Showing posts with label cannabinoid. Show all posts
Showing posts with label cannabinoid. Show all posts

Sunday, June 15, 2014

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:

Tuesday, September 3, 2013

A Chemical Peek at Modern Marijuana


Researchers ponder whether ditch weed is better for you than sinsemilla.

Australia has one of the highest rates of marijuana use in the world, but until recently, nobody could say for certain what, exactly, Australians were smoking. Researchers at the University of Sydney and the University of New South Wales recently analyzed hundreds of cannabis samples seized by Australian police, and put together comprehensive data on street-level marijuana potency across the country. They sampled police seizures and plants from crop eradication operations. The mean THC content of the samples was 14.88%, while absolute levels varied from less than 1% THC to almost 40%.  Writing in PLoS one, Wendy Swift and colleagues found that roughly ¾ of the samples contained at least 10% total THC. Half the samples contained levels of 15% or higher—“the level recommended by the Garretsen Commission as warranting classification of cannabis as a ‘hard’ drug in the Netherlands.”

In the U.S., recent studies have shown that THC levels in cannabis from 1993 averaged 3.4%, and then soared to THC levels in 2008 of almost 9%. THC loads more than doubled in 15 years, but that is still a far cry from news reports erroneously referring to organic THC increases of 10 times or more.

CBD, or cannabidiol, another constituent of cannabis, has garnered considerable attention in the research community as well as the medical marijuana constituency due to its anti-emetic properties. Like many other cannabinoids, CBD is non-psychoactive, and acts as a muscle relaxant as well. CBD levels in the U.S. have remained consistently low over the past 20 years, at 0.3-0.4%. In the Australian study, about 90% of cannabis samples contained less than 0.1% total CBD, based on chromatographic analysis, although some of the samples had levels as high as 6%.

The Australian samples also showed relatively high amounts of CBG, another common cannabinoid. CBG, known as cannabigerol, has been investigated for its pharmacological properties by biotech labs. It is non-psychoactive but useful for inducing sleep and lowering intra-ocular pressure in cases of glaucoma.

CBC, yet another cannabinoid, also acts as a sedative, and is reported to relieve pain, while also moderating the effects of THC. The Australian investigators believe that, as with CBD, “the trend for maximizing THC production may have led to marginalization of CBC as historically, CBC has sometimes been reported to be the second or third most abundant cannabinoid.”

Is today’s potent, very high-THC marijuana a different drug entirely, compared to the marijuana consumed up until the 21st Century? And does super-grass have an adverse effect on the mental health of users? The most obvious answer is, probably not. Recent attempts to link strong pot to the emergence of psychosis have not been definitive, or even terribly convincing. (However, the evidence for adverse cognitive effects in smokers who start young is more convincing).

It’s not terribly difficult to track how ditch weed evolved into sinsemilla. It is the historical result of several trends: 1) Selective breeding of cannabis strains with high THC/low CBD profiles, 2) near-universal preference for female plants (sinsemilla), 3) the rise of controlled-environment indoor cultivation, and 4) global availability of high-end hybrid seeds for commercial growing operations. And in the Australian sample, much of the marijuana came from areas like Byron Bay, Lismore, and Tweed Heads, where the concentration of specialist cultivators is similar to that of Humboldt County, California.

The investigators admit that “there is little research systematically addressing the public health impacts of use of different strengths and types of cannabis,” such as increases in cannabis addiction and mental health problems. The strongest evidence consistent with lab research is that “CBD may prevent or inhibit the psychotogenic and memory-impairing effects of THC. While the evidence for the ameliorating effects of CBD is not universal, it is thought that consumption of high THC/low CBD cannabis may predispose users towards adverse psychiatric effects….”

The THC rates in Australia are in line with or slightly higher than average values in several other countries. Can an increase in THC potency and corresponding reduction in other key cannabinoids be the reason for a concomitant increase in users seeking treatment for marijuana dependency? Not necessarily, say the investigators. Drug courts, coupled with greater treatment opportunities, might account for the rise. And schizophrenia? “Modelling research does not indicate increases in levels of schizophrenia commensurate with increases in cannabis use.”

One significant problem with surveys of this nature is the matter of determining marijuana’s effective potency—the amount of THC actually ingested by smokers. This may vary considerably, depending upon such factors as “natural variations in the cannabinoid content of plants, the part of the plant consumed, route of administration, and user titration of dose to compensate for differing levels of THC in different smoked material.”

Wendy Swift and her coworkers call for more research on cannabis users’ preferences, “which might shed light on whether cannabis containing a more balanced mix of THC and CBD would have value in the market, as well as potentially conferring reduced risks to mental wellbeing.”

Swift W., Wong A., Li K.M., Arnold J.C. & McGregor I.S. (2013). Analysis of Cannabis Seizures in NSW, Australia: Cannabis Potency and Cannabinoid Profile., PloS one, PMID:

Graphics Credit: http://420tribune.com

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