −0.01% (95% CI: −0.02, 0.01), P = 0.280; 49 434 samples from five studies, 1995–2017 or cannabis resin 0.03% (95% CI: −0.11, 0.18), P = 0.651; 11 382 samples from six studies, 1992–2017. Risk of bias was low apart from non‐random sampling in most studies. There was evidence of moderate to substantial heterogeneity.
Conclusions
Concentrations of delta‐9‐tetrahydrocannabinol (THC) in international cannabis markets increased from 1970 to 2017 while cannabidiol (CBD) remained stable. Increases in THC were greater in cannabis resin than herbal cannabis. Rising THC in herbal cannabis was attributable to an increased market share of high‐THC sinsemilla relative to low‐THC traditional herbal cannabis.
ABSTRACT
Aims In this exciting era of gene discovery, we review evidence from family, adoption and twin studies that examine the genetic basis for addiction. With a focus on the classical twin ...design that utilizes data on monozygotic and dizygotic twins, we discuss support in favor of heritable influences on alcohol, nicotine, cannabis and other illicit drug dependence.
Methods We review whether these genetic factors also influence earlier stages (e.g. experimentation) of the addictive process and whether there are genetic influences specific to each psychoactive substance.
Results Converging evidence from these studies supports the role of moderate to high genetic influences on addiction with estimates ranging from 0.30 to 0.70. The changing role of these heritable factors as a function of gender, age and cultural characteristics is also discussed. We highlight the importance of the interplay between genes and the environment as it relates to risk for addiction and the utility of the children‐of‐twins design for emerging studies of gene–environment interaction is presented.
Conclusions Despite the advances being made by low‐cost high‐throughput whole genome association assays, we posit that information garnered from twin studies, especially extended twin designs with power to examine gene–environment interactions, will continue to form the foundation for genomic research.
Aims
To quantify changes in (i) potency (concentration of Δ9‐tetrahydrocannabinol; %THC), (ii) price (euros/g of cannabis) and (iii) value (mg THC/euro) of cannabis resin and herbal cannabis in ...Europe.
Design
Repeated cross‐sectional study.
Setting and participants
Data collected from 28 European Union (EU) member states, Norway and Turkey by the European Monitoring Centre for Drugs and Drug Addiction.
Measurements
Outcome variables were potency, price and value for cannabis resin and herbal cannabis in Europe, 2006–16. Inflation was estimated using the Harmonised Indices of Consumer Prices. Mixed‐effects linear regression models were used to estimate linear and quadratic time trends, with a random intercept and slope fitted to account for variation across countries.
Findings
Resin potency increased from a mean 95% confidence interval (CI) of 8.14% THC (6.89, 9.49) in 2006 to 17.22 (15.23, 19.25) in 2016. Resin price increased from 8.21 euros/g (7.54, 8.97) to 12.27 (10.62, 14.16). Resin increased in value, from 11.00 mg THC per euro (8.60, 13.62) to 16.39 (13.68, 19.05). Quadratic time trends for resin potency and value indicated minimal change from 2006 to 2011, followed by marked increases from 2011 to 2016. Herbal cannabis potency increased from 5.00% THC (3.91, 6.23) to 10.22 (9.01, 11.47). Herbal price increased from 7.36 euros/g (6.22, 8.53) to 12.22 (10.59, 14.03). The value of herbal cannabis did not change from 12.65 mg of THC per euro (10.18, 15.34) to 12.72 (10.73, 14.73). All price trends persisted after adjusting for inflation.
Conclusions
European cannabis resin and herbal cannabis increased in potency and price from 2006 to 2016. Cannabis resin (but not herbal cannabis) increased in the quantity of Δ9‐tetrahydrocannabinol per euro spent. Marked increases in resin potency and value from 2011 to 2016 are consistent with the emergence of new resin production techniques in European and neighbouring drug markets.
Sharing of equipment used for injecting drug use (IDU) is a substantial cause of disease burden and a contributor to blood-borne virus transmission. We did a global multistage systematic review to ...identify the prevalence of IDU among people aged 15–64 years; sociodemographic characteristics of and risk factors for people who inject drugs (PWID); and the prevalence of HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) among PWID.
Consistent with the GATHER and PRISMA guidelines and without language restrictions, we systematically searched peer-reviewed databases (MEDLINE, Embase, and PsycINFO; articles published since 2008, latest searches in June, 2017), searched the grey literature (websites and databases, searches between April and August, 2016), and disseminated data requests to international experts and agencies (requests sent in October, 2016). We searched for data on IDU prevalence, characteristics of PWID, including gender, age, and sociodemographic and risk characteristics, and the prevalence of HIV, HCV, and HBV among PWID. Eligible data on prevalence of IDU, HIV antibody, HBsAg, and HCV antibody among PWID were selected and, where multiple estimates were available, pooled for each country via random effects meta-analysis. So too were eligible data on percentage of PWID who were female; younger than 25 years; recently homeless; ever arrested; ever incarcerated; who had recently engaged in sex work, sexual risk, or injecting risk; and whose main drugs injected were opioids or stimulants. We generated regional and global estimates in line with previous global reviews.
We reviewed 55 671 papers and reports, and extracted data from 1147 eligible records. Evidence of IDU was recorded in 179 of 206 countries or territories, which cover 99% of the population aged 15–64 years, an increase of 31 countries (mostly in sub-Saharan Africa and the Pacific Islands) since a review in 2008. IDU prevalence estimates were identified in 83 countries. We estimate that there are 15·6 million (95% uncertainty interval UI 10·2–23·7 million) PWID aged 15–64 years globally, with 3·2 million (1·6–5·1 million) women and 12·5 million (7·5–18·4 million) men. Gender composition varied by location: women were estimated to comprise 30·0% (95% UI 28·5–31·5) of PWID in North America and 33·4% (31·0–35·6) in Australasia, compared with 3·1% (2·1–4·1) in south Asia. Globally, we estimate that 17·8% (10·8–24·8) of PWID are living with HIV, 52·3% (42·4–62·1) are HCV-antibody positive, and 9·1% (5·1–13·2) are HBV surface antigen positive; there is substantial geographic variation in these levels. Globally, we estimate 82·9% (76·6–88·9) of PWID mainly inject opioids and 33·0% (24·3–42·0) mainly inject stimulants. We estimate that 27·9% (20·9–36·8) of PWID globally are younger than 25 years, 21·7% (15·8–27·9) had recently (within the past year) experienced homelessness or unstable housing, and 57·9% (50·5–65·2) had a history of incarceration.
We identified evidence of IDU in more countries than in 2008, with the new countries largely consisting of low-income and middle-income countries in Africa. Across all countries, a substantial number of PWID are living with HIV and HCV and are exposed to multiple adverse risk environments that increase health harms.
Australian National Drug and Alcohol Research Centre, Australian National Health and Medical Research Council, Open Society Foundation, World Health Organization, the Global Fund, and UNAIDS.
During the early 1970s Denise Kandel and her colleagues documented an ‘invariant sequence’ in initiation of drug use: starting with alcohol and tobacco, progressing to cannabis and then to other ...illicit, or ‘harder’ drugs. This observation, which became known as the ‘gateway sequence’ of drug use, has been influential in policy debates but remains highly contentious, with the area of greatest controversy focusing upon whether cannabis use increases risk causally for initiation of other illicit drugs. While numerous studies have replicated Kandel's initial findings (sequence of onset) and reported that associations between cannabis use and the use of other illicit drugs remain after controlling for potentially confounding factors, the mechanisms underlying these observed associations remain hotly debated. In particular, it is possible that the observed associations are non‐causal but reflect the influence of confounding factors which influence both early‐onset drug use and subsequent progressions. However, research employing a range of techniques to address this issue has been unable to discount the possibility that associations between earlier and subsequent drug use reflect causal processes. This paper reviews Kandel's ongoing contributions to this field, which span 45 years, and discusses both the influence of her work and the controversy that it has aroused.
Increasing mortality and morbidity associated with opioid analgesics has led to concerns about their misuse and abuse, even when obtained through a prescription. These concerns have been most ...pronounced in the United States, but limited data make it difficult to determine whether it is a problem in other countries. We investigated opioid analgesic misuse and abuse in participants from the Global Drug Survey 2015 resident in the United States (N = 1334), United Kingdom (N = 1199), France (N = 1258), Germany (N = 866), and Australia (N = 1013) who had used at least 1 prescription opioid analgesic medication in the past year. We also investigated the relationship with polysubstance use, one of the most consistent predictors of problematic opioid analgesic use. Data included misuse and abuse of codeine, hydrocodone, oxycodone, and tramadol; ability to obtain a prescription; different sources for obtaining drugs; and past-year use of benzodiazepines and illicit drugs. In multilevel models, country of residence accounted for less than 3% of the variance in opioid analgesic misuse or abuse. Adjusting for country of residence and sociodemographic factors, use of illicit drugs and benzodiazepines was associated with 4-fold greater odds of misuse (odds ratio 4.36, 95% confidence interval 3.29-5.93) and 6-fold greater odds of abuse compared with not using either drug (odds ratio 6.49, 95% confidence interval 4.0-10.48), although the strength of the association with abuse varied by country. Misuse and abuse by those prescribed opioid analgesics seem to be a problem that is not limited to the United States and warrant attention on an international scale.
People who inject drugs (PWID) are a key population affected by the global HIV and hepatitis C virus (HCV) epidemics. HIV and HCV prevention interventions for PWID include needle and syringe ...programmes (NSP), opioid substitution therapy (OST), HIV counselling and testing, HIV antiretroviral therapy (ART), and condom distribution programmes. We aimed to produce country-level, regional, and global estimates of coverage of NSP, OST, HIV testing, ART, and condom programmes for PWID.
We completed searches of peer-reviewed (MEDLINE, Embase, and PsycINFO), internet, and grey literature databases, and disseminated data requests via social media and targeted emails to international experts. Programme and survey data on each of the named interventions were collected. Programme data were used to derive country-level estimates of the coverage of interventions in accordance with indicators defined by WHO, UNAIDS, and the UN Office on Drugs and Crime. Regional and global estimates of NSP, OST, and HIV testing coverage were also calculated. The protocol was registered on PROSPERO, number CRD42017056558.
In 2017, of 179 countries with evidence of injecting drug use, some level of NSP services were available in 93 countries, and there were 86 countries with evidence of OST implementation. Data to estimate NSP coverage were available for 57 countries, and for 60 countries to estimate OST coverage. Coverage varied widely between countries, but was most often low according to WHO indicators (<100 needle-syringes distributed per PWID per year; <20 OST recipients per PWID per year). Data on HIV testing were sparser than for NSP and OST, and very few data were available to estimate ART access among PWID living with HIV. Globally, we estimate that there are 33 (uncertainty interval UI 21–50) needle-syringes distributed via NSP per PWID annually, and 16 (10–24) OST recipients per 100 PWID. Less than 1% of PWID live in countries with high coverage of both NSP and OST (>200 needle-syringes distributed per PWID and >40 OST recipients per 100 PWID).
Coverage of HIV and HCV prevention interventions for PWID remains poor and is likely to be insufficient to effectively prevent HIV and HCV transmission. Scaling up of interventions for PWID remains a crucial priority for halting the HIV and HCV epidemics.
Open Society Foundations, The Global Fund, WHO, UNAIDS, United Nations Office on Drugs and Crime, Australian National Drug and Alcohol Research Centre, University of New South Wales Sydney.
Previous research has reported increased risk for psychosis among individuals who use cannabis during adolescence. We conducted a systematic review and meta-analysis to investigate the interaction ...between adolescent cannabis use and other factors in moderating risk for psychosis later in life.
We searched four electronic databases in June 2020 for articles that assessed adolescent cannabis use, had psychosis as an outcome and analyzed for the association between adolescent cannabis use and psychosis. Analysis was done using random-effects meta-analysis and narrative synthesis.
: A total of 63 studies were included in the narrative review and 18 studies were included in the meta-analysis. Adolescent cannabis use was found to increase risk for psychosis (RR = 1.71 (95%CI, 1.47-2.00,
< 0.00001) and predict earlier onset of psychosis. The following factors moderate the relationship between cannabis use and the risk of psychosis: age of onset of cannabis use, frequent cannabis use, exposure to childhood trauma, concurrent use of other substances and genetic factors.
Adolescent cannabis use is associated with an increased risk for psychosis later in life. In addition, there are factors that moderate this relationship; therefore there is a need for research to assess the interaction between these factors, adolescent cannabis use and psychosis risk.
Abstract Background Qualitative research suggests that a shared route of administration (i.e. via inhalation) for the common forms of both tobacco (i.e. cigarettes) and cannabis (i.e. joints) may ...contribute to their co-occurring use. Methods We used data on 43,093 U.S. adults who participated in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to examine whether cannabis use and abuse/dependence were associated with smoked (cigarettes, cigars, pipes) versus smokeless (snuff, chewed tobacco) forms of tobacco use, even after controlling for socio-demographic, psychiatric and substance-related covariates. Results Tobacco smoking was associated with a 3.3–4.5 times increased risk for cannabis use and abuse/dependence respectively. After covariate adjustment, importantly for nicotine dependence, smoking tobacco (but not smokeless tobacco) was still significantly associated with both cannabis use (multinomial odds-ratio (MOR) 1.99) and cannabis dependence (MOR 1.55). In contrast, use of smokeless tobacco was not significantly correlated with elevated rates of cannabis use (MOR 0.96) or abuse/dependence (MOR 1.04). Conclusions Route of administration may play an important role in the observed association between tobacco and cannabis use. This may represent a physiological adaptation of the aero-respiratory system and/or index social and cultural influences surrounding the use of smoked versus smokeless forms of tobacco.
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