Is Marijuana a Replacement for Opioids?

Lynn R. Webster, M.D.
Vice President, Scientific Affairs

Dr. Webster will be presenting a poster at DIA 2018 in Boston on Tuesday, June 26 on A Phase 1 Pilot Trial to Explore Safety, Pharmacokinetics, and Bioavailability of Intranasal Remimazolam in Healthy Subjects.

JUNE 25, 2018

The opioid crisis is a complex problem with many components. One of them is that a large number of people suffer from undertreated or untreated pain. Physicians across the board are reducing the amount of opioids they prescribe. This leaves many people in pain with few effective and safe options. Some people believe that marijuana could be one of them. Our Dr. Lynn Webster explores:

Marijuana is not a drug. It is a plant that is composed of approximately 482 known chemical compounds including tetrahydrocannabinol (THC) and cannabinol (CBD). Perhaps 65 of those compounds may alter neurotransmitters in the brain.

Marijuana’s medicinal benefits are largely attributed to THC and CBD. These are the most biologic components of marijuana. While THC is psychoactive, CBD is nonpsychoactive. The potency of marijuana depends on several factors, including the concentrations of THC and CBD, the species of the plant, its cultivation, and the methods used for its processing and storage.

Additionally, there are three primary species of marijuana (C. sativa, C. indica, and C. ruderalis) that contain different amounts and strengths of THC and CBD. C. staiva contains more THC than CBD. According to Professor Jordan Zjawiony at the University of Mississippi, marijuana can be more hallucinogenic than lysergic acid diethylamide (LSD), depending on the strain. The higher the THC:CBD ratio, the more psychoactive effects there will be. The lower the ratio, the more sedative and relaxing effects it will produce. Therefore, it is important to know the strain and concentration ratio of the primary active components to gauge its potential good and bad effects.

Unfortunately, at this time, we are unable to reliably know the exact concentration of the active components in most marijuana products. There is no way to be assured that there is consistent purity and concentration from plant products. By contrast, conventional medications approved by the FDA must be manufactured under strictly controlled manufacturing processes that ensure consistency of content and stability of the marketed drug.

A paper recently published by a Canadian team of researchers called “Therapeutic potential of medicinal marijuana: an educational primer for health care professionals” suggests that, while more research is needed, cannabis might be an “appropriate alternative therapy option for patients who have epilepsy, movement disorders, and pain.”

However, there is conflicting evidence about how the use of marijuana might affect pain, and whether or not legalizing marijuana might lower the necessity for prescribed opioids. States where it is legal to use medical marijuana do appear to have lowered their use of opioids. There seems to be a correlation between the availability of medical marijuana and a slower rise in the increase of prescribed opioids. While it can’t be proven the two are related, the association is strong. The Rockefeller Institute of Government has found that, in states where patients have access to medical marijuana dispensaries, Medicare patients use 14.4% fewer opioids.

In one study, marijuana was shown to reduce neuropathic pain by 30 percent.

Several studies have reported that marijuana can cause significant reduction in pain, but its efficacy and safety may also depend on how the drug is administered. The amount of active drug(s) delivered depends on whether it is administered by oral tablets, oromucosal spray, vaporizing, or smoking.

In one study, marijuana was shown to reduce neuropathic pain by 30 percent. This is a reduction in pain equal to that which most opioids can provide. It may have other medical benefits as well. However, as with opioids, the analgesic effects may not be equal for all chronic pain conditions.

Every drug that has benefits also carries risks. We don’t fully know the extent of marijuana’s dangers, but it probably depends, in part, on the THC:CBD ratio. It is likely that, the higher the THC:CBD ratio, the greater the potential hazards.

The risk also depends on the route of administration. Edible marijuana products, once ingested, undergo metabolism that can produce a metabolite that is far more toxic than the parent THC molecule. This metabolite is not produced from smoking marijuana. There have been reported cases of psychosis and self-harm after oral consumption of marijuana edibles, presumably due to the THC metabolite.

Another risk is that of substance use disorder. According to National Epidemiological Survey on Alcohol and Related Conditions, marijuana addiction occurs in about 8.9% of  marijuana users. This is comparable to the risk of developing an addiction to opioids. However, the risks of overdose with marijuana and opioid users are not the same. Opioids can easily cause respiratory depression. Marijuana, on the other hand, is not known to significantly depress respirations.

The Canadian medical marijuana prescribing guidelines state that cannabis is not appropriate for patients under age 25 years, for people with a current or past substance use disorder, for those who have a personal or family history of mental illness, for patients with a significant cardio-pulmonary disease, or for a woman during pregnancy. The guidelines also note that THC is transferred through breast milk and could have long-term detrimental effects on an infant’s brain development.

Clearly, we need additional research about the clinical effects of marijuana and its chemical components, but there are some things about it we can already surmise. While the risk of overdosing on marijuana seems minimal, ingesting synthetic marijuana can have fatal results when it has been laced with fentanyl or other toxic substances. Also, synthetic marijuana might be far more potent, and thus riskier, than natural marijuana.

Because undertreated pain is responsible for so much suffering, it makes sense to explore all of the available options to ameliorate it. Acting Administrator Robert Patterson recently provided some hope that he might lead the DEA in this direction with regard to marijuana. While answering questions about the opioid epidemic posed by the House Judiciary Committee, he admitted that “marijuana and opioids aren’t comparable drugs,” and he doesn’t see marijuana as a gateway drug. He is also in favor of conducting additional research, although it would be even more helpful if Patterson took steps to lift the restrictions that currently throttle scientists’ attempts to make progress.

Marijuana or its chemical components may be a safer alternative to opioids for some pain conditions, but it’s not without risks and side effects. Further research is needed to determine under what conditions marijuana could be considered and how it should be delivered to people who may be candidates for a trial of marijuana.

Meg Richards, Ph.D., MPH
Executive Director, Scientific Affairs, Real World Solutions

Meg Richards will be speaking at DIA 2018 on Wednesday, June 27 on “Power Up: Career-Transforming Moments.”

Chronic Pain, the Opioid Crisis, and Hope for the Future

The Keynote Speaker at the Drug Information Association’s (DIA’s) Annual Meeting in Boston, MA on June 25, 2018 was Dr. Nora Volkow. Dr. Volkow is the Director of the National Institute on Drug Abuse (NIDA) at the National Institutes of Health (NIH). Some of Dr. Volkow’s most important work has been to demonstrate that drug addiction is a disease of the brain. She has used brain imaging to investigate the toxic effects of abusable drugs and to document structural changes in the frontal lobe involved with motivation, drive, and pleasure in addiction. The title of Dr. Volkow’s talk was “All Hands on Deck: Using Science to Help Solve the Opioid Crisis.”

Her title is very apt, for – as with all public health crises – there is not a single solution to the epidemic of opioid dependence, misuse, and fatality. Rather, a multi-pronged approach – led by science and driven by medical evidence – is absolutely warranted. Her title is also hopeful, as Dr. Volkow means to solve the crisis rather than simply sharing the alarming statistics of lives ruined or lost. In that same hopeful spirit, we share some of the most promising solutions currently in development. Dr. Volkow covered a lot of ground but struck a hopeful note for solving the opioid problem. It was also a call to action for everyone to do their part, scientifically and as citizens, to help mitigate this public health crisis.

For most people, opioid use begins with the need to address significant acute pain. Although opioids can effectively mitigate pain initially, our bodies develop a tolerance so that over time, more and more drug is needed. Prescription opioids don’t just slow or reduce pain signals to the brain, but they also suppress heart rate and breathing (the cause of death in an overdose) and can influence the release of chemicals that calm emotions and create a sense of pleasure (the reason for addiction.) These three properties – analgesia, respiratory/heart rate depression, and euphoria – are present in every opioid along with nausea, reduced gastrointestinal motility, sedation, and painful withdrawal. The good news is that, despite the numerous pathways involved with chronic pain, researchers have begun to develop a novel opioid that relives pain without suppressing breathing or conferring a sense of euphoria.

Non-opioid and non-drug approaches to chronic pain have also gained traction; the CDC and HHS each released in 2016 a guideline for opioid prescribing and a National Pain Strategy, respectively. Both agencies pointed to the lack of evidence of effectiveness for opioids in addressing chronic pain, and suggested physical therapy, counselling therapy, biofeedback, hypnosis, yoga, exercise, and non-opioid medications, instead. Trigger point therapy (inserting acupuncture-like dry needles or needles tipped with lidocaine into myofascial knots on the back, gluteus, or hip) has become popular with athletes and older persons suffering from injury or compression fracture.

Perhaps most important in the national conversation about chronic pain management and opioid abuse is that there is a new focus on helping patients to set realistic goals for easing their chronic pain, rather than believing that they will eliminate their pain completely. The goal is not to be pain-free, but to learn to cope and adjust with some hopefully low-level of pain that may simply be a fact of life.

Pain is a frontier in medicine that is still largely unmapped. And an individual’s threshold for, perception of, and response to pain is not unlike a fingerprint – completely unique to each person. Just as the population approach to the opioid crisis is necessarily multi-pronged, so must be an individual’s approach to his/her own pain.

HOW REAL WORLD EVIDENCE IS CHANGING PHARMA

THE FIGHT AGAINST ALS

OVERCOMING BARRIERS IN RARE DRUG DEVELOPMENT