Jodi Gilman, PhD

There has never been a drug that has inspired as much passion as marijuana. People join societies, go to cannabis events, join political causes, and even elect politicians based on their opinions about cannabis. Supporting cannabis legalization has become trendy and progressive, whereas opposing legalization is considered stodgy, conservative, and reactionary. And yet, for all its popular appeal, the science that has emerged on cannabis use does not look good, especially for the teenage brain.

Marijuana is by far the most commonly used illicit substance among adolescents and young adults, even surpassing tobacco use. About 45% of 12th graders and more than 50% of 18- to 25-year-olds have tried cannabis, and use is steadily increasing. In most Western societies, 15- to 24-year-olds have higher rates of cannabis use than those aged 25 and older, which demonstrates that marijuana use is particularly problematic among teenagers.

 Research has consistently shown that earlier use is associated with worse outcomes, primarily because the brain is still developing and is more vulnerable to the effects of drugs. Adolescent marijuana use has been associated with impaired memory, difficulty in learning, poorer life outcomes, and even changes in the structure and function of specific brain regions. Adolescents and young adults are also more likely than older adults to become addicted to marijuana, which has negative effects on physical, emotional, and psychological health.

To understand all the effects of marijuana on the brain, it is important to first understand what happens when delta-9-tetrahydrocannabinol (THC), the main psychoactive compound found in marijuana, enters the brain. THC acts on cannabinoid receptors, which are located throughout the brain. The endocannabinoid system helps regulate a variety of functions by monitoring how active neurons are and how much neurotransmitter is released. The neurotransmitters that are affected by THC affect pleasure, mood, pain, appetite, motivation, memory, and muscle activity.

The endocannabinoid system helps keep brain cell activity in balance, and when THC artificially stimulates cannabinoid receptors, this disrupts the function of the natural cannabinoids. An overstimulation of these receptors in key brain areas produces the marijuana “high,” as well as its other effects on mental processes. Over time, this overstimulation can alter the function of cannabinoid receptors, which-along with other changes in the brain-can lead to addiction and to withdrawal symptoms when drug use stops. The endocannabinoid system is also important in regulating brain development. Because it helps control neuron activity, it plays a major role in brain wiring (ie, how brain cells “learn” when to grow new synapses and how to connect to other neurons).

[[{"type":"media","view_mode":"media_crop","fid":"44419","attributes":{"alt":"Â© nisargmedia.com/shutterstock.com","class":"media-image media-image-right","height":"140","id":"media_crop_5850791849746","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4963","media_crop_rotate":"0","media_crop_scale_h":"127","media_crop_scale_w":"125","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"Â© nisargmedia.com/shutterstock.com","typeof":"foaf:Image","width":"138"}}]]One of the reasons that many people think that cannabis is harmless is that there are many myths about marijuana (

). The most common myth is that marijuana is not addictive. This has clearly been debunked by science; marijuana is addictive, particularly for young people. Marijuana addiction resembles other drug addictions: it is characterized by loss of control over consumption, loss of interest in activities not involving cannabis, recurrent use resulting in failure to fulfill major obligations, continued use despite negative consequences, and even its own cannabis withdrawal syndrome.

As with other addictions, cannabis-dependent individuals are characterized by compulsive drug-seeking, loss of control, and the use of marijuana despite significant problems associated with its consumption. About 90% of those who seek treatment for cannabis-related substance disorders report difficulty in achieving and maintaining abstinence.

 Adults who seek treatment for marijuana dependence average more than 10 years of daily or almost daily use and about 6 attempts to reduce or stop consumption.

Perhaps the myth that marijuana is not addictive began because among adults the addiction rate is 9% (meaning that drug dependence develops in 9% of marijuana users); thus, it is not as addictive as other drugs such as cocaine and tobacco (

 However, 9% of 18 million marijuana users is a considerable number. Furthermore, for adolescents, the addiction rate jumps to 17%, meaning that dependence will develop in nearly 1 out of every 6 teenage marijuana users. For daily marijuana users, it is estimated that 25% to 50% will become addicted.

The second myth is that marijuana use has no long-term effects. This is a tough myth to dispel because, unfortunately, few studies have actually examined long-term effects. Longitudinal studies in general are notoriously expensive and difficult to complete, and marijuana use in particular simply was not a focus of attention until very recently. Probably the most thorough long-term study was published in 2012.

 In this study, researchers assessed IQ in children aged 7, 9, 11, and 13 years, before the onset of cannabis use, as well as over several years in adulthood. Participants who used marijuana most regularly had an 8-point drop in IQ from childhood to adulthood. One of the most striking findings was that this IQ drop occurred only in those users who had cannabis dependence before the age of 18. Adolescent marijuana users exhibit worse cannabis-related effects on learning and memory than adult users. MRI scans show that cannabis exposure during adolescence has significant effects on brain volume, the folding patterns of the cortex, neural connectivity, and white matter integrity.

An issue to consider with long-term research is that these studies are testing people who started using cannabis 20 or 30 years ago. The marijuana that was smoked back then is very different from what is smoked today-it is practically a different drug. THC is present at much higher doses today than it was even in 1990.

 Animal studies have shown that THC has dose-dependent neurotoxic effects on brain regions rich in cannabinoid receptors, which means the effects are greater at higher doses. It is plausible that studies on long-term effects of cannabis underestimate the effects on the brain.

The media spreads many myths regarding marijuana as a treatment for mental health disorders such as depression, anxiety, and even PTSD. However, there is little evidence of this; in fact, research has shown that cannabis use is associated with an increased risk of developing mental health disorders, particularly psychotic disorders. This is especially true in persons who start using cannabis during adolescence. Although a causative role of cannabis for psychosis is still being debated, epidemiological and neurobiological research suggests that individuals with a predisposition to schizophrenia are more vulnerable to the psychosis-inducing effects of marijuana.

One of the first studies on marijuana and schizophrenia followed 50,465 Swedish adolescents over 15 years and found that individuals who used cannabis heavily by age 18 were 6 times more likely to develop schizophrenia than those who did not use cannabis.9 Several longitudinal studies have also shown an increased risk of depression in cannabis users compared with non- users, and the level of risk increases with earlier initiation and more frequent use.

 It is important to note that many other variables such as age of exposure, amount of cannabis use, childhood trauma, and a family history of psychotic illness affect the relationship between marijuana use and the development of mental health issues. But almost universally, these relationships tend to be strongest in those who start to use when they are young.

So what does all this mean for clinicians? This is a particularly important question because teenagers are likely receiving mixed messages from parents, teachers, friends, and especially the media. I would start with a few things that we can say confidently. First, we know that marijuana is addictive. Maybe not for everyone, and maybe not as addictive as tobacco, but we know that 1 in 6 teenagers will become addicted, and this addiction-just like addiction to alcohol or cigarettes or cocaine-affects neural mechanisms underlying tolerance, changes the reward system of the brain, and is associated with a distinctive withdrawal syndrome.

Second, we know that marijuana affects learning and memory. We do not know precisely how robust these effects are, how long-lasting they are, or whether they resolve after abstinence-more research needs to be done-but what we do know is that marijuana affects learning, memory, and decision-making capacity.

Third, although we may someday discover therapeutic components of cannabis that can be purified-which may eventually be useful for mental health treatment-the current state of science does not show the benefit of smoked marijuana for psychological conditions; in fact, marijuana use likely worsens symptoms. Fourth, and of greatest importance to teenagers, we know that nearly all negative effects of marijuana (eg, brain changes, neurocognitive deficits, addictive potential) are worse in teenage than in adult users.

These facts underscore the need for useful clinical interventions, including prevention, early detection, and treatment, for cannabis use disorder among adolescents. Prevention is the most promising approach to reducing cannabis use in teenagers. Many prevention programs can be implemented in schools. A meta-analysis of school-based prevention programs found that the most effective programs reduced cannabis use in adolescents by 27.9%.

Another promising area for reducing cannabis use disorders is effective screening. The CRAFFT questionnaire and the Brief Screener for Tobacco, Alcohol and Other Drugs can be used with youths.

 There are a variety of treatments to help teenagers with problematic marijuana use. Brief interventions may be effective; adolescents who received a brief motivational intervention called Project CHAT used less cannabis compared with a control group who received usual care.

More comprehensive treatment may be needed if teenagers develop patterns of problematic use. These treatments include cognitive behavioral therapy (CBT), motivational enhancement therapy (MET), family therapy, and contingency management. The largest psychotherapy trial to date is the Cannabis Youth Treatment Study, which included 600 adolescent cannabis users randomized to 5 treatment interventions that were different combinations of CBT, MET, and family therapy.

None of the 5 interventions was superior to the others, but all treatments reduced the amount of cannabis use, demonstrating that any intervention in which teenagers can talk about and reflect on their drug use may be effective. There are currently no pharmacological treatments for cannabis use disorders, although some are being developed.

Teenagers need to know that cannabis has very real effects on how they think, process information, and make decisions, and that it may even affect their mental health. Young people face unique challenges during the transition from adolescence to young adulthood, and this is a formative time for them to make important decisions about college, career choices, and relationships-decisions that require clear thought. Although everyone is entitled to their opinion on the pros and cons of marijuana legalization, health practitioners need to counter, with scientific facts, the message that cannabis is harmless to the teenage brain.

Dr Gilman is Assistant Professor in the department of psychiatry at Harvard Medical School, and a neuroscientist at the Center for Addiction Medicine of the Massachusetts General Hospital in Boston. She reports no conflicts of interest concerning the subject matter of this article.

 Jonston LD, O’Malley PM, Bachman JG, Schulenberg JE. Monitoring the future: national results on adolescent drug use. 2012. 

http://www.monitoringthefuture.org/pubs/monographs/mtf-overview2011.pdf

 Budney AJ, Hughes JR. The cannabis withdrawal syndrome. 

 Copeland J, Rooke S, Swift W. Changes in cannabis use among young people: impact on mental health. 

 Anthony JC, Warner LA, Kessler RC. Comparative epidemiology of dependence on tobacco, alcohol, controlled substances, and inhalants; basic findings from the National Comorbidity Survey. 

 Meier MH, Caspi A, Ambler A, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. 

 Lisdahl KM, Wright NE, Kirchner-Medina C, et al. The effects of regular cannabis use on neurocognition in adolescents and young adults. 

 Wrege J, Schmidt A, Walter A, et al. Effects of cannabis on impulsivity: a systematic review of neuroimaging findings. 

 Office of National Drug Control Policy: Executive Office of the President. April 2012. 

 AndrÃ©asson S, Engstrom A, Allebeck P, Rydberg U. Cannabis and schizophrenia: a longitudinal study of Swedish conscripts. 

 Brook DW, Brook JS, Zhang C, et al. Drug use and the risk of major depressive disorder, alcohol dependence, and substance use disorders. 

 Fergusson DM, Horwood LJ, Swain-Campbell N. Cannabis use and psychosocial adjustment in adolescence and young adulthood. 

 Patton GC, Carlin JB, Degenhardt L, et al. Cannabis use and mental health in young people: cohort study. 

 Rey JM, Sawyer MC, Raphael B, et al. Mental health of teenagers who use cannabis: results of an Australian survey. 

 Porath-Waller AJ, Beasley E, Beirness DJ. A meta-analytic review of school-based prevention for cannabis use. 

 Kelly SM, Gryczynski J, Mitchell SG, et al. Validity of brief screening instrument for adolescent tobacco, alcohol, and drug use. 

 Knight JR, Sherritt L, Harris SK, et al. Validity of brief alcohol screening tests among adolescents: a comparison of the AUDIT, POSIT, CAGE, and CRAFFT. 

 D’Amico EJ, Miles NJ, Stern SA, Meredith LS. Brief motivational interviewing for teens at risk of substance use consequences: a randomized pilot study in a primary care clinic. 

 Dennis M, Godley SH, Diamond G, et al. The Cannabis Youth Treatment (CYT) Study: main findings from two randomized trials. 

 Gray KM, Watson NL, Carpenter WJ, et al. N-acetylcysteine (NAC) in young marijuana users: an open-label pilot study. 

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For all its popular appeal, the science that has emerged on cannabis use does not look good--especially for the teenage brain.

Jodi Gilman, PhD

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