Misuse of illicit substances linked to higher risk of atrial fibrillation

2nd November 2022

Misuse of illicit substances such as methamphetamines, cocaine, opiates and cannabis are linked to an increased risk of atrial fibrillation

The misuse of the illicit substances methamphetamine, cocaine, opiates and cannabis has been found to increase the risk of incident atrial fibrillation (AF) according to the findings of a longitudinal analysis by Californian researchers.

Atrial fibrillation is the most frequent cardiac arrhythmia, and it has been estimated that 6 -12 million people worldwide suffer from the condition. Moreover, the presence of the arrhythmia is also independently associated with a higher risk of all-cause mortality. While it has become well established that a higher intake of alcohol as well as smoking, increases the risk of AF, the relationship with the misuse of illicit drugs is less clear. Whereas prior work has suggested that methamphetamine abuse leads to ECG changes that pose a higher risk for ventricular arrhythmias and most notably torsades de pointes, less is known about the effect on AF. However, there is some data linking an increased risk of AF from use of both cannabis and cocaine though these findings are derived from case studies. But in contrast, one study actually identified how cannabis use was associated with a lower odds of AF.

In the present study, the US researchers sought to determine whether misuse of the illicit substances, methamphetamine, cocaine, opiates and cannabis were a predictor of incident AF. The team used several California healthcare databases, e.g., emergency department and inpatient to capture repeat visits for a given patient. They extracted demographic and co-morbidity data and excluded those with known AF and looked at cases where substance use was considered present at the first healthcare encounter. The researchers then compared the baseline and clinical characteristics of patients for each of the different drugs and examined the association with AF, adjusting for covariates known to be associated with AF.

Illicit substance misuse and incident atrial fibrillation

In a total of 23,561,884 individuals, 98,271 used methamphetamine, 48,701 cocaine, 10,032 opiates and 132,834 cannabis. From this total, 4.2% developed incident AF during the period of study from 2005 to 2015. The mean age of participants ranged from 32.3 years (cannabis) to 41.1 (cocaine) and the proportion of females from 28.3% to 55%.

After adjustment for covariates, methamphetamine use was associated with an 86% higher risk of developing incident AF (Hazard ratio, HR = 1.86, 95% CI 1.81 – 1.92). Similar and significantly elevated risks were seen for cocaine (HR = 1.61), opiates (HR = 1.74) and cannabis (HR = 1.35). Interesting, polysubstance use was also associated with a higher risk of AF compared to single drug misuse (HR = 1.63, 95% CI 1.61 – 1.66).

The authors concluded that for each of the misused substances analysed, there was a higher risk of developing incident AF after controlling for conventional AF risk factors.

Citation
Lin AL et al. Cannabis, cocaine, methamphetamine, and opiates increase the risk of incident atrial fibrillation. Eur Heart J 2022

Adolescent cannabis use linked to altered neurodevelopment

25th June 2021

Increased use of cannabis among the adolescent population appears to negatively impact on neurodevelopment.

Cannabis is one of the world’s most widely used psychoactive substance with a 2015 report finding that there were around 183 million people, i.e., 3.8% of the world’s population, who reported using the drug in the past year. Moreover, in a study 4-year follow-up study of adolescent use of alcohol and cannabis, it was observed that only cannabis had an important and lasting, negative impact on cognitive functioning. Legislation aimed at de-criminalising or legalising the use of cannabis in the US appears to lead to greater levels of cannabis use disorder among adolescents. With some animal studies suggesting that exposure to cannabis during adolescence appears to affect neurodevelopment as seen by long-term impairment of specific components of learning and memory. However, there is a lack of longitudinal neuroimaging data studying the links between adolescent cannabis use and any potential impact on neurodevelopment. Given these concerns, a team of researchers from the Department of Psychiatry, University of Vermont Larner, Burlington, Canada, turned to the data held on individuals as part of the IMAGEN study. This European project makes use of both brain imaging and genetics, to examine how biological, psychological and environmental factors during adolescence might affect brain development. Within this cohort, the researchers identified cannabis naïve individuals at baseline and who had neuroimaging data both at baseline and at a 5-year follow-up. The researchers sought to determine the degree to which initiation of cannabis was associated with age-related cortical thickness change (from ages 14 to 19). With previous research indicating that cannabis use was associated with impulse control, the team focused on cannabis-related cortical thinning and 3 domains of impulsiveness using a self-reported questionnaire. In addition, baseline and follow-up questionnaires measured cannabis use in the past 30 days using a scale ranging from 0 (never) to 7 (> 40 times).

Findings
The study included 1598 MR images from 799 participants with a mean age at baseline of 14.4 years (56.3% male). Levels of self-reported cannabis use at follow-up ranged from 0 to more than 40 uses, with 161 participating reporting 10 to more than 40 uses. The MR imaging after 5 years showed evidence of a dose-dependent association between lifetime cannabis use and cortical thickness. In particular, there was a negative association cannabis use and cortical thickness in the left and right prefrontal cortices. They also observed no significant link between baseline cortical thickness and lifetime cannabis use. In other words, the neuroanatomical differences observed at follow-up, did not precede cannabis use. Cannabis-related cortical thinning was also present in the right dorsomedial prefrontal cortex, which the authors felt was related to the self-reported attentional impulsiveness at the 5-year follow-up. Finally, using PET scans, the authors found increased levels of endocannabinoid receptors in cortical areas found to have thinned at follow-up.

Discussing these results, the author suggested that the totality of their evidence pointed to how cannabis use during middle to late adolescence may be associated with altered cortical, particularly in prefrontal regions. They concluded that given the increasing de-criminalisation of the drug, further longitudinal studies of adolescent cannabis users were needed to confirm these findings.

Citation
Albaugh MD et al. Association of Cannabis Use During Adolescence with Neurodevelopment. JAMA Psychiatry 2021

Medicinal cannabis does not impair driving performance

4th December 2020

Epidemiological studies have shown that cannabis is associated with an increased risk of car crashes.

Whether or not, cannabidiol, the derivative widely used as medicinal cannabis, also impairs driving performance is largely unknown.

Cannabis is available in three different varieties (or technically, chemovars) which are cannabidiol (CBD) dominant, tetrahydrocannabinol (THC) dominant and a CBD-THC equivalent mixture. Individuals inhale the THC dominant form because of its intoxicating effects. Whether the CBD dominant form, used medicinally, has sedating properties is currently equivocal.

As a result, researchers from the Lambert Initiative for Cannabinoid Research, University of Sidney, Australia, conducted a randomised trial to examine the extent and duration to which each of the different cannabis chemovars impaired driving performance. They recruited 26 individuals with a history of occasional cannabis use and employed a cross-over design study that involved four on-road driving periods, one week apart. For the study, the participants inhaled one of vapourised cannabis containing 13.75mg CBD, THC, CBD-THC equal mixture or placebo. The driving tests twice; 40 to 100 minutes and 240 to 300 minutes post-vaporisation. The primary outcome was the mean standard deviation of lateral position (SDLP), which measures the extent of lane weaving, swerving and overcorrecting.

Findings
The mean age of the 26 individuals was 23.2 years (including 16 women), all of whom completed the 8 driving tests. At 40 to 100 minutes and following inhalation of cannabis, the mean SDLP after CBD was 84.07cm, 86.94cm after THC, 84.07cm after the CBD-THC mixture and 84.41cm after placebo and these values remained similar between 240 and 300 minutes. Pairwise comparisons revealed that both SDLP values for THC and the THC-CBD were higher than placebo at 40 to 100 minutes, but not between 240 and 300 minutes. In other words, both THC and the combination but not, CBD, impaired driving performance in the short-term, but that this effect was abolished in the longer term.

Although a limitation in the study, recognised by the authors, was that the dosages used might not reflect common usage, their data implied that CBD did not affect driving ability.

Citation
Arkell TR et al. Effect of cannabidiol and delta-nine tetrahydrocannabiniol on driving performance. A randomised clinical trial. JAMA Net Open 2020 doi:10.1001/jama.2020.21218