Gruppo Ginestra
THE HEALTH EFFECTS OF RECREATIONAL CANNABIS USE - WILEY ONLINE LIBRARY - 17 DICEMBRE 2014

David M. Fergusson and Joseph M. Boden - Article first published online: 17 DEC 2014 - © 2014 Society for the Study of Addiction

 

Article

 

The past 20 years have seen a significant increase in research on the antecedents and consequences of cannabis use in young adults. At the beginning of this period there was a relative paucity of evidence concerning both (i) factors that increased the risk of cannabis use and dependence and (ii) consequences of early and heavy cannabis use on health and adjustment. However, our understanding of these issues has increased dramatically during this period. The current state of knowledge of the effects of cannabis use on health and psychosocial functioning among young people is well summarized in Hall's scholarly review of the evidence [1]. Hall attributes this increase in knowledge to the contribution of a series of well-designed epidemiological studies, and in particular the evidence provided by longitudinal birth cohorts during a period of time in which regular cannabis use was relatively common. In his review, Hall shows that there is now substantial evidence to suggest that cannabis use by young people is associated with a range of adverse health and psychosocial outcomes, including increased risks of motor vehicle accidents, cannabis dependence, psychotic symptomatology, lower levels of educational attainment, the use of other illicit drugs, cognitive impairment and chronic bronchitis. In most cases, Hall shows that these linkages have both an age and dose–response gradient, such that these risks are stronger for those individuals who begin using cannabis at a younger age and for those who use cannabis more heavily.

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.


 

• Cass D. K., Flores-Barrera E., Thomases D. R., Vital W. F., Caballero A., Tseng K. Y. CB1 cannabinoid receptor stimulation during adolescence impairs the maturation of GABA function in the adult rat prefrontal cortex. Mol Psychiatry 2014; 19: 536–543.

 

• Battistella G., Fornari E., Annoni J.-M., Chtioui H., Dao K., Fabritius M. et al. Long-term effects of cannabis on brain structure.Neuropsychopharmacology 2014; 39: 2041–2048.

 

• Bossong M. G., Niesink R. J. M. Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia. Prog Neurobiol 2010; 92: 370–385.

 

• Yucel M., Solowij N., Respondek C., Whittle S., Fornito A., Pantelis C. et al. Regional brain abnormalities associated with long-term heavy cannabis use. Arch Gen Psychiatry 2008; 65: 694–701.

 

• Zalesky A., Solowij N., Yücel M., Lubman D. I., Takagi M., Harding I. H. et al. Effect of long-term cannabis use on axonal fibre connectivity. Brain 2012; 135: 2245–2255.

 

• Jacobus J., Goldenberg D., Wierenga C., Tolentino N., Liu T., Tapert S. Altered cerebral blood flow and neurocognitive correlates in adolescent cannabis users. Psychopharmacology (Berl) 2012; 222: 675–684.

 

• Lisdahl K. M., Wright N. E., Medina-Kirchner C., Maple K. E., Shollenbarger S. Considering cannabis: the effects of regular cannabis use on neurocognition in adolescents and young adults. Curr Addict Rep 2014; 1: 144–156.

 

• Ehlers C. L., Gizer I. R., Vieten C., Gilder D. A., Stouffer G. M., Lau P. et al. Cannabis dependence in the San Francisco Family Study: age of onset of use, DSM-IV symptoms, withdrawal, and heritability. Addict Behav 2010; 35: 102–110.

 

• Lynskey M. T., Heath A. C., Nelson E. C., Bucholz K. K., Madden P. A. F., Slutske W. S. et al. Genetic and environmental contributions to cannabis dependence in a national young adult twin sample. Psychol Med 2002; 32: 195–207.

 

• Caspi A., Moffitt T., Cannon M., McClay J., Murray R., Harrington H. et al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-o-methyltransferase gene: longitudinal evidence of a gene × environment interaction. Biol Psychiatry 2005; 57: 1117–1127.

 

• Zammit S., Spurlock G., Williams H., Norton N., Williams N., O'Donovan M. C. et al. Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use. Br J Psychiatry 2007; 191: 402-407.

 

• Zammit S., Owen M. J., Evans J., Heron J., Lewis G. Cannabis, COMT and psychotic experiences. Br J Psychiatry 2011; 199:380–385.

 

• Costas J., Sanjuan J., Ramos-Rios R., Paz E., Agra S., Tolosa A. et al. Interaction between COMT haplotypes and cannabis in schizophrenia: a case-only study in two samples from Spain. Schizophr Res 2011; 127: 22–27.

 

• Van Winkel R. Family-based analysis of genetic variation underlying psychosis-inducing effects of cannabis: sibling analysis and proband follow-up. Arch Gen Psychiatry 2011; 68: 148–157.

 

• Henquet C., Di Forti M., Morrison P., Kuepper R., Murray R. M. Gene–environment interplay between cannabis and psychosis.Schizophr Bull 2008; 34: 1111–1121.

 

• Pelayo-Teran J. M., Suarez-Pinilla P., Chadi N., Crespo-Facorro B. Gene–environment interactions underlying the effect of cannabis in first episode psychosis. Curr Pharm Des 2012; 18: 5024–5035.

 

• D'Souza D., Sewell R., Ranganathan M. Cannabis and psychosis/schizophrenia: human studies. Eur Arch Psychiatry Clin Neurosci2009; 259: 413–431.

 

• Volkow N. D., Baler R. D., Compton W. M., Weiss S. R. B. Adverse health effects of marijuana use. N Engl J Med 2014; 370:2219–2227.

 

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