NIDA’s Dark View of Teen Marijuana Use

Federal study also discusses medical marijuana.

Considering the impasse on marijuana policy between state and federal governments in the U.S., the primary government agency in charge of drug research—NIDA, the National Institute on Drug Abuse—would seem to be caught between a rock and a hard place. Neuroscientists and other marijuana investigators who do research under NIDA grants have a fine line to walk in their efforts to disseminate research findings on cannabis.

From a public health point of view, NIDA is expected to keep up the pressure against drug legalization, or at least keep out of the fight, while also researching the medical pros and cons of cannabis. So it was with some interest that drug policy officials took in a recent article in the New England Journal of Medicine by NIDA director Nora Volkow titled “Adverse Health Effects of Marijuana Use.”

While the press has understandably centered on the risk of marijuana use among teens, which is the focus of the study, the report also contains some surprising admissions about marijuana’s health benefits as well as its addictive potential.

The teen risk emphasis comes from recent studies on two fronts—impaired driving and impaired brain function. The first is seriously confounded by dual use with alcohol, and the second is based, at least in part, on a controversial long-term study showing that marijuana use in the early years demonstrably lowers adult IQs.

No one would suggest that heavy marijuana smoking is good for developing teen brains, and there is sufficient evidence to worry about impairment to memory and to certain so-called “executive” cognitive functions. It is not clear how lasting these effects can be, but lead author Volkow is confident enough to say in a prepared statement that “Physicians in particular can play a role in conveying to families that early marijuana use can interfere with crucial social and developmental milestones and can impair cognitive development.” 

That these negative effects can be the outcome of heavy pot smoking in the teen years seems established beyond reasonable doubt. The extent and duration of these negative outcomes remain the topic of vociferous debate—although it is increasingly clear that the body’s endogenous cannabinoid system plays a key role in synapse formation during early brain development.

Meanwhile, the report re-emphasized the fact that marijuana is an addictive drug for some users—a fact that should not need re-emphasizing, but, lamentably, does. As Volkow and her co-authors write: “The evidence clearly indicates that long-term marijuana use can lead to addiction. Indeed, approximately 9% of those who experiment with marijuana will become addicted.”

Moreover, as regular readers of Addiction Inbox already know, “there is also recognition of a bona fide cannabis withdrawal syndrome (with symptoms that include irritability, sleeping difficulties, dysphoria, craving, and anxiety), which makes cessation difficult and contributes to relapse.” And, in line with the report’s overall theme, “those who begin in adolescence are approximately 2 to 4 times as likely to have symptoms of cannabis dependence within 2 years after first use.”

To their credit, the investigators decline to endorse the claim that marijuana use exacerbates or initiates episodes of illness in patients with schizophrenia and other psychoses, noting that “it is inherently difficult to establish causality in these types of studies because factors other than marijuana use may be directly associated with the risk of mental illness.” Furthermore, while early marijuana use is associated with an increased risk of dropping out of school, “reports of shared environmental factors that influence the risks of using cannabis at a young age and dropping out of school suggest that the relationship may be more complex…. The relationship between cannabis use by young people and psychosocial harm is likely to be multifaceted, which may explain the inconsistencies among studies.”

Indeed. The report also declares that the effects of long-term pot smoking on the risk of lung cancer are “unclear,” and that “the smoking of cigarettes containing both marijuana and tobacco products is a potential confounding factor with a prevalence that varies dramatically among countries.”

In conclusion, the strict demands of causality mean that the long-term effect of chronic marijuana exposure is not known with any certainty. It is possible, even likely, that these effects can vary dramatically from one smoker to another. But the equally persuasive demands of common sense dictate that inhaling dried, super-heated vegetable matter on a regular basis is likely to degrade your health, the more so if you are young and healthy to begin with.

As for other health issues: “The authoritative report by the Institute of Medicine, Marijuana and Medicine, acknowledges the potential benefits of smoking marijuana in stimulating appetite, particularly in patients with the acquired immunodeficiency syndrome (AIDS) and the related wasting syndrome, and in combating chemotherapy-induced nausea and vomiting, severe pain, and some forms of spasticity. The report also indicates that there is some evidence for the benefit of using marijuana to decrease intraocular pressure in the treatment of glaucoma.”

A detailed section titled “Clinical Conditions with Symptoms That May Be Relieved by Treatment with Marijuana or other Cannabinoids” brought additional research to light:

—Glaucoma: “More research is needed to establish whether molecules that modulate the endocannabinoid system may not only reduce intraocular pressure but also provide a neuroprotective benefit in patients with glaucoma.”

—Nausea: “THC is an effective antiemetic agent in patients undergoing chemotherapy, but patients often state that marijuana is more effective in suppressing nausea…. Paradoxically, increased vomiting (hyperemesis) has been reported with repeated marijuana use. [See various blog posts by Drugmonkey and me, starting with this and this.]

—AIDS-associated conditions: “Smoked or ingested cannabis improves appetite and leads to weight gain and improved mood and quality of life among patients with AIDS.”

—Chronic pain: “Studies have shown that cannabinoids acting through central CB1 receptors, and possibly peripheral CB1 and CB2 receptors, play important roles in… various models of pain. These findings are consistent with reports that marijuana may be effective in ameliorating neuropathic pain, even at very low levels of THC.”

—Inflammation: “Cannabinoids (e.g., THC and cannabidiol) have substantial anti-inflammatory effects…. Animal models have shown that cannabidiol is a promising candidate for the treatment of rheumatoid arthritis and for inflammatory diseases of the gastrointestinal tract (e.g., ulcerative colitis and Crohn’s disease).”

—Multiple sclerosis: “Nabiximols (Sativex, GW Pharmaceuticals), an oromucosal spray that delivers a mix of THC and cannabidiol, appears to be an effective treatment for neuropathic pain, disturbed sleep, and spasticity in patients with multiple sclerosis. Sativex… is currently being reviewed in phase 3 trials in the United States in order to gain approval from the Food and Drug Administration.”

—Epilepsy: In a recent small survey of parents who use marijuana with a high cannabidiol content to treat epileptic seizures in their children, 11% reported completed freedom from seizures…. Although such reports are promising, insufficient safety and efficacy data are available on the use of cannabis botanical for the treatment of epilepsy. However, there is increasing evidence of the role of cannabidiol as an antiepileptic agent in animal models.”

Volkow N.D., Baler R.D., Compton W.M. & Weiss S.R.B.  Adverse health effects of marijuana use., The New England journal of medicine,    PMID: 24897085

Does Strong Marijuana Cause Addiction?

Strong pot matters, but maybe not the way we think.

Colorado, Washington, and some 20 additional states have now made various provisions for legal transactions involving marijuana. And since time immemorial, there has been an illegal market for marijuana. But try getting your hands on some marijuana straightforwardly, through appropriate channels, for purposes of medical research, and, well, most researchers have just said forget it.

Because in the U.S., a bizarre system of drug classification has led to the ludicrous situation of a virtual government monopoly on cannabis for experimental purposes. Can’t researchers just walk around this roadblock and procure pot in some manner that is legal in their state? No, they cannot—not if they want any serious research grants, or publication in refereed journals. Without the federal government imprimatur, marijuana research isn’t kosher, and could put researchers at legal risk. Researchers who go through channels report frequent and unpredictable delays, and this has been true for decades. Yet millions of recreational marijuana users can secure a supply of the drug, often accompanied by specific genetic information, often with relatively little effort.

The Drug Enforcement Administration (DEA) has refused to budge on its opposition to petitions for reclassification of cannabis. A recent Washington Post article  attributed the problem to “stigma associated with the drug, lack of funding and legal issues…. Scientists say they are frustrated that the federal government has not made any efforts to speed the process of research.”

However, as almost everyone knows, things are different in The Netherlands. It isn’t a big problem for researchers at the University of Amsterdam and elsewhere in that country to engage in behavioral studies of actual marijuana smokers. Participants in a recent study, the results of which appear in Addiction, were even allowed to use their own weed. (Thanks to Ivan Oransky for bringing this study to my attention.) The thesis being tested by Peggy van der Pol and colleagues is a familiar one: Do marijuana smokers “titrate” very strong pot—that is, do they modify their smoking/dosing behavior accordingly, in order to reduce overall THC exposure? If so, just because a cannabis user is ingesting high-THC plant material doesn’t mean that his or her THC blood levels are that much higher than smokers of less potent weed. But if this is NOT true—if smokers of strong pot are boosting their THC exposure significantly, the results could conceivably include impaired driving and greater rates of marijuana addiction.

Most studies that attempt to estimate the risk of cannabis dependence in pot smokers rely on a familiar yardstick—the number of days a smoker smokes per month. Dosing behavior, and other behavioral aspects of marijuana smoking that affect THC exposure, are usually ignored. The Dutch researchers found that, in a group of 600 frequent cannabis users, some smokers did in fact show “shorter puff duration and inhaled lower smoke volumes when joints with a higher THC concentration were used.” So, yes, users did engage in partial titration when they smoked stronger marijuana. However, this did not translate into the expected results. In a final sample of 98 participants, the scientists discovered that “users of stronger cannabis generally used larger amounts of cannabis to prepare their regular joint.” (The study participants smoked marijuana European-style, mixing their marijuana with tobacco.) And even though subjects smoking joints with higher THC levels did inhale at slightly lower volumes and at a slower pace, the average user of pot with THC levels of 12% or higher definitely inhaled more liters of smoked THC per month than users of less potent pot. But just to confound matters, total THC exposure over a month’s time turned out to be “a weak predictor of dependence severity, and did not remain significant after adjustment for baseline dependence severity.”

Nonetheless, even with some degree of titration, “a positive association between total puff volume and withdrawal/craving was found, indicating that a larger inhaled volume may increase the THC exposure sufficiently to result in significant effects on clinical outcomes.” (Here is the UK National Health Service take on the research.) 

It is always difficult to say for certain in a prospective, cross-sectional study of behavior whether participants are acting the way they would act in “real life,” although efforts were made to allow smoking at home, or in Dutch coffee shops, as well as the laboratory. Interestingly, the one behavior that seemed to predict dependence in post-hoc analyses was a simple one. Smokers were allowed to mix a joint however they wished, and smoke however much of it they wanted to. Smokers who finished their joints, rather than leaving a portion of it for later, were the smokers more likely to be associated with dependence in the follow-up studies. In fact, “percentage of the joint smoked may be a simple proxy for risky smoking behavior.”

In addition, certain withdrawal symptoms correlated with dependence: “Increased somatic withdrawal symptoms are predictive of relapse, and…. increased physical tension is a significant predictor of relapse.”

As with alcohol, it seems that it is not necessarily how much you smoke or drink. It is how you smoke or drink. Strong marijuana doesn't cause addiction. The way certain people use strong pot can result in addiction, however.

Earlier research has shown that higher levels of cannabis dependence are associated with greater functional impairment, and that "the average level of impairment caused by cannabis, while mild for most users, can rise to the level of tobacco withdrawal which is of well established clinical significance.”

 Physical distress, a “somatic” variable, often matters more, in terms of relapse, than the amount of marijuana smoked, or any other symptom on the roster of functional impairments—including mood and other negative affect variables.  In an earlier study published in PLOS ONE,  investigators found that “cannabis withdrawal is clinically significant because it is associated with elevated functional impairment to normal daily activities, and the more severe the withdrawal is, the more severe the functional impairment is. Elevated functional impairment from a cluster of cannabis withdrawal symptoms is associated with relapse in more severely dependent users.”

van der Pol P., Liebregts N., Brunt T., van Amsterdam J., de Graaf R., Korf D.J., van den Brink W. & van Laar M. (2014). Cross-sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study, Addiction,   n/a-n/a. DOI: 10.1111/add.12508

Marijuana Fact and Fiction

Why cannabis research is a good idea.

There is little doubt among responsible researchers that marijuana--although it is addictive for some people--is sometimes a clinically useful drug. However, there is little incentive for commercial pharmaceutical houses to pursue research on the cannabis plant itself, since they cannot patent it.

The use of marijuana in the treatment of glaucoma is well established. As for the relief of nausea caused by chemotherapy, the precise “antiemetic” mechanism has not yet been identified, but several studies show that marijuana works at least as well as the popular remedy Compazine for controlling nausea. Cancer patients have used marijuana successfully to increase appetite and combat severe weight loss.

Yet another intriguing possibility centers on Huntington’s chorea, the single-gene disease researchers spent years chasing down. Early data from the National Institutes of Health (NIH), reported in Science News, showed a loss of THC receptors in the brains of Huntington’s sufferers.

Queen Elizabeth believed that marijuana tamed her menstrual cramps back in the 16th Century, but there is no clinical and little anecdotal evidence to support this notion. Perhaps the anti-anxiety and mood elevating effects associated with marijuana are useful for menstrual irritation and mood swings, just as they are sometimes perceived to be useful by those suffering from depression.

The typical joint rolled in paper contains roughly 0.5 grams of plant matter, of which anywhere from 1 to 15 per cent is THC. THC content varies widely because some genetic strains of cannabis are more potent than others. This fact has led to intense debate in the United Kingdom over the issue of so-called “Skunk” marijuana. Skunk is not a new, lethally potent form of pot, but rather a shorthand term for describing one of several strains of strong, aromatic female marijuana plants. Most of the potent forms of marijuana for sale are hybrids resulting from cross-pollination of various strains. Of itself, “Skunk” marijuana is no more or less dangerous than other potent and popular varietals, such as “White Widow” or "Hawaiian Haze."

The half-life of marijuana is fairly short—about 50 hours for inexperienced users, and about half that for experienced users. However, THC and its metabolites are fat soluble, and are therefore easily stored in fatty tissue. Other drugs clear the system much more efficiently. The marijuana high may be history, but the metabolites live on--for up to 30 days. Blood tests can confirm THC in the body, but cannot reliably determine how recently the marijuana was smoked. There is no marijuana analysis kit comparable to the Breathalyzer test for alcohol. Drivers under the influence of cannabis may suffer some perceptual impairment. They tend to drive more slowly and take fewer risks, compared to drivers under the influence of alcohol. Possibly, cannabis smokers are hyperaware of the modest motor impairments they exhibit under the influence. Heavy drinkers are often unaware that there is anything wrong with their driving at all, as their sometimes-vociferous arguments with police officers and state troopers can attest.

As with cigarettes, chronic pot smoking can lead to chronic bronchitis. We don’t know for certain whether heavy marijuana use causes lung cancer, but it seems safe to assume that smoking vegetable matter in any form is not compatible with the long-term health of lung tissue. Patients with risk factors for cardiovascular disease are well advised not to smoke anything. Marijuana smoking can raise the resting heart rate as much as 30 per cent in a matter of minutes, and while there is no present evidence of harmful effects from this, we will have to monitor the situation more closely as pot-smoking and former pot-smoking Baby Boomers enter their cardiovascular disease years.

Other patients for whom marijuana is definitely not indicated include those suffering from respiratory disorders--asthma, emphysema, or bronchitis. In addition, schizophrenics or anyone at genetic risk for schizophrenia should shun pot, as it has been known to exacerbate or precipitate schizophrenic episodes—though it does not, as is commonly rumored, cause schizophrenia.

The evidence for significant impairment of cognitive function is equivocal—heavy marijuana use does not, like alcohol, result in gross structural brain damage. Numerous studies have addressed the possibility of subtler impairments in memory, attention, and the retention of new information. The extent to which such alterations are transient as opposed to long term is still under scientific debate.

Cannabis augments the effects of morphine in animal studies, thus allowing for a lower dose of opiates. Pain relief may be a primary attribute of anandamide—the brain’s own THC. Rats given the drug were less sensitive to pain than their non-drugged counterparts, as detailed in the Proceedings of the National Academy of Sciences. Drug companies may have closed the book on marijuana spin-offs too early. It would not be surprising if pills to selectively increase the amount of anandamide in the brain will one day augment or offer an alternative to existing anti-anxiety medications or pain relievers. On the other hand, a substance that blocks anandamide might find use as an agent to help combat memory loss.

Graphic: http://www.seedsman.com/en/health

For more, see: The Chemical Carousel: What Science Tells Us About Beating Addiction © Dirk Hanson 2008, 2009.

Related Posts: Anandamide: The Brain's Own Marijuana

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