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.
Psychedelics May Help Improve Symptoms Of Psychiatric Disorders, Review Finds
Psychedelics with and without accompanying psychotherapy have been found to reduce symptoms associated with at least eight different psychiatric diagnoses, a new scientific review reports.
“The conditions treated ranged from depression to autism, with the largest volume of research dedicated to substance use disorders,” the paper states. “The majority of studies that were reviewed demonstrated significant associations with improvement in the conditions investigated.”
While the authors noted that “it was difficult to draw definitive conclusions as most studies suffered from small sample sizes, inconsistent measures, and poor study design,” the concluded that “this body of pilot literature suggests the possibility of therapeutic benefit that could outweigh adverse events and warrants more rigorous, definitive investigation.”
The findings were published in the Journal of Psychiatric Practice earlier this month.
Last year, an estimated 5.6 million Americans reported using hallucinogens, which are illegal, though federal agencies have acknowledged their potential medical value. To better understand how these psychedelic substances may help people, researchers at the University of Texas Health Science Center at San Antonio reviewed clinical studies that involved ayahuasca, ibogaine, ketamine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) and psilocybin.
The review’s authors focused on 16 studies published between 1946 and 2017. Here’s a look at some of their findings:
- In two related studies, patients who were diagnosed with recurrent major depressive disorder saw their symptoms reduced with a single dose of ayahuasca. Though the psychedelic substance was generally well-tolerated, half of study participants experienced vomiting.
- Patients with alcohol use disorder who were given a high dose of dipropyltryptamine while attending therapy for multiple weeks “demonstrated significant improvement on multiple rating scales, including depression, self-regard, and insight” during post-testing, the review states.
- In a study of 75 participants with alcohol, cannabis and cocaine use disorders, 61 percent reported abstaining from their substance of choice for an average of five months after being treated with ibogaine and behavioral therapy.
- Researchers found that ketamine-assisted psychotherapy helped more people abstain from alcohol abuse than those who underwent the same three-month psychotherapy course without the hallucinogen. “The authors,” the review states, “reported treating over 1000 patients with ketamine psychotherapy without any reports of prolonged psychosis, flashbacks, agitation, or ketamine abuse.”
- Patients diagnosed with alcohol use disorder may find it easier to abstain from drinking with a single dose of LSD than daily use of other common medications used to treat the disorder, according to a meta-analysis reviewing six randomized controlled trials.
- A small study found that higher MDMA dosage with therapy appeared to impact chronic PTSD symptoms related to sexual trauma more than lower doses of the substance.
- Another small study found that patients with varying cancers and related anxiety saw their anxiety and depressive symptoms reduced after a moderate dose of psilocybin, though the effects were not “statistically significant” until six months after administration. Researchers also found that patients experienced a short-lived increase in heart rate and blood pressure after taking psilocybin.
“In 15 of the 16 studies, it was reported that hallucinogen monotherapy or augmentation therapy produced clinically significant reduction in symptomatology,” the review states. “Many of these improvements occurred in subjects who had previously failed to respond to traditional treatments. Furthermore, many studies demonstrated improvement in less time than commonly observed with traditional psychopharmacology or therapy.”
Additionally, the review‘s authors found that all but one of the eight studies that examined how psychedelics may affect substance use disorders reported “significant benefits.”
“While the successes reported in the studies reviewed here are intriguing, they should not be misinterpreted as an endorsement for the use of hallucinogens to medicate any of the above conditions,” the authors wrote. “This review was inherently biased by the selection criteria, and dangers of hallucinogenic drug use were not the focus of this review. This should not, however, distract from the potential benefits described.”
The review concluded by pointing out structural barriers to expanded research on psychedelics.
“Despite promising findings in therapeutic hallucinogen trials, current factors, including funding, laws, and stigma, continue to impose limitations on further research,” they wrote. “Schedule 1 classification makes study development difficult, costly, and prolonged. Funding by both government and pharmaceutical companies is nonexistent.”
Photo courtesy of Pretty Drugthings.
Feds Award $3 Million In Grants To Study Marijuana Ingredients As Alternatives To Opioids
The federal government has awarded $3 million in grants for research into the therapeutic benefits of ingredients in marijuana other than THC, emphasizing their potential as alternatives to prescription opioids.
In a notice published on Thursday, the National Institutes of Health (NIH) explained why the studies were necessary and listed grant recipients and the subjects they will investigate. That includes research into the use of CBD for arthritis pain, which will be led by New York University School of Medicine.
“The treatment of chronic pain has relied heavily on opioids, despite their potential for addiction and overdose and the fact that they often don’t work well when used on a long-term basis,” Helene Langevin, director of the National Center for Complementary and Integrative Health (NCCIH), said in a press release. “There’s an urgent need for more effective and safer options.”
A total of nine grants were issued, with NIH stating that the funds will help identify alternative treatment options for pain and provide information about the impact of consuming cannabis compounds such as CBD and other lesser-known cannabinoids as well as terpenes found in the plant.
“The cannabis plant contains more than 110 cannabinoids and 120 terpenes, but the only compound that’s been studied extensively is THC,” the press release said.
But while THC is known to treat certain forms of pain, NIH is concerned that its intoxicating effects limit its medical applicability.
“THC may help relieve pain, but its value as an analgesic is limited by its psychoactive effects and abuse potential,” David Shurtleff, deputy director of NCCIH, said. “These new projects will investigate substances from cannabis that don’t have THC’s disadvantages, looking at their basic biological activity and their potential mechanisms of action as pain relievers.”
Just released: Nine new research awards, funded by our Center, will investigate the potential pain-relieving properties and mechanisms of actions of the diverse phytochemicals in cannabis, including both minor cannabinoids and terpenes. https://t.co/03MxrycfFa
— NIH NCCIH (@NIH_NCCIH) September 19, 2019
NIH first announced that it would be issuing grants for studies into minor cannabinoids and terpenes last year.
Federal health agencies aren’t the only institutions interested in learning about marijuana compounds other than THC. On Wednesday, a Senate committee issued a spending report that called for research into CBD and CBG while also criticizing the federal drug scheduling system for inhibiting such research.
Read descriptions of the federal cannabinoid and terpene research grant awards below:
Mechanism and Optimization of CBD-Mediated Analgesic Effects; Boston Children’s Hospital, Boston,; Zhigang He, Ph.D., B.M., and Juan Hong Wang, Ph.D. This project will investigate how the pain-relieving effects of cannabidiol (CBD) and other minor cannabinoids may be modulated by the activity of potassium-chloride cotransporter 2 (KCC2), a chloride extruder expressed in most neurons. (Grant 1R01AT010779)
Neuroimmune Mechanisms of Minor Cannabinoids in Inflammatory and Neuropathic Pain; University of California, San Francisco; Judith Hellman, M.D., and Mark A. Schumacher, M.D., Ph.D. This project will explore the effects of minor cannabinoids on inflammatory and neuropathic pain in vitro and in vivo, focusing on the interactions of the cannabinoids with the peripheral receptor called TRPV1 and a cannabinoid receptor, CB1R. (Grant 1R01AT010757)
Minor Cannabinoids and Terpenes: Preclinical Evaluation as Analgesics; Research Triangle Institute, Research Triangle Park, North Carolina; Jenny L. Wiley, Ph.D. This project will evaluate purified biosynthesized minor cannabinoids and selected terpenes alone and in planned combinations to determine their potential efficacy as pain relievers against acute thermal, inflammatory, neuropathic, and visceral pain. (Grant 1R01AT010773)
Identifying the Mechanisms of Action for CBD on Chronic Arthritis Pain; New York University School of Medicine, New York City; Yu-Shin Ding, Ph.D. This project will use neuroimaging studies and behavioral assessments to investigate the mechanisms of action of CBD in the modulation of chronic pain associated with osteoarthritis in a mouse model. (Grant 1R21AT010771)
Synthetic Biology for the Chemogenetic Manipulation of Pain Pathways; University of Texas, Austin; Andrew Ellington, Ph.D. This project will use a novel method to evolve individual variants of cannabinoid receptor type 2 (CB2) that interact with high affinity with minor cannabinoids and evaluate the new variants in a mouse model of pain. (Grant 1R21AT010777)
Exploring the Mechanisms Underlying the Analgesic Effect of Cannabidiol Using Proton Magnetic Resonance Spectroscopy; University of Utah, Salt Lake City; Deborah A. Yurgelun-Todd, Ph.D. This project will use proton magnetic resonance spectroscopy (1H-MRS) to evaluate changes in brain chemistry in critical pain-processing regions after short-term administration of a cannabis extract enriched in CBD. (Grant 1R21AT010736)
Mechanistic Studies of Analgesic Effects of Terpene Enriched Extracts from Hops; Emory University, Atlanta; Cassandra L. Quave, Ph.D. This project will take a multidisciplinary approach to investigate the analgesic effects of terpenes from Humulus lupulus (hops), a plant that is closely related to cannabis and has a very similar terpene profile. (Grant 1R21AT010774)
Systematic Investigation of Rare Cannabinoids With Pain Receptors; University of Illinois at Urbana-Champaign; David Sarlah, Ph.D. This project involves synthesizing several classes of rare phytocannabinoids, systematically evaluating their anti-inflammatory potential, and examining the effects of the compounds with the strongest anti-inflammatory potential on the major receptors involved in pain sensation. (Grant 1R21AT010761)
Analgesic efficacy of single and combined minor cannabinoids and terpenes; Temple University, Philadelphia; Sara J. Ward, Ph.D. This project will use rodent models of pain to evaluate the effects of four biologically active components of cannabis that may act synergistically to protect against pain development and to assess the interactions of these four substances with morphine. (Grant 1R01AT010778)
President Influences Public Opinion On Marijuana Legalization, Study Finds
When it comes to how Americans view marijuana legalization, the person sitting in the Oval Office makes a difference, a new study reports.
“Findings indicate that confidence in the executive branch, fear of crime, and presidential drug rhetoric predict attitudes toward legalization despite controls for other factors such as estimated levels of marijuana use and arrests,” the paper states. The findings were published last month in the journal Deviant Behavior.
It’s probably not news to anyone that the president of the United States has the power to sway public opinion—they are, after all, the most powerful person in the country and a great deal of attention is paid to messaging coming out of the White House. Like the mainstream media, POTUS can therefore help shape attitudes about marijuana and other drugs.
Researchers at Kennesaw State University and Old Dominion University, however, were interested to know just how much influence a president may have, especially when it comes to how the general public views cannabis policy.
For their analysis, the study’s authors used data from the General Social Survey spanning 1972–2016 to gauge Americans’ opinions on legalizing cannabis. They also reviewed reports on estimated marijuana use as well as related arrests. To get a sense of how often presidents talked about cannabis and illicit drugs during the study period, they looked at public presidential documents, including State of the Union (SOTU) addresses and other speeches, messages and executive orders.
The study’s authors worked with several variables and control measures, and chose to conduct a multi-level model analysis in order to consider changing contexts over time. Here’s some of what they found:
- The year 2014 was a turning point for how Americans viewed marijuana legalization. For the first time since 1975, more people that year supported ending prohibition than those who didn’t.
- How much the president talks about marijuana and other drugs matters. The study found that “each annual percent increase in SOTU words about drugs predicts a decreased odds of favoring legalization of about 6%.” Also, an increase in drug-related presidential documents led to a small decrease in favor of legalization, though the number of cannabis-related documents were not as influential.
- When more people expressed having confidence in the executive branch, the odds of their supporting legalization fell about 29 percent compared to people who said they had “hardly any confidence” in the White House.
- The crack-cocaine drug panic of the late 1980s—which other researchers say was created by President Ronald Reagan’s anti-drug rhetoric—impacted how people felt about marijuana legalization: The odds of the public favoring legalization decreased by about 27 percent then compared to the other time periods.
- As more people reported consuming cannabis, the odds of supporting legalization also increased. “For every percent increase in aggregate marijuana use, the models predict a five percent increased odds of favoring marijuana legalization,” the study states.
- Political party matters. “Specifically, the model illustrates that when a Republican president is in office, each increase in confidence leads to decreased odds of favoring legalization of approximately 36%. However, when a Democratic president is in office the decreased odds of favoring legalization is reduced to 24%.”
Researchers also found that fear of crime was found to be positively associated with legalization. As they explain it, if two persons with the same individual level fear of crime are located in two different states, the respondent in the state with higher mean fear of crime will have a 52% increased odds of favoring legalization per unit increase in the mean fear of crime compared to the individual in the state with lower mean fear of crime.”
It’s possible, they added, that people have begun to question some of the fear-mongering associated with marijuana.
“While attitudes toward legalization of marijuana have varied greatly over time, so has presidential rhetoric about marijuana and drugs,” the study’s authors wrote. “The lowest support for legalization is consistently found during President Reagan’s Just Say No era. However, beginning around the election of President Clinton, a steady increase in attitudes favoring legalization…is observed. This project supports the hypothesis that presidential drug rhetoric is related to public opinion about drugs, and more specifically, about marijuana.”
As for the current occupant in the White House, President Trump has maintained that his administration will leave marijuana policy for states to decide.
Photo courtesy of Rick Proctor.