Is cbd oil for marfan’s syndrome

An interaction between warfarin and cannabidiol, a case report

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Highlights

1. Introduction

The use of cannabis products for the treatment of epilepsy and other chronic diseases is growing rapidly [1], [2]. Cannabis products include any pharmaceutical or artisanal derivatives of the cannabis plant [2]. One such agent is cannabidiol (CBD), one of the phytocannabinoids frequently used by patients with seizures. Current data regarding interactions between CBD and other pharmaceuticals are primarily limited to anti-seizure drugs [3], [4]. This case report observes a clinically significant interaction between pharmaceutical grade cannabidiol (Epidiolex®; Greenwich Biosciences, Inc.) and warfarin, one of the most widely used oral anticoagulants.

2. Case report

A 44-year-old Caucasian male with Marfan Syndrome, mechanical mitral valve replacement, warfarin therapy, and post-stroke epilepsy was enrolled in the University of Alabama at Birmingham open-label program for compassionate use of cannabidiol for the management of treatment-resistant epilepsy ( > NCT02700412). His seizures began at age 27 concurrent with diagnosis of stroke during the post-operative period from cardiac surgery. Despite initial control of seizures on monotherapy, events returned in 2011 prompting adjustment of anti-seizure medications and eventual consideration of epilepsy surgery. Following video EEG monitoring, he was determined to be a poor surgical candidate due to non-localized seizure onset. Additionally, the need for anticoagulation due to mechanical valve limited more invasive testing for localization of seizure focus as well as posed a challenge for completion of any surgical resection. He was subsequently referred to the UAB CBD program.

At the time of study enrolment, the patient was taking lamotrigine 400 mg and levetiracetam 1500 mg, both twice daily. He was also taking warfarin 7.5 mg daily with a goal International Normalized Ratio (INR) of 2–3. Prior to study entry, his INR had been stable for at least 6 months with levels ranging from 2.0 to 2.6 ( Fig. 1 ). At the initial study visit, his baseline INR was obtained and he was placed on the starting dose of CBD at 5 mg/kg/day divided twice daily. Per study protocol (www.uab.edu/cbd) CBD dose was increased in 5 mg/kg/day increments every two weeks.

INR Trend over time.

With up-titration of CBD oil, a non-linear increase in the INR was noted ( Table 1 , Fig. 1 ). Warfarin dosage adjustments were made by primary care physician in effort to maintain an INR within his therapeutic range. At the most recent study visit his warfarin dose had been reduced by approximately 30%. The patient was followed clinically without bleeding complications.

Table 1

Visit # Day # Date Weight (kg) CBD dose (mg/kg/day) CBD dose (mg BID) Coumadin dose averaged over time between visits (mg) INR
1 10/29/15 105.9 7.5 2.22
2 14 11/12/15 105.9 5 265 7.5 2.96
3 28 11/23/15 105.5 10 528 7.5 6.86
4 42 12/10/15 105.5 15 790 5.89 4.40
5 70 1/07/16 104.8 15 786 6.25 2.8
6 84 1/21/16 105.8 20 1058 6.78 3.27
7 98 2/04/16 108.2 25 1352 6.78 4.07
8 126 3/03/16 107 20 1070 6.51 2.73
9 140 3/17/16 106.8 25 1335 6.42 3.93
10 168 4/14/16 107.1 25 1338 6.07 3.49
11 238 6/23/16 105.1 25 1313 5.36 1.96
12 252 7/07/16 104.6 30 1570 5.36 2.6
13 266 7/21/16 105.7 30 1585 5.36 2.25
14 294 8/18/16 104.1 30 1562 5.36 2.41
15 322 9/15/16 104.8 35 1834 5.36 2.31
16 336 9/29/16 105.5 40 2110 5.36 2.90
17 364 10/27/16 106.9 35 1870 5.36 2.80
18 434 1/05/17 107.2 35 1876 5.36 2.88
19 518 3/30/17 103 35 1802 5.36 2.58

3. Discussion

Despite the emergence of novel oral anticoagulants, warfarin continues to be the most commonly used oral anticoagulant worldwide [5]. A potent inhibitor of vitamin K epoxide reductase complex, warfarin functions by disrupting the production of vitamin-K-dependent clotting factors [6]. The drug is comprised of R and S stereoisomers with S-warfarin being the more active of the two. Warfarin is metabolized via the CYP450 hepatic enzyme complex and cleared through the renal system, however each stereoisomer is metabolized differently. The S-isomer is predominantly metabolized by CYP2C9 and R-warfarin by way of CYP3A4 with lesser involvement of CYP1A1, CYP1A2, CYP2C8, CYP2C9, CYP2C18 and CYP2C19 [6]. Resultantly, factors that impact the CYP2C9 enzyme (genetic polymorphisms, other medications, etc.) alter warfarin activity [5], [7], [8]. Due to its narrow therapeutic index and variability of dosing requirements amongst individuals, frequent monitoring of the INR is required to both achieve and maintain appropriate anticoagulant effects on the blood. Drugs that compete as substrates for these cytochromes or inhibit their activity may increase warfarin plasma concentrations and INR, potentially increasing the risk of bleeding. Conversely, drugs which induce these metabolic pathways may decrease warfarin plasma concentrations and INR, potentially leading to reduced efficacy.

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The metabolism of CBD is also by way of the hepatic P450 enzyme system. To date there are seven major isoforms identified that contribute to this process: CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5, with CYP3A4 and CYP2C19 being the dominant contributors [9]. Five of the seven isoforms are also involved with metabolism of warfarin, including CYP2C9, which is the dominant enzyme for S-warfarin, and CYP3A4, which is the dominant enzyme for R-warfarin [7], [9]. In addition to competing for enzymes in same metabolic pathway as warfarin, CBD has been demonstrated to act as a potent competitive inhibitor of all seven of its own CYP enzymes and as such could further impair the degradation of warfarin [10], [11]. It is this combination of factors that presumably constitutes the observed rise in INR values with concomitant warfarin and CBD administration.

4. Conclusions

This finding suggests an interaction between warfarin and cannabidiol, underscoring the importance of monitoring appropriate laboratory work in patients receiving concomitant cannabis products and other pharmaceuticals, particularly those metabolized by the cytochrome P450 enzyme system. In patients taking warfarin, INR monitoring is suggested during initiation and up-titration of cannabinoids.

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My Cannabis Solution And The Cost

It is my honor to introduce myself as Park Major. I am 42 years old and a veteran of the Gulf War.

My birth year was 1972, and I was born in Knoxville, Tennessee. A lot of my early childhood memories are blurred by dysfunctional family dynamics. Presently, my thoughts are filled with memories of parental fighting, parental adultery, and substance abuse. In the days following my 10th birthday, my mother committed suicide after a prolonged period of depression. I began medicating with marijuana when I was 13 years old to deal with my depression. Many of my friends and family condemned me for doing this. During my childhood, I was abused physically by my father who was extremely abusive. After a violent confrontation with my father at the age of 17, I left home and sought my own way in life. I graduated from high school, attended college for a while, and then joined the Navy in 1991. I was assigned to the Amphibious Assault ship USS Pensacola (LSD-38). My entire Navy career was spent abstaining from cannabis. My professional accomplishments include receiving the National Defense Service Medal, 2 Humanitarian Service Medals, 2 Sea Service Deployment Ribbons, Southwest Asian Sea Theater of Operations Medal, Kuwait Liberation Medal, Enlisted Surface Warfare Pendant, and The Sailor of the Month and the Sailor of the Quarter Award. I was involved in numerous operations including Gulf War, two tours at Guantanamo Bay Cuba – Haitian Relief, three months in the North Atlantic, seven months in the Mediterranean, providing assistance with OPS Deny Flight Adriatic Sea, as well as OPS Provide Promise Adriatic Sea. Toxins and vaccines were frequently used by the military, which contributed to my illness. After I was honorably discharged in 1994, I started driving cross-country trucks. After my discharge, I began experiencing my first symptoms of medical problems about six months later. My health problems began with intestinal complaints, migraines, PTSD, and night sweats. I was diagnosed with a pituitary tumor in 1999. A lymphoma tumor the size of a golf ball was removed from my neck shortly after that. The pituitary tumor became more and more severe throughout the years, and I refused radiation treatment. I had returned to using cannabis by this time. A VA doctor informed me in 2008 that I had to stop using cannabis in order not to lose my VA medical benefits if I wanted to keep them. As a result, I quit using cannabis and started taking pharmaceutical medicines. At this point, I wasn’t well enough to work and was afraid that the VA would take my license away due to risks of seizures. Consequently, I terminated my employment and applied for a VA pension. My daily medication intake reached 35 pills in 2010. Suddenly, one night in my sleep, I had my first seizure. In conclusion, it turned out that the VA had overdosed me on medications while treating all my problems, followed by treating all the side effects from those medications. It wasn’t until I was 41 years old in June 2013 that my world really crumbled. I had been experiencing chest pains and ended up in the hospital. It was then I learned I had Marfan Syndrome. It is a genetic defect that prevents the body from making the necessary proteins for connective tissue, tendons, heart and lungs. Aortic dissection, otherwise known as “sudden death”, was the number one concern for me. This condition has been deemed incurable by the medical community. If caught early, it may be treated some but there were limited treatments at my age. Because my chest was recessed, my heart and lungs we’re compressed, making it difficult for them to function properly. The recommended age for surgery is before 15 years of age and I was 42 at this time. According to my doctor, I had maybe a year left to live. The doctor assured me that he would keep me free of pain and that I should arrange my affairs. In November of that same year, I was diagnosed with a thyroid tumor. I was told by my doctor there was no point to treating anything because my Marfan Syndrome was terminal. Immediately, I went home and contacted an organization called Undergreen Railroad, an organization that helps severely ill individuals relocate to where cannabis oil treatment is legal. As a result , I was able to contact an organization called Moving for Marijuana who began the process of helping me locate a place to live and get everything else that I needed in order to get to Colorado. In Colorado, I did, indeed, begin to put “my affairs in order.” I was now officially a Marijuana Refugee. Friends and family lost faith in my decision; some said I was “chasing a drug,” others couldn’t accept cannabis as a medicine, but I felt I was chasing a chance to live. For me, the cannabis solution was the only option. My arrival in Colorado Springs, Colorado was on February 3rd of 2014. After my arrival, I immediately started using the oil. I found out about my thyroid tumor growing in March, when I began having difficulty speaking and my lymph nodes swelled. This led me to increase my intake of oil. Cannabis has not been studied in order to see if it can treat Marfan Syndrome, but the VA refuses to treat it because they say there is no cure. To me, that means there could be a cure. When it comes to cannabis, some days are good and some days are bad, but there are a few things I can attest to. One of them is that I’m still alive! This after doctors predicted I wouldn’t be around for long. I now have the quality of life I deserve. I’m now off all of my prescription meds and am enjoying better days than not since starting this journey. But I think cannabis has made the biggest difference in my life through my art. My art was impaired after I left the military. I felt as though I had lost my talent, which exacerbated my depression. In May, after getting off the prescription pills and starting cannabis treatment, I felt compelled to draw. It had been 20 years since I last drew. An idea that started out as a sketch became my first artwork in two decades. The tears flowed. Having the ability to draw again felt amazing. Creative juices were flowing once more. For me, cannabis has rekindled a sense of happiness no pill can ever match. Even now, as I write this, I have lived nearly 9 years longer than my doctors predicted, without assistance from the VA and with little medication. My only medication has been cannabis. While I am not cured, I am beating the odds despite the bad days. I refuse to give up despite the VA giving up on me. My health care is in my own hands, and I’ve made the decision to use cannabis for healing. As well as helping me heal, my art has also enabled others to see that there is hope for healing and I am now living my dream of sharing my art with others. I hope to one day be successful enough to help fund research into whether cannabis might be able to cure Marfans Syndrome. Cannabis gave me that hope, one that helped me not only heal physically, but when I realized I had a chance to live, it helped me heal mentally too. With my newfound knowledge and compassion, I now volunteer with various groups and try to share my experiences with cannabis with others. I still have one thing that hasn’t changed since my diagnosis. After all I did during my service, VA Healthcare is still refusing to treat me as they will not waste their resources on someone in my position and are still using my cannabis consumption against me in denying me necessary medical care. Nevertheless, I will continue fighting. I may not have chosen to suffer from a disease, but I did choose my treatment and cure. Perhaps if I simply give in and take their pills and keep quiet, my VA experiences might be a little less painful. And I did it for years. Unlike some veterans, I was never very vocal. That silence also almost cost me my life earlier by the hands of the VA shoving too many pills down me. During this time, I decided that I would spend all the time physically possible telling my story, hoping that it could help others. If I am going to live or die, I want to do so on my terms. Choosing the medicine and treatment that is right for us should be up to us, as it is our bodies. Veterans should most definitely have this right. It must also apply to them, for they are the ones who have sacrificed their lives for it. As a representative of veterans suffering under the VA, I hope my story draws attention to all of them, not just me. Our bodies and minds have been ravaged by the horrors of war; now let us heal as we may. We know what we went through and we know how we should heal. But unfortunately our battle did not end with the war. My aim is merely to let others know they are not alone and to make veterans’ suffering known.

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