While Hall provides an excellent review of the evidence, an important issue that is not discussed concerns the future direction of research on cannabis. We are of the view that there are three areas of research that are of high priority:

• The role of neurophysiological factors: while there is growing evidence of the adverse impacts of cannabis on educational achievement, cognitive functioning and related outcomes, less is known about the extent to which these linkages are due to the long-term effects of cannabis on the brain. There is growing evidence from both animal and human studies that the use of cannabis can lead to changes in neurophysiological structure and functioning. These changes include alterations to the function of cannabinoid receptor CB1 [2], grey matter volume reduction [3], inhibition of synaptic pruning [4], reduction of hippocampal and amygdala volume [5], reductions in axonal connectivity [6] and reduced cerebral blood flow [7]. These effects are particularly important during adolescence [8], and may explain the linkages between adolescent cannabis use and later educational and cognitive impairment. Developing a clear understanding of how cannabis affects the brain and the consequences of this for later cognitive and related functioning is an area of high research priority.

• Genes and environment: a second important issue concerns the extent to which cannabis use and dependence is influenced by genetic factors. In particular, evidence from twin studies has suggested the presence of quite substantial heritability (h2) for cannabis dependence, with estimates ranging from 0.44 to 0.78 [9, 10]. For this reason, further research into the genetic factors that cause people to be susceptible to cannabis use and dependence may increase understanding of the effects of cannabis on psychosocial functioning.

In addition, there has been some evidence to suggest that the associations between cannabis use and psychotic symptomatology may be influenced by gene × environment interactions. Specifically, Caspi and colleagues found evidence that carriers of the catechol-O-methyltransferase (COMT) valine 158 allele were at greater risk of psychotic symptomatology after using cannabis [11]. However, these findings have not been replicated by other studies [12-15], and additional studies have examined other possible gene × environment interactions in the linkages between cannabis use and psychotic symptomatology [16-18]. It is clear that further research on possible gene × environment interactions is needed not only to elucidate the linkages between cannabis and psychosis, but also to explore the role of genetic factors in linkages between cannabis and other psychosocial outcomes.


• The changing legal environment and the use of cannabis: finally, perhaps the most important issue relating to cannabis concerns the extent to which changes in the legislation regarding cannabis have effects on population rates of consumption, and particularly rates of consumption by vulnerable young people. Recent changes to cannabis legislation in the United States and elsewhere [19] provide a number of natural experiments of both the risks and benefits of (i) legalizing medical marijuana, (ii) decriminalizing marijuana and (iii) legalizing the supply of cannabis. The next decade will provide an opportunity to document both the benefits and risks associated with the changing legal landscape regarding cannabis use. Given the emerging evidence concerning the adverse effects of cannabis use, and the fact that the legalization of the drug could arguably increase the level of risk posed by cannabis use [19], it is critical that these changes in cannabis legislation are monitored and evaluated through well-designed studies that are able to assess the impact of these law changes both at individual and population levels.

References

• Hall W. What has research over the past two decades revealed about the adverse health effects of recreational cannabis use?Addiction 2015; 110: 19–35.


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