Research Article Review:  A paper examining the genome of 1,054,365 people from four ancestral groups vs. cannabis

An article published online 11/20/2023 caught my attention.  The paper is titled “Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications”

You can find the full text here.

The article’s a rather technical read, given it describes research methods within population-level genetics.  By contrast, a highly readable short summary of the paper and its findings is published here in Nature. 

In this post I’ll cover the research article itself.

Background

As for the background or context of the study, the authors note:

  1. “More than a third of individuals who use cannabis develop cannabis use disorders…”
  2. “…evidence regarding the impact of legalization on escalating use and use disorders is mixed.”
  3. “Substantial negative health outcomes associated with chronic cannabis use include”
    • “cancers associated with inhaling combustion products”,
    • “declines in cognitive capacity and motivation”
    • “and increased risk of schizophrenia.”
  4. “Individual and societal complications that result from Cannabis Use Disorder include decreased productivity and accidents related to intoxication.”
  5. “The full range of risks and negative outcomes associated with cannabis use and Cannabis Use Disorders may not be appreciated widely.”

Findings

I’ll outline a few key findings of the research paper here, in no particular order:

  1. “Cannabis use disorder showed a unidirectional effect on lung cancer.”
  2. “…a bidirectional causal relationship between Cannabis Use Disorder and Schizophrenia.”
  3. “Cannabis Use Disorder was much more closely associated with psychopathology…”
  4. “Educational attainment…showed a positive correlation with cannabis use but a negative correlation with Cannabis Use Disorder.”
  5.  “The strongest observed positive correlations were related to smoking initiation and alcohol dependence”
  6. “…the strongest negative correlations were with ages of first intercourse and smoking cessation.”
  7. “…factor analyses showed that four factors provide the best fit for the 14 correlated traits included in the analysis.  Factors fit mostly into categories that relate to functional impairment, impulsivity and risk taking, psychopathology, and substance dependence.”
  8. “…a clear difference between cannabis use and Cannabis Use Disorder, with genetic liability to Cannabis Use Disorder being much more closely associated with psychopathology and disability.”
  9. “…Cannabis Use Disorder loads on a latent factor with other substance dependence traits, consistent with clinical observation, genetic epidemiology and prior genetic studies of other SUD traits.”

Discussion

The authors outline a number of discussion points including:

  1. Cannabis use “…harms such as dependence and consequences, reflected in underlying genetics of the trait, may need to be weighed against the potential benefits of cannabis treatment for chronic pain.”
  2. Implications in fetal exposure related to genetic-level gradations of risk for developmental delay and early-onset epileptic encephalopathy.
  3. “Fetal development may play a role in SUD susceptibility, and substance use can influence fetal development during pregnancy and health outcomes during childhood.”
  4. “Although exogenous exposure to cannabis may not occur until years or decades after birth, fetal…based heritability in this study argues a possible role for genetic effects on Cannabis Use Disorder in the developing brain independent of exposure.”
  5. “…initiation of genetic risk effects of both Schizophrenia and Cannabis Use Disorder, if validated experimentally, would provide insight into the genetic relationship between these disorders…”

Final sentence

The paper closes with this sentence: 

This study yields new insights into the genetic architecture of Cannabis Use Disorder and how this risk interacts with traits crucial to public health and raises important concerns regarding the potential adverse consequences of the secular trend toward increase cannabis use consequent to legalization.


Some of my thoughts about potential clinical relevance

Given the rising popularity of Harm Reduction and considering it as a purported medical practice (rather than its very long history of pro-social relief-bringing by various kinds of social service providers, and the very long history of the integral inclusion of a range of its principles and practices within most addiction treatment), I’ve been studying what I have called “The Harms of Use” in recent years. 

Why?  Why my interest and concern?  Mainly because I’ve spent my adult life inside addiction treatment services – helping those with chronic, complex and severe addiction illness – and that brings me a skewed perspective.  And for my narrow work I like to be prepared.  You can find an initial list of articles I’ve read here. 

And, given my life-long love of biology and philosophy coupled with my relatively long involvement in addiction treatment, I’ve read and continue to read articles like those to help me think about things like:

  • advantages and disadvantages of kinds of clinical care;
  • side effects and potential side effects of kinds of care;
  • inclusion of these topics within informed consent,
  • and informed consent as an ongoing process. 

For example, regular readers of Recovery Review already know I find it fascinating from both conceptual and clinical perspectives that almost all addiction treatment in the USA ignores and under-treats cigarette smoking, even regardless of the fact that approximately 480,000 people die in the USA each year due to smoking cigarettes. (The topic of how “ignoring” and “under-treating” can be simultaneous is beyond the scope of this writing). 

But more specifically, I find this paper thought-provoking in a number of ways, including:

  • That it evidences the function of cannabis and the related genetic structures that underlie and partially explain the phenomenon people have described as a “gateway drug”.
  • I strongly prefer that kind of empirical information about function, rather than debates about the “status” of what “is” or “is not” inside or outside of a category name..  
  • The implications and value of genetic screenings in clinical care…
    • during intake (especially as related to medication selections)
    • will probably move from intake to any point in time toward determining the safety, suitability and starting of pharmacotherapies in general (including cannabis-derived medicines)
    • and will probably become more common, less expensive, and move from best practice to a simple clinical standard of care.

Further, this kind of empirical study helps me concretize some thinking I’ve been sitting with for some time related to our field’s attempts to seemingly merge empiricism, clinical care, and social revolution. 


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