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.
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.
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.
Background: 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. Method: 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. Results: 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, p < 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. Conclusion: 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.
Randomised controlled trials (RCTs) have long been considered the gold standard of medical evidence. In relation to cannabis based medicinal products (CBMPs), this focus on RCTs has led to very ...restrictive guidelines in the UK, which are limiting patient access. There is general agreement that RCT evidence in relation to CBPMs is insufficient at present. As well as commercial reasons, a major problem is that RCTs do not lend themselves well to the study of whole plant medicines. One solution to this challenge is the use of real world evidence (RWE) with patient reported outcomes (PROs) to widen the evidence base. Such data increasingly highlights the positive impact medical cannabis can have on patients’ lives. This paper outlines the value of this approach which involves the study of interventions and patients longitudinally under medical care. In relation to CBMPs, RWE has a broad range of advantages. These include the study of larger groups of patients, the use of a broader range and ratio of components of CBMPs, and the inclusion of more and rarer medical conditions. Importantly, and in contrast to RCTs, patients with significant comorbidities–and from a wider demographic profile–can also be studied, so providing higher ecological validity and increasing patient numbers, whilst offering significant cost savings. We conclude by outlining 12 key recommendations of the value of RWE in relation to medical cannabis. We hope that this paper will help policymakers and prescribers understand the importance of RWE in relation to medical cannabis and help them develop approaches to overcome the current situation which is detrimental to patients.
The number of people entering specialist drug treatment for cannabis problems has increased considerably in recent years. The reasons for this are unclear, but rising cannabis potency could be a ...contributing factor.
Cannabis potency data were obtained from an ongoing monitoring programme in the Netherlands. We analysed concentrations of δ-9-tetrahydrocannabinol (THC) from the most popular variety of domestic herbal cannabis sold in each retail outlet (2000-2015). Mixed effects linear regression models examined time-dependent associations between THC and first-time cannabis admissions to specialist drug treatment. Candidate time lags were 0-10 years, based on normative European drug treatment data.
THC increased from a mean (95% CI) of 8.62 (7.97-9.27) to 20.38 (19.09-21.67) from 2000 to 2004 and then decreased to 15.31 (14.24-16.38) in 2015. First-time cannabis admissions (per 100 000 inhabitants) rose from 7.08 to 26.36 from 2000 to 2010, and then decreased to 19.82 in 2015. THC was positively associated with treatment entry at lags of 0-9 years, with the strongest association at 5 years, b = 0.370 (0.317-0.424), p < 0.0001. After adjusting for age, sex and non-cannabis drug treatment admissions, these positive associations were attenuated but remained statistically significant at lags of 5-7 years and were again strongest at 5 years, b = 0.082 (0.052-0.111), p < 0.0001.
In this 16-year observational study, we found positive time-dependent associations between changes in cannabis potency and first-time cannabis admissions to drug treatment. These associations are biologically plausible, but their strength after adjustment suggests that other factors are also important.
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