Although the influence of chronotype on mental health and drug use is known, the mechanism by which they interact is still elusive. A biological mechanism may explain such interactions. Both chronotype and drug use have been linked to alterations in reward processing (Hasler et al., 2017a; Taylor and Hasler, 2018), which are modulated by dopamine signaling (Arias-Carrión et al., 2010). Changes in dopamine transmission could thus mediate the relationships between the effects of the drugs of abuse, mental health and chronotype. Interestingly, late chronotype has also been associated with delayed melatonin release (Lack et al., 2009). Melatonin acts as a biochemical “signal of darkness” which entrains the sleep-wake and neuroendocrine cycles, even in the absence of environmental light changes (Zisapel, 2018). Consequently, melatonin has been linked with depression, as exemplified by the high prevalence of sleep and circadian changes in this condition (Tonon et al., 2021). The effects of melatonin are likely to extend beyond depression, as sleep changes are very common in many psychiatric disorders, and are often used as a diagnostic criterion (APA, 2013). The biochemical interaction between melatonin and dopamine may be responsible for this link in mental health disorders (Zisapel, 2001). It is therefore tempting to speculate that late chronotypes have disrupted signaling of both of these molecules, which may contribute to their increased susceptibility to the drug-related effects on mental health. Importantly, the effects of drug consumption on late chronotypes may be two-fold; evening types may not only use more drugs but they may also be more susceptible to the negative psychological effects of drugs.

Possibly, higher drug consumption in later chronotypes is due to the lack of synchrony between their biological alertness and their societal responsibilities (Wittmann et al., 2006). It is also of note that consumption patterns differ with stimulant and depressant drugs. For example, increased use of nicotine and caffeine may increase morning alertness in late chronotypes, whereas alcohol and possibly also cannabis, may decrease their high alertness at night time in order to sleep (Adan, 1994). Indeed, drug consumption is commonly used as a remedy for people with sleep problems, a common challenge for late chronotypes (Gulick and Gamsby, 2018). Interestingly, chronic use of alcohol, cannabis and tobacco have been reported to decrease rapid-eye-movement sleep duration, potentially leaving these late chronotypes even less rested, perpetuating their existing sleep problems and contributing to poorer mood and cognition (Yules et al., 1967; Stein and Friedmann, 2005; Bolla et al., 2008; Jaehne et al., 2009; Gulick and Gamsby, 2018).

Late chronotypes may also have increased sensitivity to the negative mental health effects of these drugs. Evening chronotypes have a 2–3 h delay in their circadian melatonin release and this delay is associated with higher negative emotion (Lack et al., 2009; Dolsen and Harvey, 2018). Melatonin has been shown to inhibit dopamine signaling, which may cause the increased presence of anxious or depressive symptoms in those with dysregulated melatonin (Zisapel, 2001; Zarrindast and Khakpai, 2015; Belujon and Grace, 2017). Drugs of abuse including alcohol, cannabis and tobacco dysregulate both dopamine and melatonin release, highlighting that overall drug consumption may exacerbate the existing signaling disruption in late chronotypes (Ursing et al., 2005; Koch et al., 2006; Rupp et al., 2007; Oleson and Cheer, 2012; Le Foll et al., 2014; Budygin and Weiner, 2015). Both late chronotype and high overall drug consumption could have an additive effect on dysregulating melatonin, which may in turn impact on dopamine-dependent reward signaling in the brain of late chronotypes to an even greater extent.

Existing mental health problems can also be a strong predictor of future drug abuse, with drug use and mental health having a bidirectional relationship (Swendsen et al., 2010). Both factors in this relationship can give rise to a negative spiral (Burdzovic Andreas et al., 2015). Late chronotypes may be more vulnerable to falling into this behavioral cycle via the proposed melatonin-dopamine interaction. However, further research is clearly warranted to support this assertion.