**8. Future directions in CUD research**

To date, few neuroimaging studies examine adolescent populations with CUD. Adolescent chronic cannabis use is associated with greater performance-related activation in frontotemporal areas, despite similar performance, suggesting neuroadaptations, or greater neural effort to perform memory and inhibition tasks [56]. A recent prospective cohort study scanned adolescents as they performed a working memory task prior to and after their first cannabis exposure [80]. The researchers found that those youths that would go on to use cannabis by the age of 15 (follow up), showed increased frontoparietal activity at baseline relative to the non-using group—these neural differences remained unchanged or increased when examined longitudinally. This is the first study to demonstrate frontoparietal and neurocognitive alterations prior to cannabis use. The researchers also found that at 12 years of age (baseline), the adolescents who would go on to use cannabis by the age of 15 (follow-up) had significantly lower scores on the cognitive battery. The difference scores on the cognitive battery from baseline to follow-up did not change, suggesting no significant neurocognitive changes following cannabis initiation. This prospective cohort study is one of the first to demonstrate

Given the changing compound composition of cannabis, combined with increasing THC levels and availability, understanding the effects of cannabis use on the brain and on memory, learning and reward processing should be a priority in adolescents. Accordingly, the Adolescent Brain Cognitive Development (ABCD) study recently launched by the National Institute of Health in the United States will follow 10,000 children longitudinally with multiple measures of neural, cognitive and emotional functioning [81]. This prospective cohort study will pro-

With the exception of nicotine, smoked cannabis includes many of the same chemicals and carcinogens found in tobacco that can damage lung tissue [82]. Heavy cannabis smoking is associated with chronic bronchitis and inflammation/injury in the larger airways [82]. Findings for other types of lung diseases and cancers are mixed, given high rates of comorbid tobacco use in regular cannabis users. Some of the chronic respiratory effects appear reversible, particularly in those individuals who only smoke cannabis [83, 84]. The impact of cannabis use on lung health may also change, as other methods of intake are gaining popularity,

One of the largest public health concerns with legalization of cannabis use is the effect of the drug on driving. Driving simulation studies show a relationship between blood THC levels and impaired performance, particularly with reaction time and lane position variability (i.e., weaving) [85]. One study had occasional cannabis smokers perform a visuomotor tracking task while undergoing fMRI after taking low-dose THC and found decreased psychomotor skills as well as reduced activity in fronto-parietal areas [86]. After alcohol, cannabis is the most commonly reported drug in driving accidents and fatalities [87]. There is current

specific neurocognitive features that may exist prior to cannabis exposure.

vide much-needed information on the long-term effects of cannabis use.

**7. Other harms from cannabis**

146 Recent Advances in Cannabinoid Research

such as vaping or edibles [82].

A fundamental question in cannabis research is whether observed alterations in neurobiology and cognition with heavy cannabis use persist with abstinence or whether they are reversible. The neurobiological studies are currently limited by an absence of standardized methods to characterize cannabis consumption levels as well as compound composition. The varying compounds in cannabis samples present a challenge to conducting systematic cannabis research; it is unknown how all of these might interact [28] and varying cannabinoid levels across studies may account for the diverse findings reported in the literature. Most studies rely on self-report measures of cannabis use and those that do toxicology analyses provide poor measures for quantifying exposure or the timeframe. Additionally, different measures of intake (i.e., inhaling, vaping, with/without tobacco) can also influence THC release/metabolism. Given all of the uncertainty between exposure parameters and neural substrates, many researchers are now calling for standardization of cannabis use metrics, particularly as the drug's effects appear more closely linked to dosage than duration of use [49]. Questions for future research include: (1) understanding CB1 receptor changes and relationships with reward, motivation, craving and abstinence, (2) clarifying cognitive and motivational alterations and whether these are precursors or consequences of CUD and (3) understanding the links between cannabis use and psychotic disorders. In this changing political, social, psychopharmacological and compositional landscape of cannabis, understanding the harms associated with cannabis use and CUD will be fundamental in informing policy and supporting clinicians.
