1. Selected Effects on Brain, Body
MARIJUANA:
Selected Effects on Brain, Body
& Behavior
A presentation prepared by the National Institute on Drug Abuse
February, 2012

2. Marijuana is the Most Commonly Used Illicit Drug In the U.S.
Over 106 million Americans have tried it at ….least once
An estimated 2.4 million Americans used it for ….the first time in 2010
Marijuana is the most commonly abused illicit drug in this Country. Delta-9-tetrahydrocannabinol (THC) is the main active ingredient in marijuana, responsible for many of its known effects.
Source of Statistics: Substance Abuse and Mental Health Service Adminstration (SAMHSA) National Survey on Drug Use and Health
Tetrahydrocannabinol (THC)
Active Ingredient in Marijuana
Source: National Survey on Drug Use and Health, SAMHSA, 2010.

3. High Rates of Past Year Dependence or Abuse on Marijuana (Comparison to other Drugs Among Persons 12 or older, 2010)
Marijuana was the illicit drug with the highest rate of past year dependence or abuse in 2010, followed by pain relievers and cocaine. Of the 7.1 million persons aged 12 or older classified with illicit drug dependence or abuse in 2010: 4.5 million met clinical criteria for marijuana or hashish; 1.9 million met criteria for pain relievers; and 1.0 million persons for cocaine.
(Note that these are not mutually exclusive categories. Source: NSDUH:
Numbers in Thousands
Source: SAMHSA, 2010 NSDUH

4. SOURCE: University of Michigan, 2011 Monitoring the Future Study
In 2009, Reports of Past Month Use of Marijuana Among 12th Graders Exceeded that of Cigarette for the First Time in the Survey’s History
Past month marijuana use in teens exceeds that of tobacco use. The data shown are for 12th graders, but the same pattern is seen for 8th and 10th graders, according to NIDA’s Monitoring the Future (MTF) Survey. These trends show that although we have been making progress in deterring young people from using tobacco products, we have to redouble our efforts to erode the perception that marijuana is a benign drug.
For more information on MTF, see:
SOURCE: University of Michigan, 2011 Monitoring the Future Study

5. Changes in Attitude Lead to Changes in Use: Marijuana Use and Perceived Risk in 12th Graders, (1975 to 2010)
Past Year use
Perceived Risk
Percent
Education is key, because when risk awareness goes up drug use goes down. This slide illustrates the inverse relationship between perceived risk and marijuana use. As perceived risk goes up (red line), marijuana use (blue line) goes down and vice versa. In recent years perceived risk has been decreasing, while use has been ticking up—even daily use among 12th graders is at about 6% (not shown), which is the highest its been in the history of the Monitoring the Future survey .
Source: The Monitoring the Future study, the University of Michigan

6. To Feel Good To Feel Better
Why Do People Take Drugs in The First Place? They like what it does to their brains
The question is often asked: Why would anyone abuse drugs? Research has shown that people generally take drugs to either feel good (i.e., sensation seekers, or anyone wanting to experiment with feeling high or feeling different) or to feel better (i.e., self-medicators, or individuals who take drugs in an attempt to cope with difficult problems or situations, including stress, trauma, and/or to lessen anxiety, fears, depression, or hopelessness).
To Feel Good To Feel Better
Image courtesy: Vivian Felsen

7. Drugs Can be Chemical Imposters (THC mimics a natural brain chemical)
Brain’s Chemical
Anandamide
Drug
THC
What’s so special about marijuana?
The marijuana plant (cannabis sativa) is psychoactive mainly because it contains a specific chemical, called THC that resembles a chemical that is made naturally in the brain, called anandamide. Both THC and anandamide attach to specialized proteins, called cannabinoid receptors (or CBRs), that are found in the brain and the body. CBRs are part of a vast communication network known as the endocannabinoid system (ECS), which plays a critical role in normal brain development and function. This is precisely why marijuana use has the potential to alter normal brain development and function.

8. Marijuana Acts in Many Parts of the Human Brain
Marijuana’s effects can be understood by knowing where in the brain it acts, or where in the brain cannabinoid receptors are found.
Cannabinoid receptors (CBRs) are found in high-density in areas of the brain that influence pleasure, memory, thinking, concentration, movement, coordination, and sensory and time perception. When THC interacts with these receptors, its effects are similar to those produced by naturally occurring chemicals called endogenous cannabinoids.
When someone smokes marijuana, THC stimulates the CBRs artificially, disrupting 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 CBRs, which, along with other changes in the brain, can lead to addiction and to withdrawal symptoms when drug use stops.
Source: Scientific American

9. Marijuana’s Many Acute Effects (Intoxication phase)
Euphoria
Calmness
Appetite stimulation
Altered perception of time
Impairs coordination and balance
Acute psychosis; Panic (anxiety)
Increased heart rate: %
Some evidence for increased risk of heart attack, may be exacerbated in vulnerable individuals (e.g., baby boomers)
The interaction between THC and CBRs explains a lot about MJ’s effects.
Along with euphoria, relaxation is another frequently reported effect in human studies. Other effects, which vary dramatically from person to person, include heightened sensory perception (e.g., brighter colors), laughter, altered perception of time, and increased appetite. After a while, the euphoria subsides, and the user may feel sleepy or depressed. In some users, marijuana can produce anxiety, fear, distrust, or panic.
Marijuana users who have taken large doses of the drug may experience an acute psychosis, which includes hallucinations, delusions, and a loss of the sense of personal identity. Although the specific causes of these symptoms remain unknown, they appear to occur more frequently when a high dose of cannabis is consumed in food or drink rather than smoked.
The connection between marijuana use and cardiovascular risk could be partly explained by marijuana’s ability to increase heart rate (and blood pressure—at least initially) and reduce the blood's capacity to carry oxygen. Such possibilities need to be examined more closely, particularly since current marijuana users include adults from the baby boomer generation, who may have other cardiovascular risks that increase their vulnerability.

10. Marijuana’s Many Acute Effects (Intoxication phase)
Cognitive Dysfunction
Impaired short-term memory
Difficulty with complex tasks
Difficulty learning
Impaired decision-making
Increased risky sexual behavior – HIV
Impaired Driving
Increased risk of accidents
Increased culpability
(Continued.)
Marijuana use impairs a person's ability to form new memories and to shift focus, which can be particularly disruptive to young people, who are at a stage in their lives when they should be absorbing critical information and skills needed to realize their full potential.
THC also disrupts coordination and balance by affecting information processing in the cerebellum and basal ganglia—parts of the brain that regulate balance, posture, coordination, and reaction time. Therefore, learning, doing complicated tasks, participating in athletics, and driving are also affected. Not surprisingly, because marijuana impairs judgment and motor coordination and slows reaction time, an intoxicated person has an increased chance of being involved in and being responsible for an accident. And in fact, a recent systematic review of nine independent studies concluded that acute marijuana consumption is associated with a doubling of the risk of a motor vehicle crash, especially of fatal collisions.
Acute health effects
In 2009, there were >375,000 Marijuana-related ED visits .

11. Long Term Risks of Marijuana Use
Academic failure and low professional achievement
Poorer long-term life outcomes
Mental health problems
Addiction
In light of the many claims that have been made about the long term consequences of marijuana use, what do we actually know?
Our understanding of marijuana's long-term effects on health and behavior is more limited than that of marijuana’s acute effects. Research findings on how chronic marijuana use affects brain structure, for example, have been inconsistent, although it is possible that these effects are too subtle for reliable detection by current techniques. A similar challenge arises in studies of the effects of chronic marijuana use on brain function. For example, although imaging studies (functional MRI; fMRI) in chronic users do show some consistent alterations, the relationships between these changes and cognitive functioning is less clear. This uncertainty is likely to stem from confounding factors which are notoriously difficult to rule out in human studies. They include other drug use, residual drug effects (which can occur for at least 24 hours in chronic users), withdrawal symptoms in long-term chronic users, or an underlying (sometimes even subclinical) mental illness, just to name a few.

12. Early Marijuana (and other drug) Use Linked to Dropping Out of School
Proportion of sample dropping out
between ages 16 and 18
One of the most robust associations, albeit not marijuana specific, is with dropping out of school.
Results of a longitudinal survey of 1392 adolescents (aged years) suggest that (similar to what’s seen with other drugs) marijuana initiation is positively associated with dropping out of high school. The authors concluded that the effect of marijuana initiation on the probability of subsequent high school dropout is relatively stable, with marijuana users' odds of dropping out being about 2.3 times that of non-users.
Source: Bray et al. Health Economics, 9(1), pp. 9-18, 2000.

13. Cannabis Use and Later Life Outcomes are Dose Dependent
% welfare dependent
(ages 21-25)
% Unemployed (ages 21-25)
Mean personal income
In thousands of NZ dollars
at age 25
% gained university degree
by age 25
400+
300 to 399
200 to 299
100 to 199
1 to 99
Never
Number of occasions using
Cannabis ages 14-21
Number of occasions using
Cannabis between ages 14-21
Marijuana use is strongly linked to poorer outcomes later in life.
The relationship between marijuana use and poor life outcomes appears to be dose dependent. Illustrated are the results of a 25-year longitudinal study of a New Zealand birth cohort showing associations between increasing levels of cannabis use at ages and: higher levels of welfare dependence; higher unemployment; lower income at age 25; and lower levels of academic degree attainment by age 25.
These results are consistent with an earlier study in the US showing poorer outcomes for chronic marijuana users in terms of education attained, household income, and overall life satisfaction. (Gruber, AJ et al., Psychological Medicine, 33, pp , 2003.)
Source: Fergusson and Boden. Addiction, 103, pp , 2008.

14. Adolescent Cannabis Use Increases the Risk for Adult Psychosis in Genetically Vulnerable Individuals
no adolescent cannabis use 20 18 16 14 12 10 8 6 4 2
adolescent cannabis use
% with schizophreniform disorder
at age 26
Genes make an important contribution to individual risk for suffering some long term consequences, like adult psychosis.
A series of large prospective studies that followed a group of people over time has shown a relationship between marijuana use and later development of psychosis. Marijuana use also worsens the course of illness in patients with schizophrenia and can produce a brief psychotic reaction in some users that fades as the drug wears off. At present it is difficult to establish whether marijuana can cause schizophrena-like disorders; however, the evidence suggests that amount of drug used, the age at first use, and a genetic predisposition can all influence this risk.
One example (illustrated in the slide) found an increased risk of psychosis among adults who had used marijuana in adolescence and who also carried a specific variant of the gene for catechol-O-methyltransferase (COMT). The COMT gene governs an enzyme that breaks down dopamine, a brain chemical involved in schizophrenia. It comes in two forms: "Met" and "Val." Individuals with one or two copies of the Val variant have a higher risk of developing schizophrenic-type disorders if they used cannabis during adolescence (dark bars). Those with only the Met variant were unaffected by cannabis use.
met/met
val/val
COMT genotype
Source: Caspi, A. et al., Biol. Psychiatry, 57: ; 2005.

15. 1 in 6 who start use in adolescence, 25-50% of daily users
Addiction: About 9% of cannabis users may become dependent
1 in 6 who start use in adolescence, 25-50% of daily users
Comparative Prevalence of Dependence
Among Different Drug Users
Percent of users who
Become addicted
And marijuana is addictive.
Contrary to what many people believe, long-term marijuana use can lead to addiction; that is, people have difficulty controlling their drug use and cannot stop even though they know it interferes with many aspects of their lives. It is estimated that 9 percent of people who use marijuana will become dependent on it. The number goes up to about 1 in 6 in those who start using young (in their teens) and to percent among daily users.
The slide shows the rates of addiction among users of marijuana and a variety of other substances. While not all users become addicted to any drug, it remains a risk with repeated use and is influenced by factors including genetics, age of first use, frequency, dosage used, and route of administration, among others. * *
* Nonmedical Use Source: Anthony et al. Exp. Clin. Psychopharmacol. 2(3), pp (1994)

16. Marijuana addiction is also linked to a withdrawal syndrome that can make it
hard to quit. Symptoms include:
irritability,
sleeping difficulties,
craving,
anxiety, and
increased aggression.

17. Drug Use Outcomes in Twin Pairs (n =234) Discordant for Cannabis Use Before Age 17
Illicit Drug
Abuse/Dependence
Use 7 6 5 4 3 2 1
Odds Ratio
Chronic Marijuana exposure can also lead some users to other drug use.
Not only can long-term marijuana use lead to addiction, but a study of over 300 fraternal and identical twin pairs found that the twin who had used marijuana before the age of 17 had elevated rates of other drug use and drug problems later on, compared with their twin who did not use before age 17.
Opioids
Opioids
Sedatives
Sedatives
Hallucinogens
Cannabis
Cocaine/Stimulants
Cocaine/Stimulants
Source: Lynskey, MT et al., JAMA, 289, pp , 2003.

18. Possible impact of chronic Marijuana use on brain structure and function
Does marijuana damage the brain?
Research on how chronic marijuana use affects brain structure and function is still in its early stages. Some of its effects may be just at the threshold of current detection techniques. And many of the studies report conflicting results, due to differences in methods, subjects, other drug use, abstinence vs. not, etc. Thus, we do not have a full understanding of the extent to which long term marijuana use is associated with persistent deficits in brain performance.
However, the combined results of independent human studies so far, do suggest that marijuana can negatively influence the health of the brain, at least in some users. Animal research also supports this contention. But in human studies, it is notoriously difficult to prove that marijuana causes the defects observed. There is a level of uncertainty that stems from important confounding factors, some of which may in fact be preexisting (before drug exposure) and also associated with increased risk of initiating marijuana use.
With those cautions in mind, the following 2 slides depict examples from brain imaging studies showing effects of chronic marijuana use on the structure and function of the cerebellum, a part of the brain important for motor learning and coordination and possibly other functions as well.

19. The Lower Baseline Cerebellar Metabolism in Marijuana Abusers is likely to Result in Motor Deficits
0.8
0.85
0.9
0.95 1
1.05
1.1
1.15
1.2
Control
Abuser
Cerebellum/Whole Brain
p < 0.01
Control
Marijuana Abuser
Marijuana decreases cerebellar activity in humans.
Since glucose is the main fuel in the brain, brain glucose metabolism patterns are good markers of regional brain activity. In this 1996 study, brain glucose metabolism was measured using positron emission tomography (PET) in the presence or absence of THC (the main psychoactive component in marijuana) in eight normal volunteers and in eight chronic marijuana abusers. Marijuana abusers showed lower baseline activity in the cerebellum compared to non-users, which could account for the motor deficits previously reported in these subjects.
When THC was administered (not shown), cerebellar metabolism increased in all subjects, but only abusers showed increases in cortical (orbitofrontal cortex, prefrontal cortex) and subcortical (basal ganglia) regions. Cerebellar metabolism during THC intoxication was significantly correlated with the subjective sense of intoxication. In addition, the activation of orbitofrontal cortex and basal ganglia by THC in the abusers but not in the control subjects could underlie one of the mechanisms leading to the drive and the compulsion to take the drug that is observed in addicted individuals.
Source: Volkow et al., Psychiatry Research: Neuroimaging, 67, pp (1996).

20. Heavy cannabis users display differences in cerebellar volume
The cerebellum of heavy cannabis users is larger than controls.
Illustrated are the results of a study of regional grey matter volume in cannabis users vs. controls. The areas shown in yellow and red are those with higher measured volume in heavy cannabis users, and include both the left and right anterior lobes of the cerebellum. This is a further indication that the cerebellum is one of the key brain areas that may be altered by cannabis use.
Although not shown here, the same study found that, among chronic users, there was also a link between gray matter volume and amount of drug consumed or severity of cannabis dependence in two regions that are important for learning and memory (hippocampus), and emotional learning, including fear conditioning (amygdala). Hippocampal volume was less among those who used more cannabis; amygdala volume was less in people with greater severity of dependence.
Source: Cousijn et al., Neuroimage, 59 (4), pp (2012).

21. To learn more about marijuana and other drugs of abuse visit NIDA’s website at: or NIDA’s teen site at
To order publications on these topics free of charge in English or Spanish, contact the DrugPubs Research Dissemination Center at 877-NIDA-NIH ( ; TTY/TDD: ) or