by Josh Kaplan
7 Jan 2021
Back in April, one of my students asked for an extension on an assignment, citing extended work hours at her retail store. I initially scoffed at the poor excuse: “What businesses are open during the stay-at-home order?” I asked, thinking I caught them in a lie. “The pot shop over by campus,” they responded. “We’ve been slammed.”
Indeed, while the world seemed to arrest, the cannabis industry’s pulse grew stronger. Cannabis research, though temporarily stymied as universities scrambled to get COVID-19 protocols in place, continued to plod ahead. Although the number of cannabis-related publications were down in 2020 compared to the previous year (what wasn’t, other than stock market indices?), scientists continued to unlock the mysteries of the fascinating plant.
Here are some of the top stories in cannabis research in 2020. (And for the record, the student was granted an extension.)
Improving our understanding of the endocannabinoid system
The endocannabinoid system wasn’t discovered until the 1990s, making it a relatively new system where much is still unknown. The two receptors in the endocannabinoid system, CB1 and CB2, look similar but function quite differently. As a result, it’s been difficult to find drugs that selectively activate one over the other.
The holy grail of a cannabinoid-based drug would be one designed to treat neurodegenerative disorders and pain, and to also provide neuroprotection, by selectively activating CB2 receptors without activating CB1 receptors, enabling the benefits of dampening inflammation without causing a high. To do so, drug designers need to know what both these receptors look like when resting and when activated. The problem: They’re really small.
This year, scientists were finally able to make pictures of CB1 and CB2 receptors in different activation states using a method that involves shooting electrons at receptors and measuring how they bounce off. It was a major progressive step forward, and the hope is these pictures can be used to develop specific drugs that take advantage of the immense power of the endocannabinoid system.
CB1 and CB2 receptors also play a competing role in cannabis’ rewarding effects. According to a study published at the tail-end of 2020, CB1 receptors are responsible for the pleasurable nature of low amounts of THC, but the effects of high doses become aversive due to the activation of CB2 receptors. Activating these CB2 receptors reduces the amount of dopamine, a brain chemical that codes information regarding what was good so that you can seek it out again. This counteracts the dopamine-boosting effects of activating CB1 receptors.
Therefore, the study suggests that your high, and the drive to seek it, is the result of a tug-of-war between your CB1 and CB2 receptors: If CB1 receptors are more activated, then you’ll want that high again. This points to the additional utility of targeted CB2 receptor drugs as potential therapies for substance use disorders.
Legitimizing cannabis for chronic pain treatment
Many physicians are hesitant to recommend cannabis as a pain treatment because of the lack of “good” studies, meaning evidence from placebo-controlled double-blinded clinical trials, the gold standard in clinical research.
While it’s false to say studies like that don’t exist, the case for cannabis isn’t a slam dunk in medical literature. However, two small-sample gold-standard studies were published in 2020 that lend support to cannabis’ pain-relieving benefits for chronic pain.
One study found that a 48:1 THC:CBD oil delivered sublingually via tincture substantially improved the quality of life for women suffering from fibromyalgia, a form of chronic pain that is notoriously difficult to treat. These patients consumed an average of 4.4 mg THC per day and reported that their pain was cut in half, their ability to perform at work improved, and their mood robustly improved compared to those who received a placebo. This highlights the promising effects of only a moderate THC dose in treating this debilitating condition.
A second study tested the feasibility of an inhaler-like THC delivery device in patients with chronic neuropathic pain. Although the researchers only looked at a single acute delivery, a small 1mg hit of THC was sufficient to reduce pain compared to a placebo, and its benefits persisted for over two hours.
Together, these studies support the benefits of THC in treating chronic pain symptoms. It’s important to highlight that these benefits were achieved with small or moderate THC doses, which is important to prevent tolerance to the drug and a likely loss of its therapeutic benefits.
THC doesn’t make you lazy
Many athletes are turning to cannabis to improve performance, enhance pleasure, and aid recovery. However, and in contradiction with the Reefer Madness-era propaganda, cannabis has traditionally been conceptualized as making people lazy.
Despite what anti-drug campaigns claim, THC’s effect on motivation to engage in endurance exercise isn’t well understood. We know that CB1 receptors, THC’s primary high-inducing brain targets, play an important role in motivation, but the effect of THC itself is unknown.
To better understand THC’s effect on exercise motivation, French scientists trained mice to make nose pokes in order to unlock a running wheel. They found that THC had no effect on a mouse’s preference to run, how hard they worked to gain access to the wheel, or their performance while running. These findings suggest THC does not affect the motivation to exercise and counters the belief that smoking weed will make you lazy.
However, the study authors found that genetically eliminating a mouse’s CB1 receptors did reduce their preference to run. This is important because excessive THC consumption can cause a tolerance, which one experiences as a weakening of THC’s effects, and is associated with the reduction in CB1 receptors.
This suggests that motivation can decrease with frequent use of THC-rich cannabis. But for periodic consumers, it looks like a couple of hits won’t keep you from wanting to put in the miles.
Cannabinoids may treat symptoms of Parkinson’s disease
Over the last decade, scientists have been exploring the role of CBD and THC in helping to slow the progression of age-related brain diseases such as Alzheimer’s. Recently, they’ve started to investigate their effects on Parkinson’s disease symptoms and found that the cannabinoids may help alleviate some symptoms.
For instance, tremors are a core symptom in Parkinson’s disease that can be exacerbated during periods of stress, and it was proposed that CBD’s anxiety and stress-reducing effects may help dampen tremors. To test this, Brazilian scientists conducted a double-blinded placebo-controlled trial of CBD with Parkinson’s disease patients during a simulated public speaking test. Using an accelerometer to measure tremor size, they found that a single dose of 300mg CBD reduced both anxiety and tremor compared to the placebo. These results suggest that CBD may be helpful in dampening tremor in Parkinson’s disease patients during stressful situations.
Another two core symptoms of Parkinson’s disease are slowness of movement and rigidity. To treat these symptoms, patients are commonly prescribed a drug called, L-DOPA (this is the same drug featured in the book and movie, Awakenings). The problem with this drug is it can lead to unwanted movements known as “dyskinesia.” So while L-DOPA can enable a Parkinson’s disease patient to move easier, it can tip the balance in the other direction and cause unwanted movements.
Interestingly, there are several different ways to help block these unwanted movements such as blocking CB1 receptors and activating CB2 receptors. Fortunately, THCV (tetrahydrocannabivarin), one of the many cannabinoids produced by the cannabis plant, fits the pharmacological profile needed to dampen dyskinesia.
Spanish scientists tested THCV’s utility directly against L-DOPA-induced dyskinesia in a mouse model of Parkinson’s disease. They revealed that THCV delayed L-DOPA’s effect on dyskinetic movements, and it reduced their intensity once present. These findings suggest that THCV may have promising add-on benefits to L-DOPA by reducing unwanted movements and highlights the promise of cannabinoid-based therapies for Parkinson’s disease.
A natural THC-like cannabinoid discovered
Scientists have been probing the composition of cannabis for nearly a hundred years, identifying nearly 150 cannabinoids thus far. It’s exciting when a new cannabinoid is discovered because, like recently-discovered Egyptian mummies, new cannabinoids serve as clues to better understanding the mystery behind the range of the plant’s effects.
Italian scientists isolated a new cannabinoid, THCP (tetrahydrocannabiphorol), from the FM2 strain and tested its ability to bind to the endocannabinoid receptors and affect mouse behavior. THCP mimicked the traditional effects caused by THC and seemed to do so more strongly than what others have reported of THC. This was reflected in high affinity binding to the endocannabinoid receptors, CB1 and CB2, which are needed to get one stoned, reduce pain, etc.
Comparing across studies, it appears that THCP binds around 30x more readily to CB1 receptors and 6x more readily to CB2 receptors than THC. While this doesn’t mean that THCP will get you 30x more high than THC, it implicates even low amounts of THCP as a potential culprit for why different strains have different intoxicating effects even when they have the same THC levels. For that to be the case, many questions remain to be answered. For instance, how much makes its way to the brain? Regardless, keep an eye out for more on THCP in the years ahead.