Marijuana has Long-term Effects on the Brains of Adolescents


After alcohol, marijuana is the most widely used illegal drug in the United States (I mean seriously, who hasn’t smoked up at least once? According to Pew Research Center, half of the country) But pot laws are rapidly changing in many parts of the country and soon it may be as ubiquitous as alcohol. Four states in the US have legalized marijuana for recreational use and 23 total states have some form of legal marijuana use (including D.C.). While the health effects of alcohol have been well studied and are significant (some 88,000 deaths/year, the third highest cause of preventable death in the US, according to the CDC and NIAAA), little is known how this shifting trend in marijuana use will affect the country. Another important trend is the amount of THC (Δ-9-tetrohydrocannabinol, the chemical that is primarily responsible for the psychoactive effects of marijuana) in marijuana strains has been steadily increasing over the past few decades [1, 2]. The big question that researchers are asking themselves is if legal marijuana use drastically increases, what are the long-term personal and public health consequences of marijuana use? Of course, this is a huge question with many complexities.

Significantly, Marijuana is the also the most widely used illegal substance amongst youths. Adolescence (ages 12-17) is an extremely critical period for brain development [3, 4] yet the effects of marijuana on the brains of kids have not been thoroughly studied. A recent paper out of Dr. Steven R. Laviolette’s laboratory at the University of Ontario sought to answer this question: what happens to brains of adolescent and adult rats that have been exposed to THC?

Renard et al. 2016 abstract

Why was the research done? What is the hypothesis?

 There have been a number of studies published that suggest there might be an association between prolonged marijuana use (especially of high-potency strains) and schizophrenic-like or psychotic-like symptoms [5, 6] although there is disagreement in the scientific community on the evidence [7, 8] (I may write a blog post discussing this issue in the future). It is has even been suggested that youths that smoke marijuana are more at risk for psychotic symptoms as adults [9, 10]. The author’s sought to test this directly by injecting adolescent and adult rats with THC for a number of days, waiting a period of time after the injections, then measuring the long-term effects on the rats. The team hypothesized THC would have induced long-term changes in the brains of adolescent but not adults rats, and subsequent changes in psychotic-like behavior.

How was it done?

Adolescent and adult rats were injected with THC twice daily for 11 days. The dose of THC administered was increased (escalating dose) to account for any tolerance that may occur. As an important control, separate groups of adolescent and adult rats were injected with vehicle (the solution that THC was dissolved in but minus the THC itself). Following a 30-day abstinence period after the last injection, THC-adolescent, control-adolescent, THC-adult, and control-adult rat groups were subjected to number of behavioral and molecular tests to see what effect the drug had on the animals. I need to point out that the 30-day abstinence period is significant in the rat life-span. This is enough time for the adolescent rats to become adults so what the scientists are primarily studying is the long-term effects of THC on adolescents vs adults in adulthood.

In the behavioral neuroscience field, we have devised another of tests to measure various aspects of animal behavior. Obviously we can’t inject humans with THC and see what happens so we have to use rodents and identify behaviors that approximate a similar behavior in humans. Of course, rodent behavior is no where near as complex as humans but rats are remarkably sophisticated animals (ask anyone living in New York) and scientists have developed a number of ways to measure things from motivation to social behavior to anxiety to depression.

In this experiment, a social test was used, two different types of anxiety tests and a motor activity test. The tests measured effects on motivation, exploratory-behavior (another indicator of how motivated rats are), social interaction, and anxiety.

The scientists also measured the activity of dopamine-releasing neurons in the living animal using a technique called in vivo electrophysiology. Recall from my post I am Neuron! that when activated, brain cells (called neurons) conduct an electrical current that results in the release of neurotransmitters onto another neuron. This electrical current is called an action potential and we can measure this by inserting a special probe into the those neurons in the animals brain (the probe measures electrical currents). Therefore, with in vivo electrophysiology we can measure every time a neuron fires (i.e. an action potential is generated) in a specific part of the brain. Using this technique, the scientists measured dopamine neurons in an important region of the brain called the VTA and how often these neurons fire in THC vs control rats. Check out this video for more details on in vivo electrophysiology.

Finally, brains from animals were dissected and a number of protein molecules were studied using a common technique in molecular biology called a Western blot (or known as an immunoblot). A Western blot takes advantage of antibodies that are able to recognize and stick to one specific type of protein. Therefore, this assay can tell you two main things 1) if your protein of interest is present in your sample and 2) approximately how much of your protein there is compared to other samples. In this paper, tissue from a specific brain region is used and the protein is analyzed by Western blots in order to comparing quantities of proteins between the different experimental groups. Of course, the limitation of a Western blot is if you have a good antibody for your protein of interest. Luckily there are many biotech companies such as Cell Signaling that specialize in making and testing reliable antibodies. The scientists used the Western blots to study many proteins in a region of the brain called the prefrontal cortex (PFC), which is believed to be important in self-control and other high-function brain processes. Check out this video for more details on Western Blots.

What did they find?

THC-adolescent rats exhibited deficits in numerous behavioral experiments compared to controls while THC-adult rats did not appear to have any behavioral changes.

*Recall that these experiments were conducted 30 days after the last THC dose so the author’s show that these are long-term effects of THC on the brain of adolescent rats.

In the social activity test, rats showed little interest in interacting with a stranger rat (normal rats are usually curious about the novel stranger). THC-adolescents also did not walk around or explore a new cage as much. In the two different anxiety tests, THC-rats appeared to have be more anxious (demonstrated more anxiety-like behavior).

In the electrophysiology experiment, VTA DA neurons fired more frequently for some reason in THC-adolescents compared to the other groups.

Finally, numerous protein changes in the PFC were observed in a number of important signaling pathways such as Wnt and mTOR pathways. Interestingly, THC-adolescents vs THC-adults seemed to have opposite effects on this proteins.

Limitations to the study?

  1.  The behavioral changes observed were statistically significant (meaning, most likely a real effect and not some kind of fluke of random chance) but were modest changes in some of the tests performed. Would the changes last beyond the 30 days post injection in this study?
  2. There are impressive arrays of behavioral tests that rats can perform to measure numerous aspects of cognition (for example, memory and learning) but none of these experiments were performed. A far greater range of behavioral experiments would have made this study more compelling.
  3. While the electrophysiology and Western blot data are intriguing, the author’s performed no experiments to determine if these changes are responsible for the difference in behavior (association vs causation). These changes could merely be an incidental change and have nothing to do with the behaviors studies.
  4. The doses that the mice were injected with, while based on a previous study, are somewhat arbitrary. Would the changes be more pronounced or less pronounced with higher/lower doses or a shorter/longer dosing regimen?
  5. Only male rats were studied. Would the same behavioral and molecular changes occur in female rats?

What does it mean?

Based on the behavioral and molecular data presented, this data paper suggests that adolescent rats (but not adults) exposed to THC have long-lasting changes in the brain. The author’s argue that these effects recapitulate schizophrenia-like symptoms but I am not entirely convinced. Also, THC given to rats is not the same thing as marijuana smoked by human teenagers. So it’s important to keep in mind that this is one study. In science, we never draw grand conclusions about anything based on one study. Nevertheless, several other reports have corroborated these findings (see this review paper for a summary of many of them [11]). Indeed, it does seem that marijuana use can cause long-term deficiencies in human and rodent brains. The results of this paper are certainly intriguing and, if true, a whole host of stricter regulations on marijuana use in states that have legalized it may need to put in place to help curb increasing marijuana abuse amongst youths.


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  1. Moore TH, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007;370(9584):319-28.
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  1. Rubino T, Parolaro D. Long lasting consequences of cannabis exposure in adolescence. Molecular and cellular endocrinology. 2008;286(1-2 Suppl 1):S108-13.
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  1. Renard J, et al. Long-term consequences of adolescent cannabinoid exposure in adult psychopathology. Frontiers in neuroscience. 2014;8:361.

Personality-targeted Interventions Can Reduce Alcohol and Marijuana Use Among Adolescents


Let me state the obvious: alcohol and marijuana are the two most widely used drugs of abuse in the United States. According to the annual National Survey on Drug Use and Health (NSDUH), (the most comprehensive survey of drug use and abuse in the United States conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA)) as of 2013, 86.8% of the population aged 18 or older have reported having consumed alcohol during their lifetime with over 16.6 million adults diagnosed with alcohol abuse disorder.

Of course, we all know the prevalence and extent of underage drinking, and the damage alcohol has on the developing brain has been heavily researched, not to mention all the significant secondary problems associated with alcohol abuse (car crashes, sexual assault on college campuses, falling off of balconies… ).

But here’s some numbers anyways: as of 2013, 8.7 million youths aged 12-20 reported past month alcohol use, a shockingly high number for an age group this is not legally allowed to drink alcohol…

Similarly, marijuana, which is still illegal in the vast majority of the US, is nearly as ubiquitous. According to the NSDUH 2013 survey, 19.8 million adults aged 18 or older reported past month marijuana use.

And with marijuana legalization in Colorado and Washington, a significant concern raised by many is that abuse of the drug among youths will dramatically increase even higher than it is now. The research supporting the damage marijuana can inflict on brain development is also significant.

But what if the risk of use of alcohol and marijuana by youths could be reduced? What if a teacher could be given the tools to not only identify certain risky personality traits in their students but also use that knowledge to help those at-risk students from trying and using drugs such as alcohol and marijuana? A series of studies coming out of the laboratory of Dr. Patricia A Conrod of King’s College London report having done exactly that.

SFN 2015 LogoI had the pleasure of seeing Dr. Conrod speak at the recent Society for Neuroscience Conference as part of a satellite meeting jointly organized by the National Institute on Drug Abuse (NIDA) and National Institute on Alcohol Abuse and Alcoholism (NIAAA). Dr. Conrod presented a compelling story spanning over a decade of her and her colleague’s work, in which certain personality traits amongst high risk youths, can actually be used to predict drug abuse amongst those kids. Dr. Conrod argues that by identifying different risk factors in different adolescents, a specific behavioral intervention can be designed to help reduce alcohol drinking and marijuana use in these youths. And who is best to administer such an intervention? Teachers and counselors, of course: educators that spend a great deal of time interacting with students and are in the best position to help them.

The Teacher-Delivered Personality Targeted Interventions For Substance Misuse Trial, also known as the Adventure Trial, was conducted in London during 2008-2009 and the results were first published in 2010.

This ambitious study recruited 2,643 students (between 13 and 14 years old) from 21 secondary schools in London (20 of the 21 schools were state-funded schools). Importantly, this study was a cluster-randomized control trial, which means the schools were randomly assigned to two groups: one group received the intervention while the other did not. The researchers identified four personality traits in high-risk (HR) youths that increase the risk of engaging in substance abuse. The four traits are:

  1. Anxiety sensitivity,
  2. Hopelessness
  3. Impulsivity
  4. Sensation seeking.

A specific intervention based on cognitive behavioral therapy (CBT) and motivational enhancement therapy (MET) was developed to target each of these personality traits. Teacher, mentors, counselors, and educational specialists in each school that were recruited for the study were trained in the specific interventions. In general, CBT is an approach used in psychotherapy to change negative or harmful thoughts or the patient’s relationship to these thoughts, which in turn can change the patient’s behavior. CBT has been effective in a treating a number of mental disorders such anxiety, personality disorders, and depression. MET is an approach used to augment a patient’s motivation in achieving a goal and has mostly been employed in treating alcohol abuse.

The CBT and MET interventions in this study were designed to target one of the four personality traits (for example, anxiety reduction) and were administered in two 90-minute group sessions. The specific lesson plans for these interventions were not reported in the studies but included workbooks and such activities as goal-setting exercises and CBT therapies to help students to dissect their own personal experiences through identifying and dealing with negative/harmful thoughts and how those thoughts can result in negative behaviors. Interestingly, alcohol and drug use were only a minor focus of the interventions.

The success of the interventions was determined through self-reporting. The student’s completed the Reckless Behavior Questionnaire (RBQ), which is based on a six-point scale (“never” to “daily or almost daily”) to report substance use. Obviously due to the sensitive nature of these questionnaires and need for honesty by the students, measures were taken to ensure accuracy in the self-reporting, such as strong emphasis on the anonymity and confidentiality of the reports and inclusion of several “sham” items designed to gauge accuracy of reporting over time. Surveys were completed every 6-months for 24-months (two years) which is a sufficient time frame to assess the effect of the interventions.

Most importantly, schools were blinded to which group they were placed in and teachers and students not involved in the study were not aware of the trial occurring at the school. The students involved were unaware of the real purpose and scope of the study. These factors are important to consider because it held eliminate secondary effects and helps support the direct efficacy of the interventions themselves.

The results were impressive: reduced frequency and quantity of drinking occurred in the high-risk students that received the intervention compared to the control students that did not. While HR students were overall more likely to report drinking than low-risk (LR) students, the HR students saw a significant effect of the personality-targeted interventions on drinking behavior.

Conrod et al.2013 abstract

A study of this size is incredibly complex and the statistics involved are equally complex. The author’s analyzed the data in a number of ways and published the results in several papers. A recent study modeled the data over time (the 24-months in which the surveys were collected) and used these models to predict the odds that the students would engage in risky drinking behavior. The authors reported a 29% reduction in odds of frequency of drinking by HR students receiving the interventions and a 43% reduction in odds of binge drinking  when compared to HR students not receiving the interventions.

Interestingly, the authors report a mild herd-effect in the LR students. Meaning that they believe the intervention slowed the onset of drinking in the LR students possibly due to the interactions between the HR student’s receiving the interventions and LR students. However, additional studies will need to be done in order to confirm this result.

Recall that the Reckless Behavior Questionnaire (RBQ) was utilized in this study to quantify drug-taking behavior. While the study was specifically designed to measure effects on alcohol, the RBQ also included questions about marijuana. So the authors reanalyzed their data and specifically looked at effects of the interventions on marijuana use.

Mahu et al. 2015

The found that the sensation seeking personality sub-type of HR students that received an intervention had a 75% reduction in marijuana use compared to the sensation seeking HR students that did not receive the intervention. However, unlike the findings found on alcohol use, the study was not able to detect any effect on marijuana use for the HR students in general. Nevertheless, the data suggest that the teacher/counselor administered interventions are effective at reduce marijuana use as well.

While you may be unconvinced by the modest reduction in drinking and marijuana frequency reported in these studies and may be skeptical of the long-term effect on drug use in these kids, keep in mind that the teachers and counselors that administered these interventions received only 2 or 3 days of training and the interventions themselves were very brief, only two 90-minute sessions. What I find remarkable is that such a brief, targeted program can have ANY effects at all. And most importantly, the effects well outlasted the course of the interventions for the full two-years of the follow-up interviews.

These targeted interventions have four main advantages:

  1. Administered in a real-world setting by teachers and counselors
  2. Brief (only two 90-minute group sessions)
  3. Cheap (the cost of training and materials for the group sessions)
  4. Effective!

The scope of this intervention needs to be tested on a much larger cohort of students in a larger variety of neighborhoods but it is extremely promising nonetheless. Also, it would be interesting to breakdown these data by race, socioeconomic status, and gender, all of which may impact the effectiveness of the treatments and was not considered in this analysis. Finally, how would you implement these interventions on a wide scale? I eagerly look forward to additional work on these topics.

Thanks for reading 🙂

See these other articles in Time and on King’s College for less detailed discussions of these studies.

Also see these related studies from Conrod’s group:

Castellanos-Ryan N, Conrod PJ, Vester JBK, Strain E,, Galanter M, Conrod PJ. Personality and substance misuse: evidence for a four-factor model of vulnerability. In: Vester JBK, Strain E, Galanter M, Conrod PJ, eds. Drug Abuse and Addiction in Medical Illness. Vols 1 and 2. New York, NY: Humana/Spring Press; 2012.

Conrod PJ, Pihl RO, Stewart SH, Dongier M. Validation of a system of classifying female substance abusers on the basis of personality and motivational risk factors for substance abuse. Psychol Addict Behav. 2000;14(3):243-256.

Conrod PJ, Stewart SH, Comeau N, Maclean AM. Efficacy of cognitive behavioral interventions targeting personality risk factors for youth alcohol misuse. J Clin Child Adolesc Psychol. 2006;35(4):550-563.

Conrod PJ, Castellanos-Ryan N, Strang J. Brief, personality-targeted coping skills interventions and survival as a non-drug user over a 2-year period during adolescence. Arch Gen Psychiatry. 2010;67(1):85-93.

O’Leary-Barrett M, Mackie CJ, Castellanos-Ryan N, Al-Khudhairy N, Conrod PJ. Personality-targeted interventions delay uptake of drinking and decrease risk of alcohol-related problems when delivered by teachers. J AmAcad Child Adol Psychiatry. 2010;49(9):954-963.