Commentary on Volkow et al. 2014 “Adverse Health Effects of Marijuana Use” by Michael McKinney

lab PhotoCannabis, both medical and recreational, enjoys a popular consensus among enthusiasts that it is not only a less dangerous substance than alcohol, but also effectively harmless. As the presence of Cannabis in modern day culture grows, so too does the importance of knowing what effects it has on the human body. A 2014 literature review by N.D. Volkow, the National Institute on Drug Abuse’s Director,published in the New England Journal of Medicine, clumped together a number of studies regarding Cannabis in an attempt to summarize what we know today.

The review tackles a number of issues that could be persistent effects of Cannabis. The first is the risk of addiction. The lifetime risk of addiction to marijuana is evaluated at 9% using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) definition of dependence. However, the review fails to mention the corresponding lifetime addiction rates reported by the same source for other commonly used substances. These include nicotine (32%), heroin (23%), cocaine (17%), alcohol (15%) and stimulants (11%). Also, people who are dependent on Cannabis tend to have histories of poor academic performance, deviant behavior, poor parental relationships, or a history of parental addiction problems (Hall and Degenhardt 2009).

Brain development changes have also been found through marijuana use with the most prominent effects in instances where the users were adolescents. Changes in other ages were not reported. When compared to adults who did not use marijuana at a young age, those who regularly did use it in youth had impaired neural connectivity in regions of the brain that control higher thinking, awareness, memory and learning. However, these results may be reflecting compounding factors on brain development such as other drug use. This reported study looked at a limited number of participants with only 59 Cannabis users and 33 control individuals (Zalesky et al. 2012).

Cannabis use has been linked with increased future drug use. Cannabis reduces the brain’s reactivity to dopamine, a natural reward system the body employs to keep us happy and satisfied. This inhibition of dopamine makes the user more susceptible to future drug use. However, while these findings support Cannabis as a gateway drug, nicotine and alcohol both have the same primer effect on the brain. The gateway drug concept can be explained by social interactions as well. Those who are more likely to take drugs would start with Cannabis due to its availability, and then move to more drugs through social exposure.

In terms of mental illness, an association between anxiety and depression has been partially established with Cannabis use. However, this relationship should be seen only as a correlation, not causation, because those who are openly using marijuana may be predisposed to anxiety or depression. Additionally a link has been established between psychosis, including schizophrenia, and marijuana use. This is most prominent in those with a genetic predisposition to these diseases. Again, it cannot be said that marijuana causes these diseases, as there could be other factors present in those individuals, such as other drug use or preexisting mental conditions.

An association between Cannabis and lung cancer is controversial, and undetermined. While some studies show a link between the two, when compounding factors like cigarette use are removed, the link disappears. Still, a correlation between lung cancer and marijuana cannot be exempt entirely due to the lack of investigation.

Cannabis today is widely regarded as more psychoactive than it was in years past. Figure 1A presents the change in Cannabis potency over time showing an increase in THC content since 1995. This holds interesting implications for genetic studies because the genomic regions related to THC production might have been selected for. This raises questions regarding the genetic makeup of Cannabis as humans have selected for plants with higher psychoactive compounds.

In the following figure 1B, the review presents the number of emergency room visits over the years as a result of different drugs. It shows marijuana, heroin and cocaine. The figure presents an increase in marijuana related visits reaching numbers similar to those of cocaine. However this figure leaves out a lot of relevant information, such as the total number of users for each of the drugs shown. This would allow the reader to see the proportion of users requiring hospital visits and would shed light on how often visits are realistically occurring. Our guess is that if the figure were corrected for total number of users, marijuana would have a very low proportion of ER visits compared to the other two drugs. Also, the study fails to show the number of deaths related to the three drugs, which would confirm the dangers associated with them. Finally if alcohol were included in the figure, it would be a more detailed perspective on the potential dangers of legally used substances.

Ultimately, what we know now is complicated, shallow, and above all, limited. However, figure 2A, shows that the perceived risk of marijuana use has decreased gradually over the last 35 years. This finding suggests that more accurate information is available for the public.

In addition to looking at the adverse effects marijuana presents to users, the review lists several positive medicinal uses of marijuana, including treatments for chemotherapy and AIDS related symptoms such as chronic pain, anorexia or nausea. Also, it lists multiple sclerosis and epilepsy as disorders for which medicinal marijuana has potential to become a major source of relief. More specifically, Sativex, a mixture of compounds from Cannabis is currently undergoing phase 3 trials and awaiting approval from the FDA as a proposed treatment for multiple sclerosis.

Cannabis and its effects are still being understood, and the information we have is limited. It is possible that the cases that have been looked at show a bias and are not representative of the entire population due to the illegality of Cannabis. Also, many of the effects known are only results of short-term use. Long-term effects are still unclear and are difficult to ascertain. This is because sample subjects may not be representative of the entire population of marijuana users and results can be confused by additional factors such as other drug use. Finally, the many chemical compounds of Cannabis and the different effects they have are still not fully understood.

Overall, this review, which is written by one of the authorities on drug abuse and addiction, gives an objective view of what we know about Cannabis and all of the questions that remain unanswered. Even though the paper has several weak points, it offers an impartial view on marijuana, different from the biased research published earlier this year in the Journal of Neuroscience that was severely criticized. While the review puts much of what we know into perspective, more than anything it shines light on the dearth of knowledge and conclusive research. This compels us to conclude that more research on Cannabis and its effects on the body is needed.

References:

W. Hall, L. Degenhardt. 2009. Adverse health effects of non-medical cannabis use. Lancet 374, 1383-91

N.D. Volkow, R.D. Baler, W.M. Compton, S.R.B. Weiss. 2014. Adverse Health Effects of Marijuana Use. The New England Journal of Medicine 370, 2219-2227

Zalesky A, Solowij N, Yücel M, et al. 2012. Effect of long-term cannabis use on axonal fibre connectivity. Brain 135, 2245-2255