John M. Talmadge, M.D.

A Blog Covering Many Topics

Update on Marijuana Research

The current issue of Scientific American includes an article about the increased potency of marijuana available legally in some states. Author Dianna Kwan writes: "On the street it’s called skunk for its intense, pungent odor. But the smell isn’t the only thing that’s strong about this type of marijuana. These increasingly popular strains contain high levels of delta-9-tetrahydrocannabinol (THC), the main psychoactive substance in cannabis that causes its euphoric effects. Several new studies have noted the rapid rise in marijuana potency and raised questions about the risks it poses to users."

According to a recent analysis presented at the 2015 Meeting of the American Chemical Society, the amount of THC in samples from marijuana sold in Colorado are reaching 30 percent. Three major patterns have emerged over the past few months since Andy LaFrate, Ph.D., and his lab began testing marijuana samples. Those patterns concern potency, amounts of a substance called CBD and contaminants in the products.

“As far as potency goes, it’s been surprising how strong a lot of the marijuana is,” LaFrate says. “We’ve seen potency values close to 30 percent THC, which is huge.” LaFrate is the president and director of research of Charas Scientific, one of eight labs certified by Colorado to do potency testing.

THC is an abbreviation for tetrahydrocannabinol, which is the psychoactive compound in the plant. He explains that three decades ago, THC levels were well below 10 percent. Its content has tripled in some strains because producers have been cross-breeding them over the years to meet user demands for higher potency, he says.

But an unexpected consequence of this breeding has occurred, says LaFrate. Many of the samples his lab has tested have little to no cannabidiol, or CBD. CBD is a lesser known compound in marijuana that is of increasing interest to medical marijuana proponents. Researchers are investigating CBD as a treatment for schizophrenia, Huntington’s disease and Alzheimer’s disease. It is also being considered for anxiety and depression. But unlike THC, CBD doesn’t get people high — that’s a key trait for many people who are wary of buzz-inducing drugs and for potential medical treatments for children. As for recreational users, the lack of CBD in marijuana means that many of the hundreds of strains they select from could in actuality be very similar chemically, according to LaFrate.

"What we have today is not the weed we used to smoke in the 1960's."

In a recent report researchers found that the concentration of THC sold on the streets in Denmark has tripled to an average of 28 percent in the last 20 years.
Attitudes toward marijuana are also rapidly changing. In the 1960s surveys found a mere 12 percent supported marijuana legalization—now, more than 50 percent are in favor. Over the past decade recreational/medicinal use of cannabis was legalized in the District of Columbia as well as in Alaska, Colorado, Oregon and Washington State; 19 other states also permit the use of the drug for medical purposes. As more states and countries, such as Canada and the U.K., consider following suit, advocates and critics are engaging in heated debates about the potential risks and rewards—particularly in light of the increasing prevalence of highly potent marijuana. But the evidence is nebulous—even within the scientific community, there is lack of consensus about how much harm marijuana can do to users’ brains and mental health.

In addition to THC, the other major component of marijuana that has caught the attention of researchers is cannabidiol (CBD), which scientists have linked to antipsychotic properties. Not only do THC and CBD have opposing effects, cannabis with higher THC content tends to contain lower amounts of CBD. “The relationship between CBD and THC is unique, in that the biological process required to make THC antagonizes the generation of CBD,” says Matthew Hill, a cannabinoid neuropharmacologist at the University of Calgary.

Damage to the brain?

In an article published last month in Psychological Medicine, researchers conducted a neuroimaging study to assess the effects of cannabis use on the corpus callosum, the largest collection of white matter in the brain containing fibers that facilitate communication between the two hemispheres. They found that this structure was negatively affected in those who used high potency cannabis—strains high in THC and low in CBD—compared with those who used lower strength bud or did not use at all. Moreover, the changes were similar in both those with and without previous episodes of psychosis. However, the researchers assert that they did take other drug usage into account.

Previous studies have demonstrated the importance of these confounding factors when interpreting marijuana’s effects on the brain. For example, a 2014 study in The Journal of Neuroscience reported that marijuana use was associated with changes in brain structures associated with reward processing. This effect was dose-dependent, meaning the more cannabis someone used, the more changes became apparent in their brains. In a subsequent study, published in 2015 in the same journal, another group of researchers found that once variables such as alcohol use, gender and age were controlled for, the differences between users and nonusers disappeared.

Marijuana madness?

In a study published earlier this year in Lancet Psychiatry the same group of researchers at King’s College found that using cannabis, and THC specifically, can produce acute psychotic symptoms, and some researchers suggest it increases the risk of developing schizophrenia. The link between marijuana and psychosis, however, has been a matter of heated debate in the scientific community. Researchers have argued that there are sufficient grounds to doubt the causality of this link. There are two alternative possibilities: being predisposed to schizophrenia may increase the likelihood for cannabis use or a third variable may make it more likely for people to use marijuana and develop schizophrenia. For example, previous studies have suggested that schizophrenia and cannabis share both genetic and demographic risk factors, such as low socioeconomic status.

Critics also point to the fact that all the studies to date have been correlational. But this does not immediately dismiss the possibility that causation is possible. After all, although there was a strong correlational link between smoking and cancer, it took a study of more than 30,000 British doctors to confirm causality.

According to Haney, the odds ratio—the likelihood that an exposure will lead to a certain outcome—of marijuana causing psychosis are much lower than those for smoking and cancer. “There is also an association with tobacco smoking and schizophrenia that is much stronger [than cannabis use],” Haney says. “If this relationship is causal, it is a tiny effect, which might explain why there hasn't been a dramatic upsweep in rates of schizophrenia in recent years.”

Both Haney and Evins agree that it is biologically plausible that marijuana, particularly at a young age, could increase the likelihood of negative psychiatric outcomes. The developing brain has an abundance of cannabinoid type 1 (CB1) receptors, where THC binds to exert its effects, in the prefrontal cortex, a key brain area impacted by schizophrenia. “I don't think it's a good idea for young children to be smoking marijuana at all because of their developing brains but I am extremely cautious about pinning it all on marijuana when there is a potential for many other explanations,” Haney says.

To truly determine whether marijuana causes such effects, scientists would need to track changes that occur in a large number of individuals before and after they use a drug over a long period of time. An effort to conduct this type of study is currently underway—the National Institutes of Health recently funded the multicenter Adolescent Brain Cognitive Development Study, which plans to recruit 10,000 children before they start drug use, and follow them for 10 years to assess the short-and long-term effects of using marijuana, tobacco and other drugs.

Teenagers and young adults at risk?

Cannabis has been found to impair cognitive functions such as memory and is increasingly being considered an addictive substance, especially in adolescents. There are still many questions that remain to be answered but strict regulation and lack of funding pose large barriers to conducting the required studies. The U.S. Drug Enforcement Administration still classifies marijuana in its most restrictive “Schedule I” category, which puts tight regulations on researchers who want to study its effects.

A New Zealand study found that persistent cannabis users show neuropsychological decline from childhood to midlife. These scientists found that frequent and persistent marijuana use starting in adolescence was associated with a loss of an average of 8 IQ points measured in mid-adulthood. Significantly, in that study, those who used marijuana heavily as teenagers and quit using as adults did not recover the lost IQ points.

Users who only began using marijuana heavily in adulthood did not lose IQ points. These results suggest that marijuana has its strongest long-term impact on young users whose brains are still busy building new connections and maturing in other ways. The endocannabinoid system is known to play an important role in the proper formation of synapses (the connections between neurons) during early brain development, and a similar role has been proposed for the refinement of neural connections during adolescence. If confirmed by future research, this may be one avenue by which marijuana use during adolescence produces its long-term effects. (For details see: Meier MH, Caspi A, Ambler A, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci USA. 2012;109:E2657-2664.)

The ability to draw definitive conclusions about marijuana’s long-term impact on the human brain from past studies is often limited by the fact that study participants use multiple substances, and there is often limited data about the participants’ health or mental functioning prior to the study. Over the next decade, the National Institutes of Health is planning to fund a major longitudinal study that will track a large sample of young Americans from late childhood (before first use of drugs) to early adulthood. The study will use neuroimaging and other advanced tools to clarify precisely how and to what extent marijuana and other substances, alone and in combination, affect adolescent brain development.

Scientists agree the highly potent marijuana may be better to avoid. Aside from potential long-term harm, receiving a high dose of THC can be especially risky for first-time users who are more likely to experience adverse effects such as panic or anxiety attacks. But even knowing the potency of a product, consumers might not always get what they ask for.

Because of competing laws at the state and federal level, the quality of regulation varies largely between states and regions. Although THC potency labeling is mostly required for both medical and recreational products, it is not always accurate—a study published this June in JAMA The Journal of the American Medical Association revealed that of the 75 edible marijuana products (from 47 different brands) researchers assessed only 17 percent accurately labeled their THC content.

The article states: "Edible cannabis products from 3 major metropolitan areas, though unregulated, failed to meet basic label accuracy standards for pharmaceuticals. Greater than 50% of products evaluated had significantly less cannabinoid content than labeled, with some products containing negligible amounts of THC. Such products may not produce the desired medical benefit.

"Other products contained significantly more THC than labeled, placing patients at risk of experiencing adverse effects.5,6 Because medical cannabis is recommended for specific health conditions, regulation and quality assurance are needed.

"A limited number of cities, dispensaries, and products were included. Because no source lists all dispensaries, and many products are not labeled with cannabinoid content, a true random sample was not possible and the results may not be generalizable. However, this study illustrates the variability in label accuracy for edible cannabis products within 2 of the largest medical cannabis markets in the United States."


Across labs and in homes, marijuana remains a highly debated issue. Marijuana is an extremely polarizing topic among scientists, as these articles demonstrate. My own view is that marijuana is not likely to cause someone to suffer a schizophrenic illness, but clearly what we have today is not the weed we smoked in the 1960's.