Cannabinoids as a complement in Orthopedics.
In the orthopedic field, the recent years have seen orthopedists holding back on pain medication because they felt a little responsible for this epidemic of addiction, we are facing in the United States. We can’t be proud of saying that around 13% of Total Knee Replacement will undergo a revision surgery.
A patient who has undergone a total Knee or a Total Hip reconstruction is undeniably seen ten years later, still holding on his medication to relieve pain and discomfort. Now on top of the narcotic epidemic, Cannabinoids have been approved to treat musculoskeletal problems. I was surprised when I moved my practice in the State of Florida to see how common it was to find patients using these medications, in shewing. smoking or more often in using ointment at cannabinoid base to relieve symptoms of pain. It looks like we have made some steps back in the 60’s or the 70’s.
Many orthopedists are reluctant to get involved in prescribing Cannabinoids. They simply believe that these medications may not be suitable for all orthopedic patients. There are no sufficient studies done supporting these facts. Little is known about double blind study to compare Cannabinoids to a placebo or to an actual narcotic. They are popular but they are not as safe as people can believe.
Individuals with chronic conditions in Orthopedics, like upper or Lower back pain, neck pain, spinal stenosis are turning toward Cannabinoids or traditional medicine to find remedy to their condition and improve their chronic pain. More than 30 states have already adopted legislation to allow medical marijuana or Cannabis to be publicly available. Many of us remain suspicious and concerned about this new trend of dispensing such medication as an adjunct to regular pain medication. We remain conscious of possible repercussions.
Cannabis has a long relation with humans. It is referred to the popular name of “weed”. The first contact with humans may have occurred some 12,000 years ago in Central Asia with the beginning of farming and has spread around the world for the pleasure of some and now as a wonder drug with a lot of potential. It has been used as a highly nutritious foodstuff as well as a psychoactive drug. By the years 10,000 BCE, China was known as “the land of Mulberry and Hemp” but the oldest archeologic proof was found in Taiwan.
The Aryans were nomadic invaders and conquerors who bought weed in the 1800 BCE. Further proof is found on the cuneiform tablets recovered from the library of King Ashurbanipal in Nineveh (900 BCE) near Mosul, Iraq. It spread in the Arab world. Cultivation of weed expanded to the Mediterranean Sea and to Russia. In Siberia, the seeds were found in the burial mounds. Cannabis spread to Korea and Japan and from there it went to India, the middle East and Eastern Europe with the expansion of the roman empire. By 400 AD, weed can be found in England with the Vikings and the Saxons. In the sixteenth century it was implanted in central America and finally reached the north America colonies (Nova Scotia). The British in particular wanted desperately to end their dependence on Russian imported hemp, and later founded James Town in 1607 where later King James made the cultivation of weed mandatory.
The revolutionary war and the America Independence imposed also requirements on the use of raw materials for finished products. It is said that Georges Washington preferred cannabis to alcohol and James Madison smoked hashish when he was ambassador in France. There is no evidence that the founding members used weed for it intoxicating effects. Thomas Madison grew hemp at his Monticello estate around 1815.
With the global exploration, Colonial powers like France, England, Spain needed money for their expeditions. They have superior means of transportation, military power and they were constantly fighting between them. They imposed taxes on their Europeans and colonial territories but many believe that such action may have triggered the American revolutionary war. Other battle fields started between the England and France especially the seven years’ war and the invasion of Egypt by the French army to deprive England of his passage to India. The English rapidly destroyed the French naval fleet and the French soldiers remained strained in Egypt incapable of returning home. There, they learned about the effects of weeds and adopted it when they were able to return home.
Weed (Cannabaceae) represents a separated class with two distinct herbs, the “Humulus” better known as Hops, the key ingredient in beer and “Cannabis”. It grows and spreads easily. Cannabis has been called by many exotic names: we owe to the Spanish, the name of Marijuana. The plants have different pseudo-names, depending on where you are in the world: Pot, Hash, Grass, Dope, Wacky Tobacky, dank, skunk, buddah, Ganja, broccoli, firewood, airplane, hashish, black bart to name some. These names are descriptive of the action of the plant and you do not have to be a user to guess why someone will call it a giggle weed or firewood. Marijuana may have been used for century but now, it is re-surfacing as the potential remedy to relieve chronic pain.
The term Cannabis, comes from the Greek word for hemp (kannabis) which was given by the botanist Carolus Linnaeus in 1753 but this is 30 years later in 1783 that it was recognized by Jean Baptiste Lamark that all weeds were not the same. They can grow in high altitude or thrive in poor sandy conditions. Weed is “dioecious” meaning that each plant is either male or female or occasionally hermaphrodite. It is not the leaves that are looked for recreational activities but the flowers that the female plants carry with them. Those flowers once dried, are the potent parts that are smoked for recreational use. It is said that, once the female plant is fertilized by a male, this male plant becomes less potent and can be destroyed once identified. The female plants also produce small fruits, highly nutritious for their fatty acids content used as a foodstuff or in the fabrication of soap or lamp fuel.
The 1800’s saw the spread and use of substances that became outlawed in the 19th century like Cocaine, Heroin and Hashish, physically addictive. Recreational intoxication with those substances were considered as anti-social with potential for adverse or lethal overdose. Cannabis is surely not physically addictive and may not be harmful to the health except perhaps lung damage from chronic inhalation. Hashish has a high concentration of THC, made from the resin of glands pf the female plants. That resin collected turns black with exposure to air. Hashish can be smoked or eaten or added to wine or other beverages. Its effects can be felt in the hour following ingestion but when smoked, the user can feel the effect almost immediately.
The first known physician to promote cannabis was William Brooke O’Shaughnessy in 1833 while working with the East India Cie, in Bengal. He also experimented with Hashish on humans and dogs to discover the therapeutic benefits. He realized that the drugs were ideal for their sedative effect as well as their anti-convulsive effects. He wrote extensively on his experiences. He developed with a pharmacist, Peter Squire, in London, a compound with Hash, patented it and sold it to the public. Pharmacists across England started to adopt the idea and created tinctures of their own. A lot of side effects were recorded. In the United States, medicinal hashish was introduced in 1850 to treat disease like gout, snake bites etc. The tincture was inexpensive. Medical cannabis becomes popular and the idea of tinctures, one of cannabis, one of chloroform and one of morphine become a reality.
While progress was made toward standardizing and stabilizing these products, we were hiding behind the limited knowledge we have about these medications and we remain unconvinced that Cannabinoids bring any efficacy in treating musculoskeletal disease. Director of a department of medical Cannabis at Rothman Orthopedic Institute, Ari Greis DO, explains that there are more than 100 potentially active ingredients in the Marijuana plant that can be used in the treatment of painful condition. He will cite two well-known “Tetrahydrocannabinol” which has been found responsible of most of the Vaping death in adolescent enjoying this activity, and “Cannabinol”. Both substances have stimulated an extensive medical interest to the National Institute on Drug Abuse (NIDA).
The chemical in weed that causes the psychoactive effects is the THC, a delta 9 tetrahydrocannabinol which is found in a resin throughout the plant, secreted by some hair like structures called trichomes found in abundance in the female flowers. The resin itself is amber in color and sticky. The stalks of the plants are used to make the fibers (Hemp) to create rope, textile material.
THC imposes a euphoric effect to the one looking for such sensations while CBD is better known for its anti-inflammatory effects. Emily M Lindley MD of the University of Colorado believes that both THC and CBD, tend to bind to the endogenous cannabinoid receptors but THC is mainly a partial agonist while CBD can be either agonist or antagonist. More, CBD can potentially block the effects of THC. Based on these side reactions, some have hypothesized that CBD may be able to attenuate the psychoactive side effects of the THC.
Cannabis is a Schedule I substance and as such is not approved by the FDA as a safe and effective drug for any indication. We know more that Marijuana for research is regulated by the Drug Enforcement Administration (DEA). This is why any researchers must meet specific requirements to participate in any NIH funded project. More, all marijuana used for research must be requested from the University of Mississippi which represent the only institution in the country holding a registration, allowing them to culture marijuana for research purpose.
The Colorado department of Public Health and Environment has sponsored studies using the analgesic effects of vaporized cannabis, oxycodone and their placebo on patients suffering of chronic neck and low back pain. Those drugs are also being looked at for their psychoactive and affective effects. Are people feeling high or impaired, or anxious and confused? Neurocognitive tests are being used also to evaluate attention, memory and concentration or even sobriety. The adverse reactions are closely recorded.
Emily Lindley PHD, who showed an interest in this field since 2012, is studying patients with chronic pain, being tapered off high doses of Opioid to be switched to a combination of THC (Tetrahydrocannabinol) and CBD (Cannabidiol)) or the THC alone or a placebo. She is definitely unsure that anybody can assert any conclusion on the matter but believes that research may show evidence perhaps that cannabinoids are an effective alternative to the Opioids or other medications. She based her studies on witnessing around 180 of her own patients describing substantial relief in their symptoms after self-medicating themselves with cannabis.
Many patients with osteoarthritis and rheumatoid arthritis will approach us in the office requesting cannabinoids to relive their discomfort. The trend to use a form of ointment is increasing with individual suffering from chronic symptoms. They used it too in flairs up. Those researchers claimed beneficial effects on individuals undergoing Total Knee Replacement, or neuropathic pain, fibromyalgia, complex regional pain syndrome, degenerative arthritis. Patients who have not found relief with traditional pain medicine, therapy or injection medicine, are now being offered such treatment.
There is no therapeutic dose for the drug nor a physician can tell a patient what amount of medication is needed to ease his problem. Physicians are starting to prescribe low dosages by inhalation, by capsules or tablets or even with a sublingual tincture or a topical ointment. The route of delivery for cannabis may be different than the one to use for THC or CBD.
Fortunately, federal prohibition has allowed physicians trained in dispensing the medicine to certify patients able to receive legal and medical marijuana for a typical pathology but has no control on which product they purchased. As a result, millions are having access to marijuana and may use it for multi-purpose, including recreational purposes. There is no control on the amount of drug they can receive. This fact brings a lot of risk for a practicing physician.
In 2017, a literature review was performed on more than 10,000 scientific abstracts by the National Engineering and Medicine showing that adults with chronic low back pain experienced a reduction in their symptoms with cannabinoid use. However, this drug is not free of side effects and adverse reactions. Most of the reactions are related to the THC. Cannabis used at a young age has been associated with schizophrenia and other mental health disorders especially if there is a family history of mental illness. This drug should then, be contra-indicated in such patients. Otherwise, cannabis appears to be relatively safe and even safer than many other medications of its kind.
We do believe that Cannabinoids may play a more important role in easing orthopedic patients with chronic pain. On a basic level, researchers will have to differentiate between THC and CBD. Orthopedists will have to learn the routine in prescribing the proper form of cannabinoids and keep an open mind to report their experience with the use of such medication. Side effects are going to happen and will need to be recorded. Cannabis should be used as an adjunct to orthopedic treatment. It is not a cure and surely will not bring an answer to all problems.
Clinically synthesized, cannabis can become the pain killer of the future especially in the treatment of chronic pain. I just wanted to prepare all my colleagues especially, the one reading the AMHE Newsletter, on learning how to anticipate using such cannabinoids in their medical practice. Be open minded and be ready to affront also a population of patients which may not be always cooperative in following your guidance.
Maxime Coles MD
References:
1- Marijuana: History, The Cannabis Century. 2019.
2- “What is medical marijuana?”. National Institute of Drug Abuse. July 2015. The term medical marijuana refers to using the whole unprocessed marijuana plant or its basic extracts to treat a disease or symptom.
3- Borgelt, LM, Franson, KL, Nussbaum AM, Wang GS (February 2013. “The pharmacologic and clinical effects of medical cannabis”. Pharmacology 33(2): 195-209.
4- Jensen B, Chen J, Furnish T, Wallace M (October 2015). “Medical Marijuana and Chronic Pain: A Review of Basic Science and Clinical Evidence”. Current Pain and Headache Reports. 19 (10) 50.
5- Ben Amar M (April 2006) Cannabinoids in medicine: A review of their therapeutic potential” Journal of Ethno pharmacology. 105 (1-2): 1-25.
6- “State Medical Marijuana Laws”. National Conference of State Legislatures. 27 June 2018
7- Schubart CD, Summer IE, Fusar-Poli P, de White L, Khan RS, Boks MP (January 2014) “Cannabidiol as a potential treatment for psychosis” European Neuro-psychopharmacology 24 (1) 51-64.
8- Grotenhermen F, Muller-Vahl K (July 2012). “The therapeutic potential of cannabis cannabinoids”. Deutssches Arzteblatt, Internal 109 (29-30) 495-501.
9- Wang T, Collet JP, Shapiro S, Ware MA (June 2088) “Adverse effects of medical cannabinoids: a systematic review” CMJA (Review) 178 (13) 1669-1678)
10- Volkow ND, Baker RD, Compton WM, Weiss SR (June 2014) “Adverse health effects of marijuana use.” The New England Journal of Medicine. 370(23): 2019-2017.
11- Burns TL, Ineck JR, (February 2006). “Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain”. The Annals of Pharmacology 40 (2) 251-260.