Cannabis withdrawal is heritable and shares genetic roots with abuse and dependence | Research

The takeaway

About half of the variation in cannabis withdrawal symptoms was attributable to genetic factors, and those genetic influences almost completely overlapped with genes affecting abuse and dependence.

Read this if you want to understand the genetic basis of cannabis withdrawal and why some people experience it more severely than others.

99% genetic overlap between cannabis withdrawal and abuse/dependence

What the researchers found

In a study of 2,276 Australian twins who had used cannabis at least once, 11.9% met criteria for DSM-5 cannabis withdrawal. About 50% of the variation in withdrawal symptoms was attributable to additive genetic factors, with the remaining variation due to non-shared environmental influences (unique experiences not shared between twins).

The most striking finding was that 99% of the genetic influences on cannabis withdrawal overlapped with genetic influences on abuse and dependence. This means the same genes that increase vulnerability to developing abuse or dependence also drive vulnerability to withdrawal symptoms.

Why it matters

This study provided genetic evidence supporting the inclusion of cannabis withdrawal as a diagnostic criterion in DSM-5. Finding that withdrawal shares nearly all its genetic basis with abuse/dependence suggests these are not separate phenomena but expressions of a common underlying genetic vulnerability.

The numbers in context

2,276 lifetime cannabis-using twins. 11.9% met DSM-5 withdrawal criteria. Heritability of withdrawal was approximately 50%. Genetic overlap between withdrawal and abuse/dependence was 99%.

How the study worked

Classical twin study using 2,276 lifetime cannabis-using adult Australian twins. Cannabis withdrawal was defined according to proposed DSM-5 criterion B. Cannabis abuse/dependence was defined using DSM-IV criteria. Univariate and bivariate twin models estimated genetic, shared environmental, and non-shared environmental contributions to withdrawal and its overlap with abuse/dependence.

What this study cannot tell us

Twin studies estimate heritability at the population level and cannot identify specific genes. The sample was limited to Australian twins, who may not represent other populations. Self-reported withdrawal symptoms may be affected by recall bias. The 11.9% prevalence may underestimate withdrawal given the broad range of cannabis use experience in the sample.

How to read the evidence

Well-powered twin study with appropriate methodology for estimating heritability and genetic overlap.

When this study was published

Published in 2013, timed to inform the DSM-5 revision process that added cannabis withdrawal as a diagnostic criterion.

The bigger picture

The DSM-5 was published in 2013 and included cannabis withdrawal as a new diagnostic criterion for the first time. This twin study was among the research that supported that decision by demonstrating withdrawal was a real, heritable phenomenon closely linked to the broader dependence syndrome.

Questions still open

Which specific genes underlie both cannabis withdrawal and dependence vulnerability? Does the genetic architecture of cannabis withdrawal differ across populations? Could genetic markers help predict who is most likely to experience difficult withdrawal?

Common questions

Is cannabis withdrawal genetic?

This twin study found that about 50% of the variation in cannabis withdrawal was due to genetic factors. The remaining variation was due to individual-specific environmental experiences.

How common is cannabis withdrawal?

In this sample of 2,276 Australian twins who had used cannabis, 11.9% met proposed DSM-5 criteria for cannabis withdrawal.

Read the original research

A genetic perspective on the proposed inclusion of cannabis withdrawal in DSM-5.

Psychological medicine, 43(8), 1713-22

View on PubMed ↗Publisher’s paper ↗

Citation

Verweij, K J H; Agrawal, A; Nat, N O; Creemers, H E; Huizink, A C; Martin, N G; Lynskey, M T. (2013). A genetic perspective on the proposed inclusion of cannabis withdrawal in DSM-5.. Psychological medicine, 43(8), 1713-22. https://doi.org/10.1017/S0033291712002735