The main findings of this study may be summarized succinctly as follows. Heavy cannabis use is associated with elevated total WBC count consistent with prior epidemiological studies conducted in the general population (Friedman et al., 1990; Rajavashisth et al., 2012). These studies, however, did not investigate the association of cannabis use and WBC differential counts. In the current study, neutrophils the most abundant cells of the innate immune response, had the strongest association followed by monocytes but not lymphocytes, eosinophils and basophils. These associations were evident when participants with HIV or other chronic conditions were excluded from the analyses.

Before detailed discussion of these results, several of the important study limitations merit attention. The observational nature of the study constrained causal inferences. Even though NHANES collects blood and urine specimens, drug testing is not conducted, and cannabis use was self-reported which may lead to non-differential misclassification bias. There was no available information on the route of administration of cannabis (smoking, ingestion, etc.) or cannabis preparation/potency.

Despite limitations such as these, the study findings are of interest because of the large sample size, the NHANES standardized data collection approaches, and the ability to adjust for potential confounders. Cannabis use was quantified according to the number of use days in an interval that does not require long recall (past 30 days). In addition, the study is based on fairly recent NHANES surveys (2005–16) which might be more representative of the increasing cannabis potency compared to NHANES III (1988–1994) surveys (Rajavashisth et al., 2012; ElSohly et al., 2016).

Laboratory studies reported suppression of immune responses with cannabinoid administration (Klein, 2005), and some epidemiological studies found lower levels of inflammatory biomarkers such as fibrinogen, C-reactive protein and interleukin-6 in adult cannabis users (Alshaarawy and Anthony, 2015; Keen et al., 2014; Rajavashisth et al., 2012; Alshaarawy et al., 2019). Conversely, studies in adolescence and young adults indicated that cannabis use is not associated lowered immune responses (Ferguson et al., 2019; Costello et al., 2013). The reported anti-inflammatory effects of cannabis were greatly attenuated when body weight is controlled for. This suggests that the inverse cannabis-body weight association might explain the lower levels of circulating inflammatory biomarkers in adult cannabis users (Penner et al., 2013; Le Strat and Le Foll, 2011; Alshaarawy and Anthony, 2019), given the strong association of inflammation and adiposity (Esser et al., 2014). The results of the current study indicate elevated WBC count among heavy cannabis users, and persisted after adjusting for BMI. This increase might be related to the inflammatory effects of combustion by-products as the most common mode of cannabis use is smoking (Grotenhermen, 2003). The association of cannabis and WBCs was evident in heavy users only, which might indicate increased exposure to proinflammatory chemicals generated from smoking (Wei et al., 2016).

These alterations of immune responses by cannabis use might be associated with increased susceptibility to infections and hence the higher WBC count. Indeed, Tsai et al. have reported an association between regular cannabis use and suboptimal self-rated health status, independent of tobacco smoking (Tsai et al., 2017). Yet, it is possible that the elevated WBC and suboptimal health status contributed to cannabis use rather than cannabis use caused suboptimal health. This hypothesis, though, cannot be tested as NHANES does not collect information on cannabis use motives. Another potential mechanism can be through the effect of cannabinoids on stem cells. Pre-clinical studies suggest that cannabinoids stimulate hematopoiesis (Valk et al., 1997), and hence this stimulation to bone marrow tissues can be associated with increased circulating WBC count in cannabis users.