Genetic differences may protect some who experienced childhood trauma from later marijuana dependence, study finds

WASHINGTON UNIVERSITY IN ST. LOUIS

Genetic variation within the endocannabinoid system may explain why some survivors of childhood adversity go on to become dependent on marijuana, while others are able to use marijuana without problems, suggests new research from Washington University in St. Louis.

“We have long known that childhood adversity, and in particular sexual abuse, is associated with the development of cannabis dependence. However, we understand very little about the individual difference factors that leave individuals vulnerable or resilient to these effects,” said Ryan Bogdan, PhD, assistant professor of psychological and brain sciences in Arts & Sciences and a senior author of the study.

Forthcoming in the Journal of Abnormal Psychology, the study is among the first to pinpoint a specific genetic variant that may influence susceptibility to cannabis dependence in the context of childhood trauma.

THC, the main psychoactive ingredient in marijuana, influences an array of mental and bodily functions because it closely mimics chemical enzymes that the endocannabinoid system naturally produces to send signals between neurons and other individual cells throughout the body. These signals trigger the production of other internal chemicals, such as adrenalin, which help the body modulate its response to external influences, such as fear, stress and hunger.

Like most bodily functions, the workings of the endocannabinoid system are closely programmed and controlled by a set of genetically coded instructions.

“In this study, we investigated whether variation in genes within the endocannabinoid system may be particularly important in setting the stage for cannabis dependence, especially in the context of childhood trauma,” said lead author Caitlin E. Carey, a PhD student working with Bogdan.

In phase one of the study, researchers examined genetic data from 1,558 Australian marijuana users who self-reported various types of sexual abuse as children. Carey and colleagues examined whether Single Nucleotide Polymorphisms (SNPs, pronounced “snips”) located in or near endocannabinoid system genes were associated with the

development of marijuana dependence symptoms in the context of childhood sexual abuse.

SNPs represent differences in a single DNA building block called a nucleotide and are the most common form of genetic variation in people, with an estimated 10 million SNPs in the human genome.

While little is known about many SNPs, some have been identified as key biological markers for genetic diseases. When SNPs occur within a gene or in a regulatory region near a gene, they may affect how that gene functions, perhaps raising disease risk or changing how an individual responds to certain environmental factors such as drugs or trauma.

The vast majority of SNPs, including those looked at in this study, have two different alleles at each locus; one of these alleles is inherited from the biological mother, with the other being inherited from the biological father. Alleles with two matching pieces of genetic information are called homozygotes (for example A/A or G/G), while those with mixed pairs are called heterozygotes (A/G).

Of the endocannabinoid variants examined, a single variant within the monoacylglycerol lipase (MGLL) gene demonstrated a significant interaction with childhood sexual abuse and later cannabis dependence.

More specifically, the study found that variation within this SNP (known as rs604300) in MGLL showed a clear association between child sexual abuse and cannabis dependence, such that increasing exposure to childhood sexual abuse was associated with a greater number of cannabis dependence symptoms only among individuals who were homozygous for the more common G allele. There was no association between child sexual abuse and cannabis dependence symptoms in heterozygotes, and a negative relationship between childhood sexual abuse and cannabis dependence symptoms in A allele homozygotes.

“As we expected, childhood sexual abuse was overall associated with individuals reporting a greater number of cannabis dependence symptoms,” Carey said. “But what was particularly intriguing is that this association was only seen among people with two copies of the more common G allele. People with at least one copy of the less common A allele did not show this pattern, so these data suggest that the A allele may provide some form of resiliency to the development of dependence.

The endocannabinoid system is known to play an important role in the body’s response to stress. Monoacylglycerol lipase, which MGLL codes for, regulates the availability of 2-

AG, an endocannabinoid neurotransmitter that binds to the same receptors as the THC in plant-based cannabis.

Findings replicated in second sample

In phase two of the study, Carey and colleagues attempted to replicate the findings using data from 859 American participants obtained from the Study of Addiction: Genetics and Environment. Here again, they found the same interaction between the rs604300 genotype and child abuse to be significantly associated with cannabis dependence symptoms.

Carey and colleagues speculate that the rs604300 minor A allele’s role in buffering against later cannabis dependence may be related to how the brain reacts to threat.

As Bogdan said: “The amygdala is a region of the brain critical for behavioral vigilance, including coordinating our behavioral responses to threat in the environment. Heightened amygdala reactivity has been consistently linked to anxiety disorders. Prior research has shown that endocannabinoids and marijuana, as well as prior childhood adversity, affect amygdala function. Endocannabinoid signaling, in particular, regulates reactivity to threat by facilitating a dampening of amygdala response (i.e., habituation) when threats are repeatedly presented with no adverse consequence.”

The amygdala (shown in red) is a region of the brain critical for behavioral vigilance, including coordinating physiologic and behavioral responses to threat. The A allele at rs604300 within MGLL, which conferred protection to cannabis dependence in the context of elevated childhood adversity, was associated with heightened threat-related amygdala habituation (i.e., a increased dampening of response over time) among those exposed to elevated childhood adversity. Such elevated amygdala habituation is associated with recovery from environmental stress.

If the rs604300 A allele is associated with relative increased amygdala habituation (such as a dampening of response over time) to threat in the context of childhood adversity, it is possible that child abuse survivors with this allele may be less prone to later use cannabis in an attempt to achieve the same mood-altering result, they speculated.

In a third phase of this study, they tested for this connection in an independent group of 312 undergraduate students from the Duke Neurogenetics Study and found increased amygdala habituation as a function of early life stress in minor A allele carriers, but not in GG individuals. The finding reinforces the possibility that MGLL rs604300 genotype may play a key role in decoupling the neurobiological link between early life stress and mental health outcomes in later life.

Collectively, while speculative, these data suggest that elevated amygdala habituation among individuals with the A allele who were exposed to childhood trauma may result in decreased reliance on marijuana to cope with future stressors and negative affect.

“It’s important to mention that these findings are unlikely to be informative at an individual level,” Carey said. “We won’t see a genetic test for cannabis dependence anytime soon, if ever, but it’s a start.”

Source:   http://www.eurekalert.org/pub_releases/2015-11/wuis-mdi111015.php

Few topics have been more distorted by politicians and media than claims about the criminal justice system in its various forms. When the offense involves illicit drugs (use, possession, or trafficking), the distortion becomes pronounced.

In large measure, a complicated set of data have been made even more difficult to grasp because of tendentious (and often false) assertions forwarded by drug legalization advocates, who seek to advance their own “reforms” by first misrepresenting the criminal justice facts. Moreover, though drug use overall is subject to confusion, distortion is even greater when marijuana is the drug in question. An example of agendas distorting understanding is the effort to blamedrug laws for the growth in incarceration. That effort seeks to convince a public otherwise disinclined to accept more drugs that current drug laws have created the supposed injustice of “mass incarceration.” This is demonstrably untrue.

To answer with the facts, we will address several distinct dimensions of legal institutions concerning illicit drugs: prison sentences, recidivism of released prisoners, and the relationship of drug use to the commission of criminal acts. (We addressed the parallel issue of drug arrests in a previous study, showing that they are far fewer in proportion to drug use than drug reform advocates claim.)

We start with prison inmates, found in both state and federal prisons, and contrast the cumulative numbers of those imprisoned with those entering in a single year. In all cases, we will find that the proportion of drug offenses to the overall number of prisoners has been much overstated. Cumulatively, all drug offenders in both systems constitute20 percent of inmates (303,800 out of 1,508,636 sentenced inmates).

THE FEDERAL PRISON SYSTEM:

The federal system holds 13 percent of all prisoners, but contains the larger proportion of drug offenders. This happens because many trafficking offenses, be they interstate or international, are specifically federal in nature. But even as the total number of prisoners has grown, the drug-offender percentage has declined steadily.

There were 52,568 federal prisoners in 1989 (those “under jurisdiction”), and by 2014, there were 191,374 (those “sentenced” – the categories shifted slightly over time, yielding slight variation in respective calculations). Yet the percentage of drug offenders in the total peaked in 1996, when it stood at 59.6 percent. A 2014 publication from the White House showing the cumulative total of federal prisoners broken down to show drug offenses as the most serious charge, reveals that the proportion of drug offenders had dropped to 44 percent of all offenders in 2011. By 2014, the most recent data on sentenced drug offenders in the federal prison system shifted back to 50 percent of all federal inmates, an increase from the previous ratio due largely to recent inmate releases.

When we turn to inmates entering federal prison in a single year, data are more current, but show the same trajectory. In 1998, the proportion of drug offenders incarcerated for that year was 41 percent (vs. 57.8 percent of the 1998 cumulative “jurisdiction” figure). By 2014, according to the United States Sentencing Commission (USSC), drug offenders (of all types) had fallen to only 32 percent (of 75,836 entering federal inmates, 22,193 were drug offenders). Importantly, 96.6 percent of entering inmates who were drug offenders were convicted of trafficking offenses, while only 0.9 percent were convicted of simple possession.

We can further break these data down by drug type, and by nature of the drug offense. Methamphetamine resulted in the largest subset of drug types with more than 6,304 incarcerations, while heroin produced 2,431.

Though recent legislative reforms have altered the mandatory sentencing guidelines regarding powder cocaine offenses (based on weight) compared to crack offenses (a former ratio of 100 to 1 has been amended to 18 to 1), there were only 4,959 powder cocaine convictions in 2014, compared to 2,439 crack convictions. Moreover, the number of crack cocaine inmates sentenced for simple possession was 0.3 percent, or no more than 7 people.

Finally, marijuana federal incarcerations totaled only 3,971. Marijuana offenses are overwhelmingly (97.6 percent) for trafficking, with a “simple possession offense” representing only 75 individuals (or 1.9 percent), with that conviction often resulting from downward plea-bargaining from more serious offenses.   To show the emphasis on traffickers, when asked in Congressionaltestimony how many drug possession offenders the Drug Enforcement Administration (DEA) refers for federal prosecution, Acting Deputy Administrator Jack Riley stated, “virtually none.”

What, then, is currently driving the changing distribution of the federal inmate population? To a large extent it is a rising number of immigration offenses, according to a study by the Congressional Research Service. This fact is echoed for single-year entry for prisoners as well: in 2014 the USSC shows 29 percent were immigration offenders, while 32 percent were drug offenders.

THE STATE PRISON SYSTEM: The state prison system is larger, holding 1,317,262 sentenced prisoners cumulatively in 2014. The state prison inmate population has also grown over time, and the absolute number of drug offenders within that total has nearly doubled since 1989 from 120,100 to 208,000 (sentenced) in 2014.

Yet just as with the federal system, the percentage of drug offenders has declined since the peak year 1990 when it stood at at 22 percent. For 2014, those whose most serious offense involved drugs were only 16 percent of sentenced state prison inmates (drug possession offenses are only 3.6 percent of all state inmates).

While there has been a marked increase in the state prison population over the past few decades as America has gotten more serious about combatting crime, the data do not support the idea that drug offenses are the primary driver of those increases. Further, with regard to the current push to decriminalize or legalize drug use, there is no support for the assertion that convictions for drug use/possession are responsible for the sharp increases in either state or federal prison inmates.

SENTENCING REFORM AND RECIDIVISM:

And what of sentencing reforms leading to the release of large numbers of federal drug offenders? A substantial problem is recidivism, or re-offending within a relatively short period of time, as we have elsewhere recently argued. Yet the press persists in misrepresentation. According to the Economist, advocating for prisoner release, “Given how high America’s incarceration rate is, it is fair to say reducing it won’t precipitate a crime wave. Many convicts serving long sentences were never generally dangerous, or have mellowed with age, and no longer pose a threat to the public.” But the data show otherwise. According to a Bureau of Justice Statisticsstudy of prisoners released in 2005 and tracked for five years, 32 percent were drug offenders.

Of these, fully 77 percent of those released re-offended within that five- year-period (57 percent of all offenders re-offended at only one year).

It is worth noting two features of a further breakdown of the 404,638 released prisoners in the study. First, the outcome is the same regardless of the type of drug offense (trafficking or possession); that is, either type of offense has comparable re-offense rates. Drug possession offenders had 78 percent recidivism, drug trafficking offenders, 75 percent.

Second, the percent of re-offenses where the subsequent crime specifically involved drugs reached 51 percent. More compelling, violent crimes were fully 25 percent of drug inmates’ recidivating offenses.

These data clearly show if drug offenders are released through sentencing reform, both drug and violent crime will follow; to the extent that they are released early, the effect is to compress their criminal impact into a shorter period.

Further, inmates’ prior arrest history matters. In this study, for all offenders, the mean number of prior arrests per released prisoner was nearly 11.

For those who had ten or more prior arrests, 86 percent re-offended within 5 years. (Even for those aged 40 and over, the recidivism for drug offenders was 71 percent.)

DRUG USE AND THE COMMISSION OF CRIMES:

Finally, there is the role of drugs in the commission of crime. According to another Bureau of Justice Statistics study, one third of state inmates and one quarter of federal inmates committed their offenses under the influence of illicit drugs. That holds for all crimes, not just drug offenses.

For state prisoners, 69 percent used drugs “regularly,” and for 59 percent, that drug was marijuana (with 30 percent using cocaine/crack).

For federal prisoners, 64 percent used drugs “regularly,” with 53 percent using marijuana (and 28 percent using cocaine/crack). Even for federal trafficking offenders, 34 percent were using drugs at the time of the offense.

The same pattern holds for violent offenders. Of them, 49 percent of both federal and state offenders used drugs in the month prior to the offense. The number using drugs at the time of the violent offense reached 28 percent of state and 24 percent of federal prisoners. Homicide-specific rates of drug use in the month prior to the offense were 49 percent and 45 percent, respectively for state and federal prison inmates, with a respective 27 percent and 17 percent using at the time of the homicide.

POLICY CONCLUSIONS:

By these data, we may conclude the following:

1. Sentencing reforms that result in the early release of prison inmates will increase the number of future crimes, and crime victims, through recidivism, while the effect will be concentrated in time, thereby stressing law enforcement and rehabilitation services.

2. Drug intoxication (including the most prevalent drug, marijuana), is deeply implicated in crime commission, including violent crime. It follows that enabling greater drug use

will magnify the criminal impact, with the corollary that efforts to reduce drug use prevalence should help lower the incidence of crime.

3. In particular, decriminalizing or legalizing marijuana will have virtually no impact on prison overcrowding, but the attendant increase in drug-use prevalence nationwide will likely lead to increased commission of crimes, including non-drug offenses and violent offense

Source:  http://www.hudson.org/research  Nov. 2015

Examining Linkages with Criminal Behavior and Psychopathic Features into the Mid-30s

Abstract

Objectives: Examine whether young men who chronically use marijuana are at risk for engaging in drug-related and non-drug-related criminal offending and exhibiting psychopathic personality features in their mid-30s.

Methods: Patterns of marijuana use were delineated in a sample of predominately Black and White young men from adolescence to the mid-20s using latent class growth curve analysis. Self-report and official records of criminal offending and psychopathic personality features were assessed in the mid-30s. Analyses controlled for multiple factors indicative of a pre-existing antisocial lifestyle and co-occurring use of other substances and tested for moderation by race.

Results: Four latent marijuana trajectory groups were identified: chronic high, adolescence-limited, late increasing, and low/nonusers. Relative to low/nonusers, chronic high and late increasing marijuana users exhibited more adult psychopathic features and were more likely to engage in drug-related offending during their mid-30s. Adolescence-limited users were similar to low/nonusers in terms of psychopathic features but were more likely to be arrested for drug-related crimes. No trajectory group differences were found for violence or theft, and the group differences were not moderated by race.

Conclusions: Young men who engage in chronic marijuana use from adolescence into their 20s are at increased risk for exhibiting psychopathic features, dealing drugs, and enduring drug-related legal problems in their mid-30s relative to men who remain abstinent or use infrequently.

1. Source:  http://jrc.sagepub.com/content/52/6/797  Published online before print June 29, 2015, doi:10.1177/0022427815589816Journal of Research in Crime and DelinquencyNovember 2015 vol. 52 no. 6 797-828  Email: dap38@pitt.edu

The state’s medical-marijuana industry wants to be taken seriously, but its stumbling start and questionable practices have produced exactly the opposite effect.

Its history of shoddy background checks on dispensary applicants exposed a lack of professional oversight that delayed its rollout for several months.

The state’s first dispensary, in Salem, didn’t open until June, and the second, in Brockton, just opened in August.

Patriot Care Corp., which plans to run a dispensary and cultivation facility in Lowell, is working toward a January opening.

And now we learn, thanks to an illuminating article in The Sun last Monday, that the vast majority of medical-marijuana doses provided so far went for treatments not recognized under the existing law.

To date, 2,333 prescriptions, called certifications, have been authorized for the eight state-approved conditions — ALS, Parkinson’s disease, glaucoma, HIV/AIDS, Crohn’s disease, multiple sclerosis, cancer and hepatitis C — while another 22,130 approved fall under the “other” category in the state’s database.

That’s because Massachusetts is just one of three states — along with California and New Hampshire — that give doctors the option to dispense medical marijuana for other reasons not officially sanctioned.

What’s the sense of compiling an official list of conditions if doctors can determine whether or not to prescribe medical marijuana? It takes the teeth out of this current law.

So why this additional doctors’ discretion?

We have our suspicions, which center on the current efficacy of marijuana as a prescription drug.

This same question was raised by the Journal of the American Medical Association (JAMA), which has indicated that aside from helping control the nausea and vomiting related to chemotherapy, specific pain syndromes, and some multiple-sclerosis side effects, there’s scant evidence to support other medical benefits.

According to JAMA, those excluded conditions include those approved by our state law, including hepatitis C, Crohn’s disease and Parkinson disease.

Without rigorous trials — like those required by the FDA — to certify a drug, is there no wonder why a doctor’s subjective opinion holds so much weight?

These startling numbers show the need — again — for reform in the state’s toddling medical-marijuana industry. The law should be amended to further review the conditions covered, and to limit vigorously any exceptions to that official list.

Source: http://www.lowellsun.com/opinion/ci_28922964/medical-marijuana-industry-is-critical-condition#ixzz3nigaeF1F   5th Oct. 2015

Driving after smoking even a small amount of marijuana almost doubles the risk of a fatal highway accident, according to an extensive study of 10,748 drivers involved in fatal crashes between 2001 and 2003.

A study by the French National Institute for Transport and Safety Research published in the British Medical Journal found that seven percent of drivers involved in a fatal highway crash used marijuana.

The researchers estimated that at least 2.5 percent of the 10,748 fatal crashes studied were directly caused by the use of marijuana.

Small Amounts Can Cause Impairment

The researchers concluded that the risk of being responsible for a fatal crash increased as the blood concentration of THC, the active ingredient in marijuana, increased. Even small amounts of marijuana could double the chance of a driver suffering an accident, researchers said, and larger doses could more than triple the risk.

The number of highway deaths contributed the smoking weed were significant, even though they were dwarfed by the number caused by drinking alcohol. Of the drivers involved in fatal accidents, 21.4 percent tested positive for alcohol consumption. Alcohol was estimated to be responsible for 28.6 percent of all fatal highway accidents.

The French research found that 2.9 percent of drivers involved in fatal crashes tested positive for both marijuana and alcohol. Men were more often involved in fatal crashes than women and were more often tested positive for both marijuana and alcohol.

Totally Irresponsible

Young drivers and drivers of motorcycles and mopeds were also more likely to test positive for both substances.

“Research like this proves just how dangerous it is to take drugs, and then get behind the wheel of a car,” Roger Vincent, of the Royal Society for the Prevention of Accidents, told the BBC. “It is totally irresponsible, as taking drugs such as cannabis does affect your reactions.”

Source: The study was published in the Dec. 3, 2005 issue of the British Medical Journal.  Updated June 04, 2014.

Piscataway, NJ – Although there have been calls to lower the legal drinking age from 21, a new study raises the possibility that it could have the unintended effect of boosting the high school dropout rate.

The report, published in the September issue of the Journal of Studies on Alcohol and Drugs, looked back at high school dropout rates in the 1970s to mid-80s — a time when many U.S. states lowered the age at which young people could legally buy alcohol.

Researchers found that when the minimum drinking age was lowered to 18, high school dropout rates rose by 4 to 13 percent, depending on the data source. Black and Hispanic students — who were already more vulnerable to dropping out — appeared more affected than white students.

The findings do not prove that the 18 drinking age was to blame, according to lead researcher Andrew Plunk, Ph.D., an assistant professor of paediatrics at Eastern Virginia Medical School, in Norfolk. However, he said, state drinking-age policies would likely be unrelated to the personal factors that put kids at risk of drinking problems or dropping out.

Plus, Plunk explained, states made those policy changes based on national trends at the time — mainly, the belief that with the voting age lowered to 18, the legal drinking age should drop, too. So it’s unlikely that other events happening within states would explain the connection to high school dropout rates.

And why would the legal drinking age matter when it comes to high school dropout rates?

“The minimum legal drinking age changes how easy it is for a young person to get alcohol,” Plunk said. “In places where it was lowered to 18, it’s likely that more high school students were able to get alcohol from their friends.”

And for certain vulnerable kids, that access might lower their chances of finishing high school. Policies that allowed 18-year-olds to buy alcohol showed a particular impact on minority students, as well as young people whose parents had drinking problems. In that latter group, the dropout rate rose by 40 percent.

In the mid-1980s, federal legislation returned the legal drinking age to 21 nationwide.

However, there is an ongoing debate about lowering it again — largely as a way to combat clandestine binge drinking on college campuses. The argument is that college students who can legally buy alcohol at bars and restaurants will drink more responsibly.

But Plunk said that debate is missing something: What might the effects be in high schools?

“I think this study gives us some idea of what could happen if we lower the legal drinking age,” Plunk said. “It suggests to me that we’d see this same dropout phenomenon again.”

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Plunk, A. D., Agrawal, A., Tate, W. F., Cavazos-Rehg, P., Bierut, L. J., & Grucza, R. A. (September 2015). Did the 18 drinking age promote high school dropout? Implications for current policy.  76(5), 680-689.

The Journal of Studies on Alcohol and Drugs is published by the Center of Alcohol Studies at Rutgers, The State University of New Jersey. It is the oldest substance-related journal published in the United States

Source: Journal of Studies on Alcohol and Drugs,  28th  September 2015

The Washington Traffic Safety Commission released new data showing that legalizing marijuana increases marijuana-impaired traffic fatalities. From 2010 to 2014, some 60 percent of drivers involved in fatal crashes were tested for drugs. About 20 percent (349 drivers) tested positive for marijuana. The new data can distinguish between drivers who were high at the time of the crash as opposed to those who had residual traces of marijuana in their systems from use days earlier. The number of drivers involved in fatalities who tested positive for active THC increased from 65 percent (38 of 60 drivers) in 2013 to 85 percent (75 of 89 drivers) in 2014, the year Washington implemented legal pot. About half of these drivers exceeded the 5 ng/ml THC designation denoting impairment in Washington’s legalization law. The driver with the highest THC level tested at 70 mg/ml. Half of the THC positive drivers were also impaired by alcohol, the majority exceeding 0.08 BAC. The largest increase in active THC positive drivers involved in fatal crashes were young males ages 21 to 25, from 6 in 2013 to 19 in 2014.   From 2008 to 2014, more than 1,100 people died in impaired collisions in Washington State, accounting for nearly half of all traffic deaths and more than one-fifth of serious injury collisions.

Source: marijuanareport.org.  Sept.23rd 2015

According to the National Institute on Drug Abuse, “Besides the risk of spontaneous abortion, heroin abuse during pregnancy (together with related factors like poor nutrition and inadequate prenatal care) is also associated with low birth weight, an important risk factor for later delays in development. Additionally, if the mother is regularly abusing the drug, the infant may be born physically dependent on heroin and could suffer from neonatal abstinence syndrome (NAS), a drug withdrawal syndrome in infants that requires hospitalization. According to a recent study, treating opioid-addicted pregnant mothers with buprenorphine (a medication for opioid dependence) can reduce NAS symptoms in babies and shorten their hospital stays.”

Source:   http://www.wmdt.com/news    Sept 18th 2015