The federal government plans to award $1.5 million in grants during the 2019 fiscal year to researchers who study how components of marijuana other than THC affect pain.
In a notice about the funding opportunity published on Thursday, the National Center for Complementary and Integrative Health (NCCIH) said that it was seeking applications from researchers to conduct studies on “minor cannabinoids and terpenes.” The aim of the grants will be to learn how these components work—separately and when combined—as potential pain-relieving agents.
The research is especially important given the widespread use of addictive opioid-based painkillers for pain management, NCCIH said. While THC has known analgesic properties, very little is known about the hundreds of other constituents in cannabis, which could represent viable alternatives to popular painkillers.
“Early clinical data suggest that cannabis may enhance the potency of opioids in relieving pain; and the synergy from using these products together may result in more effective pain relief with lower doses of opioids,” the agency wrote. “Yet, it is unclear which components of cannabis may have these properties. In particular, few studies have examined whether and which cannabinoids and/or terpenes interact with the opioid pain pathways.”
NCCIH, which is part of the National Institutes of Health, said that of particular interest are studies looking at cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), nyrcene, β-caryophyllene, Limonene, α-terpineol, linalool, α-phellandrene, α-pinene, β-pinene, γ-terpinene and α-humulene.
“A growing body of literature suggests that the cannabis plant may have analgesic properties; however, research into cannabis’s potential analgesic properties has been slow,” the funding opportunity says. “One key mechanism to investigate is whether potential analgesic properties of cannabis can be separated from its psychoactive properties. To address this question, more research is needed into the basic biological activity of the plant’s diverse phytochemicals, specifically minor cannabinoids and terpenes.”
NCCIH listed 11 areas of interest for prospective applicants:
* To investigate the potential analgesic properties and adverse effects of minor cannabinoids, alone or in combination with each other or terpenes;
* To investigate the mechanisms by which minor cannabinoids and terpenes may affect pain pathways, including ascending and/or descending neural pathways, cellular and molecular signaling pathways, neuroimmune interactions, or other innovative regulatory pathways related to pain;
* To explore the impact of sex, age and ethnicity on potential analgesic properties of minor cannabinoids and terpenes;
* To explore analgesic potential of minor cannabinoids and terpenes for different pain types (e.g., acute pain, chronic pain, inflammatory pain, neuropathic pain);
* To investigate the pharmacology (pharmacokinetic and pharmacodynamic profiles) of minor cannabinoids and terpenes;
* To explore binding affinities of minor cannabinoids and terpenes to cannabinoid and opioid and other pain-related receptors;
* To investigate the impact of dose and/or route of administration on potential analgesic effects of minor cannabinoids and terpenes;
* To characterize if/how specific terpenes may influence potential analgesic properties of cannabinoids;
* To explore potential opioid sparing effects of minor cannabinoids and terpenes;
* To explore the interaction between the microbiome and minor cannabinoids or terpenes;
* To improve methods to quantify systemic levels of minor cannabinoids and terpenes
Applicants are encouraged to submit letters of intent about their research proposals 30 days before the March 15 application deadline. The $1.5 million will be distributed among four grant recipients.
The agency first announced its intent to launch the funding opportunity in November.
“The mechanisms and processes underlying potential contribution of minor cannabinoids and terpenes to pain relief and functional restoration in patients with different pain conditions may be very broad,” NCCIH said. “This initiative encourages interdisciplinary collaborations by experts from multiple fields—pharmacologists, chemists, physicists, physiologists, neuroscientists, psychologists, endocrinologists, immunologists, geneticists, behavioral scientists, clinicians, and others in relevant fields of inquiry.”
The research opportunity is one of several marijuana-related projects the federal government has recently promoted. For example, NCCIH has four other grants available to researchers to study “natural products” such as cannabis, the National Institute on Drug Abuse is calling for bulk marijuana cultivators to supply research-grade cannabis and the Agency for Healthcare Research and Quality has asked the public to send them information about marijuana and Alzheimer’s disease.
Photo courtesy of Brian Shamblen.
Study Explores How Different Marijuana Extracts Kill Types Of Cancer Cells
Marijuana extracts can impair the survival of certain types of cancer cells and inhibit their spread, according to a recent study. But the effects of those extracts vary significant based on their specific chemical makeup.
Researchers found that treating cancer cells with isolated ingredients in cannabis, such as THC alone, does not appear to be especially effective—but full cannabis extracts showed more promise. However, with the plant containing hundreds of compounds that appear in different concentrations across strains and preparations, researchers had their work cut out for them in investigating how various cannabinoid combinations treated different types of cancer cells.
The team tested the antitumor effects of 12 whole cannabis extracts on 12 human cancer cell lines in order to “determine whether whole cannabis preparations with specific phytocannabinoid profiles could be advantageous as therapy for certain cancer sub-types.” The findings were published in the journal Oncotarget.
“Our results show that specific cannabis extracts impaired the survival and proliferation of cancer cell lines as well as induced apoptosis.”
Each cell sample was treated with a marijuana extract in increasing doses (2-10 µg/ml) over the course of 24 hours. There were five preparations of cannabis that proved especially potent for a wide range of cancer types but, in general, the study shows there’s significant variability in effectiveness for different cancer types—even when the cancers originated in the same organ.
For example, two distinct forms of prostate cancer cells were found to be most sensitive to entirely different marijuana extracts.
The cannabis preparations also ranged widely in their effectiveness in preventing the proliferation of cancer cells. When applied to multiplying cells, there were three extracts that reduced the growths to 37-51 percent of their original size, compared to 68 percent for the control group. But there were other extracts that failed to reduce the spread in a statistically significant manner.
Some commonalities shared among the most potent cannabis extracts include a high concentration of THC and large amounts of phytocannabinoids in their decarboxylated form.
“Taken as a whole, we concluded that medical cannabis does not consist of a single therapeutic agent but rather a heterogeneous array of treatments,” the researchers wrote. “We propose that the fate of specific cancer cells following cannabis extract application is dependent upon the synergistic effects of its phytocannabinoid composition, concentration applied, along with the cell specific characteristics (e.g. cannabimimetic receptor expression).”
“This study demonstrates the anti-cancer activity of various whole cannabis extracts on a set of human cancer cell lines.”
The study concluded that “cannabis extracts were very potent in producing cell death and some of these extracts were of [THC]-rich type” and that, as previous studies have indicated, “using whole cannabis extracts is more effective in inducing cancer cell death than applying pure [THC] on the studied cells lines.”
“Furthermore, not all [THC]-rich extracts produce the same effects when applied at the same concentrations on a specific cancer cell line,” the study authors wrote. “These findings indicate that compounds other than [THC] in these extracts might act together in a polypharmacology way and determine the extract efficacy as antitumor agents.”
Interestingly, the researchers also theorized that the the “presence or absence of [cannabinoid receptors] in the tested cell lines may explain the differential potency of the extracts towards reducing cell survival.”
The team called for further research into the “specific properties and mechanisms of cancer cell insensitivity to cannabis extract effects.”
“We hope that this study will lay the groundwork for future preclinical studies and randomized controlled clinical trials in order to provide evidence for effective cannabis treatments for many cancer subtypes,” they concluded.
Photo courtesy of Evan Johnson.
Marijuana Legalization Associated With Decreased Interest In Alcohol, Study Finds
Interest in alcohol declines after states legalize marijuana, according to a new study analyzing online behavior. But for reasons that aren’t entirely clear, interest in tobacco products increases following the policy change.
Another notable finding is that interest in cannabis among young people appears to decline after the end of prohibition.
Researchers from the University of Georgia and Syracuse University sought to identify the cross-commodity effects of legalization and used data from a “leading US-based web portal” from January 2014 to April 2017 to see how the implementation of adult-use legal marijuana programs in states changed online behavior such as web searches and engagement with advertisements.
The data set “covers over 28 million searches and 120 million ad impressions related to cannabis, alcohol and tobacco industries,” they wrote.
Published in the journal Marketing Science, the study reveals diverging trends for alcohol and tobacco.
Legalization “reduces search volume and advertising effectiveness for alcohol, but increases those for tobacco,” the authors wrote. “Hence, cannabis appears a substitute to alcohol, but not to tobacco.”
It also determined that recreational marijuana legalization leads to a nearly 17 percent increase in cannabis-related searches—however, that increase was “significantly attenuated” for young people, who did not search for marijuana more post-legalization. On the contrary, the study noted a “significant decrease in cannabis search[es] among the youth after” legalization.
“Contrary to widely held public concern after recreational cannabis is legalized, teenagers appear to lose interest, rather than gain interest,” study author Pengyuan Wang said in a press release. “Policymakers only concerned with an uptick in teen users, may want to rethink their stance.”
That finding is supported by another recent study exploring youth cannabis consumption. An analysis of federal data from 1993 to 2017 showed that self-reported past-month youth cannabis use decreased by about eight percent in states that legalized marijuana for adult use.
Alcohol searches decreased by about 11 percent after a state legalized marijuana, the researchers behind the new study found. They argued that the results show that the alcohol industry “has valid reasons to be concerned about legal cannabis and may need creative strategies to avoid market decline if [recreational cannabis legalization] passes.”
However, predictions about marijuana’s potential to disrupt the tobacco industry might have been overblown, the study indicated. Searches for tobacco products increased by almost eight percent and so “tobacco companies may need to reexamine their presumption, and that anti-cannabis legalization is not in their best interest,” Wang said.
It’s not clear whether the analysis of tobacco search trends included cannabis-adjacent products such as blunts, rolling papers or vaporizer devices, which could overlap between tobacco and marijuana consumers. Marijuana Moment reached out to Wang for clarification but she did not immediately respond.
The research team said that their study is unique because it’s the first to analyze “large-scale unobtrusive behavioral data before and after policy change to unveil the treatment effect of [recreational cannabis legalization] using a difference-in-difference approach.”
“These findings on cross-commodity relationships help resolve the conflicting literature and provide distinct implications for practitioners,” the study authors wrote.
Photo courtesy of Martin Alonso.
Legalizing Marijuana Leads To Fewer Illegal Grow Sites In National Forests, Study Finds
In news that Smokey Bear, iconic protector of all forests, would be happy to hear, research shows that reports of illegal marijuana grow operations on federally protected lands fell after states began legalizing it for adult use.
“Arguably,” the study authors write, “our models hint that outright, national recreational cannabis legalization would be one means by which illegal growing on national forests could be made to disappear.”
“[W]e find that recreational cannabis legalization is associated with decreased reports of illegal grow operations on national forests.”
The research, which was published in the journal Ecological Economics earlier this month, is thought to be the first of its kind to analyze the effects of legalization policies on illegal outdoor grows in national forests throughout the United States. A separate recent study found that cannabis cultivation on federal lands specifically in the Pacific Northwest declined after legalization.
Researchers with the United States Department of Agriculture’s Forest Service used existing data on the number of illegal grow sites reported between 2004 and 2016 in 111 national forests. In addition to incorporating other variables into their analysis (including state marijuana policies, retail price for consumers, risk of exposure and others), they also came up with six simulated scenarios with policy changes to create random effects models of the number of reported grows.
For example, in one scenario, the study’s authors estimated how many illegal grow sites would exist if current laws legalizing both recreational and medical marijuana were revoked. In another simulation, wholesale and retail sales taxes on legal marijuana were eliminated in states that had already approved the sale and consumption of cannabis in 2016.
According to the study’s findings, “policies legalizing recreational cannabis production and consumption are associated with significantly lower numbers of reported illegal grows on national forests.”
The study’s predictive models showed that eliminating current state laws legalizing access to marijuana would result in “double-digit percentage increases in reported grows on national forests, while further expansion of the set of states with such laws passed by statewide referenda in 2016 (but only instituting applicable laws in 2017 or later, post-dating our dataset) would be expected to reduce growing on national forests by a fifth or more.”
If all 23 states that had approved medical marijuana by 2016 moved to more broadly legalize for adult use, the study continues, illegal cultivation sites in national forests would decline anywhere from 35 percent to 51 percent. However, it concluded that legalization of medical cannabis across the U.S. alone would not affect grow operations in national forests.
Mere decriminalization of possession was also found to have no significant effect on the number of illegal farms, though models did show that harsher penalties for illegal production and possession of marijuana, as well as stricter regulations on CBD oil and similar products, did. Meanwhile, an increase in law enforcement presence only made a slight difference (a 2.5 percent decrease in reported illegal grows) if local agencies increased their manpower by 20 percent.
Another issue, of course, is the role of taxes. If states reduced how much they tax legal sales by 6 to 13 percent, the number of illegal grows would decline. As researchers point out, “availability of legal cannabis does not encourage illegal cultivation unless the after-tax price for legal cannabis is substantially elevated relative to the illegal product.”
“As a practical matter,” the study authors summarize, “the number of cannabis grows on national forests could be reduced in two opposite ways: (1) legalization, or (2) increased efforts to deter, incarcerate, and otherwise discourage participation in the illegal market. Redefining what is legal perhaps would yield reductions that are cost less for the Forest Service, at least in the narrow sense of cannabis law enforcement demands, and would reduce the damages associated with cannabis cultivation.”
Ecologists have raised concerns about the environmental impact illegal marijuana cultivation sites have on national forests, such as the use of highly toxic rodenticide to ward off pests.
Photo by Aphiwat chuangchoem/Pexels.