Could marijuana be an effective pain alternative to prescription medications?

July 1, 2019

Science Daily/Taylor & Francis Group

A new study has shown how cannabis could be an effective treatment option for both pain relief and insomnia, for those looking to avoid prescription and over the counter pain and sleep medications -- including opioids.

The study, published in the Journal of Psychoactive Drugs, which looked at 1,000 people taking legalized marijuana in an American state found that among the 65% of people taking cannabis for pain, 80% found it was very or extremely helpful.

This led to 82% of these people being able to reduce, or stop taking over the counter pain medications, and 88% being able to stop taking opioid painkillers.

74% of the 1,000 interviewees bought it to help them sleep -- 84% of whom said the marijuana had helped them, and over 83% said that they had since reduced or stopped taking over-the-counter or prescription sleep aids.

The study suggests that cannabis could lower opioid use. However, the researchers caution that more needs to be done to understand the potential therapeutic benefits of cannabis.

"Approximately 20% of American adults suffer from chronic pain, and one in three adults do not get enough sleep," says Dr Gwen Wurm, Assistant Professor of Clinical Pediatrics at the University of Miami Miller School of Medicine.

Traditional over the counter medications and painkillers can help, however they may have serious side effects. Opioids depress the respiratory system, meaning that overdoses may be fatal.

"People develop tolerance to opioids, which means that they require higher doses to achieve the same effect," says Dr. Julia Arnsten, Professor of Medicine at Albert Einstein College of Medicine. "This means that chronic pain patients often increase their dose of opioid medications over time, which in turn increases their risk of overdose."

Although less common, sleeping pills can lead to dependence, and can also cause grogginess the next day, interfering with people's work and social lives.

As a consequence, some people are looking to marijuana to help with their symptoms.

To find out more about these users, Wurm and her colleagues used survey data from people who purchased cannabis from two retail stores in Colorado, US, where it is legal for both medical and recreational use -- meaning any adult over 21 with a valid government ID may purchase product.

"In states where adult use of cannabis is legal, our research suggests that many individuals bypass the medical cannabis route (which requires registering with the state) and are instead opting for the privacy of a legal adult use dispensary," says Wurm.

Although the survey was conducted among customers willing to participate -- meaning the results may not reflect the overall population of dispensary customers -- other national survey data, and data from medical patients at medical cannabis dispensaries, also demonstrate that people who use cannabis to treat symptoms both decrease and stop their use of prescription medications.

The study adds weight to the theory that widening access to medical cannabis could lower the use of prescription painkillers, allowing more people to manage and treat their pain without relying on opioid prescription drugs that have dangerous side effects.

This is backed up with other research that shows that states with medical cannabis laws have a 6.38% lower rate of opioid prescribing, and that Colorado's adult-use cannabis law is associated with a relative reduction in opioid overdose death rate from 1999 to 2010.

Wurm adds: "Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen cause GI bleeding or kidney damage with chronic use. Paracetemol (Acetaminophen) toxicity is the second most common cause of liver transplantation worldwide, and is responsible for 56,000 ER visits, 2600 hospitalizations, and 500 deaths per year in the U.S."

However, the researchers caution that more research is needed to understand the health benefits and side effects of cannabis.

"The challenge is that health providers are far behind in knowing which cannabis products work and which do not. Until there is more research into which cannabis products work for which symptoms, patients will do their own "trial and error," experiments, getting advice from friends, social media and dispensary employees," says Wurm.

https://www.sciencedaily.com/releases/2019/07/190701224523.htm

Discovery of Mechanism that Processes 'THC' Type Brain Compound May Lead to New Medicines for Pain, Addiction

March 31, 2009

Science Daily/Stony Brook University Medical Center

Dale Deutsch, Ph.D., Professor of Biochemistry and Cell Biology at Stony Brook University and colleagues discovered a new molecular mechanism for the processing of endocannabinoids, brain compounds similar to THC, the active ingredient in marijuana, and essential in physiological processes such as pain, appetite, and memory.

Reported online this week in the Proceedings of the National Academy of Sciences (PNAS), the finding could pave the way for new medicines for pain, addiction, appetite control and other disorders.

Dr. Deutsch and colleagues in the Departments of Biochemistry and Cell Biology (Martin Kaczocha) and Neurobiology and Behavior (Sherrye Glaser, Ph.D.) are the first to successfully identify two known fatty acid binding proteins (FABPs) that carry the endocannabinoid anandamide (AEA), a neurotransmitter, from the cell membrane to interior of the cell where it is destroyed. This identification enabled the research team to inhibit FABPs in various laboratory experiments and thereby reduce AEA breakdown inside cells. In their study, “Identification of intracellular carriers for the endocannabinoid anandamide,” the researchers report that they decreased the breakdown of AEA in some instances by approximately 50 percent.

“Inhibiting FABPs could potentially raise the levels of AEA in the brain’s synapses,” says Dr. Deutsch. “Naturally occurring AEA levels have been shown to curb pain without the negative side effects, such as motor coordination problems, from molecules like THC. Therefore, it makes sense to target AEA for therapeutic purposes.”

He emphasizes that their groundbreaking discovery of the role of FABPs in transporting this class of neurotransmitters may prove to be a crucial step in developing novel drug targets for endocannabinoids by way of inhibiting FABPs. In support of the research, The State University of New York (SUNY) Stony Brook Office of Technology Licensing and Industry Relations (OTLIR) has filed U.S. Patent applications comprising the discovery.

The OTLIR manages all intellectual property matters for the SUNY Research Foundation. In actively marketing this unlicensed technology created by Dr. Deutsch, the Stony Brook OTLIR welcomes commercial entities interested in partnering with the University. The licensing agent for the project is Adam DeRosa of the OTLIR.

The breakdown of AEA requires two factors. First, there needs to be a mechanism for transporting AEA to the location where it is inactivated because AEA is a fatty compound and thus unable to move inside the watery cellular environment. Second, the cell must express an enzyme called FAAH, which controls the breakdown and inactivation of AEA. In the laboratory, the researchers coaxed a nonneuronal cell type (COS-7) to express FAAH. These FAAH-expressing COS-7 cells were able to break down AED efficiently, indicating that the intracellular AEA transport mechanism was already present and operation in these cells. The researchers identified these carriers as two separate FABPs.

Dr. Deutsch believes that because a transporter for the AEA class of neurotrasmitters had never been discovered until the Stony Brook findings, continued research may explain many unanswered questions about AEA. Future research may uncover more knowledge about AEA transport, as well as the entire role these neurotransmitters play in pain, inflammation, appetite control, addiction, and perhaps other physiological processes related to many human disorders.

The research was funded by the National Institute on Drug Abuse, part of the National Institutes of Health.

https://www.sciencedaily.com/releases/2009/03/090325190342.htm

Marijuana-inspired Painkiller? New Chemical Pathway Discovered

November 27, 2008

Science Daily/Scripps Research Institute

Marijuana can be an effective painkiller, but social issues and unhealthy smoke inhalation complicate its use. As a result, researchers have focused great attention on understanding the biochemical system involved so they might manipulate it by other means. Toward that end, scientists have definitively identified a chemical pathway that, in mice, imitates marijuana's painkilling effect. The work could enable the development of new pain treatments.

Marijuana kills pain by activating a set of proteins known as cannabinoid receptors, which can also regulate appetite, inflammation, and memory. The body also has chemicals known as endocannabinoids that naturally activate these same receptors, namely N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG).

These natural components of the cannabinoid system remain the focus of intense efforts to develop new treatments not only for chronic pain, but also for obesity, anxiety, and depression. However, until the new paper (citation below) specific methods to study 2-AG signaling have been lacking.

AEA's activity has been well understood for years. In past research, Cravatt and his team identified an enzyme called fatty acid amide hydrolase, or FAAH, that breaks down AEA, effectively reducing its pain killing activity. A number of compounds are now in clinical development that target and breakdown FAAH, allowing AEA to build up, reducing pain. However, FAAH does not control 2-AG metabolism in vivo, and therefore, the potential biological functions and therapeutic potential of this second endocannabinoid have remained largely unknown.

Teasing out 2-AG's specific impacts have proven challenging. Comparable to FAAH, an enzyme called monoacylglycerol lipase (MAGL) breaks down 2-AG. But, despite numerous attempts, no group had been able to develop a chemical that inhibits MAGL specifically.

"The tools—selective and efficacious MAGL inhibitors—just weren't there, " says Jonathan Long, a graduate student of the Scripps Research Kellogg School of Science and Technology who is a member of the Cravatt lab and a first author of the new paper.

But now, a MAGL-specific inhibitor is finally available, thanks to the lab's new work. Key to this success was Activity-Based Protein Profiling, a unique chemical technique the group devised and has used fruitfully in other inhibitor hunts. This system enables the rapid engineering and testing of chemical compounds against many members of enzyme families, in hope of finding effective and selective inhibitors.

For this project, the group developed about 200 compounds and found that one was a highly effective block for MAGL. The scientists dubbed the compound JZL184, named after Long's initials and the order in the series of potential inhibitors tested. JZL184 effectively blocks only MAGL among more than 40 related brain enzymes, which opened the door for the first definitive study of 2-AG's activity.

A New View of 2-AG

Unlike increased AEA, which causes only reduced pain sensation, the team found that MAGL inhibition using JZL184, and the resulting increase in 2-AG concentration, not only reduced pain in mice, but also induced other effects associated with the cannabinoid receptors, namely hypothermia and decreased movement.

"This really does suggest a sort of segregation of labor, if you will," says Cravatt of the differential effects of elevating AEA versus 2-AG as part of the overall function of the cannabinoid system. "That, I think, is a truly unique result."

While treatments based on inhibiting FAAH show great promise for controlling pain, manipulating MAGL levels could also be a boon for treatment development, especially if 2-AG's other effects, such as hypothermia, can be managed.

"There are so many different types of pain," Cravatt says, "that it's possible some types could be more effectively treated with one treatment than another."

This research was supported by the National Institutes of Health, the Helen L. Dorris Child and Adolescent Neuro-Psychiatric Disorder Institute, and the Skaggs Institute for Chemical Biology.

https://www.sciencedaily.com/releases/2008/11/081123150249.htm

Smoking marijuana provides more pain relief for men than women

August 18, 2016

Science Daily/Columbia University Medical Center

Men had greater pain relief than women after smoking marijuana, a new study has found. Despite differences in pain relief, men and women did not report differences in how intoxicated they felt or how much they liked the effect of the active cannabis.

Researchers from Columbia University Medical Center (CUMC) found that men had greater pain relief than women after smoking marijuana.

Results of the study were recently published online in Drug and Alcohol Dependence.

"These findings come at a time when more people, including women, are turning to the use of medical cannabis for pain relief," said Ziva Cooper, PhD, associate professor of clinical neurobiology (in psychiatry) at CUMC. "Preclinical evidence has suggested that the experience of pain relief from cannabis-related products may vary between sexes, but no studies have been done to see if this is true in humans."

In this study, the researchers analyzed data from two double-blinded, placebo-controlled studies looking at the analgesic effects of cannabis in 42 recreational marijuana smokers. After smoking the same amount of either an active or placebo form of cannabis, the participants immersed one hand in a a cold-water bath until the pain could no longer be tolerated. Following the immersion, the participants answered a short pain questionnaire.

After smoking active cannabis, men reported a significant decrease in pain sensitivity and an increase in pain tolerance. Women did not experience a significant decrease in pain sensitivity, although they reported a small increase in pain tolerance shortly after smoking.

Despite differences in pain relief, men and women did not report differences in how intoxicated they felt or how much they liked the effect of the active cannabis.

The authors noted that additional studies in both men and women are needed to understand the factors that impact the analgesic effects of cannabinoids, the active chemicals in cannabis products, including strength, mode of delivery (smoked versus oral), frequency of use and type of pain measured.

"This study underscores the importance of including both men and women in clinical trials aimed at understanding the potential therapeutic and negative effects of cannabis, particularly as more people use cannabinoid products for recreational or medical purposes," said Dr. Cooper.

https://www.sciencedaily.com/releases/2016/08/160818165936.htm