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Commentary
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Marijuana Threat Assessment, Part One: Recent Evidence for Health Risks of Marijuana Use

Senior Fellow
Former Senior Fellow and Vice President, Development
john_walters
john_walters
President and CEO
A man smokes a marijuana joint in a cannabis club on August 22, 2014 in Barcelona, Spain. (David Ramos/Getty Images)
Caption
A man smokes a marijuana joint in a cannabis club on August 22, 2014 in Barcelona, Spain. (David Ramos/Getty Images)

Summary:

Thanks to advances in science, we have never known so much about the effects marijuana use has on the human body, particularly, the fragile brain. Yet, in a political era when scientific research is regularly marshalled to end public policy debates, the powerful, growing scholarship on marijuana has largely been ignored or dismissed. Indeed, marijuana use seems to be one of the glaring areas in modern life where wishful thinking reigns over rationality.

Yet, as the lesson of tobacco demonstrates, when Americans are given the scientific facts about serious threats to their health, they adjust their behavior and insist on measures to safeguard their communities. In the instance of marijuana, the public can be forgiven for not knowing the true threat. With the assistance of a sympathetic media, marijuana legalization advocates, many seeking to profit off the drug, continue to sell romantic falsehoods and outright lies. They casually dismiss the growing list of serious concerns about marijuana emerging from scientific scholarship and survey research, or just cry “reefer madness” without examining the evidence.

Amidst the current marijuana public policy discussion, more than ever, concerned citizens, community leaders, lawmakers, educators, and parents need to better understand the growing body of research about this drug. What follows is a compilation and discussion of the latest research, including reports that are beginning to come in on the effects legalization has had in Colorado and neighboring states—including increased criminal activity even with legalization. While all research has limitations, what we do know is becoming clearer by the day, and it will make many question what they thought they knew about this drug of abuse.

Key Recent Findings:

* Journal of the American Medical Association: “There is little doubt about the existence of an association between substance use and psychotic illness…studies suggest that the association between cannabis use and later psychosis might be causal, a conclusion supported by studies showing that cannabis use is associated with an earlier age at onset of psychotic disorders, particularly schizophrenia.”
* Society for the Study of Addiction “Regular cannabis use in adolescence approximately doubles the risks of early school-leaving and of cognitive impairment and psychoses in adulthood. Regular cannabis use in adolescence is also associated strongly with the use of other illicit drugs.”
* World Psychiatric Association "Evidence that THC is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high-potency cannabis and synthetic cannabinoids."
* American Academy of Pediatrics “The adverse effects of marijuana have been well documented” and include “impaired short-term memory, decreased concentration, attention span, and problem solving” which “interfere[s] with learning.”
* American Psychological Association “Heavy marijuana use in adolescence or early adulthood has been associated with a dismal set of life outcomes including poor school performance, higher dropout rates, increased welfare dependence, greater unemployment and lower life satisfaction.”
* Proceedings of the National Academy of Sciences “Persistent adolescent-onset cannabis users” showed “an average 8-point IQ decline from childhood to adulthood.”
* Clinical Psychological Science Journal Duke University and UC Davis researchers “found that those dependent on cannabis experienced more financial difficulties, such as paying for basic living expenses and food, than those who were alcohol dependent.”
* Journal of Drug and Alcohol Dependence: States that have legalized “medical” marijuana find an association with higher 12th grade drop-out rates, lessened college attainment, and increases in daily smoking. Further, there is a dose/response relationship between adverse impact and years of increased exposure under legalization.
* U.S. Department of Health and Human Services, SAMHSA Since legalizing marijuana, Colorado climbed to number one among states for both youth (12-17) and college age adults (18-25) marijuana use.

Discussion:

The further acceptance of marijuana legalization and commercialization in some states will lead to a greater availability of the drug. Greater availability and acceptance will lead to greater use of marijuana, both in the sense of more users, and likely further in the sense of more frequent and greater consumption.

In states that have legalized already there is strong evidence that adult use has surged upward. There is further evidence that use by youth will also increase.

Youth use of marijuana in states that have now commercialized sales was already more extensive than national norms, however, reports since the first commercialization began in January, 2014, indicate growing use amongst all age groups.

As marijuana use intensifies, the consequences of such use and abuse accelerates. These consequences are considerable, and will impose significant costs, both personal and economic, on health and social well-being.

Finally, and perversely, evidence is strong that the consequences will include not only continued, but intensified and entrenched criminal activity associated with drug use. Indications are clear that the criminal and violent black market capitalizes on increased marijuana availability and use. Marijuana commercialization/legalization is advancing both a public health and a public safety disaster.

We shall review recent evidence of the health-related consequences in this document. In a later accompanying document we will assess the impact on use of drugs beyond marijuana, as well as the impact on further criminal drug markets.

Though comparisons between marijuana and other substances of abuse are frequently made to the effect that marijuana is not proportionally lethal, there are nevertheless other measures of the drug’s dangers. Former National Institute on Drug Abuse Director Dr. Bob DuPont has termed marijuana “the most dangerous drug,” in part because of the sheer prevalence of what is the most widely used illegal substance in the world, and in part because the effects are not always felt or experienced by those affected. They can nevertheless be measured and are real. In some instances, research shows that they appear irreversible, even after abstinence.

Among the more troubling findings are those showing a relationship between marijuana use and psychotic episodes, diminished memory, verbal skill, and other cognitive performance, lowered life achievements, criminal and anti-social behavior, school leaving and academic failure, and even lowered life satisfaction.

Most concerning, perhaps, are the findings that heavy, early marijuana use is associated with a loss of intelligence over the life course. Specific supporting citations for other statements will be found below.

Further, Dr. Wayne Hall’s twenty-year review of the literature in the journal Addiction, as we will present in greater detail in the review, showed a clear relationship between youth marijuana use and subsequent use of other drugs. As Hall has argued:

The relationships between regular cannabis use and other illicit drug use have persisted after statistical adjustment for the effects of confounding variables in both longitudinal studies and discordant twin studies… The order of involvement with cannabis and other illicit drugs, and the increased likelihood of using other illicit drugs, are the most consistent findings in epidemiological studies of drug use in young adults.

In general, the health risks of marijuana use are reasonably well known, and based on long-standing research that now consists in multiple studies across many nations, exploring many dimensions of what is a very complex drug.

The last decade has witnessed an intensification of concern and stimulated even more studies of marijuana’s manifold impact, involving several areas of the body and the mind. The comprehensive nature of the physiological impact mirrors, to some extent, the widespread dispersal of the body’s naturally-occurring endocannabinoid receptor system.

There are additional physiological concerns, many based on smoking as the manner of consumption, focused on its effects on the cardiac and respiratory systems. These threats are real and mounting.

But the most compelling investigations regarding risk are emerging from studies of the brain, however the drug is consumed. These include both the structure and the functioning of the neurophysiology of the brain, and they further extend into discoveries regarding the consequences of brain activity, as we have mentioned, such as cognition, memory, learning, executive performance, and general behavior. Moreover, they also include examinations of drug dependency and what is termed “marijuana use disorder.”

That is, both the brain as an organ as well as “the mind,” the very personhood, of the individual are affected by the chemistry of the drug. Most concern is focused on the principle intoxicating element, the THC, which shows signs of being actively toxic to the nervous system, the potency of which in modern forms is escalating dramatically under marijuana commercialization.

We must acknowledge that many studies demonstrate a risk that is emergent, and not fully known; multiple factors and confounders do coincide and must be accounted for before we argue “causation” for the effects that have been shown. Nevertheless, a substantial and repeated body of research that, taken piece by piece, showing “associations” or “correlations” or “predispositions,” must now be seen as sufficient, when taken together, to establish a clear and present danger.

In some measure, the worst effects are contingent, in the sense that not all forms of use by all individuals will produce the direst impact. But by now the evidence is compelling that certain forms of use, under certain circumstances, is deeply damaging.

Simply put, any honest observers must accept that the preponderance of evidence, as suggested by our review of recent literature which follows, demonstrates a high risk from marijuana use that is now overwhelming.

What we find is research from several related lines of inquiry, all pointing in the same direction. The risks are only worsening with time, in each line of inquiry, serving to confirm a congruence with the findings from other arena.

Studies of various marijuana disorders of behavior are being underpinned and given a basis by studies of the brain and its performance; showing consistent patterns from several interrelated domains of impact. Moreover, as over time the tools brought to bear have become more sophisticated and able to measure subtle and consequential effects, the sense of concern over what we are doing to youth is only mounting.

Though all users, even adult non-frequent users, have been shown to suffer some deficits through marijuana intoxication, and though there are further indications that even young adult casual users undergo structural brain changes, the evidence is far more robust and more worrying in other circumstances.

Danger increases, that is, when any of the following conditions are co-present with marijuana use: the existence of co-morbidities (or even predispositions), especially collateral substance dependencies or psychological deficits; certain genetic profiles that confer greater susceptibility; heavy, frequent use (daily use being the most threatening), especially of high-potency varieties; and especially exposure at a developmentally young age, during periods of highly consequential brain formation and calibration, generally ranging from prenatal or pediatric exposure up to young adulthood.

Where more than one of these factors is present, the risks escalate; where the developmentally young smoke high-potency cannabis frequently for an extended period – most markedly those with predisposing psychological deficits – the effects can be catastrophic in their lives, including dramatic “psychotic breaks.” These effects appear to be, in some cases, largely irreversible.

And it is this “worst-case scenario” that, perversely, is being fostered by state legalization and commercialization measures, thereby ensuring the greatest magnitude of damage.

A further implication of these facts concerns our emerging knowledge of the risks, given that most longitudinal studies showing long-term adult impacts were carried out without an appreciation of how the various factors above conferred greater vulnerability.

Often, studies that failed to find major impact were based on samples of adults, not adolescents, who were not exposed to heavy, frequent, newly-potent THC doses. Yet the commercialization of marijuana has resulted in marijuana potency that eclipses anything we have ever previously seen, in some cases by orders of magnitude. Highly potent “edibles” and concentrated cannabis extractions, like “shatter” are taking potency levels once common in the two- to three-percent range up to 80 percent. The consequence is that most everything we thought we knew about marijuana’s risks needs to be re-assessed under contemporary conditions, and most every danger, as we progressively uncover them, turns out to be heightened.

These finding are warnings of grave danger, with the promise of yet more to be discovered. Not all is “proven,” and not all establishes independent causation, but the evidence is strong enough, and growing daily, to activate in public policy a “precautionary principle.” That is, the evidence is strong enough to warrant a clear directive not to proceed further. Simply put, the pathway of legalization must not be pursued.

Recent Research and Findings: An Annotated Review

What has research over the past two decades revealed about the adverse health effects of recreational cannabis use? (full article, Addiction, (2014).
“Regular cannabis use in adolescence approximately doubles the risks of early school-leaving and of cognitive impairment and psychoses in adulthood. Regular cannabis use in adolescence is also associated strongly with the use of other illicit drugs.”

Unintentional Pediatric Exposures to Marijuana in Colorado: 2009-2015, JAMA Pediatrics, (2016).
“Annual RPC pediatric marijuana cases increased more than 5-fold from 2009 (9) to 2015 (47). Colorado had an average increase in RPC cases of 34% (P  .001) per year while the remainder of the United States had an increase of 19% (P  .001).”

AMA Wants Marijuana Products to Have Warnings Against Use in Pregnancy, National Council on Alcoholism and Drug Dependence, (2015).
The American Medical Association seeks warnings against marijuana use in pregnancy.

Cannabis Use and Earlier Onset of Psychosis, JAMA Psychiatry, (2011).
“There is little doubt about the existence of an association between substance use and psychotic illness. National mental health surveys have repeatedly found more substance use, especially cannabis use, among people with a diagnosis of a psychotic disorder. There is a high prevalence of substance use among individuals treated in mental health settings,6 and patients with schizophrenia are more likely to use substances than members of the wider community. Prospective birth cohort and population studies suggest that the association between cannabis use and later psychosis might be causal, a conclusion supported by studies showing that cannabis use is associated with an earlier age at onset of psychotic disorders, particularly schizophrenia.”

The Impact of Marijuana Policies on Youth: Clinical, Research, and Legal Update, American Academy of Pediatrics, (2015).
“The adverse effects of marijuana have been well documented, and studies have demonstrated the potential negative consequences of short- and long-term recreational use of marijuana in adolescents. These consequences include impaired short- term memory and decreased concentration, attention span, and problem solving, which clearly interfere with learning. Alterations in motor control, coordination, judgment, reaction time, and tracking ability have also been documented; these may contribute to unintentional deaths and injuries among adolescents (especially those associated with motor vehicles if adolescents drive while intoxicated by marijuana). Negative health effects on lung function associated with smoking marijuana have also been documented, and studies linking marijuana use with higher rates of psychosis in patients with a predisposition to schizophrenia have recently been published, raising concerns about longer-term psychiatric effects. New research has also demonstrated that the adolescent brain, particularly the prefrontal cortex areas controlling judgment and decision-making, is not fully developed until the mid-20s, raising questions about how any substance use may affect the developing brain. Research has shown that the younger an adolescent begins using drugs, including marijuana, the more likely it is that drug dependence or addiction will develop in adulthood. A recent analysis of 4 large epidemiologic trials found that marijuana use during adolescence is associated with reductions in the odds of high school completion and degree attainment and increases in the use of other illicit drugs and suicide attempts in a dose-dependent fashion that suggests that marijuana use is causative.”

American Academy of Pediatrics Reaffirms Opposition to Legalizing Marijuana for Recreational or Medical Use, American Academy of Pediatrics, (2015).
The American Academy of Pediatrics (AAP) reaffirms its opposition to legalizing marijuana, citing the potential harms to children and adolescents.

Half-Baked — The Retail Promotion of Marijuana Edibles, New England Journal of Medicine, (2015).
“[E]dibles that resemble sugary snacks pose several clear risks. One is over-intoxication....At high doses, THC can produce serious anxiety attacks and psychotic-like symptoms. This problem is augmented by differences in the pharmacokinetic and metabolic effects of marijuana when it is ingested rather than smoked. In addition, case reports document respiratory insufficiency in young children who have ingested marijuana.”

Adverse Health Effects of Marijuana Use, New England Journal of Medicine, (2014).
A review of the current state of the science related to the adverse health effects of the recreational use of marijuana, focusing on those areas for which the evidence is strongest.
A New England Journal of Medicine Article about Marijuana,
Psychology Today, (2014) summarizes the adverse health effects as published in the New England Journal of Medicine.

UN: cannabis law changes pose 'very grave danger to public health', The Guardian, (2014).
United Nations International Narcotics Control Board warns of “very grave danger” from legalizing marijuana.

Damaging Effects of Cannabis Use on the Lungs, Advances in Experimental Medicine and Biology, (2016).
"Cannabis smoke affects the lungs similarly to tobacco smoke, causing symptoms such as increased cough, sputum, and hyperinflation. It can also cause serious lung diseases with increasing years of use. Cannabis can weaken the immune system, leading to pneumonia. Smoking cannabis has been further linked with symptoms of chronic bronchitis. Heavy use of cannabis on its own can cause airway obstruction. Based on immuno-histopathological and epidemiological evidence, smoking cannabis poses a potential risk for developing lung cancer."

Marijuana use in adolescence may increase risk for psychotic symptoms, American Journal of Psychiatry, (2016).
Regular marijuana use significantly increased risk for subclinical psychotic symptoms, particularly paranoia and hallucinations, among adolescent males.

Heavy, persistent pot use linked to economic, social problems at midlife: Study finds marijuana not 'safer' than alcohol, Clinical Psychological Science, (2016).
Science Daily's review of a research study that followed children from birth up to age 38 has found that people who smoked cannabis four or more days of the week over many years ended up in a lower social class than their parents, with lower-paying, less skilled and less prestigious jobs than those who were not regular cannabis smokers. These regular and persistent users also experienced more financial, work-related and relationship difficulties, which worsened as the number of years of regular cannabis use progressed.

The impact of adolescent exposure to medical marijuana laws on high school completion, college enrollment and college degree completion,
Drug & Alcohol Dependence, (2016).
States that have legalized marijuana find an association with higher 12th grade drop out rates, lessened college attainment, and increases in daily smoking. Further, there is a dose/response relationship between adverse impact and years of increased exposure under legalization.

Early marijuana use associated with abnormal brain function, lower IQ, Lawson Health Research Institute, (2016).
“Previous studies have suggested that frequent marijuana users, especially those who begin at a young age, are at a higher risk for cognitive dysfunction and psychiatric illness, including depression, bipolar disorder and schizophrenia.”

Marijuana Users Have Abnormal Brain Structure and Poor Memory, Northwestern Medicine, (2013).
“Teens who were heavy marijuana users -- smoking it daily for about three years -- had abnormal changes in their brain structures related to working memory and performed poorly on memory tasks, reports a new Northwestern Medicine® study. A poor working memory predicts poor academic performance and everyday functioning. The brain abnormalities and memory problems were observed during the individuals’ early twenties, two years after they stopped smoking marijuana, which could indicate the long-term effects of chronic use. Memory-related structures in their brains appeared to shrink and collapse inward, possibly reflecting a decrease in neurons.”

Young adult sequelae of adolescent cannabis use: an integrative analysis, Lancet Psychiatry, (2014).
Adolescent cannabis use has adverse consequences in young adulthood:
“We recorded clear and consistent associations and dose-response relations between the frequency of adolescent cannabis use and all adverse young adult outcomes. After covariate adjustment, compared with individuals who had never used cannabis, those who were daily users before age 17 years had clear reductions in the odds of high-school completion…and degree attainment…, and substantially increased odds of later cannabis dependence…, use of other illicit drugs…, and suicide attempt.”

Traditional marijuana, high-potency cannabis and synthetic cannabinoids: increasing risk for psychosis, World Psychiatry, (2016).
"Evidence that [THC] is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high-potency cannabis and synthetic cannabinoids."

Monitoring Marijuana Use in the United States; Challenges in an Evolving Environment, JAMA,(2016).
“Use of marijuana or any of its components, especially in younger populations, is associated with an increased risk of certain adverse health effects, such as problems with memory, attention, and learning, that can lead to poor school performance and reduced educational and career attainment, early-onset psychotic symptoms in those at elevated risk, addiction in some users, and altered brain development.”

Marijuana use and use disorders in adults in the USA, 2002–14: analysis of annual cross-sectional surveys, Lancet Psychiatry, (2016).
Commenting on this study to the Associated Press, Dr. Wilson Compton, Deputy Director of NIDA said, "if anything, science has shown an increasing risk that we weren't as aware of years ago.” He added that other research has increasingly linked marijuana use to mental impairment, and early, heavy use by people with certain genes to increased risk of developing
psychosis.

Prenatal marijuana exposure, age of marijuana initiation, and the development of psychotic symptoms in young adults, Psychological Medicine, (2015).
Prenatal marijuana exposure linked to bad childhood outcomes; if effect is further “mediated” through early onset marijuana use, strong association with negative adult outcomes, such as arrest, low educational performance, unemployment.

One in six children hospitalized for lung inflammation positive for marijuana exposure, American Academy of Pediatrics, (2016).
Colorado: 16% of exposed children admitted to hospital for lung inflammation tested positive for MJ metabolite.

Cannabis use increases risk of premature death, American Journal of Psychiatry, (2016).
Cannabis use in youth increases the risk of early death.

Scientists Call for Action Amidst Mental Health Concerns, The Guardian, (2016).
“Most research on cannabis, particularly the major studies that have informed policy, are based on older low-potency cannabis resin.” According to Sir Robin Murray, professor of psychiatric research at King’s College London: “It’s not sensible to wait for absolute proof that cannabis is a component cause of psychosis. There’s already ample evidence to warrant public education around the risks of heavy use of cannabis, particularly the high-potency varieties. For many reasons, we should have public warnings.””

Marijuana use in adolescence may increase risk for psychotic symptoms, American Journal of Psychiatry, (2016).
Chronic marijuana use in adolescent boys increases risk of developing persistent subclinical psychotic symptoms (hallucinations, paranoia). “For each year adolescent boys engaged in regular marijuana use … subsequent symptoms increased by 21% and… paranoia or hallucinations increased by 133% and 92%, respectively. This effect persisted even when [study] participants stopped using marijuana for 1 year.”

Heavy, persistent pot use linked to economic, social problems at midlife, Clinical Psychological Science, (2016).
"Regular long-term [marijuana] users also had more antisocial behaviors at work, such as stealing money or lying to get a job, and experienced more relationship problems, such as intimate partner violence and controlling abuse.”

Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review, JAMA Psychiatry, (2016).
This longitudinal study documented adolescent-onset (but not adult-onset) persistent cannabis users showed neuropsychological decline ages 13 to 38 years. “Longitudinal investigations show a consistent association between adolescent cannabis use and psychosis. Cannabis use is considered a preventable risk factor for psychosis... strong physiological and epidemiological evidence supporting a mechanistic link between cannabis use and schizophrenia... raise[s] the possibility that our current, limited knowledge may only apply to the ways in which the drug was used in the past."

Marijuana use disorder is common and often untreated, National Institute of Health/NESARC, (2016).
“People with marijuana use disorder are vulnerable to other mental health disorders … onset of the disorder was found to peak during late adolescence. …People with marijuana use disorder…experience considerable mental disability. ...Previous studies have found that such disabilities persist even after remission of marijuana use disorder."

The health and social effects of nonmedical cannabis use, World Health Organization, (2016).
“There is a worrying increasing demand for treatment for cannabis use disorders and associated health conditions in high- and middle-income countries, and there has been increased attention to the public health impacts of cannabis use and related disorders in international policy dialogues.”

AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers, Translational Psychiatry, (2016).
“Smoking cannabis daily doubles an individual’s risk of developing a psychotic disorder, yet indicators of specific vulnerability have proved largely elusive. Genetic variation is one potential risk modifier.”

What's That Word? Marijuana May Affect Verbal Memory, JAMA Internal Medicine, (2016).
Researchers found a "dose-dependent independent association between cumulative lifetime exposure to marijuana and worsening verbal memory in middle age.”

Adolescent Cannabinoid Exposure Induces a Persistent Sub-Cortical Hyper-Dopaminergic State and Associated Molecular Adaptations in the Prefrontal Cortex., Cerebral Cortex, (2016).
"We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations…. findings demonstrate a profound dissociation in relative risk profiles for adolescent versus adulthood exposure to THC in terms of neuronal, behavioral, and molecular markers resembling neuropsychiatric pathology.”

Cannabis increases the noise in your brain, Biological Psychiatry, (2015).
"At doses roughly equivalent to half or a single joint, ∆9-THC produced psychosis-like effects and increased neural noise in humans. The dose-dependent and strong positive relationship between these two findings suggest that the psychosis-like effects of cannabis may be related to neural noise which disrupts the brain's normal information processing activity.”

Marijuana Use: Detrimental to Youth, American College of Pediatricians, (2016).
"Marijuana is the leading illicit substance mentioned in adolescent emergency department admissions and autopsy reports, and is considered one of the major contributing factors leading to violent deaths and accidents among adolescents."

Chronic Adolescent Marijuana Use as a Risk Factor for Physical and Mental Health Problems in Young Adult Men, Psychology of Addictive Behaviors, (2015).
Evidence suggests that youth who use marijuana heavily during adolescence may be particularly prone to health problems in later adulthood (e.g., respiratory illnesses, psychotic symptoms).

Developmental Trajectories of Marijuana Use among Men, Journal of Research in Crime and Delinquency, (2015).
"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."

Appraising the Risks of Reefer Madness, Cerebrum, (2015).
"Cannabis is generally accepted as a cause of schizophrenia (though less so in North America, where this topic has received little attention),” notes Dr. R. Murray, an Oxford University Professor of Psychiatry.

Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons, Proceedings of the National Academy of Sciences, (2015).
"Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.” “This study demonstrates that remarkable detrimental consequences of embryonic THC exposure on adult-brain function, which are evident long after THC withdrawal, are solely due to the impact of THC on CB1 receptors located on developing cortical neurons.” Embryonic exposure increased seizures in adulthood and the consequences of prenatal THC were lifelong; even though the cannabinoid receptors after withdrawal appear normal, there is an apparent impact on connectivity.

Association Between Use of Marijuana and Male Reproductive Hormones and Semen Quality: A Study Among 1,215 Healthy Young Men, American Journal of Epidemiology, (2015).
"Regular marijuana smoking more than once per week was associated with a 28% … lower sperm concentration and a 29% … lower total sperm count after adjustment for confounders.”

Is Marijuana Use Associated With Health Promotion Behaviors Among College Students? Health-Promoting and Health-Risk Behaviors Among Students Identified Through Screening in a University Student Health Services Center, Journal of Drug Issues, (2015).
"Results showed marijuana users were more likely to use a variety of substances and engage in hazardous drinking than non-users."

Psychosocial sequelae of cannabis use and implications for policy: findings from the Christchurch Health and Development Study, Social Psychiatry and Psychiatric Epidemiology, (2015).
"Findings…suggest that individuals who use cannabis regularly, or who begin using cannabis at earlier ages, are at increased risk of a range of adverse outcomes, including: lower levels of educational attainment; welfare dependence and unemployment; using other, more dangerous illicit drugs; and psychotic symptomatology."

Young brains on cannabis: It's time to clear the smoke, Clinical Pharmacology and Therapeutics, (2015).
"There is certainly cause for concern about the amount and frequency of cannabis use among youth....Recent evidence shows that early and frequent use of cannabis has been linked with deficits in short-term cognitive functioning, reduced IQ, impaired school performance, and increased risk of leaving school early – all of which can have significant consequences on a young person's life trajectory....Heavy cannabis use in adolescence is also a risk factor for psychosis....Youth aged 15-24 spent the largest number of days in a hospital for a primary diagnosis of mental and behavioral disorders due to the use of cannabinoids."

Association Between Lifetime Marijuana Use and Cognitive Function in Middle Age and Long-term Marijuana Use and Cognitive Impairment in Middle Age, JAMA Internal Medicine, (2016).
“These studies have generally shown reduced activity in those with long-term marijuana use in brain regions involved in memory and attention, as well as structural changes in the hippocampus, prefrontal cortex, and cerebellum.”

"Denial of Petition To Initiate
Proceedings To Reschedule Marijuana()":https://www.deadiversion.usdoj.gov/fed_regs/rules/2016/fr0812_2.pdf, Federal Register/DEA Review of “Scientific Evidence of [Marijuana’s] Pharmacological Effects, If Known”, (2016).
“Individuals with a diagnosis of marijuana misuse or dependence who…initiated marijuana use before the age of 15 years, showed deficits in performance on tasks assessing sustained attention, impulse control, and general executive functioning compared to non-using controls. These deficits were not seen in individuals who initiated marijuana use after the age of 15 years…. Additionally, in a prospective longitudinal birth cohort study of 1,037 individuals, marijuana dependence or chronic marijuana use was associated with a decrease in IQ and general neuropsychological performance compared to pre-marijuana exposure levels in adolescent onset users. The decline in adolescent-onset users’ IQ persisted even after reduction or abstinence of marijuana use for at least 1 year…. The deficits in IQ seen in adolescent-onset users increased with the amount of marijuana used. Moreover, when comparing scores for measures of IQ, immediate memory, delayed memory, and information-processing speeds to pre-drug-use levels, the current, heavy, chronic marijuana users showed deficits in all three measures.”

"The health and social effects of
nonmedical cannabis use()":http://www.who.int/substance_abuse/publications/msb_cannabis_report.pdf…, World Health Organization, (2016).
"Cannabis is globally the most commonly used psychoactive substance under international control. In 2013, an estimated 181.8 million people aged 15−64 years used cannabis for nonmedical purposes globally (uncertainty estimates 128.5–232.1 million) (UNODC, 2015). There is a worrying increasing demand for treatment for cannabis use disorders and associated health conditions in high- and middle-income countries, and there has been increased attention to the public health impacts of cannabis use and related disorders in international policy dialogues.[...] This publication builds on contributions from a broad range of experts and researchers from different parts of the world. It aims to present the current knowledge on the impact of nonmedical cannabis use on health."