Medical Practice

Understanding the practical aspects of cannabidiol (CBD) and tetrahydrocannabinol (THC)

 

Virginia Thornley, M.D., Board-certified Neurologist, Epileptologist

@VThornleyMD

July 15, 2018

Introduction 

This serves as medical information for educational purposes only not medical advice. Please consult with your treating  physician.

In contrast to the rest of the blog which is more scientific, this gives more practical information in the day to day workings of recommending medical cannabis. It gives the behind the scenes processes that happens before a patient can even begin to start their medical product. It is not a magic pill but because it is unlawful in Florida, a physician cannot even write it on a prescription pad. It takes one hour or more to evaluate, counsel and go over the registration process when presenting for the first time to a doctor.

For more detailed information and scientific references for specific indications please refer to
https://neurologybuzz.com/

Medical cannabis is one of the most misunderstood and controversial medications in the world. Long suppressed for over a century, it is one of the most misunderstood medications known to mankind despite being used for thousands of years with medical intent.

This is to give a brief basic background of mechanisms, rationale for ratios, combinations, pitfalls of isolates and synthetics and legal implications.

Background

The endocannabinoid system is found naturally in our body. It is responsible for the runner’s high people get. It gives a sense of wellbeing, not endorphins like most people think, those molecules are too large to pass the blood-brain-barrier. There are 2 receptors:(1) the CB1 receptor found mostly in the nervous system and (2) the CB2 receptor which is more abundantly found in the immune system. Anandamide works on the CB1 receptor, tetrahydrocannabinol (THC) is similar to this and works on the CB1 receptor. CBD or cannabidiol is from the cannabis sativa plant and is also a phytocannabinoid. One needs 100 times the CBD to get the euphoria as THC. CBD is not intoxicating, legal and works on a wide variety of symptoms including pain, seizures and anxiety. CBD is similar to 2-arachidonoyl glycerol which is a natural cannabinoid. When the 2 are combined together, CBD will offset side effects of THC including paranoia, hyperactivity and agitation. This is a not known fact to those who self-medicate with pure THC.   Because of this THC is medically recommended in conjunction with CBD. Smoking is illegal and not medically recommended as most people think. https://neurologybuzz.com/2018/04/02/medical-marijuana-vlog-series-part-i-mechanisms-medical-benefits-of-non-intoxicating-cannabidiol-and-tetrahydrocannabinol/

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Pitfalls of self-medication

Sometimes patients self-medicate and smoke pure THC from dubious sources to alleviate symptoms, which is illegal and not medically recommended in Florida.  However, the intoxicating effects are not seen when recommended medically using oral forms, cream or patch. At low doses, as is done when recommended medically, THC is non-euphoric. When THC is combined with CBD the side effects of THC are offset. The dangers of patients who self-medicate is that they do not know where the products are coming from and it can be mixed with potentially dangerous substances that can be potentially fatal. In addition, there are highly potent synthetic illegal cannabinoids known as K2 and spice which at high doses can cause cardiotoxicity and fatalities. Self-medicating with THC from an unknown source is highly discouraged as there may be mold involved with the processing. https://neurologybuzz.com/2018/05/31/the-fatal-effects-and-mechanisms-of-synthetic-cannabinoids-including-jwh-compounds-used-recreationally/

Why is a CBD and THC combination important?

In regulated licensed dispensaries, CBD is combined to offset the side effects of THC allowing better tolerance. THC is not recommended by itself because of side effects including paranoia, agitation and hyperactivity.

CBD by itself

With pure CBD, there are certain medical symptoms that are alleviated.

It is legal. There are many companies with CBD products but it is difficult to know how pure these products are, even if you have a small amount of hemp it can be marketed as CBD hence, its ineffectiveness. Some of the most effective CBD products can be found from Colorado and California, anecdotally. Everything else is hit or miss.

In the state of Florida, there are very few medically beneficial CBD products, it’s trial and error. The purer the form such as full spectrum CBD oil the more expensive it will be because processing organic products are costly. A cheap product will likely not be as pure just because of the huge amount of work that goes into extracting the cannabidiol. In addition, some may have flavors, cutting agents and other agents to dilute it but because it’s unregulated.

Ratios

CBD alone has no psychoactivity but medical value. CBD is combined with THC in order to offset its side effects of paranoia, agitation and hyperactivity.

Time of onset and duration

There are different ways of trying it: vaporizer lasts 1 hour and takes about 10 minutes to get into your system. Because the vaporizer is inhaled into the lungs the onset is the fastest because of the rich supply of blood vessels in the lungs. It is advisable to try the vaporizer at home or at night before setting out to see how it affects you. Oral forms last 6 to 7 hours and takes about 1/2 hour to get into your system. Oral form comes in oil concentrate and tincture. Cream and patch last about 12 hours or longer depending on the preparation. Medical marijuana is NOT recommended by physicians to be smoked. Recreational marijuana by smoking is prohibited and unlawful in Florida. This law varies by state. When different parts of the plant are taken together including the terpenes it gives an entourage effect which is more medically valuable than when components are isolated for its use.https://youtu.be/Ir4rwgF2iNc

Are there any edibles in Florida?

As of July 2018, there are no edibles in the state of Florida. It will take an enormous amount of submitting documentation and providing capital before edibles will be implemented in Florida. The dispensaries are working on this.

Registration process: what to expect in Florida

The process includes an evaluation by a qualified licensed physician. https://neurologybuzz.com/2018/07/12/legalities-and-application-process-in-the-state-of-florida/A qualified physician undergoes a 2-hour course and holds a full medical license in the state of Florida. One is evaluated and if patient meets the stringent criteria, they obtain a registry number. The patient undergoes registration which takes between 2-4 weeks. An e-mail arrives before the card then one is instructed to call the office so that recommendations are placed in the system. Oftentimes, if you don’t hear back in 4 weeks it is advisable to give the registry a call. It may be a misentering of an e-mail causing a delay.

Regulated dispensaries in the Florida

In Florida, there are 13 medical marijuana treatment centers and 43 retail dispensaries as of July 2018. In the state of Florida, patients can only obtain the Cannabis products recommended from their treating physicians from these dispensaries. It is illegal to smoke. There are 4 ways of taking it: oral, vaporizer, cream and patch. It is advisable to visit one of the licensed dispensaries in person so that the exact instructions can be given. Physicians recommend orders which are entered into the system. So long as the product is within the number of mg dispensed and the way it is recommended (oral, vaporizer, cream or patch) patients are at the liberty to change the ratio or dosage so long as it is within the orders.

Once you are registered

An e-mail with the marijuana card number comes before the physical card. It is advisable to call the physician office so the orders are placed then physically visit the dispensary of your choice so specific instructions can be taken. Because this is not a pharmacy, doctors do not have immediate access to the dispensary. One should be aware of which product they are taking before their next checkup. This can be easily accessed through the website of the dispensary.

The orders will expire after 70 days after which there is a processing fee of renewal at the office. The certification for medical marijuana expires after 1 year. One must be re-evaluated by their physician before then.

CBD is purely cannabidiol, it is non-psychoactive and legal. THC at low doses is non-intoxicating. Dispensaries combine CBD and THC to offset side effects.  It is federally illegal. It is advisable to be registered under a medical doctor who is qualified to determine if one meets criteria. Medical cannabis products can only be dispensed from a regulated licensed dispensary. Medical marijuana products outside of the jurisdiction of Florida regulates licensed dispensaries cannot be advocated.

Legal implications of THC

In some states, such as Florida, medical use of cannabis is recognized. THC is still considered federally illegal. Recreational use of cannabis is illegal. Smoking THC is illegal. Physicians cannot prescribe it since it is a schedule 1 drug but can recommend it. Schedule 1 drugs are considered illicit and labeled as having no medical use. A statement before the qualifying course on medical cannabis states that the physician can be questioned at any time by the FBI and authorities.

In other states, medical and recreational use is allowed.

In other states, medical and recreational use is completely banned.

The law also varies regarding cultivation of the cannabis sativa plant.

Countries will vary in their marijuana laws.

The laws change very rapidly. Regulations are changed nearly every month with more documentation required from physician offices including consent, doctors’ notes, patient information with indication. As each month goes by another new document is required for submission from the physician office. There is increasing bureaucracy likely signifying resistance at some upper levels against its use related to economic and political reasons. Dispensaries have an equally challenging time. Even worse are small farms applying for licenses huge amounts of capital and documents are required.

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Legal implications of CBD

CBD is legal throughout the US. Countries may vary in their laws since they both come from the cannabis sativa plant.

FDA approved medications and products approved in Europe with CBD and THC

A medication called Epidiolex for seizures with CBD has recently been approved for seizures. Because it comes from a strain from the cannabis sativa plant, cannabis will need to be deregulated from the schedule I category before Epidiolex can be marketed to the public.

Dronabinol has long been approved for nausea and can only prescribed for patients with cancer with chemotherapy induced nausea. It is a synthetic THC and is FDA approved.

In Europe, the medication Sativex which is a combination of CBD:THC has long been used for spasms in multiple sclerosis. This is not available in the US.

In summary

For patients, it is beneficial to have a working understanding of the different strains, different forms that are available in order to obtain the best benefit.  Dispensaries have a huge breadth of products. It is easier to understand as much as possible before facing the overwhelming number of options. Patients must understand all the legal implications in your state as they change rapidly. It is not only a medication it is affected by state and federal laws that change in a blink of an eye which can affect the patient if they are not aware.  One must be mindful that there are different types of practices recommending medical cannabis. The best practices are those that are an already established practice which added medical marijuana to their repertory. Practices that are solely for medical marijuana may be of dubious quality. There are already horror stories of patients never getting a card after several months and phone calls not being advisef on what to do, being examined in a conference hall. As with any new innovative service, there will be legitimate practices and there will be those who meet the minimum requirement of care and service. http://www.tampabay.com/investigations/2018/05/04/floridas-medical-marijuana-program-is-attracting-troubled-doctors-its-like-the-wild-wild-west/

For doctors recommending, one must be well-versed in understanding the potential side effects, drug interactions, the latest scientific research since these are the only guidelines that are guiding us from a scientific level. Pre-clinical studies cannot be ignored nor studies on synthetics to have a better grasp of understanding how it works. One must have a basic understanding in the effects of the phytocannabinoids which is best taken in combination and not in isolation. Patients come with complex medical problems it is always prudent to do due diligence in understanding as much as possible before recommending a product that was never studied for medical purposes in medical school. Patients will ask tough questions, physicians should understand as much as possible and do their due diligence being up to date on legislations as well as the most recent research. The hard questions will come.

One must also follow the legal implications, current regulations which are frequently updated. It is the physician’s responsibility to understand the mechanisms, be current on the literature because this is a pioneering science. Those recommending right now are trailblazing and should still be mindful of the great role you play in understanding what literature is available and to read voraciously.

Last thoughts

While much is still unknown about CBD, THC and mechanisms, there is great anecdotal data from history and clinical anecdotal experience supporting its benefits. While many traditionally trained physicians scoff at the prospect of introducing alternative treatments, one must bear in mind cannabis was not an alternative medication before it was banned in 1830.

While scientists are working overtime in elucidating the mechanisms to combat diseases such as cancer, one must bear in mind that medical cannabis is beneficial when taken in combination with other terpenes found in the plant and the components are not isolated from each other. THC works best in combination with CBD and with other components from the cannabis sativa plant.

When components are isolated from each other and products become synthetic and manufactured much of the benefits are lost and significant side effects result. https://neurologybuzz.com/2018/05/31/the-fatal-effects-and-mechanisms-of-synthetic-cannabinoids-including-jwh-compounds-used-recreationally/

Once it becomes synthetic and components are isolated, the benefits will be substantially altered.

Now is a optimal time to try the benefits of medical cannabis while it is still all organic and being produced on farms and regulated for its use, unsullied by synthetic forms where the risk of side effects are greater.

While much is still to be learned, for a medicine that can easily cover 5 symptoms in one setting, it is an extraordinary time to be recommending and benefiting from medical cannabis while it is still organically natural and pure.

 

Introduction/Disclaimer

About

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Glaucoma

Tetrahydrocannabinol and novel mechanisms in reducing intraocular pressure in glaucoma

Virginia Thornley, M.D.,  Neurologist, Epileptologist

February 28, 2018

Introduction

The endocannabinoid system is composed of 3 systems: (the cannabinoid receptors, (2) endocannabinoid transportation system and (3) enzymes that break down the ligands. Two endocannabinoids anandamide (AEA) and 2-arachidonyl glycerol (2-AG) are elevated in response to a wide variety of pathological events. This suggests a compensatory response of endocannabinoids in response to damage or pathology within the system (3). Activation of the endocannabinoid system appears to correlate with cell repair and survival. The G-receptors discovered called CB1 and CB2 trigger transducer signal cascades and influence peripheral central cell functions.

13909252_10154408552708841_6462398358021475581_o.jpg

Cannabidiol in glaucoma

Cannabidiol is becoming a topic of hot debate in pain, anti-tumor effects, epilepsy and in glaucoma.  Glaucoma can result in increased intraocular pressure resulting in damage to the optic nerve at the retinal attachment. There is the narrowing of the visual field and eventual blindness through retinal damage. and blindness. Cannabinoid receptors have been found in the ocular cells leading to speculation of benefits of cannabinoids in glaucoma.

In one study of 32 different types of cannabinoids, it was found that certain derivatives of delta 9THC and delta 8THC were more effective at lowering intraocular pressure in glaucoma than the parent derivative cannabidiol (1).

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Mechanism for treating glaucoma

One possible mechanism in ameliorating intraocular pressure is by suppressing N-methyl D-aspartate or NMDA receptor excitability, increasing neural vasculature circulation, suppressing apoptosis and damaging free radicals. Separation of the novels effects appears possible from the toxic side effect through novel technique (2).

Involvement of cannabinoid and their receptors in retinal cells have been well documented in fish cells to primates and more recently in neurodegeneration and neuroprotection. There is a fine balance of biosynthetic and degrading enzymes that influence endocannabinoids and exert neuroprotection during trauma, inflammation, ischemia and neurotoxicity found in brain damage (4).

In addition, in one study in 21 dogs, when 2% of tetrahydrocannabinol was applied, the intraocular pressure was reduced (5) which was found statistically significant.

 

https://neurologybuzz.com/

Introduction/Disclaimer

About

References

  1. ElSohly, et al, “Cannabinoids in glaucoma II: the effect of different cannabinoids on intraocular pressure on rabbits,”Current Eye Research, 1984, Jun., 3(6):841-50.
  2. Jarvinen, T., “Cannabinoids in treatment of glaucoma,” 2002, Aug., 95(2):203-20.
  3.  Karanian, et al, “Cannabinoid drugs and enhancement of endocannabinoid responses: strategies for a wide array of disease states,” Current Molecular Med., 2006, Sep., 6(6):677-84.
  4.  Rapino, et al, “Neuroprotection by endocannabinoids in glaucoma and retinal neurodegenerative diseases,” Current Neuropharmacology, 2017, Jul., doi:10.2174 (Epub ahead of print)
  5. Fischer, et al, “Effects of a topically applied 2% delta-9-tetrahydrocannabinol ophthalmic solution on intraocular pressure and aqueous humor flow rate in clinically normal dogs,” American J. Vet. Res., 2013, Feb., 74(2):275-80.

 

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Glaucoma, Uncategorized

9Tetrahydrocannabinol and novel mechanisms in reducing intraocular pressure in glaucoma

Virginia Thornley, M.D.,  Neurologist, Epileptologist

February 28, 2018

Introduction

The endocannabinoid system is composed of 3 systems: (the cannabinoid receptors, (2) endocannabinoid transportation system and (3) enzymes that break down the ligands. Two endocannabinoids anandamide (AEA) and 2-arachidonyl glycerol (2-AG) are elevated in response to a wide variety of pathological events. This suggests a compensatory response of endocannabinoids in response to damage or pathology within the system (3). Activation of the endocannabinoid system appears to correlate with cell repair and survival. The G-receptors discovered called CB1 and CB2 trigger transducer signal cascades and influence peripheral central cell functions.

13909252_10154408552708841_6462398358021475581_o

Cannabidiol in glaucoma

Cannabidiol is becoming a topic of hot debate in pain, anti-tumor effects, epilepsy and in glaucoma.  Glaucoma can result in increased intraocular pressure resulting in damage to the optic nerve at the retinal attachment. There is the narrowing of the visual field and eventual blindness through retinal damage. Cannabinoid receptors have been found in the ocular cells leading to speculation of benefits of cannabinoids in glaucoma.

Mechanism for treating glaucoma

One possible mechanism in ameliorating intraocular pressure is by suppressing N-methyl D-aspartate or NMDA receptor excitability, increasing neural vasculature circulation, suppressing apoptosis and damaging free radicals. Separation of the novels effects appears possible from the toxic side effect through novel technique (2).

Involvement of cannabinoid and their receptors in retinal cells have been well documented in fish cells to primates and more recently in neurodegeneration and neuroprotection. There is a fine balance of biosynthetic and degrading enzymes that influence endocannabinoids and exert neuroprotection during trauma, inflammation, ischemia, and neurotoxicity found in brain damage (4).

THC studies and glaucoma

In a rabbit model, 9THC showed improved penetration to the anterior chamber with reduction of intraocular pressure using a prodrug. THC is an established neuroprotectant and has the possibility of being an effective IOP lowering agent. THC and THC-Val-HS reached the retina choroid(5).

 

In one study of 32 different types of cannabinoids, it was found that certain derivatives of delta 9THC and delta 8THC were more effective at lowering intraocular pressure in glaucoma than the parent derivative cannabidiol (1).

37608_434614963840_3006668_n

 

Introduction/Disclaimer

https://neurologybuzz.com/

About

 

References

  1. ElSohly, et al, “Cannabinoids in glaucoma II: the effect of different cannabinoids on intraocular pressure on rabbits,”Current Eye Research, 1984, Jun., 3(6):841-50.
  2. Jarvinen, T., “Cannabinoids in treatment of glaucoma,” 2002, Aug., 95(2):203-20.
  3.  Karanian, et al, “Cannabinoid drugs and enhancement of endocannabinoid responses: strategies for a wide array of disease states,” Current Molecular Med., 2006, Sep., 6(6):677-84.
  4.  Rapino, et al, “Neuroprotection by endocannabinoids in glaucoma and retinal neurodegenerative diseases,” Current Neuropharmacology, 2017, Jul., doi:10.2174 (Epub ahead of print)
  5.  Goutham, et al, ” Development of a 9tetrahydrocannabidiol amino acid dicarboxylate prodrug with improved ocular bioavailablity,” Investigative Ophthalmology and Visual Science, 2017, Apr., 58(4):2167-2179.

 

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