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Common Gene Variant May Offer Protection Against Marijuana Dependence

New research shows that specific variations in the cannabis receptor gene (CB1) may be
associated with the development of one or more symptoms of marijuana dependence in
adolescents. This is one of the first studies looking specifically at the link between marijuana
dependence and CB1 variations.

Background: Marijuana is the most commonly abused illegal substance among adolescents and
young adults, and those who begin using at this stage are about twice as likely as adults to
become dependent. Genetic variations in the CB1 receptor—the brain target for the psychoactive
ingredient in marijuana—is a logical candidate gene to study as a potential contributor to
vulnerability to marijuana dependence. Therefore, researchers examined the associations between
specific variants in the CB1 gene and the rates of marijuana dependence.

Study Design: The scientists collected DNA from 541 youths aged 17 or older who had used
marijuana at least five times recently. After interviews to identify one or more DSM-IV symptoms of dependence, 327 were established as cases; the remaining 214 had no symptoms and served as controls. All subjects were genotyped for four specific DNA sequence variations of the CB1 gene.

What They Found: One CB1 variant (found in 21 percent of the general population) was associated with a lower rate of having one or more marijuana dependence symptoms, while two others (present in 12 percent of the general population) were linked to increased likelihood of developing dependence symptoms.


Comments from the Authors: Identifying gene variants that may afford some protection against
marijuana dependence may have important implications for intervention. However, it is likely that multiple genes and their interactions with environmental events influence marijuana and other drug addictions. Therefore, some level of genetic protection may not necessarily protect an adolescent from becoming dependent on drugs or suffering other related health consequences.

What’s Next: Future studies should examine these genetic variants for other drug-related traits, as
well as additional DNA sequence variations for possible drug abuse associations.

Publication: The study, led by Dr. Christian J. Hopfer of the University of Colorado, was published
in volume 141B, pages 895-901 (2006) of the American Journal of Medical Genetics Part B
(Neuropsychiatric Genetics)

NIDA NewsScan, August 22, 2007

Adolescents Also Can Experience Marijuana Withdrawal Symptoms; Differences In
Severity Between Teens, Adults Noted

Scientists at the University of Vermont report that adolescents who smoke marijuana regularly and are trying to quit can experience the same withdrawal symptoms as adults, although the prevalence and magnitude of these symptoms are lower than those seen in previous research among adults.

The scientists collected information from 72 adolescents--primarily young white males between 14 and 19 years of age seeking outpatient treatment for marijuana abuse. Their substance abuse behavior was measured by means of self-report questionnaires and interviews. The participants also rated the presence and severity of specific symptoms known to be associated with drug withdrawal.

The scientists observed that 78 percent of the participants reported having at least 2 symptoms, 58 percent reported at least 4 symptoms, and 44 percent reported at least 6 symptoms. The most common symptoms were craving for marijuana, depression, irritability, restlessness, sleeping difficulties, hostility, loss of appetite, increased aggression, anxiety, and headache. At least 22 individuals rated their marijuana craving, depression, irritability, and sleep problems as moderate, with craving for marijuana being the only symptom listed as severe.


What it means: Much of the research on marijuana withdrawal has been conducted in adults, yet youth age 20 and under comprise over half of all U.S. treatment admissions for marijuana abuse. This study shows that adolescents who abuse marijuana experience withdrawal symptoms similar to those seen in adults upon drug abstention. However, difference in symptom severity in adolescents compared with adults may reflect less frequent use of the drug by teens. The withdrawal syndrome could have a negative impact on and contribute to its continued use in young people who attempt to stop.

Graduate student Ryan Vandrey, Dr. Alan Budney, and their colleagues published these NIDA-supported findings in the May 9, 2005 issue of Drug and Alcohol Dependence.

NIDA NewsScan, September 7, 2005

A Healthy Start: Some Parenting Practices May Protect Youth From Early Marijuana Use

Parenting practices during the middle years of elementary school, such as supervision and monitoring, may affect adolescent initiation of marijuana use, according to a new NIDA-supported study conducted by Dr. Chuan-Yu Chen and colleagues from the Johns Hopkins University Bloomberg School of Public Health.

The scientists followed 1,222 youth from elementary school through young adulthood to determine if early parenting practices protect youth from early onset of marijuana use. The researchers measured three dimensions of parenting--parental monitoring, parental involvement/reinforcement, and coercive parental discipline parenting (attempts to correct child behavior by using serious threats such as physical and nonphysical punishment)--as well as opportunity to first try marijuana.

The scientists found that children with the lowest levels of parental monitoring and parental involvement/ reinforcement were almost 30 percent more likely to try marijuana for the first time when compared with the most highly monitored children. Similarly, children with higher levels of coercive discipline were more likely to try the drug for the first time. Overall, the scientists observed a delay and reduction in the opportunity to first try marijuana among children with the highest levels of parental involvement/reinforcement, which lasted through early adulthood.


What it means: Numerous studies have documented associations between parenting practices and an array of health-compromising behaviors in adolescents. The results of this study expand upon existing evidence and suggest that parenting practices such as early increased monitoring and supervision may have lasting effects by reducing and delaying marijuana use through young adulthood. Additional research is needed to better understand the role of parental practices in preventing and delaying adolescent drug use.

This study was published in the June 2005 issue of Pediatrics.

NIDA NewsScan, September 7, 2005

Heavy Abuse of Marijuana Linked to Inferior Decision-making Skills, Altered Brain Activity

Men who smoke marijuana heavily are less successful than moderate smokers or nonsmokers on tasks requiring decision-making. This difference remains even after a brief period of abstinence, according to a study by Dr. Karen Bolla of The Johns Hopkins Medical Institutions.

She and her colleagues recruited 11 adult male marijuana smokers and 11 healthy male controls. When the marijuana smokers had been abstinent for 25 days, the scientists tested the participants to identify decisionmaking differences. Then, using positron emission tomography (PET), the researchers were able to see and record which brain regions the individuals used during the test.

The scientists noted that heavy marijuana abusers performed significantly worse than moderate marijuana abusers. PET scans showed that heavy marijuana abusers had less activation in regions of the right side of the brain that are involved in decision-making, and greater activation in areas on the left side of the brain. The scientists speculate that the brains of these individuals are recruiting other regions, like the left cerebellum, to compensate for the poorly functioning decision-making areas.


What it means: These findings suggest that heavy marijuana abuse has a harmful effect on key processes within the brain, and may make the individual more sensitive to immediate rewards, less sensitive to losses, and slow to learn from previous mistakes. Damage to areas of the brain associated with decision-making can significantly increase a person's vulnerability to addictive behaviors and make them more resistant to treatment.

The scientists published the study in the June 2005 issue of the journal NeuroImage.

NIDA NewsScan, August 23, 2005

Smoking Marijuana Alters Blood Flow in the Brain

A recent report shows that marijuana smokers experience changes in blood flow patterns in their brains, and these changes persist in heavy users of the drug even after a month of abstinence.

Scientists led by Dr. Ronald Herning of NIDA's Intramural Research Program measured blood flow through the anterior and middle cerebral arteries in 54 marijuana users (11 light, 23 moderate, and 20 heavy) and compared the results with observations of blood flow in 18 similarly aged adults who did not use the drug. They took measurements after 3 days of admission to the study, and after 28-30 days of monitored abstinence.

Results showed that the speed of blood flow through the arteries at the beginning and end of the study was significantly higher in all 3 groups of marijuana users than in the control group. Measurements taken at the beginning of the study also showed that marijuana users demonstrated higher resistance to blood flow through their brain arteries. This observation persisted in the heavy marijuana users during the 30 days of not smoking, while resistance to blood flow improved in the other 2 groups.


What it means: The findings suggest that smoking marijuana, the most commonly used illegal substance in the United States, may alter blood vessels in the brain. Future research is needed to determine whether the increased resistance to blood flow seen in heavy users of the drug is reversible and determines the health consequences. The findings from this study also could help explain the drug's effects on memory, learning, and problem solving.

The researchers published their findings in the February 8, 2005 issue of the journal Neurology.

NIDA NewsScan, August 23, 2005

Study Investigates Short-Term Effects of Marijuana Use on HIV+ Patients

Researchers from the University of California, San Francisco, have found that patients infected with the human immunodeficiency virus (HIV) may not experience adverse effects on cell counts or viral load from short-term marijuana use.

In the 3-week trial, the researchers assigned 62 HIV+ patients to use marijuana cigarettes, cannabinoid capsules, or a placebo three times a day before meals. All of the patients were on antiretroviral regimens containing protease inhibitors for at least 8 weeks before the study began. Fifty-eight percent of the patients entered the study with levels of HIV circulating in their blood below the limit currently detectable by the usual tests.

Overall, there were no significant changes in the levels of HIV in the patients’ blood. Compared to the placebo group, CD4+ and CD8+ T cell levels rose slightly in the marijuana and cannabinoid capsule groups.


What it means: This study indicates that short-term use of marijuana may not substantially elevate viral load in individuals with HIV infections who are receiving stable antiretroviral regimens containing protease inhibitors. However, the researchers say that these findings need to be confirmed with larger and longer trials. They also caution that these results cannot be extrapolated to the potential effects of marijuana available on the street because the marijuana used in this study was of known potency and content.

Dr. Donald Abrams and colleagues published this study, funded in part by the National Institute on Drug Abuse, in the August 19 issue of the Annals of Internal Medicine.

NIDA NewsScan, December 12, 2003

Starting Marijuana Use in Mid-Teens or Younger May Result in Cognitive Impairment Later in Life But Reasons are Unclear

There is evidence that individuals who start to smoke marijuana at an early age—while the brain is still developing—show deficits in cognition which are not seen in individuals who begin use of the drug when they are older. The reasons for this difference are unclear.

Scientists from the Harvard Medical School and from the intramural research program of the National Institute on Drug Abuse (NIDA) found lasting cognitive deficits in those who started to smoke marijuana before age 17. The researchers analyzed neuropsychological test results from 122 long-term heavy users of marijuana and 87 subjects who had used marijuana only a few times (control subjects). Sixty-nine of the 122 users started using marijuana at age 17 or before. The subjects were between the ages of 30 and 55 at the time of the study, and all had refrained from any drug use 28 days prior to testing.

Individuals who started using marijuana at age 17 or younger performed significantly worse on the tests assessing verbal functions such as verbal IQ and memory of word lists than did those who started using marijuana later in life or who had used the drug sparingly. There were virtually no differences in test results among the individuals who started marijuana use after age 17 and the control subjects.


The investigators suggest three possible hypotheses that might explain these differences. One possibility is that early-onset smokers had lower innate cognitive skills before they ever started smoking marijuana. A second possibility is poor learning of certain cognitive skills by young users of marijuana who neglect school and academic pursuits. The third and most ominous possibility is that marijuana itself has a neurotoxic effect on the developing brain. According to the authors, further research will be required to determine the relative contributions of these three factors.

What it means: Youth who use marijuana before their midteens may show long-term deficits in certain verbal skills—but the reasons for these deficits are not yet clear.

Dr. Harrison Pope and colleagues published the study in the March 2003 issue of the journal Drug and Alcohol Dependence.

NIDA NewsScan, May 2, 2003

Concurrent Use of Tobacco and Marijuana May Hamper Cigarette Smoking Cessation Efforts

Tobacco smokers who also smoke marijuana may be less likely to quit smoking tobacco and less likely to try to quit than those who do not smoke marijuana, according to a study by researchers at The Johns Hopkins University. Dr. Daniel Ford and colleagues interviewed 431 adults who had reported being current tobacco smokers in a study conducted 13 years earlier. In the baseline interview, more than 40 percent of the participants reported having smoked marijuana, with more than 25 percent reporting using it within the previous 30 days (recent use) and 9 percent reported daily use for two weeks or more. At the 13-year follow-up, 79 percent of participants who had reported smoking tobacco at baseline were still smoking it.

Recent and daily use of marijuana at baseline were more predictive of continued tobacco smoking than use of marijuana more than a month prior to baseline. Participants who reported recent use were about twice as likely to continue to smoke tobacco 13 years later compared those who did not use marijuana within the preceding 30 days. Those who reported daily marijuana use were over three times more likely to still smoke tobacco. About 66 percent of recent marijuana users reported trying to quit tobacco during the following 13 years compared to 80 percent of those who had never used marijuana.


What it means: These findings suggest that marijuana use may interfere with tobacco cessation attempts. However, there is no evidence that marijuana use can substitute for tobacco use.

This study, funded by the National Institute on Drug Abuse, was published in the August 2002 issue of Drug and Alcohol Dependence.

NIDA NewsScan, April 9, 2003

Alcohol Use Prior to Smoking Marijuana Results in Increased THC Absorption

Scientists at McLean Hospital/Harvard Medical School observed that male volunteers who drank alcohol (vodka mixed with orange juice) prior to smoking marijuana detected the effects of marijuana more quickly, reported more episodes of euphoria, and had higher levels of THC in their blood than did subjects who smoked marihuana without first ingesting alcohol.

The investigators concluded that alcohol might increase the absorption of THC, the active ingredient of marijuana, into the body, resulting in a higher high than is experienced when using marijuana alone.


What it means: Marijuana and alcohol are often used together, but little is known about why they are combined. The results of this experiment suggest that these two drugs are used to maximize the desired effects of the drug experience and so may explain the popularity of this combination.

The study was published in Volume (issue): 64 (2) 2001 of the journal Drug and Alcohol Dependence by lead investigator Dr. Scott E. Lukas.

NIDA NewsScan, January 30, 2002

Scientists Show Marijuana Use Affects Learning, Other Memory Skills

Researchers at the McLean Hospital/Harvard Medical School have found that heavy, long-term marijuana use produces memory impairment for days or even weeks after users stop smoking.

To ascertain the effects of marijuana use on memory and other cognitive skills, the Harvard research team recruited 180 individuals between the ages of 30 and 55. About one-third of the subjects were current heavy users who had smoked marijuana at least 5,000 times in their lives (equivalent to using the drug at least once a week for 13 or more years) and who were smoking daily at the time they entered the study; another third were former heavy users. Individuals inthe control group had used marijuana at least once but fewer than 50 times in their lives. All of the subjects were asked to abstain from marijuana for 28 days, and their drug abstinence was confirmed by urine samples. They were administered a battery of tests to assess general intellectual function, abstraction ability, attention span, verbal fluency, and ability to learn and to recall new verbal and visuospatial information just before and then on the 1st, 7th, and 28th days ofabstinence. At days 0, 1, and 7,


current heavy users of marijuana scored significantly lower than the control subjects on recall of word lists, but by day 28, there were virtually no differences among the groups on any of the tests.

Cognitive deficits were detectable at least 7 days after heavy marijuana use, but these changes appeared to dissipate within a few weeks, after THC (tetrahydrocannabinol), the active ingredient of marijuana, and its metabolites have cleared the body.

What it means: This study clearly points out that marijuana is not a benign substance. By impairing memory and other cognitive functions, smoking marijuana can negatively affect academic achievement and other life skills.

Lead investigator Dr. Harrison G. Pope, Jr. published the study in the October 2001 issue of Archives of General Psychiatry.

NIDA NewsScan, October 16, 2001


Adult Male Mice Exposed to Methamphetamine In Utero Have Increased Neurotoxicity Risk

Researchers at the University of Chicago, in experiments with mice, have found that prenatal exposure to methamphetamine increases response to the toxic effects of the drug in adult males. Some effects of prenatal methamphetamine exposure were observed in female offspring, but were much less than those seen in the males.

The investigators say these findings may raise concerns for male methamphetamine abusers whose mothers used the drug while pregnant. The neurotoxic risk from using methamphetamine as adults may be greater for men who were exposed prenatally. Methamphetamine toxicity is characterized by persistent decreases in the levels


of dopamine and serotonin in certain brain regions. It is known that in humans, dopamine deficits are associated with symptoms of Parkinson's disease.

What it means: This finding, coupled with the increasing use of club drugs, such as methamphetamine, by women of childbearing age, makes this issue a potential public health concern.

The researchers, led by Dr. Alfred Heller, published their findings in the August 2001 issue of the Journal of Pharmacology and Experimental Therapeutics.

NIDA NewsScan, October 16, 2001

Study Finds That Beliefs About Health Effects of Cigarette Smoking Change with Age

Surveys of more than 7,000 individuals questioned periodically from middle school through their mid-30’s about their beliefs concerning the risks from smoking cigarettes and the value they place on health reveal that these attitudes change with age.

A research team from Arizona State University and Indiana University drew participants for the study from a large, Midwestern community. At the most recent assessment, 26 percent smoked cigarettes. The researchers found that:

• Between the ages of 11 and 14, the perception that smoking would harm one’s own health decreased. However, between the ages of 15 and 18 and continuing to age 24, there was an increased belief that smoking can be harmful to one’s personal health.
• Throughout adolescence and young adulthood, there was a small but statistically significant increase in the belief that cigarette smoking is harmful to people’s health in general.
• Between the ages of 15 and 18, the value that adolescents placed on health decreased. However, the value placed on health increased starting at age 19 and continued to increase up to age 29.
• Between ages 11 and 14, belief in the positive psychological


consequences of smoking increased; however this trend reversed between ages 15 and 18.
• Between 11 and 14, the belief that cigarettes are addicting decreased, but between the ages of 15 and 18 and between ages 19 and 24, both smokers and nonsmokers increased their belief that cigarettes are addicting.
• Across all age groups, those who smoked were significantly less likely to believe that smoking is harmful to either health in general or to their own personal health, and smokers placed significantly less value on health than did nonsmokers.

What it means: Smoking interventions aimed at adolescents must counter the perception among middle school students that cigarette smoking does not pose a risk of addiction or a risk to one’s own health, and must counter the declining values placed on health by high school students.

The research team led by Drs. Laurie Chassin and Clark Presson from Arizona State University and Dr. Steven J. Sherman from Indiana University published the study in the September, 2001 issue of Health Psychology.

NIDA NewsScan, January 30, 2002

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