What marijuana research in humans tells us so far about the drug’s benefits and drawbacks.
By Jennifer Walter
(Credit: Poylock19/Shutterstock)
It’s mid-October, and Staci Gruber is preparing to testify
before Congress. It’s not the first time she’s brought her expertise
before policymakers; she’s studied marijuana in brains young and old for
the better part of three decades.
Besides being on the psychiatry faculty at Harvard University, Gruber is the director of Marijuana Investigations for Neuroscientific Discovery (MIND) and the director of the Cognitive and Clinical Neuroimaging Core at McLean Hospital outside of Boston. Her research focuses on clinical studies in marijuana users, often employing functional MRI (fMRI) technology to see exactly what parts of the brain the drug affects.
“The important part is to try to leave the emotional rhetoric aside,” she says, ahead of her testimony before lawmakers. “What matters is what the data and the science tell us.”
And the research landscape, so far, is about as complicated as the drug itself. Some studies show that marijuana may provide relief for patients with a slew of conditions, such as anxiety, chronic pain and even cancer. Yet others find that the drug can slow cognitive function and may worsen some mental health conditions.
We also still don’t have a clear picture of how marijuana works in different people, Gruber says. Just five years ago, when she started MIND, Gruber spotted a research gap — virtually no clinical studies were conducted on the effects of medical marijuana on the brain. “I could find nothing in the literature,” she says.
Data on how marijuana works in people over time are sparse. U.S. research on cannabis remains bottlenecked because of limitations on studying the Cannabis sativa plant, some parts of which remain a Schedule I drug. Even though medical marijuana containing the psychoactive compound THC is legal now in 33 states and the District of Columbia, the Drug Enforcement Administration still defines it as a substance with “no currently accepted medical use” and a “high potential for abuse.” Policymakers, eager to better understand how to regulate the drug, occasionally hold sessions with scientists, including Gruber. But with scarce clinical results, she and her American peers find it hard to draw broad conclusions. In countries like Israel and Canada, where barriers to studying cannabis are lower, piecing together the puzzle of who marijuana affects, and how, is only slightly easier.
In a 2011 report on recreational users, Gruber and her team recruited 34 chronic marijuana smokers and divided them into two groups according to when they started using. They were then given a number of cognitive tests. The team found that those in the study who started using marijuana before age 16 had the worst test performances — and smoked twice as often as other users.
But a 2018 clinical study on medical marijuana users showed very different effects on the brain. The study looked at patients with a variety of conditions, including pain, anxiety, sleep disorders and gastrointestinal problems, before and after taking marijuana via their preferred method of use — s
moking, eating or topically applying. Three months after patients started treatment, varying from one or two doses a week to multiple doses per day, the researchers observed that their brains had more activity in the prefrontal cortex, the area associated with cognition, decision-making and executive function. They also saw an increase in task performance among the users, signifying a boost in cognitive function.
In addition, the treatment quelled their symptoms — most medical marijuana users in the study saw an increase in quality of life and alleviation of their ailments. The results weren’t a huge shock for Gruber.
“Recreational consumers and medical users just aren’t the same,” she says. “The goal of use is totally different.”
That could explain why some recreational users seek out super-loaded quantities of tetrahydrocannabinol (THC) in the strains they smoke. THC is what makes users high; its sister component, cannabidiol (CBD), does not. From 1995 to 2014, THC content in recreational marijuana increased from 4 to 12 percent, while the CBD content in modern-day weed is barely 0.15 percent.
CBD, on the other hand, is growing in popularity as a medicinal treatment for inflammation, pain and anxiety. But the jury’s still out on how well the compound works as a remedy. In 2018, Gruber’s team began the first clinical trial on CBD in patients with anxiety, with results expected as early as this year.
In a 2017 clinical trial of 88 patients with schizophrenia, researchers in the U.K. administered 1,000 milligrams of CBD each day to about half of the study participants. They took the supplement along with their typical regimen of antipsychotic medications. At the end of six weeks of treatment, the people who received CBD reported greater alleviation of symptoms than those who only stuck to their normal medications.
But another study from just this year found that weed might actually correlate with an onset of psychosis. Researchers in the U.K. surveyed more than 900 patients who had been diagnosed with their first psychotic episode, and over 1,200 participants who had not been diagnosed with psychosis.
They asked about lifetime cannabis use and found that daily marijuana users had the highest risk of developing the condition.
That risk may be linked to the concentration of THC in a particular cannabis product, however. In the same study, researchers split weed users into two groups: those who typically smoked marijuana with a THC concentration of less than 10 percent, and those who used high-potency pot with a concentration of 10 percent or higher. They found that high-potency users had a fivefold increased chance of developing psychosis. Taken together, these findings help show that our brains have very different reactions to CBD and THC — which might be why medicinal users often experience such different results from recreational users.
A small clinical study published in the German journal Der Schmerz indicated that an oral medication form of synthetic marijuana, known as dronabinol, helped relieve pain in patients older than 80.
According to the results, released in October, more than half of patients experienced some level of pain relief after a year of taking the medication.
And a much larger study found positive results among a slightly younger crowd. In Israel, a team of researchers administered a questionnaire about quality of life before and after patients at a specific clinic started using cannabis. The results compiled data from over 2,700 patients older than 65, most of whom had chronic pain or cancer symptoms. More than 90 percent of patients noted an improvement in their condition after six months of using the drug.
In another study, the same researchers also analyzed data from cancer patients who routinely used medical marijuana to manage their symptoms. Drawing results from just over 1,200 patients, they found that over 95 percent reported an improvement in their symptoms, which ranged from sleep problems and lack of appetite to weakness, nausea and pain.
The German and Israeli studies concluded that the drug was safe and effective in older populations seeking relief from pain or cancer-related symptoms. Marijuana might be a positive alternative for older folks looking for relief — although not every medical condition responds as drastically to treatment as others.
The largest randomized clinical study on MS and marijuana to date, according to the National Multiple Sclerosis Society, found that different oral THC medications helped patients manage symptoms like spasticity and sleep struggles, while there was no improvement in tremor or bladder symptoms. And another clinical study done in the U.K. in 2013 showed that oral THC, while not unsafe, didn’t slow the progression of the disease.
But a 2012 study did find that short-term marijuana use may help with those physical symptoms.
Researchers at the Center for Medicinal Cannabis Research at the University of California, San Diego, studied the effects of inhaled cannabis on pain levels and spasticity control. Thirty participants smoked marijuana once a day for three days, and noted that their spasticity and pain levels decreased more than for those who took a placebo.
Preliminary results from a 2019 study show the picture is different when it comes to the mental effects of marijuana on MS patients. Researchers in Canada followed study participants, who had been smoking at least four times a week for many years, as they abstained from marijuana for 28 days. The research team took fMRI scans as they were weaned off the drug, and noted that they showed an increase in cognitive function. Certain areas of the brain that were normally inactive in the participants started to reawaken, and their performances improved in cognition tests.
To date, only a few medications — dronabinol, nabilone and cannabidiol — have received FDA approval. But they’re intended for use by a select group of patients: those with rare forms of epilepsy, those who have side effects from chemotherapy or those with severe weight loss caused by AIDS.
Dronabinol and nabilone, which are both oral synthetic forms of cannabis, are defined as Schedule II and III drugs. That means the DEA sees a moderate to high potential for dependence or abuse, although certain patients are still allowed to use the drug for its medicinal benefits. In 2018, a CBD-derived oral medication called Epidiolex was approved as a Schedule V, meaning it is regulated as a drug with the least potential for abuse.
But with recreational marijuana use on the rise, researchers like Gruber are pushing for more concrete evidence on the drug’s effects. She’s certain that it’s far from vanishing from the public eye.
“It’s like rock ’n’ roll,” she says. “It’s here to stay.”
Besides being on the psychiatry faculty at Harvard University, Gruber is the director of Marijuana Investigations for Neuroscientific Discovery (MIND) and the director of the Cognitive and Clinical Neuroimaging Core at McLean Hospital outside of Boston. Her research focuses on clinical studies in marijuana users, often employing functional MRI (fMRI) technology to see exactly what parts of the brain the drug affects.
“The important part is to try to leave the emotional rhetoric aside,” she says, ahead of her testimony before lawmakers. “What matters is what the data and the science tell us.”
And the research landscape, so far, is about as complicated as the drug itself. Some studies show that marijuana may provide relief for patients with a slew of conditions, such as anxiety, chronic pain and even cancer. Yet others find that the drug can slow cognitive function and may worsen some mental health conditions.
We also still don’t have a clear picture of how marijuana works in different people, Gruber says. Just five years ago, when she started MIND, Gruber spotted a research gap — virtually no clinical studies were conducted on the effects of medical marijuana on the brain. “I could find nothing in the literature,” she says.
Data on how marijuana works in people over time are sparse. U.S. research on cannabis remains bottlenecked because of limitations on studying the Cannabis sativa plant, some parts of which remain a Schedule I drug. Even though medical marijuana containing the psychoactive compound THC is legal now in 33 states and the District of Columbia, the Drug Enforcement Administration still defines it as a substance with “no currently accepted medical use” and a “high potential for abuse.” Policymakers, eager to better understand how to regulate the drug, occasionally hold sessions with scientists, including Gruber. But with scarce clinical results, she and her American peers find it hard to draw broad conclusions. In countries like Israel and Canada, where barriers to studying cannabis are lower, piecing together the puzzle of who marijuana affects, and how, is only slightly easier.
Complicated Cognition
How does weed affect cognition? That might depend on how and when people use it. Some teenagers who use marijuana recreationally appear to have slower brain function and lower IQs. On the other hand, people with medical conditions who stay slightly baked to manage their symptoms may actually see an increase in brain function.In a 2011 report on recreational users, Gruber and her team recruited 34 chronic marijuana smokers and divided them into two groups according to when they started using. They were then given a number of cognitive tests. The team found that those in the study who started using marijuana before age 16 had the worst test performances — and smoked twice as often as other users.
But a 2018 clinical study on medical marijuana users showed very different effects on the brain. The study looked at patients with a variety of conditions, including pain, anxiety, sleep disorders and gastrointestinal problems, before and after taking marijuana via their preferred method of use — s
moking, eating or topically applying. Three months after patients started treatment, varying from one or two doses a week to multiple doses per day, the researchers observed that their brains had more activity in the prefrontal cortex, the area associated with cognition, decision-making and executive function. They also saw an increase in task performance among the users, signifying a boost in cognitive function.
In addition, the treatment quelled their symptoms — most medical marijuana users in the study saw an increase in quality of life and alleviation of their ailments. The results weren’t a huge shock for Gruber.
“Recreational consumers and medical users just aren’t the same,” she says. “The goal of use is totally different.”
That could explain why some recreational users seek out super-loaded quantities of tetrahydrocannabinol (THC) in the strains they smoke. THC is what makes users high; its sister component, cannabidiol (CBD), does not. From 1995 to 2014, THC content in recreational marijuana increased from 4 to 12 percent, while the CBD content in modern-day weed is barely 0.15 percent.
CBD, on the other hand, is growing in popularity as a medicinal treatment for inflammation, pain and anxiety. But the jury’s still out on how well the compound works as a remedy. In 2018, Gruber’s team began the first clinical trial on CBD in patients with anxiety, with results expected as early as this year.
Mind Under Matter
Our understanding of marijuana’s effect on mental health is murky. Some studies suggest it might exacerbate conditions like schizophrenia or psychosis, but the results aren’t always black and white.In a 2017 clinical trial of 88 patients with schizophrenia, researchers in the U.K. administered 1,000 milligrams of CBD each day to about half of the study participants. They took the supplement along with their typical regimen of antipsychotic medications. At the end of six weeks of treatment, the people who received CBD reported greater alleviation of symptoms than those who only stuck to their normal medications.
But another study from just this year found that weed might actually correlate with an onset of psychosis. Researchers in the U.K. surveyed more than 900 patients who had been diagnosed with their first psychotic episode, and over 1,200 participants who had not been diagnosed with psychosis.
They asked about lifetime cannabis use and found that daily marijuana users had the highest risk of developing the condition.
That risk may be linked to the concentration of THC in a particular cannabis product, however. In the same study, researchers split weed users into two groups: those who typically smoked marijuana with a THC concentration of less than 10 percent, and those who used high-potency pot with a concentration of 10 percent or higher. They found that high-potency users had a fivefold increased chance of developing psychosis. Taken together, these findings help show that our brains have very different reactions to CBD and THC — which might be why medicinal users often experience such different results from recreational users.
Grandpa’s Weed
Marijuana use is skyrocketing among the elderly — reports have suggested it has increased as much as tenfold among seniors over the past decade. And the drug might be an effective measure to treating chronic pain and chemotherapy side effects like nausea, which could explain the climbing usage rates.A small clinical study published in the German journal Der Schmerz indicated that an oral medication form of synthetic marijuana, known as dronabinol, helped relieve pain in patients older than 80.
According to the results, released in October, more than half of patients experienced some level of pain relief after a year of taking the medication.
And a much larger study found positive results among a slightly younger crowd. In Israel, a team of researchers administered a questionnaire about quality of life before and after patients at a specific clinic started using cannabis. The results compiled data from over 2,700 patients older than 65, most of whom had chronic pain or cancer symptoms. More than 90 percent of patients noted an improvement in their condition after six months of using the drug.
In another study, the same researchers also analyzed data from cancer patients who routinely used medical marijuana to manage their symptoms. Drawing results from just over 1,200 patients, they found that over 95 percent reported an improvement in their symptoms, which ranged from sleep problems and lack of appetite to weakness, nausea and pain.
The German and Israeli studies concluded that the drug was safe and effective in older populations seeking relief from pain or cancer-related symptoms. Marijuana might be a positive alternative for older folks looking for relief — although not every medical condition responds as drastically to treatment as others.
A Mixed Bag for MS
While a handful of studies have found marijuana to be a potential treatment for the pain and spasticity that come with multiple sclerosis (MS), not all clinical research shows a benefit.The largest randomized clinical study on MS and marijuana to date, according to the National Multiple Sclerosis Society, found that different oral THC medications helped patients manage symptoms like spasticity and sleep struggles, while there was no improvement in tremor or bladder symptoms. And another clinical study done in the U.K. in 2013 showed that oral THC, while not unsafe, didn’t slow the progression of the disease.
But a 2012 study did find that short-term marijuana use may help with those physical symptoms.
Researchers at the Center for Medicinal Cannabis Research at the University of California, San Diego, studied the effects of inhaled cannabis on pain levels and spasticity control. Thirty participants smoked marijuana once a day for three days, and noted that their spasticity and pain levels decreased more than for those who took a placebo.
Preliminary results from a 2019 study show the picture is different when it comes to the mental effects of marijuana on MS patients. Researchers in Canada followed study participants, who had been smoking at least four times a week for many years, as they abstained from marijuana for 28 days. The research team took fMRI scans as they were weaned off the drug, and noted that they showed an increase in cognitive function. Certain areas of the brain that were normally inactive in the participants started to reawaken, and their performances improved in cognition tests.
Smoke in the Wind
The bottom line is this: Research on marijuana remains inconclusive. Results differ from person to person, depending on why and how they use the drug.To date, only a few medications — dronabinol, nabilone and cannabidiol — have received FDA approval. But they’re intended for use by a select group of patients: those with rare forms of epilepsy, those who have side effects from chemotherapy or those with severe weight loss caused by AIDS.
Dronabinol and nabilone, which are both oral synthetic forms of cannabis, are defined as Schedule II and III drugs. That means the DEA sees a moderate to high potential for dependence or abuse, although certain patients are still allowed to use the drug for its medicinal benefits. In 2018, a CBD-derived oral medication called Epidiolex was approved as a Schedule V, meaning it is regulated as a drug with the least potential for abuse.
But with recreational marijuana use on the rise, researchers like Gruber are pushing for more concrete evidence on the drug’s effects. She’s certain that it’s far from vanishing from the public eye.
“It’s like rock ’n’ roll,” she says. “It’s here to stay.”
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