- Meehan-Atrash, J., Luo. W., McWhirter, K.J., Strongin, R.M. Aerosol gas-phase components from cannabis e-cigarettes and dabbing: mechanistic insight and quantitative risk analysis. ACS Omega. 2019, Sep. 16,;4(14):6111-16120
- Hughes, B., Herron, C.E., Cannabidiol reverses deficits in hippocampal LTP in a model of Alzheimer’s disease. Neurochem. Res. 2019, Mar. 44(3):703-713
This is medical information not medical advice. Please consult with your physician.
Virginia Thornley, M.D., Neurologist, Epileptologist
August 1, 2018
Cannabinoids are gaining more recognition in treatment not only of pain, seizures and mood disorder but also in a wide variety of conditions. There have been 3 decades of pre-clinical research studying the mechanisms as it relates to the different organ systems. There has been an exponential increase in cannabinoid research especially in light of the demand by grassroot movements for it availability in treating a wide variety of conditions.
As more and more physicians start to recommend it, more symptoms are coming to light which can be ameliorated with medical cannabis. One of the most sought after answer is the deadliest of diseases which is cancer. This seeks to study the mechanisms by which cannabinoids may play a role in reduction of tumor load.
There are many studies demonstrating the involvement of the endocannabinoid system in modulating the pathogenesis of tumors.
There are no published human clinical trials using cannabinoids in the treatment of the actual underlying pancreatic cancer. Cannabis is labelled under the schedule 1 classification, with that comes the difficulty with procuring the agent because of the bureaucracy and legal red tape that accompanies it. Regardless, there has been an exponential increase in pre-clinical studies in in vitro and in vivo studies.
Detection of pancreatic duct cancer using a CB2 probe
A study showed that the CB2 receptor is highly expressed in pancreatic duct cancer which seems to correlate with the aggressiveness of the tumor (1). One study reports on using fluorescence imaging on pancreatic duct cancer using an NIR (near infrared) CB2 receptor targeted probe (2). The study found a high level of expression of CB2 receptors in patient samples with pancreatic cancer compared to normal pancreatic tissue. This is significant because it gives information on a specific target for diagnostic and treatment purposes.
Cannabinoid involvement in autophagy through the AMPK pathway
In one study the cannabinoid receptor ligands were discovered to cause autophagy and activate AMPK in pancreatic cancer. In previous works by the same authors, cannabinoids were found to increase the radical oxygen species. In another study ROS was found to interact with the mitochondria where ATP is produced. AMP is upregulated instead leading to AMPK production which reduces mTOR1c and leads to an increase in autophagy and reduction of cell growth (3).
Possible therapeutic role of CB1 and CB2 receptor ligands on pancreatic cancer
In another study using pancreatic cancer cell lines Panc1, 2 cannabinoid receptor ligands were applied to study the mechanisms of cannabinoids and its possible anti-tumor effect. Cannabinoid ligands GW405833 and arachidonoyl cyclopropramide. The study showed that the cannabinoid ligands were involved in the down-regulation and up-regulation of proteins associated with regulation of cell growth and their energy metabolism. This could be a potential target for therapeutic approaches in pancreatic cancer (4).
Synergistic responses occur when CBD is combined with radiation
Cannabidiol can augment the tumor killing potential when combined with radiation therapy in pancreatic cancer which was studied under in vitro studies. Synergistic responses were noted when 5 micrograms of CBD was combined with 4Gy of radiation therapy in a clonogenic assay. In the same study using mice, there was increased survival in mice with pancreatic tumor using CBD compared to a control cohort. When CBD was added with SRB or smart biomaterials (agents which are sensitive to environmental factors that allow delivery of other agents in this case CBD to the tumor cells) the mice survived compared to the control cohort with just CBD application alone. This study demonstrates that CBD in conjunction with radiation therapy enhances the tumor killing properties in the treatment of pancreatic cancer (5).
SRB’s or smart radiotherapy biomaterials allow the insertion of payloads which allow the abscopal effects of radiation therapy thereby boosting its results (6). Abscopal refers to the idea that radiation treatment can affect tumors distant from the area treated.
While there may be a dearth of human clinical trials using cannabinoids for treatment in pancreatic cancer, the pre-clinical studies demonstrate that the endocannabinoid system may play a potential role in the mechanisms, diagnosis and treatment of pancreatic cancer, one of the deadliest tumors, and should not be discounted. More studies are needed especially human clinical trials.
This is info only not medical advice.
July 18, 2018
This looks into the role cannabinoids may play in the treatment of gliomas under which glioblastoma multiforme is categorized. Every mechanism is key in providing valuable information in targeting various mechanisms to assist with treatment.
Cannabinoid system and evidence of a role in gliomas
Phytocannabinoids have been identified from the plant cannabis sativa including delta-9-tetraydrocannabinol and cannabidiol. There are 2 significant receptors CB1 receptor and CB2 receptors. Within the endocannabinoid system there are 2 well-studied endocannabinoids, 2-arachidonoylglycerol (2-AG) and anandamide (AEA) and G-related proteins (1). delta-9-tetrahydrocannabinol is a pharmacomimetic of anandamide while cannabidiol is a mimetic of 2-AG. Anandamide is metabolized by fatty acid amide hydrolase or FAAH while 2-AG is metabolized through monoacylglycerol lipase (MAGL).
The receptors are of 2 types. The CB1 receptor is found predominantly in the nervous system in areas subserving pain modulation, memory, and movement. The CB2 receptor is peripherally found in the immune system. The CB2 receptor is found to a lesser extent in other organ systems including adrenal, cardiac, endocrine, pulmonary, gastrointestinal and gynecological organs. Cannabinoids react with the TRPV receptor or the transient receptor cation channel subfamily V. They can act on G receptors including GPR55 which is thought to influence inhibition of seizures. Other receptors include GPR12, GPR18, and GPR119 (2).
In glioblastoma multiforme, degrading enzymes of anandamide were found to be reduced with 60% reduction of fatty acid amide hydrolase (FAAH). Anandamide was found to be significantly increased compared to non-tumor tissue. In meningiomas, 2-AG were found to be significantly increased. This points towards elevation of levels of endogenous cannabinoids in the presence of tumor cells which may possibly signal an anti-tumor process by modulating cannabinoid receptor mechanisms (3).
There are various mechanisms by which cannabinoid can modulate the pathogenesis in tumors including proliferation, invasion, cell survival. Cannabinoids are thought to be involved mechanistically in the anti-proliferative, anti-migration and apoptotic effects of tumor cells in gliomas.
Cannabinoids may make tumor cells in gliomas more susceptible to radiation
One study found that cannabinoids may make tumor cells in gliomas more strongly susceptible to irradiation. When heat shock proteins were treated with CBD, they were upregulated. This did not occur in the setting of THC. Heat shock proteins are important in degradation, assembly, and transcription factor regulation. They are important in cell survival in the setting of abnormal pH, temperature and inflammation which may be caused by abnormal stability in the cell related to hypoxia, oxidative stress and temperature. Heat shock proteins are associated with resistance of tumor cells to treatment and a poorer prognosis (5). Heat shock proteins can inadvertently promote cancer cell survival, hence, their presence may correlate with a poorer prognosis. Cannabinoids were found to increase reactive oxidative stress leading to an alteration in the expression of HSP’s by increasing it. Increased HSP’s may alter the cytotoxicity of CBD towards cancer cells. By using an HSP inhibitor in conjunction with CBD, there may be better impact of irradiation of tumor cells. In summary, CBD along with HSP inhibitors may make tumor cells in gliomas more vulnerable to tumor irradiation (6).
Cannabinoids causes tumor cell death through apoptotic mechanisms
In one study, cannabinoids were found to have an anti-proliferative effect on tumors. Apoptosis is reduced by mechanisms where cannabinoids stimulate the pro-apoptotic ceramide which subsequently has impact on cell proliferation, differentiation and apoptosis in tumors (7).
In another study, there is supportive evidence that sphingolipid metabolism changes. This causes tetrahydrocannabinol to change the sphingolipid content in the endoplasmic reticulum, autolysosomes and autophagosomes. This contributes towards cell death promotion by autolysosomes which are stimulated by the cannabinoids (8).
Another study confirms that arachidonoylethanolamide (AEA) or anandamide which is the most potent endogenous cannabinoid works through anomalously expressed vanilloid receptor-1 (VR-1) in activating apoptosis in glioma cell lines through this receptor (9). THC is a mimetic of anandamide and may induce apoptosis through this mechanism. This may represent a potential specific molecular mechanism where therapeutic agents may be developed.
Cannabinoids reduce angiogenesis and proliferation of glioma cell lines
In the human cell glioma cell lines U-87MG and T98G, cannabidiol was found to inhibit the proliferation and cell invasion of these cancer cell lines. These results are significant since aggressive tumors have an ability for normal tissue invasion and proliferation leading to a poor outcome. The doses required for reduction of invasion was less compared to the dosage needed to prevent proliferation. Cannabidiol demonstrated the ability to inhibit different proteins necessary for cell invasion of the 2 cell lines including MMP-9, TIMP-1, TIMP-4, uPA, VEGF and SerpinE1-PAI. Their roles play a significant part in metastasis and vascular proliferation (10). Interestingly, T98G cell lines were found to be delta-9-THC resistant.
Cannabinoids reduce MMP9 which is important in tumor cell invasiveness
MMP are proteases and are increased in the presence of gliomas signaling the invasiveness of the tumor. Cannabinoid inhibition of MMP9 may be the way by which invasiveness of the tumor is reduced. Inhibition of TIMP was also noted in the presence of cannabinoids, which is demonstrated in clinically aggressive gliomas (10).
Cannabinoids inhibits HIF-1 which allows tumor cells to thrive in hypoxic settings
Another significant concept produced by the research is cannabidiol inhibition of HIF1-alpha (or hypoxia induced factor) which is a transcription factor serving a regulatory role in the setting of hypoxia. Hypoxia occurs in fast-growing tumors when the demands for oxygen are outpaced and hypoxia results. In the setting of hypoxia, HIF1-alpha allows tumor cells to thrive in hypoxic conditions through migration, survival and vascular proliferation allowing these tumors to be resistant to chemotherapy (10).
Cannabinoids can modulate mechanistic properties of tumor cells in gliomas
One study demonstrated that cell “stiffness” correlates with the aggressiveness of invasion from tumor cell lines and may represent a mechanistic cell marker to signal invasiveness of a tumor. Cannabinoids can modulate the mechanistic properties of tumors and may be a potential anti-tumor therapeutic target in glioma cell lines(11).
In summary, cannabinoids are demonstrated to have a role in significant mechanisms involved in tumor activities including anti-proliferation, anti-migration, anti-angiogenesis and anti-survival. Cannabidiol inhibit conditions where transcription factors cause cancer cells to thrive in hypoxic environments which is crucial in the aggressive profile of malignant tumors. Cannabidiol reduces MMP9 significant in invasiveness. Cannabidiol along with HIF inhibitors can make gliomas more radiation susceptible.
The pre-clinical studies are accumulating rapidly which each discovery. Every mechanism elucidated counts towards potential therapeutic targets in gliomas. Pre-clinical studies do not always translate to human studies but the science is gaining headway.
Wang, et al. Quantitative Determination of delta 9-tetrahydrocannabinol, CBG, CBD, their acid precursors and five other neutral cannabinoids by UHPLC-UV-MS. Planta. Med, 2019, Mar., 84 (4):260-266
Landa, et al, “Medical cannabis in the treatment of cancer pain and spastic conditions and options of drug delivery in clinical practice,”Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 2018, Mar; 162(1):18-25
Petersen, G., Moesgaard, B., Schmid, P.C., Broholm, H., Kosteljanetz, M., Hansen, H.S. Endocannaboinoid metabolism in human glioblastomas and meningiomas compared to human non-tumour brain tissue. J. Neurochem. 2005, Apr., 93 (2):299-309
- Sredni, S.T., Huang, C.C., Suzuki, M., Chou, P., Tomita, T. Spontaneous involution of pediatric low-grade gliomas: high expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system. Childs Nerv. Sys.t 2016, Nov, 32(11):2061-2067
- Calderwood, S.K., Khaleque, A., Sawyer, D.B., Ciocca, D.R., Heat shock proteins in cancer: chaperones to tumorigenesis. Trends in Biochemical Sciences. 2006, Mar. 31(3):164-172
Scott, K.A., Dennis, J.L., Dalgeish, A.G., Liu, W.M. Inhibiting heat shock proteins can potentiate the cyototoxic effect of cannabidiol in human glioma cells. Anticancer Research. 2015, Nov., 35 (11):5827-583
Ellert-Miklaszewska, A., Ciechomska, I., Kaminska, B. Cannabinoid signaling in glioma cells. Adv. Exp. Med. Biol. 2013, 986:209-220
Hernandez-Tiedra, s., Fabrias, G., Davila, D., Salanueva, I.J., Casas, J., Montes, L.R., Anton, Z., Garcia-Taboada, E., Salazar-Roa, M., Lorente, M., Nylandsted, J., Armstrong, J., Lopez-Valero, I., McKee, C.S., Serrano-Puebla, A., Garcia-Lopez, R., Gonzale-Martinez, J., Abad, J.L.,, Hanada, K., Boya, P., Goni, F., Guzman, M., Lovat, P., Jaatela, M., Alonso, A., Velasco, G. Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization. Autophagy, 2016, Nov. 12 (11):2213-2229
Contassot, E., Wilmotte, R., Tenan, M., Belkouch, M.C., Schuriger, V., de Tribolet, N., Burkhardt, K., Dietrich, P.Y. Arachidonoylethanolamide induces apoptosis of human glioma cells through vanilloid receptor-1. J. Neuropathol. Exp. Neurol. 2004 Sep, 63(9):956-63
Solinas, M., Massi, P., Cinquina, V., Valenti, M., Bolognini, D., Gariboldi, M., Monti, E., Rubino, T., Parolaro, D. Cannabidiol, a non-psychoactive cannabinoid compound, inhibits proliferation and invasion in U87-MG and T98G glioma cells through multitarget effect. PLoS One 2013, 8(10):e76918
Hohmann, T., Grabiec, U., Ghadban, C., Feese, K., Dehghani, F. The influence of biomechanical properties and cannabinoids on tumor invasion. Cell Adh Migr 2017, 11(1):54-67
Virginia Thornley, M.D., Neurologist, Epileptologist
July 16, 2018
As medical marijuana emerges from the caves of obscurity in treating illnesses, physicians are at the forefront of rediscovering ailments that can be treated by medical cannabis. While most traditional scientists and trained clinicians do not think highly of anecdotal research, patients in clinical practice are the best parameters in judging whether a medication is working or not. Oftentimes, even with the best research, clinical practice conveys side effects that were never found during the short period of time of the study. Additionally, as hundreds of thousands of patients start using a new product it is only then one can observe the true efficacy and safety profile which accounts for why research does not always correlate with clinical practice.
Sometimes, one comes across a medication where certain other symptoms may be alleviated not listed on the indications. As a growing number of patients are recommended medical cannabis, they are presenting with a variety of symptoms that are incidentally relieved.
Background of endacannabinoids and relationship to areas in the brain subserving movement
One of the areas where the brain is rich in endocannabinoid receptors CB1 and CB2 receptors are in the basal ganglia which subserves the function of movement modulation. There likely exists a role of endogenous cannabinoids in the regulation of movement given its abundance in this area. The CB1 receptors are found in the striatum and caudate nucleus which are rich in GABA-ergic neurons, and pre-terminals of the internal and external globus pallidus, and substantia nigra. They are found in the glutamatergic pathways within the cortical systems and in the subthalamic nucleus (1).
The endocannabinoid system appears to inhibit glutamatergic pathways and increases GABAergic activity in the basal ganglia. It affects the dopaminergic pathway (2). It is speculated that the endocannabinoids may play a role in modulating the various neurotransmitter systems. While large clinical randomized controlled clinical trials may be lacking there is evidence that cannabinoids may reduce the clinical manifestations of motor tics (2).
Review of case studies and case series
There is a paucity of clinical trials studying the role of cannabis in movement disorders. Most of the data is from pre-clinical studies or case reports. Clinical research undoubtedly has been stunted given the scheduling of the agent under a schedule I category and other related factors.
In a small study of 12 patients, tetrahydrocannabinol was studied to determine effectiveness in treatment of tics(3). The Tourette Syndrome Symptom List (TSSL) was utilized for self-evaluations by patients. The examiners used the Yale Global Tic Severity List, Shapiro Tourette Syndrome Severity Scale for rating the severity of tics. A randomized controlled clinical trial was carried out. Those in the group where delta-9-tetrahydrocannabinol showed improvement compared to the placebo control group. There was great improvement using the TSSL with a p=0.15. Significant improvement found with complex motor tics using examiner ratings. Simple and vocal tics showed improvement (3).
In a case series of 19 patients, there were 60% who had much less motor tics after treatment with cannabinoids. There were 18 patients who felt they significantly improved (4).
The fact that the endocannabinoid system on which cannabinoids work is widely found within the basal ganglia which modulates fine movement correlates the function it has with modulation of movement.
While the scarcity of clinical trials is evident, cannabinoids continue to be used in clinical practice with some modicum of success for treatment of motor tics.
Koppel, B. Cannabis in the treatment of dystonia, dyskinesias, and tics. Neurotherapeutics. 2015, Oct. 12(4):788-792
Muller-Vahl, K.R., Kolbe, H., Schneider, U., Emrich, H.M. Cannabis in movement disorders. Forsch Komplementarmed. 1999. Oct. 6 Suppl 3:23-27.
Muller-Vahl, K.R., Schneider, U., Koblenz, A., Jobges, M., Kolbe, H., Daldrup, T., Emrich, H.M. Treatment of Touterret’s syndrome with delta 9-tetrahydrocannabinol (THC) a randomized crossover trial. Pharmacopsychiatry. 2002, Mar. 35(2):57-61
Abi-Jaoude, E., Chen, L., Cheung, P., Bhirkram, T., Sandor, P. J. Neuropsychiatry Clin Neurosci. 2017 29(4):391-400
Virginia Thornley, M.D., Board-certified Neurologist, Epileptologist
July 15, 2018
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
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.
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/
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.
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.
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.
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.
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.
Virginia Thornley, M.D., Neurologist, Epileptologist
June 25, 2018
Alzheimer’s disease is not a natural progression of senescence. It is a neurological disorder involving deposition of beta amyloid peptides in senile plaques and accumulation of amyloid precursor proteins within the cerebrum particularly in areas affecting memory and cognition. Current pharmaceutic agents at best can only slow the progression of this disorder. There is no cure. Because it not a devastating illness in that it does not decrease the longevity per se, nonetheless, it is devastating to the patient and family members around him or her.
With the advent of cannabinoids into the pharmaceutic fold, attention is turning towards medical value outside its well-known repertory including anti-inflammatory and neuroprotective properties. Can cannabinoids slow the inflammatory process that is involved in this neurodegenerative condition? This seeks to explore mechanisms by which cannabinoids may play a role in ameliorating the clinical effects seen in Alzheimer’s disease.
As an overview, the endocannabinoids system is found naturally within the body consisting of endocannabinoids, enzymes and receptors. There are 2 receptors the CB1 receptor which is concentrated in the nervous system and found to a lesser extent in other organ systems and the CB2 receptor which is found mostly in the immune system and in other systems. Anandamide is an endocannabinoid that exerts its actions on the CB1 receptor, while di-arachidonoylglycerol has a low affinity for the CB1 receptor and interacts with the TPRV or transient receptor potential channels of the vanilloid subtype and the G-coupled receptor family.
Within the cannabis sativa plant are 2 most well-studied phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The CB1 receptor is where delta-9-tetrahydrocannabinol (THC), a mimetic of Anandamide, interacts and can cause psychoactive effects. Cannabidiol is a mimetic of di-arachidonoylglyerol with a lower affinity to the CB1 receptor where 100 times the amount of CBD is required to achieve the same psychoactivity as THC. When CBD and THC are combined there are less side effects since the CBD acts as a non-competitive allosteric modulator at the CB1 receptor. When the 2 are combined there is an effect that is increased together compared to when each cannabinoid is taken alone, where the effect is significantly much different. The presence of CBD offsets side effects of THC. Common side effects include agitation, hyperactivity and paranoia.
Senile plaques are found to express CB1 and CB2 receptors within the brain in addition to microglial activation markers. The neurons are rich in CB1 receptors but seem to be greatly reduced in microglial activated areas. CB1 receptor expression and G-related coupled protein are reduced in brains with Alzheimer’s disease. Nitration of proteins are enhanced especially in CB1 and CB2 proteins in Alzheimer’s diseased brains. Adding synthetic cannabinoid WIN55-212-2 to rats caused an inhibition of microglial activation and neuron marker loss. Cannabinoids were found to ameliorate neurotoxicity caused by microglial activation (1).
Another study demonstrates the role of cannabinoids on inflammation in the mouse model using synthetic cannabinoids JWH-133 and WIN55.212-2. Cognition and inflammation were studied. FDG uptake on PET scan was used to assess areas of metabolic uptake. The amyloid precursor protein mice showed poor object recognition. After administration of the JWH compound, cognitive impairments were reversed. There was reduced FDG uptake in the hippocampal areas. No changes were seen using WIN55.212-2. Beta amyloid proteins were significantly reduced in the mice models when cannabinoids were applied. Microglia was elevated in the APP mice which was reduced after cannabinoid administration (2).
In another mouse study, CB2 receptors were at a low level found in the neurons of unmanipulated mice whereas there was a noted increase in the CB2 receptors in mice that underwent chronic inflammation in the microglia surrounding plaques. This suggests that there is an upregulation of CB2 receptors in the presence of pathological inflammation. This may be a potential target in therapeutic agents in the future (3).
These pre-clinical studies demonstrate a neuroprotective and anti-inflammatory role of cannabinoids on Alzheimer’s disease. The CB2 appears to be upregulated around activated microglial cells around plaques implying a possible therapeutic target for future treatments. While pre-clinical studies are not human trials, elucidating these mechanisms may play a role in the future therapeutic benefits of cannabinoids on Alzheimer’s disease.
Ramirez, B.G., Blazquez, C., del Pulgar, T.G., Guzman, M., de Ceballos, M.L. Prevention of Alzheimer’s disease pathologyby cannabinoids: neuroprotection mediated by blockade of microglial activation. J. Neurosci. 2005, 25:1904-13
Martín-Moreno, A.M., Brera, B., Spuch, C., Carro, E., García-García, L., Delgado, M., Pozo, M.A., Innamorato, N.G., Cuadrado, A., de Ceballos, M.L. Prolonged oral cannabinoid administration prevents neuroinflammation, lowers b-amyloid levels and improves cognitive performance in Tg APP 2576 mice. J. Neuroinflam. 2012, 9:8
Lopez, A., Aparicio, N., Pazos, M.R., Grande, M.T., Barredo-Manso, M.A., Benito-Cuesta, I., Vazquez, C., Amores, M., Ruiz-Perez, G., Garcia-Garcia, E., Beatka, M., Tolon, R.M., Dittel, B.N., Hillard, C.J., Romero, J. Cannabinoid CB2 receptors in the mouse brain: relevance for Alzheimer’s disease. J. Neuroinflam. 2018, May, 15:158