Marti Fig 2

Should cannabis be legalized in the United States, and if so, under what conditions? Current research on medical consequences of cannabis use suggest that heavy use of cannabis can have longlasting effects on lung, cardiovascular and mental health, but casual use seems of little harm compared to cigarettes and alcohol. Brain scans of regular marijuana users suggest that people who are not addicted (yet) already have structural abnormalities in cannaboid sensitive brain areas, the amygdala and nucleus accumbens. Policy makers should consider that some (mental) health effects of even moderate use have yet to be discovered, and that youth particularly need to be warned and protected if cannabis is legalized in their state.

Figure 1 ~ A ‘Coffeeshop’ or legal cannabis selling point in Amsterdam, The Netherlands. picture: Ricardo Liberato (free to use with credit- CC)

While in high school in the Netherlands, our biology teacher taught us about the effects and risks of various recreational drugs as part of our curriculum. He personally believed that weed, cannabis, and derived products such as marijuana (Figure 2) should be at least as socially accepted as nicotine or alcohol. We frowned, but he had a point: a stoner won’t get into a pub fight or hit his kids, and at that point cigarettes were a much clearer health risk then joints. Too bad my teacher was later fired for smoking a joint during a school trip. Even in a country that is relatively accepting of cannabis use, it can still get people into serious trouble. Are the health risks really as dire as the social stigma suggests?

Figure 2 ~ Uses of the Cannabis sativa Plant

The recent surge in decriminalization and legalization of weed in the US suggests that policymakers see the pragmatic benefits of allowing marijuana use such as reduced burden on police, tax revenue and taking business away from cartels. However, recently published research adds to a growing body of evidence suggesting that weed may cause more neurological problems than were known when Amsterdam’s coffee shops first opened their doors.

So does cannabis still fit in the category of recreational drugs that are harmless enough to tolerate like alcohol and nicotine? You might say legalization of recreational cannabis use is only a realistic way to regulate a market that is there anyway. Or you could say it sends the wrong message about a common but not harmless drug. To create the best policy, it is important to understand how dangerous cannabis use actually is.

Research into the health consequences of cannabis use is limited by a bias of study subjects not wanting to admit to illicit drug use or using multiple drugs at the same time. For example, looking at lung tissue in marijuana smokers suggest there is a higher risk for developing lung cancer based on cellular stress and pre-malignant transformation of the lung lining upon marijuana smoking [1]. But the link between smoking marijuana and full flown lung cancer was not significant once the data was corrected for concurrent tobacco use [2]. Cannabis use has been associated with cognitive and psychological problems such as memory loss, loss of concentration, and higher chances of psychosis later on for young adult users. A recent study in Massachusetts, where cannabis possession has been decriminalized, sought to determine what happens in the brain of young cannabis users who admitted to regular use but did not use other drugs at the same time.

Regular use of cannabis during young adulthood leads to structural changes of the brain, according to this study at Massachusetts General Hospital in Boston [3]. The active ingredient in cannabis is tetrahydrocannabinol (THC). THC has effects in many different brain regions, particularly the nucleus accumbens and the amygdala. The research group led by Prof. Hans Breiter argued that the latter two must be very important for how our brain responds to THC because they can sense cannaboids like THC very well and are linked to rewarding pleasant feelings from drug use [4,5]. Moreover, THC causes molecular and structural changes in the nucleus accumbens and amygdala in lab animals[6,7].

To better understand the neurological consequences of cannabis use on the human brain, the researchers decided to look for structural changes of the amygdala and nucleus accumbens in cannabis users and non-users. They invited 20 marijuana users and 20 non-users in the age group 18-25 years for brain scans by Magnetic Resonance Imaging (MRI). The users smoked once a week but were not addicted by psychology standards; the non-users had not smoked within the past year and not more than five times in their lives. No one was addicted to other illegal drugs.

All the study participants underwent MRI scanning of the nucleus accumbens and amygdala to look at each structure’s shape, volume and density of these brain regions, as well as how these characteristics were related to each other. The authors found that, in particular, the amygdala of cannabis users was denser and slightly misshapen, but of a similar volume compared to non-users. On average, the more cannabis an individual used, the denser the amygdala was found to be. This is different from previous studies which found that heavy users have smaller amygdalas and addicts have a lower density. According to the article this could mean they detected an earlier state of structural changes in THC sensitive brain areas in people that are not yet heavy or addicted users.

So does it make a difference in reality whether someone uses cannabis sometimes, very often, or is addicted to it? According to two review articles on scientific evidence before 2003 there is no difference between casual and heavy users in terms of long- term memory loss and other cognitive abilities [8,9]. However, persistent use of cannabis did matter in a recent large study following people from pre-drug use childhood into their late thirties. Specifically, those who used cannabis regularly during adolescence reported more loss of memory and thinking skills upon aging, even despite having quit using for a year or more[10]. The risk of developing a psychosis may also be tied to how much cannabis is used, with one study suggesting that heavy users are twice as likely to be affected compared to non-cannabis using control subjects [11].

In conclusion, there is little evidence that occasional cannabis use is damaging beyond the temporary cognitive impairment from a high and the inhalation of toxic smoke into the lungs. There is evidence for more severe and longterm consequences for heavy users, and recent MRI studies suggest that moderate users may already develop abnormalities in brain areas called the amygdala and the nucleus accumbens. How should this knowledge impact public policy towards cannabis? It will be up to politicians to decide whether there is enough evidence to indicate that casual use causes an acceptable level of health problems, and legalization does not increase the number of heavy or addicted users. Moreover, legalization should not interfere with adolescents’ development and education by being more accessible via older friends or fake ID’s, and being marketed to children by the newly legal industry, as is done by the tobacco industry [12,13].  Teenagers are a particularly important group to protect since their brains are still developing and underequipped for assessing consequences of their drug use. If cannabis is legalized, policy has to be in place discouraging use by youth via enforcement, education, and a ban on any kind of marketing.

So what would you tell your representative?

Marti Borkent is an MD-PhD candidate at Erasmus University in Rotterdam, The Netherlands, performing her doctoral work on induced pluripotent stem cells at Massachusetts General Hospital. Many thanks for insight and information from Andreas Kinneging, Hanneke van Ewijk, Serena Shen and Aerjen Tamminga.

References

1. Barsky SH, Roth MD, Kleerup EC, et al. Histopathologic and molecular alterations in bronchial epithelium in habitual smokers of marijuana, cocaine, and/or tobacco. J Natl Cancer Inst 1998; 90:1198.

2. Mehra R, Moore BA, Crothers K, et al. The association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med 2006; 166:1359.

3. Gilman JM, Kuster JK, Lee S, et al. Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users. J Neurosci. 2014 Apr 16;34(16):5529-38.

4. Gilman JM, Ramchandani VA, Davis M, Bjork JW, HommerDW. Why we like to drink: a functional magnetic resonance imaging study of the rewarding and anxiolytic effects of alcohol. J Neurosci 2008 28:4583– 4591

5. Breiter HC, Gollub RL, Weisskoff RM, et al. Acute effects of cocaine on human brain activity and emotion. Neuron 1997 19:591– 611.

6. Azad SC, Monory K, Marsicano G, et al. Circuitry for associative plasticity in the amygdala involves endocannabinoid signaling. J Neurosci 2004 24:9953–9961.

7. Kolb B, Gorny G, Limebeer CL, Parker LA. Chronic treatment with Delta-9-tetrahydrocannabinol alters the structure of neurons in the nucleus accumbens shell and medial prefrontal cortex of rats. Synapse 2006 60:429–436.

8. Grant I, Gonzalez R, Carey CL, et al. Non-acute (residual) neurocognitive effects of cannabis use: a meta-analytic study. J Int Neuropsychol Soc 2003; 9:679.

9. Lyketsos CG, Garrett E, Liang KY, Anthony JC. Cannabis use and cognitive decline in persons under 65 years of age. Am J Epidemiol 1999; 149:794.

10. Meier MH, Caspi A, Ambler A, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci U S A 2012; 109:E2657.

11. Moore TH, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007; 370:319.

12. http://www.huffingtonpost.com/sue-rusche/underage-marijuana-use_b_2079404.html

13. http://www.ftc.gov/sites/default/files/documents/reports/federal-trade-commission-cigarette-report-2011/130521cigarettereport.pdf, Page 6.

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