THC, the psychoactive compound behind the cannabis high, may also be able to treat potentially deadly lung inflammations, according to new research.
Published in the British Journal of Pharmacology, the new study found that THC could relieve inflamed pathways in the lungs of lab mice, as well as benefit the bacteria living the rodents’ lungs and guts.
In the lungs
If a person’s lungs become inflamed following an infection, breathing can become a lot harder. As a consequence, many tissues can become starved of vital oxygen and the body can enter a deadly spiral of organ failure. This life-threatening condition is termed acute respiratory distress syndrome (ARDS).
Because of the coronavirus pandemic, cases of ARDS have become more prevalent in hospitals all over the world.
But as there are no drugs currently approved to act on ARDS by the US Food and Drug Administration, most cases in the US are primarily treated with breathing machines and antibiotics, should the infection be bacterial – which Covid-19 is not.
To investigate whether THC could be an effective therapeutic for ARDS, researchers at the University of South Carolina first induced the syndrome in lab mice by infecting the rodents with a toxin from Staphylococcus aureus bacteria. Each mouse was then given three doses of THC during the first 48 hours of the infection.
After analyzing the mice’s lung tissue and fecal matter, the researchers concluded that the cannabinoid had successfully reduced lung inflammation.
“Analysis demonstrated that THC could attenuate acute lung injury, reduce congestion and minimize [a blood clot protein] in mice with ARDS which was accompanied by a decrease in the infiltration of the immune cells in the lung tissues when compared to vehicle controls,” the researchers wrote.
So, what’s behind this anti-inflammatory effect? Well, the researchers believe it has something to do with the mice’s cytokines, the small proteins that coordinate an immune response and set off inflammation. If too many cytokines are released, the subsequent “cytokine storm” can trigger ARDS. But THC, the researchers say, can inhibit cytokine production, thus reducing unnecessary inflammation.
“Cytokine storm is a huge clinical issue which leads to multiorgan failure and often death,” Prakash Nagarkatti, vice president for research at the University of South Carolina and co-author of the study, said in a statement.
“We have been working on cannabinoids for over 20 years and found that cannabinoids such as THC are highly anti-inflammatory,” he added.
Prakash and his colleagues also found that THC boosted the proportion of beneficial bacteria found in the mice’s lungs – a biological change that could improve an infection response.
“The results demonstrated that THC could significantly increase the species of Ruminococcus gnavus, but significantly decrease the species of Akkermansia muciniphila systemically following [toxin] exposure,” the researchers wrote.
Ruminococcus gnavus helps to modulate the production of mucus in the lungs, which is key to managing infections. As such, R. gnavus could be considered beneficial bacteria. Akkermansia muciniphila is known to increase cytokine production in the colon, so a fall in the numbers of the bacteria could help reduce unnecessary inflammation.
A Covid connection?
As morbidity of ARDS has become more notable during the coronavirus pandemic, more attention has been given to new potential treatments. THC, the South Carolina researchers say, is one such promising treatment.
“Our studies raise the exciting suggestion to test THC against ARDS seen in Covid-19 patients,” Nagarkatti said in a statement.
But even if THC’s effects on Covid-19 are further investigated and trialed, it will likely be years before researchers come to a clinical consensus on its viability. And during such studies, new findings may make researchers question the value of THC’s anti-inflammatory effects.
As Kevin Hill, an associate professor of psychiatry at Harvard Medical School – who was not involved in the new THC study – wrote recently in Cannabis and Cannabinoid Research, “Cannabinoids could possibly be a part of a treatment regimen, with nonsteroidal anti-inflammatory drugs (NSAIDs) and other medications that target immune pathways, that could downregulate the cytokine storm.”
“[But] anti-inflammatory activity may not be an advantage when combating viruses because it may mitigate host immune responses to acute viral infections, leading to disease progression and possibly death.”
Trauma patients who consumed cannabis pre-injury may recover from their trauma more quickly than their cannabis-free counterparts, according to the results of a new retrospective review.
The study, published in the Journal of Surgical Research, reviewed patient data from two large regional trauma centers and found that some trauma patients who tested positive for THC, the major intoxicant in cannabis, went on to spend less time in hospital or in intensive care.
While the cannabis-consuming patients were on average 15 years younger than the other patients – a factor that could help them recover from injuries at a faster rate – the study’s authors still say THC could have afforded some protective effect.
TBI and severely injured patients spend less time in recovery
The deidentified patient data used in the retrospective review came from patients admitted between 2014 and 2018 to two American College of Surgeons-accredited trauma centers similar in terms of location and sociodemographic.
After excluding data from patients under the age of 18, those who were not drug tested, or those who screened positive for other substances, the researchers were left with 4,849 patient records to examine. Of these, just under one-third of the remaining patients tested positive for THC.
The researchers used multivariable binary logistic regression analysis to examine any potential effect of preinjury cannabis use on trauma patient outcomes, and saw several trends deemed statistically significant.
THC-positive trauma patients with traumatic brain injury (TBI) had a median length of stay in hospital that was two days shorter than their THC-negative counterparts. These THC-positive TBI patients also needed less time on mechanical ventilation, spending a median of one less day on the apparatus.
Patients who were more severely injured – as assessed by an established medical tool, the Injury Severity Score – and who tested THC-positive also spent a lower amount of time in the intensive care unit and had a reduced mortality rate (19.3 percent mortality versus 25 percent) compared to non-users.
Overall mortality first appeared to be lower for the THC-positive patients. But, notably, this trend disappeared following the multivariate analysis.
While the researchers note that the study design does not allow for establishing causation, they hypothesize that the initial reduction in mortality could have been because the patients in the cannabis-consuming cohort were generally younger patients. With a 15-year age gap between the median age for the THC-positive and -negative cohorts, the researchers suggest that the younger cannabis users may just be “more physically robust” and able to recover at a faster rate. Although, the study’s authors cannot completely rule out the possibility that cannabis use could have afforded some protective effect.
Why would cannabis use affect traumatic injury recovery?
At first glance, there might not seem to be any obvious link between cannabis use and the potential recovery and outcomes of sustaining a traumatic injury. But beneath the surface, there is a lot of complex biology at play.
Traumatic injury elicits a rapid innate immune response as the body immediately tries to counteract disruption from the breaking of the skin, the breaking of cell membranes, and injury to organs. As a part of this, the body will trigger an inflammatory response. In some cases, a poor balance of this pro- and anti-inflammatory action may lead to the development of systemic inflammatory response syndrome (SIRS), which can damage the organs not damaged by the initial traumatic injury, eventually leading to multiorgan dysfunction.
THC and CBD, the major cannabinoids in cannabis, have both been shown to display some significant anti-inflammatory and immunomodulatory effects. As the trends identified in this study demonstrate, it is possible that with the use of cannabis pre-injury the presence of these cannabinoids in the body may offer some protection against the effects of the posttraumatic immune response. Though again, further studies will be needed to properly determine whether such a protective effect exists.
Cannabis and trauma
The effect of cannabis on recovery from traumatic injury has become a topic of some prominence in recent years.
In 2019, the Flowering HOPE Foundation and Clover Leaf University launched the first American clinical study to investigate the effects of plant-derived cannabinoids supplements in patients recovering from traumatic brain injury.
Earlier this year, researchers at the University of Miami Miller School of Medicine received a grant worth $1.6 million from a psychedelics research company to fund further studies into the use of CBD and the psychedelic compound psilocybin on mild traumatic brain injury (mTBI) and post-traumatic stress disorder.
Having already researched the effects of CBD on brain injury for several years, the Miami researchers believe in the compound’s ability to minimize some of the subsequent conditions that commonly result from mTBI, such as cognitive and memory issues. With some studies indicating psilocybin’s potential usefulness in altering fear conditioning, and the common co-occurrence of mTBI and PTSD following traumatic injury, the scientists hope to develop a useful combination treatment that can effectively assist in both physical and psychological recovery after traumatic injury.
Funding given to cannabis research in the United States, Canada, and the United Kingdom totaled more than $1.5 billion US dollars between the year 2000 and 2018, a new analysis has found.
Under close review, analysts found that significantly more funding was given to research into the negative effects of cannabis and cannabis misuse than on its medical and therapeutic uses.
More than $1.4 billion goes to American research projects
The analysis stems from a newly released database of grant data compiled by Jim Hudson, a consultant expert specializing in health research. Hudson collected and collated publicly available data from 50 major funders, including the likes of the US National Institutes of Health, the European Research Council, and a number of charities such as the Multiple Sclerosis Society.
They found that the total amount of cannabis research funding made available increased substantially year-on-year over the course of the last two decades. In the year 2000, less than $31 million went towards cannabis research projects. But by 2018, this annual figure had grown to over $151 million.
While the vast majority of that funding came in the form of project grants, several hundred million was spent on career grants, program grants, training, and assorted infrastructure over the analysis period.
The lion’s share of research funding went to research projects based in the US; American researchers received a total of over $1.4 billion between 2000 and 2018.
British research projects were the next most funded, attracting a total of $39.9 million. This figure was narrowly followed by the Canadian research project total of $36.1 million.
The database does look at some funding data for other countries; the European Research Council gives out grants Europe-wide and the EuropePMC’s open-access repository includes data on other European funders. But due to the limited data coverage for these other countries, the analysis chose to stick with a focus on the US, UK, and Canadian projects.
In terms of funding sources by organization, the US National Institutes of Health (NIH) lead the way, contributing a massive $1.47 billion in funding for cannabis-related research. Other big contributors included the Canadian Institutes of Health (CIHR), which gave $24.8 million, and the UK Medical Research Council (MRC), which raised $24.8 million.
What is being studied?
One important piece of nuance to keep in mind is that not all cannabis research is one hundred percent focused on cannabis; cannabis can be relevant to wider studies on drug use, addiction, health, and physiology.
In order to properly determine what should count as cannabis research and which cannabis research areas are receiving funds, the database analysis assigned a weighting score to each relevant funding grant. These weights reflected whether a study was:
The analysis found that between 2000 and 2018, the top-funded categories of cannabis research were, in descending order:
Upon closer analysis, it was seen that significantly more funding was given to researching the negative effects of cannabis and cannabis misuse than on the medical and therapeutic use of cannabis and its derived cannabinoids. As the majority of total funding came from the US NIH, this focus could be interpreted as a bias of the federal organization.
“The government’s budget is a political statement about what we value as a society,” wrote Daniel Mallinson, a cannabis policy researcher at Pennsylvania State University, who reviewed the funding data for Science. “The fact that most of the cannabis money is going to drug abuse and probably to cannabis use disorder versus medical purposes – that says something.”
Research topic funding for the UK, like in the US, was similarly dominated by topics surrounding the potential harms of cannabis. However, in Canada, the top-funded research category was endocannabinoid research, which accounted for around 43 percent of all Canadian funding. There was also interesting variation in funding focus noted between different organizations and national institutes; more than one-third of the funding provided by the Natural Science and Engineering Research Council went towards research focused on improving the commercialization of cannabis.
There were also some interesting geographic variations in cannabis research funding uncovered within the US. While the overall funding patterns in the US were very similar to the general patterns observed due to American projects receiving most of the funds, there was some notable state-level variance. For example, states which had fully legalized cannabis by 2019 were more likely to have received funds for the study of cannabis as a medical treatment.
The analysis also found that relative overall funding levels for projects focused on preventing cannabis use/abuse decreased over the years, while relative funding for those looking at cannabis and cannabinoids as a treatment for specific medical conditions increased.
Barriers to cannabis research
Notably, the analysis found that research on cannabinoids as a medical treatment received over 15 times more funding than research into treatments using cannabis itself.
The analysis does not speculate on any possible causes for this, but the nature of the data would imply that current American restrictions on cannabis research are playing a large part in this imbalance.
Cannabis’ status as a Schedule I drug means that researchers must go through a long and burdensome application process to get the necessary licenses to study the drug. By being a Schedule I drug, cannabis also comes with the associated assertion that the plant has “no currently accepted medical use.” And so, despite the existence of many state-level medical cannabis programs, it can be difficult for researchers to secure funding for medical research projects.
Even if a license and funding could be guaranteed, under current rules, researchers would only be permitted to use cannabis supplied by a singular authorized cultivation site, based within the University of Mississippi. The cannabis material supplied by this site has been criticized for being genetically closer to hemp than the cannabis strains currently available in state-legal markets and for its alleged poor quality.
But since the US Food and Drug Administration issued new draft guidance aimed at encouraging cannabis-related clinical research, and the Drug Enforcement Administration is seemingly on the path to improving cannabis access for researchers, there is cautious optimism among the research community that the tide could be changing.
“I have a lot of hope. The need is so clear,” Dr Joshua Levy, an assistant professor of otolaryngology and director of resident research at Emory University’s Department of Otolaryngology, told Analytical Cannabis last month.
“I am not aware of any compound in the history of drug development that is so widely used for medicinal purposes, yet still regulated [in this way]. I think the need and the market will, in its own right, push for reform.”